Q3 2021 Amgen Inc Earnings Call

My name is Erica and I will be your conference facilitator today for Amgen's third quarter 2021, the financial results Conference call.

Operator: The last speaker's prepared remarks. In order to ensure that everyone has a chance to participate, we would like to request that you limit yourself to asking one question during the Q&A session. To ask a question, please press the star, then the number one on your telephone keypad. To withdraw your question, press the pound key. I would now like to introduce Arvind Sood, Vice President of Investor Relations. Mr. Sood, you may

Lines have been placed on mute to prevent any background noise. It will be a question and answer session at the conclusion of the last speaker's prepared remarks in order to ensure that everyone has a chance to participate we would like to request that you limit yourself to asking one question during the Q&A session to ask a question. Please press Star then the number.

Arvind Sood: Erica, thank you. Good afternoon, everybody.

Arvind Sood: Welcome to our Q3 call. I think the three key themes for this quarter are continued execution, pipeline advancement, and preparedness to launch important new products. So let's get started.

One on your telephone keypad to withdraw your question press the pound key.

I'd now like to introduce Arvind Sood, Vice President of Investor Relations. Mr. Sood, you may now begin.

Arvind Sood: The slides have been posted. A quick reminder that we'll use non-GAF financial measures in our presentation, and some of the statements will be forward-looking statements. Our SEC filings identify factors that could cause our actual results to differ materially.

Erika. Thank you good afternoon, everybody welcome to our Q3 call.

I think the three key themes for this quarter, our continued execution pipeline advancement and preparedness.

Important new product.

So let's get started the slides have been posted quick reminder, that we'll use non-GAAP financial measures in our presentation and some of the statements will be forward looking statements.

Arvind Sood: So with that, I would like to turn the call over to our Chairman and CEO, Bob Bradway. Bob? Okay. Hello, everyone, and thank you for joining us.

Bob Bradway: Thank you for joining us on our call. There was another solid quarter of growth for Amgen, with total revenues rising 4%, driven by volume growth of 8%, which reflects the strong global demand for many of our innovative medicines, such as Repatha and Prolia, as well as for our high-quality biosimilars. Earnings per share for the quarter grew 11% thanks to disciplined management of our operating expenses. Shifting to the future, as we begin to see beyond COVID-19, I believe we've set ourselves up well to deliver attractive growth over the long term.

Our SEC filings identify factors that could cause our actual results to differ materially.

So with that I would like to turn the call over to our chairman and CEO, Bob Bradway Bob.

Hello, everyone and thank you for joining our call.

It was another solid quarter of growth for Amgen with total revenues rising, 4% driven by volume growth of 8%.

Which reflects the strong global demand for many of our innovative medicines such as the pass on Prolia as well as for our high quality Biosimilars.

Earnings per share for the quarter grew 11%, thanks to disciplined management of our operating expenses.

Bob Bradway: As an example, I'll draw your attention to our immunology and oncology portfolios, where we are building

Bob Bradway: Where we are building on our successful track record through a combination of internally generated innovation and strategic business development, which we expect to contribute to our long-term growth.

Shifting to the future as we begin to see beyond COVID-19, I believe we've set ourselves up well to deliver attractive growth over the long term.

Way of example, I'll draw your attention to our immunology and oncology portfolios.

Bob Bradway: In inflammation, we're very excited about tezepilumab, the first in class.

Where we are building on our successful track record through a combination of internally generated innovation and strategic business development, which we expect to contribute to our long term growth.

Bob Bradway: [inaudible] Given the millions of patients for whom existing asthma therapies are inadequate, we believe tezepilumab will be a significant growth driver for us for years to come. This product builds on our many years of success in treating inflammation. First with Enbrel and now, of course, with Otesla. We remain optimistic about the growth potential of Otesla, and as the next step, we're eagerly awaiting an expanded indication in the U.S. for mild to moderate plaque psoriasis.

In inflammation, we are very excited about because it tells you ma'am our first in class treatment for severe asthma that we hope to launch in the U S next year.

Given the millions of patients for whom existing asthma therapies are inadequate, we believe because it will be a significant growth driver for us for years to come.

This product builds on our many years of success and inflammation.

Bob Bradway: Particularly at a time when concerns have emerged about some potential new competitors.

First with Enbrel and now of course with Tesla.

We remain optimistic about the growth potential of Tesla and.

Bob Bradway: We also continue to grow Tesla globally, with the product now available in over 40 countries, up from 32 countries when we acquired it. Looking a bit further into the future, we expect to bring Amgevita, our biosimilar to Humira, to the U.S. in 2023, and we expect it to replicate the success.

And as the next step we are eagerly awaiting an expanded indication in the U S were mild to moderate plaque psoriasis.

Particularly at a time when concerns have emerged for some potential new competitors.

We also continued to grow at Tesla globally with the product now available in over 40 countries up from 32 countries when we acquired it.

Bob Bradway: We've worked with Amgevita and many other markets around the world. We're also enthusiastic.

Looking a bit further into the future, we expect to bring EM davita, our biosimilar to humira to the U S. In 2023.

Bob Bradway: Let's talk about AMG451, a Phase III ready, potential first-in-class treatment for atopic dermatitis that we're studying with our partners, Keoa Kirin, as well as a number of Amgen-discovered therapies currently in Phase II for lupus and celiac disease. In oncology, we're happy with the recent launch in the U.S. of Lumicras, our first-in-class KRAS G12C inhibitor, which treats non-small cell lung cancer.

We expect to replicate the success, we've had with MTA visa and many other markets around the world.

We're also enthusiastic about AMG 451 phase III ready potential first in class treatment for atopic dermatitis that we're studying with our partners kyowa Kirin as well as a number of Amgen discovered therapies currently in phase two for lupus and celiac disease.

Bob Bradway: [inaudible]

Bob Bradway: LumaCraft joins a portfolio of medicines already generating some $10 billion a year in sales. Several of these medicines delivered double-digit sales growth in the third quarter, including Kaprolos, Blincito, and Imvas. Looking ahead, we're excited about the growth potential of several other oncology assets in our pipeline. We have already initiated our first phase three trial for bemratuzumab, a potential first-in-class molecule to treat gastric and gastroesophageal junction cancer. We're also making good progress with several of our internally discovered solid tumor bite molecules, including one for prostate cancer.

In oncology, we're happy with the recent launch in the U S. As Luma Kras are first in class K Ras G 12, <unk> inhibitor, which treats non small cell lung cancer.

And we look forward to additional approvals and launches in major markets around the world as we roll forward.

Lula Kras joins a portfolio of medicines already generating some $10 billion a year.

A year in sales several of these medicines delivered double digit sales growth in the third quarter, including Kyprolis Lynn Sito and embassy.

Looking ahead, we're excited about the growth potential of several other oncology assets in our pipeline.

We've initiated already our first phase III trial for <unk>, a potential first in class molecule to treat gastric and gastroesophageal junction cancers.

Bob Bradway: [inaudible] In short, we have a number of products now on the market with plenty of room to grow.

We're also making good progress with several of several of our internally discovered solid bite.

Bob Bradway: More coming over the next several years from our pipeline. A compelling discovery research engine to continuously replenish that pipeline, and the wherewithal to take advantage of compelling business development opportunities as they arise. All that gives me confidence in our ability to serve more patients around the world and to deliver strong financial performance for our shareholders. On a final note, I'd like to thank my Amgen colleagues for their continued commitment to patients and to our business.

Solid tumor bite molecules, including one for prostate cancer and another for small cell lung cancer.

In short we have a number of products now on the market with plenty of room to grow more coming over the next several years from our pipeline of.

A compelling discovery research engine to continuously replenished that pipeline and the wherewithal to take advantage of compelling business development opportunities as they arise.

All that gives me confidence in our ability to serve more patients around the world and to deliver strong financial performance for our shareholders.

Bob Bradway: We were delighted to be named last week by Fortune Magazine as one of the 25 best workplaces in the world, and that's a reflection of our people and the passion and excellence they bring to their work.

On final note I'd like to thank my Amgen colleagues for their continued commitment to patients and to our business.

We were delighted to be named last week by Fortune magazine as one of the 25 best workplaces in the World and that's a reflection of our people and the passion and excellence they bring to their work Dave.

Dave Let me turn it over to you.

Thanks, Bob and good afternoon, everyone I.

Dave: Dave, let me turn it over to you. Thanks, Bob. Good afternoon, everyone. I would like to begin by welcoming our new colleagues from Teneo Bio, who bring expertise and technologies that will accelerate our innovation. One of our core areas of interest in research in molecular engineering is the development of multi-specific drugs to make undruggable targets tractable. Teneo Bioacquisition, combined with our previous incorporation of New Evolution and its DNA encoded library technology, provides capabilities to develop both large and small molecule multi-specifics and is a good example of how we are combining internal and external sources of innovation to advance the R&D portfolio. More than 60% of the molecules in our preclinical pipeline are multi-specifics. We will have more to say as those programs advance.

I would like to begin by welcoming our new colleagues from <unk> bio who bring expertise and technologies that will accelerate our innovation.

One of our core areas of interest in research in molecular engineering is the development of multi specific drugs to make undruggable targets tractable.

<unk> bio acquisition combined with our previous incorporation of new evolution and its DNA encoded library technology provides capabilities to develop both large and small molecule multi specifics and is a good example of how we are combining internal and external sources of innovation to advance the R&D portfolio.

More than 60% of the molecules in our preclinical pipeline or multi specifics, we will have more to say as those programs advance.

Cross R&D, we are focused on building a portfolio of complementary assets in certain disease areas to help drive the long term growth of the company.

Turning to our clinical programs I'll highlight a few areas, where we have made significant progress and are advancing multiple first in class molecules.

In oncology <unk>.

Key area of focus is lung cancer, and you'll hear from Murdo alumina Kras launch is off to an excellent start and the clinical programs remain on track we have initiated the phase II study of Luna Kras monotherapy in first line non small cell lung cancer for patients with SDK 11 mutant <unk> PDL one negative.

Dave: Across R&D, we have focused on building a portfolio of complementary assets in certain disease areas to help drive the long-term growth of the company. Turning to our clinical programs, I'll highlight a few areas where we have made significant progress and are advancing multiple first-in-class molecules. In oncology, one key area of focus is lung cancer. As you'll hear from Murdo, the Lumicrast launch is off to an excellent start, and the clinical programs remain on track. We have initiated a phase two study of Lumicrast monotherapy and first-line non-small cell lung cancer for patients with STK-11 mutant and or PD-L1 negative tumors.

<unk> we.

We continue to expect the top line results from the Phase III confirmatory study versus Docetaxel.

As data from our PD, one combination and ship combination.

Cohorts in the first half of next year.

And the <unk> or AMG 757, bite program targeting DLL, three and small cell lung cancer, some patients with very advanced disease and the phase one trial have now had responses lasting over a year supporting our potentially registrational phase II study, which we intend to launch by year end.

Finally in squamous non small cell lung cancer, we will initiate a phase one b study of the merit to the Mab directed against FGF are to be in the coming months.

Turning to gastrointestinal cancers, we will.

Dave: We continue to expect top-line results from the Phase III Confirmatory Study versus DOSA-Taxel, as well as data from our PD-1 combination and SHIP combination cohorts, in the first half of next year. In the Tarlatumab, or AMG-757, BITE program targeting DLL-3 and small cell lung cancer, some patients with very advanced disease in the Phase 1 trial have now had responses lasting over a year, supporting our potentially registrational Phase 2 study, which we intend to launch by year end. Finally, in squamous non-small cell lung cancer, we will initiate a Phase 1B study of bimerituzumab directed against FGFR2B in the coming months.

Enrolling a phase III trial of Luma Kras in combination with Vectibix in third line colorectal cancer in the coming weeks in first line gastric cancer. We have initiated the first of multiple phase III studies with <unk> with additional trial starts in the coming months. These studies will.

The address regional differences in the treatment of gastric cancer by exploring <unk> in combination with <unk>.

Either backbone chemotherapy or chemotherapy, plus a checkpoint inhibitor.

Prostate cancer is another area of focus in oncology.

With the acquisition of <unk> bio we now have two distinct bi specific T cell engage your technologies targeting <unk>.

We anticipate decisions, enabling data from the expansion cohort and the eight cap had a mab AMG 160 <unk> program in the first half of next year and are now exploring outpatient administration.

AMG AMG 340, <unk>, formerly <unk> hundred 85 continues to progress through dose escalation and we anticipate having informative data by the middle of next year as well, allowing us to determine the best path forward for one or both of these psm's molecules finally, rounding out our prostate cancer.

Dave: Turning to gastrointestinal cancers, we will be enrolling a phase 3 trial of lumacrass in combination with vectibix and third-line colorectal cancer in the coming weeks. In first-line gastric cancer, we have initiated the first of multiple phase 3 studies with pomerituzumab, with additional trial starts in the coming months. These studies will address regional differences in the treatment of gastric cancer by exploring omerituzumab in combination with either backbone chemotherapy or chemotherapy plus a checkpoint inhibitor.

Portfolio is AMG 509 targeting steep one which is also progressing through dose escalation, we anticipate having decision making data next year.

In inflammation, we spoke at length, a few weeks ago about the increasing activity in our portfolio are both innovative and biosimilar molecules regulatory approvals and launches expected in each of the next several years and the <unk> program regulatory reviews in severe asthma are proceeding with an FDA.

Dave: Prostate cancer is another area of focus in oncology. With the acquisition of Teneo Bio, we now have two distinct bi-specific T cell engager technologies targeting PSMA. We anticipate decision-enabling data from the expansion cohort in the ACAP-ADMAB AMG-160 program in the first half of next year and are now exploring outpatient administration. AMG 340, formerly TNB 585, continues to progress through dose escalation, and we anticipate having informative data by the middle of next year as well, allowing us to determine the best path forward for one or both of these PSMA molecules. Finally, rounding out our prostate cancer portfolio is AMG509, targeting STEEP1, which is also progressing through dose escalation. We anticipate having decision-making data next year.

FDA action date in the first quarter of 2022.

Studies in three additional indications are in progress to investigate the utility of <unk> across a range of inflammatory diseases.

And skin autoimmune diseases. The FDA review of Tesla for mild to moderate psoriasis continues with a <unk> date in December.

A few weeks ago, we presented results from a phase two study of AMG five one thk 40 83 first in class Dual Act action anti Ox 40 antibody, we are developing for atopic dermatitis in collaboration with Kyowa Kirin.

These data were very well received by the medical community is there is a clear need for innovative therapies with differentiated mechanisms of action for these patients. We have had productive regulatory interactions on the program and plan to launch phase III trials in the first half of 2022.

Finally, we also expect phase III data from Biosimilar candidates to Stora Eylea and Soliris in the inflammation portfolio next year.

In cardio metabolic disease, and ether of Sclerosus through a path of the silliest trial phase III outcome study of approximately 12000 patients at high cardiovascular risk, but without prior myocardial infarction or stroke is expected to complete enrollment in the coming weeks.

Dave: Inflammation, we spoke at length a few weeks ago about the increasing activity in our portfolio of both innovative and biosimilar molecules, regulatory approvals, and launches expected in each of the next several years. For example, in the tezapelimab program, regulatory reviews for severe asthma are proceeding with an FDA action date in the first quarter of 2022. Studies and three additional indications are in progress to investigate the utility of tezapelumab across a range of inflammatory diseases.

Pass or in small interfering RNA targeting LP little a and our first RNA based therapy remains on track to read out phase <unk> data by the middle of 2022 and provides a potential complement to <unk> in the treatment of <unk> cardiovascular disease by serving patients whose pathology is <unk>.

Driven by LDL cholesterol.

In conclusion with an innovative portfolio, where approximately three quarters of our clinical stage programs have first in class potential and a growing portfolio of Biosimilars. We are well positioned to continue to deliver important new medicines for patients and growth for shareholders over the near and long term murdo.

Dave: In skin autoimmune diseases, the FDA review of Otesla for mild to moderate psoriasis continues with a PDUFA date in December. A few weeks ago, we presented results from a Phase II study of AMG451, KHK4083, the first-in-class dual-action anti-Ox40 antibody we are developing for atopic dermatitis in collaboration with KeoWacurin.

Thank you, Dave third quarter product sales increased 4% year over year <unk>.

Volumes increased 8% globally, and we had record quarterly sales for several of our key products, including of entity Kyprolis ex Java and plate.

Our ex U S business grew 19% with volume growth of 25% year over year.

We continue to execute our volume driven growth strategy and see gradual recovery in our business from the impact of the pandemic during.

Dave: These data were very well received by the medical community, as there is a clear need for innovative therapies with differentiated mechanisms of action for these patients. We have had productive regulatory interactions on the program and plan to launch phase three trials in the first half of 2022. Finally, we also expect Phase 3 data from biosimilar candidates for Stelara, Ilea, and Sileris in the inflammation portfolio next year. Opassaran, a small interfering RNA targeting LpA, and our first RNA-based therapy, remains on track to read out Phase IIb data by the middle of 2022 and provides a potential complement to Repatha in the treatment of atherosclerotic cardiovascular disease by serving patients whose pathology is not driven by LDL cholesterol.

During the early part of Q3.

You'll see in patient care dynamics due to a surge in COVID-19, as we progressed through the quarter, we saw improvement in patient visits and diagnosis.

Customer activity improved during Q3, however face to face customer interactions remain below 2019 levels.

Now, let me review some product details beginning with our general medicine portfolio, which includes prolia as entity with Piper <unk>.

Overall revenue for our general Medicine portfolio grew 22% year over year with 24% volume growth.

In bone health Prolia sales grew 15% year over year, driven by double digit volume growth.

In the third quarter, new and repeat patient demand continued to improve as osteoporosis diagnoses rates reached over 90% of pre COVID-19 levels.

<unk>, which complements prolia in our bond portfolio had record sales of $149 million for the third.

Third quarter, driven by strong volume growth.

Given the severe impact of fractures on the lives of post menopausal women as entity provides an excellent therapy to build bone first.

Dave: In conclusion, with an innovative portfolio where approximately three-quarters of our clinical stage programs have first-in-class potential and a growing portfolio of biosimilars, we are well positioned to continue to deliver important new medicines for patients and growth for shareholders over the near and long term.

Moving to Rip asset.

Which remains the global leader in the <unk> class.

Sales increased 33% year over year, driven by 42% volume growth in the U S. We saw 64% year over year volume growth. This was partially offset by lower net selling price stemming from an increase in the number of Medicare part D patients receiving their path.

And who entered the donut hole.

Outside the U S volumes grew volumes grew 24% year over year, we remain confident in our ability to grow repass globally to address the significant unmet medical need in treating high risk cardiovascular patients.

Murdo: Thank you, Dave. Third quarter product sales increased 4% year over year. Volumes increased 8% globally, and we had record quarterly sales for several of our key products, including Avenity, Kyprolis, Xgeva, and Endplate. Our ex-U.S. business grew 19%, with volume growth of 25% year over year. We continue to execute our volume-driven growth strategy and see gradual recovery in our business from the impact of the pandemic. During the early part of Q3, we saw volatility in patient care dynamics due to a surge in COVID-19. As we progressed through the quarter, we saw improvement in patient visits and diagnosis. Total customer activity also improved during Q3. However, face-to-face customer interactions remain below the 2019 level.

