Q4 2023 Amgen Inc Earnings Call

9% volume growth osteoporosis disproportionately impacts post menopausal women in the diagnosis and treatment rates for these patients are low.

In the U S only 6% a very high risk patients with osteoporosis are treated with a bone builder, creating an urgent need for treatment with an effect of therapy.

<unk> is an important therapy to address this unmet needs as it is the only bone builder that works with the body's natural ability to increase bone formation and also decrease bone resorption.

We see strong growth potential for <unk> and will continue to apply our proven experience in bone health to ensure it reaches all the patients who need it.

Earliest sales grew 12% year over year to a record $1 1 billion for the fourth quarter volume growth of 10% was supported by real world evidence reaffirming prolia superiority in reducing fracture risk when compared to alendronate in treatment naive patients with postmenopausal osteoporosis at a high risk of fracture.

Sure.

Moving to our oncology business, which includes split insightful luma Kras, Vectibix Kyprolis and plate Nx jiva.

Sales of the six innovative products grew 5% year over year for the fourth quarter with 3% volume growth full year sales grew 12% year over year, driven by 12% volume growth.

<unk> sales grew 47% year over year to a record $241 million for the fourth quarter volume growth of 55% was supported by broad prescribing to patients with acute lymphoblastic leukemia in frontline consolidation treatment.

Long term, we see significant growth potential for billing cycle from utilization earlier in the frontline as part of induction treatment.

<unk> sales increased 8% year over year for the fourth quarter, we see future growth opportunities for <unk> coming from launches in new markets and additional indications.

<unk> sales increased 5% and Kyprolis sales grew 8% year over year for the fourth quarter, both driven by volume growth and place sales decreased 18% year over year for the fourth quarter driven by volume decline related to timing of orders placed by the U S government, partially offset by volume growth across our.

Regions full year sales increased 13%, primarily driven by volume growth, including U S government orders.

Excluding U S government orders and place sales grew 23% year over year for the fourth quarter and 8% for the full year.

Transitioning to our inflammation business, so Tesla sales increased 2% year over year for the fourth quarter driven by favorable changes to estimated sales deductions and 3% volume growth, partially offset by lower inventory levels and lower net selling price.

Full year sales decreased 4% driven by lower net selling price and lower inventory levels, partially offset by 2% volume growth.

New patient starts for Tesla grew 6% in the fourth quarter, driven by strong execution and increased investment.

<unk> free drug programs had a reduced impact in the quarter.

Tesla is uniquely positioned to grow in 2024 and beyond given its indication for all severities of psoriasis combined with an established clinical profile broad payer coverage, a lack of testing required for initiation and convenient oral administration.

Enbrel sales decreased 8% year over year for fourth quarter, driven by a 4% impact from unfavorable changes to estimated sales deductions and lower net selling price.

Volume grew 1% in the fourth quarter supported by an increase in new patients starting treatment as a result of improved payer coverage going forward, we expect net selling price to continue to decline year over year, driven by higher rebase to maintain broad first line payer coverage and changes in patient mix.

Test fire continues a strong launch trajectory with $177 million in sales in the fourth quarter and $567 million for the full year sales.

Sales increased 10% sequentially driven by volume growth our successful launch of our self administered pre filled single use 10 allowed us to expand coverage with major pharmacy benefit managers to over 80% contributing to higher new patient growth as the year progressed moving forward. We expect this expanded coverage will allow test.

Fire to help even more patients with severe uncontrolled asthma.

Sales of Tod Nielsen were $44 million in the quarter and $134 million for the full year in the fourth quarter, we saw 17% quarter over quarter volume growth in the U S. Proximately 2700 patients have now been treated with <unk> by over 1700 healthcare professionals.

Looking forward, we will continue to leverage our expertise in nephrology and inflammation to bring tap needless to even more patients with <unk> associated vasculitis.

Sales for our Biosimilars portfolio grew 10% year over year for the fourth quarter and 5% for the full year, driven by 27% and 29% volume growth.

This volume growth was partially offset by net selling price decline over time, we expect long term growth in our biosimilars business to be driven by the addition of new molecules and additional launches.

Overall, our execution is strong across the business underscored by our foundational commitment to serve patients. The four pillars of our portfolio position us well to serve many more patients around the world, who can benefit from our innovative therapies and with that I'll turn it over to Vikram, who will cover our rare disease portfolio.

Vikram: Thanks Murdo I.

Vikram: I am glad to share an update on our rare disease business now that we're four months after deal close.

Vikram: We are now fully operating as part of Amgen with integration activities ongoing.

Vikram: As mentioned before we are excited to be amgen's fourth pillar of long term growth.

Vikram: I wanted to make sure you are aware that we are not reporting the full quarter in press release and slides, which reflect sales from October six onwards, and totaled $954 million.

Vikram: This excludes $41 million of sales that occurred in the first week of October prior to deal close.

For the full quarter, our rare disease brands from horizon delivered product sales of $995 million.

Vikram: Representing 6% year over year sales growth.

Vikram: Throughout the remainder of my remarks, I will reference full quarter product sales.

Vikram: It depends a an IGF one our monoclonal antibody for patients with thyroid eye disease generated $467 million of sales during the entire fourth quarter, representing 3% quarter over quarter growth.

Vikram: This is the third quarter in a row of quarter over quarter growth, both the peso with the growth largely driven by the U S. B.

Vikram: We saw a number of positive leading indicators, including a record number of unique depends on prescribers total patient enrollment forms and patient starts in 2023.

Vikram: Additionally, thanks to our efforts, we've been able to generate favorable medical policy changes or greater than 50% of U S covered lives and we expect to continue this momentum throughout 2024.

Vikram: We continue to see approximately 100000 patients with moderate to severe disease in the U S who could benefit from.

Vikram: With the majority of these patients in low clinical activity score settings.

Vikram: Given positive leading indicators and high unmet need we see a long term growth opportunity for <unk> in the U S. While also recognizing there is some time lag between our execution efforts and the realization of increased patient numbers.

Vikram: International expansion also remains a meaningful long term growth opportunity for the peso.

Vikram: <unk> is approved in Brazil, and we are progressing towards approval in additional countries.

Vikram: Our expansion into both Japan, and Europe is a high priority with regulatory review underway in Japan and filings in the EU throughout the year.

Vikram: KRYSTEXXA, a pegylated uricase enzyme for patients with chronic refractory gout delivered a record $280 million in sales for the entire fourth quarter, representing 30% year over year growth driven by continued strong commercial execution.

Vikram: Sales are now Annualizing $80 billion run rate.

Performance was driven by execution across all pieces of the patient journey demand generation stakeholder engagement and adherence to treatment.

Vikram: Uplift and anti CD 19, monoclonal antibody, which is now the fastest growing biologic and <unk>.

Vikram: Livered a record $70 million in sales for the entire fourth quarter, representing 68% year over year growth.

Vikram: International expansion is also underway with <unk> now launched in multiple ex U S markets.

Vikram: Our remaining ultra rare portfolio generated $178 million of sales for the entire fourth quarter, primarily driven by our ultra rare medicines probity process be and afternoon.

Vikram: Looking ahead of 2024 by leveraging Amgen's World class biologics capabilities decades of experience in inflammation and extensive global presence, we are ready to reach more patients than ever before.

Vikram: I will now turn it over to Jay.

Jay: Thank you Vikram and good afternoon, everyone.

Jay: I'd like to take a minute to convey how thrilled I am joined the Amgen R&D organization and this leadership team.

Jay: The creativity of our discovery research expert expedited clinical development.

Jay: Authoritative bio manufacturing organization in the industry all were well known to me before joining.

Jay: But now on staff at Amgen I appreciate the strong sense of service for patients facing serious illness.

Jay: The likeminded commitment towards the impact of our medicines and our business and the share conviction in this remarkable portfolio of potential first in class and best in class medicines.

Jay: In 2023, we executed with speed across our clinical pipeline achieving excellent enrollment in key programs and setting up 2024, as a year with significant data readouts across the portfolio for medicines with the potential to transform patient care.

Key highlights in 2023 included the delivery of promising data from four key oncology assets and the attainment of three breakthrough therapy designations in oncology.

We initiated pivotal phase III studies for <unk> in small cell lung cancer, Lumia kras, non small cell lung cancer and colorectal cancer, along with gateway <unk> in Shogun syndrome.

Jay: And general Medicine as previously disclosed top line 52 week data from the 592 patient Maritime Phase II study.

Jay: Expected by late 2024.

Leveraging the durability of weight loss served in phase, one and rapid enrollment and Jordan phase III.

Jay: Recently added a part two to this study to explore the durable weight loss beyond 52 weeks.

Jay: Our planning for our comprehensive phase III program across multiple indications remains on track.

Jay: Lastly, you may have seen that yesterday nature metabolism published manuscript from Amgen R&D that provides the integration of maritime preclinical and phase one data.

Jay: Beyond Maritime our obesity strategy consists of several assets with AMG 786 in phase, one and additional preclinical assets advancing.

Jay: Our approach is tailored to meet the dynamic needs of obesity treatment, demonstrating a longitudinal commitment to innovation and patient care in this field.

Jay: The phase III outcome study of ore pass around our potentially best in class LP Little a targeting small interfering RNA molecule in atherosclerotic cardiovascular disease has enrolled more than 7000 patients globally.

Jay: This rapid enrollment accomplished in just one year across 34 countries and over 700 sites underscores the medical community strong interest in <unk> and the potential impact of <unk>.

Jay: We've deliberately expanded our initial enrollment target from 6000 to over 7000 patients.

Jay: To ensure comprehensive demographic representation.

Jay: And to satisfy regional regulatory requirements.

Jay: We are on track to complete enrollment in first half of 2024.

Jay: In oncology, we're focused on approaching high conviction targets with differentiated therapies for large effect sizes.

Jay: We're pleased to announce that the FDA granted priority review for <unk> in early stage television 19 positive.

Jay: With a <unk> date of June 21, 2024.

Jay: The ongoing phase III Golden Gate study is enrolling patients to evaluate the effectiveness of alternate England szeto with low intensity chemotherapy.

Jay: Here in older adults diagnosed with Philadelphia chromosome negative.

Jay: We're also planning to amend the study to evaluate subcutaneous administration of <unk> <unk> with initiation anticipated in the second half of 2020 for potentially allowing us to serve more patients and treating physicians.

Jay: Lastly, we're pleased to announce that just today the American journal of Hematology published a manuscript highlighting data from the dose expansion phase of our ongoing phase <unk> study of subcutaneous <unk> as a single agent in adult patients with heavily pretreated relapsed refractory <unk> out of 27 evaluable patients treated we observe.

Jay: And 85% complete response rate with 75% where MRV negative.

Jay: Subcutaneous Blinatumomab was well tolerated with no observed great for cytokine release syndrome.

Jay: Turning to chart latter map a first in class DLL three targeting bite molecule.

Jay: Granted priority review following promising results from the phase II <unk> III <unk>, one clinical trial and a <unk> date of June 12 2024.

Jay: We are rapidly advancing <unk> into earlier lines of treatment, where we have initiated two phase III studies and plan to initiate a third in the first half of 2024.

Jay: <unk> to make a first in class steep one bi specific molecule being studied in metastatic castrate resistant prostate cancer continues to progress following the presentation of encouraging phase one data last fall.

Jay: We are ahead of schedule with the monotherapy dose expansion and expect complete enrollment in the coming weeks.

Jay: We've opened a reduced monitoring cohort and are making significant progress in dose range finding studies in combination with novel hormonal therapy combinations.

Jay: For AMG 193, an oral MTA cooperative PMT five inhibitor, we're encouraged by nine responses, we've seen across seven <unk> solid tumors.

Jay: <unk> hundred nine three is a terrific example of our medicine targeting a genetically defined synthetically reality in our first clinical translation of our induced proximity platform.

Jay: We're now swiftly moving forward with dose expansion studies and plan to enter mastered.

Jay: Master protocols and thoracic in gastrointestinal malignancies exploring combinations with standard of care in the first half of 2024.

Jay: In our inflammation portfolio, we continue to explore 10 spire in indications beyond severe asthma, including separate phase III studies in chronic rhinosinusitis with nasal polyps, where topline data are expected in the second half of 2024 as well as in eosinophilic esophagitis.

Jay: We also remain on track to present phase III COPD data in the first half of 2024.

Jay: Our rocket Phase III program for <unk>, a first in class anti F 40, monoclonal antibody has successfully enrolled over 2400 patients with moderate to severe atopic dermatitis.

Jay: We're introducing an eighth study to the rocket program to explore an auto injector.

Jay: We are planning to initiate both the phase III study in Perugia, non soliris and a phase II study in asthma. This year as we seek to broadly explore the potential of rockets in the map.

Jay: Lastly, we are encouraged by the advancements of our rare disease pipeline with several mid to late stage opportunities.

Jay: In December to peso received orphan drug designation in Japan, where we have also recently submitted a new drug application for <unk> in <unk> disease.

Jay: To serve additional patients in Japan, we have a phase III study underway in the setting of chronic disease with a low clinical activity score.

Jay: Beyond Japan, we are progressing to peg a subcutaneous administration to drive increased adoption and improve patient experience and plan to initiate a phase III study in thyroid eye disease. This year.

With a prisoner, we anticipate important phase III data readouts this year in myasthenia gravis and <unk> related disease.

Jay: Both diseases with significant unmet need and where we have the potential to make a real difference for patients.

Jay: <unk>, an innovative CD 40 ligand inhibitor fusion protein has entered phase III for Sjogren syndrome.

Jay: This follows encouraging phase II data with efficacy across patients with moderate to severe systemic disease and patients with high symptom burden.

<unk> is the first therapy to demonstrate efficacy in this latter patient population.

Jay: Closing out our rare disease efforts, we're excited about <unk> Alfa <unk>.

Jay: And El par one antagonist being studied in idiopathic pulmonary fibrosis.

Jay: On track for a phase II proof of concept data readouts in the second half of 2024.

Speaker Change: In closing I am delighted to report on the important progress we make advancing our innovative pipeline and I'm looking forward to sharing more pipeline milestones through 2024.

Speaker Change: I'll now turn it over to you Peter.

Peter: Thank you Jay we're pleased with our strong execution and performance in the fourth quarter and for the full year 2023 in the fourth quarter total revenue of $8 2 billion grew 20% year over year and non-GAAP EPS of $4 71 grew 15% year over year.

Peter: For the full year, we delivered total revenue of $28 2 billion, 7% growth year over year, and non-GAAP EPS of $18 65, 5% growth year over year as a reminder, both Q4 and the full year results include Horizons results beginning October six when the acquisition closed through our financial results will exclude approx.

Peter: <unk> one week of Horizon's result from our fourth quarter results.

Peter: I will review the details of our fourth quarter and full year financial results before discussing our outlook for 2020 for.

Peter: The financial results are shown on slide 54 to 56 of the slide deck, turning to our fourth quarters total revenue of $8 2 billion. We saw product sales increased 20% year over year, driven by volume growth of 23% offset by net selling price declined to 3%, excluding the impact of horizon product sales increased five.

Peter: 5% year over year, driven by volume growth of 9% all.

Peter: Full year total revenues of $28 2 billion grew 7% year over year product sales increased 9% year over year, driven by 15% volume growth other revenues decreased 16% year over year, primarily due to lower profit and cost sharing from our COVID-19 collaboration with Lilly in 2022.

Peter: Expense discipline resulted in a 50% non-GAAP operating margin as a percentage of product sales for the full year 2023.

Peter: While we continue to focus on both internal and external innovation investing $4 7 billion in our pipeline and $27 8 billion and our acquisition of horizon.

Peter: <unk> product sales volume growth at 23% in Q4, and 15% for the full year, we still efficiently manage the operating expenses of the business Q4, non-GAAP operating expenses, increasing 18% year over year, while full year non-GAAP operating expenses increased 9%.

Peter: Excluding the impact of Horizon, Q4, non-GAAP operating expenses increased 3% and full year non-GAAP operating expenses increased 5%.

Peter: On a non-GAAP basis Q4 cost of sales as a percentage of product sales was flat on a year over year basis of 16, 3%.

Peter: For the full year cost of sales as a percentage of product sales increased by one one percentage points to 17.0% full year increase was primarily driven by higher profit share and changes in our product mix.

Peter: Partially offset by the replacement of the Puerto Rico excise tax with an income tax beginning in 2023.

Peter: non-GAAP R&D spend in the fourth quarter increased 16% year over year, and 8% year over year for the full year, primarily due to higher spend on later stage clinical programs and marketed product support including spend on programs acquired from the horizon acquisition and continuing investment in our pipeline, including Mary Todd.

Peter: Q4, non-GAAP SG&A expenses increased 20% year over year, primarily driven by commercial and G&A expenses related to the horizon acquisition.

Peter: Full year non-GAAP SG&A expenses increased 5% year over year, primarily driven by commercial and G&A expenses related to the horizon acquisition, partially offset by a decline in other marketed products.

Peter: non-GAAP Alliant <unk> were about $635 million in expense in the fourth quarter of $168 million increase year over year, primarily driven by increased interest expense related to the debt issued for the horizon acquisition full year, non-GAAP <unk> was favorable $279 million year over year Prime.

Peter: Merrily driven by the change in accounting for the Beijing investment.

Peter: The fair value Mark to market method and by gains related to early debt retirement, partially offset by higher net interest expense.

Peter: Our non-GAAP tax rate increased two five percentage points year over year to 15, 9% in the fourth quarter and two seven percentage points year over year to 16, 5% for the full year, primarily due to the 2022, Puerto Rico tax law change mentioned previously.

Peter: The company generated $7 $4 billion of free cash flow in 2023, compared with $8 8 billion in 2022.

Peter: The decrease is driven by.

Peter: The horizon transaction and integration costs higher repatriation tax payments and higher capital expenditures, we expect to continue to generate strong cash flows with the addition of horizon and are on track with our deleveraging plans to return to more efficient capital structure by the end of 2025 and.

Peter: In summary, we continue to execute on our multiple capital allocation priorities.

Peter: First we continue to prioritize investments in both internal and external innovation.

Peter: Our increased spending in non-GAAP R&D of 8% and 23 over 'twenty two coupled with the acquisition of Horizon Therapeutics continues to broaden and strengthen our balanced portfolio across therapeutic areas.

Peter: With our strong late stage innovative pipeline moving forward through development, we expect our non-GAAP R&D to continue to increase in 2024.

Peter: Second we continue investing in our business for long term growth, including our state of the art manufacturing facilities in Ohio, and North Carolina.

Peter: Amgen, Ohio, our new advanced Assembly and final product packaging plant has just received licensure from the FDA for commercial production in January roughly two years. After we broke ground on our innovative drug substance plant under construction in North Carolina is expected to be operational by 2020. In addition, we position.

Peter: The organization to accelerate investments in innovation, including leveraging the power of generalists artificial intelligence and third we returned capital to shareholders through growing dividends, including $2 13 per share in the quarter. This represented a 10% increase over that pay nature of 2022 to four quarters.

Peter: Okay.

Peter: Turning to the outlook for the business for 2024 first because this is the first full year incorporating the impact of horizon, we're providing some additional granularity on our guidance, which we don't expect to repeat to the same extent in the future for.

Peter: For 2024, we're expecting revenue up $32 4 billion to $33 8 billion and non-GAAP earnings per share of $18 90 to $20 30.

Peter: As we continue to integrate horizon, we expect the acquisition to be accretive to non-GAAP EPS in 2024, and we're on track to meet the synergies target previously communicated of at least $500 million in pre tax pre tax cost by year three after closing or in 2026.

Peter: Our revenue range reflects our strong growth outlook driven by numerous opportunities across our core therapeutic area pillars, we will record a full year of legacy horizon product sales and we expect continued volume driven growth and our priority products for Panther is higher of entity or <unk>.

Peter: System with industry trends and our recent history, we expect mid single digit price decline for our portfolio in 2024.

Peter: As a reminder, as you model the first quarter of 2024 and consistent with our historic trends, we expect first quarter product sales to be the lowest quarter as a percentage of the full year due to the benefit plan changes insurance re verifications and increased co pay charges.

Peter: So we expect the first quarter of 2020 for total revenue to grow roughly 20% year over year.

Peter: For the full year, we expect other revenue to be in the range of approximately one three to $1 4 billion.

Peter: And we continue to efficiently run the business through our disciplined approach to managing operating expenses in 2024, we're making incremental R&D investments to support our promising late stage pipeline, including our rapidly advancing oncology programs as discussed following ESMO in October and other programs, including maritime.

Peter: Furthermore, The addition of Horizon has an impact on the 2024 operating margin given the given the timing of linked synergies are realized.

Peter: As a result, we project the full year non-GAAP operating margin as a percentage of product sales to be roughly 48%.

Peter: Note that we expect non-GAAP operating margin growth to accelerate in each of the quarters. Following the first quarter.

Peter: There are primarily three reasons for this first typical lower product sales in Q1, as I mentioned above and in each of the following quarters.

Peter: Increased spend on our commercial brands, we'll continue building on the investments we made in the second half of 2023, including our path of old Tesla in our loan portfolio or entity and Prolia.

Peter: And third Q1 2024 reflects the addition of horizon for which we are just at the beginning stages of realizing synergies given the acquisition close date of October six.

Peter: We expect non-GAAP operating margin to be roughly 43% in the first quarter.

Peter: I would reiterate that we expect operating margin growth to accelerate in each of the quarters. Following the first quarter.

Peter: Project non-GAAP cost of sales to be in the range of 17% to 18% as a percentage of product sales for the 2024 year taking into account the full year horizon related expenses, we expect non-GAAP R&D expenses in 2024 to increase approximately 20% year over year with investments also increasing to advanced key pipeline.

Peter: Asset, including AMG 193, maritime broker <unk> entire that amount.

Peter: We see significant potential in our innovative pipeline and it is important that we strategically invest now to fully unlock the opportunities ahead and create long term value for patient SaaS and shareholders.

Peter: And for non-GAAP SG&A spend we.

Peter: We expect 2020 for full year amount as a percentage of product sales to be between 21 and 22%.

Peter: We anticipate non-GAAP <unk> to be in the range of 262 7 billion as mentioned on our Q3 23 call 24 guidance includes the interest expense related to the $28 billion of debt rates for the horizon acquisition.

Peter: We expect a non-GAAP tax rate of 16% to 17% our guidance our guidance is primarily being driven by two factors. The first is the jurisdictional mix of income, including the full year benefits associated with the horizon transaction and the legal entity rationalization undertaken in the fourth quarter of 2023 and part to integrate them.

Peter: Horizon entities into our existing U.

Peter: U S headquartered legal entity structure.

Peter: Is the benefit from our planned payment to the IRS as an advanced deposits as we've done in the past to stop the accrual of interest on uncertain tax positions.

Peter: There is no change in our belief in the merits of our legal arguments with the IRS as we prepare for trial given the interest rate environment, although the deposit negatively affects our cash flow in 'twenty four if any of the deposit is returned to us on the resolution of our litigation those funds would accrue interest income therefore, the radar arbitrage makes.

Peter: This payment a prudent use of our capital once again out of an abundance of clarity. This represents no change in our belief in the merits of the tax court case.

Peter: The guidance also includes the impact of the adoption of the OECD, 15% minimum tax by certain jurisdictions based on our individual footprint. We don't anticipate any significant effects of the new rules in 2024, while we are closely watching the global tax landscape for future impacts as the framework continues to be considered by additional jurisdictions.

Peter: Actions and new rules take effect, we expect governments around the world, including the United States to continue to look for more sources of tax revenue from large multinational corporations that could result in higher taxes in the coming years.

Peter: Similar to 2023, we expect share repurchases not exceed $500 million in 2024, we expect that we will continue to increase our dividend. We expect capital expenditures of approximately $1 1 billion in 2024, consistent with our capital allocation priority to invest in our business, including the Ohio and North Carolina.

Peter: Facilities, I mentioned ahead and into the rare disease pillar.

Peter: In summary, we delivered another strong year of financial results in 2023, our confidence in the long term growth of Amgen is strong and we believe that our new rare disease pillar one of our four pillars will be an important additive source of growth for the company. This concludes the financial update my Thanks, My approximately <unk>.

Peter: 7000, plus colleagues at Amgen around the world for their commitment to our mission of serving patients and their tireless efforts in 2023.

Peter: Turn it back to Bob for Q&A.

Bob: Okay. Thank you.

Bob: On the line and we will take questions from our callers Julianne why don't you remind them of the procedures. So we can get through these questions here efficiently for everyone.

Thank you. Thank you I would like to ask a question. Please press star followed by one on your telephone keypad.

Julianne: If for any reason you would like to remove that question. Please press star followed by one again to ask a question press Star one.

Julianne: Our first question comes from Michael Yee from Jefferies. Please go ahead. Your line is open.

Speaker Change: Hey, guys. Good afternoon, and thanks for good results and good guidance.

Michael J. Yee: We have a question on <unk>.

Michael J. Yee: On 133 of course, you had the publication yesterday I feel like it was the most scrutinized page one publication, but maybe you could just talk to maybe Jay can talk to your interpretation of some of the markers for example, lipids <unk> blood pressure and all that kind of thing and maybe talk about your confidence level about the profile of it.

Speaker Change: Versus competitors. Thank you so much.

Jay: Yes, Thanks, a lot Michael we really appreciate the consideration in the phase one papers receiving from the community.

Jay: It's exciting to report these data for those who haven't seen it. This was a randomized double blind placebo controlled study 49 patients looking at safety PK PD.

Jay: Single ascending dose seven cohorts multiple ascending dose three cohorts three monthly doses.

Jay: Patients with obesity BMI greater than 30%.

Jay: And where we.

Jay: We were quite pleased with the outcome and looking at the 420 milligram dose as an example, which was the highest dose studied 14, 5% weight loss. It only day 85.

Jay: Moreover, quite durable coming off of that medicine out to 150 days, all with relatively mild gastrointestinal side effects and so to answer your last question first.

Jay: We find the phase one data, which we're pleased to share with the community to be quite supportive of our ongoing work to develop this medicine to the greatest possible benefit of patients suffering from obesity and <unk>.

Ask questions around some of the measurements on this study lipid blood pressure in <unk> and I would just caution that this is a phase one trial that numbers are very small that the duration of treatment is rather short, but even with all of those caveat.

Jay: While hard to draw conclusions from such such small numbers.

Jay: Especially labor all measurements like blood pressure and lipids.

Jay: All are directionally favorable.

Jay: So we have we take no concern whatsoever from those measurements on this study.

Speaker Change: Okay. Thank you Mike have discretion.

Speaker Change: Thank you Michael our next question comes from <unk> Richter from Goldman Sachs. Please go ahead. Your line is open.

Salveen Richter: Good afternoon. Thanks for taking my question. Another one here on the obesity program. So post the published phase one data how are you thinking about differentiation on Gi Tolerability is the dose range being evaluated in the phase two study similar to that in the peso and the thank you.

Speaker Change: Yes. Thanks for the question I'll take this one as well.

Speaker Change: As you may or May not know the phase two study, which is ongoing at present and going very well.

Speaker Change: Floors 11 dosing cohorts with.

Speaker Change: Relevant placebo controls and through that study, we will have a chance to gaining experience with a longer exposure to maritime.

Speaker Change: <unk> in different ways. We've recently added a part two to this study that will allow us to explore even more durable weight loss beyond 52 weeks.

Speaker Change: Enabled by just very rapid enrollment and these four dosing cohorts will go on to test dose level in an.

Speaker Change: And even less frequent dosing schedules of <unk> monthly.

Speaker Change: And so.

Speaker Change: These phase two data.

Speaker Change: Even by end of year will be strongly instructive as to finding a safe and tolerated and efficacious dose to carry into phase III clinical investigation.

Speaker Change: Yes, the only thing I would add is we're starting from a basis of a monthly dosing.

Speaker Change: Cadence and schedule and so the additional dosing cohorts would look at potential.

Speaker Change: Dosing schedule beyond monthly and the data are pretty clear in the market right now.

Speaker Change: Gi toxicity or Gi side effects are generally related to the day of dosing of the <unk> ones, which are dose weekly.

We see some of that same Gi side effect profile in kind of the first dose of the dose titration, but there is an opportunity here to potentially spread the dosing intervals out further and further improve tolerability and are in our program and as Jay clearly described we've got.

Speaker Change: All of the different aspects of that being studied in the phase III program.

Jay: Thanks, Julian well go to next question.

Jay: Thank you. Our next question comes from Jay Olson from Oppenheimer. Please go ahead. Your line is open.

Jay: Okay.

Jay Olson: Oh, Hey, thank you so much for taking my question and congrats on the progress another question on 133.

Jay Olson: Talk about whether or not that we.

Jay Olson: Later this year will.

Jay Olson: We will include patients from two of the study.

Jay Olson: Do you think it's possible that <unk> could be <unk>.

Jay Olson: Two or three months and also if you could just comment on the rollover rate of patients from part one.

Jay Olson: Sure.

Speaker Change: Sure. It could you could you catch all that some of what J S was broken out the third part was a little bit broken up with your question I heard a better explanation of part to frequency of dosing and then I did not hear your third party.

Speaker Change: Five months, if you could just.

Speaker Change: I meant on the rate of patients rolling over.

Speaker Change: Part one part two thanks, Okay. Yes. Thank you for the question Jay Let me give a little bit of context on this part two study that I think will help answer them.

Speaker Change: In part to the intent is to really look at durable weight loss beyond 52 weeks.

Speaker Change: And so by durable weight loss patients eligible for part two which begins at the end of 52 weeks will be.

Speaker Change: Responding to this medicine, and then there'll be re randomized two four cohorts that will test dose level and again this even less frequent dosing schedule.

Speaker Change: We have not disclosed the granularity on the dosing schedule. This is a competitive environment.

Speaker Change: But we are afforded this chance because the ADC the antibody.

Speaker Change: Core of maritime like so many immunoglobulin therapeutics.

Speaker Change: <unk> for the opportunity to use it much less frequently.

Speaker Change: The rate of patients rolling over to part two will be established as the.

Speaker Change: <unk> Phase II study continues to progress this year.

Speaker Change: Okay.

Speaker Change: Alright, Thank you Julien on our next question.

Speaker Change: Our next question comes from Chris Schott from J P. Morgan. Please go ahead. Your line is open.

Chris Schott: Great. Thanks, very much just maybe to pivot over to pass up for a question can you just talk a little bit about the dynamics for 2024. It seems like the products come back to growth, but I'm just trying to get a sense of now that Amgen owns the asset and has more time with it what are your top priorities and how do you think about continuing to kind of grow the new patient base here.

Speaker Change: Thank you sure crisp, who will take US a couple of parts, but vikram gosh hearing your thoughts first.

Vikram: Yes. Thank you for the question.

Vikram: If you focus a little bit on what are the underlying factors that are driving.

Vikram: The growth we saw a record number of unique prescribers.

Vikram: We saw an increase in patient enrollment forms and patient starts.

Vikram: In addition, we've made pretty significant progress on payer coverage as we've as we've seen.

Vikram: Our covered lives have not increased to greater than 50% of U S covered lives and thats important educating some of those stakeholders on the new clinical data updated indication. It continues to drive uptake across the full spectrum up to 80 patients and finally, what holds all of this together it is a really robust patient service.

Vikram: Model.

Vikram: <unk> supports patient access I think we continue to make progress and execute towards each one of these important leading indicators and we shouldnt forget that.

Vikram: Still low penetration of the roughly 300000 patients that can be eligible for this medicine in the U S alone.

Vikram: No.

Vikram: One one last.

Vikram: The point here is that as we've noted before there continues to be a time lag between the execution of all of these efforts and the realization of increased patient numbers as we've said before can take up to 90 days.

Vikram: Once a patient is identified for therapy for that patient to actually get on therapy, but we're pretty happy with with all of our leading indicators and the execution that we have seen coming out of last year.

Speaker Change: Chris The only thing I would add is building on what Vikram said in his prepared remarks, we're excited about the international opportunity as well.

Speaker Change: Can you characterize that.

Speaker Change: Well previously.

Speaker Change: And we're also excited about what we see as ongoing opportunities to invest in innovation for the benefit of <unk>.

Speaker Change: <unk> patients so all in all feel.

Speaker Change: I'm excited about the rare disease pillar that we've established and the role that the peso play in them.

Julien: Our next question Julien.

Julien: Thank you Chris Our next question comes from Evan <unk> from BMO Capital markets. Please go ahead. Your line is open.

Evan: Hi, guys. Thank you so much for taking my question I wanted to touch on test spire, specifically in COPD.

Evan: How are you planning to differentiate given pretty competitive data, we saw from <unk> and how should investors be looking at the data from an efficacy bar are there nuances in this trial that need to be clarified that might make it harder to do an apples to apples comparison.

Speaker Change: Yes, and thanks for the question Murdo why don't I start and then you add on.

Speaker Change: So it's a great and timely question.

Speaker Change: The phase III COPD study of test fire, we expect data in the first half of this year.

Speaker Change: This was a big study 337 patients moderate severe to severe COPD.

Murdo: They're having an exacerbation despite being on triple therapy, and so reflective of the current unmet need and inadequacy of therapy for patients with COPD.

Murdo: This is a slightly broader population than dupee that we're studying here we're totally on track for the readout, we quite like the mechanism here.

Murdo: You must know that.

Murdo: Slipped works.

Murdo: As a signaling factor upstream and by blocking it with our unique.

Murdo: Biotherapeutic, we block cheese slip IL 25, IL 33 signaling T. Slippage. So many cell types modulating. This airway type two response by.

Murdo: By hitting T. Slim upstream, we think we can really have an impact on the disease biology, we see T slip elevated serum of patient and bronchial me Koza and Bronchoalveolar lavage fluid it.

Murdo: It is released by airway epithelium, there's just a lot of signals from the basic biology of this disease pointing to a medicine of this nature and by looking at the broader population than they did with <unk>, we have a chance to really figure out who the responder. It's murdo I think you've covered all the bases I would just add this even with the unique.

Murdo: A differentiated mechanism as Jay described we hope we can treat a broader population of patients and perhaps the currently available therapies and we also recognize that there are patients who are refractory to those currently available therapies and we would obviously want to understand if they would be responders to test.

Murdo: Tests buyer I think we've got strong commercial capabilities.

Including with our partners at Astrazeneca and are well positioned to take a product like this into the market. If we're successful in phase III.

Speaker Change: Great Alright, Thank you Julian next question.

Speaker Change: Thank you Evan our next question comes from Omar <unk> from Evercore ISI. Please go ahead. Your line is open.

Omar: Hi, guys. Thanks for taking my question I wanted to touch up on AMG 133, as well two part question first on the discontinuation is at the high dose we know about our <unk> did not finish the full duration of the study, but there was a second.

Omar: Arm also of this high dose 420 milligram with 10 patients, which was not reported this was the one with digital tools could you speak to the discontinuation rate and that arm. There was a 420 done separately, which is not part of the paper and secondly, I know this is a case of liver enzyme elevation of the 280 Meg dose, but this patient also had COVID-19 could you perhaps speak to the.

Omar: Timing of liver enzyme elevation relative to the Covid episode, Thank you very much.

Speaker Change: Yes, thanks tumor I won't be able to provide patient level insights to phase one study at this time, but I do appreciate your question.

Speaker Change: Your interest in the report.

Speaker Change: Speaks to drop out of the phase one at the 420 milligram dose, which was four out of the eight patients.

Speaker Change: First it's notable to say that the high dose.

Speaker Change: Cohort and the multiple ascending dose receiving the three doses of <unk> experienced.

Speaker Change: Will weight loss real benefit of 14, 5%. After these three monthly doses. This was the group that prove actually quite durable out to day 150.

Four subjects declined to participate in this clinical study setting largely logistical reasons, the aes and other characteristics were comparable to all the other patients in the study.

Speaker Change: Now the second question around the digital group I don't have insight into the phase III.

Speaker Change: No I mean, we can get back to you on that I don't know that we reported that those data and the discontinuation rate.

Speaker Change: Alright.

Speaker Change: Julien. So then the next question.

Speaker Change: Thank you Omar our next question comes from Colin Bristow from UBS. Please go ahead. Your line is open.

Geoff Meacham: Good afternoon, and thanks for taking the questions.

Geoff Meacham: Moral maritime.

Geoff Meacham: First could you provide some insight into the dosing I mean, obviously these are pretty large doses if we look at.

Geoff Meacham: Passive for 20 milligrams takes over five minutes by infusion or three consecutive injections I was wondering if you've given the insight.

Geoff Meacham: And then in terms of the relative affinity for.

Geoff Meacham: Monotype team.

Geoff Meacham: Preferentially favor much more than competitor molecules.

Geoff Meacham: I think the ultimate clinical profile it more closely resemble that of a long acting <unk> one versus compared to the clips.

Speaker Change: Yes, Thanks, Colin appreciate the deep consideration of the molecule, especially.

Speaker Change: I'd start by saying I don't regard these doses as high on new here.

Speaker Change: 420 milligrams for our biotherapeutic Thats, an antibody drug conjugate with a peptide antibody ratio two one seems well in scope for modern biotherapeutic products.

Speaker Change: I don't need to tell this community paying so close such close attention to Amgen that this is a very sophisticated biotherapeutics organization and on the manufacturing side. Just every patient every time and we have all the capabilities necessary to deliver this medicine that whichever of these three or other dose and schedule.

Speaker Change: We arrived at.

Speaker Change: So no concerns there for me whatsoever.

Speaker Change: Regarding the balance of the pharmacology.

Speaker Change: You do invoke a difference between our medicine and medicines developed by peer pharmaceutical companies, namely Mechanistically the core antibody of maritime inhibits.

Speaker Change: The gift receptor, whereas these other peptide medicines agonize it we feel very secure and our choice to inhibit that receptor supported by just the finest level of experimental data available experiments of nature.

Speaker Change: That genome wide Association studies in very large populations have pointed to a need and opportunity to inhibit the gift receptor to deliver lower BMI as observed with variance and that receptor in downstream signaling pathways that correlate with reduced body mass index in large populations.

Speaker Change: As to the balance, which you asked between inhibition of gift receptor agonism of <unk> one.

Speaker Change: These are very difficult measurements to make in humans, but our modeling suggests that with the therapeutic doses and exposures that we observe that we are achieving both.

Speaker Change: And Colin this murdo I would just add that from a patient experience perspective.

Speaker Change: We've learned a lot from other biologics and Amgen has a world class.

Speaker Change: Process development manufacturing and device team and we've done a lot of work on this one and we anticipate very positive and simple patient experience.

Speaker Change: On at least a monthly dosing schedule.

Speaker Change: And we've learned a lot from <unk>, specifically and there is more to follow on <unk> from that but we continue to work to improve patient experience with with our biologic injectables.

Speaker Change: So as we go to the next question, let me observe there are almost up to the hour that we actually will sell side because I know, we still have quite a few questions in the queue. So I'm trying to get one question per caller here and get through will stay.

Speaker Change: The Q calls or questions rather.