Moving to our inflammation portfolio of Tesla sales increased 13% year over year with 7% volume growth since its launch you'll Tesla has been used by over 750000 patients globally.

And in the U S. It is the leader in bio naive psoriasis patient share.

But Tesla is 92% commercial payer coverage is an affordable safe and efficacious option for psoriasis and Psoriatic arthritis patients. We are now preparing for the anticipated U S approval of the mild to moderate psoriasis indication in the fourth quarter.

When we will have the opportunity for the first time to promote the use of Oh Tesla in this patient population.

Enbrel sales decreased 3% year over year, driven by a 2% decline in volume. This is the second straight quarter of swelling volume declined. Thanks to Enbrel has a long track record of.

All of the efficacy and safety.

Together with our partner Astrazeneca, we're preparing for the launch of <unk> in the U S with an expected <unk> date in early Q1 2022.

Murdo: Now, let me review some product details, beginning with our general medicine portfolio, which includes Prolia, Avenity, Repafa, and Imovic. Overall revenue for our general medicine portfolio grew 22% year over year with 24% volume growth. In bone health, Prolia sales grew 15% year over year, driven by double-digit volume growth. In the third quarter, new and repeat patient demand continued to improve as osteoporosis diagnosis rates reached over 90% of pre-COVID levels. Ivanity, which complements Prolia in our bone portfolio, had record sales of $149 million for the third quarter, driven by strong volume growth. Given the severe impact of fractures on the lives of post-menopausal women, Eventi provides an excellent therapy to build bone first.

Our sales force is fully staffed trained and has been deployed to provide disease state education.

We are actively engaging with payers to ensure access to patients for this breakthrough medicine.

We look forward to bringing <unk> to the 2.5 million people around the world, who live with severe uncontrolled asthma.

Moving to the hematology and oncology business sales of our six innovative products and are investing in <unk> biosimilars collectively totaled $1 8 billion.

In the quarter growing 12% year over year.

Several brands had record sales in the quarter, including ex Java, Kyprolis and plate and billing cycle.

Neulasta on probe maintained 50% volume share in the quarter and continues to be the preferred choice for physicians and patients. The most recent published average selling price for Neulasta in the U S declined 38% year over year, and 10% quarter over quarter going forward, we expect increased competition.

To result in continued net price and volume erosion.

Our launch of <unk> is off to a strong start with revenues of $36 million in Q3, and cumulative sales of $45 million through the end of the third quarter.

Within the Kras has been prescribed by over 500 oncologists in both academic and community settings. A majority of clinical laboratory have updated their testing reports to reflect <unk> as an actionable mutation and approximately 75% of patients with non small cell lung cancer are now being tested for.

Murdo: Moving to Repasa, which remains the global leader in the PCSK9 class, Repata sales increased 33% year over year driven by 42% volume growth. In the U.S., we saw 64% year over year volume growth. However, this was partially offset by a lower net selling price stemming from an increase in the number of Medicare Part D patients receiving Repata and who entered the donut hole.

The mutation at the time of diagnosis.

Having been a part of several lung cancer launches in my career I'm very pleased with the <unk> launch uptake in the U S. Thanks to our broad payer access and the positive reaction from the oncology community.

The U S health authorities have also approval in the Kras in Canada, and Luna Kras in the U K.

Murdo: As I've said, U.S. volumes grew 24% year over year. We remain confident in our ability to grow Repatha globally to address the significant unmet medical need for treating high-risk cardiovascular patients. Moving to our inflammation portfolio, Tesla sales increased 13% year over year with 7% volume growth. Since its launch, Otezla has been used by over 750,000 patients globally, and in the U.S., it is the leader in bio-naive psoriasis patient share. Well, Tesla has 92% commercial payer coverage and is an affordable, safe, and efficacious option for psoriasis and psoriatic arthritis patients.

Overall I am pleased with our results for the quarter, our record sales across a number of products and our increasing levels of customer activity and with that I'll turn it to Peter.

Thank you Murdo I will briefly walk through our third quarter financial results before discussing 2021 guidance.

Teens quality of execution during the past 18 challenging months continues to provide us with the strength to make timely prudent investments as we see them in both internal and external innovation that will deliver long term growth.

Let's now turn to the business.

The third quarter marked another period of solid performance with year over year revenue growth of 4% and non-GAAP EPS growth of 11%.

At Murdo described strong volume growth continued in the quarter with 8% year over year growth driven by Prolia of entity, we're path and empathy.

In addition, this quarter includes 147 million of favorable changes to estimated sales deductions previously recorded.

Murdo: We are now preparing for the anticipated U.S. approval of the mild to moderate psoriasis indication in the fourth quarter, when we will have the opportunity for the first time to promote the use of Otezola in this patient population. Enbrel's sales decreased 3% year-over-year, driven by a 2% decline in volume. This is the second straight quarter of slowing volume declines, thanks to Enbrel's long track record of efficacy and safety. Together with our partner AstraZeneca, we're preparing for the launch of tezapilimab in the U.S., with an expected PDUFA date in early Q1 2022.

In the third quarter last year, the favorable estimated sales deductions were $36 million, resulting in a $111 million year over year benefit in this quarter.

Our established products.

Which include Neulasta Neupogen, Epogen, Aeronef parse a bit insensitive par declined 21% year over year, driven by volume declines and lower net selling price.

These products will continue to contribute meaningful cash flows to our broader portfolio and also to innovation.

We do expect increased competition to result in additional erosion of these established products.

Other revenues at $386 million increased 21% year over year, primarily driven by shipments of the COVID-19 antibody therapy to Lilly.

We expect full year 2021, other revenues to be in a range of one five to $1 7 billion.

Third quarter total non-GAAP operating expenses were flat year over year as continued focus on execution productivity and efficiency fueled investments to drive long term growth, including the third quarter share of the approximately $200 million of operating expenses expected for.

Murdo: Our sales force is fully staffed, trained, and has been deployed to provide disease state education. We're actively engaging with payers to ensure access to patients for this breakthrough medicine. We look forward to bringing Tezapelimab to the 2.5 million people around the world who live with severe uncontrolled asthma.

For the full year related to the rodeo five prime and <unk> bio acquisitions as well as the <unk> collaboration.

Through focused expense discipline, we now expect full year operating expenses on an absolute basis to increase approximately 3% to 4% over last year inclusive of the approximately $200 million related to these transactions.

Murdo: Moving to the hematology and oncology business, sales of our six innovative products and our Mvasi and Kangenti biosimilars collectively totaled $1.8 billion in the quarter, growing 12% year over year. Several brands had record sales in the quarter, including Xtiva, Kyprolis, Endplate, and Bonsight. The new LASPA OnPro maintained 50% volume share in the quarter and continues to be the preferred choice for physicians and patients. However, the most recent published average selling price for Nulasta in the US declined 38% year-over-year and 10% quarter-over-quarter.

We will continue to execute on opportunities to allocate capital to important internal and external innovation opportunities.

On a non-GAAP basis cost of sales as a percent of product sales increased one five percentage points on a year over year basis to 15, 8% driven primarily by product mix, including COVID-19 antibody shipments to Lilly.

For the full year, we continue to expect cost of sales as a percent of product sales.

16% to 17%.

Non-GAAP R&D spend in the quarter decreased 4% year over year for.

For the full year, we expect non-GAAP R&D spend will increase in the mid single digit percentage range as we progress our innovative pipeline programs, including the launch of registration, enabling trials in lung and gastric cancer.

Murdo: Going forward, we expect increased competition to result in continued net price and volume erosion. However, our launch of Lumacraz is off to a strong start, with revenues of $36 million in Q3 and cumulative sales of $45 million through the end of the third quarter. Lumacraz has been prescribed by over 500 oncologists in both academic and community settings. A majority of clinical laboratories have updated their testing reports to reflect KRAS-G12C as an actionable mutation, and approximately 75% of patients with non-small cell lung cancer are now being tested for the mutation at the time of diagnosis.

Non-GAAP SG&A expense in the quarter decreased 5% and we expect the full year to also decline as we continue our focus on execution efficiency and digitalization.

Non-GAAP other income and expense net expenses increased on a year over year basis due to increased losses from our 20% share of <unk> results recorded under the equity method of accounting one quarter in arrears.

We expect full year net expense in the range of one three to $1 4 billion.

We have financial flexibility with $12 9 billion in cash and investments on our balance sheet and strong cash flows. Additionally, our third quarter dividend was $1 76 per share an increase of 10% over last year.

Turning to the outlook for the business for 2021.

We have invested in internal and external innovation to advance our pipeline in 2021 and continue to set ourselves up well for long term growth.

Moving to revenue based on underlying market dynamics, we are updating our 2021 revenue guidance range to $25 8 billion to $26 2 billion.

Murdo: Having been a part of several lung cancer launches in my career, I'm very pleased with the Lumicraz launch uptake in the U.S., thanks to our broad payer access and the positive reaction from the oncology community. Outside the U.S., health authorities have also approved Lumicraz in Canada and the U.K. Overall, I'm pleased with our results for the quarter, our record sales across a number of products, and our increasing levels of customer activity. And with that, I'll turn it to Peter.

We are increasing our non-GAAP EPS guidance range to $16 50.

$17.10.

Our non-GAAP tax rate range is updated to 13.0% to 14.0%.

Our capital expenditure guidance remains at $900 million and our capital expenditures continue to include investments supporting our environmental activities and also support our commitment to attain carbon neutrality.

We expect share repurchases for 2021 to be in the upper end of our range of $3 billion to $5 billion.

We executed effectively in the third quarter and are well positioned for long term growth before turning it over to Bob I'd like to thank and recognize our 24000 Amgen colleagues around the world for delivering another strong quarter of execution.

Peter: Thank you, Murdo. I will briefly walk through our third quarter financial results before discussing 2021 guidance. Our team's quality of execution during the past 18 challenging months continues to provide us with the strength to make timely, prudent investments as we see them in both internal and external innovation that will deliver long-term growth. Let's now turn to the business.

Bob.

Okay. Thank you Peter.

Can we open up the call now for questions, let's remind our callers of the procedures and the requests that we limit our questions to just one.

On the first go.

As a reminder to ask a question you will need to press star one on your telephone.

Question press the pound key please standby, while we compile the Q&A roster.

Your first question comes from the line of Michael <unk> with Jefferies.

Peter: The third quarter marked another period of solid performance with year-over-year revenue growth of 4% and non-GAAP EPS growth of 11%. As Murdo described, strong volume growth continued in the quarter with 8% year-over-year growth driven by Prolea, Avenida, Repatha, and Embatha. In addition, this quarter includes $147 million of favorable changes to estimated sales deductions previously recorded. In the third quarter last year, the favorable estimated sales deductions were $36 million, resulting in a $111 million year-over-year benefit this quarter.

Hi, guys. Good afternoon, good evening.

Just a question about the financials and how to think about go forward I just sort of a high level question, but as you think about the results. This year sort of the narrowing of guidance. This year company that typically seems to come in at the higher end and I know, there's a COVID-19 pandemic ongoing how do you think about the push and pull dynamics as we enter 2022.

I know you don't give 2022 guidance. So I would just love you to comment on the high level. Realizing we're in a in a pandemic. Thank you.

Yes, Michael you're right, we're not going to give 'twenty to 2022 guidance at this point I think what you can see as we continue to manage the <unk>.

<unk>.

Effectively.

I think reflected in the 4% on the top line and 11% on the bottom line EPS growth and we will continue to invest in opportunities that we think can deliver growth.

Peter: Our established products, which include Neulasta, Neupogen, Epogen, Aranes, Parasibiv, and Sensipar, decline 21% year over year, driven by volume declines and lower net selling prices. These products will continue to contribute meaningful cash flows to our broader portfolio and also to innovation. However, we do expect increased competition to result in additional erosion of these established products.

Were very clear that as we look at the future, we expect to be able to deliver growth for our for our shareholders and we'll have more to say about that when we give guidance for the next period.

Thank you.

Your next question comes from the line of Geoff Meacham with Bank of America.

Yes.

Hey, guys, it's Aspen on for Jeff. Thanks for the question.

Obviously talked about pad three over 3000 patient number.

Treated with Democrats that include some patients on studies I guess I just wanted to get a sense of what percentage of that.

Maybe the nonpaying borrowers has been converted over to paying and whats the timeline for moving through the rest of them. Thanks.

Peter: Other revenues at $386 million increased 21% year over year, primarily driven by shipments of the COVID-19 antibody therapy to Lilly. We expect full year 2021 other revenues to be in a range of $1.5 to $1.7 billion. Third quarter total non-GAAP operating expenses were flat year over year, as continued focus on execution, productivity, and efficiency fueled investments to drive long-term growth, including the third quarter's share of the approximately $200 million of operating expenses expected for the full year related to the Rodeo, 5 Prime, and Teneo bioacquisitions, as well as the Kiowa-Kirin collaboration, through focused expense, We now expect full-year operating expenses, on an absolute basis, to increase approximately 3-4% over last year, inclusive of the approximately $200 million related to these transactions.

Yeah, Hi, it's mark Thanks for the question.

We're roughly at about 75% of early access programs or patients who were enrolled in clinical trials converting to commercial supply.

The two major markets, where that's happening or the U S. Obviously and.

And in France, while we have not been approved in Europe, yet, we do have access to the <unk> program in France, where.

Patients coming out of our early access program can roll into the <unk> program, where we actually are booking revenue.

Thanks.

Your next question comes from the line of Chris Raymond with Piper Sandler.

Okay. Thank you.

A question on aim of vigor or maybe more strategically youre neurology presence.

So just for the drug.

Obviously revenue and script trends have kind of stalled.

I think it's pretty obvious that the oral <unk> that are sort of having an impact on the market.

Murdo I kind of noticed that you're sort of skipped over that one in the prepared comments, maybe just sort of talk about your commitment to neurology now with this market dynamic.

Is this a category that we should expect more investment in from a product offering standpoint is there.

Maybe some other plan here.

Peter: We will continue to execute on opportunities to allocate capital to important internal and external innovation opportunities. On a non-GAAP basis, cost of sales as a percent of product sales increased 1.5 percentage points on a year-over-year basis to 15.8%, driven primarily by product, including COVID-19 antibody shipments to Lilly. For the full year, we continue to expect cost of sales as a percent of product sales to be 16 to 17 percent. Non-GAAP R&D spend in the quarter decreased 4% year over year.

You could maybe talk about.

<unk>.

Sure. Thanks, Chris.

The first thing I would say is.

<unk> continues to be an important product to help patients suffering from migraine and we continue to believe that there are there is a large population of my migraine sufferers, who have yet to.

Be helped by the advent of the <unk> category.

Obviously as the market leaders in the sub cutaneous category of CGI P products, we have given up share to the oral is as they've come into the market, but they've also expanded the market.

Beyond the preventative setting and into the acute setting and even the preventative setting has grown with the advent of the of the oral so we expect that the market still has quite a bit of growth in headroom for growth, we expect to be able to continue.

Peter: For the full year, we expect non-GAAP R&D spend to increase in the mid-single-digit percentage range as we progress our innovative pipeline programs, including the launch of registration-enabling trials in lung and gastric cancer. Non-GAAP SG&A expense in the quarter decreased 5%, and we expect the full year to also decline as we continue our focus on execution efficiency and digitalization. Non-GAAP other income and net expenses increased on a year-over-year basis due to increased losses from our 20% share of Beijing's results recorded under the equity method of accounting one-quartered in arrears.

To maintain our leadership share position in total prescriptions.

We have over five years and that of safety and efficacy data in the market.

We continue now to have all of the U S commercial responsibility for <unk>.

Given recent work to consolidate what Novartis was previously contributing.

So we've actually increased our neurology presence in the last few months and then the last piece that we're excited about is we're awaiting our head to head superiority data versus topiramate.

To be published and after which we'll be able to promote that too.

General Neurologists headache specialists uneven.

Peter: We expect full-year net expenses in the range of $1.3 to $1.4 billion. We have financial flexibility with $12.9 billion in cash and investments on our balance sheet and strong cash flows. Additionally, our third-quarter dividend was $1.76 per share, an increase of 10% over last year.

Many primary care physicians, who are using <unk> to help their patients who are chronic migraine suffers so.

Headroom.

Right on the oral evolution, taking some growth out and also a little bit of net price in the quarter, taking some growth out of it as well.

Strategically we will continue to look and see if we can find products that fit well with the franchise that we're building will continue to look for those.

Thank you.

Your next question comes from the line of Omar <unk> with Evercore ISI.

Peter: Turning to the Outlook for the business for 2021, we have invested in internal and external innovation to advance our pipeline for 2021 and continue to set ourselves up well for long-term growth. Moving to revenue.

Hi, guys. Thanks for taking my question.

I feel like Amgen went through this period of getting a fair amount of credit for the clinical development and the lumen Kras program and and we might be sort of entering that phase where a lot of competitors have clinical stage programs on K, Ras and and we're about to get a lot of data over the next few months and I guess my question as well.

Peter: Based on underlying market dynamics, we are updating our 2021 revenue guidance range to $25.8 billion to $26.2 billion. Additionally, we are increasing our non-GAAP EPS guidance range to $16.50 to $17.10. Our non-GAAP tax rate range is updated to 13.0% to 14.0%. Our capital expenditure guidance remains at $900 million, and our capital expenditures continue to include investments supporting our environmental activities and also support our commitment to attain carbon neutrality. We expect share repurchases for 2021 to be in the upper end of our range of $3 to $5 billion.

What's your base case on how sort of the clinical data across the field shakes out is this going to be a PD one like situation of everybody about the same or could you end up seeing approaches like rason inhibitors et cetera.

Look any different known resistance mutations and a follow up to that also.

I feel like as we think about amgen's leadership on the <unk> target in the first place should we expect Amgen to file an IND on other kiosks mutations like <unk> or G. Tobey. Thank you.

Yeah. Thanks Omar this is Dave as you mentioned of course there are.

Multiple competitors coming behind Luma Kras.

We feel very good about our position I have not seen anything to.

To tell us that we don't have.

Really outstanding molecule and many of those are very very early just coding starting dose escalation. So I think it's premature.

Peter: We executed effectively in the third quarter and are well positioned for long-term growth. Before turning it over to Bob, I'd like to thank and recognize our 24,000 Amgen colleagues around the world for delivering another strong quarter of execution.

Premature to speculate on potential differentiated mechanism of action.

Or these sorts of things we also have a very broad based global program.

As we've mentioned we're now under regulatory review I think at last count that is now in over 15 jurisdictions or countries.

<unk>, the EMA and Japan, where our reviews are progressing and those are of course to vary.

Large market. So I feel very good about where we are we've got a large combination therapy program. There's lots to learn yet it took 40 years to get into the clinic and we're sorting out a lot of biology, but I feel very good about the molecule, we've got and where we are.

Bob Bradway: Okay, thank you, Peter. Why don't we open up the call now for questions? And let's remind our callers of the procedures and the request that we limit our questions to just one on the first go. Thanks.

Dave you want to say anything else about our <unk> program sorry.

For the reminder, in terms of.