Speaker Change: Still waiting for us.

Speaker Change: Some of you might have to drop so, let's let's move forward Joseph Yes. Julian next question. Please.

Julian: Thank you Colin our next question comes from year round Weber from TD Cowen. Please go ahead. Your line is open.

Julian: Alright, great. Thanks. This is brendan on for Ron Thanks for taking my question just a quick one from us actually.

Julian: Okay. So my data you've seen so far and maybe some feedback from physicians that you heard.

Julian: This is all in place now.

Brendan: Where do you kind of see a pleasant fitting into many GE treatment paradigm, given all the competition there, but maybe more to the point, how youre thinking about expansion.

Brendan: Expansion opportunities given all the different auto immune indications you might.

Brendan: Just trying to understand the longer term growth.

Brendan: First why don't we ask Vikram just to address the performance of the product right now in <unk> and then a combination of JM, Dave can talk about the other.

Brendan: Activities or other potential applications.

Brendan: Applications.

Yes, thanks for the question.

Vikram: This is actually growing quite nicely and quite fun and <unk>.

As you know it is the it is now the fastest growing biologic in animals.

Vikram: We continue to execute across a variety of fronts, I mean, where we see this product nicely positioned versus.

Vikram: As it's appropriate for <unk>.

Most of the patients.

Vikram: And within the within the competitive environment that we operate in and we've continued to make significant progress over the last 18 months or so maybe even longer of continuing to drive more growth with newer prescribers.

Vikram: And even a desk with existing prescribers so.

Vikram: Product producer do well and I think we.

Vikram: We hope to continue to deliver good execution on this medicine in animals.

Vikram: Jay you want to talk about the second question, Yes, no I'm happy to.

Jay Olson: As you know.

Jay Olson: Meanwhile, the hematologists setting CD, 19% terrific target is expressed really on all b cells and stairs plasma cells and therefore.

Jay Olson: Considering indication expansion as you've asked there's a large number of diseases that could potentially be approached with a prisoner to the real benefit of patients with unmet need far beyond the application of.

Jay Olson: The prevailing CD 20 that target just a subset of b cells is it not loss on our team and we're working through indication expansion priorities.

Jay Olson: Presently alright.

Jay Olson: Alright.

Speaker Change: Let's go to the next question.

Speaker Change: Thank you. Our next question comes from Mohit Bansal from Wells Fargo. Please go ahead. Your line is open.

Mohit Bansal: Great. Thank you very much for taking my question I have a question regarding the subcutaneous delivery of the beds that you do have plan to initiate a phase three study can you talk a little bit about.

Mohit Bansal: Which technology, you're using is just at the peak.

Mohit Bansal: Interesting.

Mohit Bansal: That technology or are you using some of the guys from this envelope. Thank you.

Speaker Change: I'm, sorry, I had trouble understanding the question. So my question is what technology, we are using for the subcutaneous injectable form.

Yes, Hey.

Speaker Change: Ill jump in we're not commenting at this point on the provider. We're just said that we're going forward with the sub Q.

Speaker Change: Great. Okay, Julien I'll go to the next question.

Julien: Our next question comes from Geoff Meacham from Bank of America. Please go ahead. Your line is open.

Geoff Meacham: Hey, guys. Thanks for the question another one on about $1 33.

Geoff Meacham: When you think about the phase III program I just wanted to know what sort of informs the next indications youre going to go after.

Geoff Meacham: That need is it the potential for differentiation on 133, and the timing of that do you think that youll you'd want to have the phase II data in hand or is this something that you could rollout sort of at risk. Thank you.

Speaker Change: Yes. Thanks for the question, Jeff really appreciate it as you know obesity is a major public health crisis, maybe 40% of Americans with a BMI over 30 massively costly so huge burden to the.

Speaker Change: But to the global <unk>.

Speaker Change: Third party payers and societies.

Speaker Change: The obesity related disease list is quite long and expanding from cardiovascular disease and heart failure type two diabetes obstructive sleep apnea.

Speaker Change: Nash NFL the kidney.

Speaker Change: Kidney disease.

Speaker Change: These are chronic conditions that really demand medicine that can deliver durable.

Speaker Change: And chronic weight loss and so we think we have a really strong offering for these.

Speaker Change: Obesity related diseases rising in our phase II program as you know.

Speaker Change: And obesity is a strong genetic component and we locked down to <unk> inhibition.

Speaker Change: Based on genetic insights.

Speaker Change: So the opportunity space is quite large you asked the question what indications and perhaps even in what sequence and when we have all the requisite data will remark in due course, but we intend all indications where this dual mechanism.

Speaker Change: Improved public health.

Speaker Change: And we are actively planning and on track for an expansive phase III program and in terms of the day, if you want to add to.

Speaker Change: Regulatory fees.

Speaker Change: Yes, I think Jeff This is Dave <unk> I would just add that.

Dave: We're planning a very expansive phase III program. So you can expect to see multiple indications move forward in parallel.

Dave: As Jay indicated as we start to see data, we will begin launching those trials and we will discuss them and then in addition.

Dave: As Youre aware regulatory authorities around the world require a certain body of safety data before phase III launches.

And so of course, we will be compliant with that but our goal is to launch phase III as quickly as possible. Once we have the requisite dataset and regulatory approval.

Julian will go to next question. Please.

Julian: Thank you Jeff. Our next question comes from David Risinger from Leerink Partners. Please go ahead. Your line is open.

David Risinger: Yes, thanks, very much so I have another question on AMG 130 employees could.

David Risinger: You have some more color on.

David Risinger: Your expectations for the impacts on blood pressure and lipids in phase two.

David Risinger: Specifically, whether you anticipate towards appetite like efficacy on those metrics.

Speaker Change: Thanks very much.

Speaker Change: Yes, Thanks, David I mean, we're making all of these measurements and I'm not going to try to forecast the outcome.

Speaker Change: Of that pharmacology at this time as.

Speaker Change: As you've seen in our phase one program, the medicines very well tolerated delivering durable weight loss and benefit without significant excursion of some of those measurements I just think it's.

Speaker Change: Too early to try to answer your question, we will have all that data at the end of.

Speaker Change: The first part of phase two.

Towards the end of this calendar year and the best Extrapolation that you can have is from the preclinical data that were just published that urge you to take a look at that.

Speaker Change: Okay.

Speaker Change: Hey, Julien I'll go to the next question. Please.

Thank you David Our next question comes from Michael Schmidt from Guggenheim Securities. Please go ahead. Your line is open.

Speaker Change: Okay.

Michael J. Yee: For Michael Thanks for taking our questions. So quick one on that.

Michael J. Yee: <unk> will be the Mac.

Michael J. Yee: Can you talk about your plan of data disclosure this year in your current thinking on the potential registration path. How do you think about the positioning of this agent relative to some of the other margin agents based on different mechanism, such as EDC or <unk> prostate cancer. Thank you.

Speaker Change: Yes. Thanks for this outstanding question Michael.

And.

Speaker Change: Zeller endemic is.

Speaker Change: A very interesting and exciting molecule for those on the call. This is a steep one CD three by specific.

Speaker Change: We have been studying this in advanced castrate resistant.

Speaker Change: State cancer.

Speaker Change: We have.

Speaker Change: Expanded cohort in the phase one monotherapy.

Speaker Change: Opening to reduce monitoring as well as as you invoke the <unk>.

Speaker Change: Existing and novel androgen receptor modulators integrators, we're exploring combinations with novel agents in that domain as well.

Speaker Change: Priorities for the program right now are to establish reduce monitoring this will be important to reach just all the patients who can benefit.

Speaker Change: We're looking at the feasibility of reduced monitoring we have great experience with these T cell engaging bi specifics as well as the possibility of outpatient therapy.

Speaker Change: The.

Speaker Change: Approach to the regulatory path will present in due course.

Speaker Change: There'll be no surprises there.

Speaker Change: Our path to bring medicines to patients with castrate resistant prostate cancer alone and ultimately in combination has is well worn thankfully and we know how to deliver there.

Speaker Change: You asked about differentiation of other medicines. These are often apples to oranges comparisons.

Speaker Change: <unk> looked at that of course, and we really like the offering of Delaware to make the patients treated in our study had quite advanced disease, even more advanced disease than.

The demographics of the patients as reported on.

Speaker Change: Other mechanism medicines, such as radio ligand therapies and the response rates, we're seeing are really cleaning the clinically meaningful to patients and that gives us great encouragement to develop a medicine more ambitiously in the next few years.

Speaker Change: In terms of the data sharing.

Speaker Change: Sure.

Speaker Change: Data availability as Jay mentioned, we are nearly complete in terms of dose expansion enrollment so as those data roll forward over the course of the year, we will provide guidance as to when we might have the next look at that data, but that's probably the next meaningful set of data we will get to look at either later this year or early into next year.

Speaker Change: Hey, Julien I'll go to the next question. Please.

Julien: Thank you Michael Our next question comes from Tim Anderson from Wolfe Research. Please go ahead. Your line is open.

Timothy Minton Anderson: Thank you very much so Eli Lilly today made a couple of sets of comments about.

Timothy Minton Anderson: This topic of JP agonism versus antagonism and they also weighed in on the data you published yesterday and I am wondering and as much as you heard that or read those comments is there any context to add or anything thats factually incorrect or anything to refute.

Timothy Minton Anderson: The covered quite a few points.

Timothy Minton Anderson: They continue to express their view, which was agonism is the best way not antagonism.

Timothy Minton Anderson: Hey, Tim This is Jay it open it up to anyone else who wants to contribute to this.

Jay Olson: Uh huh.

Jay Olson: I don't I don't believe it.

Speaker Change: Yes, they are engaging in a dialogue around this has as much to the.

To the narrative, rather I would say that the.

The argument.

Speaker Change: Sure.

Speaker Change: Kipp receptor antagonism comes from just the highest level of scientific data the human experience across populations with.

Speaker Change: 1 million patient studied.

Among among those who have variation.

Speaker Change: In the genes associated with this pathway, where that variation is directionally inhibitory the BMI is lower.

Speaker Change: And so we're hoping to replicate that pharmacology with this medicine.

Speaker Change: We feel great about the offering in this domain.

Speaker Change: Okay <unk> next question please.

Speaker Change: Thank you Tim Our next question comes from Robyn <unk> from <unk> Securities. Please go ahead. Your line is open.

Speaker Change: Hi, good evening. Thanks, so much for taking my question. This is Nicole on for Robyn.

Nicole: On camera.

Speaker Change: Getting all key seven.

Speaker Change: Can you talk about your level of confidence.

Speaker Change: Sorry about that.

Speaker Change: Thank you Paul and near term.

Speaker Change: Thank you.

Paul: Sure Jamie.

Jamie: Well, it's very early days with this medicine, there is strong preclinical support from the published literature and our.

Jamie: Our own preclinical work.

Jamie: It's nicely for patients a very competitive landscape, but this is.

Jamie: The earliest phases of clinical investigation and so we're going to approach this with total equipoise and bring the medicine to the patients that stand to benefit the best based on the biology underlying yes.

Jamie: The target as you mentioned is one that helps control some of the central signaling that drives some of the autoimmune diseases.

Jamie: That are being investigated here at.

Jamie: At this point I think.

Jamie: All efforts towards generating clinical data.

Speaker Change: Okay. Julian next question please.

Thank you Nichol. Our next question comes from James Shannon from Deutsche Bank. Please go ahead. Your line is open.

Hey, Thanks for taking the question I have one for Jan I, just kind of want to piggyback on what Tim was alluding to.

Geoff Meacham: JP antagonism horse agonism I'm looking at the nature paper it looks like 130 threes portal for 20 milligram dose had a slight blip in triglyceride that eventually fades.

Jan: It does seem like antagonism is behaving a little differently from the literature for agonism.

Jan: Is it too early to chalk it up to antagonism burst of Agonism. Your view just wanted to get your thoughts there.

Jan: And the short answer is it's too early to chalk it up to antagonism versus agonism, as I said before and I meant it.

Jan: These lipids are labile and indirect biomarker of this pharmacology. This is an early stage study that had one or three monthly doses of the medicine.

Jan: And so we are not reading anything into the lipids.

Jan: Conclusively from this trial, we are making all these measurements in the active phase II.

Speaker Change: Great and I think we have time for one more Julien.

Julien: Thank you James our last question will come from Carter Gould from Barclays. Please go ahead. Your line is open.

Carter Gould: Good evening, Thanks for taking the questions. Maybe just one on 786 can you walk through exactly what's sort of driving maybe let me take a step back maybe first if you could outline sort of how you are setting expectations, there and any color on what's driving the delay there. It seems like it's taking a long time to enroll 72 patients. Thank you.

Speaker Change: Sure no. Thank you for your question.

Speaker Change: For the broader group AMG 786 is an oral medicine being developed for obesity.

Speaker Change: Is not an increase that we have not as yet disclose the target or pathway.

Speaker Change: This study is progressing fine the readout of the phase one is on track for the first half of 2024.

Speaker Change: We've completed initial dose escalation cohorts and we're just collecting and analyzing data I'm expecting the readout.

Speaker Change: In the first half of this year great.

Speaker Change: Julien, we're going to turn it back to Bob for some closing remarks, okay. Thank you all for joining the call.

Bob: As you've heard we're excited about the opportunities that we see for growing our business.

Bob: Across all four of our pillars general medicine oncology inflammation in rare disease.

Bob: Last October we shared an in depth look at oncology in connection with the ESMO Medical meeting and we'll plan to do an introductory review of rare diseases.

Bob: Our rare disease pillar in late February to give you more information about the medicines that we already have on the market as well as some of those that are advancing through our pipelines. So we're encouraged by the questions that we've heard on this call about.

Bob: Those molecules.

Bob: We're excited about them and their prospects. So we will host a call, which <unk> will share with you here over the next few days and look forward to having that opportunity in the meantime, again. Thank you for your support and we'll look forward to talking to you that they are rare disease day or at our first quarter results call. Thank you.

Speaker Change: This concludes our 2023 Q4 earnings call you may now disconnect.

Speaker Change: [music].

Speaker Change: Yes.

Speaker Change: Oh.

Speaker Change: [music].

Sure.

Speaker Change: [music].

Speaker Change: Yeah.

Speaker Change: [music].

Speaker Change: Yes.

Speaker Change: [music].

Operator: Justin Claeys, Vice President of Investor Relations. Mr. Claeys, you may now begin.

Operator: Justin Claeys, Vice President of Investor Relations. Mr. Claeys, you may now begin.

Operator: --Justin Claeys , Vice President of Investor Relations. Mr. Claeys, you may now begin.

Justin Claeys: Thank you, Justin. Good afternoon, and welcome to our fourth quarter 2023 earnings call.

Justin Claeys: Thank you, Justin. Good afternoon, and welcome to our fourth quarter 2023 earnings call.

Justin Claeys: Thank you Julien. Good afternoon and welcome to our fourth quarter 2023 earnings call. Bob Bradway will lead the call and be followed by a broader review of our performance by Murdo Gordon, Vikram Carmony, Jay Bradner who I'm pleased to welcome and is joining us for the first time on our quarterly earnings call and Peter Griffith. Dave Reese will also be available during the Q&A session.

Peter Griffith: Bob Bradway will lead the call and be followed by a broader review of.

Bob Bradway will lead the call and be followed by a broader review of.

Speaker Change: Bob Bradway will lead the call and be followed by a broader review of our performance by Murdo Gordon Vikram Carmony, Jay Bradner I'm pleased to welcome and is joining us for the first time on our quarterly earnings call and Peter Griffith. Dave Reese will also be available during the Q&A session.

Justin Claeys: Our performance by Murdo Gordon, Vikram Karnani, Jay Bradner, who I'm pleased to welcome and is joining us for the first time on our quarterly earnings call and.

Our performance by Murdo Gordon, Vikram Karnani, Jay Bradner, who I'm pleased to welcome and is joining us for the first time on our quarterly earnings call and.

Peter Griffith: Peter Griffith, Dave Reese will also be.

Peter Griffith, Dave Reese will also be.

Justin Claeys: Available during the Q&A session. Given the timing of the Horizon Therapeutics acquisition close, the results as shown in our press release and slides include contribution from the Horizon business from 6 October onwards.

Available during the Q&A session. Given the timing of the Horizon Therapeutics acquisition close, the results as shown in our press release and slides include contribution from the Horizon business from 6 October onwards.

Dave Reese will also be available during the Q&A session.

Speaker Change: Given the timing of the Horizon Therapeutics acquisition close, the results as shown in our press release and slides include contribution from the Horizon business from October six onwards. For the avoidance of doubt, this will also be the basis for our filed financial results. To supplement this information, Vikram will also provide sales information for these products for the full fourth quarter, including the first week of October as further context in his remarks.

Peter Griffith: For the avoidance of doubt, this will.

For the avoidance of doubt, this will.

Justin Claeys: Also be the basis for our filed financial results. To supplement this information, BCRAM will also provide sales information for these products for the full fourth quarter, including the first week of October. As further context in his remarks through.

Also be the basis for our filed financial results. To supplement this information, BCRAM will also provide sales information for these products for the full fourth quarter, including the first week of October. As further context in his remarks through.

Speaker Change: For the avoidance of doubt this will also be the basis for our filed financial results to.

Speaker Change: To supplement this information Vikram will also provide sales information for these products for the full fourth quarter, including the first week of October as further context in his remarks.

Peter Griffith: The course of our discussion today, we'll.

The course of our discussion today, we'll.

Justin Claeys: We use non-GAAP financial measures to describe our performance and have provided appropriate reconciliations within the materials that accompany this call. We will also make some forward-looking statements, which are qualified by our safe harbor statement, and please note that actual results can vary materially.

We use non-GAAP financial measures to describe our performance and have provided appropriate reconciliations within the materials that accompany this call. We will also make some forward-looking statements, which are qualified by our safe harbor statement, and please note that actual results can vary materially.

Speaker Change: Through the course of our discussion today, we will use non-GAAP financial measures to describe our performance and have provided appropriate reconciliations within the materials that accompany this call. We will also make some forward-looking statements, which are qualified by our Safe Harbor statement. And please note that actual results can vary materially. With that, over to you Bob. 

Peter Griffith: With that, over to you Bob.

With that, over to you Bob.

Robert Bradway: Okay, thank you Justin, and let me thank all of you for joining our call. 2023 was another year of performance and progress for Amgen, further positioning us to deliver attractive growth through the end of the decade and beyond. Last year we delivered double digit volume growth in all four quarters with balanced growth across products and geographies. 18 of our medicines generated record annual sales including Repatha, Prolia, Evenity, Tezspire, Blincyto, Krystexxa, and Uplizna. The acquisition of Horizon, which is completed on 6 October 2023, gives us a significant new rare disease business that now stands as a fourth pillar of growth alongside our leading general medicine, oncology, and inflammation businesses.

Bob Bradway: Okay, thank you Justin, and let me thank all of you for joining our call. 2023 was another year of performance and progress for Amgen, further positioning us to deliver attractive growth through the end of the decade and beyond. Last year we delivered double digit volume growth in all four quarters with balanced growth across products and geographies. 18 of our medicines generated record annual sales including Repatha, Prolia, Evenity, Tezspire, Blincyto, Krystexxa, and Uplizna. The acquisition of Horizon, which is completed on 6 October 2023, gives us a significant new rare disease business that now stands as a fourth pillar of growth alongside our leading general medicine, oncology, and inflammation businesses.

Bob Bradway: Okay, thanks Justin. And let me thank all of you for joining our call. 2023 was another year of performance and progress for Amgen further positioning us to deliver attractive growth through the end of the decade and beyond.

Speaker Change: 2023 was another year of performance and progress for Amgen further positioning us to deliver attractive growth through the end of the decade and beyond.

Last year, we delivered double digit volume growth in all four quarters with balanced growth across products and geographies. 18 of our medicines generated record annual sales, including REPATHA, PROLIA, [inaudible], KRYSTEXXA and [inaudible].

Speaker Change: 18 of our medicines generated record annual sales, including <unk> prolia of entity tests buyer, when <unk> KRYSTEXXA and <unk>.

Speaker Change: The acquisition of Horizon was completed on October 6th. It gives us a significant new rare disease business that now stands as the fourth pillar of growth alongside our leading general medicine, oncology, and inflammation businesses.

Speaker Change: It was completed on October six gives us a significant new rare disease business that now stands as the fourth pillar of growth alongside our leading general medicine oncology and inflammation businesses.

Robert Bradway: The medicines we acquired are all very early in their life cycles and by leveraging Amgen's world-class biologics manufacturing, decades of experience in inflammation, and our extensive global presence, we believe these products have the potential to reach many more patients around the world. Last year we also advanced the deepest and most diverse pipeline in our history with promising molecules at all stages of development, and across our four pillars of growth. We anticipate well over a dozen significant pipeline milestones this year.

The medicines we acquired are all very early in their life cycles and by leveraging Amgen's world-class biologics manufacturing, decades of experience in inflammation, and our extensive global presence, we believe these products have the potential to reach many more patients around the world. Last year we also advanced the deepest and most diverse pipeline in our history with promising molecules at all stages of development, and across our four pillars of growth. We anticipate well over a dozen significant pipeline milestones this year.

Speaker Change: The medicines we acquired are all very early in their life cycles and by leveraging Amgen's world class biologics manufacturing, decades of experience in the inflammation and our extensive global presence, we believe these products have the potential to reach many more patients around the world. Last year, we also advanced the deepest and most diverse pipeline in our history with promising molecules at all stages of development and across our four pillars of growth. We anticipate well over a dozen significant pipeline milestones this year. I'll touch on a few. 

The medicines we acquired are all very early in their life cycles and by leveraging Amgen's world class biologics manufacturing, decades of experience in the inflammation and our extensive global presence, we believe these products have the potential to reach many more patients around the world.

Speaker Change: And by leveraging Amgen's World class Biologics manufacturing decades of experience in the inflammation and our extensive global presence.

Speaker Change: We believe these products have the potential to reach many more patients around the world.

Last year, we also advanced the deepest and most diverse pipeline in our history with promising molecules at all stages of development and across our four pillars of growth. We anticipate well over a dozen significant pipeline milestones this year. I'll touch on a few.

Speaker Change: Last year, we also advanced the deepest and most diverse pipeline in our history with promising molecules at all stages of development. Our four pillars of growth. We anticipate well over a dozen significant pipeline milestones this year.

Speaker Change: Our four pillars of growth. We anticipate well over a dozen significant pipeline milestones this year.

Speaker Change: We anticipate well over a dozen significant pipeline milestones this year.

Robert Bradway: Touch on a few in general medicine. We'll generate phase 2 data this year for our lead obesity molecule MariTide, and we're excited, of course, to learn more about this asset. We're also advancing a number of early-stage assets in this space. In oncology, we have a 12 June 2024 PDUFA date for the FDA to complete its priority review of tarlatamab as a third-line treatment for small cell lung cancer. Tarlatamab is the first bispecific T-cell engager shown to be effective in addressing a major solid tumor, in this case one for which there's been no new treatment in decades and which today has a five-year survival rate of just 3%.

Touch on a few in general medicine. We'll generate phase 2 data this year for our lead obesity molecule MariTide, and we're excited, of course, to learn more about this asset. We're also advancing a number of early-stage assets in this space. In oncology, we have a 12 June 2024 PDUFA date for the FDA to complete its priority review of tarlatamab as a third-line treatment for small cell lung cancer. Tarlatamab is the first bispecific T-cell engager shown to be effective in addressing a major solid tumor, in this case one for which there's been no new treatment in decades and which today has a five-year survival rate of just 3%.

Speaker Change: In General Medicine, we'll generate phase two data this year for our lead obesity molecule Maritime and were excited of course to learn more about this asset. We're also advancing a number of early stage assets in this space. In oncology, we have a June 12th PDUFA date for the FDA to complete its priority review of [inaudible] as a third line treatment for small cell lung cancer.

Speaker Change: In General Medicine will generate phase two data this year for our <unk> obesity molecule Maritime and were excited of course to learn more about this asset. We're also advancing a number of early stage assets in this space.

Speaker Change: We're also advancing a number of early stage assets in this space.

Speaker Change: In oncology, we have a June 12th Paducah date for the FDA to complete its priority review of <unk> as a third line treatment for small cell lung cancer.

Speaker Change: [inaudible] is the first bi specific T cell engager shown to be effective in addressing a major solid tumor in this case, one for which there has been no new treatments in decades, and which today has a five year survival rate of just 3%.

Robert Bradway: We're studying tarlatamab in earlier lines of treatment and hope over the fullness of time to be able to serve the tens of thousands of patients diagnosed with small cell lung cancer each year in the US and major markets around the world. We've done this very successfully now with our first BiTE, Blincyto, which has steadily moved into earlier lines of treatment for acute lymphoblastic leukemia. We'll take the same approach with yet another promising BiTE, that being zaliridomag in prostate cancer. In inflammation, we'll have phase 3 data from rocatinlimab and atopic dermatitis from the first of what are now eight trials in the rocket program. In rare disease, we'll have phase 3 data from Uplizna and myasthenia gravis, and IgG4-related disease.

We're studying tarlatamab in earlier lines of treatment and hope over the fullness of time to be able to serve the tens of thousands of patients diagnosed with small cell lung cancer each year in the US and major markets around the world. We've done this very successfully now with our first BiTE, Blincyto, which has steadily moved into earlier lines of treatment for acute lymphoblastic leukemia. We'll take the same approach with yet another promising BiTE, that being zaliridomag in prostate cancer. In inflammation, we'll have phase 3 data from rocatinlimab and atopic dermatitis from the first of what are now eight trials in the rocket program. In rare disease, we'll have phase 3 data from Uplizna and myasthenia gravis, and IgG4-related disease.

Speaker Change: We're studying [inaudible] in earlier lines of treatment and hope over the fullness of time to be able to serve the tens of thousands of patients diagnosed with small cell lung cancer each year in the US and major markets around the world. We've done this very successfully now with our first [inaudible], which has steadily moved into earlier lines of treatment for acute lymphoblastic leukemia, and we will take the same approach with yet another promising bite, that being [inaudible] in prostate cancer.

Speaker Change: We've done this very successfully now with our first fight Glen Silo, which has steadily moved into earlier lines of treatment for acute lymphoblastic leukemia, and we will take the same approach with yet another promising bite that beings algorithmic and prostate cancer.

In inflammation, we will have phase III data from [inaudible] in atopic dermatitis from the first of what are now eight trials in the Rocket Program. And in rare disease, we will have phase III data from [inaudible] and myasthenia gravis and IGG4 related disease. At a time when a rapidly aging global population needs more innovation, Amgen is delivering both with the medicines we have on the market today and with the promising new medicines that are advancing in our pipeline.

In inflammation, we will have phase III data from [inaudible] in atopic dermatitis from the first of what are now eight trials in the Rocket Program. And in rare disease, we will have phase III data from [inaudible] and myasthenia gravis and IGG4 related disease.

Speaker Change: Program. And in rare disease will have phase III data from a prisoner in myasthenia gravis and <unk> related disease. At a time when a rapidly aging global population needs more innovation Amgen is delivering. With the medicines, we have on the market today and with a promising new medicines that are advancing in our pipeline.

Speaker Change: And in rare disease will have phase III data from a prisoner in myasthenia gravis and <unk> related disease. At a time when a rapidly aging global population needs more innovation Amgen is delivering. With the medicines, we have on the market today and with a promising new medicines that are advancing in our pipeline.

Robert Bradway: At a time when a rapidly aging global population needs more innovation, Amgen is delivering both with the medicines we have on the market today and with the promising new medicines that are advancing in our pipeline. We're also excited by the rapid convergence of biotech and tech, which is enabling us to innovate more quickly and confidently. We've been preparing for this hinge moment for more than a decade and recently named Dave Reese as our first ever Chief Technology Officer to ensure that we're capitalizing on technologies like generative artificial intelligence, not just in R&amp;D, but across the entire company. Succeeding Dave as Amgen's Head of R&amp;D is Jay Bradner. Jay is a physician, scientist, and a seasoned R&amp;D leader, having served for many years as President of the Novartis Institutes for Biomedical Research.

At a time when a rapidly aging global population needs more innovation, Amgen is delivering both with the medicines we have on the market today and with the promising new medicines that are advancing in our pipeline. We're also excited by the rapid convergence of biotech and tech, which is enabling us to innovate more quickly and confidently. We've been preparing for this hinge moment for more than a decade and recently named Dave Reese as our first ever Chief Technology Officer to ensure that we're capitalizing on technologies like generative artificial intelligence, not just in R&amp;D, but across the entire company. Succeeding Dave as Amgen's Head of R&amp;D is Jay Bradner. Jay is a physician, scientist, and a seasoned R&amp;D leader, having served for many years as President of the Novartis Institutes for Biomedical Research.

At a time when a rapidly aging global population needs more innovation, Amgen is delivering both with the medicines we have on the market today and with the promising new medicines that are advancing in our pipeline.

Speaker Change: At a time when a rapidly aging global population needs more innovation Amgen is delivering. With the medicines, we have on the market today and with a promising new medicines that are advancing in our pipeline.

Speaker Change: With the medicines, we have on the market today and with a promising new medicines that are advancing in our pipeline.

Speaker Change: We're also excited by the rapid convergence of biotech and tech, which is enabling us to innovate more quickly and confidently. We've been preparing for this hinge moment for more than a decade and recently named Dave Reese as our first-ever Chief Technology officer to ensure that we're capitalizing on technologies like generative artificial intelligence, not just in R&D, but across the entire company.

We've been preparing for this hinge moment for more than a decade and recently named Dave Reese as our first ever Chief Technology officer to ensure that we're capitalizing on technologies like generative artificial intelligence not just in R&D, but across the entire company.

Speaker Change: Succeeding Dave as Amgen's head of R&D is Jay Bradner. Jay is a Physician Scientist and a seasoned R&D leader having served for many years as president of the Novartis Institute for Biomedical Research. Jay previously also served as a faculty member at Harvard Medical School and prior to joining Amgen, was a practicing oncologist at the Dana Farber Cancer Institute. We're delighted to have Jay on board and excited by the work that he, Dave and the rest of our team will do together to accelerate innovation at Amgen for the good of patients and for the long term growth of our business.

Robert Bradway: Jay previously also served as a faculty member at Harvard Medical School and prior to joining Amgen, was a practicing oncologist at the Dana-Farber Cancer Institute. We're delighted to have Jay on board and excited by the work that he, Dave, and the rest of our team will do together to accelerate innovation at Amgen for the good of patients and for the long term growth of our business. With that, I want to thank our 27,000 employees around the world for their many contributions to our success. Let me now ask Murto to talk about our commercial performance in 2023.

Jay previously also served as a faculty member at Harvard Medical School and prior to joining Amgen, was a practicing oncologist at the Dana-Farber Cancer Institute. We're delighted to have Jay on board and excited by the work that he, Dave, and the rest of our team will do together to accelerate innovation at Amgen for the good of patients and for the long term growth of our business. With that, I want to thank our 27,000 employees around the world for their many contributions to our success. Let me now ask Murto to talk about our commercial performance in 2023.

Speaker Change: We're delighted to have Jay on board and excited by the work that he, Dave and the rest of our team will do together to accelerate innovation at Amgen for the good of patients and for the long term growth of our business.

With that, I want to thank our 27,000 employees around the world for their many contributions to our success and let me now ask Murdo to talk about our commercial performance in 2023.

Murdo Gordon: Thanks Bob. I'm very pleased with our performance in 2023. Execution was strong across the business, resulting in record sales in the year for 18 brands and robust volume growth across the four pillars of our business. Full year product sales increased 9% year over year. Volume growth was 15% with strength across our regions. US volume growth was 14% and volume growth in our Europe, Latin America, Middle East, and Canada region was 10%. Asia Pacific continues to be our fastest growing region with 41% volume growth. These results include $954 million of sales from the Legacy Horizon portfolio from the period of 6 October 2023 through 31 December 2023. I'll start with our general medicine business, which includes Repatha, Prolia, Evenity, and Aimovig.

Murdo Gordon: Thanks Bob. I'm very pleased with our performance in 2023. Execution was strong across the business, resulting in record sales in the year for 18 brands and robust volume growth across the four pillars of our business. Full year product sales increased 9% year over year. Volume growth was 15% with strength across our regions. US volume growth was 14% and volume growth in our Europe, Latin America, Middle East, and Canada region was 10%. Asia Pacific continues to be our fastest growing region with 41% volume growth. These results include $954 million of sales from the Legacy Horizon portfolio from the period of 6 October 2023 through 31 December 2023. I'll start with our general medicine business, which includes Repatha, Prolia, Evenity, and Aimovig.

Murdo Gordon: Thanks, Bob and I'm very pleased with our performance in 2023. Execution was strong across the business, resulting in record sales in the year for 18 brands and robust volume growth across the four pillars of our business.

Full year product sales increased 9% year over year. Volume growth was 15% with strength across our regions. U.S volume growth was 14% and volume growth in our Europe, Latin America, Middle East and Canada region was 10%. Asia Pacific continues to be our fastest growing region with 41% volume growth. These results include $954 million of sales from the legacy horizon portfolio from the period of October 6th through December 31st.

Vikram Carmony: Volume growth in our Europe, Latin America, Middle East and Canada region was 10%.

Vikram Carmony: Asia Pacific continues to be our fastest growing region with 41% volume growth.

Vikram: These results include $954 million of sales from the legacy horizon portfolio. From the period of October six through December 31st.

Vikram: From the period of October six through December 31st.

Vikram: I'll start with our general medicines business, which includes REPATHA, PROLIA, EVENITY and [inaudible]. Overall revenue for these four products grew 15% year over year in the fourth quarter and 17% for the full year, driven by 18 and 20% volume growth respectively.

Murdo Gordon: Overall revenue for these four products grew 15% year over year in the fourth quarter and 17% for the full year, driven by 18% and 20% volume growth respectively. Repatha sales increased 25% year over year in the fourth quarter with volume growth of 35% partially offset by lower net selling price. Outside of the US we saw 25% volume growth with strength across our regions. In the US volume growth of 48% was driven by a 66% increase in the number of new patients starting treatment. We saw a decline in net selling price in the US primarily driven by new formulary coverage. We expect this additional coverage to lead to strong volume growth, which will more than offset declining net selling price. In addition, some payers have recently removed prior authorization for some patients which will further ease their access to Repatha.

Murdo Gordon: Overall revenue for these four products grew 15% year over year in the fourth quarter and 17% for the full year, driven by 18% and 20% volume growth respectively. Repatha sales increased 25% year over year in the fourth quarter with volume growth of 35% partially offset by lower net selling price. Outside of the US we saw 25% volume growth with strength across our regions. In the US volume growth of 48% was driven by a 66% increase in the number of new patients starting treatment. We saw a decline in net selling price in the US primarily driven by new formulary coverage. We expect this additional coverage to lead to strong volume growth, which will more than offset declining net selling price. In addition, some payers have recently removed prior authorization for some patients which will further ease their access to Repatha.

Vikram: REPATHA sales increased 25% year over year in the fourth quarter with volume growth of 35% partially offset by lower net selling price. Outside of the US, we saw 25% volume growth with strength across our regions. In the US, volume growth of 4% to 8% was driven by a 66% increase in the number of new patients starting treatment.

Vikram: In the U S volume growth of 4% to 8% was driven by a 66% increase in the number of new patients starting treatment.

Vikram: We saw a decline in net selling price in the US, primarily driven by new formulary coverage. We expect this additional coverage to lead to strong volume growth, which will more than offset declining net selling price. In addition, some payers have recently removed prior authorization for some patients which will further ease their access to REPATHA.

Murdo Gordon: We remain committed to the urgent need to educate physicians and patients on the importance of LDL C lowering to reduce the risk of cardiovascular events. In the US, we activated more than 20,000 new prescribing physicians in 2023 in both the primary care and cardiology settings. While we're pleased with this progress, we'll continue to work tirelessly for the many, many more patients around the world who can benefit from Repatha. Transitioning to bone health, Evenity had record sales of $318 million for the quarter, driven by 39% volume growth. Osteoporosis disproportionately impacts postmenopausal women, and the diagnosis and treatment rates for these patients are low. In the US, only 6% of very high risk patients with osteoporosis are treated with a bone builder, creating an urgent need for treatment with an effective therapy. Evenity is an important therapy to address this unmet need as it is the.

We remain committed to the urgent need to educate physicians and patients on the importance of LDL C lowering to reduce the risk of cardiovascular events. In the US, we activated more than 20,000 new prescribing physicians in 2023 in both the primary care and cardiology settings. While we're pleased with this progress, we'll continue to work tirelessly for the many, many more patients around the world who can benefit from Repatha. Transitioning to bone health, Evenity had record sales of $318 million for the quarter, driven by 39% volume growth. Osteoporosis disproportionately impacts postmenopausal women, and the diagnosis and treatment rates for these patients are low. In the US, only 6% of very high risk patients with osteoporosis are treated with a bone builder, creating an urgent need for treatment with an effective therapy. Evenity is an important therapy to address this unmet need as it is the.

Vikram: We remain committed to the urgent need to educate physicians and patients on the importance of LDLC lowering to reduce the risk of cardiovascular events. In the US, we activated more than 20,000 new prescribing physicians in 2023 in both the primary care and cardiology settings. And while we're pleased with this progress, we will continue to work tirelessly for the many, many more patients around the world who can benefit from REPATHA.

And while we're pleased with this progress, we will continue to work tirelessly for the many, many more patients around the world who can benefit from REPATHA.

Vikram: Transitioning to bone health, of EVENITY had record sales of $318 million for the quarter driven by 39% volume growth. Osteoporosis disproportionately impacts post menopausal women and the diagnosis and treatment rates for these patients are low.

Vikram: In the US, only 6% of very high risk patients with osteoporosis are treated with a bone builder, creating an urgent need for treatment with an effective therapy. EVENITY is an important therapy to address this unmet need as it is the only bone builder that works with the body's natural ability to increase bone formation and also decrease bone resorption. We see strong growth potential for EVENITY and we will continue to apply our proven experience in bone health to ensure it reaches all the patients who need it.

Vikram: <unk> is an important therapy to address this unmet needs as it is the only bone builder that works with the body's natural ability to increased bone formation and also decrease bone resorption.

Justin Claeys: Only bone builder that works with the.

Only bone builder that works with the.

Murdo Gordon: Evenity's natural ability to increase bone formation and also decrease bone resorption. We see strong growth potential for Evenity and will continue to apply our proven experience in bone health to ensure it reaches all the patients who need it. Prolia sales grew 12% year over year to a record $1.1 billion for the fourth quarter. Volume growth of 10% was supported by real-world evidence reaffirming Prolia's superiority in reducing fracture risk when compared to alendronate in treatment-naive patients with postmenopausal osteoporosis at a high risk of fracture. Moving to our oncology business, which includes Blincyto, Lumakras, Vectibix, Kyprolis, Nplate, and Xgeva, sales of these six innovative products grew 5% year over year for the fourth quarter with 3% volume growth. Full-year sales grew 12% year over year driven by 12% volume growth.

Evenity's natural ability to increase bone formation and also decrease bone resorption. We see strong growth potential for Evenity and will continue to apply our proven experience in bone health to ensure it reaches all the patients who need it. Prolia sales grew 12% year over year to a record $1.1 billion for the fourth quarter. Volume growth of 10% was supported by real-world evidence reaffirming Prolia's superiority in reducing fracture risk when compared to alendronate in treatment-naive patients with postmenopausal osteoporosis at a high risk of fracture. Moving to our oncology business, which includes Blincyto, Lumakras, Vectibix, Kyprolis, Nplate, and Xgeva, sales of these six innovative products grew 5% year over year for the fourth quarter with 3% volume growth. Full-year sales grew 12% year over year driven by 12% volume growth.

Vikram: We see strong growth potential for <unk>, and we will continue to apply our proven experience in bone health to ensure it reaches all the patients who need it.

Vikram: PROLIA sales grew 12% year over year to a record $1.1 billion for the fourth quarter. Volume growth of 10% was supported by real world evidence reaffirming PROLIA's superiority in reducing fracture risk when compared to alendronate in the treatment of naive patients with postmenopausal osteoporosis at a high risk of fracture.

Vikram: Moving to our oncology business, which includes, [inaudible], LUMAKRAS, VECTIBIX, KYPROLIS, NPLATE and XGEVA. Sales of these six innovative products grew 5% year over year for the fourth quarter with 3% volume growth. Full year sales grew 12% year over year, driven by 12% volume growth.

Vikram: Sales of these six innovative products grew 5% year over year for the fourth quarter with 3% volume growth full year sales grew 12% year over year, driven by 12% volume growth.

Murdo Gordon: Blincyto sales grew 47% year over year to a record $241 million, and for the fourth quarter volume growth of 55% was supported by broad prescribing to patients with acute lymphoblastic leukemia in frontline consolidation treatment. Long-term, we see significant growth potential for Blincyto from utilization earlier in the front line as part of induction treatment. Lumakras sales increased 8% year over year for the fourth quarter. We see future growth opportunities for Lumakras coming from launches in new markets and additional indications. Vectibix sales increased 5% and Kyprolis sales grew 8% year over year for the fourth quarter, both driven by volume growth. Nplate sales decreased 18% year over year for the fourth quarter driven by volume decline related to timing of orders placed by the US government, partially offset by volume growth across our regions.

Blincyto sales grew 47% year over year to a record $241 million, and for the fourth quarter volume growth of 55% was supported by broad prescribing to patients with acute lymphoblastic leukemia in frontline consolidation treatment. Long-term, we see significant growth potential for Blincyto from utilization earlier in the front line as part of induction treatment. Lumakras sales increased 8% year over year for the fourth quarter. We see future growth opportunities for Lumakras coming from launches in new markets and additional indications. Vectibix sales increased 5% and Kyprolis sales grew 8% year over year for the fourth quarter, both driven by volume growth. Nplate sales decreased 18% year over year for the fourth quarter driven by volume decline related to timing of orders placed by the US government, partially offset by volume growth across our regions.

Vikram: [inaudible] sales grew 47% year over year to a record $241 million for the fourth quarter. Volume growth of 55% was supported by broad prescribing to patients with acute lymphoblastic leukemia in frontline consolidation treatment. Long term, we see significant growth potential for [inaudible] from utilization earlier in the frontline as part of induction treatment.

Vikram: Long term, we see significant growth potential for [inaudible] from utilization earlier in the frontline as part of induction treatment.

Vikram: LUMAKRAS sales increased 8% year over year for the fourth quarter. We see future growth opportunities for LUMAKRAS coming from launches in new markets and additional indications.

Vikram: VECTIBIX sales increased 5% and KYPROLIS sales grew 8% year over year for the fourth quarter, both driven by volume growth. NPLATE sales decreased 18% year over year for the fourth quarter driven by volume decline related to timing of orders placed by the US government, partially offset by volume growth across our regions. 

VECTIBIX sales increased 5% and KYPROLIS sales grew 8% year over year for the fourth quarter, both driven by volume growth.

NPLATE sales decreased 18% year over year for the fourth quarter driven by volume decline related to timing of orders placed by the US government, partially offset by volume growth across our regions.

Murdo Gordon: Full year sales increased 13%, primarily driven by volume growth including US government orders, excluding US government orders. Enbrel sales grew 23% year over year for the fourth quarter and 8% for the full year, transitioning to our inflammation business. So Tezspire sales increased 2% year over.

Full year sales increased 13%, primarily driven by volume growth including US government orders, excluding US government orders. Enbrel sales grew 23% year over year for the fourth quarter and 8% for the full year, transitioning to our inflammation business. So Tezspire sales increased 2% year over.

Geoff Meacham: Full year sales increased 13%, primarily driven by volume growth, including US government orders. Excluding US government orders NPLATE sales grew 23% year over year for the fourth quarter and 8% for the full year.

Jay: Excluding U S government orders and place sales grew 23% year over year for the fourth quarter and 8% for the full year.

Jay: Transitioning to our inflammation business, OTEZLA sales increased 2% year over year for the fourth quarter, driven by favorable changes to estimated sales deductions and 3% volume growth, partially offset by lower inventory levels and lower net selling price. Full year sales decreased 4% driven by lower net selling price and lower inventory levels, partially offset by 2% volume growth.

Vikram Karnani: Year for the fourth quarter driven by.

Year for the fourth quarter driven by.

Murdo Gordon: Favorable changes to estimated sales deductions and 3% volume growth, partially offset by lower inventory levels and lower net selling price. Full year sales decreased 4% driven by lower net selling price and lower inventory levels, partially offset by 2% volume growth. New patient starts for Otezla grew 6% in the fourth quarter, driven by strong execution and increased investment. Competitor free drug programs had a reduced impact in the quarter. Otezla is uniquely positioned to grow in 2024 and beyond given its indication for all severities of psoriasis combined with an established clinical profile, broad payer coverage, a lack of testing required for initiation, and convenient oral administration.

Favorable changes to estimated sales deductions and 3% volume growth, partially offset by lower inventory levels and lower net selling price. Full year sales decreased 4% driven by lower net selling price and lower inventory levels, partially offset by 2% volume growth. New patient starts for Otezla grew 6% in the fourth quarter, driven by strong execution and increased investment. Competitor free drug programs had a reduced impact in the quarter. Otezla is uniquely positioned to grow in 2024 and beyond given its indication for all severities of psoriasis combined with an established clinical profile, broad payer coverage, a lack of testing required for initiation, and convenient oral administration.

Jay: Full year sales decreased 4% driven by lower net selling price and lower inventory levels, partially offset by 2% volume growth.

Jay: New patient starts for OTEZLA grew 6% in the fourth quarter, driven by strong execution and increased investment. Competitor free drug programs had a reduced impact in the quarter. OTEZLA is uniquely positioned to grow in 2024 and beyond given its indication for all severities of psoriasis combined with an established clinical profile, broad payer coverage, a lack of testing required for initiation and convenient oral administration.

Jay: The tariff free drug programs had a reduced impact in the quarter.

Tesla is uniquely positioned to grow in 2024 and beyond given its indication for all severities of psoriasis combined with an established clinical profile broad payer coverage, a lack of testing required for initiation and convenient oral administration.

Murdo Gordon: Enbrel sales decreased 8% year over year.

Enbrel sales decreased 8% year over year.

Jay: ENBREL sales decreased 8% year over year for the fourth quarter, driven by a 4% impact from unfavorable changes to estimated sales deductions and lower net selling price. US volume grew 1% in the fourth quarter supported by an increase in new patients starting treatment as a result of improved payer coverage. Going forward, we expect net selling price to continue to decline year over year, driven by higher rebase to maintain broad, first line payer coverage and changes in patient mix.

Vikram Karnani: For the fourth quarter driven by a.

For the fourth quarter driven by a.

Murdo Gordon: 4% impact from unfavorable changes to estimated sales deductions and lower net selling price. US volume grew 1% in Q4 supported by an increase in new patients starting treatment as a result of improved payer coverage. Going forward, we expect net selling price to continue to decline year over year driven by higher rebates to maintain broad first line payer coverage and changes in patient mix.

4% impact from unfavorable changes to estimated sales deductions and lower net selling price. US volume grew 1% in Q4 supported by an increase in new patients starting treatment as a result of improved payer coverage. Going forward, we expect net selling price to continue to decline year over year driven by higher rebates to maintain broad first line payer coverage and changes in patient mix.

Jay: US volume grew 1% in the fourth quarter supported by an increase in new patients starting treatment as a result of improved payer coverage. Going forward, we expect net selling price to continue to decline year over year, driven by higher rebase to maintain broad, first line payer coverage and changes in patient mix.

Murdo Gordon: Tezspire continues a strong launch trajectory with $177 million in sales in the fourth quarter and $567 million for the full year. Sales increased 10% sequentially, driven by volume growth. Our successful launch of a self-administered pre-filled single-use pen allowed us to expand coverage with major pharmacy benefit managers to over 80%, contributing to higher new patient growth as the year progressed. Moving forward, we expect this expanded coverage will allow Tezspire to help even more patients with severe uncontrolled asthma. Sales of Tavneos were $44 million in the quarter and $134 million for the full year. In the fourth quarter, we saw 17% quarter-over-quarter volume growth in the US, approximately 2,700 patients have now been treated with Tavneos by over 1,700 healthcare professionals.

Tezspire continues a strong launch trajectory with $177 million in sales in the fourth quarter and $567 million for the full year. Sales increased 10% sequentially, driven by volume growth. Our successful launch of a self-administered pre-filled single-use pen allowed us to expand coverage with major pharmacy benefit managers to over 80%, contributing to higher new patient growth as the year progressed. Moving forward, we expect this expanded coverage will allow Tezspire to help even more patients with severe uncontrolled asthma. Sales of Tavneos were $44 million in the quarter and $134 million for the full year. In the fourth quarter, we saw 17% quarter-over-quarter volume growth in the US, approximately 2,700 patients have now been treated with Tavneos by over 1,700 healthcare professionals.

Jay: TEZSPIRE continues its strong launch trajectory with $177 million in sales in the fourth quarter and $567 million for the full year. Sales increased 10% sequentially driven by volume growth.

Jay: Sales increased 10% sequentially driven by volume growth.

Jay: Our successful launch of a self administered, pre-filled single use 10 allowed us to expand coverage with major pharmacy benefit managers to over 80%, contributing to higher new patient growth as the year progressed. Moving forward, we expect this expanded coverage will allow TEZSPIRE to help even more patients with severe uncontrolled asthma.

Jay: Sales of TAVNEOS were $44 million in the quarter and $134 million for the full year. In the fourth quarter, we saw 17% quarter over quarter volume growth in the US. Approximately 2,700 patients have now been treated with TAVNEOS by over 1,700 healthcare professionals. Looking forward, we will continue to leverage our expertise in nephrology and inflammation to bring TAVNEOS to even more patients with [inaudible] associated vasculitis.

Jay: Sales of <unk> were $44 million in the quarter and $134 million for the full year in the fourth quarter, we saw 17% quarter over quarter volume growth in the U S. Approximately 2700 patients have now been treated with <unk> by over 1700 healthcare professionals.

Murdo Gordon: Looking forward, we will continue to leverage our expertise in nephrology and inflammation to bring TAVNEOS to even more patients with ANCA-associated vasculitis. Sales for our biosimilars portfolio grew 10% year over year for the fourth quarter, and 5% for the full year driven by 27%, and 29% volume growth. This volume growth was partially offset by net selling price decline over time. We expect long-term growth in our biosimilars business to be driven by the addition of new molecules, and additional launches. Overall, our execution is strong across the business underscored by our foundational commitment to serve patients. The four pillars of our portfolio position us well to serve many more patients around the world who can benefit from our innovative therapies. And with that I'll turn it over to Vikram who will cover our rare disease portfolio.

Looking forward, we will continue to leverage our expertise in nephrology and inflammation to bring TAVNEOS to even more patients with ANCA-associated vasculitis. Sales for our biosimilars portfolio grew 10% year over year for the fourth quarter, and 5% for the full year driven by 27%, and 29% volume growth. This volume growth was partially offset by net selling price decline over time. We expect long-term growth in our biosimilars business to be driven by the addition of new molecules, and additional launches. Overall, our execution is strong across the business underscored by our foundational commitment to serve patients. The four pillars of our portfolio position us well to serve many more patients around the world who can benefit from our innovative therapies. And with that I'll turn it over to Vikram who will cover our rare disease portfolio.

Jay: Looking forward, we will continue to leverage our expertise in nephrology and inflammation to bring tap needless to even more patients with <unk> associated vasculitis.

Jay: Sales for our biosimilars portfolio grew 10% year over year for the fourth quarter and 5% for the full year, driven by 27% and 29% volume growth. This volume growth was partially offset by net selling price decline. Over time, we expect long term growth in our biosimilars business to be driven by the addition of new molecules and additional launches.

Jay: This volume growth was partially offset by net selling price decline over time, we expect long term growth in our biosimilars business to be driven by the addition of new molecules and additional launches.

Jay: Overall, our execution is strong across the business underscored by our foundational commitment to serve patients. The four pillars of our portfolio position us well to serve many more patients around the world who can benefit from our innovative therapies. And with that, I'll turn it over to Vikram who will cover our rare disease portfolio.

Vikram Karnani: Thanks, Murdo. I am glad to share an update on our rare disease business now that we are four months past the close. We are now fully operating as part of Amgen with integration activities ongoing. As Bob has mentioned before, we are excited to be Amgen's fourth pillar of long-term growth. I wanted to make sure you're aware that we are not reporting the full quarter in press release and slides which reflect sales from 6 October onwards and total $954 million. This excludes $41 million of sales that occurred in the first week of October prior to deal close. For the full quarter our rare disease brands from Horizon delivered product sales of $995 million representing 6% year-over-year sales growth. Throughout the remainder of my remarks I will reference full quarter product sales.

Vikram Karnani: Thanks, Murdo. I am glad to share an update on our rare disease business now that we are four months past the close. We are now fully operating as part of Amgen with integration activities ongoing. As Bob has mentioned before, we are excited to be Amgen's fourth pillar of long-term growth. I wanted to make sure you're aware that we are not reporting the full quarter in press release and slides which reflect sales from 6 October onwards and total $954 million. This excludes $41 million of sales that occurred in the first week of October prior to deal close. For the full quarter our rare disease brands from Horizon delivered product sales of $995 million representing 6% year-over-year sales growth. Throughout the remainder of my remarks I will reference full quarter product sales.

Vikram Carmony: Thanks Murdo. I'm glad to share an update on our rare disease business now that we're four months pass deal close. We are now fully operating as part of Amgen with integration activities ongoing. As Bob has mentioned before, we are excited to be Amgen's fourth pillar of long term growth.

Vikram Carmony: I'm glad to share an update on our rare disease business now that we're four months as deal close.

Jay: We are now fully operating as part of Amgen with integration activities ongoing as Bob has mentioned before we are excited to be amgen's fourth pillar of long term growth.

Speaker Change: I wanted to make sure you are aware that we are not reporting the full quarter in press release and slides, which reflect sales from October 6th onward and totaled $954 million. This excludes $41 million of sales that occurred in the first week of October prior to deal close. For the full quarter, our rare disease brands from Horizon delivered product sales of $995 million, representing 6% year over year sales growth.

Jay: Which reflect sales from October six onward and totaled $954 million. This excludes $41 million of sales that occurred in the first week of October prior to deal close. For the full quarter, our rare disease brands from horizon delivered product sales of $995 million. Representing 6% year over year sales growth.

This excludes $41 million of sales that occurred in the first week of October prior to deal close. For the full quarter, our rare disease brands from horizon delivered product sales of $995 million. Representing 6% year over year sales growth.

For the full quarter, our rare disease brands from horizon delivered product sales of $995 million. Representing 6% year over year sales growth.

Jay: Representing 6% year over year sales growth.

Throughout the remainder of my remarks, I will reference full quarter product sales. TEPEZZA, an IGF1  monoclonal antibody for patients with thyroid eye disease generated $467 million of sales during the entire fourth quarter, representing 3% quarter over quarter growth. This is the third quarter in a row of quarter over quarter growth for TEPEZZA with the growth largely driven by the US. We saw a number of positive leading indicators, including a record number of unique TEPEZZA prescribers, total patient enrollment forms and patient starts in 2023.

Vikram Karnani: Tepezza, an IGF-1R monoclonal antibody for patients with thyroid eye disease, generated $467 million of sales during the entire fourth quarter, representing 3% quarter over quarter growth. This is the third quarter in a row of quarter over quarter growth for Tepezza, with the growth largely driven by the US, we saw a number of positive leading indicators including a record number of unique Tepezza prescribers, total patient enrollment forms, and patient starts in 2023. Additionally, thanks to our efforts we've been able to generate favorable medical policy changes for greater than 50% of US covered lives and we expect to continue this momentum throughout 2024. We continue to see approximately 100,000 patients with moderate to severe disease in the US who could benefit from Tepezza, with the majority of these patients in low clinical activity score settings.

Tepezza, an IGF-1R monoclonal antibody for patients with thyroid eye disease, generated $467 million of sales during the entire fourth quarter, representing 3% quarter over quarter growth. This is the third quarter in a row of quarter over quarter growth for Tepezza, with the growth largely driven by the US, we saw a number of positive leading indicators including a record number of unique Tepezza prescribers, total patient enrollment forms, and patient starts in 2023. Additionally, thanks to our efforts we've been able to generate favorable medical policy changes for greater than 50% of US covered lives and we expect to continue this momentum throughout 2024. We continue to see approximately 100,000 patients with moderate to severe disease in the US who could benefit from Tepezza, with the majority of these patients in low clinical activity score settings.

Jay: It depends a an IGF one our monoclonal antibody for patients with thyroid eye disease generated $467 million of sales during the entire fourth quarter, representing 3% quarter over quarter growth.

Jay: This is the third quarter in a row of quarter over quarter growth, both the peso with the growth largely driven by the U S. B.

Jay: We saw a number of positive leading indicators, including a record number of unique depends on prescribers total patient enrollment forms and patient starts in 2023.

Jay: Additionally, thanks to our efforts, we've been able to generate favorable medical policy changes or greater than 50% of US covered lives and we expect to continue this momentum throughout 2024.

Jay: We continue to see approximately 100,000 patients with moderate to severe disease in the US who could benefit from TEPEZZA, with the majority of these patients in low clinical activity score settings. Given positive leading indicators and high unmet need, we see a long term growth opportunity for TEPEZZA in the US while also recognizing there is some time lag between our execution efforts and the realization of increased patient numbers.

Jay: With the majority of these patients in low clinical activity score settings. Given positive leading indicators and high unmet need we see a long term growth opportunity for <unk> in the U S. While also recognizing that is some time lag between our execution efforts and the realization of increased patient numbers.

Vikram Karnani: Given positive leading indicators and high unmet need, we see a long-term growth opportunity for Tepezza in the US while also recognizing there is some time lag between our execution efforts and the realization of increased patient numbers. International expansion also remains a meaningful long-term growth opportunity for Tepezza. Tepezza is approved in Brazil, and we are progressing towards approval in additional countries. Our expansion into both Japan and Europe is a high priority with regulatory review underway in Japan and filings in the EU throughout the year. Krystexxa, a pegylated uricase enzyme for patients with chronic refractory gout, delivered a record $280 million in sales for the entire Q4, representing 30% year-over-year growth driven by continued strong commercial execution. Sales are now annualizing at a $1 billion run rate.

Given positive leading indicators and high unmet need, we see a long-term growth opportunity for Tepezza in the US while also recognizing there is some time lag between our execution efforts and the realization of increased patient numbers. International expansion also remains a meaningful long-term growth opportunity for Tepezza. Tepezza is approved in Brazil, and we are progressing towards approval in additional countries. Our expansion into both Japan and Europe is a high priority with regulatory review underway in Japan and filings in the EU throughout the year. Krystexxa, a pegylated uricase enzyme for patients with chronic refractory gout, delivered a record $280 million in sales for the entire Q4, representing 30% year-over-year growth driven by continued strong commercial execution. Sales are now annualizing at a $1 billion run rate.

Jay: Given positive leading indicators and high unmet need we see a long term growth opportunity for <unk> in the U S. While also recognizing that is some time lag between our execution efforts and the realization of increased patient numbers.

Jay: International expansion also remains a meaningful long term growth opportunity for the TEPEZZA. TEPEZZA is approved in Brazil and we are progressing towards approval in additional countries. Our expansion into both Japan and Europe is a high priority with regulatory review underway in Japan and filings in the EU throughout the year.

Jay: Panther is approved in Brazil, and we are progressing towards approval in additional countries.

Jay: Our expansion into both Japan, and Europe is a high priority with regulatory review underway in Japan and filings in the EU throughout the year.

Jay: KRYSTEXXA, a PEGylated uricase enzyme for patients with chronic refractory gout delivered a record $280 million in sales for the entire fourth quarter, representing 30% year over year growth driven by continued strong commercial execution. Sales are now annualizing at a billion dollar run rate. Performance was driven by execution across all phases of the patient journey, demand generation, stakeholder engagement and adherence to treatment. [inaudible], an anti-CD 19 monoclonal antibody, which is now the fastest growing biologic and in [inaudible] delivered a record $70 million in sales for the entire fourth quarter, representing 68% year over year growth. International expansion is also underway with [inaudible] now launched in multiple ex-US markets. Our remaining ultra rare portfolio generated $178 million of sales for the entire fourth quarter, primarily driven by our ultra rare medicines [inaudible].

Jay: Sales are now Annualizing a billion dollar run rate <unk>. Performance was driven by execution across all pieces of the patient journey. And generation stakeholder engagement and adherence to treatment. Uplift and anti CD 19, monoclonal antibody, which is now the fastest growing biologic and <unk> delivered a record $70 million in sales for the entire fourth quarter, representing 68% year over year growth. International expansion is also underway with <unk> now launched in multiple ex U S markets. Our remaining ultra rare portfolio generated $178 million of sales for the entire fourth quarter, primarily driven by our ultra rare medicines <unk> process be and afternoon.

Vikram Karnani: Performance was driven by execution across all phases of the patient journey, demand generation, stakeholder engagement, and adherence to treatment. Uplizna, an anti-CD19 monoclonal antibody which is now the fastest-growing biologic in NMOSD, delivered a record $70 million in sales for the entire fourth quarter, representing 68% year-over-year growth. International expansion is also underway with Uplizna now launched in multiple ex-US markets. Our remaining ultra-rare portfolio generated $178 million of sales for the entire fourth quarter, primarily driven by our ultra-rare medicines Ravicti, Procysbi, and Actimmune. Looking ahead to 2024 by leveraging Amgen's world-class biologics capabilities, decades of experience in inflammation, and extensive global presence, we are ready to reach more patients than ever before. I will now turn it over to.

Performance was driven by execution across all phases of the patient journey, demand generation, stakeholder engagement, and adherence to treatment. Uplizna, an anti-CD19 monoclonal antibody which is now the fastest-growing biologic in NMOSD, delivered a record $70 million in sales for the entire fourth quarter, representing 68% year-over-year growth. International expansion is also underway with Uplizna now launched in multiple ex-US markets. Our remaining ultra-rare portfolio generated $178 million of sales for the entire fourth quarter, primarily driven by our ultra-rare medicines Ravicti, Procysbi, and Actimmune. Looking ahead to 2024 by leveraging Amgen's world-class biologics capabilities, decades of experience in inflammation, and extensive global presence, we are ready to reach more patients than ever before. I will now turn it over to.

Jay: Performance was driven by execution across all pieces of the patient journey. And generation stakeholder engagement and adherence to treatment. Uplift and anti CD 19, monoclonal antibody, which is now the fastest growing biologic and <unk> delivered a record $70 million in sales for the entire fourth quarter, representing 68% year over year growth. International expansion is also underway with <unk> now launched in multiple ex U S markets. Our remaining ultra rare portfolio generated $178 million of sales for the entire fourth quarter, primarily driven by our ultra rare medicines <unk> process be and afternoon.

Jay: And generation stakeholder engagement and adherence to treatment. Uplift and anti CD 19, monoclonal antibody, which is now the fastest growing biologic and <unk> delivered a record $70 million in sales for the entire fourth quarter, representing 68% year over year growth. International expansion is also underway with <unk> now launched in multiple ex U S markets. Our remaining ultra rare portfolio generated $178 million of sales for the entire fourth quarter, primarily driven by our ultra rare medicines <unk> process be and afternoon.

Jay: Uplift and anti CD 19, monoclonal antibody, which is now the fastest growing biologic and <unk> delivered a record $70 million in sales for the entire fourth quarter, representing 68% year over year growth. International expansion is also underway with <unk> now launched in multiple ex U S markets. Our remaining ultra rare portfolio generated $178 million of sales for the entire fourth quarter, primarily driven by our ultra rare medicines <unk> process be and afternoon.

Jay: International expansion is also underway with <unk> now launched in multiple ex U S markets. Our remaining ultra rare portfolio generated $178 million of sales for the entire fourth quarter, primarily driven by our ultra rare medicines <unk> process be and afternoon.

Jay: Our remaining ultra rare portfolio generated $178 million of sales for the entire fourth quarter, primarily driven by our ultra rare medicines <unk> process be and afternoon.

Jay: Looking ahead at 2024, by leveraging Amgen's world class biologics capabilities, [inaudible] experience in inflammation and extensive global presence, we are ready to reach more patients than ever before. I will now turn it over to Jay.

Jay: Use of experience in inflammation and extensive global presence. We are ready to reach more patients than ever before.

Jay: We are ready to reach more patients than ever before.

Peter Griffith: Jay.

Jay.

Jay: I will now turn it over to Jay.

Justin Claeys: Thank you, Vikram, and good afternoon, everyone.

Jay Bradner: Thank you, Vikram, and good afternoon, everyone.

Jay Bradner: Thank you Vikram and good afternoon everyone. I'd like to take a minute to convey how thrilled I am to join the Amgen R&D organization and its leadership team.

Murdo Gordon: I'd like to take a minute to.

I'd like to take a minute to.

Justin Claeys: Convey how thrilled I am to join the Amgen R&D organization and this leadership team. The creativity of our discovery research, expert expedited clinical development, most authoritative biomanufacturing organization in the industry, all were well known to me before joining, but now on staff at Amgen, I appreciate the strong sense of service to patients facing serious illness, the like-minded commitment to growing the impact of our medicines and our business, and the shared conviction in this remarkable portfolio of potential first-in-class and best-in-class medicines. In 2023 we executed with speed across our clinical pipeline, achieving excellent enrollment in key programs and setting up 2024 as a year with significant data readouts across the portfolio for medicines with the potential to transform patient care.

Convey how thrilled I am to join the Amgen R&D organization and this leadership team. The creativity of our discovery research, expert expedited clinical development, most authoritative biomanufacturing organization in the industry, all were well known to me before joining, but now on staff at Amgen, I appreciate the strong sense of service to patients facing serious illness, the like-minded commitment to growing the impact of our medicines and our business, and the shared conviction in this remarkable portfolio of potential first-in-class and best-in-class medicines. In 2023 we executed with speed across our clinical pipeline, achieving excellent enrollment in key programs and setting up 2024 as a year with significant data readouts across the portfolio for medicines with the potential to transform patient care.

Geoff Meacham: Like to take a minute to convey how thrilled I am to join the Amgen R&D organization and this leadership team.

Speaker Change: The creativity of our discovery research, expert expedited clinical development, most authoritative biomanufacturing organization in the industry, all were well known to me before joining. But now on staff at Amgen, I appreciate the strong sense of service to patients facing serious illness, the likeminded commitment towards the impact of our medicines and our business and the shared conviction in this remarkable portfolio of potential first-in-class and best-in-class medicines.

Peter H. Griffith: Now on staff at Amgen I appreciate the strong sense of service to patients facing serious illness.

Peter H. Griffith: The likeminded commitment towards the impact of our medicines and our business and the shared conviction in this remarkable portfolio of potential first in class and best in class medicines.

Peter: In 2023, we executed with speed across our clinical pipeline, achieving excellent enrollment in key programs and setting up 2024 as a year with significant data readouts across the portfolio for medicines with the potential to transform patient care.

Justin Claeys: Key highlights in 2023 included the delivery of promising data from four key oncology assets and the attainment of three breakthrough therapy designations in oncology. We initiated pivotal phase 3 studies for tarlatamab and small cell lung cancer, Lumakras and non-small cell lung cancer, and colorectal cancer, along with dazodalibep in Sjogren's syndrome in general medicine. As previously disclosed, top-line 52-week data from the 592-patient MariTide phase 2 study is expected by late 2024. Leveraging the durability of weight loss observed in phase 1 and rapid enrollment enjoyed in phase 2, we recently added a part 2 to this study, which explores durable weight loss beyond 52 weeks. Our planning for a comprehensive phase 3 program across multiple indications remains on track.

Key highlights in 2023 included the delivery of promising data from four key oncology assets and the attainment of three breakthrough therapy designations in oncology. We initiated pivotal phase 3 studies for tarlatamab and small cell lung cancer, Lumakras and non-small cell lung cancer, and colorectal cancer, along with dazodalibep in Sjogren's syndrome in general medicine. As previously disclosed, top-line 52-week data from the 592-patient MariTide phase 2 study is expected by late 2024. Leveraging the durability of weight loss observed in phase 1 and rapid enrollment enjoyed in phase 2, we recently added a part 2 to this study, which explores durable weight loss beyond 52 weeks. Our planning for a comprehensive phase 3 program across multiple indications remains on track.

Peter: Key highlights in 2023 included the delivery of promising data from four key oncology assets and the attainment of three breakthrough therapy designations in oncology. We initiated pivotal phase III studies for [inaudible] in small cell lung cancer, LUMAKRAS in non-small cell lung cancer and colorectal cancer, along with [inaudible] in Shogun syndrome. And general medicine, as previously disclosed, top line 52 week data from the 592 patient maritime phase II study is expected by late 2024. Leveraging the durability of weight loss observed in phase one and rapid enrollment enjoyed in phase II, we recently added a part two to this study which explores durable weight loss beyond 52 weeks. Our planning for a comprehensive phase III program across multiple indications remains on track.

Peter: We initiated pivotal phase III studies for <unk> in small cell lung cancer, Lumia kras, non small cell lung cancer and colorectal cancer, along with gateway <unk> in Shogun syndrome.

Peter: And general Medicine as previously disclosed top line 52 week data from the 592 patient Maritime Phase II study is expected by late 2024. Leveraging the durability of weight loss observed in phase, one and rapid enrollment and Jordan phase III. We recently added a part two to this study which explores durable weight loss beyond 52 weeks.

Peter: Leveraging the durability of weight loss observed in phase, one and rapid enrollment and Jordan phase III. We recently added a part two to this study which explores durable weight loss beyond 52 weeks.

Peter: Our planning for our comprehensive phase III program across multiple indications remains on track.

Justin Claeys: Lastly, you may have seen that yesterday Nature Metabolism published a manuscript from Amgen R&amp;D that provides the integration of MariTide, preclinical, and phase 1 data beyond MariTide. Our obesity strategy encompasses several assets with AMG 786 in phase 1 and additional preclinical assets advancing. Our approach is tailored to meet the dynamic needs of obesity treatment, demonstrating a longitudinal commitment to innovation and patient care in this field.

Lastly, you may have seen that yesterday Nature Metabolism published a manuscript from Amgen R&amp;D that provides the integration of MariTide, preclinical, and phase 1 data beyond MariTide. Our obesity strategy encompasses several assets with AMG 786 in phase 1 and additional preclinical assets advancing. Our approach is tailored to meet the dynamic needs of obesity treatment, demonstrating a longitudinal commitment to innovation and patient care in this field.

Peter: Lastly, you may have seen that yesterday nature metabolism published manuscript from Amgen R&D that provides the integration of maritime preclinical and phase one data. Beyond Maritime our obesity strategy encompasses several assets with AMG 786 in phase, one and additional preclinical assets advancing.

Peter: Beyond Maritime our obesity strategy encompasses several assets with AMG 786 in phase, one and additional preclinical assets advancing.

Peter: Our approach is tailored to meet the dynamic needs of obesity treatment, demonstrating a longitudinal commitment to innovation and patient care in this field. The phase III outcome study [inaudible] around our potentially best in class LP little a targeting small interfering RNA molecule in atherosclerotic cardiovascular disease has enrolled more than 7,000 patients globally. This rapid enrollment accomplished in just one year across 34 countries and over 700 sites underscores the medical community's strong interest in and the potential impact of [inaudible]. We've deliberately expanded our initial enrollment target from 6,000 to over 7,000 patients to ensure comprehensive demographic representation and to satisfy regional regulatory requirements.

Our approach is tailored to meet the dynamic needs of obesity treatment, demonstrating a longitudinal commitment to innovation and patient care in this field. The phase III outcome study [inaudible] around our potentially best in class LP little a targeting small interfering RNA molecule in atherosclerotic cardiovascular disease has enrolled more than 7,000 patients globally. This rapid enrollment accomplished in just one year across 34 countries and over 700 sites underscores the medical community's strong interest in and the potential impact of [inaudible].

Justin Claeys: The phase 3 outcomes study of Opasiran, our potentially best-in-class LP(a)-targeting small interfering RNA molecule for atherosclerotic cardiovascular disease, has enrolled more than 7,000 patients globally. This rapid enrollment, accomplished in just one year across 34 countries and over 700 sites, underscores the medical community's strong interest in and the potential impact of Opasiran. We've deliberately expanded our initial enrollment target from 6,000 to over 7,000 patients to ensure comprehensive demographic representation and to satisfy regional regulatory requirements. We are on track to complete enrollment in H1 2024.

The phase 3 outcomes study of Opasiran, our potentially best-in-class LP(a)-targeting small interfering RNA molecule for atherosclerotic cardiovascular disease, has enrolled more than 7,000 patients globally. This rapid enrollment, accomplished in just one year across 34 countries and over 700 sites, underscores the medical community's strong interest in and the potential impact of Opasiran. We've deliberately expanded our initial enrollment target from 6,000 to over 7,000 patients to ensure comprehensive demographic representation and to satisfy regional regulatory requirements. We are on track to complete enrollment in H1 2024.

Peter: The phase III outcome study of ore pass around our potentially best in class LP Little a targeting small interfering RNA molecule in atherosclerotic cardiovascular disease has enrolled more than 7000 patient globally. This rapid enrollment accomplished in just one year across 34 countries and over 700 sites. Underscores the medical community is strong interest in and the potential impact of <unk>. We've deliberately expanded our initial enrollment target from 6000 to over 7000 patients to ensure comprehensive demographic representation. And to satisfy regional regulatory requirements.

Peter: This rapid enrollment accomplished in just one year across 34 countries and over 700 sites. Underscores the medical community is strong interest in and the potential impact of <unk>. We've deliberately expanded our initial enrollment target from 6000 to over 7000 patients to ensure comprehensive demographic representation. And to satisfy regional regulatory requirements.

Peter: Underscores the medical community is strong interest in and the potential impact of <unk>. We've deliberately expanded our initial enrollment target from 6000 to over 7000 patients to ensure comprehensive demographic representation. And to satisfy regional regulatory requirements.

Peter: We've deliberately expanded our initial enrollment target from 6000 to over 7000 patients to ensure comprehensive demographic representation. And to satisfy regional regulatory requirements.

We've deliberately expanded our initial enrollment target from 6,000 to over 7,000 patients to ensure comprehensive demographic representation and to satisfy regional regulatory requirements. We are on track to complete enrollment in the first half of 2024.

Peter: And to satisfy regional regulatory requirements.

Peter: We are on track to complete enrollment in the first half of 2024.

Justin Claeys: In oncology, we're focused on approaching high conviction targets with differentiated therapies for large effect size. We're pleased to announce that the FDA granted priority review for Blincyto, an early-stage CD19-positive B-ALL with a PDUFA date of 21 June 2024. The ongoing phase 3 Golden Gate Study is enrolling patients to evaluate the effectiveness of alternating Blincyto with low-intensity chemotherapy in older adults diagnosed with Philadelphia chromosome-negative B-ALL. We're also planning to amend this study to evaluate subcutaneous administration of blinatumomab with initiation anticipated in H2 2024, potentially allowing us to serve more patients and treating physicians.

In oncology, we're focused on approaching high conviction targets with differentiated therapies for large effect size. We're pleased to announce that the FDA granted priority review for Blincyto, an early-stage CD19-positive B-ALL with a PDUFA date of 21 June 2024. The ongoing phase 3 Golden Gate Study is enrolling patients to evaluate the effectiveness of alternating Blincyto with low-intensity chemotherapy in older adults diagnosed with Philadelphia chromosome-negative B-ALL. We're also planning to amend this study to evaluate subcutaneous administration of blinatumomab with initiation anticipated in H2 2024, potentially allowing us to serve more patients and treating physicians.

Peter: In oncology, we're focus on approaching high conviction targets with differentiated therapies for large effect sizes. We're pleased to announce that the FDA granted priority review for [inaudible] in early stage CD-19 positive BAOL with a PDUDFA date of June 21st, 2024.

Peter: We're pleased to announce that the FDA granted priority review for <unk> in early stage CD 19 positive. With a <unk> date of June 21, 2024.

Peter: With a <unk> date of June 21, 2024.

Peter: The ongoing phase III Golden Gate study is enrolling patients to evaluate the effectiveness of alternating [inaudible] with low intensity chemotherapy here in older adults diagnosed with Philadelphia chromosome negative BAOL. We're also planning to amend this study to evaluate subcutaneous administration of [inaudible] with initiation anticipated in the second half of 2024, potentially allowing us to serve more patients and treating physicians.

Peter: Here in older adults diagnosed with Philadelphia chromosome negative <unk>. We're also planning to amend the study to evaluate subcutaneous administration of blended tumor mab with initiation anticipated in the second half of 2020 for potentially allowing us to serve more patients and treating physicians.

Peter: We're also planning to amend the study to evaluate subcutaneous administration of blended tumor mab with initiation anticipated in the second half of 2020 for potentially allowing us to serve more patients and treating physicians.

Justin Claeys: Lastly, we're pleased to announce that just today the American Journal of Hematology published a manuscript highlighting data from the dose expansion phase of our ongoing phase 1b study of subcutaneous blinatumomab as a single agent in adult patients with heavily pretreated relapsed refractory B-cell. All of 27 evaluable patients treated, we observed an 85% complete response rate, of which 75% were MRD negative. Subcutaneous blinatumomab was well tolerated with no observed grade 4 cytokine release syndrome. Turning to tarlatamab, a first-in-class DLL3-targeting BiTE molecule, the FDA granted priority review following promising results from the Phase 2 DeLLphi-301 clinical trial and a PDUFA date of 12 June 2024. We are rapidly advancing tarlatamab into earlier lines of treatment where we have initiated two phase 3 studies and plan to initiate a third in the first half of 2024.