Operator: As a reminder, to ask a question, you will need to press star 1 on your telephone. To withdraw your question, press the pound key. Please stand by while we compile the Q&A roster. Your first question comes from the line of Michael Yee with Jeffreys

We are interested in other targets.

As many of you know there are seven or eight.

Specific K Ras mutations that are now potentially attractive although they are different on a structural basis in each one.

<unk> distinct challenges, we do have some work ongoing.

As that progresses, we will say more about that publicly.

Michael J. Yee: Hi guys. Good afternoon. Good evening.

Thank you.

Michael J. Yee: Um, just say a question about the financials and how to think about going forward at sort of a high level. But, you know, as you think about the results this year, the narrowing of guidance this year, a company that typically seems to come in on the higher end, and I know there's a COVID pandemic ongoing. How do you think about the push and pull dynamics as we enter 2022? I know you don't give 2022 guidance. So I would just love for you to comment on the high level, realizing we're in a pandemic. Thank you. Yeah, Michael.

Your next question comes from the line of yarn <unk> with Cowen.

Hey, this is gabe on for your own. Thanks for taking my question just for Luma Kras to follow up so for the data with Hambro. That's expected in the first half of next year can you kind of give us some maybe set the stage a little bit for.

Whether the data will be mature enough for to get a good look at efficacy we have TPS status available for all patients and then just for the second ship to combination arm that you recently added.

The insight you can share into the thinking behind adding <unk> five was there any any difference in the profile.

The breadth of med molecule that you would highlight that might be a better overlap with Luna kras. Thank you.

Unknown Executive: Yeah, Michael, you're right. We're not going to give 2022 guidance at this point. I think what you can see is we continue to manage the business effectively. That's, I think, reflected in the 4% on the top line, 11% on the bottom line EPS growth, and we'll continue to invest in opportunities that we think can deliver growth. We're very clear that as we look ahead, we expect to be able to deliver growth for our shareholders, and we'll have more to say about that when we give guidance for the next period.

Yes, Thanks, Dave.

In terms of the what I would say broadly the checkpoint inhibitor combination data, we do expect to have.

A fulsome enough data set when we.

When we have everything together and present it at some point in the first half of next year to I think give good insights to the field.

About what these combinations look like in terms of the <unk>.

Various ship two inhibitors.

For which we're pursuing combinations there are some biochemical differences.

Between those drugs.

I think it's well worth our while given the potential importance in the mechanistic rationale of shift to as a combination target for us to examine those various molecules and so we are pressing forward on all fronts. Thank you.

Operator: Your next question comes from the line of Geoff Meacham with Bank of America.

Aspen: Hey guys, it's Aspen. I'm for Geoff. Thanks for the question. So you previously talked about that $3,000...

Thank you.

Your next question comes from the line of Geoffrey Porges with SBB Leerink.

Aspen: Over 3,000 patient numbers were created with LumaCraft that includes some patients in studies.

Very much for taking my question, maybe just another slightly big picture one.

Aspen: I guess I just want to get a sense of what percentage of that, maybe the non-paying bolus, has been converted over to paying and what the timeline is for moving through the rest of them.

BARDA Murdo I know you pay close attention to what's going on in D. C and I'd be interested in whether you think that we are close to having a deal on drug pricing reform and particularly could you give us a sense of what the financial impact on Amgen would be of the proposed part D changes and then secondly.

Aspen: The timeline for moving through the rest of them is, thanks. Yeah, hi, it's Murdo.

Murdo: Thanks for the question. We are roughly at about 75% of early access programs or patients who were enrolled in clinical trials converting to commercial supply. The two major markets where that's happening are the U.S., obviously, and in France. While we've not been approved in Europe yet, we do have access to the ATU program in France, where patients coming out of our early access program can roll into the ATU program where we actually are booking revenue.

Do you believe that you have any molecules that would be subject to negotiation under the proposed.

February negotiation with the selected part B drugs in the language.

Thanks, Jeff.

Obviously very premature for anybody to pretend like they know what the shape of the <unk>.

Let me legislation will be I don't think anybody is really seen any meaningful draft language.

We are aware of of course is that there is some tweeting and some back and forth between.

The house incentives, including.

Moderates in both.

Adjusting that theyre close in the third.

Operator: Your next question comes from the line of Chris Raymond with Piper Sandler.

We have a framework that they can align around so.

We will need to wait and see the details and as you would expect we will be focused on seeing whether.

Christopher Joseph Raymond: Thank you. I've got a question on Aimovig or, maybe more strategically, your neurology presence. So just for the drug, you know, obviously revenue and script trends have kind of stalled, and I think it's pretty obvious that it's the oral CGRPs that are sort of having an impact on the market. And, you know, Murdo, I kind of noticed that you sort of skipped over that one in the prepared comments, maybe just sort of talking about your commitment to neurology now with this market dynamic.

They are proposing leads to better access for patients to medicines.

<unk>.

Whether it does that while preserving the ecosystem that enables all of us to innovate the way we.

The way, we do and the way, we think we need to for the country. So.

Stay tuned Jeff again, very premature I know you guys would love to have.

A picture of that.

You could share with your investors in the picture that would make some sense, but I think everybody is trying to draw one at this point is really doing it in the way of sculpting fog.

Thank you okay. Thank you.

Your next question comes from the line of Matthew Harrison with Morgan Stanley.

Christopher Joseph Raymond: Is this a category that we should expect more investment in from a product offering standpoint? Maybe there is some other plan here that you could maybe talk about. Sure. Thanks, Chris. The first thing I would say is Imavig continues to be an important product to help patients suffering from migraine, and we continue to believe that there is a large population of migraine sufferers who have yet to be helped by the advent of the CGRP category. So a bit of headroom. You're right about oral evolution taking some growth out, and also a little bit of net price in the quarter taking some growth out as well.

Great. Good evening. Thanks for taking the question I was wondering if we could just touch a little bit on your outlook for product guidance. It looks like you've raised other revenue guidance, but you also took down the high end of your total company guidance. So maybe you could just talk about and that looks like about <unk>.

$800 million swing, if you add the two together so maybe you could just talk about what's the driver there.

Where youre seeing the pressure thanks.

Yes, Matthew Thank you Peter.

Peter here listen.

On the revenue range.

25, 8% to 2006 to reflect the latest market dynamics as Murdo shared with your volume growth year over year from products Prolia. Okay is there a path of entity Biosimilars.

Murdo: And strategically, we'll continue to look and see if we can find products that fit well with the franchise that we're building.

Competition against the mature products as I mentioned, but great cash flow producers for us.

The sharper recovery, we'd anticipated early hasnt materialized at the rate, we projected but the recovery continues at a steady but more gradual rate as murdo to describe for you.

Operator: Your next question comes from the line of Umer Raffat with Evercore ISI.

We continue to build into guidance.

Umer Raffat: Hi guys, thanks for taking my question. I feel like Amgen went through this period of getting a fair amount of credit for the clinical development LumaCRAS program, and we might be sort of entering that phase where a lot of competitors have clinical stage programs on KRAS, and we're about to get a lot of data over the next few months. And I guess my question is, what's your base case on how the clinical data across the field shakes out?

Mid single digit net price declines in 'twenty, one and we've got other revenue at 105 to $1 seven.

The increase year over year, driven primarily by the Lilly manufacturing reimbursement profit share, which began in the second quarter as we've said.

Yes.

And so those are the dynamics around the top side of the of the guidance and just Matt I might just observe that relative to the beginning of the year when we gave.

You gave your original guidance.

The Covid impact has lingered longer than I think we thought when we looked at this at the beginning of the year in particular in terms of the face to face visits and the number of patient diagnosis inside doctors' offices. So by now looking through the retrospective scope.

Umer Raffat: Is this going to be a PD-1-like situation where everybody's about the same? Or could you end up seeing approaches like RAS on inhibitors, etc., look any different on resistance mutations? And a follow-up to that,

It's pretty clear that the surge had an impact on the.

The number of patients going to see their doctors and term prescriptions being written so I don't think we're experiencing anything different from our peers, but.

It's the start of the year, we were hopeful that vaccines and other things.

Our enabled us to be further along in saying goodbye to this pandemic and I think we are right now but.

Umer Raffat: So I feel like as we think about Amgen's leadership on the KRAS target in the first place, should we expect Amgen to file INDs on other KRAS mutations like G12d or G12d? Thank you. Thanks, Umer. This is Dave.

Otherwise business performing well.

Consistent with where we hope to end of the year.

Your next question comes from the line of Alethia Young with Cantor Fitzgerald.

Hey, guys. Thanks for taking my question, maybe just follow up a little bit along with that.

Can you just talk a little bit about with like were positive and we made some of the selling price pressure that you've seen and do you think that kind of a.

Dave: You know, as you mentioned, there are multiple competitors coming behind LumaCraft. But we feel very good about our position. I've not seen anything to tell us that we don't have a really outstanding molecule. And many of those are very, very early, just starting to do dose escalation. So I think it's premature to speculate on potential differentiated mechanisms of action, or these sorts of things.

Slow step down or is it kind of.

Something that will happen more periodically thank you.

At least it did you say <unk> and <unk> is that right, yes, okay, yes, okay sure.

So <unk> in the quarter is more a function of what we've been able to do.

Since lowering the price in terms of increasing our penetration in the Medicare part D population. So we've seen some really nice growth there, but what happens when you grow in Medicare part D. As you also grow in the number of patients that enter the donut hole and Thats what were really seeing in Q3, and we expect that the continued in Q4.

Dave: We also have a very broad-based global program. As we mentioned, we're now under regulatory review in 15 jurisdictions or countries, including the EMA and Japan, where reviews are progressing. And those are, of course, two very large markets.

The good news side of that equation is we're growing nicely in Medicare, we're seeing much less patient abandonment.

In Medicare and that should be a compounding source of growth for us on a pro forma basis, but I would expect a pattern.

Of <unk>.

Q3, and Q4 net price drag is a function of the.

Dave: So I feel very good about where we are. We've got a large combined therapy program. There's lots to learn yet. It took 40 years to get into the clinic, and we're still sorting out a lot of biology. But I feel very good about the molecule we've got and where we are. Dave, do you want to say anything else about our G12 D or V program? Oh, sorry. Thanks for the reminder. In terms of, we are interested in other targets.

Medicare part D coverage gap unless of course that changes and whatever is brewing in D C. But that's how that's happened right now.

My name is it gets a little bit different. It's just it's really the annualized Asian of contracted business with Pbms in general Theres been fairly competitive activity there to maintain preferred formulary positions on national Pbms.

Dave: As many of you know, there are seven or eight. I'm going to be talking about the specific KRAS mutations that are now potentially tractable, although they are different on a structural basis, and each one poses distinct challenges. We do have some work ongoing, and as that progresses, we will say more about that publicly.

And we don't have the same amount of volume growth on the <unk>, but we do expect.

For that to be more stable going forward. So overall I think.

Major price effects have stabilized and we're actually now seeing some good top line volume drop to the bottom.

Yeah.

Your next question comes from the line of Jay Olson with Oppenheimer.

Gabe: Hey, this is Gabe on for yourself. Thanks for taking my question. Just for LumaCraft to follow up. So for the data with Pembroke that's expected in the first half of next year, can you kind of set the stage a little bit for whether the data will be mature enough for us to get a good look at efficacy? Will we have TPS status available for all patients?

Oh, Hey, thanks for taking the question is there any color you could provide on the pace of enrollment for phase two study will pass around and also any comments you could share on how you anticipate to.

Competitive landscape to evolve.

Yeah.

Like a protein any market with pellet Carson.

Essentially getting approved before old passerine thank you.

Dave: Yeah. Thanks, Dave.

Yes, Thanks, Jay in terms of the Phase II study is actually completed enrollment.

Dave: In terms of what I would say broadly, the checkpoint inhibitor combination data, we do expect to have a fulsome enough data set when we have everything together and present it at some point in the first half of next year to, I think, give good insights to the field about what these combinations look like. In terms of the various SHP2 inhibitors for which we're pursuing combinations, there are some biochemical differences between those drugs.

Of course these patients are followed for some time and.

As I noted in my remarks, we expect data in the middle of 2022, where we are quite pleased with the long term follow up we've seen from the phase one trial in terms of LP little a lowering in the preliminary safety profile of the molecule. So that that program is on track or if anything a little ahead of schedule.

As you note. There is another molecule ahead of US we have a slightly different mechanism as a small interfering RNA.

Mike.

The molecule quite a bit this is a large population of patients.

Dave: And, you know, I think it's well worth our while, given the potential importance and the mechanistic rationale of SHP2 as a combined target for us to examine those various molecules. And so we're pressing forward on all fronts. Thank you.

Recall that about 50%.

<unk> <unk> chronic cardiovascular diseases, not driven by LDL cholesterol and probably the majority of that is LP little a driven so we believe there are many many patients around the world that can be served by LP little a lowering agents.

So were quite eager to see the full phase II data.

Great. Thanks for taking the question.

Operator: Your next question comes from the line of Geoffrey Porges with SBB Lyrinc.

Your next question comes from the line of Ronny Gal with Bernstein.

Geoffrey Christopher Meacham: Thank you very much for taking my question. Maybe just another slightly bigger picture one. Bob and Murdo, I know you pay close attention to what's going on in D.C., and I'd be interested in whether you think that we're close to having a deal on drug pricing reform, and particularly, could you give us a sense of what the financial impact on Amgen would be of the proposed Part D changes? And then, secondly, do you believe that you have any molecules that would be subject to negotiation under the proposed federal Thanks.

Good afternoon, and thank you for taking my question. So we typically ask you about the negative impact of a potential deal in Washington, and I was wondering if we can reverse it and talk about the benefits so to the extent there are any.

A deal which limits patients out of pocket cost what drugs will benefit from increased use here what are the what other drugs, where you see significant abandonment in Medicare part D that might take might get a more use.

Second you've started at integer interchangeability trials for Humira Biosimilars can you just talk a little bit about your change your perspective here do you believe that each entity ability will be required longer chapter participated in this market and if not what's the justification for that for the trial.

Yeah.

Thanks, Ronny it's murdo. So so hypothetically speaking should there be an out of pocket cap for patients in part D introduced in some change in legislation I think it would help in our portfolio.

Bob Bradway: Thanks, Geoff. It's obviously very premature for anybody to pretend like they know what the shape of any legislation will be. I don't think anybody's really seen any meaningful draft language yet. What we are aware of, of course, is that there's been some tweeting and some back and forth between the House and the Senate, including moderates in both suggesting that they're close and that they think they have a framework that they can align around.

We've been advocates for changes to part D in that regard.

For for quite a while where we do think that the out of pocket expenditures in the <unk>.

List price equation for co pays for patients are disincentives to drug adherence and maybe even for initial Phil So I think.

Bob Bradway: So we'll need to wait and see the details, and as you would expect, we'll be focused on seeing whether what they're proposing leads to better access for patients to medicines and whether it does that while preserving the ecosystem that enables all of us to innovate the way we do and the way we think we need to in the country. So stay tuned, Geoff. Again, very premature. I know you guys would love to have a picture that you could share with your investors and a picture that would make some sense, but I think anybody trying to draw one at this point is really doing it in the way of sculpting fog.

Products like our path.

Where we are largely a Medicare part D population.

Benefit from out of pocket caps now would depend obviously what that travels with does it travel with more.

Commitment from the manufacturer in the catastrophic phase, where we pick up more of the top so it needs to be equated with other things that could be in any proposed legislation but.

I hope that out of pocket caps come into play because I think patients.

Who are in part D are sometimes.

Treated poorly.

Unknown Executive: [inaudible]

And our sub optimally treated because of that.

Operator: Your next question comes from the line of Matthew Harrison with Morgan Stanley.

And it would improve their affordability.

Matthew Harrison: Great. Good evening.

To the question on the MTV the interchange ability study, we we continue to feel very good about our opportunity with Amgen Vita.

Matthew Harrison: Thanks for taking the question. I was wondering if we could just touch on your outlook for product guidance. It looks like you raised other revenue guidance, but you also took down the high end of your total company guidance. So maybe you could just talk about that, and that looks like about a $800 million swing if you add the two together. So maybe you could just talk about what's the driver there and where you're seeing the pressure. Thanks.

Being in that first wave and potentially alone in the first wave of Biosimilar launches to humira in the U S affords us an opportunity to.

Work with payers to work with.

The pbms and with providers to establish a leadership position.

We look at every parameter of a biosimilar product and this is experience from MTO Vita itself in Europe, but it's also the experience from our other biosimilar portfolio in the U S and we look at things like latex free citrate free we look at needle gauge, we look at device and of course, we look at enter.

Peter: Matthew, thank you. Peter here.

Peter: Listen, on the revenue range, you know, we're 25.8 to 26.2. This reflects the latest market dynamics, as Murdo shared with you. Volume growth year over year from products, Prolea, Otesla, Repath, Eventi, Biosimilars, Competition Against the Mature Products, as I mentioned, but great cash flow producers for us. You know, the sharper recovery we'd anticipated early hasn't materialized at the rate we projected, but the recovery continues at a steady but more gradual rate, as Murdo described for you.

Changeability so while we don't think it's essential we think its just another.

Attribute of the product that could augment our success in in that launch in 2023. So that's really why we've initiated the trial running.

Thank you.

Your next question comes from the line of Kennan Mackay with RBC capital markets.

Hi, This is Sudan Logan Nathan on for Kennan. Thank you in advance for taking your questions. So first I wanted to ask on alumina kras. So how much of an impact are you expecting.

Peter: So, you know, we continue to build into guidance, you know, mid single-digit net price declines in 21. We've got other revenue at 1.5 to 1.7. The increase year over year is driven primarily by the Lilly Manufacturing Reimbursement Profit Share, which began in the second quarter, as we've said. And so, you know, those are the dynamics around the top side of the guidance. And just, Matt, I might just observe that relative to the beginning.

Democrats, having on the updated top and your guidance that you updated for 2021, and then taking into account any competition entering the market in 2022, how do you plan to formulate.

Right, we do guidance based on that for 'twenty, two and then secondly.

In regards to limit Kras perspective.

Hum.

Combo program for colorectal cancer.

Going forward.

How could this.

What could this mean for Vectibix if approved can we expect some growth in that program.

Peter: I just observed that relative to the beginning of the year, you know, when we gave the original guidance, the COVID impact has lingered longer than I think we thought when we looked at this at the beginning of the year, particularly in terms of face-to-face visits and the number of patient diagnoses inside doctors' offices. So by now, looking through the retrospectoscope, you know, it's pretty clear that the surge had an impact on the number of patients going to see the doctors and, in turn, prescriptions being written.

<unk> combination gets.

Through to approval and then.

Thirdly, just wanted to ask about the antibody manufacturing agreement with <unk>.

COVID-19 is that still something we can expect that to be included in the other revenue line item going forward.

Updates on that just based on the pandemic.

Hi.

Environment, Let's take the first question and we can answer that in the rescue Columbia. Later this is arvind from Investor Relations and we can address those questions separately.

If maybe you can address the question about global Cross I think it was yes, I think murdo.

Peter: So I don't think we're experiencing anything different from our peers. But you know, at the start of the year, we were hopeful that vaccines and other things might have made us or enabled us to be further along in saying goodbye to this pandemic than I think we are right now. But again, otherwise, business is performing well and consistent with where we hope to end the year.