Lastly, we're pleased to announce that just today the American Journal of Hematology published a manuscript highlighting data from the dose expansion phase of our ongoing phase 1b study of subcutaneous blinatumomab as a single agent in adult patients with heavily pretreated relapsed refractory B-cell. All of 27 evaluable patients treated, we observed an 85% complete response rate, of which 75% were MRD negative. Subcutaneous blinatumomab was well tolerated with no observed grade 4 cytokine release syndrome. Turning to tarlatamab, a first-in-class DLL3-targeting BiTE molecule, the FDA granted priority review following promising results from the Phase 2 DeLLphi-301 clinical trial and a PDUFA date of 12 June 2024. We are rapidly advancing tarlatamab into earlier lines of treatment where we have initiated two phase 3 studies and plan to initiate a third in the first half of 2024.

Peter: Lastly, we're pleased to announce that just today the American Journal of Hematology published a manuscript highlighting data from the dose expansion phase of our ongoing phase 1B study of subcutaneous [inaudible] as a single agent in adult patients with heavily pretreated relapsed refractory B cell AOL. Of the 27 evaluable patients treated, we observed an 85% complete response rate of which 75% were MRD negative. Subcutaneous [inaudible] was well tolerated with no observed grade four cytokine release syndrome.

Peter: And 85% complete response rate of which 75% were <unk> negative. Subcutaneous Blinatumomab was well tolerated with no observed great for cytokine release syndrome.

Peter: Subcutaneous Blinatumomab was well tolerated with no observed great for cytokine release syndrome.

Peter: Turning to [inaudible], our first in class CLO III targeting bite molecule, the FDA granted priority review following promising results from the phase II Delphi 301 clinical trial and a PDUFA date of June 12th, 2024. We are rapidly advancing [inaudible] into earlier lines of treatment where we have initiated two phase III studies and plan to initiate a third in the first half of 2024. [inaudible], our first in class steep one bi specific molecule being studied in metastatic castrate resistant prostate cancer continues to progress following the presentation of encouraging phase one data last fall.

Turning to [inaudible], our first in class CLO III targeting bite molecule, the FDA granted priority review following promising results from the phase II Delphi 301 clinical trial and a PDUFA date of June 12th, 2024. We are rapidly advancing [inaudible] into earlier lines of treatment where we have initiated two phase III studies and plan to initiate a third in the first half of 2024.

Peter: We are rapidly advancing <unk> into earlier lines of treatment, where we have initiated two phase III studies and plan to initiate a third in the first half of 2024.

Justin Claeys: Zaliridomag, a first-in-class STEAP1 bispecific molecule being studied in metastatic castrate-resistant prostate cancer, continues to progress following the presentation of encouraging phase 1 data last fall. We are ahead of schedule with the monotherapy dose expansion and expect to complete enrollment in the coming weeks. We've opened a reduced monitoring cohort and are making significant progress in dose range finding studies in combination with novel hormonal therapy. Combinations for AMG 193, an oral MTAP-cooperative PRMT5 inhibitor, we're encouraged by nine responses we've seen across seven MTAP-null solid tumors. AMG 193 is a terrific example of a medicine targeting a genetically defined synthetic lethality and a first clinical translation of our induced proximity platform. We're now swiftly moving forward with dose expansion studies and plan to enter master protocols in thoracic and gastrointestinal malignancies, exploring combinations with standard of care in the first half of 2024.

Zaliridomag, a first-in-class STEAP1 bispecific molecule being studied in metastatic castrate-resistant prostate cancer, continues to progress following the presentation of encouraging phase 1 data last fall. We are ahead of schedule with the monotherapy dose expansion and expect to complete enrollment in the coming weeks. We've opened a reduced monitoring cohort and are making significant progress in dose range finding studies in combination with novel hormonal therapy. Combinations for AMG 193, an oral MTAP-cooperative PRMT5 inhibitor, we're encouraged by nine responses we've seen across seven MTAP-null solid tumors. AMG 193 is a terrific example of a medicine targeting a genetically defined synthetic lethality and a first clinical translation of our induced proximity platform. We're now swiftly moving forward with dose expansion studies and plan to enter master protocols in thoracic and gastrointestinal malignancies, exploring combinations with standard of care in the first half of 2024.

Peter: <unk> to make a first in class steep one bi specific molecule being studied in metastatic castrate resistant prostate cancer continues to progress following the presentation of encouraging phase one data last fall.

[inaudible], our first in class steep one bi specific molecule being studied in metastatic castrate resistant prostate cancer continues to progress following the presentation of encouraging phase one data last fall. We are ahead of schedule with the monotherapy dose expansion and expect to complete enrollment in the coming weeks.

Peter: We are ahead of schedule with the monotherapy dose expansion and expect to complete enrollment in the coming weeks.

Peter: We've opened a reduced monitoring cohort and are making significant progress in dose range finding studies in combination with novel hormonal therapy combination. For AMG 193 in oral MTA cooperative PMRT5 inhibitor, we're encouraged by nine responses we've seen across seven [inaudible] solid tumors.

We've opened a reduced monitoring cohort and are making significant progress in dose range finding studies in combination with novel hormonal therapy combination.

For AMG 193 in oral MTA cooperative PMT five inhibitor, we're encouraged by nine responses, we've seen across seven <unk> solid tumors.

For AMG 193 in oral MTA cooperative PMRT5 inhibitor, we're encouraged by nine responses we've seen across seven [inaudible] solid tumors. AMG 193 is a terrific example of a medicine targeting a genetically defined synthetically [inaudible] in our first clinical translation of our induced proximity platform.

Peter: AMG 193 is a terrific example of a medicine targeting a genetically defined synthetically [inaudible] in our first clinical translation of our induced proximity platform.

Peter: We're now swiftly moving forward with dose expansion studies and plan to enter master protocols in thoracic and gastrointestinal malignancies exploring combinations with standard of care in the first half of 2024.

Peter: Master protocols and thoracic in gastrointestinal malignancies exploring combinations with standard of care in the first half of 2024.

Justin Claeys: In our inflammation portfolio, we continue to explore Tezspire and indications beyond severe asthma, including separate Phase 3 studies in chronic rhinosinusitis with nasal polyps where top-line data are expected in the second half of 2024 as well as in eosinophilic esophagitis. We also remain on track to present Phase 2 COPD data in the first half of 2024. Our ROCKET Phase 3 program for rocatinlimab, a first-in-class anti-OX40 monoclonal antibody, has successfully enrolled over 2,400 patients with moderate to severe atopic dermatitis. We're introducing an eighth study to the ROCKET program to explore an auto-injector and we are planning to initiate both a Phase 3 study in prurigo nodularis and a Phase 2 study in asthma this year as we seek to broadly explore the potential of rocatinlimab.

In our inflammation portfolio, we continue to explore Tezspire and indications beyond severe asthma, including separate Phase 3 studies in chronic rhinosinusitis with nasal polyps where top-line data are expected in the second half of 2024 as well as in eosinophilic esophagitis. We also remain on track to present Phase 2 COPD data in the first half of 2024. Our ROCKET Phase 3 program for rocatinlimab, a first-in-class anti-OX40 monoclonal antibody, has successfully enrolled over 2,400 patients with moderate to severe atopic dermatitis. We're introducing an eighth study to the ROCKET program to explore an auto-injector and we are planning to initiate both a Phase 3 study in prurigo nodularis and a Phase 2 study in asthma this year as we seek to broadly explore the potential of rocatinlimab.

Peter: In our inflammation portfolio, we continue to explore TEZSPIRE in indications beyond severe asthma, including separate phase III studies in chronic rhinosinusitis with nasal polyps where topline data are expected in the second half of 2024 as well as in eosinophilic esophagitis. We also remain on track to present phase II COPD data in the first half of 2024.

We also remain on track to present phase III COPD data in the first half of 2024.

Peter: Our Rocket Phase III program for [inaudible], our first in class anti F 40 monoclonal antibody has successfully enrolled over 2,400 patients with moderate to severe atopic dermatitis. We're introducing an eighth study to the rocket program to explore an auto injector and we're planning to initiate both the phase III study in [inaudible] and a phase II study in asthma this year as we seek to broadly explore the potential of [inaudible].

Peter: We're introducing an eighth study to the rocket program to explore an auto injector. We're planning to initiate both the phase III study in Perugia, non soliris and a phase III study in asthma. This year as we seek to broadly explore the potential of brokerage in the lab.

Peter: We're planning to initiate both the phase III study in Perugia, non soliris and a phase III study in asthma. This year as we seek to broadly explore the potential of brokerage in the lab.

Justin Claeys: Lastly, we are encouraged by the advancements of our rare disease pipeline with several mid to late stage opportunities. In December, Tepezza received orphan drug designation in Japan, but we've also recently submitted a new drug application for Tepezza and thyroid eye disease to serve additional patients in Japan. We have a phase 3 study underway in the setting of chronic disease with a low clinical activity score. Beyond Japan, we are progressing Tepezza subcutaneous administration to drive increased adoption and improved patient experience and plan to initiate a phase 3 study in thyroid eye disease this year with aplisma. We anticipate important phase 3 data readouts this year in myasthenia gravis and IgG4 related disease, both diseases with significant unmet need and where we have the potential to make a real difference for patients. Dazodalibep, an innovative CD40 ligand inhibitor fusion protein, has entered phase 3 for Sjogren's syndrome.

Lastly, we are encouraged by the advancements of our rare disease pipeline with several mid to late stage opportunities. In December, Tepezza received orphan drug designation in Japan, but we've also recently submitted a new drug application for Tepezza and thyroid eye disease to serve additional patients in Japan. We have a phase 3 study underway in the setting of chronic disease with a low clinical activity score. Beyond Japan, we are progressing Tepezza subcutaneous administration to drive increased adoption and improved patient experience and plan to initiate a phase 3 study in thyroid eye disease this year with aplisma. We anticipate important phase 3 data readouts this year in myasthenia gravis and IgG4 related disease, both diseases with significant unmet need and where we have the potential to make a real difference for patients. Dazodalibep, an innovative CD40 ligand inhibitor fusion protein, has entered phase 3 for Sjogren's syndrome.

Peter: Lastly, we are encouraged by the advancements of our rare disease pipeline with several mid to late stage opportunities. In December, TEPEZZA received orphan drug designation in Japan where we have also recently submitted a new drug application for TEPEZZA in [inaudible] disease. To serve additional patients in Japan, we have a phase III study underway in the setting of chronic disease with a low clinical activity score.

Peter: In December to peso received orphan drug designation in Japan, where we have also recently submitted a new drug application for <unk> in <unk> disease. To serve additional patients in Japan, we have a phase III study underway and the setting of chronic disease with a low clinical activity score.

Peter: To serve additional patients in Japan, we have a phase III study underway and the setting of chronic disease with a low clinical activity score.

Beyond Japan, we are progressing TEPEZZA's subcutaneous administration to drive increased adoption and improve patient experience and plan to initiate a phase III study in [inaudible] disease this year. With [inaudible], we anticipate important phase III data readouts this year in myasthenia gravis and [inaudible] related disease, both diseases with significant unmet need and where we have the potential to make a real difference for patients. [inaudible], an innovative CD-40 ligand inhibitor fusion protein has entered phase III for Sjogren syndrome. This follows encouraging phase two data with efficacy across patients with moderate to severe systemic disease and patients with high symptom burden. [inaudible] is the first therapy to demonstrate efficacy in this latter patient population.

Beyond Japan, we are progressing TEPEZZA's subcutaneous administration to drive increased adoption and improve patient experience and plan to initiate a phase III study in [inaudible] disease this year. With [inaudible], we anticipate important phase III data readouts this year in myasthenia gravis and [inaudible] related disease, both diseases with significant unmet need and where we have the potential to make a real difference for patients.

Peter: With <unk>, we anticipate important phase III data Readouts this year in myasthenia gravis and <unk> related disease.

Peter: Both diseases with significant unmet need and where we have the potential to make a real difference for patients. <unk>, an innovative CD 40 ligand inhibitor fusion protein has entered phase III for Sjogren syndrome. This follows encouraging phase two data with efficacy across patients with moderate to severe systemic disease and patients with high symptom burden. <unk> the first therapy to demonstrate efficacy in this latter patient population.

Peter: <unk>, an innovative CD 40 ligand inhibitor fusion protein has entered phase III for Sjogren syndrome. This follows encouraging phase two data with efficacy across patients with moderate to severe systemic disease and patients with high symptom burden. <unk> the first therapy to demonstrate efficacy in this latter patient population.

[inaudible], an innovative CD-40 ligand inhibitor fusion protein has entered phase III for Sjogren syndrome. This follows encouraging phase two data with efficacy across patients with moderate to severe systemic disease and patients with high symptom burden. [inaudible] is the first therapy to demonstrate efficacy in this latter patient population.

Justin Claeys: This follows encouraging phase 2 data with efficacy across patients with moderate to severe systemic disease and patients with high symptom burden. Dazodalibep is the first therapy to demonstrate efficacy in this latter patient population. Closing out our rare disease efforts. We're excited about our LPAR1 antagonist being studied in idiopathic pulmonary fibrosis. On track for a phase 2 proof of concept data readout in the second half of 2024. In closing, I'm delighted to report on the important progress we make advancing our innovative pipeline, and I'm looking forward to sharing more pipeline milestones through 2024.

This follows encouraging phase 2 data with efficacy across patients with moderate to severe systemic disease and patients with high symptom burden. Dazodalibep is the first therapy to demonstrate efficacy in this latter patient population. Closing out our rare disease efforts. We're excited about our LPAR1 antagonist being studied in idiopathic pulmonary fibrosis. On track for a phase 2 proof of concept data readout in the second half of 2024. In closing, I'm delighted to report on the important progress we make advancing our innovative pipeline, and I'm looking forward to sharing more pipeline milestones through 2024.

Peter: This follows encouraging phase two data with efficacy across patients with moderate to severe systemic disease and patients with high symptom burden. <unk> the first therapy to demonstrate efficacy in this latter patient population.

Peter: <unk> the first therapy to demonstrate efficacy in this latter patient population.

Peter: Closing out our rare disease efforts, we're excited about [inaudible] one antagonist being studied in idiopathic pulmonary fibrosis on track for a phase II proof of concept data readout in the second half of 2024.

Speaker Change: In closing, I am delighted to report on the important progress we make advancing our innovative pipeline and I'm looking forward to sharing more pipeline milestones through 2024. I'll now turn it over to you Peter.

Peter Griffith: I'll now turn over to you, Peter. Thank you, Jay. We're pleased with our strong execution and performance in the fourth quarter and for the full year 2023. In the fourth quarter, total revenue of $8.2 billion grew 20% year over year, and non-GAAP EPS of $4.71 grew 15% year over year. For the full year, we delivered total revenue of $28.2 billion, 7% growth year over year, and non-GAAP EPS of $18.65, 5% growth year over year. As a reminder, both Q4 and the full year results include Horizon's results beginning 6 October 2023 when the acquisition closed. So our financial results will exclude approximately one week of Horizon's results from our fourth quarter results. I'll review the details of our fourth quarter and full year financial results before discussing our outlook for 2024. The financial results are shown on slides.

I'll now turn over to you, Peter.

Peter Griffith: Thank you, Jay. We're pleased with our strong execution and performance in the fourth quarter and for the full year 2023. In the fourth quarter, total revenue of $8.2 billion grew 20% year over year, and non-GAAP EPS of $4.71 grew 15% year over year. For the full year, we delivered total revenue of $28.2 billion, 7% growth year over year, and non-GAAP EPS of $18.65, 5% growth year over year. As a reminder, both Q4 and the full year results include Horizon's results beginning 6 October 2023 when the acquisition closed. So our financial results will exclude approximately one week of Horizon's results from our fourth quarter results. I'll review the details of our fourth quarter and full year financial results before discussing our outlook for 2024. The financial results are shown on slides.

Peter: I'll now turn it over to you Peter.

Peter Griffith: Thank you Jay. We're pleased with our strong execution and performance in the fourth quarter and for the full year 2023. In the fourth quarter, total revenue of $8.2 billion grew 20% year over year and non-GAAP EPS of $4.71 grew 15% year over year.

Peter: For .he full year, we delivered total revenue of $28 2 billion, 7% growth year over year, and non-GAAP EPS of $18.65, 5% growth year over year. As a reminder, both Q4 and the full year results include Horizon's results beginning October 6th when the acquisition closed. So our financial results will exclude approximately one week of Horizon's result from our fourth quarter results.

For the full year, we delivered total revenue of $28 2 billion, 7% growth year over year, and non-GAAP EPS of $18.65, 5% growth year over year.

As a reminder, both Q4 and the full year results include Horizon's results beginning October 6th when the acquisition closed. So our financial results will exclude approximately one week of Horizon's result from our fourth quarter results.

Peter: <unk> one week of Horizon's result from our fourth quarter results.

Peter: I will review the details of our fourth quarter and full year financial results before discussing our outlook for 2024. The financial results are shown on slide 54 to 56 of the slide deck.

Justin Claeys: 54 to 56 of the slide deck.

54 to 56 of the slide deck.

Peter: The financial results are shown on slide 54 to 56 of the slide deck. Turning to our fourth quarter total revenue of $8.2 billion, we saw product sales increased 20% year over year, driven by volume growth of 23%, offset by net selling price decline to 3%. Excluding the impact of Horizon, product sales increased 5% year over year, driven by volume growth of 9%.

The financial results are shown on slide 54 to 56 of the slide deck.

Peter Griffith: Turning to our fourth quarter's total revenue of $8.2 billion, we saw product sales increase 20% year over year, driven by volume growth of 23%, offset by net selling price decline of 3%. Excluding the impact of Horizon, product sales increased 5% year over year, driven by vol growth of 9% full year. Total revenues of $28.2 billion grew 7% year over year. Product sales increased 9% year over year, driven by 15% volume growth. Other revenues decreased 16% year over year, primarily due to lower profit and cost sharing from our COVID-19 collaboration with Lilly in 2022. Strong expense discipline resulted in a 50% non-GAAP operating margin as a percentage of product sales for the full year 2023. While we continue to focus on both internal and external innovation, investing $4.7 billion in our pipeline and $27.8 billion in our acquisition of Horizon.

Turning to our fourth quarter's total revenue of $8.2 billion, we saw product sales increase 20% year over year, driven by volume growth of 23%, offset by net selling price decline of 3%. Excluding the impact of Horizon, product sales increased 5% year over year, driven by vol growth of 9% full year. Total revenues of $28.2 billion grew 7% year over year. Product sales increased 9% year over year, driven by 15% volume growth. Other revenues decreased 16% year over year, primarily due to lower profit and cost sharing from our COVID-19 collaboration with Lilly in 2022. Strong expense discipline resulted in a 50% non-GAAP operating margin as a percentage of product sales for the full year 2023. While we continue to focus on both internal and external innovation, investing $4.7 billion in our pipeline and $27.8 billion in our acquisition of Horizon.

Turning to our fourth quarter total revenue of $8.2 billion, we saw product sales increased 20% year over year, driven by volume growth of 23%, offset by net selling price decline to 3%. Excluding the impact of Horizon, product sales increased 5% year over year, driven by volume growth of 9%.

Peter: 5% year over year, driven by volume growth of 9% full.

Peter: Full year total revenues of $28.2 billion grew 7% year over year. Product sales increased 9% year over year, driven by 15% volume growth. Other revenues decreased 16% year over year, primarily due to lower profit and cost sharing from our COVID-19 collaboration with Lilly in 2022.

Peter: Other revenues decreased 16% year over year, primarily due to lower profit and cost sharing from our COVID-19 collaboration with Lilly in 2022.

Strong expense discipline resulted in a 50% non-GAAP operating margin as a percentage of product sales for the full year 2023. While we continue to focus on both internal and external innovation, investing $4.7 billion in our pipeline and $27.8 billion in our acquisition of Horizon.

Peter: While we continue to focus on both internal and external innovation investing $4 7 billion in our pipeline and $27 8 billion and our acquisition of horizon.

Peter Griffith: With product sales volume growth at 23% in Q4 and 15% for the full year, we still efficiently manage the operating expenses of the business. Q4 non-GAAP operating expenses increasing 18% year-over-year, while full-year non-GAAP operating expenses increased 9%, excluding the impact of Horizon. Q4 non-GAAP operating expenses increased 3%, and full-year non-GAAP operating expenses increased 5% on a non-GAAP basis. Q4 cost of sales as a percentage of product sales was flat on a year-over-year basis at 16.3%; for the full year, cost of sales as a percentage of product sales increased by 1.1 percentage points to 17.0%.

With product sales volume growth at 23% in Q4 and 15% for the full year, we still efficiently manage the operating expenses of the business. Q4 non-GAAP operating expenses increasing 18% year-over-year, while full-year non-GAAP operating expenses increased 9%, excluding the impact of Horizon. Q4 non-GAAP operating expenses increased 3%, and full-year non-GAAP operating expenses increased 5% on a non-GAAP basis. Q4 cost of sales as a percentage of product sales was flat on a year-over-year basis at 16.3%; for the full year, cost of sales as a percentage of product sales increased by 1.1 percentage points to 17.0%.

Peter: With product sales volume growth at 23% in Q4 and 15% for the full year, we still efficiently manage the operating expenses of the business. Q4 non-GAAP operating expenses increased 18% year over year, while full year non-GAAP operating expenses increased 9%.

Peter: Excluding the impact of Horizon, Q4 non-GAAP operating expenses increased 3% and full year non-GAAP operating expenses increased 5%.

Peter: On a non-GAAP basis, Q4 cost of sales as a percentage of product sales was flat on a year over year basis of 16.3%.

Peter: For the full year, cost of sales as a percentage of product sales increased by 1.1 percentage points to 17.0%. The full year increase was primarily driven by higher profit share and changes in our product mix, partially offset by the replacement of the Puerto Rico excise tax with an income tax beginning in 2023.

Peter Griffith: The full year increase was primarily driven by higher profit share and changes in our product mix, partially offset by the replacement of the Puerto Rico excise tax with an income tax beginning in 2023. Non-GAAP R&D spend in the fourth quarter increased 16% year over year and 8% year over year for the full year, primarily due to higher spend on later stage clinical programs and marketed product support, including spend on programs acquired from the Horizon acquisition and continuing investment in our pipeline including MariTide. Q4 non-GAAP SG&A expenses increased 20% year over year, primarily driven by commercial and G&A expenses related to the Horizon acquisition. Full year non-GAAP SG&A expenses increased 5% year over year, primarily driven by commercial and G&A expenses related to the Horizon acquisition, partially offset by a decline in other marketed product spends.

The full year increase was primarily driven by higher profit share and changes in our product mix, partially offset by the replacement of the Puerto Rico excise tax with an income tax beginning in 2023. Non-GAAP R&D spend in the fourth quarter increased 16% year over year and 8% year over year for the full year, primarily due to higher spend on later stage clinical programs and marketed product support, including spend on programs acquired from the Horizon acquisition and continuing investment in our pipeline including MariTide. Q4 non-GAAP SG&A expenses increased 20% year over year, primarily driven by commercial and G&A expenses related to the Horizon acquisition. Full year non-GAAP SG&A expenses increased 5% year over year, primarily driven by commercial and G&A expenses related to the Horizon acquisition, partially offset by a decline in other marketed product spends.

Peter: Non-GAAP R&D spend in the fourth quarter increased 16% year over year and 8% year over year for the full year, primarily due to higher spend on later stage clinical programs and marketed product support including spend on programs acquired from the Horizon acquisition and continuing investment in our pipeline, including Maritime.

Peter: Q4 non-GAAP SG&A expenses increased 20% year over year, primarily driven by commercial and G&A expenses related to the Horizon acquisition. Full year non-GAAP SG&A expenses increased 5% year over year, primarily driven by commercial and G&A expenses related to the Horizon acquisition, partially offset by a decline in other marketed products spend.

Peter: Q4, non-GAAP SG&A expenses increased 20% year over year, primarily driven by commercial and G&A expenses related to the horizon acquisition.

Peter: Full year non-GAAP SG&A expenses increased 5% year over year, primarily driven by commercial and G&A expenses related to the horizon acquisition, partially offset by a decline in other marketed products.

Peter Griffith: Non-GAAP OIE were about $635 million in expense in the fourth quarter, $168 million increase year over year, primarily driven by increased interest expense related to the debt issued for the Horizon acquisition. Full year non-GAAP OIE was favorable $279 million year over year, primarily driven by the change in accounting for the Beijing investment to the fair value mark-to-market method and by gains related to early debt retirement, partially offset by higher net interest expense. Our non-GAAP tax rate increased 2.5 percentage points year over year to 15.9% in the fourth quarter and 2.7 percentage points year over year to 16.5% for the full year, primarily due to the 2022 Puerto Rico tax law change mentioned previously. The company generated $7.4 billion of free cash flow in 2023 compared with $8.8 billion in 2022.

Non-GAAP OIE were about $635 million in expense in the fourth quarter, $168 million increase year over year, primarily driven by increased interest expense related to the debt issued for the Horizon acquisition. Full year non-GAAP OIE was favorable $279 million year over year, primarily driven by the change in accounting for the Beijing investment to the fair value mark-to-market method and by gains related to early debt retirement, partially offset by higher net interest expense. Our non-GAAP tax rate increased 2.5 percentage points year over year to 15.9% in the fourth quarter and 2.7 percentage points year over year to 16.5% for the full year, primarily due to the 2022 Puerto Rico tax law change mentioned previously. The company generated $7.4 billion of free cash flow in 2023 compared with $8.8 billion in 2022.

Peter: Non-GAAP OINE were about $635 million in expense in the fourth quarter, a $168 million increase year over year, primarily driven by increased interest expense related to the debt issued for the Horizon acquisition.

Peter: Full year non-GAAP OINE was favorable $279 million year over year, primarily driven by the change in accounting for the Beijing investments to the fair value mark to market method and by gains related to early debt retirement, partially offset by higher net interest expense.

Peter: Our non-GAAP tax rate increased 2.5 percentage points year over year to 15.9% in the fourth quarter and 2.7 percentage points year over year to 16.5% for the full year, primarily due to the 2022 Puerto Rico tax law change mentioned previously.

Peter: The company generated $7.4 billion of free cash flow in 2023 compared with $8.8 billion in 2022. The decrease is driven by the Horizon transaction and integration costs, higher repatriation tax payments and higher capital expenditures. We expect to continue to generate strong cash flows with the addition of Horizon and are on track with our deleveraging plans to return to more efficient capital structure by the end of 2025.

Peter Griffith: The decrease is driven by the Horizon transaction and integration costs, higher repatriation tax payments, and higher capital expenditures. We expect to continue to generate strong cash flows with the addition of Horizon and are on track with our deleveraging plans to return to our efficient capital structure by the end of 2025. In summary, we continue to execute on our multiple capital allocation priorities. First, we continue to prioritize investments in both internal and external innovation. Our increased spending and non-GAAP R&D of 8% in 2023 over 2022, coupled with the acquisition of Horizon Therapeutics, continues to broaden and strengthen our balanced portfolio across therapeutic areas. With our strong late-stage innovative pipeline moving forward through development, we expect our non-GAAP R&D to continue to increase in 2024.

The decrease is driven by the Horizon transaction and integration costs, higher repatriation tax payments, and higher capital expenditures. We expect to continue to generate strong cash flows with the addition of Horizon and are on track with our deleveraging plans to return to our efficient capital structure by the end of 2025. In summary, we continue to execute on our multiple capital allocation priorities. First, we continue to prioritize investments in both internal and external innovation. Our increased spending and non-GAAP R&D of 8% in 2023 over 2022, coupled with the acquisition of Horizon Therapeutics, continues to broaden and strengthen our balanced portfolio across therapeutic areas. With our strong late-stage innovative pipeline moving forward through development, we expect our non-GAAP R&D to continue to increase in 2024.

Peter: The decrease is driven by the horizon transaction and integration costs higher repatriation tax payments and higher capital expenditures, we expect to continue to generate strong cash flows with the addition of horizon and are on track with our deleveraging plans to return to more efficient capital structure by the end of 2025.

Peter: In summary, we continue to execute on our multiple capital allocation priorities first we continue to priorities. First we continue to prioritize investments in both internal and external innovation. Our increased spending in non-GAAP R&D of 8% in '23 over '22 coupled with the acquisition of Horizon Therapeutics continues to broaden and strengthen our balanced portfolio across therapeutic areas.

Peter: Our increased spending in non-GAAP R&D of 8% and 23 over 'twenty two coupled with the acquisition of Horizon Therapeutics continues to broaden and strengthen our balanced portfolio across therapeutic areas.

Peter: With our strong late stage innovative pipeline moving forward through development, we expect our non-GAAP R&D to continue to increase in 2024. Second, we continue investing in our business for long term growth, including our state of the art manufacturing facilities in Ohio and North Carolina.

Peter Griffith: Second, we continue investing in our business for long-term growth including our state-of-the-art manufacturing facilities in Ohio and North Carolina. Amgen Ohio, our new advanced assembly and final product packaging plant, has just received licensure from the FDA for commercial production in January, roughly two years after we broke ground, and our innovative Drug Substance plant under construction in North Carolina is expected to be operational by 2026. In addition, we've positioned the organization to accelerate investments in innovation including leveraging the power of generative artificial intelligence, and third, we returned capital to shareholders through growing dividends including $2.13 per share in the quarter. This represented a 10% increase over that paid in each of 2022's four quarters.

Second, we continue investing in our business for long-term growth including our state-of-the-art manufacturing facilities in Ohio and North Carolina. Amgen Ohio, our new advanced assembly and final product packaging plant, has just received licensure from the FDA for commercial production in January, roughly two years after we broke ground, and our innovative Drug Substance plant under construction in North Carolina is expected to be operational by 2026. In addition, we've positioned the organization to accelerate investments in innovation including leveraging the power of generative artificial intelligence, and third, we returned capital to shareholders through growing dividends including $2.13 per share in the quarter. This represented a 10% increase over that paid in each of 2022's four quarters.

Robert A. Bradway: Second we continue investing in our business for long term growth, including our state of the art manufacturing facilities in Ohio, and North Carolina.

Robert A. Bradway: Amgen, Ohio, our new advanced assembly and final product packaging plant has just received licensure from the FDA for commercial production in January roughly two years after we broke ground. And our innovative drug substance plant under construction in North Carolina is expected to be operational by 2026.

Michael J. Yee: In addition, we position the organization to accelerate investments in innovation, including leveraging the power of generative artificial intelligence. And third we returned capital to shareholders through growing dividends, including $2.13 per share in the quarter. This represented a 10% increase over that pay nature of 2022 to four quarters. 

Peter Griffith: Turning to the outlook for the business for 2024 first, because this is the first full year incorporating the impact of Horizon, we're providing some additional granularity in our guidance, which we don't expect to repeat to the same extent in the future. For 2024 we're expecting revenue of $32.4 billion to $33.8 billion and non-GAAP earnings per share of $18.90 to $20.30. As we continue to integrate Horizon, we expect the acquisition to be accretive to non-GAAP EPS in 2024, and we're on track to meet the synergies target previously communicated of at least $500 million in pre-tax costs by year three after closing or in 2026. Our revenue range reflects our strong growth outlook driven by numerous opportunities across our four therapeutic area pillars.

Turning to the outlook for the business for 2024 first, because this is the first full year incorporating the impact of Horizon, we're providing some additional granularity in our guidance, which we don't expect to repeat to the same extent in the future. For 2024 we're expecting revenue of $32.4 billion to $33.8 billion and non-GAAP earnings per share of $18.90 to $20.30. As we continue to integrate Horizon, we expect the acquisition to be accretive to non-GAAP EPS in 2024, and we're on track to meet the synergies target previously communicated of at least $500 million in pre-tax costs by year three after closing or in 2026. Our revenue range reflects our strong growth outlook driven by numerous opportunities across our four therapeutic area pillars.

Michael J. Yee: Okay.

Speaker Change: Turning to the outlook for the business for 2024. First, because this is the first full year incorporating the impact of Horizon, we're providing some additional granularity on our guidance, which we don't expect to repeat to the same extent in the future.

Jay: For 2024, we're expecting revenue up $32.4 billion to $33.8 billion and non-GAAP earnings per share of $18.90 to $20.30. As we continue to integrate Horizon, we expect the acquisition to be accretive to non-GAAP EPS in 2024, and we are on track to meet the synergies target previously communicated of at least $500 million in pre-tax cost by year three after closing or in 2026.

Jay: As we continue to integrate horizon, we expect the acquisition to be accretive to non-GAAP EPS in 2024, and we are on track to meet the synergies target previously communicated of at least $500 million in pre tax pre tax cost by year three after closing or in 2026.

Jay: Our revenue range reflects our strong growth outlook driven by numerous opportunities across our core therapeutic area pillars. We will record a full year of legacy Horizon product sales and we expect continued volume driven growth in our priority products: REPATHA, [inaudible], EVENITY, [inaudible]. Consistent with industry trends and our recent history, we expect mid single digit price decline for our portfolio in 2024.

Peter Griffith: We will record a full year of legacy Horizon product sales, and we expect continued volume driven growth in our priority products Repatha, Tezspire, Evenity, Otezla, Prolia, and Blincyto. Consistent with industry trends in our recent history, we expect mid single digit price declines for our portfolio in 2024.

We will record a full year of legacy Horizon product sales, and we expect continued volume driven growth in our priority products Repatha, Tezspire, Evenity, Otezla, Prolia, and Blincyto. Consistent with industry trends in our recent history, we expect mid single digit price declines for our portfolio in 2024.

Jay: System with industry trends and our recent history, we expect mid single digit price decline for our portfolio in 2024.

Peter Griffith: As a reminder, as you model the first quarter of 2024 and consistent with our historical trends, we expect first quarter product sales to be the lowest quarter as a percentage of the full year due to benefit plan changes, insurance reverifications, and increased copay charges. So we expect the first quarter of 2024 total revenue to grow roughly 20% year over year. For the full year we expect other revenue to be in the range of approximately $1.3 to 1.4 billion and we continue to efficiently run the business through our disciplined approach to managing operating expenses. In 2024, we're making incremental R&amp;D investments to support our promising late stage pipeline including our rapidly advancing oncology programs as discussed following ESMO in October and other programs including MariTide.

As a reminder, as you model the first quarter of 2024 and consistent with our historical trends, we expect first quarter product sales to be the lowest quarter as a percentage of the full year due to benefit plan changes, insurance reverifications, and increased copay charges. So we expect the first quarter of 2024 total revenue to grow roughly 20% year over year. For the full year we expect other revenue to be in the range of approximately $1.3 to 1.4 billion and we continue to efficiently run the business through our disciplined approach to managing operating expenses. In 2024, we're making incremental R&amp;D investments to support our promising late stage pipeline including our rapidly advancing oncology programs as discussed following ESMO in October and other programs including MariTide.

Jay: As a reminder, as you model the first quarter of 2024 and consistent with our historical trends, we expect first quarter product sales to be the lowest quarter as a percentage of the full year due to the benefit plan changes, insurance re verifications, and increased co pay charges.

Jay: We expect the first quarter of 2024 total revenue to grow roughly 20% year over year. For the full year, we expect other revenue to be in the range of approximately 1.3 to 1.4 billion. And we continue to efficiently run the business through our disciplined approach to managing operating expenses. In 2024, we're making incremental R&D investments to support our promising late stage pipeline, including our rapidly advancing oncology programs as discussed following ESMO in October and other programs, including maritime.

Jay: For the full year, we expect other revenue to be in the range of approximately one three to one 4 billion. And we continue to efficiently run the business through our disciplined approach to managing operating expenses in 2024, we're making incremental R&D investments to support our promising late stage pipeline, including our rapidly advancing oncology programs as discussed following ESMO in October and other programs, including maritime.

Jay: And we continue to efficiently run the business through our disciplined approach to managing operating expenses in 2024, we're making incremental R&D investments to support our promising late stage pipeline, including our rapidly advancing oncology programs as discussed following ESMO in October and other programs, including maritime.

Peter Griffith: Furthermore, the addition of Horizon has an impact on the 2024 operating margin given the timing of when synergies are realized. As a result, we project the full year non-GAAP operating margin as a percentage of product sales to be roughly 48%. Note that we expect non-GAAP operating margin growth to accelerate in each of the quarters following the first quarter. There are primarily three reasons for this. First, typical lower product sales in Q1 as I mentioned above than in each of the following quarters.

Furthermore, the addition of Horizon has an impact on the 2024 operating margin given the timing of when synergies are realized. As a result, we project the full year non-GAAP operating margin as a percentage of product sales to be roughly 48%. Note that we expect non-GAAP operating margin growth to accelerate in each of the quarters following the first quarter. There are primarily three reasons for this. First, typical lower product sales in Q1 as I mentioned above than in each of the following quarters.

Salveen Richter: Furthermore, the addition of Horizon has an impact on the 2024 operating margin given the given the timing of linked synergies are realized. As a result, we project the full year non-GAAP operating margin as a percentage of product sales to be roughly 48%.

Salveen Richter: As a result, we project the full year non-GAAP operating margin as a percentage of product sales to be roughly 48%.

Speaker Change: Note that we expect non-GAAP operating margin growth to accelerate in each of the quarters following the first quarter. There are primarily three reasons for this. First, lower product sales in Q1, as I mentioned above and in each of the following quarters. Second, increased spend on our commercial brands. We'll continue building on the investments we made in the second half of 2023, including REPATHA, OTEZLA and our loan portfolio or EVENITY and PROLIA. And third, Q1 2024 reflects the addition of Horizon for which we are just at the beginning stages of realizing synergies given the acquisition close date of October 6th. So we expect non-GAAP operating margins to be roughly 43% in the first quarter.

Speaker Change: And there are primarily three reasons for this first.

Speaker Change: Lower product sales in Q1, as I mentioned above and in each of the following quarters.

Peter Griffith: Second, increased spend on our commercial brands will continue building on the investments we made in the second half of 2023, including Repatha, Otezla, and our bone portfolio of Evenity and Prolia. And third, Q1 2024 reflects the addition of Horizon, for which we are just at the beginning stages of realizing synergies given the acquisition close date of 6 October 2023, so we expect non-GAAP operating margin to be roughly 43% in the first quarter. I would reiterate that we expect operating margin growth to accelerate in each of the quarters following the first quarter. We project non-GAAP cost of sales to be in the range of 17% to 18% as a percentage of product sales for the 2024 year, taking into account the full year of Horizon-related expenses.

Second, increased spend on our commercial brands will continue building on the investments we made in the second half of 2023, including Repatha, Otezla, and our bone portfolio of Evenity and Prolia. And third, Q1 2024 reflects the addition of Horizon, for which we are just at the beginning stages of realizing synergies given the acquisition close date of 6 October 2023, so we expect non-GAAP operating margin to be roughly 43% in the first quarter. I would reiterate that we expect operating margin growth to accelerate in each of the quarters following the first quarter. We project non-GAAP cost of sales to be in the range of 17% to 18% as a percentage of product sales for the 2024 year, taking into account the full year of Horizon-related expenses.