Revenue in the competition, yes more of a commercial question so.

We obviously don't provide product level revenue guidance, but.

I'll say this.

I've worked in oncology for many years now.

I've been a part of some important law.

Cancer product launches.

And this this launch after 40 years of trying to solve the <unk>.

Operator: Your next question comes from the line of Alethea Young with Cantor Fitzgerald.

<unk> under him in lung cancer. This launch has been very special and the team has done an excellent job of executing across the payer customers our provider customers and of course for patients and I was very proud of what our R&D organization was able to do and the speed at which they brought this product to market and I feel that the medical.

Unknown Attendee: Hey guys, thanks for taking my question. Maybe to follow a little bit along with that, can you just talk a little bit about Repata and Amovic, some of the selling price pressure you've seen, and do you think that it's kind of, you know, kind of a slow step down, or is it kind of, you know, something that will happen more periodically? Thank you.

And commercial organizations have taken the customer facing stage in the go to market stage of this launch extremely.

Seriously and with a lot of responsibility and so far it's early days, but so far they've done very very well and so I'm pleased with the trajectory.

Unknown Executive: Aletha, did you say Repatha in Amavig? Is that what you're asking? Yeah. Yeah, okay. Yeah. Okay, sure.

What we're seeing is.

Unknown Executive: So Repatha in the quarter is more a function of what we've been able to do since lowering the price in terms of increasing our penetration in the Medicare Part D population. So we've seen some really nice growth there. But what happens when you grow Medicare Part D is you also grow the number of patients that enter the donut hole. And that's what we're really seeing in Q3. And we expect that to continue to happen in Q4.

Many academic centers are changing their testing protocols in lung cancer.

So that everybody knows their <unk> status. Many large community oncology networks have done the same now we still have a few large community oncology networks to go.

So we will be working on those in the fourth quarter, but I.

Couldnt be more pleased with the way in which we've entered the market and I think.

Unknown Executive: The good news side of that equation is we're growing nicely in Medicare; we're seeing much less patient abandonment in Medicare. And that should be a compounding source of growth for us on a going forward basis. But I would expect a pattern of Q3, Q4 net price drag as a function of the Medicare Part D coverage gap unless, of course, that changes in whatever is brewing in DC. But that's how it's stabilized, and we're actually now seeing some good top line volume drop to the bottom.

That bodes well for our ability to establish a strong leaders leadership position and help many many patients who are unfortunately progressing from first line into second line disease.

Before competitors come in yes, it's hugely rewarding to launch a product like this where you hear stories of patients who have been told that their options are limited and that they should sign up for hospice care.

Coming out of hospice and getting treated with Linda kras with commercial drug and responding and the drug is working well in the marketplace. We're hearing those anecdotal stories coming back from prescribers and we will continue to do everything within our power to continue to launch limit kras quickly around the world and help menu.

Operator: Your next question comes from the line of Jay Olson with Oppenheimer. Oh, hey, thanks for taking the question.

More patients great. Thanks, Murdo Erica let's take the next question. Please.

Jay Olson: Well, hey, thanks for taking the question. Is there any color you could provide on the pace of enrollment for the phase two study of El Pasaran? And also, any comments you could share on how you anticipate the competitive landscape to evolve in the Lycoprotein A market with Pelicarcerin? [inaudible] Yeah, thanks, Jay.

Your next question comes from the line of Robyn <unk> with <unk> Securities.

Hi, Thanks for taking my question, maybe a glass half empty one in a glass half full one.

I'll start off with the glass.

Half half empty.

When I look at what's going on with your business.

I think what we've heard on the call a lot of its pricing pressure. Despite your growth and your great marketing strategy and then you've got a pipeline. That's got a lot of competitors that are going to compete with that because a lot of people out there with either similar molecules are competing molecule. So on.

Dave: Yeah, in terms of the phase two study, it has actually completed enrollment. And, of course, these patients are followed for some time. And as I noted in my remarks, we expect data in the middle of 2022, or we're quite pleased with the long-term follow-up we've seen from the phase one trial in terms of LP little a lowering in the preliminary safety profile of the molecule, so that that program is on track, or, if anything, a little ahead of schedule.

On that question.

Any change in strategy for development and picking next generation R&D candidates going forward for any tool kits or platforms that you might need.

The drug and then the house.

Dave: As you know, there is another molecule ahead of us; we have a slightly different mechanism as a small interfering RNA. But we like the molecule quite a bit. This is a large population of patients. Recall that about 50% of atherosclerotic cardiovascular disease is not driven by LDL cholesterol. And probably the majority of that is LP little a driven. So we believe there are many, many patients around the world that can be served by LP little a lowering agents. And so we're quite eager to see the full phase of data.

Final question.

This is a great opportunity in lung you did a great job with the kras developing that drug can you talk a little bit about marketing strategy.

You could have competition here, but you can stay ahead of that competition with all the drugs that youre developing walk us through where.

Minus the <unk>.

Raj you had amgen for for making sure that you are the dominant player even in a multiple multiplayer environment. Thanks.

Let's go in reverse order Murdo why don't you start and then Dave can punch.

Well not to belabor the point, but again.

<unk>.

The oncology field for a number of years and what I've seen since coming to Amgen is real strength.

Operator: Your next question comes from the line about Ronnie Gale with Bernstein.

Unknown Attendee: Good afternoon, and thank you for taking my question. So we typically ask you about the negative impact of a potential deal in Washington. I was wondering if we can reverse that and talk about the benefits. So to the extent there are any, a deal that limits patients' out-of-pocket costs, what are the drugs that will benefit?

In the legacy of Amgen, which is of course, the supportive care products that we have we've augmented that.

Recently with the launch of our Biosimilar portfolio.

And then most recently of course with the launch alumina Kras and when I sit down with Ceos of cancer networks or academic cancer centers. They are very interested in talking to Amgen.

Unknown Executive: [inaudible]

Unknown Executive: Do you believe that interchangeability will be required longer-term to participate in this market, and if not, what's the justification for the drop?

And they are also interested in talking to us about the very rich pipeline of products that Dave recent R&D colleagues are developing so I think we are very much a leader in oncology I think that our commercial position with innovative products and biosimilars.

Murdo: Thanks Ronnie, it's Murdo. So, hypothetically speaking, should there be an out-of-pocket cap for patients in Part D introduced as some change in legislation, I think it would help our portfolio. We've been advocates for changes to Part D in that regard for quite a while, where we do think that the out-of-pocket expenditures and the list price equation for co-pays for patients are disincentives to drug adherence and maybe even for initial fill.

And launches of new therapeutics puts us in a very strong account position and I think.

In a world where a lot of care is delivered in community oncology.

Our relationships there are extremely strong.

<unk> been able to make some customer visits this year. Despite some of the interruptions of the pandemic and most of my visits have been in support of the <unk> launch and I can tell you.

Murdo: So I think products like Repatha, where we are largely a Medicare Part D population, could benefit from out-of-pocket caps. Now, it would obviously depend on what that travels with. Does it travel with more commitment from the manufacturer in the catastrophic phase where we pick up more of the tab? So it needs to be equated with other things that could be in any proposed legislation. But I hope that out-of-pocket caps come into play because I think patients who are in Part D are sometimes treated poorly and are sub-optimally treated because of that, and it would improve their affordability.

They have been very very good at working with us to develop testing programs look back programs entering flags <unk>, making sure patients are flagged for treatment.

And it's those systems and those processes that being first on the ground, we should be able to.

To build and sustain longer term of course, it will be the continuation of being <unk>.

First with indications and being brought in the development of the asset and then supporting it with additional products in lung cancer.

Dave is developing in our pipeline.

Murdo: You know, to the question on the Amgivita interchangeability study, we continue to feel very good about our opportunity with Amgivita. Being in that first wave and potentially alone in the first wave of biosimilar launches to Humira in the U.S. affords us an opportunity to work with payers, work with the PBMs, and with providers to establish a leadership position. We look at every parameter of a biosimilar product, and this is experience from Amgivita itself in Europe, but it's also experience from our other biosimilar portfolio in the U.S., and we look at things like latex re-citrate-free. We look at needle gauge. We look at the device. And, of course, we look at interchangeability. So while we don't think it's essential, we think it's just another thing.

Great. Thanks.

Robin Yes in terms of Toolkits, we could obviously talked probably for hours about the tool kits that we've got in discovery research into our clinical trials. Let me focus on just a couple of things for the purposes of this discussion.

We are building what I think is an industry leading capability in what I call human data.

Which means the collection integration and interrogation of data ranging from various ohmic data genomic data transcript don't make data proteomics data through clinical trials data through real world evidence and real world data and it's one of our core belief.

That the coming few decades.

We'll be one by those who understand how to make use of.

Operator: Your next question comes from Kinnon McKay with RBC Capital Markets.

In particular analyze for giant tsunami of data that is now starting to wash over us now that data of course generates drug targets.

Unknown Attendee: Hi, this is Sudan Loganathan on behalf of Kennan. Thank you in advance for taking our question.

And pathways and as I mentioned in my prepared remarks. So we're building extensive capabilities for the development of multi specific molecules either small molecules large molecules or hybrid molecules about 80% to 85% of the currently validated.

Unknown Attendee: So first, I wanted to ask about Lumocrast. So, you know, how much of an impact are you expecting Lumocrast to have on the updated top-end revenue guidance that you updated for 2021? And then, taking into account any competition entering the market in 2022, how do you plan to formulate, you know, revenue guidance based on that for 2022? And then, secondly, in regards to the Lumocrast plus Vectabix third-line combo program for colorectal cancer, looking forward, what could this mean for Vectabix? If approved, you know, can we expect some growth in that program if this combination gets, you know, through to approval? And then

<unk> are currently not approachable with existing technologies.

We are building the capability to go after what I think will be a good traction of those undruggable targets. So I feel great about the platforms that we've got in place and are continuing to build on and a lot more on this over the next year or two.

Your next question comes from the line of Cory <unk> with J P. Morgan.

Hi, This is gavin on for Cory Thanks for taking our question maybe one for Murdo just.

Unknown Attendee: And then thirdly, just wanted to ask about the Antibody Manufacturing Agreement for COVID-19. Is that still something we can expect to see?

Just curious about the expected impact of.

Mild to moderate and label expansion, specifically should we expect immediate uptake in 2022 or is it something that will be a little more gradual and then secondly, just geographic expansion was underscores a key strategy for the growth profile for this product.

Unknown Executive: [inaudible]

Unknown Executive: Deepthorn, that's just based on the pandemic.

Unknown Executive: [inaudible]

Arvind Sood: Yeah, let's take the first question, and we can answer that, and the rest, you know, call me later. This is Arvind from Investor Relations, and we can address those questions separately. So Dave, maybe you can address the question about LumaCross.

And rest of World has been around 20% of total sales. So just curious.

That trend is going to continue.

Yes, Thank you Kevin.

Yeah.

When we acquired hotels I thought it would be a really good add to the portfolio and our strength in immunology, both with dermatology and rheumatology and obviously, we had to make a certain set of assumptions about how that product would evolve in our ownership.

Operator: Erika, let's take the next question.

Operator: Your next question comes from the line of Robyn Karnauskas with Truist Securities.

Robyn Kay Shelton Karnauskas: Hi, thanks for taking my question. Maybe a glass half-empty one and a glass half-full one.

So far I have to say I'm, even more pleased with the with the strength that the product brings to Amgen. We've been successful as you highlight in.

Robyn Kay Shelton Karnauskas: So I'm going to start off with a glass half empty. So when I look at what's going on with your business, I mean, I think what we've heard on the call a lot is pricing pressure despite your growth and your great marketing strategy. And then you've got a pipeline that's got a lot of competitors that are going to compete with it because there are a lot of people out there with either similar molecules or competing molecules.

Demonstrating the product's efficacy and safety in the mild to moderate patient setting, which is a perfect sweet spot for this product given the convenience of its oral dosing given the.

Well demonstrated safety and efficacy of the product.

We also recently.

Had a decision on the patent.

For <unk>, low, which definitely helps make it a very strategic product for us a very important product for the growth of the company and the <unk>.

It is just perfect. It we've integrated the legacy Celgene team fully into Amgen, we've got.

Robyn Kay Shelton Karnauskas: So on that question, it's how any change in strategy for development and picking next generation R&D candidates going forward for any toolkits or platforms that you might need to develop a drug? And then the half-full question is, you have this great opportunity in lung cancer, or you did a great job with LumaCraft developing that drug.

Enbrel Ando Tesla now being promoted in rheumatology and dermatology.

And we've seen we've seen volume growth improve in most most markedly in the last part of Q3, but that continues into Q4.

We didn't plan on a pandemic when we did the transaction, obviously, but we've weathered it well the team is staying focused.

Murdo: So, you know, remind us of the strategy at Amgen for making sure that you're the dominant one.

Unknown Executive: [inaudible]

Murdo: Let's go in reverse order. Murdo, why don't you start, and then Dave, you can finish.

And we are well prepared for the mild to moderate launch youre anticipating a decision on that soon from the FDA. We have the resources available. We have the teams trained we have an increased footprint in dermatology in anticipation of the approval and we expect to be able to execute very effectively we also have very.

Murdo: Well, you know, not to belabor the point, but again, you know, I've worked in the oncology field for a number of years, and what I've seen since coming to Amgen is real strength in the legacy of Amgen, which is, of course, the supportive care products that we have. We've augmented that recently with the launch of our biosimilar portfolio, and then most recently, of course, with the launch of Lumic

Strong payer coverage here and we think that the majority of these mild to moderate patients and we're targeting a specific subset. We're targeting those patients that have larger body surface area or very difficult to treat areas with topical so thats about a $1 5 million patient population so it.

Murdo: And they are also interested in talking to us about the very rich pipeline of products that Dave Reese and his R&D colleagues are developing. So I think we are very much a leader in oncology. I think that our commercial position with innovative products and biosimilars and launches of new therapeutics puts us in a very strong account position. And I think, you know, in a world where a lot of care is delivered in community oncology, our relationships there are extremely strong.

A large opportunity, but we think that the.

The profile of the product the price point of the product versus biologics puts us in a very very strong position.

Two to treat these patients the other thing I would add that we expect to benefit from somewhat more so than the PSA area versus psoriasis, but the safety concerns of the Jack's right now quite frankly are helping of Tesla and the overall perception of our safety and or efficacy and I think that might bode.

Murdo: You know, I've been able to make some customer visits this year, despite some of the interruptions of the pandemic, and most of my visits have been in support of the Lumicraz launch, and I can tell you they have been very, very good at working with us to develop testing programs, look back programs, entering flags in EMRs, and making sure patients are flagged for treatment. And it's those systems and those processes that, being first on the ground, we should be able to build and sustain.

Well for future competition.

Thats currently.

In the process I guess are being filed with the FDA.

Your next question comes from the line of Carter Gould with Barclays.

Great. Good evening, Thanks for taking the question maybe to change it up a little bit I wanted to ask around the.

The the line extension strategy for <unk>.

How do you think about the attractiveness of <unk> given that it's increasingly caught the attention of larger biopharma and I guess alongside that when your partner disclose the orphan drug designation. They talked about a planned phase III should that be the expectation that youll move straight into phase III versus doing some phase II work here. Thank you.

Murdo: Longer term, of course, it'll be the continuation of being first with indications and broad in the development of the asset and then supporting it with additional products in lung cancer that Dave is developing in our pipeline.

Yes, Thanks Carter.

Eosinophilic esophagitis or <unk>.

As it's called in the field.

Dave: Thanks, Robyn. Yeah, in terms of toolkits, we could obviously talk for hours about the toolkits that we've got in discovery research and our clinical trials. You know, we are building what I think is an industry-leading capability in what I call human data, which means the collection, integration, and interrogation of data ranging from various omics data, genomic data, transcriptomic data, proteomic data, through clinical trial data, through real-world evidence, and real-world data.

And increasingly diagnose stomach condition.

Patients with heartburn on now who typically would have been diagnosed with reflux over the previous decade, a fair number of those are now recognized to have eosinophilic esophagitis, given the mechanism of action of <unk>, given what we've seen in some of our <unk>.

Barker and tissue acquisition.

Studies in asthma based on eosinophil depletion in target tissue.

It makes a lot of sense and that is why with our partners.

We are carrying this soft forward into phase III based on.

The phase one data that we've generated so I think the evidence package across the molecule here that supports that.

Dave: And it's one of our core beliefs that the coming few decades will be won by those who understand how to make use of and, in particular, analyze the giant tsunami of data that is now starting to wash over us. Now, that data, of course, generates drug targets and pathways. And, as I mentioned in my prepared remarks, we are building extensive capabilities for the development of multispecific molecules, either small molecules, large molecules, or hybrid molecules.

Because we are getting close to the top of the hour why don't we take one more question after which I'll ask Bob to make some concluding comments.

Your final question comes from the line of Michael Schmidt with Guggenheim.

Hey, this is kelsey on for Michael Thanks for taking our question could you maybe just discuss kind of your latest thoughts around potential accelerated approval opportunity in the frontline setting for lung cancer and maybe when you might expect to have kind of a clear.

<unk> forward, one way or the other from the FDA. Thank you.

Dave: About 80 to 85 percent of the currently validated targets are currently not approachable with existing technologies, and we are building the capability to go after what I think will be a good fraction of those undruggable targets. So I feel great about the platforms that we've got in place and are continuing to build on, and a lot more on this over the next year or two.

Yes, thanks for the question.

<unk> has just been generally clear that in the first line setting all randomized data are required.

Okay.

As I indicated conducting a trial in patients with SDK 11 or <unk>.

<unk> PDL one.

Negative or low.

Tumors, where checkpoint inhibitors are not particularly effective.

When we have those phase two data available of course, if we saw interesting data we would have the appropriate.

Operator: Your next question comes from the line of Corey Casimo with J.P. Morgan.

Discussions with regulators, but I think the general expectation is that barring significant results one will expect randomized trials in frontline lung cancer.

Unknown Attendee: Hi, this is Gavin on behalf of Corey. Thanks for taking our question. Maybe one for Murdo.

Murdo: Just curious about the expected impact of Tesla's mild to moderate labor expansion. Specifically, should we expect immediate uptake in 2022, or just something that will be a little more gradual? And then, secondly, geographic expansion was underscored as a key strategy.

Okay, well, let me.

Let me. Thank all of you again for your for joining our call and we look forward to having opportunity to meet with you in the new year. When we report on the fourth quarter. We obviously have a lot of exciting things happening between now and then again, starting we'd expect quickly.

Expanded labor protests loans will be followed by the launch label for <unk> in the beginnings of a number of new phase III trial programs as we indicated on the call. So exciting time for us to look forward to gathering with you in the new year again, thanks for your support great. Thanks, everybody.

Unknown Executive: [inaudible]

Murdo: Yeah, thank you, Gavin. You know, when we acquired Otezla, I thought it would be a really good addition to the portfolio and our strength in immunology, both in dermatology and in rheumatology. And, you know, obviously, we had to make a certain set of assumptions about how that product would evolve under our ownership. And, you know, so far, I have to say, I'm even more pleased with the strength that the product brings to Amgen.