Speaker Change: Increased spend on our commercial brands, we'll continue building on the investments we made in the second half of 2023, including our path of old Tesla in our loan portfolio or entity and Prolia.

Speaker Change: And third, Q1 2024 reflects the addition of Horizon for which we are just at the beginning stages of realizing synergies given the acquisition close date of October 6th.

Speaker Change: So we expect non-GAAP operating margins to be roughly 43% in the first quarter.

Speaker Change: I would reiterate that we expect operating margin growth to accelerate in each of the quarters following the first quarter. We project non-GAAP cost of sales to be in the range of 17% to 18% as a percentage of product sales for the 2024 year. Taking into account the full year Horizon related expenses, we expect non-GAAP R&D expenses in 2024 to increase approximately 20% year over year with investments also increasing to advance key pipeline assets, including AMG 193, maritime, [inaudible].

Speaker Change: We project non-GAAP cost of sales to be in the range of 17% to 18% as a percentage of product sales for the 2024 year taking into account the full year horizon related expenses, we expect non-GAAP R&D expenses in 2024 to increase approximately 20% year over year with investments also increasing to advanced key pipeline. Asset, including AMG 193, maritime broker <unk> in Thailand amount.

Peter Griffith: We expect non-GAAP R&D expenses in 2024 to increase approximately 20% year over year, with investments also increasing to advance key pipeline assets including AMG 193, MariTide, rocatinlimab, and tarlatamab. We see significant potential in our innovative pipeline, and it is important that we strategically invest now to fully unlock the opportunities ahead to create long-term value for patients, staff, and shareholders, and for non-GAAP SG&A spend. We expect 2024 full-year amounts as a percentage of product sales to be between 21% and 22%. We anticipate non-GAAP OIE to be in the range of $2.6 to 2.7 billion. As mentioned on our Q3 2023 call, the 2024 guidance includes the interest expense related to the $28 billion of debt raised for the Horizon acquisition. We expect a non-GAAP tax rate of 16% to 17%.

We expect non-GAAP R&D expenses in 2024 to increase approximately 20% year over year, with investments also increasing to advance key pipeline assets including AMG 193, MariTide, rocatinlimab, and tarlatamab. We see significant potential in our innovative pipeline, and it is important that we strategically invest now to fully unlock the opportunities ahead to create long-term value for patients, staff, and shareholders, and for non-GAAP SG&A spend. We expect 2024 full-year amounts as a percentage of product sales to be between 21% and 22%. We anticipate non-GAAP OIE to be in the range of $2.6 to 2.7 billion. As mentioned on our Q3 2023 call, the 2024 guidance includes the interest expense related to the $28 billion of debt raised for the Horizon acquisition. We expect a non-GAAP tax rate of 16% to 17%.

Speaker Change: Asset, including AMG 193, maritime broker <unk> in Thailand amount.

We see significant potential in our innovative pipeline and it is important that we strategically invest now to fully unlock the opportunities ahead to create long term value for patients staff and shareholders. And for non-GAAP SG&A spend, we expect 2024 full year amount as a percentage of product sales to be between 21 and 22%.

Speaker Change: And for non-GAAP SG&A spend we expect 2020 for full year amount as a percentage of product sales to be between 21 and 22%.

Speaker Change: We anticipate non-GAAP OINE to be in the range of 2.6-2.7 billion. As mentioned on our Q3 '23 call, the '24 guidance includes the interest expense related to the $28 billion of debt rates for the Horizon acquisition.

Jay Olson: We expect a non-GAAP tax rate of 16% to 17%. Our guidance is primarily being driven by two factors. The first is the jurisdictional mix of income, including the full year benefits associated with the Horizon transaction and the legal entity rationalization undertaken in the fourth quarter of 2023 in part to integrate the Horizon entities into our existing  US headquartered legal entity structure. The second is the benefit from a planned payment to the IRS as an advanced deposit. As we've done in the past to stop the accrual of interest on uncertain tax positions,

We expect a non-GAAP tax rate of 16% to 17%. Our guidance is primarily being driven by two factors. The first is the jurisdictional mix of income, including the full year benefits associated with the Horizon transaction and the legal entity rationalization undertaken in the fourth quarter of 2023 in part to integrate the Horizon entities into our existing US headquartered legal entity structure. 

Peter Griffith: Our guidance is primarily being driven by two factors. The first is the jurisdictional mix of income, including the full year benefits associated with the Horizon transaction and the legal entity rationalization undertaken in Q4 2023, in part to integrate the Horizon entities into our existing US-headquartered legal entity structure. The second is the benefit from a planned payment to the IRS as an advance deposit, as we've done in the past to stop the accrual of interest on uncertain tax positions. There is no change in our belief in the merits of our legal arguments with the IRS as we prepare for trial given the interest rate environment. Although the deposit negatively affects our cash flow in 2024, if any of the deposit is returned to us upon the resolution of our litigation, those funds would accrue interest income.

Our guidance is primarily being driven by two factors. The first is the jurisdictional mix of income, including the full year benefits associated with the Horizon transaction and the legal entity rationalization undertaken in Q4 2023, in part to integrate the Horizon entities into our existing US-headquartered legal entity structure. The second is the benefit from a planned payment to the IRS as an advance deposit, as we've done in the past to stop the accrual of interest on uncertain tax positions. There is no change in our belief in the merits of our legal arguments with the IRS as we prepare for trial given the interest rate environment. Although the deposit negatively affects our cash flow in 2024, if any of the deposit is returned to us upon the resolution of our litigation, those funds would accrue interest income.

Jay Olson: Horizon entities into our existing 

Jay Olson: US headquartered legal entity structure. The second is the benefit from a planned payment to the IRS as an advanced deposit. As we've done in the past to stop the accrual of interest on uncertain tax positions,

The second is the benefit from a planned payment to the IRS as an advanced deposit. As we've done in the past to stop the accrual of interest on uncertain tax positions, there is no change in our belief in the merits of our legal arguments with the IRS as we prepare for trial. Given the interest rate environment, although the deposit negatively affects our cash flow in '24, if any of the deposit is returned to us upon the resolution of our litigation, those funds would accrue interest income therefore, the radar arbitrage makes  this payment a prudent use of our capital. Once again, out of an abundance of clarity, this represents no change in our belief in the merits of the tax court case.

Speaker Change: there is no change in our belief in the merits of our legal arguments with the IRS as we prepare for trial. Given the interest rate environment, although the deposit negatively affects our cash flow in '24, if any of the deposit is returned to us upon the resolution of our litigation, those funds would accrue interest income therefore, the radar arbitrage makes 

Peter Griffith: Therefore, the rate arbitrage makes this payment a prudent use of our capital. Once again, out of an abundance of clarity, this represents no change in our belief in the merits of the Tax Court case. The guidance also includes the impact of the adoption of the OECD 15% minimum tax by certain jurisdictions. Based on our individual footprint, we don't anticipate any significant effects of the new rules in 2024, but we're closely watching the global tax landscape for future impacts. As the framework continues to be considered by additional jurisdictions and new rules take effect, we expect governments around the world, including the United States, to continue to look for more sources of tax revenue from large multinational corporations that could result in higher taxes in the coming years. Similar to 2023, we expect share repurchases now to exceed $500 million in 2024.

Therefore, the rate arbitrage makes this payment a prudent use of our capital. Once again, out of an abundance of clarity, this represents no change in our belief in the merits of the Tax Court case. The guidance also includes the impact of the adoption of the OECD 15% minimum tax by certain jurisdictions. Based on our individual footprint, we don't anticipate any significant effects of the new rules in 2024, but we're closely watching the global tax landscape for future impacts. As the framework continues to be considered by additional jurisdictions and new rules take effect, we expect governments around the world, including the United States, to continue to look for more sources of tax revenue from large multinational corporations that could result in higher taxes in the coming years. Similar to 2023, we expect share repurchases now to exceed $500 million in 2024.

Speaker Change: this payment a prudent use of our capital. Once again, out of an abundance of clarity, this represents no change in our belief in the merits of the tax court case.

Speaker Change: The guidance also includes the impact of the adoption of the OECD 15% minimum tax by certain jurisdictions. Based on our individual footprint, we don't anticipate any significant effects of the new rules in 2024 but we are closely watching the global tax landscape for future impacts as the framework continues to be considered by additional jurisdictions and new rules take effect.

Speaker Change: We expect governments around the world, including the United States to continue to look for more sources of tax revenue from large multinational corporations that could result in higher taxes in the coming years.

Speaker Change: Similar to 2023, we expect share repurchases not to exceed $500 million in 2024. We expect that we will continue to increase our dividend. We expect capital expenditures of approximately $1.1 billion in 2024, consistent with our capital allocation priority to invest in our business, including the Ohio and North Carolina facilities I mentioned ahead and into the rare disease pillar.

Peter Griffith: We expect that we will continue to increase our dividend. We expect capital expenditures of approximately $1.1 billion in 2024, consistent with our capital allocation priority, to invest in our business, including the Ohio, and North Carolina facilities I mentioned ahead and into the rare disease pillar. In summary, we delivered another strong year of financial results in 2023. Our confidence in the long term growth of Amgen is strong, and we believe that our new rare disease pillar, one of our four pillars, will be an important additive source of growth for the company. This concludes the financial update. My thanks to my approximately 27,000-plus colleagues at Amgen around the world for their commitment to our mission of serving patients and their tireless efforts in 2023. I'll turn it back to Bob for Q&A.

We expect that we will continue to increase our dividend. We expect capital expenditures of approximately $1.1 billion in 2024, consistent with our capital allocation priority, to invest in our business, including the Ohio, and North Carolina facilities I mentioned ahead and into the rare disease pillar. In summary, we delivered another strong year of financial results in 2023. Our confidence in the long term growth of Amgen is strong, and we believe that our new rare disease pillar, one of our four pillars, will be an important additive source of growth for the company. This concludes the financial update. My thanks to my approximately 27,000-plus colleagues at Amgen around the world for their commitment to our mission of serving patients and their tireless efforts in 2023. I'll turn it back to Bob for Q&A.

Chris Schott: Facilities, I mentioned ahead and into the rare disease pillar.

Speaker Change #100: In summary, we delivered another strong year of financial results in 2023. Our confidence in the long term growth of Amgen is strong and we believe that our new rare disease pillar, one of our four pillars will be an important additive source of growth for the company. This concludes the financial update. My thanks to my approximately 27,000 plus colleagues at Amgen around the world for their commitment to our mission of serving patients and their tireless efforts in 2023. I'll turn it back to Bob for Q&A.

Speaker Change: 1000, plus colleagues at Amgen around the world for their commitment to our mission of serving patients and their tireless efforts in 2023.

Vikram: I'll turn it back to Bob for Q&A.

Robert Bradway: Okay, thank you. Let's open the line and we'll take questions from our callers. Julianne, why don't you remind them of the procedures so we can get through these questions here efficiently for everyone.

Bob Bradway: Okay, thank you. Let's open the line and we'll take questions from our callers. Julianne, why don't you remind them of the procedures so we can get through these questions here efficiently for everyone.

Bob Bradway: Okay, thank you. Let's open the line and we will take questions from our callers. Julien, why don't you remind them of the procedures so we can get through these questions here efficiently for everyone.

Robert A. Bradway: Okay. Thank you. Open the line and we will take questions from our callers julianne, whether or to remind them of the procedures. So we can get through these questions here efficiently for everyone.

Robert A. Bradway: Open the line and we will take questions from our callers julianne, whether or to remind them of the procedures. So we can get through these questions here efficiently for everyone.

Operator: Thank you. If you would like to ask a question, please press star followed by one on your telephone keypad. If for any reason you would like to remove that question, please press star followed by one again. To ask a question, press star one. Our first question comes from Michael Yee from Jefferies. Please go ahead. Your line is open.

Operator: Thank you. If you would like to ask a question, please press star followed by one on your telephone keypad. If for any reason you would like to remove that question, please press star followed by one again. To ask a question, press star one. Our first question comes from Michael Yee from Jefferies. Please go ahead. Your line is open.

Operator: Thank you. If you would like to ask a question, please press star followed by one on your telephone keypad. If for any reason you would like to remove that question, please press star followed by one. Again to ask a question, press star one.

Vikram: Any reason you would like to remove that question. Please press star followed by one. Wanted to ask a question press star one.

Vikram: Wanted to ask a question press star one.

Operator: Our first question comes from Michael Yee from Jefferies. Please go ahead. Your line is open.

Robert Bradway: Hey guys, good afternoon, and thanks for.

Michael Yee: Hey guys, good afternoon, and thanks for.

Michael J. Yee: Hey guys, good afternoon, and thanks for the good results and good guidance. We have a question on obesity. On 133 of course, you had the publication yesterday, I feel like it was the most scrutinized phase one publication, but maybe you could just talk to maybe Jay can talk to your interpretation of some of the markers for example, lipids, A1C, blood pressure and all that kind of thing and maybe talk about your confidence level about the profile versus competitors. Thank you so much.

Justin Claeys: Good results and good guidance.

Good results and good guidance.

Robert Bradway: We had a question on obesity on 133.

We had a question on obesity on 133.

Michael J. Yee: We have a question on <unk>. 133 of course, you had the publication yesterday I feel like it was the most scrutinized phase one publication, but maybe you could just talk to maybe Jay can talk to their interpretation of some of the markers for example, lipids <unk> blood pressure and all that kind of thing and maybe talk about your confidence level about the profile of <unk> versus competitors. Thank you so much.

Justin Claeys: Of course you had the publication yesterday.

Of course you had the publication yesterday.

Michael J. Yee: 133 of course, you had the publication yesterday I feel like it was the most scrutinized phase one publication, but maybe you could just talk to maybe Jay can talk to their interpretation of some of the markers for example, lipids <unk> blood pressure and all that kind of thing and maybe talk about your confidence level about the profile of <unk> versus competitors. Thank you so much.

Robert Bradway: I feel like it was the most.

I feel like it was the most.

Justin Claeys: Scrutinized Phase 1 publication.

Scrutinized Phase 1 publication.

Robert Bradway: Maybe you could just talk to.

Maybe you could just talk to.

Justin Claeys: Maybe Jay could talk to your interpretation.

Maybe Jay could talk to your interpretation.

Robert Bradway: Of some of the markers, for example.

Of some of the markers, for example.

Justin Claeys: Lipids, A1C, blood pressure, and all that kind of thing, and maybe talk about your confidence level about the profile versus competitors. Thank you so much. Yeah, thanks a lot, Michael. We really appreciate the consideration the Phase 1 paper is receiving from the community. It's exciting to report these data for those who haven't seen it. This was a randomized, double-blind, placebo-controlled study: 49 patients looking at safety, PK, PD, single ascending dose, seven cohorts, multiple ascending dose, three cohorts, three monthly doses, patients with obesity, BMI greater than 30. We were quite pleased with the outcome, looking at the 420mg dose as an example, which was the highest dose study: 14.5% weight loss at only day 85 and, moreover, quite durable coming off of that medicine out to 150 days, all with relatively mild gastrointestinal side effects.

Lipids, A1C, blood pressure, and all that kind of thing, and maybe talk about your confidence level about the profile versus competitors. Thank you so much.

Jay Bradner: Yeah, thanks a lot, Michael. We really appreciate the consideration the Phase 1 paper is receiving from the community. It's exciting to report these data for those who haven't seen it. This was a randomized, double-blind, placebo-controlled study: 49 patients looking at safety, PK, PD, single ascending dose, seven cohorts, multiple ascending dose, three cohorts, three monthly doses, patients with obesity, BMI greater than 30. We were quite pleased with the outcome, looking at the 420mg dose as an example, which was the highest dose study: 14.5% weight loss at only day 85 and, moreover, quite durable coming off of that medicine out to 150 days, all with relatively mild gastrointestinal side effects.

Speaker Change #101: Thank you so much.

Jay Bradner: Yeah, thanks a lot Michael. We really appreciate the consideration the phase one paper is receiving from the community. It's exciting to report these data. For those who haven't seen it, this was a randomized double blind placebo controlled study 49 patients looking at safety, PK, PD single ascending dose seven cohorts, multiple ascending dose three cohorts, three monthly doses in patients with obesity, BMI greater than 30% and we were quite pleased with the outcome. We're looking at the 420 milligram dose as an example, which was the highest dose studied, 14.5% weight loss at only day 85. And moreover, quite durable coming off of that medicine out to 150 days, all with relatively mild gastrointestinal side effects.

Vikram: Exciting to report these data for those who haven't seen it. This was a randomized double blind placebo controlled study 49 patients looking at safety PK PD single ascending dose seven cohorts multiple ascending dose three cohorts three monthly doses. Patients with obesity, BMI greater than 30% and. And where. We were quite pleased with the outcome. We're looking at the 420 milligram dose as an example, which was the highest dose studied 14, 5% weight loss. It only day 85.

Vikram: Patients with obesity, BMI greater than 30% and. And where. We were quite pleased with the outcome. We're looking at the 420 milligram dose as an example, which was the highest dose studied 14, 5% weight loss. It only day 85.

Vikram: And where. We were quite pleased with the outcome. We're looking at the 420 milligram dose as an example, which was the highest dose studied 14, 5% weight loss. It only day 85.

Speaker Change: We were quite pleased with the outcome. We're looking at the 420 milligram dose as an example, which was the highest dose studied 14, 5% weight loss. It only day 85.

Speaker Change: And moreover, quite durable coming off of that medicine out to 150 days, all with relatively mild gastrointestinal side effects. And so to answer your last question first, we find the phase one data, which we're pleased to share with the community to be quite supportive of our ongoing work to develop this medicine to the greatest possible benefit of patients suffering from obesity. You've asked questions around some of the measurements on this study, lipid, blood pressure, and A1C and I would just caution that this is a phase one trial, the numbers are very small, the duration of treatment is rather short, but even with all of those caveats while hard to draw conclusions from such small numbers, especially labile measurements like blood pressure and lipids, all are directionally favorable so we take no concern whatsoever from those measurements on the study.

And moreover, quite durable coming off of that medicine out to 150 days, all with relatively mild gastrointestinal side effects.

Justin Claeys: To answer your last question, first we find the Phase 1 data which we're pleased to share with the community to be quite supportive of our ongoing work to develop this medicine to the greatest possible benefit of patients suffering from obesity. Now, you've asked questions around some of the measurements on this study, lipids, blood pressure, and A1C, and I would just caution that this is a Phase 1 trial. A number of Ns are very small, that the duration of treatment is rather short. But even with all of those caveats, while hard to draw conclusions from such small numbers, especially labile measurements like blood pressure and lipids, all are directionally favorable. And so we take no concern whatsoever from those measurements on the study.

To answer your last question, first we find the Phase 1 data which we're pleased to share with the community to be quite supportive of our ongoing work to develop this medicine to the greatest possible benefit of patients suffering from obesity. Now, you've asked questions around some of the measurements on this study, lipids, blood pressure, and A1C, and I would just caution that this is a Phase 1 trial. A number of Ns are very small, that the duration of treatment is rather short. But even with all of those caveats, while hard to draw conclusions from such small numbers, especially labile measurements like blood pressure and lipids, all are directionally favorable. And so we take no concern whatsoever from those measurements on the study.

And so to answer your last question first, we find the phase one data, which we're pleased to share with the community to be quite supportive of our ongoing work to develop this medicine to the greatest possible benefit of patients suffering from obesity. You've asked questions around some of the measurements on this study, lipid, blood pressure, and A1C and I would just caution that this is a phase one trial, the numbers are very small, the duration of treatment is rather short, but even with all of those caveats while hard to draw conclusions from such small numbers, especially labile measurements like blood pressure and lipids, all are directionally favorable so we take no concern whatsoever from those measurements on the study.

Speaker Change: We find the phase one data, which we're pleased to share with the community to be quite supportive of our ongoing work to develop this medicine to the greatest possible benefit of patients suffering from obesity and <unk>. <unk> questions around some of the measurements on this study lipid blood pressure in <unk> and I would just caution that this is a phase one trial. The numbers are very small at the duration of treatment is rather short, but even with all of those caveat. While hard to draw conclusions from such such small numbers. Especially labor all measurements like blood pressure and lipids. All are directionally favorable. So we have we take no concern whatsoever from those measurements on the study.

Evan: <unk> questions around some of the measurements on this study lipid blood pressure in <unk> and I would just caution that this is a phase one trial. The numbers are very small at the duration of treatment is rather short, but even with all of those caveat. While hard to draw conclusions from such such small numbers. Especially labor all measurements like blood pressure and lipids. All are directionally favorable. So we have we take no concern whatsoever from those measurements on the study.

Evan: While hard to draw conclusions from such such small numbers. Especially labor all measurements like blood pressure and lipids. All are directionally favorable. So we have we take no concern whatsoever from those measurements on the study.

Evan: Especially labor all measurements like blood pressure and lipids. All are directionally favorable. So we have we take no concern whatsoever from those measurements on the study.

Speaker Change #103: All are directionally favorable. So we have we take no concern whatsoever from those measurements on the study.

Speaker Change #104: So we have we take no concern whatsoever from those measurements on the study.

Operator: Thank you, Michael.

Operator: Thank you, Michael.

Robert Bradway: Okay, let's go to the next question.

Bob Bradway: Okay, let's go to the next question.

Operator: Thank you Michael. Our next question comes from Salveen Richter from Goldman Sachs. Please go ahead. Your line is open.

Operator: Thank you, Michael. Our next question comes from Salveen Richter from Goldman Sachs. Please go ahead. Your line is open.

Operator: Thank you, Michael. Our next question comes from Salveen Richter from Goldman Sachs. Please go ahead. Your line is open.

Operator: Thank you Michael our next question comes from selling Richter from Goldman Sachs. Please go ahead. Your line is open.

Robert Bradway: Good afternoon.

Salveen Richter: Good afternoon.

[Analyst]: Thanks for taking my question. Another one here on the obesity program. So post the published Phase 1 data. How are you thinking about differentiation on GI tolerability? Is the dose range being evaluated in the Phase 2 study similar to that in the Phase 1?

Thanks for taking my question. Another one here on the obesity program. So post the published Phase 1 data. How are you thinking about differentiation on GI tolerability? Is the dose range being evaluated in the Phase 2 study similar to that in the Phase 1?

Salveen Richter: Good afternoon, thanks for taking my question. Another one here on the obesity program. So post the published phase one data, how are you thinking about differentiation on Gi tolerability? Is the dose range being evaluated in a phase two study similar to that in the phase one? Thank you.

Peter Griffith: Thank you.

Thank you.

Justin Claeys: Yes, thanks for the question. I'll take this one as well. As you may or may not know, the phase 2 study, which is ongoing at present and going very well, explores 11 dosing cohorts with relevant placebo controls. Through that study, we'll have a chance to gain an experience with a longer exposure to MariTide dosed in different ways. We've recently added a part 2 to this study that will allow us to explore even more durable weight loss beyond 52 weeks, enabled by just very rapid enrollment. These four dosing cohorts will go on to test dose level and even less frequent dosing schedules than monthly. And so.

Jay Bradner: Yes, thanks for the question. I'll take this one as well. As you may or may not know, the phase 2 study, which is ongoing at present and going very well, explores 11 dosing cohorts with relevant placebo controls. Through that study, we'll have a chance to gain an experience with a longer exposure to MariTide dosed in different ways. We've recently added a part 2 to this study that will allow us to explore even more durable weight loss beyond 52 weeks, enabled by just very rapid enrollment. These four dosing cohorts will go on to test dose level and even less frequent dosing schedules than monthly. And so.

Jay Bradner: Yes, thanks for the question, I'll take this one as well. As you may or may not know, the phase two study, which is ongoing at present and going very well explores 11 dosing cohorts with relevant placebo controls and through that study we will have a chance to gain experience with a longer exposure to maritime dose in different ways. We've recently added a part two to this study that will allow us to explore even more durable weight loss beyond 52 weeks enabled by just very rapid enrollment and these four dosing cohorts will go on to test dose level in even less frequent dosing schedules other than monthly. And so these phase two data, even by end of year will be strongly instructive as to finding a safe and tolerated and efficacious dose to carry into phase III clinical investigation.

Speaker Change #106: As you may or May not know the phase two study, which is ongoing at present and going very well. Floors 11 dosing cohorts. Relevant placebo controls and through that study will have a chance to gaining experience with a longer exposure to maritime.

Murdo: Floors 11 dosing cohorts. Relevant placebo controls and through that study will have a chance to gaining experience with a longer exposure to maritime.

Murdo: Relevant placebo controls and through that study will have a chance to gaining experience with a longer exposure to maritime.

Murdo: Most in different ways. We've recently added a part two to this study that will allow us to explore even more durable weight loss beyond 52 weeks. Enabled by just very rapid enrollment and these four dosing cohorts will go on to test dose level in an even less. Less frequent dosing schedules of <unk> monthly. And so. These phase two data. Even by end of year will be strongly instructive as to finding a safe and tolerated and efficacious dose to carry into phase III clinical investigation.

Murdo: Enabled by just very rapid enrollment and these four dosing cohorts will go on to test dose level in an even less. Less frequent dosing schedules of <unk> monthly. And so. These phase two data. Even by end of year will be strongly instructive as to finding a safe and tolerated and efficacious dose to carry into phase III clinical investigation.

Murdo: Less frequent dosing schedules of <unk> monthly. And so. These phase two data. Even by end of year will be strongly instructive as to finding a safe and tolerated and efficacious dose to carry into phase III clinical investigation.

Murdo Gordon: And so. These phase two data. Even by end of year will be strongly instructive as to finding a safe and tolerated and efficacious dose to carry into phase III clinical investigation.

Justin Claeys: These Phase 2 data, even by end of year, will be strongly instructive as to finding a safe and tolerated and efficacious dose to carry into Phase 3 clinical investigation. Yeah, the only thing I would add.

These Phase 2 data, even by end of year, will be strongly instructive as to finding a safe and tolerated and efficacious dose to carry into Phase 3 clinical investigation.

Murdo Gordon: These phase two data. Even by end of year will be strongly instructive as to finding a safe and tolerated and efficacious dose to carry into phase III clinical investigation.

Murdo Gordon: Even by end of year will be strongly instructive as to finding a safe and tolerated and efficacious dose to carry into phase III clinical investigation.

Murdo Gordon: Yeah, the only thing I would add.

Murdo Gordon: As we're starting from a basis of a monthly dosing cadence and schedule. And so the additional dosing cohorts would look at potential dosing schedule beyond monthly.

As we're starting from a basis of a monthly dosing cadence and schedule. And so the additional dosing cohorts would look at potential dosing schedule beyond monthly.

Murdo Gordon: Yeah, the only thing I would add is we're starting from a basis of a monthly dosing cadence and schedule and so the additional dosing cohorts would look at potential dosing schedule beyond monthly and the data are pretty clear in the market right now that the Gi toxicity or Gi side effects are generally related to the day of dosing of the GLP ones, which are dosed weekly. We see some of that same Gi side effect profile in kind of the first dose part of the dose titration, but there is an opportunity here to potentially spread the dosing intervals out further and further improve tolerability in our program. And as Jay clearly described, we've got all of the different aspects of that being studied in the phase II program.

Cadence and schedule and so the additional dosing cohorts would look at potential. Dosing schedule beyond monthly and the data are pretty clear in the market right now. Gi toxicity or Gi side effects are generally related to the day of dosing of the <unk> ones, which are dose weekly. We see some of that same Gi side effect profile in kind of the first dose of the dose titration, but there is an opportunity here to potentially spread the dosing intervals out further and further improve tolerability and are in our program and as Jay clearly described we've got. All of the different aspects of that being studied in the phase III program.

Justin Claeys: And, you know, the data are.

And, you know, the data are.

Dosing schedule beyond monthly and the data are pretty clear in the market right now. Gi toxicity or Gi side effects are generally related to the day of dosing of the <unk> ones, which are dose weekly. We see some of that same Gi side effect profile in kind of the first dose of the dose titration, but there is an opportunity here to potentially spread the dosing intervals out further and further improve tolerability and are in our program and as Jay clearly described we've got. All of the different aspects of that being studied in the phase III program.

Murdo Gordon: Pretty clear in the market right now that the GI toxicity or GI side effects are generally related to the day of dosing of the GLP1s, which are dosed weekly. We see some of that same GI side effect profile in kind of the first dose part of the dose titration. But there's an opportunity here to potentially spread the dosing intervals out further and further improve tolerability in our program. And as Jay clearly described, we've got all of the different aspects of that being studied in the phase 2 program.

Murdo Gordon: Pretty clear in the market right now that the GI toxicity or GI side effects are generally related to the day of dosing of the GLP1s, which are dosed weekly. We see some of that same GI side effect profile in kind of the first dose part of the dose titration. But there's an opportunity here to potentially spread the dosing intervals out further and further improve tolerability in our program. And as Jay clearly described, we've got all of the different aspects of that being studied in the phase 2 program.

Murdo: Gi toxicity or Gi side effects are generally related to the day of dosing of the <unk> ones, which are dose weekly. We see some of that same Gi side effect profile in kind of the first dose of the dose titration, but there is an opportunity here to potentially spread the dosing intervals out further and further improve tolerability and are in our program and as Jay clearly described we've got. All of the different aspects of that being studied in the phase III program.

Omar: We see some of that same Gi side effect profile in kind of the first dose of the dose titration, but there is an opportunity here to potentially spread the dosing intervals out further and further improve tolerability and are in our program and as Jay clearly described we've got. All of the different aspects of that being studied in the phase III program.

Omar: All of the different aspects of that being studied in the phase III program.

Justin Claeys: Thanks, Julianne. We'll go to the next question.

Justin Claeys: Thanks, Julianne. We'll go to the next question.

Justin Claeys: Thanks Julien. We'll go to next question.

Operator: Thank you, Salveen. Our next question comes from Jay Olson from Oppenheimer. Please go ahead. Your line is open.

Operator: Thank you, Salveen. Our next question comes from Jay Olson from Oppenheimer. Please go ahead. Your line is open.

Operator: Thank you Salveen. Our next question comes from Jay Olson from Oppenheimer. Please go ahead. Your line is open.

Robert Bradway: Hello.

Bob Bradway: Hello.

Justin Claeys: Hey, thank you so much for taking the question and congrats on the progress. Another question on 133. Talk about whether or not the data that we see later this year will include patients from part two of the study. And do you think it's possible that 133 could be dosed once every two or three months? And also if you could just comment on the rollover rate of patients from part one to part two. Thank you.

Jay Olson: Hey, thank you so much for taking the question and congrats on the progress. Another question on 133. Talk about whether or not the data that we see later this year will include patients from part two of the study. And do you think it's possible that 133 could be dosed once every two or three months? And also if you could just comment on the rollover rate of patients from part one to part two. Thank you.

Jay Olson: Hey, thank you so much for taking my question and congrats on the progress. Another question on 133, talk about whether or not we will later this year [inaudible] will include patients from phase two of the study. Do you think it's possible that 133 could be dosed every two or three months? And also if you could just comment on the rollover rate of patients from part one part two. Thank you.

Jay Olson: Oh, Hey, thank you so much for taking my question and congrats on the progress another question on 133. About whether or not to.

Speaker Change: About whether or not to.

Speaker Change #108: Later this year will. We will include patients from two of the study. Do you think it's possible that <unk> could be tones tweets every two or three months and also if you could just comment on the rollover rate of patients from part one part two thank you.

Speaker Change #108: We will include patients from two of the study. Do you think it's possible that <unk> could be tones tweets every two or three months and also if you could just comment on the rollover rate of patients from part one part two thank you.

Speaker Change: Do you think it's possible that <unk> could be tones tweets every two or three months and also if you could just comment on the rollover rate of patients from part one part two thank you.

Robert Bradway: Jay, could you catch all that? Some of what Jay asked was broken up at the beginning, the third part.

Bob Bradway: Jay, could you catch all that? Some of what Jay asked was broken up at the beginning, the third part.

Speaker Change #109: Jay, could you catch all that? Some of what Jay asked was broken up in the beginning. The third part was a little bit broken up of your question. I heard a better explanation of part two frequency of dosing and then I did not hear your third part.

Murdo Gordon: Jay, could you catch all that? Some of what Jay asked was broken up in the beginning.

Justin Claeys: was a little bit broken up of your question. I heard a better explanation of part 2, frequency of dosing, and then I did not hear your third part.

Jay Olson: was a little bit broken up of your question. I heard a better explanation of part 2, frequency of dosing, and then I did not hear your third part.

Jay Bradner: The third part was a little bit broken up of your question. I heard a better explanation of part two frequency of dosing and then I did not hear your third part.

Vikram Karnani: It was five months later.

Justin Claeys: It was five months later.

Robert Bradway: Oh.

Bob Bradway: Oh.

Justin Claeys: If you just comment on the rate of patients rolling over from part one to part two?

Jay Olson: If you just comment on the rate of patients rolling over from part one to part two?

Speaker Change #110: If you'd just comment on the rate of patients rolling over some part one to part two, thanks. Okay, thank you for the question Jay. Let me give a little bit of context on this part two study that I think will help answer that. In part two the intent is to really look at durable weight loss beyond 52 weeks. By durable weight loss patients eligible for part two which begins at the end of 52 weeks will be responding to this medicine, and then they'll be re randomized to four cohorts that will test dose level and again with even less frequent dosing schedule. We have not disclosed the granularity on the dosing schedule. This is a competitive environment but we are afforded this chance because the ADC, the antibody core of maritime like so many immunoglobulin therapeutics allows for the opportunity to use it much less frequently. The rate of patients rolling over to part two will be established as the phase II study continues to progress this year.

Jay Olson: If you'd just comment on the rate of patients rolling over some part one to part two, thanks.

Robert Bradway: Thanks.

Thanks.

Justin Claeys: Okay. Yeah, thank you for the question, Jay. Let me give a little bit of context on this part two study that I think will help answer them. In part two, the intent is to really look at durable weight loss beyond 52 weeks. And so by durable weight loss, patients eligible for part two, which begins at the end of 52 weeks, will be responding to this medicine. And then they'll be re randomized to four cohorts that'll test dose level and again, this even less frequent dosing schedule. We have not disclosed the granularity on the dosing schedule. This is a competitive environment, but we're.

Jay Olson: Okay. Yeah, thank you for the question, Jay. Let me give a little bit of context on this part two study that I think will help answer them. In part two, the intent is to really look at durable weight loss beyond 52 weeks. And so by durable weight loss, patients eligible for part two, which begins at the end of 52 weeks, will be responding to this medicine. And then they'll be re randomized to four cohorts that'll test dose level and again, this even less frequent dosing schedule. We have not disclosed the granularity on the dosing schedule. This is a competitive environment, but we're.

Jay Bradner: Okay, thank you for the question Jay. Let me give a little bit of context on this part two study that I think will help answer that. In part two the intent is to really look at durable weight loss beyond 52 weeks. By durable weight loss patients eligible for part two which begins at the end of 52 weeks will be responding to this medicine, and then they'll be re randomized to four cohorts that will test dose level and again with even less frequent dosing schedule. We have not disclosed the granularity on the dosing schedule. This is a competitive environment but we are afforded this chance because the ADC, the antibody core of maritime like so many immunoglobulin therapeutics allows for the opportunity to use it much less frequently. The rate of patients rolling over to part two will be established as the phase II study continues to progress this year.

Speaker Change #110: In part to the intent is to really look at durable weight loss beyond 52 weeks. By durable weight loss patients eligible for part two which begins at the end of 52 weeks. B. Funding to this medicine, and then there'll be re randomized two four cohorts that will test dose level and again this even less frequent dosing schedule. We have not disclosed. Granularity on the dosing schedule. This is a competitive environment. But we are afforded this chance because the ADC the antibody core of maritime like so many immunoglobulin therapeutics. Allows for the opportunity to use it much less frequently. The rate of patients rolling over to part two will be established as the. Phase II study continues to progress this year.

Speaker Change: By durable weight loss patients eligible for part two which begins at the end of 52 weeks. B. Funding to this medicine, and then there'll be re randomized two four cohorts that will test dose level and again this even less frequent dosing schedule. We have not disclosed. Granularity on the dosing schedule. This is a competitive environment. But we are afforded this chance because the ADC the antibody core of maritime like so many immunoglobulin therapeutics. Allows for the opportunity to use it much less frequently. The rate of patients rolling over to part two will be established as the. Phase II study continues to progress this year.

B. Funding to this medicine, and then there'll be re randomized two four cohorts that will test dose level and again this even less frequent dosing schedule. We have not disclosed. Granularity on the dosing schedule. This is a competitive environment. But we are afforded this chance because the ADC the antibody core of maritime like so many immunoglobulin therapeutics. Allows for the opportunity to use it much less frequently. The rate of patients rolling over to part two will be established as the. Phase II study continues to progress this year.

Speaker Change: Funding to this medicine, and then there'll be re randomized two four cohorts that will test dose level and again this even less frequent dosing schedule. We have not disclosed. Granularity on the dosing schedule. This is a competitive environment. But we are afforded this chance because the ADC the antibody core of maritime like so many immunoglobulin therapeutics. Allows for the opportunity to use it much less frequently. The rate of patients rolling over to part two will be established as the. Phase II study continues to progress this year.

Geoff Meacham: We have not disclosed. Granularity on the dosing schedule. This is a competitive environment. But we are afforded this chance because the ADC the antibody core of maritime like so many immunoglobulin therapeutics. Allows for the opportunity to use it much less frequently. The rate of patients rolling over to part two will be established as the. Phase II study continues to progress this year.

Geoff Meacham: Granularity on the dosing schedule. This is a competitive environment. But we are afforded this chance because the ADC the antibody core of maritime like so many immunoglobulin therapeutics. Allows for the opportunity to use it much less frequently. The rate of patients rolling over to part two will be established as the. Phase II study continues to progress this year.

Peter Griffith: Afforded this chance because the ADC,

Afforded this chance because the ADC,

Geoff Meacham: But we are afforded this chance because the ADC the antibody core of maritime like so many immunoglobulin therapeutics. Allows for the opportunity to use it much less frequently. The rate of patients rolling over to part two will be established as the. Phase II study continues to progress this year.

Justin Claeys: Antibody core of MariTide, like so many immunoglobulin therapeutics, allows for the opportunity to use it much less frequently. The rate of patients rolling over to part two will be established as the Phase 2 study continues to progress this year.

Antibody core of MariTide, like so many immunoglobulin therapeutics, allows for the opportunity to use it much less frequently. The rate of patients rolling over to part two will be established as the Phase 2 study continues to progress this year.

Geoff Meacham: Allows for the opportunity to use it much less frequently. The rate of patients rolling over to part two will be established as the. Phase II study continues to progress this year.

Geoff Meacham: The rate of patients rolling over to part two will be established as the. Phase II study continues to progress this year.

Geoff Meacham: Phase II study continues to progress this year.

Peter Griffith: Thank you.

Jay Olson: Thank you.

Justin Claeys: Julianne, go to the next question.

Justin Claeys: Julianne, go to the next question.

Justin Claeys: Alright, thank you. Julien, our next question.

Operator: Thank you, Jay. Our next question comes from Chris Schott from JPMorgan. Please go ahead. Your line is open.

Operator: Thank you, Jay. Our next question comes from Chris Schott from JPMorgan. Please go ahead. Your line is open.

Operator: Thank you Jay. Our next question comes from Chris Schott from JP. Morgan. Please go ahead. Your line is open.

Justin Claeys: Great, thanks very much. Just maybe to pivot over to Tepezza for a question.

Chris Schott: Great, thanks very much. Just maybe to pivot over to Tepezza for a question.

Chris Schott: Great. Thanks very much. Just maybe to pivot over to TEPEZZA for a question, can you just talk a little bit about the dynamics for 2024? It seems like the products come back to growth, but I'm just trying to get a sense of now that Amgen owns the asset and has more time with it, what are your top priorities and how do you think about continuing to kind of grow the new patient base here? Thank you.

Robert Bradway: Can you just talk a little bit?

Can you just talk a little bit?

Justin Claeys: About the dynamics for 2024? It seems like the products come back to growth, but I'm just trying to get a sense of now that Amgen owns the asset and has more time with it. What are your top priorities and how do you think about continuing to grow the new patient base here?

About the dynamics for 2024? It seems like the products come back to growth, but I'm just trying to get a sense of now that Amgen owns the asset and has more time with it. What are your top priorities and how do you think about continuing to grow the new patient base here?

Vikram Karnani: Thank you.

Thank you.

Peter Griffith: Sure.

Bob Bradway: Sure.

Robert Bradway: Chris, maybe we'll take it a couple parts. But Vikram, share your thoughts first.

Bob Bradway: Chris, maybe we'll take it a couple parts. But Vikram, share your thoughts first.

Murdo Gordon: Sure Chris, maybe it will take us a couple of parts. Vikram, share your thoughts first.

Peter Griffith: Yep.

Vikram Karnani: Yep.

Chris Schott: Share your thoughts first.

Vikram Karnani: Thank you for the question. I think.

Thank you for the question. I think.

Vikram Carmony: Yes, thank you for the question. If you focus a little bit on what are the underlying factors that are driving TEPEZZA growth, we saw a record number of unique TEPEZZA prescribers. We saw an increase in patient enrollment forms and patient starts. In addition, we've made pretty significant progress on payer coverage. As we've seen, our covered lives have not increased to greater than 50% of US covered lives and that's important. Educating some of those stakeholders on the new clinical data, updated indication, it continues to drive uptake across the full spectrum of GED patients. And finally, what holds all of this together is a really robust patient service

Vikram Carmony: Yes, thank you for the question. If you focus a little bit on what are the underlying factors that are driving TEPEZZA growth, we saw a record number of unique TEPEZZA prescribers. We saw an increase in patient enrollment forms and patient starts. In addition, we've made pretty significant progress on payer coverage. As we've seen, our covered lives have not increased to greater than 50% of US covered lives and that's important. Educating some of those stakeholders on the new clinical data, updated indication, it continues to drive uptake across the full spectrum of GED patients.

Vikram Karnani: If you focus a little bit on what are the underlying factors that are driving Tepezza growth. We saw a record number of unique types of prescribers. We saw an increase in patient enrollment forms and patient starts. In addition, we've made pretty significant progress on payer coverage. As we've seen, our covered lives have now increased to greater than 50% of US covered lives. And that's important, educating some of those stakeholders on the new clinical data, updated indication. It continues to drive uptake across the full spectrum of TED patients. Finally, what holds all of this together is a really robust patient service model that supports patient access. I think we continue to make progress and execute towards each one of these important leading indicators.

If you focus a little bit on what are the underlying factors that are driving Tepezza growth. We saw a record number of unique types of prescribers. We saw an increase in patient enrollment forms and patient starts. In addition, we've made pretty significant progress on payer coverage. As we've seen, our covered lives have now increased to greater than 50% of US covered lives. And that's important, educating some of those stakeholders on the new clinical data, updated indication. It continues to drive uptake across the full spectrum of TED patients. Finally, what holds all of this together is a really robust patient service model that supports patient access. I think we continue to make progress and execute towards each one of these important leading indicators.

Speaker Change: Thanks. If you focus a little bit on what are the underlying factors that are driving deposit growth. We saw a record number of unique prescribers.

Speaker Change: If you focus a little bit on what are the underlying factors that are driving deposit growth. We saw a record number of unique prescribers.

Speaker Change: We saw an increase in patient enrollment forms and patient starts. In addition, we've made pretty significant progress on payer coverage as we've as we've seen. Our covered lives have not increased to greater than 50% of U S covered lives and thats important educating some of those stakeholders on the new clinical data updated indication. It continues to drive uptake across the full spectrum up to 80 patients and finally, what holds all of this together a really robust patient service.

Speaker Change: In addition, we've made pretty significant progress on payer coverage as we've as we've seen. Our covered lives have not increased to greater than 50% of U S covered lives and thats important educating some of those stakeholders on the new clinical data updated indication. It continues to drive uptake across the full spectrum up to 80 patients and finally, what holds all of this together a really robust patient service.

Speaker Change: Our covered lives have not increased to greater than 50% of U S covered lives and thats important educating some of those stakeholders on the new clinical data updated indication. It continues to drive uptake across the full spectrum up to 80 patients and finally, what holds all of this together a really robust patient service.

Vikram Carmony: And finally, what holds all of this together is a really robust patient service model that supports patient access. So I think we continue to make progress and execute towards each one of these important leading indicators and we shouldn't forget that there's still low penetration of the roughly 100,000 patients that can be eligible for this medicine in the US alone. One last point here is that as we've noted before, there continues to be a time lag between the execution of all of these efforts and the realization of increased patient numbers. As we've said before, it can take up to 90 days once a patient is identified for therapy for that patient to actually get on therapy. But we're pretty happy with all of our leading indicators and the execution that we have seen coming out of last year.

Speaker Change: model that supports patient access. So I think we continue to make progress and execute towards each one of these important leading indicators and we shouldn't forget that there's still low penetration of the roughly 100,000 patients that can be eligible for this medicine in the US alone. One last point here is that as we've noted before, there continues to be a time lag between the execution of all of these efforts and the realization of increased patient numbers. As we've said before, it can take up to 90 days once a patient is identified for therapy for that patient to actually get on therapy. But we're pretty happy with all of our leading indicators and the execution that we have seen coming out of last year. Chris, the only thing I would add is building on what Vikram said in his prepared remarks, we're excited about the international opportunity as well. I think you characterized that well previously and we're also excited about what we see as ongoing opportunities to invest in innovation for the benefit of TED patients. So all in all, we feel excited about the rare disease pillar that we've established and the role that TEPEZZA will play in that.

model that supports patient access. So I think we continue to make progress and execute towards each one of these important leading indicators and we shouldn't forget that there's still low penetration of the roughly 100,000 patients that can be eligible for this medicine in the US alone. One last point here is that as we've noted before, there continues to be a time lag between the execution of all of these efforts and the realization of increased patient numbers. As we've said before, it can take up to 90 days once a patient is identified for therapy for that patient to actually get on therapy. But we're pretty happy with all of our leading indicators and the execution that we have seen coming out of last year.

Speaker Change: That supports patient access I think we continue to make progress and execute towards each one of these important leading indicators and we shouldnt forget that. Still low penetration of the roughly 300000 patients that can be eligible for this medicine in the U S alone. No. One last. The point here is that as we've noted before there continues to be a time lag between the execution of all of these efforts and the realization of increased patient numbers as we've said before it can take up to 90 days. Once a patient is identified for therapy for that patient to actually get on therapy, but we're pretty happy with with all of our leading indicators and the execution that we have seen coming out of last year. The only thing I would add is building on what Vikram said in his prepared remarks, we're excited about the international opportunity as well. Can you characterize that. Well previously. And we're also excited about what we see as ongoing opportunities to invest in innovation for the benefit of. TD patients so all in all feel. I'm excited about the rare disease pillar that we've established and the role of the puzzle would play in them.

Vikram Karnani: We shouldn't forget that there is still low penetration of the approximately 100,000 patients that can be eligible for this medicine in the US alone. Now, just one last.

We shouldn't forget that there is still low penetration of the approximately 100,000 patients that can be eligible for this medicine in the US alone. Now, just one last.

Speaker Change: Still low penetration of the roughly 300000 patients that can be eligible for this medicine in the U S alone. No. One last. The point here is that as we've noted before there continues to be a time lag between the execution of all of these efforts and the realization of increased patient numbers as we've said before it can take up to 90 days. Once a patient is identified for therapy for that patient to actually get on therapy, but we're pretty happy with with all of our leading indicators and the execution that we have seen coming out of last year. The only thing I would add is building on what Vikram said in his prepared remarks, we're excited about the international opportunity as well. Can you characterize that. Well previously. And we're also excited about what we see as ongoing opportunities to invest in innovation for the benefit of. TD patients so all in all feel. I'm excited about the rare disease pillar that we've established and the role of the puzzle would play in them.

Speaker Change: No. One last. The point here is that as we've noted before there continues to be a time lag between the execution of all of these efforts and the realization of increased patient numbers as we've said before it can take up to 90 days. Once a patient is identified for therapy for that patient to actually get on therapy, but we're pretty happy with with all of our leading indicators and the execution that we have seen coming out of last year. The only thing I would add is building on what Vikram said in his prepared remarks, we're excited about the international opportunity as well. Can you characterize that. Well previously. And we're also excited about what we see as ongoing opportunities to invest in innovation for the benefit of. TD patients so all in all feel. I'm excited about the rare disease pillar that we've established and the role of the puzzle would play in them.

Vikram Karnani: point here is that as we've noted before, there continues to be a time lag between the execution of all of these efforts and the realization of increased patient numbers. As we said before, it can take up to 90 days once a patient is identified for therapy, for that patient to actually get on therapy. But we're pretty happy with all of our leading indicators and the execution that we have seen coming out of last year.

point here is that as we've noted before, there continues to be a time lag between the execution of all of these efforts and the realization of increased patient numbers. As we said before, it can take up to 90 days once a patient is identified for therapy, for that patient to actually get on therapy. But we're pretty happy with all of our leading indicators and the execution that we have seen coming out of last year.

Speaker Change: One last. The point here is that as we've noted before there continues to be a time lag between the execution of all of these efforts and the realization of increased patient numbers as we've said before it can take up to 90 days. Once a patient is identified for therapy for that patient to actually get on therapy, but we're pretty happy with with all of our leading indicators and the execution that we have seen coming out of last year. The only thing I would add is building on what Vikram said in his prepared remarks, we're excited about the international opportunity as well. Can you characterize that. Well previously. And we're also excited about what we see as ongoing opportunities to invest in innovation for the benefit of. TD patients so all in all feel. I'm excited about the rare disease pillar that we've established and the role of the puzzle would play in them.

Speaker Change: The point here is that as we've noted before there continues to be a time lag between the execution of all of these efforts and the realization of increased patient numbers as we've said before it can take up to 90 days. Once a patient is identified for therapy for that patient to actually get on therapy, but we're pretty happy with with all of our leading indicators and the execution that we have seen coming out of last year. The only thing I would add is building on what Vikram said in his prepared remarks, we're excited about the international opportunity as well. Can you characterize that. Well previously. And we're also excited about what we see as ongoing opportunities to invest in innovation for the benefit of. TD patients so all in all feel. I'm excited about the rare disease pillar that we've established and the role of the puzzle would play in them.

Speaker Change: Once a patient is identified for therapy for that patient to actually get on therapy, but we're pretty happy with with all of our leading indicators and the execution that we have seen coming out of last year. The only thing I would add is building on what Vikram said in his prepared remarks, we're excited about the international opportunity as well. Can you characterize that. Well previously. And we're also excited about what we see as ongoing opportunities to invest in innovation for the benefit of. TD patients so all in all feel. I'm excited about the rare disease pillar that we've established and the role of the puzzle would play in them.

Murdo Gordon: Chris, the only thing I would add is building on what Vikram said in his prepared remarks, we're excited about the international opportunity as well. I think you characterized that well previously and we're also excited about what we see as ongoing opportunities to invest in innovation for the benefit of TED patients. So all in all, we feel excited about the rare disease pillar that we've established and the role that TEPEZZA will play in that.

Robert Bradway: Chris, the only thing I would add is building on what Vikram said in his prepared remarks. We're excited about the international opportunity as well, and I think he characterized that well previously. We're also excited about what we see as ongoing opportunities to invest in innovation for the benefit of TED patients. So all in all, we feel excited about the rare disease pillar that we've established and the role that Tepezza will play in that.

Bob Bradway: Chris, the only thing I would add is building on what Vikram said in his prepared remarks. We're excited about the international opportunity as well, and I think he characterized that well previously. We're also excited about what we see as ongoing opportunities to invest in innovation for the benefit of TED patients. So all in all, we feel excited about the rare disease pillar that we've established and the role that Tepezza will play in that.

Geoff Meacham: The only thing I would add is building on what Vikram said in his prepared remarks, we're excited about the international opportunity as well. Can you characterize that. Well previously. And we're also excited about what we see as ongoing opportunities to invest in innovation for the benefit of. TD patients so all in all feel. I'm excited about the rare disease pillar that we've established and the role of the puzzle would play in them.

Can you characterize that. Well previously. And we're also excited about what we see as ongoing opportunities to invest in innovation for the benefit of. TD patients so all in all feel. I'm excited about the rare disease pillar that we've established and the role of the puzzle would play in them.

Speaker Change #112: Well previously. And we're also excited about what we see as ongoing opportunities to invest in innovation for the benefit of. TD patients so all in all feel. I'm excited about the rare disease pillar that we've established and the role of the puzzle would play in them.

Speaker Change #112: And we're also excited about what we see as ongoing opportunities to invest in innovation for the benefit of. TD patients so all in all feel. I'm excited about the rare disease pillar that we've established and the role of the puzzle would play in them.

Speaker Change: TD patients so all in all feel. I'm excited about the rare disease pillar that we've established and the role of the puzzle would play in them.

Speaker Change: I'm excited about the rare disease pillar that we've established and the role of the puzzle would play in them.

Peter Griffith: All right, next question.

Justin Claeys: All right, next question.

Justin Claeys: Julianne.

Julianne.

Operator: Thank you, Chris. Our next question comes from Evan Segerman from BMO Capital Markets. Please go ahead. Your line is open.

Operator: Thank you, Chris. Our next question comes from Evan Segerman from BMO Capital Markets. Please go ahead. Your line is open.

Justin Claeys: Our next question Julien.

Operator: Thank you Chris Our next question comes from Evan <unk> from BMO Capital markets. Please go ahead. Your line is open.

Vikram Karnani: Hi guys.

Evan Seigerman: Hi guys.

Justin Claeys: Thank you so much for taking my question. I wanted to touch on Tezspire specifically in COPD. How are you planning to differentiate given the pretty competitive data we saw from Dupixent? And how should investors be looking at this data from an efficacy bar? Are there nuances in this trial that.

Thank you so much for taking my question. I wanted to touch on Tezspire specifically in COPD. How are you planning to differentiate given the pretty competitive data we saw from Dupixent? And how should investors be looking at this data from an efficacy bar? Are there nuances in this trial that.

Evan Seigerman: Hi, guys. Thank you so much for taking my question. I wanted to touch on TEZSPIRE specifically in COPD. How are you planning to differentiate given the pretty competitive data we saw from DUPIXENT and how should investors be looking at that data from an efficacy bar? Are there nuances in this trial that need to be clarified that might make it harder to do an apples to apples comparison?

Evan: How are you planning to differentiate given pretty competitive data, we saw from <unk> and how should investors be looking at that data from an efficacy bar are there nuances in this trial that need to be clarified that might make it harder to do an apples to apples comparison.

Peter Griffith: Need to be clarified that might make.

Need to be clarified that might make.

Justin Claeys: it harder to do an apples-to-apples comparison?

it harder to do an apples-to-apples comparison?

Justin Claeys: Yeah. Then thanks for the question, Myrtle. Why don't I start and then you add on? So it's a great and timely question. The Phase 2 COPD study of Tezspire. We expect data in the first half of this year. This was a big study. 337 patients, moderate to severe COPD. They're having exacerbations despite being on triple therapy. And so reflective of the current unmet need and inadequacy of therapy for patients with COPD. This is a slightly broader population than Dupixent that we're studying here. We're totally on track for the readout. We quite like the mechanism here. You must know that TSLP works as a signaling factor upstream. And by blocking it with our unique biotherapeutic, we block TSLP IL-25 IL-33 signaling. TSLP hits so many cell types modulating this airway type 2 response.

Jay Olson: Yeah. Then thanks for the question, Myrtle. Why don't I start and then you add on? So it's a great and timely question. The Phase 2 COPD study of Tezspire. We expect data in the first half of this year. This was a big study. 337 patients, moderate to severe COPD. They're having exacerbations despite being on triple therapy. And so reflective of the current unmet need and inadequacy of therapy for patients with COPD. This is a slightly broader population than Dupixent that we're studying here. We're totally on track for the readout. We quite like the mechanism here. You must know that TSLP works as a signaling factor upstream. And by blocking it with our unique biotherapeutic, we block TSLP IL-25 IL-33 signaling. TSLP hits so many cell types modulating this airway type 2 response.

Jay Bradner: Yes, and thanks for the question. Murdo, why don't I start and then you add on. So it's a great and timely question. The phase II COPD study of TEZSPIRE, we expect data in the first half of this year, this was a big study, 337 patients, moderate to severe COPD. They're having an exacerbation despite being on triple therapy, and so reflective of the current unmet need and inadequacy of therapy for patients with COPD. This is a slightly broader population than DUPI that we're studying here. We're totally on track for the readout. We quite like the mechanism here. You must know that T slip is the signaling factor upstream and by blocking it with our unique biotherapeutic, we block T slip IL 25, IL 33 signaling T slip, so many cell types modulating this airway type two response. 

Julian: So it's a great and timely question. The phase III COPD study of test fire, we expect data in the first half of this year. This was a big study 337 patients moderate severe to severe COPD. They're having an exacerbation despite being on triple therapy, and so reflective of the current unmet need and inadequacy of therapy for patients with COPD.

Julian: The phase III COPD study of test fire, we expect data in the first half of this year. This was a big study 337 patients moderate severe to severe COPD. They're having an exacerbation despite being on triple therapy, and so reflective of the current unmet need and inadequacy of therapy for patients with COPD.

Brendan: This was a big study 337 patients moderate severe to severe COPD. They're having an exacerbation despite being on triple therapy, and so reflective of the current unmet need and inadequacy of therapy for patients with COPD.

Brendan: They're having an exacerbation despite being on triple therapy, and so reflective of the current unmet need and inadequacy of therapy for patients with COPD.

Speaker Change #114: This is a slightly broader population than dupee that we're studying here we're totally on track for the readout, we quite like the mechanism here. You must know that. Slipped works. The signaling factor upstream and by blocking it with our unique. Biotherapeutic, we block cheese slip IL 25, IL 33 signaling T. Slippage. So many cell types modulating. This airway type two response by.

You must know that. Slipped works. The signaling factor upstream and by blocking it with our unique. Biotherapeutic, we block cheese slip IL 25, IL 33 signaling T. Slippage. So many cell types modulating. This airway type two response by.

Brendan: Slipped works. The signaling factor upstream and by blocking it with our unique. Biotherapeutic, we block cheese slip IL 25, IL 33 signaling T. Slippage. So many cell types modulating. This airway type two response by.

The signaling factor upstream and by blocking it with our unique. Biotherapeutic, we block cheese slip IL 25, IL 33 signaling T. Slippage. So many cell types modulating. This airway type two response by.

Vikram: Biotherapeutic, we block cheese slip IL 25, IL 33 signaling T. Slippage. So many cell types modulating. This airway type two response by.

Justin Claeys: By hitting TSLP upstream, we think we can really have an impact on the disease biology. We see TSLP elevated in the serum of patients in bronchial mucosa and bronchoalveolar lavage fluid. It's released by airway epithelium. So there's just a lot of signals from the basic biology of this disease pointing to a medicine of this nature. And by looking at the broader population than they did with Dupixent, we have a chance to really figure out who the responder is. Murdo, I think you've covered all the bases. I would just add this, Evan, that.

By hitting TSLP upstream, we think we can really have an impact on the disease biology. We see TSLP elevated in the serum of patients in bronchial mucosa and bronchoalveolar lavage fluid. It's released by airway epithelium. So there's just a lot of signals from the basic biology of this disease pointing to a medicine of this nature. And by looking at the broader population than they did with Dupixent, we have a chance to really figure out who the responder is. Murdo,

Vikram: By hitting T Slip upstream, we think we can really have an impact on the disease biology. We see T slip elevated in the [inaudible] patient in bronchial [inaudible] and bronchoalveolar lavage fluid, it's released by airway epithelium. There's just a lot of signals from the basic biology of this disease pointing to a medicine of this nature and by looking at the broader population than they did with DUPI, we have a chance to really figure out who the responder is. Murdo? I think you've covered all the bases. I would just add this Evan, with the unique and differentiated mechanism as Jay described, we hope we can treat a broader population of patients and perhaps the currently available therapies. And we also recognize that there are patients who are refractory to those currently available therapies and we would obviously want to understand if they would be responders to TEZSPIRE. I think we've got strong commercial capabilities including with our partners at Astra Zeneca and are well positioned to take a product like this into the market if we're successful in phase III.

By hitting T Slip upstream, we think we can really have an impact on the disease biology. We see T slip elevated in the [inaudible] patient in bronchial [inaudible] and bronchoalveolar lavage fluid, it's released by airway epithelium. There's just a lot of signals from the basic biology of this disease pointing to a medicine of this nature and by looking at the broader population than they did with DUPI, we have a chance to really figure out who the responder is. Murdo?

Vikram: CRM a patient in bronchial <unk> Khoza Bronchoalveolar lavage fluid it's. It's released by airway epithelium, there's just a lot of signals from the basic biology of this disease pointing to a medicine of this nature and by looking at the broader population than they did with <unk>, we have a chance to really figure out who the responder. It's murdo I think you've covered all the bases I would just add this even with the unique. A differentiated mechanism as Jay described we hope we can treat a broader population of patients and perhaps the currently available therapies and we also recognize that there are patients who are refractory to those currently available therapies and we would obviously want to understand if they would be responders to test. Test fire I think we've got strong commercial capabilities. Including with our partners at Astrazeneca and are well positioned to take a product like this into the market. If we're successful in phase III.

Vikram: It's released by airway epithelium, there's just a lot of signals from the basic biology of this disease pointing to a medicine of this nature and by looking at the broader population than they did with <unk>, we have a chance to really figure out who the responder. It's murdo I think you've covered all the bases I would just add this even with the unique. A differentiated mechanism as Jay described we hope we can treat a broader population of patients and perhaps the currently available therapies and we also recognize that there are patients who are refractory to those currently available therapies and we would obviously want to understand if they would be responders to test. Test fire I think we've got strong commercial capabilities. Including with our partners at Astrazeneca and are well positioned to take a product like this into the market. If we're successful in phase III.

Murdo Gordon: I think you've covered all the bases. I would just add this, Evan, that.

Murdo Gordon: I think you've covered all the bases. I would just add this Evan, with the unique and differentiated mechanism as Jay described, we hope we can treat a broader population of patients and perhaps the currently available therapies. And we also recognize that there are patients who are refractory to those currently available therapies and we would obviously want to understand if they would be responders to TEZSPIRE. I think we've got strong commercial capabilities including with our partners at Astra Zeneca and are well positioned to take a product like this into the market if we're successful in phase III.

Murdo Gordon: With the unique and differentiated mechanism as Jay described, we hope we can treat a broader population of patients than perhaps the currently available therapies. We also recognize that there are patients who are refractory to those currently available therapies. We would obviously want to understand if they would be responders to Tezspire. I think we've got strong commercial capabilities, including with our partners at AstraZeneca, and are well positioned to take a product like this into the market if we're successful in phase 3.

With the unique and differentiated mechanism as Jay described, we hope we can treat a broader population of patients than perhaps the currently available therapies. We also recognize that there are patients who are refractory to those currently available therapies. We would obviously want to understand if they would be responders to Tezspire. I think we've got strong commercial capabilities, including with our partners at AstraZeneca, and are well positioned to take a product like this into the market if we're successful in phase 3.

Vikram: A differentiated mechanism as Jay described we hope we can treat a broader population of patients and perhaps the currently available therapies and we also recognize that there are patients who are refractory to those currently available therapies and we would obviously want to understand if they would be responders to test. Test fire I think we've got strong commercial capabilities. Including with our partners at Astrazeneca and are well positioned to take a product like this into the market. If we're successful in phase III.

Jay: Test fire I think we've got strong commercial capabilities. Including with our partners at Astrazeneca and are well positioned to take a product like this into the market. If we're successful in phase III.

Jay Olson: Including with our partners at Astrazeneca and are well positioned to take a product like this into the market. If we're successful in phase III.

Peter Griffith: Great. All right, thank you, Julia.

Justin Claeys: Great. All right, thank you, Julia.

Justin Claeys: Next question.

Justin Claeys: Next question.

Justin Claeys: Alright. Thank you Julian, next question.

Operator: Thank you, Evan. Our next question comes from Umar Rafat from Evercore ISI. Please go ahead. Your line is open.

Operator: Thank you, Evan. Our next question comes from Umar Rafat from Evercore ISI. Please go ahead. Your line is open.

Operator: Thank you Evan our next question comes from Omar <unk> from Evercore ISI. Please go ahead. Your line is open.

Justin Claeys: Hi, guys.

Umer Raffat: Hi, guys.

Peter Griffith: Thanks for taking my question. I wanted to touch on AMG 133 as well. Two-part question. First, on the discontinuations at the high dose.

Thanks for taking my question. I wanted to touch on AMG 133 as well. Two-part question. First, on the discontinuations at the high dose.

Umer Raffat: Hi, guys. Thanks for taking my question. I wanted to touch up on AMG 133 as well, two parts question. First, on the discontinuation is at the high dose, we know 5 out of 8 did not finish the full duration of the study, but there was a second arm also of this high dose 420 milligram with 10 patients, which was not reported. This was the one with digital tools. Could you speak to the discontinuation rate in that arm? There was a 420 done separately, which is not part of the paper. And secondly, I know this is a case of liver enzyme elevation of the 280 Meg dose, but this patient also had COVID-19 could you perhaps speak to the timing of liver enzyme elevation relative to the COVID episode? Thank you very much.

Justin Claeys: We know five out of eight did.

We know five out of eight did.

Peter Griffith: Not finish the full duration of the study. But there was a second arm also of this high dose 420 mg with 10 patients, which was not reported. This was the one with digital tools. Could you speak to the discontinuation rate in that arm? This is a 420 done separately, which is not part of the paper. And secondly, I know there's a case of liver enzyme elevation at the 280 mg dose, but this patient also had COVID. Could you perhaps speak to the timing of liver enzyme elevation relative to the COVID episode? Thank you very much.

Not finish the full duration of the study. But there was a second arm also of this high dose 420 mg with 10 patients, which was not reported. This was the one with digital tools. Could you speak to the discontinuation rate in that arm? This is a 420 done separately, which is not part of the paper. And secondly, I know there's a case of liver enzyme elevation at the 280 mg dose, but this patient also had COVID. Could you perhaps speak to the timing of liver enzyme elevation relative to the COVID episode? Thank you very much.

Mohit Bansal: Arm also of this high dose 420 milligram with 10 patients, which was not reported this was the one with digital tools could you speak to the discontinuation rate and that arm. There was a 420 done separately, which is not part of the paper and secondly, I know this is a case of liver enzyme elevation of the 280 Meg dose, but this patient also had COVID-19 could you perhaps speak to the.

Mohit Bansal: Timing of liver enzyme elevation relative to the Covid episode, Thank you very much.

Justin Claeys: Yeah, thanks, Umer. I won't be able to provide patient-level insights to the Phase 1 study at this time, but I do appreciate your question and your interest in the report. I'll speak to the dropouts of the Phase 1 at the 420mg dose, which was four out of the eight patients. First, it's notable to say that the high dose cohort in the multiple ascending dose receiving the three doses of 420 experienced real weight loss, real benefit of 14.5% after these three monthly doses. This was the group that proved actually quite durable. Up to day 154, subjects declined to participate in this clinical study setting largely for logistical reasons. The AES and other characteristics were comparable to all the other patients in the study.

Jay Bradner: Yeah, thanks, Umer. I won't be able to provide patient-level insights to the Phase 1 study at this time, but I do appreciate your question and your interest in the report. I'll speak to the dropouts of the Phase 1 at the 420mg dose, which was four out of the eight patients. First, it's notable to say that the high dose cohort in the multiple ascending dose receiving the three doses of 420 experienced real weight loss, real benefit of 14.5% after these three monthly doses. This was the group that proved actually quite durable. Up to day 154, subjects declined to participate in this clinical study setting largely for logistical reasons. The AES and other characteristics were comparable to all the other patients in the study.

Murdo Gordon: Yes, thanks Umer. I won't be able to provide patient level insights to the phase one study at this time, but I do appreciate your question and your interest in the report. I'll speak to the drop outs of the phase one at the 420 milligram dose, which was four out of the eight patients. First, it's notable to say that the high dose cohort and the multiple ascending dose receiving the three doses of 420 experienced real weight loss, real benefit of 14.5% after these three monthly doses. This was the group that prove actually quite durable out to day 150. Four subjects declined to participate in this clinical study setting largely logistical reasons. The AEs and all the other characteristics were comparable to all the other patients in the study. Now the second question around the digital group, I don't have insight into that. Dave, do you? No, we can get back to you on that. I don't know that we reported those data and the discontinuation rate.

Murdo Gordon: Yes, thanks Umer. I won't be able to provide patient level insights to the phase one study at this time, but I do appreciate your question and your interest in the report. I'll speak to the drop outs of the phase one at the 420 milligram dose, which was four out of the eight patients. First, it's notable to say that the high dose cohort and the multiple ascending dose receiving the three doses of 420 experienced real weight loss, real benefit of 14.5% after these three monthly doses. This was the group that prove actually quite durable out to day 150. Four subjects declined to participate in this clinical study setting largely logistical reasons. The AEs and all the other characteristics were comparable to all the other patients in the study. Now the second question around the digital group, I don't have insight into that. Dave, do you?

Speaker Change #116: Your interest in the report. Pizza the drop outs of the phase one at the 420 milligram dose, which was four out of the eight patients. First it's notable to say that the high dose co. Cohort and the multiple ascending dose receiving the three doses of <unk> experienced. Will weight loss real benefit of 14, 5%. After these three monthly doses. This was the group that prove actually quite durable out to day 150. Four subjects declined to participate in this clinical study setting largely logistical reasons, the aes and other characteristics were comparable to all the other patients in the study. Now the second question around the digital group I don't have insight into that Dave you know I mean, we can get back to you on that I don't know that we reported that those data and the discontinuation rate.

Speaker Change #116: Pizza the drop outs of the phase one at the 420 milligram dose, which was four out of the eight patients. First it's notable to say that the high dose co. Cohort and the multiple ascending dose receiving the three doses of <unk> experienced. Will weight loss real benefit of 14, 5%. After these three monthly doses. This was the group that prove actually quite durable out to day 150. Four subjects declined to participate in this clinical study setting largely logistical reasons, the aes and other characteristics were comparable to all the other patients in the study. Now the second question around the digital group I don't have insight into that Dave you know I mean, we can get back to you on that I don't know that we reported that those data and the discontinuation rate.

Geoff Meacham: First it's notable to say that the high dose co. Cohort and the multiple ascending dose receiving the three doses of <unk> experienced. Will weight loss real benefit of 14, 5%. After these three monthly doses. This was the group that prove actually quite durable out to day 150. Four subjects declined to participate in this clinical study setting largely logistical reasons, the aes and other characteristics were comparable to all the other patients in the study. Now the second question around the digital group I don't have insight into that Dave you know I mean, we can get back to you on that I don't know that we reported that those data and the discontinuation rate.

Geoff Meacham: Cohort and the multiple ascending dose receiving the three doses of <unk> experienced. Will weight loss real benefit of 14, 5%. After these three monthly doses. This was the group that prove actually quite durable out to day 150. Four subjects declined to participate in this clinical study setting largely logistical reasons, the aes and other characteristics were comparable to all the other patients in the study. Now the second question around the digital group I don't have insight into that Dave you know I mean, we can get back to you on that I don't know that we reported that those data and the discontinuation rate.

Will weight loss real benefit of 14, 5%. After these three monthly doses. This was the group that prove actually quite durable out to day 150. Four subjects declined to participate in this clinical study setting largely logistical reasons, the aes and other characteristics were comparable to all the other patients in the study. Now the second question around the digital group I don't have insight into that Dave you know I mean, we can get back to you on that I don't know that we reported that those data and the discontinuation rate.

Four subjects declined to participate in this clinical study setting largely logistical reasons, the aes and other characteristics were comparable to all the other patients in the study. Now the second question around the digital group I don't have insight into that Dave you know I mean, we can get back to you on that I don't know that we reported that those data and the discontinuation rate.

Justin Claeys: Now the second question around the digital group. I don't have insight into that, Dave, do you?

Now the second question around the digital group. I don't have insight into that, Dave, do you?

Speaker Change #117: Now the second question around the digital group I don't have insight into that Dave you know I mean, we can get back to you on that I don't know that we reported that those data and the discontinuation rate.

Robert Bradway: No, I mean we can get back to you on that. I don't know that we reported those.

Dave Reese: No, I mean we can get back to you on that. I don't know that we reported those.

David M. Reese: No, we can get back to you on that. I don't know that we reported those data and the discontinuation rate.

Justin Claeys: Data in the discontinuation rate. All right, good. Julianne, go to the next question.

Data in the discontinuation rate. All right, good. Julianne, go to the next question.

Justin Claeys: Alright. Julien, please go to the next question.

Speaker Change: Julien. So then the next question.

Operator: Thank you, Umer. Our next question comes from Colin Bristow from UBS. Please go ahead, your line is open.

Operator: Thank you, Umer. Our next question comes from Colin Bristow from UBS. Please go ahead, your line is open.

Operator: Thank you Umer. Our next question comes from Colin Bristow from UBS. Please go ahead. Your line is open.

[Analyst]: Good afternoon, and thanks for taking the questions. Maybe a couple more on MariTide first. Could you provide some insight into the dosing? I mean, obviously these are pretty large doses, and if we look at like the dose of 420mg takes over five minutes by infusion or three consecutive injections. So I was wondering if you could give any insight there, and then in terms of the relative affinity for GIP versus GLP, MariTide seems to have or preferentially favor GLP much more than competitor molecules, and so do you think the ultimate clinical profile is more closely going to resemble that of a long-acting GLP-1 versus competitive GLPs?

Colin Bristow: Good afternoon, and thanks for taking the questions. Maybe a couple more on MariTide first. Could you provide some insight into the dosing? I mean, obviously these are pretty large doses, and if we look at like the dose of 420mg takes over five minutes by infusion or three consecutive injections. So I was wondering if you could give any insight there, and then in terms of the relative affinity for GIP versus GLP, MariTide seems to have or preferentially favor GLP much more than competitor molecules, and so do you think the ultimate clinical profile is more closely going to resemble that of a long-acting GLP-1 versus competitive GLPs?

Colin Nigel Bristow: Good afternoon, and thanks for taking the questions. Maybe a couple more on maritime. First, could you provide some insight into the dosing? I mean, obviously these are pretty large doses and if we look at REPATHA for 20 milligrams takes over five minutes by as usual three consecutive injections so I was wondering if you could give any insight there. And then in terms of the relative affinity for [inaudible] seems to have preferentially favor [inaudible] more than competitor molecules. Do you think the ultimate clinical profile is more closely going to resemble that of a long acting [inaudible] one versus competitor [inaudible]?

First could you provide some insight into the dosing I mean, obviously these are pretty large doses and if we look at. Passive for 20 milligrams takes over five minutes by as usual three consecutive injections. I was wondering if you could give any insight that and then in terms of the relative affinity forget things Glenn. Monotype scenes. Preferentially favor. More than competitor molecules. Do you think the ultimate clinical profile it more closely resemble that of a long acting <unk> one.

Speaker Change: Passive for 20 milligrams takes over five minutes by as usual three consecutive injections. I was wondering if you could give any insight that and then in terms of the relative affinity forget things Glenn. Monotype scenes. Preferentially favor. More than competitor molecules. Do you think the ultimate clinical profile it more closely resemble that of a long acting <unk> one.

Speaker Change: I was wondering if you could give any insight that and then in terms of the relative affinity forget things Glenn. Monotype scenes. Preferentially favor. More than competitor molecules. Do you think the ultimate clinical profile it more closely resemble that of a long acting <unk> one.

Speaker Change: Monotype scenes. Preferentially favor. More than competitor molecules. Do you think the ultimate clinical profile it more closely resemble that of a long acting <unk> one.

Speaker Change: Preferentially favor. More than competitor molecules. Do you think the ultimate clinical profile it more closely resemble that of a long acting <unk> one.

Speaker Change: More than competitor molecules. Do you think the ultimate clinical profile it more closely resemble that of a long acting <unk> one.

Speaker Change: Do you think the ultimate clinical profile it more closely resemble that of a long acting <unk> one.

Peter Griffith: Thanks.

Thanks.

Speaker Change: As compared to the clips.

Justin Claeys: Yeah, thanks, Colin. I appreciate the deep consideration of the molecule, especially. I'd start by saying I don't regard these doses as high. I'm new here, but 420mg for a biotherapeutic that's an antibody drug conjugate with a peptide antibody ratio 2 to 1 seems well in scope for a modern biotherapeutic product. I don't need to tell this community paying such close attention to Amgen that this is a very sophisticated biotherapeutics organization, and on the manufacturing side, just every patient every time, and we have all the capabilities necessary to deliver this medicine at whichever of these three or other doses and schedule we arrive at. So no concerns there for me whatsoever regarding the balance of the pharmacology. You know, you do invoke a difference between our medicine and medicines developed by pure pharmaceutical companies.

Jay Bradner: Yeah, thanks, Colin. I appreciate the deep consideration of the molecule, especially. I'd start by saying I don't regard these doses as high. I'm new here, but 420mg for a biotherapeutic that's an antibody drug conjugate with a peptide antibody ratio 2 to 1 seems well in scope for a modern biotherapeutic product. I don't need to tell this community paying such close attention to Amgen that this is a very sophisticated biotherapeutics organization, and on the manufacturing side, just every patient every time, and we have all the capabilities necessary to deliver this medicine at whichever of these three or other doses and schedule we arrive at. So no concerns there for me whatsoever regarding the balance of the pharmacology. You know, you do invoke a difference between our medicine and medicines developed by pure pharmaceutical companies.