And this concludes amgen's third quarter 2021 financial results Conference call you may now disconnect.

[music].

Murdo: We've been successful, as you highlight, in demonstrating the product's efficacy and safety in the mild to moderate patient setting, which is a perfect sweet spot for this product, given the convenience of its oral dosing and given the well-demonstrated safety and efficacy of the product. We also recently had a decision on the patent for Otezla, which definitely helps make it a very strategic product for us, a very important product for the growth of the company. And, you know, the fit is just perfect.

Yes.

[music].

Murdo: You know, we have integrated the legacy Celgene team fully into Amgen. We've got both Enbrel and Otezla now being promoted in rheumatology and dermatology. And we've seen volume growth improve and most markedly in the last part of Q3, but that continues into Q4. You know, we didn't plan on a pandemic when we did the transaction, obviously, but we've weathered it well. The team is staying focused.

Murdo: And we are well prepared for the mild to moderate launch. We're anticipating a decision on that soon from the FDA. We have the resources available. We have the teams trained.

Murdo: We have an increased footprint in dermatology and anticipation of the approval, and we expect to be able to execute very effectively. We also have very, very strong payer coverage here. And we think that the majority of these mild to moderate patients, and we're targeting a specific subset; we're targeting those patients that have larger body surface areas or very difficult to treat areas with topicals. So that's about a 1.5 million patient population.

Murdo: So it's a big opportunity, but we think that the profile of the product, the price point of the product versus biologics puts us in a very, very strong position to treat these patients. The other thing I would add that we expect to benefit from somewhat more so in the PSA area versus psoriasis, but the safety concerns of the jacks right now are helping our Tesla and the overall perception of our safety and our efficacy. And I think that might bode well for future competition. That's currently in the process of being filed with the FDA.

[music].

Operator: Your next question comes from the line of Carter Gould with Barclays.

Carter Gould: Good evening. Thanks for taking the time to answer the question. Maybe to change it up a little bit, I wanted to ask you about the line extension strategy for Tezapelumab into EOE, how you think about the attractiveness of EOE, given that it's increasingly caught the attention of larger biopharma, and I guess alongside that, when your partner disclosed the orphan drug designation, they talked about a planned phase three. Should that be the expectation, that you'll move straight into phase three versus doing some Thanks, Carter.

Dave: Eosinophilic esophagitis, or EOE, as it's called in the field, is an increasingly diagnosed condition that, you know, patients with heartburn now, who typically would have been diagnosed with reflux over the previous decade, a fair number of those are now recognized to have eosinophilic esophagitis, given the mechanism of action of tezapelimab, given what we've This makes a lot of sense, and that is why, with our partners, we are carrying this forward into phase three, based on the phase one data that we have generated.

Dave: So I think it's the evidence package across the molecule here that supports that. Eric, as we're getting close to the top of the hour, why don't we take one more question, after which I'll ask Bob to make

Unknown Executive: Your final question comes from the line of Michael Smith with Guggenheim.

Michael Smith: Hey, this is Kelsey speaking on behalf of Michael. Thanks for taking our question. Could you maybe just discuss kind of your latest thoughts around potential accelerated approval opportunities

Unknown Executive: [inaudible]

Unknown Executive: Thanks for the question. The FDA

Unknown Executive: The FDA has been generally clear that in the first-line setting, randomized data are required. We are, as I indicated, conducting a trial in patients with SPK-11 and or PD-L1 negative or low tumors, where checkpoint inhibitors are not particularly effective. We've had discussions with regulators, but I think the general expectation is that, you know, barring significant results, one will expect randomized trials in the front line.

Bob Bradway: Okay, well, let me thank all of you again for joining our call, and we'll look forward to having an opportunity to meet with you in the new year when we report on the fourth quarter. We obviously have a lot of exciting things happening between now and then again, starting with the expanded label for Tesla to be followed by the launch label for Tesla PeliMab and the beginning of a number of new phase three trial programs, as we indicated on the call. So, an exciting time for us. I look forward to gathering with you in the new year. Again, thanks for your support. And this concludes Amgen's third quarter 2021 financial results.

Operator: And this concludes Amgen's third quarter 2021 financial results conference call. You may now disconnect.

Operator: [inaudible] ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? , , , , , , , , ,

Operator: My name is Erica, and I will be your conference facilitator today for Amgen's third quarter 2021 financial results conference call. All lines have been placed on mute to prevent any background noise.

Arvind Sood: There will be a question and answer session at the conclusion of the last speaker's prepared remarks. In order to ensure that everyone has a chance to participate, we would like to request that you limit yourself to asking one question during the Q&A session. To ask a question, please press star then the number one on your telephone keypad. To withdraw your question, press the pound key. I would now like to introduce Arvind Sood, Vice President of Investor Relations. Mr. Sood, you may now begin.

Arvind Sood: Erica, thank you. Good afternoon, everybody.

Arvind Sood: Welcome to our Q3 call. I think the three key themes for this quarter are continued execution, pipeline advancement, and preparedness to launch important new products. So let's get started.

Arvind Sood: The slides have been posted. Quick reminder that we'll use non-GAF financial measures in our presentation, and some of the statements will be forward-looking statements. Our SEC filings identify factors that could cause our actual results to differ materially. So with that, I would like to turn the call over to our Chairman and CEO, Bob Bradway.

[music].

Bob Bradway: Okay. Hello, everyone, and thank you for joining our call.

Bob Bradway: There was another solid quarter of growth for Amgen, with total revenues rising 4%, driven by volume growth of 8%, which reflects the strong global demand for many of our innovative medicines, such as Repatha and Prolia, as well as for our high-quality biosimilars. Earnings per share for the quarter grew 11% thanks to disciplined management of our operating expenses. Moving to the future, as we begin to see beyond COVID-19, I believe we've set ourselves up well to deliver attractive growth over the long term. By way of example, I'll draw your attention to

Unknown Executive: [inaudible]

Bob Bradway: We are building on our successful track record through a combination of internally generated innovation and strategic business development, which we expect to contribute to our long-term growth.

Bob Bradway: In inflammation, we're very excited about tezepilumab.

Unknown Executive: [inaudible] Given the millions of patients who

Unknown Executive: For whom existing asthma therapies are inadequate,

Bob Bradway: We believe Tezapelumab will be a significant growth driver for us for years to come. This product builds on our many years of...

Bob Bradway: Our Many Years of Success in Inflammation, First

Bob Bradway: First with Enbrel and now, of course, with Otesla. We remain optimistic about the growth potential of Otesla, and as the next step, we're eagerly awaiting an expanded indication in the U.S. for mild to moderate plaque psoriasis. Particularly at a time when concerns have emerged for some potential new competitors. We also continue to grow Tesla globally, with the product now available in over 40 countries, up from 32 countries when we acquired it.

Bob Bradway: Looking a bit further into the future, we expect to bring Amgevita, our biosimilar to Humira, to the U.S. in 2023. We expect to replicate the success we've had with Amgevita and many other markets around the world. We're also enthusiastic about AMG451, a Phase 3 ready, potential first-in-class treatment for atopic dermatitis that we're studying with our partners, Keela Kieran, as well as a number of Amgen-discovered therapies currently in Phase 2 for lupus and celiac disease. In oncology, we're happy with the recent launch in the US of

Bob Bradway: Lumacrass, our first-in-class KRAS G12C inhibitor, which treats...

Unknown Executive: [inaudible] LumaCraft joins a portfolio of medicines already generating some $10 billion a year in sales. Several of these medicines delivered double-digit sales growth in the third quarter, including Kaprolos, Blincito, and Imvas. Looking ahead, we're excited about the growth potential of several

Bob Bradway: We have several other oncology assets in our pipeline.

Bob Bradway: We've already initiated our first phase 3 trial for bemrituzumab, a potential first-in-class molecule to treat gastric and gastroesophageal junction cancer. We're also making good progress with several of our

[music].

Unknown Executive: Rafferty. Thank you. Thank you. Thank you.

Unknown Executive: Nathaniel, Daniel Lundquist, David Reese, Arvind Sood, Yaron Werber, Salveen Richter, Daniel Lundquist, Jamie Shen, Robert Bradway, Murdo Gordon, David Reese, Arvind Sood, Yaron In short, we have a number of products now on the market with plenty of room to grow, with more coming over the next several A compelling discovery research engine to continuously replenish that pipeline, and the wherewithal to take advantage of compelling business development opportunities as they arise.

My name is Erica and I will be your conference facilitator today for Amgen's third quarter 2021, the financial results Conference call. All lines have been placed on mute to prevent any background noise.

Unknown Executive: All that gives me confidence in our ability to serve more patients around the world and to deliver strong financial performance for our shareholders. On a final note, I'd like to thank my Amgen colleagues for their continued commitment to patients and to our business. We were delighted to be named last week by Fortune Magazine as one of the 25 best workplaces in the world, and that's a reflection of our people and the passion and excellence they bring to their work.

A question and answer session at the conclusion of the last speaker's prepared remarks in order to ensure that everyone has a chance to participate we would like to request that you limit yourself to asking one question during the Q&A session to ask a question. Please press Star then the number one on your telephone keypad to withdraw your question press the pound key.

I would now like to introduce Arvind Sood, Vice President of Investor Relations. Mr. Sood, you may now begin.

Dave: Dave, let me turn it over to you. Thanks, Bob. Good afternoon, everyone.

Erica. Thank you good afternoon, everybody welcome to our Q3 call.

Dave: I would like to begin by welcoming our new colleagues from Teneo Bio, who bring expertise and technologies that will accelerate our innovation. One of our core areas of interest in research in molecular engineering is the development of multi-specific drugs to make undruggable targets tractable. Teneo Bioacquisition, combined with our previous incorporation of New Evolution and its DNA encoded library technology, provides capabilities to develop both large and small molecule multispecifics and is a good example of how we are combining internal and external sources of innovation to advance the R&D portfolio. More than 60% of the molecules in our preclinical pipeline are multi-specifics. We will have more to say as those programs progress.

I think the three key themes for this quarter, our continued execution pipeline advancement and preparedness to launch important new products.

So let's get started the slides have been posted quick reminder, that we'll use non-GAAP financial measures in our presentation and some of the statements will be forward looking statements.

Our SEC filings identify factors that could cause our actual results to differ materially.

So with that I would like to turn the call over to our chairman and CEO, Bob Bradway Bob.

Hello, everyone and thank you for joining our call.

It was another solid quarter of growth for Amgen with total revenues rising, 4% driven by volume growth of 8%, which.

Which reflects the strong global demand for many of our innovative medicines such as the pass on Prolia as well as for our high quality Biosimilars.

Earnings per share for the quarter grew 11%, thanks to disciplined management of our operating expenses.

Dave: Across R&D, we have focused on building a portfolio of complementary assets in certain disease areas to help drive the long-term growth of the company. Turning to our clinical programs, I'll highlight a few areas where we have made significant progress and are advancing multiple first-in-class smaller molecules. In oncology, one key area of focus is lung cancer. As you'll hear from Murdo, the Lumicrast launch is off to an excellent start, and the clinical programs remain on track. We have initiated a phase two study of Lumicrast monotherapy and first-line non-small cell lung cancer for patients with STK-11 mutant and or PD-L1 negative tumors.

Shifting to the future as we begin to see beyond COVID-19, I believe we've set ourselves up well to deliver attractive growth over the long term.

By way of example, I'll draw your attention to our immunology and oncology portfolios.

Where we are building on our successful track record through a combination of internally generated innovation and strategic business development, which we expect to contribute to our long term growth.

In inflammation, we are very excited about <unk>, our first in class treatment for severe asthma that we hope to launch in the U S next year.

Given the millions of patients for whom existing asthma therapies are inadequate. We believe <unk> will be a significant growth driver for us for years to come.

This product builds on our many years of success and inflammation.

First with Enbrel and now of course with Oh Tesla.

We remain optimistic about the growth potential of a Tesla and is the next step we are eagerly awaiting an expanded indication in the U S for mild to moderate plaque psoriasis.

Dave: We continue to expect top-line results from the Phase 3 confirmatory study versus dosotaxel as well as data from our PD-1 combination and SHIP combination cohorts in the first half of next year. In the Tarlatumab, or AMG757, BITE program targeting DLL3 and small cell lung cancer, some patients with very advanced disease in the Phase 1 trial have now had responses lasting over a year, supporting our potentially registrational Phase 2 study, which we intend to launch by year end.

Particularly at a time when concerns have emerged for some potential new competitors.

We also continued to grow at Tesla globally with the product now available in over 40 countries up from 32 countries when we acquired them.

Looking a bit further into the future, we expect to bring EM davita, our biosimilar to humira to the U S. In 2023.

We expect to replicate the success, we've had with MTA visa and many other markets around the world.

We're also enthusiastic about AMG four of five one phase III ready potential first in class treatment for atopic dermatitis that we're studying with our partners kyowa Kirin as well as a number of Amgen discovered therapies currently in phase two for lupus and celiac disease.

Dave: Quinley, and Squamous Non-Small Cell Lung Cancer, we will initiate a Phase 1B study of bimerituzumab directed against FGFR2B in the coming months. Turning to gastrointestinal cancers, we will be enrolling a phase 3 trial of Lumicrast in combination with Vectabix and third-line colorectal cancer in the coming weeks. In first-line gastric cancer, we have initiated the first of multiple phase three studies with primarituzumab, with additional trial starts in the coming months. These studies will address regional differences in the treatment of gastric cancer by exploring pomerituzumab in combination with either backbone chemotherapy or chemotherapy plus a checkpoint inhibitor.

In oncology, we're happy with the recent launch in the U S. As Luma Kras are first in class K, Ras <unk> inhibitor, which treats non small cell lung cancer.

And we look forward to additional approvals and launches in major markets around the world as we roll forward.

Luma Kras joins a portfolio of medicines already generating some $10 billion a year in sales several of these medicines delivered double digit sales growth in the third quarter, including Kyprolis <unk> and <unk>.

Looking ahead, we're excited about the growth potential of several other oncology assets in our pipeline.

We've initiated already our first phase III trial for <unk>, a potential first in class molecule to treat gastric and gastroesophageal junction cancers.

We're also making good progress with several of several of our internally discovered solid bite.

Dave: Prostate cancer is another area of focus in oncology. Through the acquisition of Teneo Bio, we now have two distinct bi-specific T cell engager technologies targeting PSMA. We anticipate decision-enabling data from the expansion cohort in the ACAP-ADMAB AMG-160 program in the first half of next year and are now exploring outpatient administration. MG340, formerly TNB585, continues to progress through dose escalation, and we anticipate having informative data by the middle of next year as well, allowing us to determine the best path forward for one or both of these PSMA molecules. Finally, rounding out our prostate cancer portfolio is AMG509, targeting STEEP1, which is also progressing through dose escalation. We anticipate having decision-making data next year.

All tumor bite molecules, including one for prostate cancer and another for small cell lung cancer.

In short we have a number of products now on the market with plenty of room to grow more coming over the next several years from our pipeline.

Our compelling discovery research engine to continuously replenished that pipeline and the wherewithal to take advantage of compelling business development opportunities as they arise.

All that gives me confidence in our ability to serve more patients around the world and to deliver strong financial performance for our shareholders.

Final note I'd like to thank my Amgen colleagues for their continued commitment to patients and to our business we.

We were delighted to be named last week by Fortune magazine as one of the 25 best workplaces in the World and that's a reflection of our people and the passion and excellence they bring to their work Dave.

Dave Let me turn it over to you.

Thanks, Bob and good afternoon, everyone I.

I would like to begin by welcoming our new colleagues from <unk>, who bring expertise and technologies that will accelerate our innovation.

One of our core areas of interest in research in molecular engineering is the development of multi specific drugs to make undruggable targets tractable.

Dave: Inflammation, we spoke at length a few weeks ago about the increasing activity in our portfolio of both innovative and biosimilar molecules, regulatory approvals, and launches expected in each of the next several years. For the tezapelimab program, regulatory reviews for severe asthma are proceeding with an FDA action date in the first quarter of 2022. Studies and three additional indications are in progress to investigate the utility of tezapelumab across a range of inflammatory diseases.

<unk> bio acquisition combined with our previous incorporation of new evolution and its DNA encoded library technology provides capabilities to develop both large and small molecule multi specifics and is a good example of how we are combining internal and external sources of innovation to advance the R&D portfolio.

More than 60% of the molecules in our preclinical pipeline, our multi specifics we will have more to say as those programs advance.

Cross R&D, we are focused on building a portfolio of complementary assets in certain disease areas to help drive long term growth of the company.

Turning to our clinical programs I'll highlight a few areas, where we have made significant progress and are advancing multiple first in class molecules.

Dave: In skin autoimmune diseases, the FDA review of Otesla for mild to moderate psoriasis continues with a PDUFA date in December. A few weeks ago, we presented results from a Phase II study of AMG451, KHK4083, the first-in-class dual-action anti-Ox40 antibody we are developing for atopic dermatitis in collaboration with Keowacurin.

In oncology <unk>.

Key area of focus is lung cancer as Youll hear from Murdo alumina Kras launch is off to an excellent start and the clinical programs remain on track we have initiated the phase II study of Luna Kras monotherapy in first line non small cell lung cancer for patients with SDK 11, mutant <unk> PD lone negative.

<unk> we continue.

To expect the top line results from the Phase III confirmatory study versus Docetaxel as well as data from our PD, one combination and shipped combination.

Dave: These data were very well received by the medical community, as there is a clear need for innovative therapies with differentiated mechanisms of action for these patients. We have had productive regulatory interactions on the program and plan to launch phase three trials in the first half of 2022. Finally, we also expect Phase 3 data from biosimilar candidates for Stelara, Ilea, and Saliris in the inflammation portfolio next year. [inaudible] Opassaran, a small interfering RNA targeting LPa, and our first RNA-based therapy, remains on track to read out Phase IIb data by the middle of 2022 and provides a potential complement to Repatha in the treatment of atherosclerotic cardiovascular disease by serving patients whose pathology is not driven by LDL cholesterol.

<unk> in the first half of next year.

And the <unk> or AMG 757, bite program targeting DLL, three and small cell lung cancer, some patients with very advanced disease and the phase one trial have now had responses lasting over a year supporting our potentially registrational phase II study, which we intend to launch by year end.

Finally in squamous non small cell lung cancer, we will initiate a phase <unk> study of <unk> directed against <unk> in the coming months.

Turning to gastrointestinal cancers, we will begin enrolling a phase III trial of Luna Kras in combination with Vectibix in third line colorectal cancer in the coming weeks and first line gastric cancer. We have initiated the first multiple phase III studies with <unk> with additional trial starts in the coming.

Months. These studies will address regional differences in the treatment of gastric cancer by exploring <unk> in combination with either backbone chemotherapy or chemotherapy plus a checkpoint inhibitor.

Dave: In conclusion, with an innovative portfolio where approximately three-quarters of our clinical stage programs have first-in-class potential and a growing portfolio of biosimilars, we are well positioned to continue to deliver important new medicines for patients and growth for shareholders over the near and long term.

Prostate cancer is another area of focus in oncology with the acquisition of <unk>. We now have two distinct bi specific T cell engage our technologies targeting <unk> we.