Jay Bradner: Yes, thanks, Colin appreciate the deep consideration of the molecule, especially. I'd start by saying I don't regard these doses as high. I'm new here, but 420 milligrams for a biotherapeutic that's an antibody drug conjugate with a peptide antibody ratio of two to one seems well in scope for a modern biotherapeutic product. I don't need to tell this community paying such close attention to Amgen that this is a very sophisticated biotherapeutics organization and on the manufacturing side just every patient, every time and we have all the capabilities necessary to deliver this medicine that whichever of these three or other dose and schedule we arrive that. So no concerns there for me whatsoever.

Speaker Change #120: I'd start by saying I don't regard these doses as high on new here, but 420 milligrams for our biotherapeutic, that's an antibody drug conjugate with a peptide antibody ratio of two to one seems well in scope for modern biotherapeutic products. I don't need to tell this community paying so close such close attention to Amgen that this is a very sophisticated biotherapeutics organization and on the manufacturing side. Just every patient every time and we have all the capabilities necessary to deliver this medicine that whichever of these three or other dose.

Dave: I don't need to tell this community paying so close such close attention to Amgen that this is a very sophisticated biotherapeutics organization and on the manufacturing side. Just every patient every time and we have all the capabilities necessary to deliver this medicine that whichever of these three or other dose.

Dave: And schedule, we arrived that. So no concerns there for me whatsoever.

Speaker Change #121: So no concerns there for me whatsoever.

Speaker Change #121: Regarding the balance of the pharmacology, you do invoke a difference between our medicine and medicines developed by peer pharmaceutical companies, namely mechanistically the core antibody of maritime inhibits the [inaudible] receptor, whereas these other peptide medicines agonize it. We feel very secure in our choice to inhibit that receptor supported by just the finest level of experimental data available, experiments of nature that genome wide association studies in very large populations have pointed to a need and opportunity to inhibit the [inaudible] receptor to deliver lower BMI as observed with variance in that receptor in downstream signaling pathways that correlate with reduced body mass index in large populations. As to the balance, which you asked between inhibition of [inaudible] receptor agonism of GLP1, these are very difficult measurements to make in humans, but our modeling suggests that with the therapeutic doses and exposures that we observe that we are achieving both.

Speaker Change #121: You do invoke a difference between our medicine medicines developed by peer pharmaceutical companies, namely Mechanistically the core antibody of maritime inhibits. To get receptor, whereas these other peptide medicines agonize. It we feel very secure in our choice to inhibit that receptor supported by just the finest level of experimental data available experiments of nature. That genome wide Association studies in very large populations have pointed to a need and opportunity to inhibit the gift receptor to deliver lower BMI as observed with variance in that receptor in downstream signaling pathways that correlate with reduced body mass index in large populations.

Justin Claeys: Namely, mechanistically, the core antibody of MariTide inhibits the GIP receptor, whereas these other peptide medicines agonize it. We feel very secure in our choice to inhibit that receptor, supported by just the finest level of experimental data available: experiments of nature that genome-wide association studies in very large populations have pointed to a need, an opportunity, to inhibit the GIP receptor to deliver lower BMI, as observed with variants in that receptor and downstream signaling pathways that correlate with reduced body mass index in large populations. As to the balance, which you ask, between inhibition of GIP receptor and agonism of GLP1, these are very difficult measurements to make in humans. But our modeling suggests that with the therapeutic doses and exposures that we observe, that we're achieving both.

Namely, mechanistically, the core antibody of MariTide inhibits the GIP receptor, whereas these other peptide medicines agonize it. We feel very secure in our choice to inhibit that receptor, supported by just the finest level of experimental data available: experiments of nature that genome-wide association studies in very large populations have pointed to a need, an opportunity, to inhibit the GIP receptor to deliver lower BMI, as observed with variants in that receptor and downstream signaling pathways that correlate with reduced body mass index in large populations. As to the balance, which you ask, between inhibition of GIP receptor and agonism of GLP1, these are very difficult measurements to make in humans. But our modeling suggests that with the therapeutic doses and exposures that we observe, that we're achieving both.

David Risinger: To get receptor, whereas these other peptide medicines agonize. It we feel very secure in our choice to inhibit that receptor supported by just the finest level of experimental data available experiments of nature. That genome wide Association studies in very large populations have pointed to a need and opportunity to inhibit the gift receptor to deliver lower BMI as observed with variance in that receptor in downstream signaling pathways that correlate with reduced body mass index in large populations.

David Risinger: That genome wide Association studies in very large populations have pointed to a need and opportunity to inhibit the gift receptor to deliver lower BMI as observed with variance in that receptor in downstream signaling pathways that correlate with reduced body mass index in large populations.

Speaker Change: As to the balance, which you asked between inhibition of gift receptor agonism of <unk> one. These are very difficult measurements to make in humans, but our modeling suggests that with the therapeutic doses and exposures that we observe that we are achieving both.

These are very difficult measurements to make in humans, but our modeling suggests that with the therapeutic doses and exposures that we observe that we are achieving both.

Murdo Gordon: And Colin, it's Murto. I would just add from a patient experience perspective, we've learned a lot from other biologics, and Amgen has a world class process development, manufacturing, and device team.

Murdo Gordon: And Colin, it's Murto. I would just add from a patient experience perspective, we've learned a lot from other biologics, and Amgen has a world class process development, manufacturing, and device team.

Murdo Gordon: And Colin, this is Murdo, I would just add that from a patient experience perspective, we've learned a lot from other biologics and Amgen has a world class process development manufacturing and device team and we've done a lot of work on this one and we anticipate a very positive and simple patient experience on at least a monthly dosing schedule. And we've learned a lot from REPATHA specifically and there is more to follow on REPATHA from that but we continue to work to improve patient experience with our biologic injectables.

Speaker Change: We've learned a lot from other biologics and Amgen has a world class. Process development manufacturing and device team and we've done a lot of work on this one and we anticipate a very positive and simple patient experience. On at least a monthly dosing schedule. And we've learned a lot from <unk>, specifically and there is more to follow on <unk> from that but we continue to work to improve patient experience with with our biologic injectables.

Michael J. Yee: Process development manufacturing and device team and we've done a lot of work on this one and we anticipate a very positive and simple patient experience. On at least a monthly dosing schedule. And we've learned a lot from <unk>, specifically and there is more to follow on <unk> from that but we continue to work to improve patient experience with with our biologic injectables.

Justin Claeys: We've done a lot of work.

We've done a lot of work.

Murdo Gordon: On this one, and we anticipate a positive and simple patient experience.

On this one, and we anticipate a positive and simple patient experience.

Murdo Gordon: On at least a monthly dosing schedule. And we've learned a lot from Repatha specifically, and there's more to follow on Repatha from that. But we continue to work to improve patient experience with our biologic injectables.

On at least a monthly dosing schedule. And we've learned a lot from Repatha specifically, and there's more to follow on Repatha from that. But we continue to work to improve patient experience with our biologic injectables.

Michael J. Yee: On at least a monthly dosing schedule. And we've learned a lot from <unk>, specifically and there is more to follow on <unk> from that but we continue to work to improve patient experience with with our biologic injectables.

Michael J. Yee: And we've learned a lot from <unk>, specifically and there is more to follow on <unk> from that but we continue to work to improve patient experience with with our biologic injectables.

Robert Bradway: Just as we go to the next question, let me observe that. We're almost up to the hour that we ask you all to set aside, but I know we still have quite a few questions in the queue. So we'll try to get one question per caller here and get through. We'll stay through the queue of calls or questions rather, that's still waiting for us. But I know some of you may have to drop, so let's move forward.

Bob Bradway: Just as we go to the next question, let me observe that. We're almost up to the hour that we ask you all to set aside, but I know we still have quite a few questions in the queue. So we'll try to get one question per caller here and get through. We'll stay through the queue of calls or questions rather, that's still waiting for us. But I know some of you may have to drop, so let's move forward.

Speaker Change #122: Just as we go to the next question, let me observe that we're almost up to the hour reassure all of a sudden sorry, because I know, we still have quite a few questions in the queue. So I'm trying to get one question per caller here and get through. We'll stay through the queue of questions that's still waiting for us, but I know some of you might have to drop. So let's let's move forward Justin. Julian, next question please.

Just as we go to the next question, let me observe that we're almost up to the hour reassure all of a sudden sorry, because I know, we still have quite a few questions in the queue. So I'm trying to get one question per caller here and get through. We'll stay through the queue of questions that's still waiting for us, but I know some of you might have to drop. So let's let's move forward Justin.

Speaker Change: Through the Q calls or questions rather. Still waiting for us, but I know some of you might have to drop so let's let's move forward Joseph Yes. Julian next question. Please.

Still waiting for us, but I know some of you might have to drop so let's let's move forward Joseph Yes. Julian next question. Please.

Peter Griffith: Justin? Yep.

Justin?

Justin Claeys: Yep.

Justin Claeys: All right, Julianne, next question please.

All right, Julianne, next question please.

Justin Claeys: Julien, next question please.

Operator: Thank you, Colin. Our next question comes from Yaron Werber from TD Cowen. Please go ahead. Your line is open.

Operator: Thank you, Colin. Our next question comes from Yaron Werber from TD Cowen. Please go ahead. Your line is open.

Operator: Thank you Colin. Our next question comes from Uron Weber from TD Cowen. Please go ahead. Your line is open.

[Analyst]: All right, great, thanks. This is Brendan on for Yaron. Thanks for taking the question. Just a quick one from us, actually, based on the data that you've seen so far and maybe some feedback from physicians that you've heard. This is on where do you kind of see a business fitting into maybe the MD treatment paradigm given all the competition there. But maybe more to the point, how you're thinking about expansion opportunities given all the different autoimmune indications you could potentially pursue. Just trying to kind of understand how you see longer-term growth there.

[Analyst]: All right, great, thanks. This is Brendan on for Yaron. Thanks for taking the question. Just a quick one from us, actually, based on the data that you've seen so far and maybe some feedback from physicians that you've heard. This is on where do you kind of see a business fitting into maybe the MD treatment paradigm given all the competition there. But maybe more to the point, how you're thinking about expansion opportunities given all the different autoimmune indications you could potentially pursue. Just trying to kind of understand how you see longer-term growth there.

Speaker Change #123: Alright, great. Thanks. This is Brendan on for Uron. Thanks for taking my question. Just a quick one from us actually, based on the data you've seen so far and maybe some feedback from physicians that you've heard, this is on [inaudible], where do you kind of see a question that's getting into many mg treatment paradigm, given all the competition there, but maybe more to the point how you're thinking about expansion opportunities given all the different autoimmune indications you expect to pursue, just trying to kind of understand the longer term growth here. First of all, we'll ask Vikram just to address the performance of the product right now [inaudible] and then a combination of Jay and Dave can talk about the other activities or other potential applications.

Brendan Mychal Smith: Alright, great. Thanks. This is Brendan on for Uron. Thanks for taking my question. Just a quick one from us actually, based on the data you've seen so far and maybe some feedback from physicians that you've heard, this is on [inaudible], where do you kind of see a question that's getting into many mg treatment paradigm, given all the competition there, but maybe more to the point how you're thinking about expansion opportunities given all the different autoimmune indications you expect to pursue, just trying to kind of understand the longer term growth here.

Brendan: Okay. So my data that <unk> seen so far and maybe some feedback from physicians that you heard.

Brendan: This is on the uplift.

Speaker Change: Where do you kind of see a question that's getting into many mg treatment paradigm, given all the competition there, but maybe more to the point, how youre thinking about. Expansion opportunities given all the different autoimmune indications to pursue just trying to kind of understand the longer term growth. First of all we ask Vikram just to address the performance of the product right now in <unk> and then a combination of JM, Dave can talk about the other.

Speaker Change: Expansion opportunities given all the different autoimmune indications to pursue just trying to kind of understand the longer term growth. First of all we ask Vikram just to address the performance of the product right now in <unk> and then a combination of JM, Dave can talk about the other.

Robert Bradway: First, why don't we ask Vikram just to address the performance of the product right now in NMOSD and then. A combination of Jay and Dave can talk about the other.

Bob Bradway: First, why don't we ask Vikram just to address the performance of the product right now in NMOSD and then. A combination of Jay and Dave can talk about the other.

Speaker Change: First of all we ask Vikram just to address the performance of the product right now in <unk> and then a combination of JM, Dave can talk about the other.

Murdo Gordon: First of all, we'll ask Vikram just to address the performance of the product right now [inaudible] and then a combination of Jay and Dave can talk about the other activities or other potential applications.

Robert Bradway: Activities or other potential applications.

Bob Bradway: Activities or other potential applications.

Speaker Change: Activities or other. Central applications.

Vikram Karnani: Yep, thanks for the question. Yeah, Uplizna is actually growing quite nicely and quite well in NMOSD. As you know, it is now the fastest growing biologic in NMOSD. We continue to execute across a variety of fronts. I mean we see this product nicely positioned versus, you know, as it's appropriate for NMOSD patients and within the, within the competitive environment that we operate in. And we've continued to make significant progress over the last 18 months or so, maybe even longer, of continuing to drive more growth with newer prescribers and even depth with existing prescribers. So, you know, the product continues to do well and I think we hope to continue to deliver good execution on this medicine and NMOSD maybe. Jay, you want to talk about the second question?

Vikram Karnani: Yep, thanks for the question. Yeah, Uplizna is actually growing quite nicely and quite well in NMOSD. As you know, it is now the fastest growing biologic in NMOSD. We continue to execute across a variety of fronts. I mean we see this product nicely positioned versus, you know, as it's appropriate for NMOSD patients and within the, within the competitive environment that we operate in. And we've continued to make significant progress over the last 18 months or so, maybe even longer, of continuing to drive more growth with newer prescribers and even depth with existing prescribers. So, you know, the product continues to do well and I think we hope to continue to deliver good execution on this medicine and NMOSD maybe. Jay, you want to talk about the second question?

Speaker Change: Central applications.

Vikram Carmony: Yeah, thanks for the question. [inaudible] is actually growing quite nicely and quite [inaudible]. As you know, it is now the fastest growing biologic in [inaudible]. We continue to execute across a variety of fronts. We see this product nicely positioned versus as it's appropriate for [inaudible] patients and within the competitive environment that we operate in. And we've continued to make significant progress over the last 18 months or so, maybe even longer of continuing to drive more growth with newer prescribers and even a desk with existing prescribers. So the product continues to do well and I think we hope to continue to deliver good execution on this medicine in [inaudible]. Maybe Jay you want to talk about the second question. 

Speaker Change #124: One is actually growing quite nicely and quite fun and <unk>. As you know it is the it is now the fastest growing biologic in animals. We continue to execute across a variety of fronts. We see this product nicely positioned. <unk>. As it's appropriate for <unk>. <unk> patients.

Speaker Change: As you know it is the it is now the fastest growing biologic in animals. We continue to execute across a variety of fronts. We see this product nicely positioned. <unk>. As it's appropriate for <unk>. <unk> patients.

Speaker Change: We continue to execute across a variety of fronts. We see this product nicely positioned. <unk>. As it's appropriate for <unk>. <unk> patients.

Speaker Change: We see this product nicely positioned. <unk>. As it's appropriate for <unk>. <unk> patients.

Speaker Change: <unk>. As it's appropriate for <unk>. <unk> patients.

Speaker Change: As it's appropriate for <unk>. <unk> patients.

Speaker Change: <unk> patients.

Speaker Change: And within the within the competitive environment that we operate in and we've continued to make significant progress over the. The last 18 months or so maybe even longer. To drive more growth with newer prescribers and even a desk with existing prescribers. So. Product producer do well and I think we.

Speaker Change: The last 18 months or so maybe even longer. To drive more growth with newer prescribers and even a desk with existing prescribers. So. Product producer do well and I think we.

Speaker Change: To drive more growth with newer prescribers and even a desk with existing prescribers. So. Product producer do well and I think we.

Speaker Change: Product producer do well and I think we.

Speaker Change: We hope to continue to deliver good execution on this medicine in animals.

Justin Claeys: Yeah, no, I'm happy to. As you may know, I'm a hematologist. I think CD19 is a terrific target. It's expressed really on all B cells and spares plasma cells and therefore.

Jay Bradner: Yeah, no, I'm happy to. As you may know, I'm a hematologist. I think CD19 is a terrific target. It's expressed really on all B cells and spares plasma cells and therefore.

Jay Bradner: Yeah, I'm happy to. As you may know I'm a hematologist. I think CD 19 is a terrific target. It's expressed really on all B cells and stairs, plasma cells and therefore, considering indication expansion as you've asked, there's a large number of diseases that could potentially be approached with [inaudible] to the real benefit of patients with unmet need far beyond the application of the prevailing CD 20 that targets just a subset of B cells that is not lost on our team and we're working through indication expansion priorities presently.

Jay: As you May know I'm, a hematologist setting CD 19 to terrific target is expressed really on all b cells and stairs plasma cells and therefore. Considering indication expansion as you've asked there's a large number of diseases that could potentially be approached with a <unk> to the real benefit of patients with unmet need far beyond the application of. The prevailing CD 20 that target just a subset of b cells is it not loss on our team and we're working through indication expansion priorities presently.

Justin Claeys: Considering indication expansion. As you've asked, there's a large number of diseases that could potentially be approached with a PLSNA to the real benefit of patients with unmet need far beyond the application of the prevailing CD 20s that target just a subset of B cells. This is not lost on our team, and we're working through indication expansion priorities presently. Julian, let's go to the next question.

Considering indication expansion. As you've asked, there's a large number of diseases that could potentially be approached with a PLSNA to the real benefit of patients with unmet need far beyond the application of the prevailing CD 20s that target just a subset of B cells. This is not lost on our team, and we're working through indication expansion priorities presently.

Timothy Minton Anderson: Considering indication expansion as you've asked there's a large number of diseases that could potentially be approached with a <unk> to the real benefit of patients with unmet need far beyond the application of. The prevailing CD 20 that target just a subset of b cells is it not loss on our team and we're working through indication expansion priorities presently.

Timothy Minton Anderson: The prevailing CD 20 that target just a subset of b cells is it not loss on our team and we're working through indication expansion priorities presently.

Justin Claeys: Julian, let's go to the next question.

Justin Claeys: Hi, Julien, let's go to the next question.

Operator: Thank you. Our next question comes from Mohit Bansal from Wells Fargo. Please go ahead. Your line is open.

Operator: Thank you. Our next question comes from Mohit Bansal from Wells Fargo. Please go ahead. Your line is open.

Operator: Thank you. Our next question comes from Mohit Bansal from Wells Fargo. Please go ahead. Your line is open.

Peter Griffith: Great.

Mohit Bansal: Great.

Justin Claeys: Thank you very much for taking my question.

Thank you very much for taking my question.

Vikram Karnani: I have a question regarding the subcutaneous delivery of Tepezza. You do have plan to initiate a phase 3 study.

I have a question regarding the subcutaneous delivery of Tepezza. You do have plan to initiate a phase 3 study.

Mohit Bansal: Great. Thank you very much for taking my question. I have a question regarding the subcutaneous delivery of the TEPEZZA. You do have plans to initiate a phase three study, can you talk a little bit about which technology you are using? Is that [inaudible] technology or are you using [inaudible], thank you. I'm sorry, I had trouble understanding the question. The question is what technology we are using for the subcutaneous injectable form of TEPEZZA. Maybe I'll just jump in. Mohit, we're not commenting at this point on the provider. We just said that we're going forward with the sub Q.

Mohit Bansal: Great. Thank you very much for taking my question. I have a question regarding the subcutaneous delivery of the TEPEZZA. You do have plans to initiate a phase three study, can you talk a little bit about which technology you are using? Is that [inaudible] technology or are you using [inaudible], thank you. I'm sorry, I had trouble understanding the question. The question is what technology we are using for the subcutaneous injectable form of TEPEZZA.

Mohit Bansal: Great. Thank you very much for taking my question. I have a question regarding the subcutaneous delivery of the TEPEZZA. You do have plans to initiate a phase three study, can you talk a little bit about which technology you are using? Is that [inaudible] technology or are you using [inaudible], thank you.

[Analyst]: Can you talk a little bit about?

Can you talk a little bit about?

Vikram Karnani: Which technology you are using? Is this with the pre-existing Halozyme?

Which technology you are using? Is this with the pre-existing Halozyme?

Jay: Which technology are using existed. Existing. Is that technology or are you using some of the guys from this thank you. I'm, sorry, I had trouble understanding the question. So my question is what technology, we are using for the subcutaneous injectable form. Yes. Ill jump in we're not commenting at this point on the provider. We're just said that we're going forward with the sub Q.

Justin Claeys: Technology or are you using something else for this development? Thank you.

Technology or are you using something else for this development? Thank you.

Speaker Change: Existing. Is that technology or are you using some of the guys from this thank you. I'm, sorry, I had trouble understanding the question. So my question is what technology, we are using for the subcutaneous injectable form. Yes. Ill jump in we're not commenting at this point on the provider. We're just said that we're going forward with the sub Q.

Speaker Change: Is that technology or are you using some of the guys from this thank you. I'm, sorry, I had trouble understanding the question. So my question is what technology, we are using for the subcutaneous injectable form. Yes. Ill jump in we're not commenting at this point on the provider. We're just said that we're going forward with the sub Q.

Mohit Bansal: I'm sorry, I had trouble understanding the question. The question is what technology we are using for the subcutaneous injectable form of TEPEZZA.

Murdo Gordon: I'm sorry, I had trouble understanding the question.

Robert Bradway: Sorry, I had trouble understanding.

Bob Bradway: Sorry, I had trouble understanding.

Murdo Gordon: The question is what technology we're using for the subcutaneous injector form of?

Murdo Gordon: The question is what technology we're using for the subcutaneous injector form of?

Speaker Change #126: I'm, sorry, I had trouble understanding the question. So my question is what technology, we are using for the subcutaneous injectable form. Yes. Ill jump in we're not commenting at this point on the provider. We're just said that we're going forward with the sub Q.

David M. Reese: The question is what technology we are using for the subcutaneous injectable form of TEPEZZA.

Jay Bradner: Maybe I'll just jump in. Mohit, we're not commenting at this point on the provider. We just said that we're going forward with the sub Q.

Justin Claeys: Maybe I'll just jump in. Mohit, we're not commenting at this point on the provider. We just said that we're going forward.

Justin Claeys: Maybe I'll just jump in. Mohit, we're not commenting at this point on the provider. We just said that we're going forward.

Speaker Change: Yes. Ill jump in we're not commenting at this point on the provider. We're just said that we're going forward with the sub Q.

Speaker Change #127: Ill jump in we're not commenting at this point on the provider. We're just said that we're going forward with the sub Q.

Vikram Karnani: With the sub Q.

With the sub Q.

Peter Griffith: Great.

Mohit Bansal: Great.

Justin Claeys: Okay, Julianne, we'll go to the next question.

Justin Claeys: Okay, Julianne, we'll go to the next question.

Justin Claeys: Great. Okay, Julien, we'll go to next question.

Operator: Thank you, Mohit. Our next question comes from Jeff Meacham from Bank of America. Please go ahead. Your line is open.

Operator: Thank you, Mohit. Our next question comes from Jeff Meacham from Bank of America. Please go ahead. Your line is open.

Operator: Our next question comes from Geoff Meacham from Bank of America. Please go ahead. Your line is open.

Justin Claeys: Hey guys, thanks for the question.

Geoff Meacham: Hey guys, thanks for the question.

Peter Griffith: Another one on 133.

Another one on 133.

Geoff Meacham: Hey guys, thanks for the question. Another one on 133, when you think about the phase III program, just wanted to know what sort of informs the next indications you're going to go after, is it unmet need, is it the potential for differentiation on 133, and the timing of that, do you think that you'd want to have the phase II data in hand or is there something that you could rollout sort of at risk? Thank you.

Justin Claeys: When you think about the phase 3 program, just wanted to know what sort of informs the next indications you're going to go after. Is it unmet need? Is it the potential for differentiation on 133 and the timing of that? Do you think that you'd want to have the phase 2 data in hand or is this something that you could.

When you think about the phase 3 program, just wanted to know what sort of informs the next indications you're going to go after. Is it unmet need? Is it the potential for differentiation on 133 and the timing of that? Do you think that you'd want to have the phase 2 data in hand or is this something that you could.

Geoff Meacham: When you think about the phase III program, just wanted to know what sort of informs the next indications youre going to go after unmet. The unmet need is at the potential for differentiation on 133, and the timing of that do you think that you'd want to have the. Phase II data in hand, or is there something that you could rollout sort of at risk. Thank you.

Robyn: The unmet need is at the potential for differentiation on 133, and the timing of that do you think that you'd want to have the. Phase II data in hand, or is there something that you could rollout sort of at risk. Thank you.

Nicole: Phase II data in hand, or is there something that you could rollout sort of at risk. Thank you.

Peter Griffith: Roll out sort of at risk?

Roll out sort of at risk?

Justin Claeys: Thank you. Yeah, thanks for the question, Jeff. Really appreciate it. As you know, obesity is a major public health crisis. Maybe 40% of Americans with a BMI over 30, massively costly, so huge burden.

Jay Bradner: Thank you. Yeah, thanks for the question, Jeff. Really appreciate it. As you know, obesity is a major public health crisis. Maybe 40% of Americans with a BMI over 30, massively costly, so huge burden.

Jay Bradner: Yeah, thanks for the question, Jeff, really appreciate it. As you know, obesity is a major public health crisis, maybe 40% of Americans with a BMI over 30 massively costly so huge burden to the global third party payers and societies. The obesity related disease list is quite long and expanding from cardiovascular disease and heart failure, type two diabetes, obstructive sleep apnea, Nash NFL kidney disease. These are chronic conditions that really demand medicine that can deliver durable and chronic weight loss and so we think we have a really strong offering for these obesity related diseases rising in our phase II program as you know. And obesity has a strong genetic component and we locked down to [inaudible] inhibition based on genetic insights. So the opportunity space is quite large. You asked the question what indications and perhaps even in what sequence and when we have all the requisite data we'll remark in due course. But we intend all indications where this dual mechanism can improve public health and we are actively planning and on track for an expansive phase III program. And in terms of--Dave, do you want to add the regulatory piece?

Jay Bradner: Yeah, thanks for the question, Jeff, really appreciate it. As you know, obesity is a major public health crisis, maybe 40% of Americans with a BMI over 30 massively costly so huge burden to the global third party payers and societies. The obesity related disease list is quite long and expanding from cardiovascular disease and heart failure, type two diabetes, obstructive sleep apnea, Nash NFL kidney disease. These are chronic conditions that really demand medicine that can deliver durable and chronic weight loss and so we think we have a really strong offering for these obesity related diseases rising in our phase II program as you know. And obesity has a strong genetic component and we locked down to [inaudible] inhibition based on genetic insights. So the opportunity space is quite large. You asked the question what indications and perhaps even in what sequence and when we have all the requisite data we'll remark in due course. But we intend all indications where this dual mechanism can improve public health and we are actively planning and on track for an expansive phase III program.

Justin Claeys: To the global third-party payers and societies. The obesity-related disease list is quite long and expanding from cardiovascular disease and heart failure, type 2 diabetes, obstructive sleep apnea, NASH and NAFLD, kidney disease. These are chronic conditions that really demand medicines that can deliver durable and chronic weight loss. And so we think we have a really strong offering for these obesity-related diseases with our Phase 2 program. As you know, obesity has a strong genetic component and we locked onto GIP inhibition, you know, based on genetic insights. So the opportunity space is quite large. You ask the question, you know, what indications and perhaps even in what sequence. When we have all the requisite data, we'll remark in due course, but we intend all indications where this dual mechanism can improve public health.

To the global third-party payers and societies. The obesity-related disease list is quite long and expanding from cardiovascular disease and heart failure, type 2 diabetes, obstructive sleep apnea, NASH and NAFLD, kidney disease. These are chronic conditions that really demand medicines that can deliver durable and chronic weight loss. And so we think we have a really strong offering for these obesity-related diseases with our Phase 2 program. As you know, obesity has a strong genetic component and we locked onto GIP inhibition, you know, based on genetic insights. So the opportunity space is quite large. You ask the question, you know, what indications and perhaps even in what sequence. When we have all the requisite data, we'll remark in due course, but we intend all indications where this dual mechanism can improve public health.

Paul: But to the global third party payers and societies. <unk> related disease list is quite long and expanding from cardiovascular disease and heart failure type two diabetes obstructive sleep apnea Nash NFL kidney disease. These are chronic conditions that really demand medicine that can deliver durable. And chronic weight loss and so we think we have a really strong offering. For these. Obesity related diseases rising in our phase II program as you know. And obesity is a strong genetic component and we locked down to <unk> inhibition. Based on genetic insights. So the opportunity space is quite large you asked the question what indications and perhaps even in what sequence and when we have all the requisite data will remark in due course, but we intend all indications where this dual mechanism. <unk> public health. And we are actively planning and on track for an expansive phase III program and in terms of the day, if you want to add to the regulatory piece yes.

Jamie: <unk> related disease list is quite long and expanding from cardiovascular disease and heart failure type two diabetes obstructive sleep apnea Nash NFL kidney disease. These are chronic conditions that really demand medicine that can deliver durable. And chronic weight loss and so we think we have a really strong offering. For these. Obesity related diseases rising in our phase II program as you know. And obesity is a strong genetic component and we locked down to <unk> inhibition. Based on genetic insights. So the opportunity space is quite large you asked the question what indications and perhaps even in what sequence and when we have all the requisite data will remark in due course, but we intend all indications where this dual mechanism. <unk> public health. And we are actively planning and on track for an expansive phase III program and in terms of the day, if you want to add to the regulatory piece yes.

Jamie: These are chronic conditions that really demand medicine that can deliver durable. And chronic weight loss and so we think we have a really strong offering. For these. Obesity related diseases rising in our phase II program as you know. And obesity is a strong genetic component and we locked down to <unk> inhibition. Based on genetic insights. So the opportunity space is quite large you asked the question what indications and perhaps even in what sequence and when we have all the requisite data will remark in due course, but we intend all indications where this dual mechanism. <unk> public health. And we are actively planning and on track for an expansive phase III program and in terms of the day, if you want to add to the regulatory piece yes.

And chronic weight loss and so we think we have a really strong offering. For these. Obesity related diseases rising in our phase II program as you know. And obesity is a strong genetic component and we locked down to <unk> inhibition. Based on genetic insights. So the opportunity space is quite large you asked the question what indications and perhaps even in what sequence and when we have all the requisite data will remark in due course, but we intend all indications where this dual mechanism. <unk> public health. And we are actively planning and on track for an expansive phase III program and in terms of the day, if you want to add to the regulatory piece yes.

Jamie: For these. Obesity related diseases rising in our phase II program as you know. And obesity is a strong genetic component and we locked down to <unk> inhibition. Based on genetic insights. So the opportunity space is quite large you asked the question what indications and perhaps even in what sequence and when we have all the requisite data will remark in due course, but we intend all indications where this dual mechanism. <unk> public health. And we are actively planning and on track for an expansive phase III program and in terms of the day, if you want to add to the regulatory piece yes.

Jamie: Obesity related diseases rising in our phase II program as you know. And obesity is a strong genetic component and we locked down to <unk> inhibition. Based on genetic insights. So the opportunity space is quite large you asked the question what indications and perhaps even in what sequence and when we have all the requisite data will remark in due course, but we intend all indications where this dual mechanism. <unk> public health. And we are actively planning and on track for an expansive phase III program and in terms of the day, if you want to add to the regulatory piece yes.

Jamie: And obesity is a strong genetic component and we locked down to <unk> inhibition. Based on genetic insights. So the opportunity space is quite large you asked the question what indications and perhaps even in what sequence and when we have all the requisite data will remark in due course, but we intend all indications where this dual mechanism. <unk> public health. And we are actively planning and on track for an expansive phase III program and in terms of the day, if you want to add to the regulatory piece yes.

Jamie: Based on genetic insights. So the opportunity space is quite large you asked the question what indications and perhaps even in what sequence and when we have all the requisite data will remark in due course, but we intend all indications where this dual mechanism. <unk> public health. And we are actively planning and on track for an expansive phase III program and in terms of the day, if you want to add to the regulatory piece yes.

Julian: So the opportunity space is quite large you asked the question what indications and perhaps even in what sequence and when we have all the requisite data will remark in due course, but we intend all indications where this dual mechanism. <unk> public health. And we are actively planning and on track for an expansive phase III program and in terms of the day, if you want to add to the regulatory piece yes.

Justin Claeys: We are actively planning and on track for an expansive phase 3 program.

We are actively planning and on track for an expansive phase 3 program.

Geoff Meacham: <unk> public health. And we are actively planning and on track for an expansive phase III program and in terms of the day, if you want to add to the regulatory piece yes.

Geoff Meacham: And we are actively planning and on track for an expansive phase III program and in terms of the day, if you want to add to the regulatory piece yes.

Robert Bradway: And in terms of Dave, you want to add to the regulatory piece? Yeah, I think you know, Jeff, this is Dave Reese. I would just add that, you know, we're planning a very expansive phase 3.

Bob Bradway: And in terms of Dave, you want to add to the regulatory piece?

Murdo Gordon: And in terms of--Dave, do you want to add the regulatory piece?

Dave Reese: Yeah, I think you know, Jeff, this

Dave Reese: is Dave Reese. I would just add that, you know, we're planning a very expansive phase 3.

David M. Reese: Geoff, this is Dave Reese. I would just add that we're planning a very expansive phase III program so you can expect to see multiple indications move forward in parallel. And as Jay indicated, as we start to see data we will begin launching those trials and we will discuss them. And then in addition, as you're aware regulatory authorities around the world require a certain body of safety data before phase III launches. So of course, we will be compliant with that but our goal is to launch phase III as quickly as possible once we have the requisite dataset and regulatory approval.

Justin Claeys: Program so you can expect to see multiple indications move forward in parallel.

Program so you can expect to see multiple indications move forward in parallel.

Robert Bradway: As Jay indicated, as we start to see data, we will begin launching those trials and we'll discuss them. Then, in addition, you know, as you're aware, regulatory authorities around.

As Jay indicated, as we start to see data, we will begin launching those trials and we'll discuss them. Then, in addition, you know, as you're aware, regulatory authorities around.

Jan: And as Jay indicated. We start to see data, we will begin launching those trials and we will discuss them and then in addition. As Youre aware regulatory authorities around the world require a certain body of safety data before phase III launches. So of course, we will be compliant with that but our goal is to launch phase III as quickly as possible. Once we have the requisite dataset and regulatory approval.

Jan: We start to see data, we will begin launching those trials and we will discuss them and then in addition. As Youre aware regulatory authorities around the world require a certain body of safety data before phase III launches. So of course, we will be compliant with that but our goal is to launch phase III as quickly as possible. Once we have the requisite dataset and regulatory approval.

Jan: As Youre aware regulatory authorities around the world require a certain body of safety data before phase III launches. So of course, we will be compliant with that but our goal is to launch phase III as quickly as possible. Once we have the requisite dataset and regulatory approval.

Justin Claeys: The world require a certain body of.

The world require a certain body of.

Robert Bradway: Safety data before Phase 3 launches. So of course we will be compliant with that. But our goal is to launch Phase 3.

Safety data before Phase 3 launches. So of course we will be compliant with that. But our goal is to launch Phase 3.

Jan: So of course, we will be compliant with that but our goal is to launch phase III as quickly as possible. Once we have the requisite dataset and regulatory approval.

Justin Claeys: Three as quickly as possible once we have the requisite data set and regulatory approval. Great. All right, Julian, go to the next question please.

Three as quickly as possible once we have the requisite data set and regulatory approval.

Geoff Meacham: Great.

Justin Claeys: All right, Julian, go to the next question please.

Justin Claeys: Alright  Julien, go to the next question please.

Operator: Thank you, Jeff. Our next question comes from Dave Risinger from Leerink Partners. Please go ahead. Your line is open.

Operator: Thank you, Jeff. Our next question comes from Dave Risinger from Leerink Partners. Please go ahead. Your line is open.

Operator: Thank you Geoff. Our next question comes from David Risinger from Leerink Partners. Please go ahead. Your line is open.

Justin Claeys: Yes, thanks very much. So I have another question on AMG 133 please. Could you add some more color on your expectation for the impacts on blood pressure and lipids in Phase 2, specifically whether you anticipate tirzepatide-like efficacy on those metrics. Thanks very much. Yeah, thanks, David. I mean we're making all these measurements and I'm not going to try to forecast the outcome of that pharmacology at this time. As you've seen in our Phase 1 program, the medicine's very well tolerated, delivering durable weight loss and benefit without significant excursion of some of those measurements. I just think it's too early to try to answer your question. And we'll have all that data at the end of the first part of Phase 2 towards the end of this calendar year and the best extrapolation that.

David Risinger: Yes, thanks very much. So I have another question on AMG 133 please. Could you add some more color on your expectation for the impacts on blood pressure and lipids in Phase 2, specifically whether you anticipate tirzepatide-like efficacy on those metrics. Thanks very much.

David Risinger: Yes, thanks very much. So I have another question on AMG 132, please could you add some more color on your expectations for the impacts on blood pressure and lipids in phase two, specifically whether you anticipate [inaudible] like efficacy on those metrics. Thanks very much.

Speaker Change #131: Could you add some more color on. Your expectations for the impacts. On blood pressure and lipids in phase two. And specifically, whether you anticipate towards appetite like efficacy on those metrics. Thanks very much.

Speaker Change #131: Your expectations for the impacts. On blood pressure and lipids in phase two. And specifically, whether you anticipate towards appetite like efficacy on those metrics. Thanks very much.

Speaker Change #132: On blood pressure and lipids in phase two. And specifically, whether you anticipate towards appetite like efficacy on those metrics. Thanks very much.

Speaker Change #133: And specifically, whether you anticipate towards appetite like efficacy on those metrics.

Jay Bradner: Yeah, thanks, David. I mean we're making all these measurements and I'm not going to try to forecast the outcome of that pharmacology at this time. As you've seen in our Phase 1 program, the medicine's very well tolerated, delivering durable weight loss and benefit without significant excursion of some of those measurements. I just think it's too early to try to answer your question. And we'll have all that data at the end of the first part of Phase 2 towards the end of this calendar year

Speaker Change #134: Thanks very much.

Jay Bradner: Yeah, thanks David. I mean, we're making all of these measurements and I'm not going to try to forecast the outcome of that pharmacology at this time. As you've seen in our phase one program, the medicine is very well tolerated delivering durable weight loss and benefit without significant excursion of some of those measurements. I just think it's too early to try to answer your question, we will have all that data at the end of the first part of phase two towards the end of this calendar year. And the best extrapolation that you can have is from the preclinical data that were just published, I'd urge you to take a look at that.

Jay Bradner: Yeah, thanks David. I mean, we're making all of these measurements and I'm not going to try to forecast the outcome of that pharmacology at this time. As you've seen in our phase one program, the medicine is very well tolerated delivering durable weight loss and benefit without significant excursion of some of those measurements. I just think it's too early to try to answer your question, we will have all that data at the end of the first part of phase two towards the end of this calendar year.

Speaker Change: As you've seen in our phase one program, the medicines very well tolerated delivering durable weight loss and benefit without significant excursion of some of those measurements I just think it's. Too early to try to answer your question, we will have all that data at the end of. The first part of phase two. Towards the end of this calendar year and the best Extrapolation that you can have is from the preclinical data that were just published I'd urge you to take a look at that.

Speaker Change: Too early to try to answer your question, we will have all that data at the end of. The first part of phase two. Towards the end of this calendar year and the best Extrapolation that you can have is from the preclinical data that were just published I'd urge you to take a look at that.

Speaker Change: The first part of phase two. Towards the end of this calendar year and the best Extrapolation that you can have is from the preclinical data that were just published I'd urge you to take a look at that.

Dave Reese: and the best extrapolation that.

Murdo Gordon: And the best extrapolation that you can have is from the preclinical data that were just published, I'd urge you to take a look at that.

Speaker Change: Towards the end of this calendar year and the best Extrapolation that you can have is from the preclinical data that were just published I'd urge you to take a look at that.

Robert Bradway: You can have this from the preclinical data that were just published.

You can have this from the preclinical data that were just published.

Justin Claeys: I'd urge you to take a look at that. Okay, Julianne, we'll go to the next question, please.

I'd urge you to take a look at that.

Justin Claeys: Okay, Julianne, we'll go to the next question, please.

Justin Claeys: Okay, Julien, we'll go to the next question please.

Operator: Thank you, David. Our next question comes from Michael Schmidt from Guggenheim Securities. Please go ahead. Your line is open.

Operator: Thank you, David. Our next question comes from Michael Schmidt from Guggenheim Securities. Please go ahead. Your line is open.

Operator: Thank you David. Our next question comes from Michael Schmidt from Guggenheim Securities. Please go ahead. Your line is open.

Justin Claeys: Hey, it's Yi Gaehyung for Michael. Thanks for taking our questions. A quick one on Xaluritamig. Can you talk about your plan of data disclosure this year and your current thinking on the potential registration path? How do you think about the positioning of this agent relative to some of the other emergent agents based on different mechanisms such as ADC or AR degraders in prostate cancer? Thank you.

[Analyst] (Guggenheim): Hey, it's Yi Gaehyung for Michael. Thanks for taking our questions. A quick one on Xaluritamig. Can you talk about your plan of data disclosure this year and your current thinking on the potential registration path? How do you think about the positioning of this agent relative to some of the other emergent agents based on different mechanisms such as ADC or AR degraders in prostate cancer? Thank you.

Unknown: Hey, it's [inaudible] on for Michael, thanks for taking our questions. So quick one, [inaudible], can you talk about your plan of data disclosure this year and your current thinking on the potential registration path, how do you think about the positioning of this agent relative to some of the other emerging agents based on different mechanisms such as EDC or [inaudible] prostate cancer? Thank you.

Michael J. Yee: Michael Thanks for taking our questions. So quick one on that will be the Mac. Can you talk about your plan of data disclosure this year in your current thinking on the potential registration path. How do you think about the positioning of this agent relative to some of the other margin. Agents based on different mechanism, such as EDC or <unk> prostate cancer. Thank you.

Michael: Can you talk about your plan of data disclosure this year in your current thinking on the potential registration path. How do you think about the positioning of this agent relative to some of the other margin. Agents based on different mechanism, such as EDC or <unk> prostate cancer. Thank you.

Bob: Agents based on different mechanism, such as EDC or <unk> prostate cancer. Thank you.

Justin Claeys: Yeah, thanks for this outstanding question, Michael.

Jay Bradner: Yeah, thanks for this outstanding question, Michael.

Jay Bradner: Yeah, thanks for this outstanding question Michael. [inaudible] is a very interesting and exciting molecule. For those on the call, this is a steep one CD3 bi specific. We have been studying this in advanced castrate resistant prostate cancer. We have expanded a cohort in the phase one monotherapy. We're opening to reduce monitoring as well as as you invoke the existing and novel androgen receptor modulators integrators, we're exploring combinations with novel agents in that domain as well.

Justin Claeys: Zalerinomig is.

Zalerinomig is.

And. Zeller endemic is. A very interesting and exciting molecule for those on the call. This is a steep one CD three by specific. We have been studying this in advanced castrate resistant. State cancer.

Speaker Change #137: Zeller endemic is. A very interesting and exciting molecule for those on the call. This is a steep one CD three by specific. We have been studying this in advanced castrate resistant. State cancer.

Justin Claeys: A very interesting and exciting molecule for those on the call. This is a STEAP1 CD3 bispecific. We have been studying this in advanced castrate-resistant prostate cancer. We have expanded a cohort, the phase I monotherapy we're opening to reduce monitoring as well as as you invoke the existing and novel androgen receptor modulators, inhibitors, we're exploring combinations with novel agents in that domain as well. The priorities for the program right now are to establish reduced monitoring. This will be important to reach just all the patients who can benefit. We're looking at the feasibility of reduced monitoring.

A very interesting and exciting molecule for those on the call. This is a STEAP1 CD3 bispecific. We have been studying this in advanced castrate-resistant prostate cancer. We have expanded a cohort, the phase I monotherapy we're opening to reduce monitoring as well as as you invoke the existing and novel androgen receptor modulators, inhibitors, we're exploring combinations with novel agents in that domain as well. The priorities for the program right now are to establish reduced monitoring. This will be important to reach just all the patients who can benefit. We're looking at the feasibility of reduced monitoring.

Speaker Change #138: A very interesting and exciting molecule for those on the call. This is a steep one CD three by specific. We have been studying this in advanced castrate resistant. State cancer.

Speaker Change #139: We have been studying this in advanced castrate resistant. State cancer.

Speaker Change: State cancer.

Speaker Change: We have. Expanded a cohort in the phase one monotherapy. We're opening to reduce monitoring as well as as you invoke the. Existing and novel androgen receptor modulators integrators, we're exploring combinations with novel agents in that domain as well.

Speaker Change: Expanded a cohort in the phase one monotherapy. We're opening to reduce monitoring as well as as you invoke the. Existing and novel androgen receptor modulators integrators, we're exploring combinations with novel agents in that domain as well.

Speaker Change: We're opening to reduce monitoring as well as as you invoke the. Existing and novel androgen receptor modulators integrators, we're exploring combinations with novel agents in that domain as well.

Speaker Change: Existing and novel androgen receptor modulators integrators, we're exploring combinations with novel agents in that domain as well.

Speaker Change: The priorities for the program right now are to establish reduced monitoring. This will be important to reach just all the patients who can benefit. We're looking at the feasibility of reduced monitoring, we have great experience with these T cell engaging bi specifics as well as the plausibility of outpatient therapy. The approach to the regulatory path will present in due course. There'll be no surprises there. The path to bring medicines to patients with castrate resistant prostate cancer alone and ultimately in combination is well worn thankfully and we know how to deliver there. You asked about differentiation to other medicines, these are often apples to oranges comparisons, we have looked at that of course, and we really like the offering of [inaudible]. The patients treated in our study had quite advanced disease, even more advanced disease than the demographics of the patients as reported on other mechanism medicines, such as radio ligand therapies and the response rates we're seeing are really clinically meaningful to patients and that gives us great encouragement to develop the medicine more ambitiously in the next few years. Dave, in terms of the data sharing, do you to want to share?

The priorities for the program right now are to establish reduced monitoring. This will be important to reach just all the patients who can benefit. We're looking at the feasibility of reduced monitoring, we have great experience with these T cell engaging bi specifics as well as the plausibility of outpatient therapy. The approach to the regulatory path will present in due course. There'll be no surprises there. The path to bring medicines to patients with castrate resistant prostate cancer alone and ultimately in combination is well worn thankfully and we know how to deliver there. You asked about differentiation to other medicines, these are often apples to oranges comparisons, we have looked at that of course, and we really like the offering of [inaudible]. The patients treated in our study had quite advanced disease, even more advanced disease than the demographics of the patients as reported on other mechanism medicines, such as radio ligand therapies and the response rates we're seeing are really clinically meaningful to patients and that gives us great encouragement to develop the medicine more ambitiously in the next few years.

Peter Griffith: We have great experience with these T.

We have great experience with these T.

Speaker Change: Looking at the feasibility of reduced monitoring we have great experience with these T cell engaging bi specifics as well as the possibility of outpatient therapy. The APA. Approach to the regulatory path will present in due course. There'll be no surprises there. The path to bring medicines to patients with castrate resistant prostate cancer alone and ultimately in combination as well worn thankfully and we know how to deliver there. You asked about differentiation to other medicines. These are often apples to oranges comparisons we have looked at that of course, and we really like the offering of Delaware to make the patients treated in our study had quite advanced disease, even more advanced disease. Then the demographics of the patients as reported on. Other mechanism medicines, such as radio ligand therapies and the response rates, we're seeing are really cleaning the clinically meaningful to patients and that gives us great encouragement to develop a medicine more ambitiously in the next few years. Terms of the data sharing.

Justin Claeys: Cell-engaging bispecifics as well as the plausibility of outpatient therapy.

Cell-engaging bispecifics as well as the plausibility of outpatient therapy.

Justin Claeys: The approach to the regulatory path will present in due course. There'll be no surprises there. The path to bring medicines to patients with castrate-resistant prostate cancer alone and ultimately in combination is well worn, thankfully, and we know how to deliver there. You asked about differentiation to other medicines. These are often apples-to-oranges comparisons. We have looked at that, of course, and we really like the offering of Zaliridomag. The patients treated on our study had quite advanced disease, even more advanced disease than the demographics of the patients as reported on other mechanism medicines such as radioligand therapies. The response rates we're seeing are really clinically meaningful to patients. That gives us great encouragement to develop the medicine more ambitiously in the next few years.

The approach to the regulatory path will present in due course. There'll be no surprises there. The path to bring medicines to patients with castrate-resistant prostate cancer alone and ultimately in combination is well worn, thankfully, and we know how to deliver there. You asked about differentiation to other medicines. These are often apples-to-oranges comparisons. We have looked at that, of course, and we really like the offering of Zaliridomag. The patients treated on our study had quite advanced disease, even more advanced disease than the demographics of the patients as reported on other mechanism medicines such as radioligand therapies. The response rates we're seeing are really clinically meaningful to patients. That gives us great encouragement to develop the medicine more ambitiously in the next few years.

Speaker Change: The APA. Approach to the regulatory path will present in due course. There'll be no surprises there. The path to bring medicines to patients with castrate resistant prostate cancer alone and ultimately in combination as well worn thankfully and we know how to deliver there. You asked about differentiation to other medicines. These are often apples to oranges comparisons we have looked at that of course, and we really like the offering of Delaware to make the patients treated in our study had quite advanced disease, even more advanced disease. Then the demographics of the patients as reported on. Other mechanism medicines, such as radio ligand therapies and the response rates, we're seeing are really cleaning the clinically meaningful to patients and that gives us great encouragement to develop a medicine more ambitiously in the next few years. Terms of the data sharing.

Speaker Change: Approach to the regulatory path will present in due course. There'll be no surprises there. The path to bring medicines to patients with castrate resistant prostate cancer alone and ultimately in combination as well worn thankfully and we know how to deliver there. You asked about differentiation to other medicines. These are often apples to oranges comparisons we have looked at that of course, and we really like the offering of Delaware to make the patients treated in our study had quite advanced disease, even more advanced disease. Then the demographics of the patients as reported on. Other mechanism medicines, such as radio ligand therapies and the response rates, we're seeing are really cleaning the clinically meaningful to patients and that gives us great encouragement to develop a medicine more ambitiously in the next few years. Terms of the data sharing.

Speaker Change: There'll be no surprises there. The path to bring medicines to patients with castrate resistant prostate cancer alone and ultimately in combination as well worn thankfully and we know how to deliver there. You asked about differentiation to other medicines. These are often apples to oranges comparisons we have looked at that of course, and we really like the offering of Delaware to make the patients treated in our study had quite advanced disease, even more advanced disease. Then the demographics of the patients as reported on. Other mechanism medicines, such as radio ligand therapies and the response rates, we're seeing are really cleaning the clinically meaningful to patients and that gives us great encouragement to develop a medicine more ambitiously in the next few years. Terms of the data sharing.

Speaker Change: The path to bring medicines to patients with castrate resistant prostate cancer alone and ultimately in combination as well worn thankfully and we know how to deliver there. You asked about differentiation to other medicines. These are often apples to oranges comparisons we have looked at that of course, and we really like the offering of Delaware to make the patients treated in our study had quite advanced disease, even more advanced disease. Then the demographics of the patients as reported on. Other mechanism medicines, such as radio ligand therapies and the response rates, we're seeing are really cleaning the clinically meaningful to patients and that gives us great encouragement to develop a medicine more ambitiously in the next few years. Terms of the data sharing.

Speaker Change: You asked about differentiation to other medicines. These are often apples to oranges comparisons we have looked at that of course, and we really like the offering of Delaware to make the patients treated in our study had quite advanced disease, even more advanced disease. Then the demographics of the patients as reported on. Other mechanism medicines, such as radio ligand therapies and the response rates, we're seeing are really cleaning the clinically meaningful to patients and that gives us great encouragement to develop a medicine more ambitiously in the next few years. Terms of the data sharing.

Speaker Change: Then the demographics of the patients as reported on. Other mechanism medicines, such as radio ligand therapies and the response rates, we're seeing are really cleaning the clinically meaningful to patients and that gives us great encouragement to develop a medicine more ambitiously in the next few years. Terms of the data sharing.

Other mechanism medicines, such as radio ligand therapies and the response rates, we're seeing are really cleaning the clinically meaningful to patients and that gives us great encouragement to develop a medicine more ambitiously in the next few years. Terms of the data sharing.

Robert Bradway: Jay, in terms of the data sharing.

Bob Bradway: Jay, in terms of the data sharing.

Murdo Gordon: Dave, in terms of the data sharing, do you to want to share?

Justin Claeys: Do you want to share?

Do you want to share?

Speaker Change: Terms of the data sharing.

[Analyst]: Yeah.

Dave Reese: Yeah.

Robert Bradway: In terms of data availability, you know, as Jay mentioned, we're nearly complete in.

In terms of data availability, you know, as Jay mentioned, we're nearly complete in.

David M. Reese: Yeah, in terms of data availability, as Jay mentioned, we are nearly complete in terms of dose expansion enrollment so as those data roll forward over the course of the year, we will provide guidance as to when we might have the next look at that data, but that's probably the next meaningful set of data we will get to look at either later this year or early into next year.

Speaker Change #141: Availability as Jay mentioned, we are nearly complete in terms of dose expansion enrollment so as those data roll forward over the course of the year, we will provide guidance as to when we might have the next look at that data, but that's probably the next meaningful set of data we will get to look at either later this year or early into next year.

Justin Claeys: Terms of dose expansion, enrollment.

Terms of dose expansion, enrollment.

Robert Bradway: As those data roll forward over.

As those data roll forward over.

Justin Claeys: the course of the year, we'll provide guidance as to when we might have the next look at that data, but that's probably the next meaningful set of.

the course of the year, we'll provide guidance as to when we might have the next look at that data, but that's probably the next meaningful set of.

Robert Bradway: Data we'll get a look at either.

Data we'll get a look at either.

Justin Claeys: Later this year or early into next year. Okay, Julianne, we'll go to the next question, please.

Later this year or early into next year.

Justin Claeys: Okay, Julianne, we'll go to the next question, please.

Justin Claeys: Hey, Julien, we'll go to next question please.

Operator: Thank you, Michael. Our next question comes from Tim Anderson from Wolfe Research. Please go ahead. Your line is open.

Operator: Thank you, Michael. Our next question comes from Tim Anderson from Wolfe Research. Please go ahead. Your line is open.

Operator: Thank you Michael. Our next question comes from Tim Anderson from Wolfe Research. Please go ahead. Your line is open.

Robert Bradway: Thank you very much. So Eli Lilly today made a couple of sets of comments about, you know.

Tim Anderson: Thank you very much. So Eli Lilly today made a couple of sets of comments about, you know.

Timothy Minton Anderson: Thank you very much. So Eli Lilly today made a couple sets of comments about this topic of GIP agonism versus antagonism and they also weighed in on the data you published yesterday. And I am wondering in as much as you heard that or read those comments, is there any context to add or anything that's factually incorrect or anything to refute because they covered quite a few points and they continue to express their view, which was agonism is the best way not antagonism.

Timothy Minton Anderson: Today made a couple of sets of comments about. This topic of JP agonism versus antagonism and they also weighed in on the data you published yesterday and I am wondering and as much as you heard that or read those comments is there any context to add or anything thats factually incorrect or anything to refute.

Justin Claeys: This topic of GIP agonism versus antagonism.

This topic of GIP agonism versus antagonism.

Timothy Minton Anderson: This topic of JP agonism versus antagonism and they also weighed in on the data you published yesterday and I am wondering and as much as you heard that or read those comments is there any context to add or anything thats factually incorrect or anything to refute.

Robert Bradway: They also weighed in on the data you published yesterday. I'm wondering, you know, in as much as you heard that or read those comments, is there any context to add or anything that's factually incorrect or anything to refute? Because they covered quite a few points and you know, they continue to express their view, which is agonism is the.

They also weighed in on the data you published yesterday. I'm wondering, you know, in as much as you heard that or read those comments, is there any context to add or anything that's factually incorrect or anything to refute? Because they covered quite a few points and you know, they continue to express their view, which is agonism is the.

Timothy Minton Anderson: The covered quite a few points. They continue to express their view, which was agonism is the best way not antagonism.

Timothy Minton Anderson: They continue to express their view, which was agonism is the best way not antagonism.

Murdo Gordon: Best way, not antagonism.

Best way, not antagonism.

Justin Claeys: Hey Tim, this is Jay. Open it up to anyone else that wants to contribute to this.

Jay Olson: Hey Tim, this is Jay. Open it up to anyone else that wants to contribute to this.

Jay Bradner: Hey Tim, this is Jay. This open to anyone else who wants to contribute to this. I don't believe that-- yeah, engaging in a dialogue around this adds much to the narrative. Rather I would say that the argument for [inaudible] receptor antagonism comes from just the highest level of scientific data, the human experience across populations with a million patient studied among among those who have variation in the genes associated with this pathway, where that variation is directionally inhibitory, the BMI is lower. And so we're hoping to replicate that pharmacology with this medicine. We feel great about the offering in this domain.

Peter Griffith: You know.

You know.

Justin Claeys: I don't believe that.

I don't believe that.

Jay: I don't I don't believe it. Yes, they are engaging in a dialogue around this has as much to the. The narrative, rather I would say that the. The argument. Sure. Kipp receptor antagonism comes from just the highest level of scientific data the human experience across populations with. 1 million patient studied. Among among those who have variation. In the genes associated with this pathway, where that variation is directionally inhibitory the BMI is lower. And so we're hoping to replicate that pharmacology with this medicine. We feel great about the offering in this domain.

Justin Claeys: Yeah, that engaging in a dialogue around this adds much to the, to the narrative. Rather, I'd say that the argument for GIP receptor antagonism comes from just the highest level of scientific data, the human experience across populations with a million patients studied.

Yeah, that engaging in a dialogue around this adds much to the, to the narrative. Rather, I'd say that the argument for GIP receptor antagonism comes from just the highest level of scientific data, the human experience across populations with a million patients studied.

Jay: Yes, they are engaging in a dialogue around this has as much to the. The narrative, rather I would say that the. The argument. Sure. Kipp receptor antagonism comes from just the highest level of scientific data the human experience across populations with. 1 million patient studied. Among among those who have variation. In the genes associated with this pathway, where that variation is directionally inhibitory the BMI is lower. And so we're hoping to replicate that pharmacology with this medicine. We feel great about the offering in this domain.

Jay: The narrative, rather I would say that the. The argument. Sure. Kipp receptor antagonism comes from just the highest level of scientific data the human experience across populations with. 1 million patient studied. Among among those who have variation. In the genes associated with this pathway, where that variation is directionally inhibitory the BMI is lower. And so we're hoping to replicate that pharmacology with this medicine. We feel great about the offering in this domain.

Jay: The argument. Sure. Kipp receptor antagonism comes from just the highest level of scientific data the human experience across populations with. 1 million patient studied. Among among those who have variation. In the genes associated with this pathway, where that variation is directionally inhibitory the BMI is lower. And so we're hoping to replicate that pharmacology with this medicine. We feel great about the offering in this domain.

Jay: Sure. Kipp receptor antagonism comes from just the highest level of scientific data the human experience across populations with. 1 million patient studied. Among among those who have variation. In the genes associated with this pathway, where that variation is directionally inhibitory the BMI is lower. And so we're hoping to replicate that pharmacology with this medicine. We feel great about the offering in this domain.

Jay: Kipp receptor antagonism comes from just the highest level of scientific data the human experience across populations with. 1 million patient studied. Among among those who have variation. In the genes associated with this pathway, where that variation is directionally inhibitory the BMI is lower. And so we're hoping to replicate that pharmacology with this medicine. We feel great about the offering in this domain.

Jay: 1 million patient studied. Among among those who have variation. In the genes associated with this pathway, where that variation is directionally inhibitory the BMI is lower. And so we're hoping to replicate that pharmacology with this medicine. We feel great about the offering in this domain.

Justin Claeys: Among those who have variation in the genes associated with this pathway, where that variation is directionally inhibitory, the BMI is lower. And so we're hoping to replicate that pharmacology with this medicine. We feel great about the offering in this domain.

Among those who have variation in the genes associated with this pathway, where that variation is directionally inhibitory, the BMI is lower. And so we're hoping to replicate that pharmacology with this medicine. We feel great about the offering in this domain.

Jay: Among among those who have variation. In the genes associated with this pathway, where that variation is directionally inhibitory the BMI is lower. And so we're hoping to replicate that pharmacology with this medicine. We feel great about the offering in this domain.

Jay: In the genes associated with this pathway, where that variation is directionally inhibitory the BMI is lower. And so we're hoping to replicate that pharmacology with this medicine. We feel great about the offering in this domain.

Jay: And so we're hoping to replicate that pharmacology with this medicine. We feel great about the offering in this domain.

Jay: We feel great about the offering in this domain.

Justin Claeys: Okay, Julianne, we'll go to next question please.

Justin Claeys: Okay, Julianne, we'll go to next question please.

Justin Claeys: Okay. Julien, we'll go to the next question please.

Operator: Thank you, Tim. Our next question comes from Robyn Karnakis from Truist Securities. Please go ahead. Your line is open.

Operator: Thank you, Tim. Our next question comes from Robyn Karnakis from Truist Securities. Please go ahead. Your line is open.

Operator: Thank you Tim. Our next question comes from Robyn Karnauskas from Truist Securities. Please go ahead. Your line is open.

Operator: Hi, good evening. Thanks so much for taking my question. This is Nicole on the.

[Analyst] (Truist Securities): Hi, good evening. Thanks so much for taking my question. This is Nicole on the.

Nicole Germino: Hi, good evening. Thanks so much for taking my question. This is Nicole on for Robyn. So on the [inaudible] targeting [inaudible], can you talk about your level of confidence in this target competitive landscape what you're expecting to see near term.

Robert Bradway: For Robin.

For Robin.

Operator: So on Daxdilimab targeting ILT7 for lupus. Can you talk about your level of confidence in this target in light of the competitive landscape and what you expect to see near term from safety and efficacy?

So on Daxdilimab targeting ILT7 for lupus. Can you talk about your level of confidence in this target in light of the competitive landscape and what you expect to see near term from safety and efficacy?

Nicole: So on the MRO. Getting all key seven. Can you talk about your level of confidence. Sorry about that. Competitive. Thank you Paul and near term.

Speaker Change #144: Getting all key seven. Can you talk about your level of confidence. Sorry about that. Competitive. Thank you Paul and near term.

Nicole: Can you talk about your level of confidence. Sorry about that. Competitive. Thank you Paul and near term.

Speaker Change #145: Sorry about that. Competitive. Thank you Paul and near term.

Speaker Change #145: Competitive. Thank you Paul and near term.

Speaker Change #145: Thank you Paul and near term.

Robert Bradway: Sure, Jay and Dave.

Bob Bradway: Sure, Jay and Dave.

Speaker Change #146: Sure Jay and Dave? Well, it's very early days with this medicine. There is strong preclinical support from the published literature and our own preclinical work. It's nicely for patients a very competitive landscape, but this is the earliest phases of clinical investigation and so we're going to approach this with total equipoise and bring the medicine to the patients that stand to benefit the best based on the biology underlying. I'd say the target as you mentioned is one that helps control some of the central signaling that drives some of the autoimmune diseases that are being investigated here. At this point, I think all effort is towards generating clinical data.

Sure Jay and Dave? Well, it's very early days with this medicine. There is strong preclinical support from the published literature and our own preclinical work. It's nicely for patients a very competitive landscape, but this is the earliest phases of clinical investigation and so we're going to approach this with total equipoise and bring the medicine to the patients that stand to benefit the best based on the biology underlying.

Murdo Gordon: Sure Jay and Dave?

Jay Bradner: Well, it's very early days with this medicine. There is strong preclinical support from the published literature and our own preclinical work. It's nicely for patients a very competitive landscape, but this is the earliest phases of clinical investigation and so we're going to approach this with total equipoise and bring the medicine to the patients that stand to benefit the best based on the biology underlying.

Paul: Sure Jamie. Well, it's very early days with this medicine, there is strong preclinical support from the published literature and. Our own preclinical work. It's nicely for patients a very competitive landscape, but this is. The earliest phases of clinical investigation and so we're going to approach this with total equipoise and bring the medicine to the patients that stand to benefit the best based on the biology underlying yes.

Justin Claeys: Yeah, well, it's very early days with this medicine. There's strong preclinical support from the published literature and our own preclinical work. You know, it's nicely for patients a very competitive landscape. But this is, you know, the earliest phases of clinical investigation. And so, you know, we're going to approach this with total equipoise and bring the medicine to the patients that stand to benefit the best based on the biology underlying.

Jay Bradner: Yeah, well, it's very early days with this medicine. There's strong preclinical support from the published literature and our own preclinical work. You know, it's nicely for patients a very competitive landscape. But this is, you know, the earliest phases of clinical investigation. And so, you know, we're going to approach this with total equipoise and bring the medicine to the patients that stand to benefit the best based on the biology underlying.

Jamie: Well, it's very early days with this medicine, there is strong preclinical support from the published literature and. Our own preclinical work. It's nicely for patients a very competitive landscape, but this is. The earliest phases of clinical investigation and so we're going to approach this with total equipoise and bring the medicine to the patients that stand to benefit the best based on the biology underlying yes.

Jamie: Our own preclinical work. It's nicely for patients a very competitive landscape, but this is. The earliest phases of clinical investigation and so we're going to approach this with total equipoise and bring the medicine to the patients that stand to benefit the best based on the biology underlying yes.

Jamie: It's nicely for patients a very competitive landscape, but this is. The earliest phases of clinical investigation and so we're going to approach this with total equipoise and bring the medicine to the patients that stand to benefit the best based on the biology underlying yes.

Jamie: The earliest phases of clinical investigation and so we're going to approach this with total equipoise and bring the medicine to the patients that stand to benefit the best based on the biology underlying yes.

Robert Bradway: Yeah, I would say, you know, the target, as you mentioned, is one that.

Dave Reese: Yeah, I would say, you know, the target, as you mentioned, is one that.

David M. Reese: I'd say the target as you mentioned is one that helps control some of the central signaling that drives some of the autoimmune diseases that are being investigated here. At this point, I think all effort is towards generating clinical data.

Justin Claeys: Helps control some of the central signaling that drives some of the autoimmune diseases that are being investigated here.

Helps control some of the central signaling that drives some of the autoimmune diseases that are being investigated here.

Jamie: The target as you mentioned is one that helps control some of the central signaling that drives some of the autoimmune diseases. That are being investigated here at. At this point I think. All efforts towards generating clinical data.

Robert Bradway: You know, at this point, I think, you know, it's all efforts towards.

You know, at this point, I think, you know, it's all efforts towards.

Jamie: That are being investigated here at. At this point I think. All efforts towards generating clinical data.

Jamie: At this point I think. All efforts towards generating clinical data.

Justin Claeys: Generating the clinical data.

Generating the clinical data.

Jamie: All efforts towards generating clinical data.

Justin Claeys: Okay, Julia, next question, please.

Justin Claeys: Okay, Julia, next question, please.

Justin Claeys: Okay. Julien, next question please.

Operator: Thank you, Nicole. Our next question comes from James Shin from Deutsche Bank.

Operator: Thank you, Nicole. Our next question comes from James Shin from Deutsche Bank.

Operator: Thank you Nichol. Our next question comes from Jamie Shen from Deutsche Bank. Please go ahead. Your line is open.

Justin Claeys: Please go ahead.

Please go ahead.

Operator: Your line is open.

Operator: Your line is open.

Peter Griffith: Hey, thanks for taking a question.

James Shin: Hey, thanks for taking a question.

Justin Claeys: I have one for Jay.

I have one for Jay.

Peter Griffith: I just kind of want to piggyback on what Tim was alluding to. The GIP antagonism versus agonism. I'm looking at the Nature paper.

I just kind of want to piggyback on what Tim was alluding to. The GIP antagonism versus agonism. I'm looking at the Nature paper.

Jamie Shen: Hey, thanks for taking the question. I have one for Jay. I just kind of want to piggyback on what Tim was alluding to. The GIP antagonism versus agonism I'm looking at the nature paper, it looks like 133's 420 milligram dose had a slight blip in triglyceride that eventually fades but it does seem like antagonism is behaving a little differently from the literature for agonism. Is it too early to chalk it up to antagonism versus agonism your view? Just wanted to get your thoughts there.

Jamie Shen: JP antagonism horse agonism I'm looking at the nature paper it looks like 130 threes ports sold for 20 milligram dose had a slight blip in triglyceride that eventually fades. It does seem like antagonism is behaving a little differently from the literature for agonism.

Vikram Karnani: It looks like 133's 420mg dose has.

It looks like 133's 420mg dose has.

Justin Claeys: A slight blip in triglycerides that eventually fades. But it does seem like antagonism is.

A slight blip in triglycerides that eventually fades. But it does seem like antagonism is.

Peter Griffith: Behaving a little differently from the literature for agonism.

Behaving a little differently from the literature for agonism.

Jay: It does seem like antagonism is behaving a little differently from the literature for agonism.

Justin Claeys: Is it too early to chalk it up to antagonism versus agonism in your view? Just wanted to get your thoughts there. The short answer is it's too early to chalk it up to antagonism versus agonism. As I said before, and I meant it, that these lipids are labile and indirect biomarker of this pharmacology. This is an early stage study that.

Is it too early to chalk it up to antagonism versus agonism in your view? Just wanted to get your thoughts there.

Jay: Is it too early to chalk it up to antagonism burst of Agonism. Your view just wanted to get your thoughts there.

Jay Bradner: The short answer is it's too early to chalk it up to antagonism versus agonism. As I said before, and I meant it, that these lipids are labile and indirect biomarker of this pharmacology. This is an early stage study that.

Jay Bradner: The short answer is, it's too early to chalk it up to antagonism versus agonism. As I said before and I meant it these lipids are labile and indirect biomarker of this pharmacology. This is an early stage study that had one or three monthly doses of the medicine and so we are not reading anything into the lipids conclusively from this trial. We are making all these measurements in the active phase II.

Jay: These lipids are labile and indirect biomarker of this pharmacology. This is an early stage study that had one or three monthly doses of the medicine. And so we are not reading anything into the lipids. Conclusively from this trial, we are making all these measurements in the active phase II.

Peter Griffith: Had one or three monthly doses of the medicine.

Had one or three monthly doses of the medicine.

Justin Claeys: And so we are not reading anything into the lipids conclusively from this trial. We are making all these measurements in the active phase 2.

And so we are not reading anything into the lipids conclusively from this trial. We are making all these measurements in the active phase 2.

Jay: And so we are not reading anything into the lipids. Conclusively from this trial, we are making all these measurements in the active phase II.

Jay: Conclusively from this trial, we are making all these measurements in the active phase II.

Vikram Karnani: Great.

James Shin: Great.

Justin Claeys: I think we have time for one more, Julian.

Justin Claeys: I think we have time for one more, Julian.

Justin Claeys: Great. And I think we have time for one more Julien.

Operator: Thank you, James. Our last question will come from Carter Gould from Barclays. Please go ahead. Your line is open.

Operator: Thank you, James. Our last question will come from Carter Gould from Barclays. Please go ahead. Your line is open.

Operator: Thank you James. Our last question will come from Carter Gould from Barclays. Please go ahead. Your line is open.

Justin Claeys: Good evening.

Carter Gould: Good evening.

Robert Bradway: Thanks for taking the questions.

Thanks for taking the questions.

Justin Claeys: Maybe just one on 786, can you?

Maybe just one on 786, can you?

Carter Gould: Good evening, thanks for taking the questions. Maybe just one on 786, can you walk through exactly what's sort of driving--Maybe let me take a step back. Maybe first if you could outline sort of how you are setting expectations there and any color on what's driving the delay there. It seems like it's taking a long time to enroll 72 patients. Thank you.

Robert Bradway: Walk through exactly what's sort of driving.

Walk through exactly what's sort of driving.

[Analyst]: Maybe, let me take a step.

Maybe, let me take a step.

Robert Bradway: Back, maybe first kind of if you.

Back, maybe first kind of if you.

Justin Claeys: Could outline sort of how you're setting expectations there and any color on what's driving the delay there. It seems like it's taking a long time to enroll 72 patients.

Could outline sort of how you're setting expectations there and any color on what's driving the delay there. It seems like it's taking a long time to enroll 72 patients.

Peter Griffith: Thank you. Sure.

Thank you.

Jay Bradner: Sure.

Justin Claeys: No, thank you for your question. For the broader group, AMG 786 is an oral medicine being developed for obesity. It is not an incretin. Though we've not as yet disclosed its target or pathway. This study is progressing fine. The readout of the phase 1 is on track for H1 2024. We've completed initial dose escalation cohorts and we're just collecting and analyzing data, expecting the readout in H1 2024. Julianne, we're going to turn it back to Bob for some closing remarks.

No, thank you for your question. For the broader group, AMG 786 is an oral medicine being developed for obesity. It is not an incretin. Though we've not as yet disclosed its target or pathway. This study is progressing fine. The readout of the phase 1 is on track for H1 2024. We've completed initial dose escalation cohorts and we're just collecting and analyzing data, expecting the readout in H1 2024.

Jay Bradner: Sure, thank you for your question. For the broader group AMG 786 is an oral medicine being developed for obesity. It is not an increase and we have not yet disclosed that target or pathway. This study is progressing fine. The readout of the phase one is on track for the first half of 2024. We've completed initial dose escalation cohorts and we're just collecting and analyzing data. I'm expecting the readout in the first half of this year.

Speaker Change #151: For the broader group AMG 786 is an oral medicine being developed for obesity.

Speaker Change #152: Is not an increase that we have not as yet disclosed that's target or pathway.

Speaker Change #153: This study is progressing fine the readout of the phase one is on track for the first half of 2024.

Speaker Change #153: We've completed initial dose escalation cohorts and we're just collecting and analyzing data I'm expecting the readout.

Justin Claeys: Julianne, we're going to turn it back to Bob for some closing remarks.

Speaker Change #153: In the first half of this year great.

Justin Claeys: Julien, we're going to turn it back to Bob for some closing remarks. Thank you all for joining the call.

Justin Claeys: Julien, we're going to turn it back to Bob for some closing remarks.

Robert Bradway: Okay. Thank you all for joining the call. As you heard, we're excited about the opportunities that we see for growing our business across all four of our pillars, general medicine, oncology, inflammation, and rare disease. Last October, we shared an in-depth look at oncology in connection with the ESMO medical meeting, and we plan to do an introductory review of rare diseases and our rare disease pillar in late February to give you more information about the medicines that we already have on the market, as well as some of those that are advancing through our pipeline. So we're encouraged by the questions that we heard on this call about those molecules, and we're excited about them and their prospects. So we'll host a call which IR will share with you here over the next few days and look forward to having that opportunity in the meantime.

Bob Bradway: Okay. Thank you all for joining the call. As you heard, we're excited about the opportunities that we see for growing our business across all four of our pillars, general medicine, oncology, inflammation, and rare disease. Last October, we shared an in-depth look at oncology in connection with the ESMO medical meeting, and we plan to do an introductory review of rare diseases and our rare disease pillar in late February to give you more information about the medicines that we already have on the market, as well as some of those that are advancing through our pipeline. So we're encouraged by the questions that we heard on this call about those molecules, and we're excited about them and their prospects. So we'll host a call which IR will share with you here over the next few days and look forward to having that opportunity in the meantime.

Bob Bradway: Thank you all for joining the call. As you've heard, we're excited about the opportunities that we see for growing our business across all four of our pillars: general medicine, oncology, inflammation and rare disease. Last October we shared an in depth look at oncology in connection with the ESMO Medical meeting and we plan to do an introductory review of rare diseases and our rare disease pillar in late February to give you more information about the medicines that we already have on the market as well as some of those that are advancing through our pipeline. So we're encouraged by the questions that we've heard on this call about all those molecules and  we're excited about them and their prospects. So we will host a call, which IR will share with you here over the next few days and look forward to having that opportunity. In the meantime, again, thank you for your support and we look forward to talking to you at our Rare Disease Day or at our first quarter results call. Thank you.

Robert A. Bradway: As you've heard, we're excited about the opportunities that we see for growing our business across all four of our pillars: general medicine, oncology, inflammation and rare disease. Last October we shared an in depth look at oncology in connection with the ESMO Medical meeting and we plan to do an introductory review of rare diseases

Robert A. Bradway: Across all four of our pillars general medicine oncology inflammation in rare disease.

Robert A. Bradway: Last October we shared an in depth look at oncology in connection with the ESMO Medical meeting and we'll plan to do an introductory review of rare diseases.

Robert A. Bradway: and our rare disease pillar in late February to give you more information about the medicines that we already have on the market as well as some of those that are advancing through our pipeline. So we're encouraged by the questions that we've heard on this call about all those molecules and 

Robert A. Bradway: Those molecules.

Robert A. Bradway: we're excited about them and their prospects. So we will host a call, which IR will share with you here over the next few days and look forward to having that opportunity. In the meantime, again, thank you for your support and we look forward to talking to you at our Rare Disease Day or at our first quarter results call. Thank you.

Robert Bradway: Again, thank you for your support and we'll look forward to talking to you at the Rare Disease Day or at our Q1 results call.

Again, thank you for your support and we'll look forward to talking to you at the Rare Disease Day or at our Q1 results call.

Justin Claeys: Thank you.

Thank you.

Robert A. Bradway: Okay.