Murdo: Thank you Dave. Third quarter product sales increased 4% year over year. Volumes increased 8% globally, and we had record quarterly sales for several of our key products, including Avenity, Kyprolis, Xgeva, and Endplate. Our ex-U.S. business grew 19%, with volume growth of 25% year over year. We continue to execute our volume-driven growth strategy and see gradual recovery in our business from the impact of the pandemic. During the early part of Q3, we saw volatility in patient care dynamics due to a surge in COVID-19. As we progressed through the quarter, we saw improvement in patient visits and diagnosis. Total customer activity also improved during Q3. However, face-to-face customer interactions remain below the 2019 level.

We anticipate decisions, enabling data from the expansion cohort and the a cap out a mab AMG 160 <unk> program in the first half of next year and are now exploring outpatient administration.

AMG AMG 340, <unk>, formerly <unk> hundred 85 continues to progress through dose escalation and we anticipate having informative data by the middle of next year as well, allowing us to determine the best path forward for one or both of these <unk> molecules.

Finally, rounding out our costate cancer portfolio is AMG 509 targeting steep one which is also progressing through dose escalation, we anticipate having decision making data next year.

In inflammation, we spoke at length, a few weeks ago about the increasing activity in our portfolio are both innovative and biosimilar molecules regulatory approvals and launches expected in each of the next several years.

And the <unk> program regulatory reviews in severe asthma proceeding with an FDA FDA action date in the first quarter of 2022 study.

Murdo: Now, let me review some product details, beginning with our general medicine portfolio, which includes Prolia, Ivenity, Repafa, and Imovic. Overall revenue for our general medicine portfolio grew 22% year over year with 24% volume growth. In bone health, Prolia sales grew 15% year-over-year, driven by double-digit volume growth. In the third quarter, new and repeat patient demand continued to improve as osteoporosis diagnoses rates reached over 90% of pre-COVID levels. Ivanity, which complements Prolia in our bone portfolio, had record sales of $149 million for the third quarter, driven by strong volume growth. Given the severe impact of fractures on the lives of patients,

Studies in three additional indications are in progress to invest investigate the utility of <unk> across a range of inflammatory diseases.

And skin autoimmune diseases. The FDA review of Tesla for mild to moderate psoriasis continues with a <unk> date in December.

A few weeks ago, we presented results from a phase two study of AMG 451, <unk> $4 83, a first in class Dual Act action anti ox 40 antibody, we are developing for atopic dermatitis in collaboration with Kyowa Kirin.

These data were very well received by the medical community is there is a clear need for innovative therapies with differentiated mechanisms of action for these patients. We have had productive regulatory interactions on the program and plan to launch phase III trials in the first half of 2022.

Murdo: Excellent Therapy to Build Bone First. Moving on to Repasa, which remains the global leader in the PCSK9 class. Repata sales increased 33% year over year, driven by 42% volume growth. In the U.S., we saw 64% year over year volume growth. This was partially offset by a lower net selling price stemming from an increase in the number of Medicare Part D patients receiving Repata and who entered the donut hole. Outside the U.S., volumes grew 24% year-over-year.

Finally, we also expect phase III data from Biosimilar candidates to Stora Eylea and Soliris in the inflammation portfolio next year.

In cardio metabolic disease, and ether of Sclerosus through a path of the silliest trial phase III outcome study of approximately 12000 patients at high cardiovascular risk, but without prior myocardial infarction or stroke is expected to complete enrollment in the coming weeks.

Pass or in a small interfering RNA targeting LP little a and our first RNA based therapy remains on track to read out phase <unk> data by the middle of 2022 and provides a potential complement to <unk> in the treatment of <unk> cardiovascular disease by serving patients whose pathology is <unk>.

Murdo: We remain confident in our ability to grow Repatha globally to address the significant unmet medical need for treating high-risk cardiovascular patients. Moving to our inflammation portfolio, Otesla sales increased 13% year over year with 7% volume growth. Since its launch, Tesla has been

Driven by LDL cholesterol.

In conclusion with an innovative portfolio, where approximately three quarters of our clinical stage programs have first in class potential and a growing portfolio of Biosimilars. We are well positioned to continue to deliver important new medicines for patients and growth for shareholders over the near and long term murdo.

Murdo: A lot has been used by over 750,000 patients globally.

Murdo: And in the U.S., it is the leader in bio-naive psoriasis patient share. Well, Tesla has 92% commercial payer coverage and is an affordable, safe, and efficacious option for psoriasis and psoriatic arthritis patients. We are now preparing for the anticipated U.S. approval of the mild to moderate psoriasis indication in the fourth quarter, when we will have the opportunity for the first time to promote the use of Otezola in this patient population. NBRL sales decreased 3% year-over-year, driven by a 2% decline in volume.

Thank you, Dave third quarter product sales increased 4% year over year <unk>.

Volumes increased 8% globally, and we had record quarterly sales for several of our key products, including of entity Kyprolis ex Java and <unk>.

Our ex U S business grew 19% with volume growth of 25% year over year.

We continue to execute our volume driven growth strategy and see gradual recovery in our business from the impact of the pandemic during.

Murdo: This is the second straight quarter of slowing volume declines, thanks to NBRL's long track record of efficacy and safety. Together with our partner AstraZeneca, we're preparing for the launch of tezapilimab in the U.S., with an expected PDUFA date in early Q1 2022. Our sales force is fully staffed, trained, and has been deployed to provide disease state education. We're actively engaging with payers to ensure access to patients for this breakthrough medicine. We look forward to bringing Tezapelimab to the 2.5 million people around the world who live with severe uncontrolled asthma.

During the early part of Q3 saw volatility in patient care dynamics due to a surge in COVID-19, as we progressed through the quarter, we saw improvement in patient visits and diagnosis.

Total customer activity improved during Q3, however face to face customer interactions remain below 2019 levels now.

Now, let me review some product details beginning with our general medicine portfolio, which includes prolia as entity with Panther and a mosaic.

Overall revenue for our general Medicine portfolio grew 22% year over year with 24% volume growth.

In bone health Prolia sales grew 15% year over year, driven by double digit volume growth.

In the third quarter, new and repeat patient demand continued to improve as osteoporosis diagnoses rates reached over 90% of pre COVID-19 levels.

<unk>, which complements prolia in our bond portfolio had record sales of $149 million for the third.

Murdo: Moving to the hematology and oncology business, sales of our six innovative products and our Mvasi and Kangenti biosimilars collectively totaled $1.8 billion in the quarter, growing 12% year over year. Several brands had record sales in the quarter, including Xtiva, Kyprolis, Enplate, and Bonsai Tech. New Alaska OnPro maintained 50% volume share in the quarter and continues to be the preferred choice for physicians and patients. However, the most recent published average selling price for Nulasva in the US declined 38% year-over-year and 10% quarter-over-quarter.

Third quarter, driven by strong volume growth.

Given the severe impact of fractures on the lives of post menopausal women as entity provides an excellent therapy to build bone first.

Moving to <unk>.

Which remains the global leader in the <unk> canine class.

Sales increased 33% year over year, driven by 42% volume growth in the U S. We saw 64% year over year volume growth. This was partially offset by lower net selling price stemming from an increase in the number of Medicare part D patients receiving <unk>.

And who entered the donut hole.

Outside the U S volumes grew volumes grew 24% year over year, we remain confident in our ability to grow repass globally to address the significant unmet medical need in treating high risk cardiovascular patients.

Murdo: Going forward, we expect increased competition to result in continued net price and volume erosion. However, our launch of Lumacraz is off to a strong start, with revenues of $36 million in Q3 and cumulative sales of $45 million through the end of the third quarter. Lumacraz has been prescribed by over 500 oncologists in both academic and community settings. A majority of clinical laboratories have updated their testing reports to reflect KRAS-G12C as an actionable mutation, and approximately 75% of patients with non-small cell lung cancer are now being tested for the mutation at the time of diagnosis.

Moving to our inflammation portfolio of Tesla sales increased 13% year over year with 7% volume growth since its launch a Tesla has been used by over 750000 patients globally.

And in the U S. It is the leader in bio naive psoriasis patient share.

What Tesla is 92% commercial payer coverage is an affordable safe and efficacious option for psoriasis and Psoriatic arthritis patients. We are now preparing for the anticipated U S approval of the mild to moderate psoriasis indication in the fourth quarter.

When we will have the opportunity for the first time to promote the use of Oh Tesla in this patient population.

Enbrel sales decreased 3% year over year, driven by a 2% decline in volume. This is the second straight quarter of swelling volume declines. Thanks to Enbrel has long track record of efficacy and safety.

Murdo: Having been a part of several lung cancer launches in my career, I'm very pleased with the Lumicraz launch uptake in the U.S., thanks to our broad payer access and the positive reaction from the oncology community. Outside the U.S., health authorities have also approved Lumicraz in Canada and the U.K. Overall, I'm pleased with our results for the quarter, our record sales across a number of products, and our increasing levels of customer activity. And with that, I'll turn it to Peter.

Together with our partner Astrazeneca, we're preparing for the launch of <unk> in the U S with an expected <unk> date in early Q1 2022.

Our sales force is fully staffed trained and has been deployed to provide disease state education.

We are actively engaging with payers to ensure access to patients for this breakthrough medicine.

We look forward to bringing <unk> to the 2.5 million people around the world, who live with severe uncontrolled asthma.

Moving to the hematology and oncology business sales of our six innovative products and are investing in <unk> biosimilars collectively totaled $1 8 billion in the quarter growing 12% year over year.

Peter: Thank you, Murdo. I will briefly walk through our third quarter financial results before discussing 2021 guidance. Our team's quality of execution during the past 18 challenging months continues to provide us with the strength to make timely, prudent investments as we see them in both internal and external innovation that will deliver long-term growth. Let's now turn to the business.

Several brands had record sales in the quarter, including ex Java, Kyprolis and plate and billing cycle.

Neulasta on probe maintained 50% volume share in the quarter and continues to be the preferred choice for physicians and patients.

Most recent published average selling price for Neulasta in the U S declined 38% year over year, and 10% quarter over quarter going forward. We expect increased competition to result in continued net price and volume erosion.

Peter: The third quarter marked another period of solid performance with year-over-year revenue growth of 4% and non-GAAP EPS growth of 11%. As Murdo described, strong volume growth continued in the quarter with 8% year-over-year growth driven by Prolia, Avenity, Repatha, and Inbox. In addition, this quarter includes $147 million of favorable changes to estimated sales deductions previously recorded. In the third quarter last year, the favorable estimated sales deductions were $36 million, resulting in a $111 million year-over-year benefit this quarter.

Our launch of <unk> is off to a strong start with revenues of $36 million in Q3, and cumulative sales of $45 million through the end of the third quarter.

<unk> has been prescribed by over 500 oncologists in both academic and community settings. A majority of clinical laboratory has updated their testing reports to reflect <unk> as an actionable mutation and approximately 75% of patients with non small cell lung cancer are now being tested for.

The mutation at the time of diagnosis.

Having been a part of several lung cancer launches in my career I'm very pleased with the <unk> launch uptake in the U S. Thanks to our broad payer access and the positive reaction from the oncology community.

Peter: Our established products, which include Neulasta, Neupogen, Epogen, Aranes, Parsibis, and Sensipar, decline 21% year-over-year, driven by volume declines and lower net selling prices. These products will continue to contribute meaningful cash flows to our broader portfolio and also to innovation. However, we do expect increased competition to result in additional erosion of these established products.

The U S health authorities have also approval in the Kras in Canada, and Linda Kras in the UK.

Overall, I'm pleased with our results for the quarter, our record sales across a number of products and our increasing levels of customer activity and with that I'll turn it to Peter.

Thank you Murdo I will briefly walk through our third quarter financial results before discussing 2021 guidance.

Our team's quality of execution during the past 18 challenging months.

Continues to provide us with the strength to make timely prudent investments as we see them in both internal and external innovation that will deliver long term growth.

Peter: Other revenues at $386 million increased 21% year over year, primarily driven by shipments of the COVID-19 antibody therapy to Lilly. We expect full year 2021 other revenues to be in a range of $1.5 to $1.7 billion. Third quarter total non-GAAP operating expenses were flat year over year, as continued focus on execution, productivity, and efficiency fueled investments to drive long-term growth, including the third quarter's share of the approximately $200 million of operating expenses expected for the full year related to the Rodeo, 5 Prime, and Teneo bioacquisitions, as well as the Kiowa-Kirin collaboration, through focused expense, We now expect full-year operating expenses, on an absolute basis, to increase approximately 3-4% over last year, inclusive of the approximately $200 million related to these transactions.

Let's now turn to the business.

The third quarter marked another period of solid performance with year over year revenue growth of 4% and non-GAAP EPS growth of 11%.

At Murdo described strong volume growth continued in the quarter with 8% year over year growth was driven by Prolia of entity <unk>.

In addition, this quarter includes 147 million of favorable changes to estimated sales deduction previously recorded.

In the third quarter last year, the favorable estimated sales deductions were $36 million.

<unk> and a $111 million year over year benefit in this quarter.

Our established products, which include Neulasta Neupogen Epogen aeronef parts of this incentive par declined 21% year over year, driven by volume declines and lower net selling price.

These products will continue to contribute meaningful cash flows to our broader portfolio and also to innovation.

We do expect increased competition to result in additional erosion of these established products.

Other revenues at $386 million increased 21% year over year, primarily driven by shipments of the COVID-19 antibody therapy to Lilly.

We expect full year 2021, other revenues to be in a range of one five to $1 7 billion.

Peter: We will continue to execute on opportunities to allocate capital to important internal and external innovation opportunities. On a non-GAAP basis, cost of sales as a percent of product sales increased 1.5 percentage points on a year-over-year basis to 15.8 percent, driven primarily by product, including COVID-19 antibody shipments to Lilly. For the full year, we continue to expect cost of sales as a percent of product sales to be 16 to 17 percent. Non-GAAP R&D spend in the quarter decreased 4% year over year.

Third quarter total non-GAAP operating expenses were flat year over year as continued focus on execution productivity and efficiency fueled investments to drive long term growth, including the third quarter share of the approximately $200 million of operating expenses expected for.

For the full year related to the rodeo five prime and <unk> bio acquisitions as well as the <unk> collaboration.

Through focused expense discipline, we now expect full year operating expenses on an absolute basis to increase approximately 3% to 4% over last year inclusive of the approximately $200 million related to these transactions.

We will continue to execute on opportunities to allocate capital to important internal and external innovation opportunities.

Peter: For the full year, we expect non-GAAP R&D spend to increase in the mid-single-digit percentage range as we progress our innovative pipeline programs, including the launch of registration-enabling trials in lung and gastric cancer. Non-GAAP SG&A expense in the quarter decreased 5%, and we expect the full year to also decline as we continue our focus on execution efficiency and digitalization. Non-GAAP other income and net expenses increased on a year-over-year basis due to increased losses from our 20% share of Beijing's results recorded under the equity method of accounting one-quartered in arrears.

On a non-GAAP basis cost of sales as a percent of product sales increased one five percentage points on a year over year basis to 15, 8% driven primarily by product mix, including COVID-19 antibody shipments to Lilly.

For the full year, we continue to expect cost of sales as a percent of product sales.

16% to 17%.

Non-GAAP R&D spend in the quarter decreased 4% year over year for.

For the full year, we expect non-GAAP R&D spend will increase in the mid single digit percentage range as we progress our innovative pipeline programs, including the launch of registration, enabling trials in lung and gastric cancer.

Non-GAAP SG&A expense in the quarter decreased 5% and we expect the full year to also decline as we continue our focus on execution efficiency and digitalization.

Peter: We expect full-year net expenses in the range of $1.3 to $1.4 billion. We have financial flexibility with $12.9 billion in cash and investments on our balance sheet and strong cash flows. Additionally, our third-quarter dividend was $1.76 per share, an increase of 10% over last year.

Non-GAAP other income and expense net expenses increased on a year over year basis due to increased losses from our 20% share of <unk> results recorded under the equity method of accounting one quarter in arrears.

We expect full year net expense in the range of one three to $1 4 billion.

Peter: Turning to the outlook for the business for 2021, we have invested in internal and external innovation to advance our pipeline for 2021 and continue to set ourselves up well for long-term growth. Moving to revenue.

We have financial flexibility with $12 9 billion in cash and investments on our balance sheet and strong cash flows. Additionally, our third quarter dividend was $1 76 per share an increase of 10% over last year.

Peter: Based on underlying market dynamics, we are updating our 2021 revenue guidance range to $25.8 billion to $26.2 billion. Additionally, we are increasing our non-GAAP EPS guidance range to $16.50 to $17.10. Our non-GAAP tax rate range is updated to 13.0% to 14.0%. Our capital expenditure guidance remains at $900 million, and our capital expenditures continue to include investments supporting our environmental activities and also support our commitment to attain carbon neutrality. We expect share repurchases for 2021 to be in the upper end of our range of $3 to $5 billion.

Turning to the outlook for the business for 2021.

We have invested in internal and external innovation to advance our pipeline in 2021 and continue to set ourselves up well for long term growth.

Moving to revenue based on underlying market dynamics, we are updating our 2021 revenue guidance range to $25 8 billion to $26 2 billion.

We are increasing our non-GAAP EPS guidance range to $16 50.

$17.10.

Our non-GAAP tax rate range is updated to 13.0% to 14.0%.

Our capital expenditure guidance remains at $900 million and our capital expenditures continue to include investments supporting our environmental activities and also support our commitment to attain carbon neutrality.

Peter: We executed effectively in the third quarter and are well-positioned for long-term growth. Before turning it over to Bob, I'd like to thank and recognize our 24,000 Amgen colleagues around the world for delivering another strong quarter of execution.

We expect share repurchases for 2021 to be in the upper end of our range of $3 billion to $5 billion.

Bob Bradway: Okay. Thank you, Peter. Why don't we open up the call now for questions, and let's remind our callers of the procedures and the request that we limit our questions to just one on the first go. Thanks.

We executed effectively in the third quarter and are well positioned for long term growth before turning it over to Bob I'd like to thank and recognize our 24000 Amgen colleagues around the world for delivering another strong quarter of execution.

Operator: As a reminder, to ask a question, you will need to press star one on your telephone. To withdraw your question, press the pound key. Please stand by while we compile the Q&A roster. Your first question comes from the line of Michael Yee with Jeffreys.

Bob.

Okay. Thank you Peter.

Can we open up the call now for questions, let's remind our callers of the procedures and the requests that we limit our questions to just one.

On the first go.

As a reminder to ask a question you will need to press star one on your telephone withdraw your question press the pound key please standby, while we compile the Q&A roster.

Michael J. Yee: Hi guys. Good afternoon. Good evening.

Michael J. Yee: Um, just say a question about the financials and how to think about going forward at sort of a high level. But, you know, as you think about the results this year, the narrowing of guidance this year, a company that typically seems to come in on the higher end, and I know there's a COVID pandemic ongoing. How do you think about the push and pull dynamics as we enter 2022? I know you don't give 2022 guidance. So I would just love for you to comment on the high level, realizing we're in a pandemic. Thank you. Yeah, Michael.

Your first.

First question comes from the line of Michael <unk> with Jefferies.

Hi, guys. Good afternoon, good evening.

Say a question about the financials and how to think about go forward I just sort of a high level question, but as you think about the results. This year sort of the narrowing of guidance. This year company that typically seems to come in at the higher end and I know Theres, a COVID-19 pandemic ongoing how do you think about the push and pull dynamics as we enter 2022.

Unknown Executive: Yeah, Michael, you're right. We're not going to give 2022 guidance at this point. I think what you can see is we continue to manage the business effectively. That's, I think, reflected in the 4% on the top line, 11% on the bottom line EPS growth, and we'll continue to invest in opportunities that we think can deliver growth. We're very clear that as we look ahead, we expect to be able to deliver growth for our shareholders, and we'll have more to say about that when we give guidance for the next period.

I know you don't give 2022 guidance. So I would just love you to comment on the high level, realizing where on a in a pandemic. Thank you.

Yes, Michael you're right, we're not going to give 'twenty to 'twenty to 'twenty two guidance at this point I think what you can see as we continue to manage the <unk>.

This.

Effectively.

I think reflected in the 4% on the top line and 11% on the bottom line EPS growth and we will continue to invest in opportunities that we think can deliver growth.

Were very clear that as we look at the future, we expect to be able to deliver growth for our for our shareholders and we will have more excited about that when we give guidance for the next period.

Operator: Your next question comes from the line of Geoff Meacham with Bank of America.

Geoff Meacham: So you have previously talked about that.

Thank you.

Unknown Executive: [inaudible]

Unknown Executive: Maybe the non-paying bolus has been converted over to paying, and what's the timeline for moving through the rest?

Your next question comes from the line of Joseph <unk> with Bank of America.

Okay.

Hey, guys, it's Aspen on for Jeff. Thanks for the question Steve.

Unknown Executive: me what the timeline for moving through the rest of them is. Thanks. Yeah, hi, it's Murdo.

Obviously talked about pad three over 3000 patient number treated with Democrats that include some patients on studies I guess I just wanted to get a sense of what percentage of that.

Murdo: Thanks for the question. We are roughly at about 75% of early access programs or patients who were enrolled in clinical trials converting to commercial supply. The two major markets where that's happening are the U.S., obviously, and in France. While we've not been approved in Europe yet, we do have access to the ATU program in France, where patients coming out of our early access program can roll into the ATU program where we actually are booking revenue.

Maybe the nonpaying bolus has been converted over to paying and whats the timeline for moving through the rest of them.

Yeah, Hi, it's mark Thanks for the question.

We are roughly at about 75% of early access programs or patients who were enrolled in clinical trials converting to commercial supply.

The two major markets, where that's happening or the U S. Obviously.

And.

And in France, while we've not been approved in Europe, yet because we do have access to the <unk> program in France, where.

Operator: Your next question comes from the line of Chris Raymond with Piper Sandler.

Christopher Joseph Raymond: Thank you. I've got a question on AMIVIG, or maybe more strategically, your neurology presence. So just for the drug, you know, obviously, revenue and script trends have kind of stalled, and I think it's pretty obvious that it's the oral CGRPs that are sort of having an impact on the market. And, you know, Murdo, I kind of noticed that you sort of skipped over that one in the prepared comments, maybe just sort of talking about your commitment to neurology now with this market dynamic. Is this a category from which we should expect more?

Patients coming out of our early access program can roll into the <unk> program, where we actually are booking revenue.

Thanks.

Your next question comes from the line of Chris Raymond with Piper Sandler.

Okay. Thank you.

A question on aim of vigor or maybe more strategically youre neurology presence.

So just for the drug.

Obviously revenue and script trends have kind of stalled.

I think it's pretty obvious that the oral <unk> that are sort of having an impact on the market.

Murdo I kind of noticed that you're sort of skipped over that one in the prepared comments, maybe just sort of talk about your commitment to neurology now with this market dynamic.

Is this a category that we should expect more investment in from a product offering standpoint is there.

Maybe some other plan here.

Unknown Executive: More investment from a product offering standpoint is our

That you could maybe talk about thanks.

Sure. Thanks, Chris.

The first thing I would say is.

Unknown Executive: Maybe there is some other plan here that you could maybe talk about. Thanks. Sure. Thanks, Chris. The first thing I would say is Imovig continues to be an important product to help patients suffering from migraine, and we continue to believe that there is a large population of migraine sufferers who have yet to be helped by the advent of the CGRP category. So, there is a bit of headroom. You're right on oral evolution taking some growth out, and also a little bit of net price in the quarter taking some growth out as well.

<unk> continues to be an important product to help patients suffering from migraine and we continue to believe that there are there is a large population of my migraine sufferers, who have yet to.

Be helped by the advent of the <unk> category.

Obviously as the market leaders in the sub cutaneous category of CGI P products, we have given up share to the oral is as they've come into the market, but they've also expanded the market.

Beyond the preventative setting and into the acute setting and even the preventative setting has grown with the advent of the of the oral so.

We expect that the market still has quite a bit of growth in headroom for growth, we expect to be able to continue to maintain our leadership share position in total prescriptions.

We have over five years and that of <unk>.

<unk> and efficacy data in the market.

We continue now to have all of the U S commercial responsibility for <unk>.

Murdo: And strategically, we'll continue to look and see if we can find products that fit well with the franchise that we're building.

Given recent work to consolidate what Novartis was previously contributing.

So we've actually increased our neurology presence in the last few months and then the last piece that we're excited about is we're awaiting our head to head superiority data versus topiramate.

Operator: Your next question comes from the line of Umer Raffat with Evercore ISI. (inaudible)

To be published and after which we will be able to promote that too.

General Neurologists headache specialists uneven.

Many primary care physicians, who are using <unk> to help their patients who are chronic migraine suffers so that.

Umer Raffat: Hi guys, thanks for taking my question. I feel like Amgen went through this period of getting a fair amount of credit for the clinical development LumaCRAS program, and we might be sort of entering that phase where a lot of competitors have clinical stage programs on KRAS, and we're about to get a lot of data over the next few months. And I guess my question is, what's your base case on how the clinical data across the field shakes out?

<unk> headroom.

Alright on the oral evolution, taking some growth out and also a little bit of net price in the quarter, taking some growth out as well and strategically we will continue to look and see if we can find products that fit well with the franchise that we're building will continue to look for those.

Thank you.

Your next question comes from the line of Omar <unk> with Evercore ISI.

Hi, guys. Thanks for taking my question.

I feel like Amgen went through this period of getting a fair amount of credit for the clinical development and the lumen Kras program and and we might be sort of entering that phase where a lot of competitors have clinical stage programs on K Ras and.

Umer Raffat: Is this going to be a PD-1-like situation where everybody's about the same, or could you end up seeing approaches like RAS-on inhibitors, et cetera, look any different on resistance mutations? And a follow-up to that also, I feel like as we think about Amgen's leadership on KRAS targets in the first place, should we expect Amgen to file INDs on other KRAS mutation Thanks, Umer. This is Dave.

And we're about to get a lot of data over the next few months and I guess my question is what's your base case on how sort of the clinical data across the field shakes out as it's going to be a PD one like situation, where everybody about the same or could you end up seeing approaches like rason inhibitors et cetera look any different known resistance mutations and a follow up to that also.

Dave: You know, as you mentioned, there are multiple competitors coming behind LUMICRAS. But we feel very good about our position. I've not seen anything to tell us that we don't have a really outstanding molecule. And many of those are very, very early, just starting to do dose escalation. So I think it's premature to speculate on potential differentiated mechanisms of action, or these sorts of things.

I feel like as we think about amgen's leadership on care at target in the first place should we expect Amgen to file and he's on other K Ras mutations like <unk>. Thank you.

Yes. Thanks Omer. This is Dave as you mentioned of course there are.

Competitors.

Coming behind Luma Kras.

We feel very good about our position I have not seen anything.

To tell us that we don't have.

Dave: We also have a very broad-based global program. As we mentioned, we're now under regulatory review in 15 jurisdictions or countries, including the EMA and Japan, where reviews are progressing. And those are, of course, two very large markets.

Really outstanding molecule.

Any of those are very very early just coding starting dose escalation. So I think it's.

Premature to speculate on potential differentiated mechanism of action.

Or these sorts of things we also have a very broad based global program.

Dave: So I feel very good about where we are. We've got a large combined therapy program. There's lots to learn yet. It took 40 years to get into the clinic.

As we mentioned we're now under regulatory review I think at last count that is now in over 15 jurisdictions or countries.

Dave: And we're sort of getting out a lot of biology, but I feel very good about the molecule we've got and where we are. Dave, do you want to say anything else about our G12 D or V program? Oh, sorry. Thanks for the reminder. In terms of, we are interested in other targets. As many of you know, there are seven or eight. These are specific KRAS mutations that are now potentially tractable, although they are different on a structural basis, and each one poses distinct challenges. We do have some work ongoing, and as that progresses, we will say more about that publicly.

<unk>, the EMA and Japan, where our reviews are progressing and those are of course to vary.

Large market. So I feel very good about where we are we've got a large combination therapy program. There's lots to learn yet it took 40 years to get into the clinic and we're sorting out a lot of biology, but I feel very good about the molecule, we've got and where we are.

Dave you want to say anything else about our <unk> program sorry.

For the reminder, in terms of.

We are interested in other targets.

As many of you know there are seven or eight.

Sure.

Specific K Ras mutations that are now potentially attractive although they are different on a structural basis in each one.

As distinct challenges, we do have some work ongoing.

As that progresses, we will say more about that publicly.

Thank you.

Operator: Your next question comes from the line of Yaron Werber with Cowan.

Your next question comes from the line of yarn <unk> with Cowen.

Yaron Werber: Hey, this is Gabe on for your own. Thanks for taking my question.

Hey, this is gabe on for your own. Thanks for taking my question just for Luma Kras the follow up so for the data with Hambro. That's expected in the first half of next year can you kind of give us some maybe set the stage a little bit for whether that data will be mature enough for to get a good look at efficacy we have TPS status available for.

Gabe: For Lumicrast, for the data with Pembroke that's expected in the first half of next year, can you kind of give us some, maybe set the stage a little bit for whether they'll

All patients and then just for the second ship to combination arm that you recently added.

Unknown Executive: [inaudible] Ah, yeah.

Dave: Yeah, thanks, Dave. The Yeah, in terms of what I would say broadly, the checkpoint inhibitor combination data, we do expect to have a fulsome enough data set when we when we have everything together and present at some point in the first half of next year to give good insights to the field about what these combinations look like. In terms of the various SHIP-2 inhibitors for which we're pursuing combinations, there are some biochemical differences between those drugs.

The insight you can share into the thinking behind adding <unk> five was there any any difference in the profile.

To the Rep med molecule that you would highlight that might be a better overlap with Luna kras. Thank you.

Yes, Thanks, Dave.

In terms of the what I would say broadly the checkpoint inhibitor combination data, we do expect to have.

A fulsome enough data set when we when we have everything together and present it at some point in the first half of next year to I think give good insights to the field.

Dave: And, you know, I think it's well worth our while given the potential importance and the mechanistic rationale of SHIP-2 as a combined target for us to examine those various molecules. And so we're pressing forward on all fronts. Thank you.

About what these combinations look like in terms of the <unk>.

Various ship two inhibitors.

For which we're pursuing combinations there are some biochemical differences.

Between those drugs.

I think it's well worth our while given the potential importance in the mechanistic rationale of shift to as a combination target for us to examine those various molecules and so we are pressing forward on all fronts. Thank you.

Operator: Your next question comes from the line of Geoffrey Porges with SBB Lyrinc.

Geoffrey Christopher Meacham: Thank you very much for taking my question. Maybe just another slightly bigger picture one. Bob and Murdo, I know you pay close attention to what's going on in D.C., and I'd be interested in whether you think that we are close to having a deal on drug pricing reform. And, particularly, could you give us a sense of what the financial impact on Amgen would be of the proposed Part D changes? And then, secondly, do you believe that you have any molecules that would be subject to negotiation under the proposed federal negotiation of Part B, selected Part B drugs in the current language? Thanks.

Thank you.

Your next question comes from the line of Geoffrey Porges with SBB Leerink.

So much for taking my question, maybe just another slightly big picture one.

Bob Murdo I know you pay close attention to what's going on in D. C and I'd be interested in whether you think that we are close to having a deal on drug pricing reform and particularly could you give us a sense of what the financial impact on the Amgen would be of the proposed part D changes and then secondly.

Bob Bradway: Yeah, thanks, Geoff. It's obviously very premature for anybody to pretend like they know what the shape of the legislation will be. I don't think anybody's really seen any meaningful draft language yet. What we are aware of, of course, is that there's been some tweeting and some back and forth between the House and the Senate, including moderates in both suggesting that they're close and that they think they have a framework that they can align around.

Do you believe that you have any molecules that would be subject to negotiation under the proposed.

February negotiation with the selected part B drugs in the language.

Thanks, Jeff.

Obviously very premature for anybody to pretend like they know what the shape of it.

Any legislation will be I don't think anybody is really seeing any meaningful draft language.

Bob Bradway: We'll need to wait and see the details, but as you would expect, we'll be focused on seeing whether what they're proposing leads to better access for patients to medicines and whether it does that while preserving the ecosystem that enables all of us to innovate the way we do and the way we think we need to in the country. Stay tuned, Geoff. Again, very premature. I know you guys would love to have a picture that you could share with your investors and a picture that would make some sense, but I think anybody trying to draw one at this point is really doing it in the way of sculpting fog. Okay, thank you.

We are aware of of course is that there is some tweeting and some back and forth between.

The house incentives, including.

Moderates in both.

Adjusting that they are close.

We have a framework that they can align around so.

We will need to wait and see the details and as you would expect we will be focused on seeing whether.

They are proposing leads to better access for patients to medicines.

<unk>.

Whether it does that while preserving the ecosystem that enables all of us to innovate the way.

The way, we do and the way, we think we need to for the country. So.

Stay tuned Jeff again, very premature I know you guys would love to have.

Unknown Executive: [inaudible]

Operator: Your next question comes from the line of Matthew Harrison with Morgan Stanley.

A picture of that.

You could share with your investors in the picture that would make some sense, but I think everybody is trying to draw on at this point is really doing it in the way of sculpting fog.

Matthew Harrison: Great. Good evening.

Matthew Harrison: Thanks for taking the question. I was wondering if we could just touch on your outlook for product guidance. It looks like you raised other revenue guidance, but you also took down the high end of your total company guidance. So maybe you could just talk about that, and that looks like about a $800 million swing if you add the two together. So maybe you could just talk about what's the driver there and where you're seeing the pressure. Thanks.

Great. Thank you okay. Thanks, Jim.

Your next question comes from the line of Matthew Harrison with Morgan Stanley.

Great. Good evening. Thanks for taking the question I was wondering if we could just touch a little bit on your outlook for product guidance. It looks like you raised other revenue guidance, but you also took down the high end of your total company guidance and maybe you could just talk about and that looks like about eight.

<unk> hundred million dollars swing, if you add the two together so maybe you could just talk about what's the driver there.

Where youre seeing the pressure thanks.

Yes, Matthew Thank you Peter.

Peter here listen on the on the <unk>.

Peter: Matthew, thank you. Peter here.

On the revenue range.

Peter: Listen, on the on the revenue range, you know, we're 25.8 to 26.2. This reflects the latest market dynamics, as Murdo shared with you, volume growth year over year from products, Prolea, Otesla, Repath, Avenity, Biosimilars, Competition Against the Mature Products, as I mentioned, but great cash flow producers for us. You know, the sharper recovery we'd anticipated early hasn't materialized at the rate we projected, but the recovery continues at a steady but more gradual rate, as Murdo described for you.

25, 8% to 2006 to reflect the latest market dynamics as Murdo shared with your volume growth year over year from products, Prolia hotels or a path of entity Biosimilars.

Competition against the mature products as I mentioned, but great cash flow producers for us.

Look the sharper recovery, we'd anticipated early hasnt materialized at the rate, we projected but the recovery continues at a steady but more gradual rate as murdo to describe for you.

We continue to build into guidance.

Mid single digit net price declines in 'twenty, one and we've got other revenue at 105 to 107.

The increase year over year, driven primarily by the Lilly manufacturing reimbursement profit share, which began in the second quarter as we've said.

Yes.

So those are the dynamics around the top side of the of the guidance.

Matt I might just observe that relative to the beginning of the year when we gave.

You gave your original guidance.

Yes.

Covid impact has lingered longer than I think we thought when we looked at this at the beginning of the year in particular in terms of the face to face visits and the number of patient diagnosis <unk> doctors offices. So by now looking through the retrospective scope.

Peter: So, you know, we continue to build into guidance, you know, mid single-digit net price declines in 21. We've got other revenue at 1.5 to 1.7, the increase year over year driven primarily by the Lilly Manufacturing Reimbursement Profit Share, which began in the second quarter, as we've said. And so, you know, those are the dynamics around the top side of the guidance.

It was pretty clear that the surge had an impact on the.

The number of patients going to see their doctors and in turn prescriptions being written so I don't think we're experiencing anything different from our peers, but.

At the start of the year, we were hopeful that vaccines and other things.

Our enabled us to be further along in saying goodbye to this pandemic and I think we are right now but.

Otherwise business, performing well and consistent with where we hope to end of the year.

Your next question comes from the line of Alicia Young with Cantor Fitzgerald.

Peter: I might just observe that relative to the beginning of the year, you know, when we gave the original guidance, the COVID impact has lingered longer than I think we thought when we looked at this at the beginning of the year, particularly in terms of face-to-face visits and the number of patient diagnoses inside doctors' offices. So by now, looking through the retrospectoscope, you know, it's pretty clear that the surge had an impact on the number of patients going to see the doctors and, in turn, prescriptions being written.

Hey, guys. Thanks for taking my question, maybe just follow up a little bit along with that.

Can you just talk a little bit about with what were positive and we made some of the selling price pressure you've seen and do you think that kind of a.

Thus flow step down or is it kind of.

Something that will happen more periodically thank you.

Alicia did you say <unk> and <unk>.

Yeah, Okay, Okay sure.

So <unk> in the quarter is more a function of what we've been able to do.

Since lowering the price in terms of increasing our penetration in the Medicare part D population. So we've seen some really nice growth there, but what happens when you grow in Medicare part D. As you also grow in the number of patients that enter the donut hole and that's what we're really seeing in Q3, and we expect that the continued in Q4.

Peter: So I don't think we're experiencing anything different from our peers. But, you know, at the start of the year, we were hopeful that vaccines and other things might have made us or enabled us to be further along in saying goodbye to this pandemic than I think we are right now. But again, otherwise, business is performing well and consistent with where we hope to end the year.

The good news side of that equation is we're growing nicely in Medicare, we're seeing much less patient abandonment.

In Medicare and that should be a compounding source of growth for us on a pro forma basis, but I would expect a pattern.

Of <unk>.

Q3, and Q4 net price drag is a function of the.

Medicare part D coverage gap unless of course that changes and whatever is brewing in D C. But that's how that's happened right now.

Operator: Your next question comes from the line of Alethea Young with Cantor Fitzgerald.

My name is it gets a little bit different. It's just it's really the annualized Asian of contracted business with Pbms in general there has been fairly competitive activity there to maintain preferred formulary physicians on national Pbms.

Unknown Attendee: Aletha, did you say Repatha in Amavig? Is that what you're asking? Yeah. Yeah.

Operator: Your next question comes from the line by Jay Olson with Oppenheimer. Oh, hey, thanks for joining us.

And we don't have the same amount of volume growth on the <unk>, but we do expect.

That to be more stable going forward. So overall I think.

Jay Olson: Oh, hey, thanks for taking the question. Is there any color you could provide on the pace of enrollment for the phase two study of El Pasaran? And also, any comments you could share on how you anticipate the competitive landscape to evolve in the Lipoprotein A Market with Pelicarcerin. [inaudible] Yeah, thanks, Jay. Yeah, in terms of the phase two study, it has actually completed enrollment. So, of course, these patients are followed for some time.

Major price effects have stabilized and we're actually now seeing some good top line volume dropped to the bottom.

Yes.

Your next question comes from the line of Jay Olson with Oppenheimer.

Oh, Hey, thanks for taking the question is there any color you could provide on the pace of enrollment for the phase two study of El Paso ran in.

Also any comments you could share on how you anticipate the.

Competitive landscape to evolve.

Like the protein a market with pellet Carson.

Jay Olson: And as I noted in my remarks, we expect data in the middle of 2022, or we're quite pleased with the long-term follow-up we've seen from the phase one trial in terms of LP little a lowering in the preliminary safety profile of the molecule, so that that program is on track, or, if anything, a little ahead of schedule. As you know, there is another molecule ahead of us; we have a slightly different mechanism as a small interfering RNA.

<unk> getting approved before passerine thank you.

Yes, Thanks, Jay in terms of the Phase II study is actually completed enrollment.

Of course these patients are.

Followed for some time and.

As I noted in my remarks, we expect data in the middle of 2022, we're quite pleased with the long term follow up we've seen from the phase one trial in terms of LP little a lowering in the preliminary safety profile of the molecule. So that that program is on track or if anything a little ahead of schedule.

Jay Olson: We like the molecule quite a bit. This is a large population of patients, you know. Recall that about 50% of atherosclerotic cardiovascular disease is not driven by LDL cholesterol. And probably the majority of that is driven by LP little a. So we believe there are many, many patients around the world that can be served by LP little a lowering agents. And so we're quite eager to see the full phase to be data

As you note. There is another molecule ahead of US we have a slightly different mechanism as a small interfering RNA wed.

We like.

The molecule quite a bit this is a large population of patients recall that about 50%.

Of atherosclerotic cardiovascular disease is not driven by LDL cholesterol.

And probably the majority of that is LP little a driven so we believe there are many many patients around the world.

Dave: Your next question comes from the line about Ronnie Gale with Bernstein.

Operator: Good afternoon, and thank you for taking my question. So we typically ask you about the negative impact of a potential deal in Washington. I was wondering if we could reverse that and talk about the benefits. So to the extent there are any, a deal that limits patients' out-of-pocket costs, what are the drugs that will benefit from increased use here? What are the drugs where you see significant advantages?

That can be served by LP little a lowering agents.

So were quite eager to see the full phase II data.

Great. Thanks for taking the question.

Your next question comes from the line of Ronny Gal with Bernstein.

Good afternoon, and thank you for taking my question. So we typically ask you about the negative impact of a potential deal in Washington, I was wondering if we can reverse it and talk about the benefits so to the extent there are any.

Unknown Attendee: [inaudible]

Unknown Executive: And second, we've started a...

A deal which limits patients out of pocket costs, what are the drags will benefit from increased use here what are the what does the drugs, we see significant abandonment.

Unknown Executive: [inaudible]

Unknown Executive: Bansal, Yaron Werber, David Reese, Arvind Sood, Yaron Werber, David Reese, Amgen Bansal

Medicare part D that Mike.

Mike might get more use.

Murdo: Thanks Ronnie, it's Murdo. So, hypothetically speaking, should there be an out-of-pocket cap for patients in Part D introduced as some change in legislation, I think it would help our portfolio. We've been advocates for changes to Part D in that regard for quite a while, where we do think that the out-of-pocket expenditures and the list price equation for co-pays for patients are disincentives to drug adherence and maybe even for initial fill. So I think products like Repatha, where we are largely a Medicare Part D population, could benefit from out-of-pocket caps. Now it would obviously depend on what that travels with.

And second you started at integer interchange ability to trial for Humira Biosimilars can you just talk a little bit about your change your perspective here.

Do you believe that each entity ability will be required longer chance to participate in this market and if not what's the justification for the trial.

Thanks, Ronny, it's murdo, so hypothetically speaking should there be an out of pocket cap for patients in part D introduced in some change in legislation I think it would help in our portfolio.

Been advocates for changes to part D in that regard.

For for quite a while where we do think that the out of pocket expenditures and the list price equation for co pays for patients are disincentives to drug adherence and maybe even for initial Phil So I think I.

Murdo: Does it travel with more commitment from the manufacturer in the catastrophic phase where we pick up more of the tab? So it needs to be equated with other things that could be in any proposed legislation. But I hope that out-of-pocket caps come into play because I think patients who are in Part D are sometimes treated poorly and are sub-optimally treated because of that, and it would improve their affordability.

Think products like where path.

Where we are largely a Medicare part D population.

Could benefit from out of pocket caps would depend obviously, what that travels with does it travel with more.

Commitment from the manufacturer in the catastrophic phase, where we pick up more of the top so it needs to be equated with other things that could be in any proposed legislation but.

Operator: You know, to the question on the Amgivita interchangeability study, we continue to feel very good about our opportunity with Amgivita. Being in that first wave and potentially alone in the first wave of biosimilar launches to Humira in the U.S. affords us an opportunity to work with payers, work with the PBMs, and with providers to establish a leadership position. We look at every parameter of a biosimilar product, and this is experience from Amgivita itself in Europe, but it's also experience from our other biosimilar portfolio in the U.S., and we look at things like latex-free and citrate-free.

I hope that out of pocket caps come into play because I think patients.

Who are in part D are sometimes.

Treated poorly.

And our sub optimally treated because of that.

And it would improve their affordability.

To the question on AMG of EDA interchange ability study, we we continue to feel very good about our opportunity with Mgo Vita.

And that first wave and potentially alone in the first wave of Biosimilar launches to humira in the U S affords us an opportunity to.

Work with payers to work with.

The pbms and with providers to establish a leadership position.

We look at every parameter of a biosimilar product and this has experienced from Amgen Vita itself in Europe, but its also experience from our other biosimilar portfolio in the U S and we look at things like latex free citrate free we look at needle gauge when you look at device and of course, we look at <unk>.

Operator: We look at needle gauge. We look at device. And, of course, we look at interchangeability. So while we don't think it's essential, we think it's just another attribute of the product that could augment our success with that launch in 2023. So that's really why we've initiated the trial run.

Changeability so while we don't think it's essential we think its just another.

Attribute of the product that could augment our success in in that launch in 2023. So that's really why we've initiated the trial running.

Unknown Attendee: Your next question comes from Kinnon McKay with RBC Capital Markets.

Thank you.

Your next question comes from the line of Kennan Mackay with RBC capital markets.

Unknown Attendee: Hi, this is Sudan Loganathan on behalf of Kennan. Thank you in advance for taking our questions.

Hi, This is Sudan Logan Nathan on for Kevin. Thank you in advance for taking our questions. So first I wanted to ask on all Democrats. So how much of an impact are you expecting.

Unknown Attendee: So first, I wanted to ask you on LumaCraft, so you know, how much of an impact are you expecting?

Democrats, having on the updated top end, Greg your guidance that you updated for 2021, and then taking into account any competition entering the market in 2022, how do you plan to formulate.

Unknown Executive: [inaudible]

Right, we do guidance based on that for 2022, and then secondly.

Unknown Executive: And then thirdly, just wanted to ask about the antibody manufacturing agreement for COVID-19. Is that still something we can expect to see?

In regards to a little Kras perspective VIX.

Hum.

Combo program for colorectal cancer.

Looking forward.

How could this.

What could this mean for Vectibix if approved.

I expect some growth in that program.

Unknown Executive: [inaudible]

Unknown Executive: Arvind Sood, Yaron Werber, Salveen Richter, Daniel Lundquist, Robert Bradway, Murdo Gordon

Combination gets.

Through to approval and then.

Thirdly, just wanted to ask about the antibody manufacturing agreement with a.

Murdo: I think it was Murdo, the revenue and competition. Yeah, more of a commercial question.

COVID-19 is that still something we can expect that to be included in the other revenue line item going forward.

Updates on that just based on the pandemic.

Hi.

Murdo: So we obviously don't provide product-level revenue guidance, but I'll say this: I've worked in oncology for many years now, and I've been a part of some important lung cancer product launches. And this launch, after 40 years of trying to solve the KRAS G12C conundrum in lung cancer, this launch has been very special, and the team has done an excellent job of executing across the payer customers, our provider customers, and, of course, for patients.

Environment, let's take the first question and we can answer that and the rest of the economy. Later this is arvind from Investor Relations and we can address those questions separately.

Maybe you can address the question about global crop.

It was yes I think.

Revenue in competition, yes, more of a commercial question. So we obviously don't provide product level revenue guidance, but.

I'll say this.

I've worked in oncology for many years.

I've been a part of some important.

Cancer product launches.

And this this launch after 40 years of trying to solve the <unk>.

Murdo: I was very proud of what our R&D organization was able to do and the speed at which they brought this product to market. And I feel that the medical and commercial organizations have taken the customer-facing stage and the go-to-market stage of this launch extremely seriously and with a lot of responsibility. And so far, it's early days, but so far, they've done very, very well. And so I'm pleased with the trajectory.

<unk> lung cancer. This launch has been very special and the team has done an excellent job of executing across the payer customers our provider customers and of course for patients and I was very proud of what our R&D organization was able to do and the speed at which they brought this product to market and I feel that the medical.

Murdo: What we're seeing is that many academic centers are changing their testing protocols in lung cancer so that everybody knows their KRAS G12C status. Many large community oncology networks have done the same. Now we still have a few large community oncology networks to go, so we will be working on those in the fourth quarter, but I couldn't be more pleased with the way in which we've entered the market. And I think that bodes well for our ability to establish a strong leadership position and help many, many patients who are unfortunately progressing from first line to second line disease before competitors come in.

And commercial organizations have taken the customer facing stage in the go to market stage of this launch extremely.

Seriously and with a lot of responsibility and so far it's early days, but so far they've done very very well and so I'm pleased with the trajectory.

What we're seeing is.

Many academic centers are changing their testing protocols in lung cancer.

So that everybody knows their <unk> status. Many large community oncology networks have done the same now we still have a few large community oncology networks to go.

So we will be working on those in the fourth quarter, but I.

I couldnt be more pleased with the way in which we've entered the market and I think.

That bodes well for our ability to establish a strong leader leadership position and help many many patients who are unfortunately progressing from first line into second line disease.

Before competitors come in yes, it's hugely rewarding to launch a product like this where you hear stories of patients who have been told that their options are limited and that they should sign up for hospice care.

Coming out of hospice and getting treated with Linda kras with commercial drug and responding and the drug is working well in the marketplace. We're hearing those anecdotal stories coming back from prescribers and we will continue to do everything within our power to continue to launch limit kras quickly around the world and help menu.

Murdo: You know, it's hugely rewarding to launch a product like this, where you hear stories of patients who have been told that their options are limited and that they should sign up for hospice care, coming out of hospice and getting treated with Limicraz, a commercial drug, and responding. And the drug is working well in the marketplace. We're hearing those anecdotal stories coming back from prescribers, and we will continue to do everything within our power to continue to launch Limicraz quickly around the world and help many, many more patients. Great, thanks, Murdoch. Erica, let's take the next one.

Many more patients alright, thanks, Murdo Erica let's take the next question. Please.

Your next question comes from the line of Robyn <unk> with <unk> Securities.

Alright, Thanks for taking my question, maybe a glass half empty one in a glass half full one.

I'll start off with the glass.

Half half empty.

So when I look at what's going on with your business I mean, I think what we've heard on the call a lot of it's pricing pressure. Despite your growth and your great marketing strategy and then you've got a pipeline. That's got a lot of competitors that are going to compete with that you can take a lot of people out there with either similar molecules are competing molecule. So on.

And that question.

Any change in strategy for development and picking next generation R&D candidates going forward for any tool kit or platforms that you might need.

Operator: Let's take the next question, please.

About the drug and then the half full question.

Murdo: Let's go in reverse order. Murdo, why don't you start and then Dave can finish? Well, you know, not

This is a great opportunity in lung he did a great job with the kras developing that drug can you talk a little bit about marketing strategy.

You could have competition here, but you can stay ahead of that competition with all the drugs that youre developing walk us through.

Murdo: Well, you know, not to belabor the point, but again, you know, I've worked in the oncology field for a number of years, and what I've seen since coming to Amgen is real strength in the legacy of Amgen, which is, of course, the supportive care products that we have. We've augmented that recently with the launch of our biosimilar portfolio, and then most recently, of course, with the launch of Lumic And they are also interested in talking to us about the very rich pipeline of products that Dave Reese and his R&D colleagues are developing.

Mind us.

<unk> Amgen for for making sure that you are the dominant player even in a multiple multiple player environment. Thanks.

Let's go in reverse order Murdo why don't you start and then Dave and pumps.

Well not to belabor the point, but again.

<unk>.

The oncology field for a number of years and what I've seen since coming to Amgen is real strengths.

In the legacy of Amgen, which is of course, the supportive care products that we have we've augmented that.

Recently with the launch of our Biosimilar portfolio.

And then most recently of course with the launch of <unk> and when I sit down with Ceos of cancer networks or academic cancer centers. They are very interested in talking to Amgen.

Murdo: So I think that our commercial position with innovative products and biosimilars and launches of new therapeutics puts us in a very strong account position. And I think, you know, in a world where a lot of care is delivered in community oncology, our relationships there are extremely strong. You know, I've been able to make some customer visits this year, despite some of the interruptions of the pandemic. And most of my visits have been in support of the Lumicraz launch.

And they are also interested in talking to us about the very rich pipeline of products that Dave recent as R&D colleagues are developing so I think we are very much a leader in oncology I think that our commercial position with innovative products and biosimilars.

And the launches of new therapeutics puts us in a very strong account position and I think.

In a world where a lot of care is delivered in community oncology.

Murdo: And I can tell you they have been very, very good at working with us to develop testing programs, look back programs, entering flags in EMRs, making sure patients are flagged for treatment. And it's those systems and those processes that, being first on the ground, we should be able to build and sustain. Longer term, of course, it'll be the continuation of being first with indications and broad in the development of the asset and then supporting it with additional products in lung cancer that Dave is developing in our pipeline. Thanks, Robyn.

Our relationships there are extremely strong.

I've been able to make some customer visits this year. Despite some of the interruptions of the pandemic and most of my visits have been in support of the <unk> launch and I can tell you.

They have been very very good at working with us to develop testing programs look back programs entering flags <unk>, making sure patients are flagged for treatment.

And it's those systems and those processes that being first on the ground, we should be able to.

To build and sustain longer term of course, it will be the continuation of being <unk>.

Dave: Yeah, in terms of toolkits, we could obviously talk for hours about the toolkits that we've got in discovery research and our clinical trials. But you know, let me focus on just a couple of things for the purposes of this discussion. You know, we are building what I think is an industry-leading capability in what I call human data, which means the collection, integration, and interrogation of data ranging from various omics data, genomic data, transcriptomic data, proteomic data, through clinical trial data, through real-world evidence, and real-world data.

First with indications and being brought in the development of the asset and then supporting it with additional products in lung cancer.

Dave is developing in our pipeline.

Great. Thanks.

Robin Yes in terms of Toolkits, we could obviously talked probably for hours about the toolkits that we've got in discovery research and our clinical trials. Let me focus on just a couple of things for the purposes of this discussion.

We are building what I think is an industry leading capability in what I call human data.

Which means the collection integration and interrogation of data ranging from various ohmic date us genomic data transcript don't make data proteomics data through clinical trials data through real world evidence and real world data and it's one of our core belief.

Dave: And it's one of our core beliefs that the coming few decades will be won by those who understand how to make use of and, in particular, analyze the giant tsunami of data that is now starting to wash over us. Now, that data, of course, generates drug targets and pathways. And, as I mentioned in my prepared remarks, we are building extensive capabilities for the development of multispecific molecules, either small molecules, large molecules, or hybrid molecules.

That the coming few decades.

We'll be won by those who understand how to make use of.

In particular analyze the giant tsunami of data that is now starting to wash over us now that data of course generates drug targets.

Dave: About 80 to 85 percent of the currently validated targets are currently not approachable with existing technologies, and we are building the capability to go after what I think will be a good fraction of those undruggable targets. So I feel great about the platforms that we've got in place and are continuing to build on, and a lot more on this over the next year or two.

And pathways and as I mentioned in my prepared remarks. So we're building extensive capabilities for the development of multi specific molecules either small molecules large molecules or hybrid molecules about 80% to 85% of the currently validated.

<unk> are currently not approachable with existing technologies.

Operator: Your next question comes from the line of Corey Casimov with J.P. Morgan.

We are building the capability to go after what I think will be a good fraction of those undruggable targets. So I feel great about the platforms that we've got in place and are continuing to build on and a lot more on this over the next year or two.

Unknown Attendee: Hi, this is Gavin on behalf of Corey. Thanks for taking our question.

Murdo: Maybe one for Murdo, just curious about the expected impact of Tesla's mild to moderate label expansion. Specifically, should we expect immediate uptake in 2022?

Your next question comes from the line of Cory <unk> with J P. Morgan.

Gavin: Or just something that will be a little more gradual. And then, secondly, just a geographic expansion was underscored as a key strategy for the growth profile of this product. And the rest of the world.

Hi, This is gavin on for Cory Thanks for taking our question maybe one for Murdo just.

Just curious about the expected impact of.

Unknown Executive: And the rest of the world has been around 20% of total sales; they're just curious if that trend is going to continue.

Mild to moderate label expansion, specifically should we expect immediate uptake in 2022 or is this something that will be a little more gradual and then secondly, just geographic expansion was underscores a key strategy for the growth profile for this product.

Murdo: Yeah, thank you, Gavin. You know, when we acquired Otezla, I thought it would be a really good addition to the portfolio and our strength in immunology, both in dermatology and in rheumatology. And, you know, obviously, we had to make a certain set of assumptions about how that product would evolve under our ownership. And, you know, so far, I have to say, I'm even more pleased with the strength that the product brings to Amgen.

Rest of World has been around 20% of total sales. So just curious.

If that trend is going to continue.

Yes, Thank you Kevin.

When we acquired hotels I thought it would be a really good add to the portfolio and our strength in immunology, both with dermatology and rheumatology.

Murdo: We've been successful, as you highlight, in demonstrating the product's efficacy and safety in the mild to moderate patient setting, which is a perfect sweet spot for this product, given the convenience of its oral dosing and given the well-demonstrated safety and efficacy of the product. We also recently had a decision on the patent for Otezla, which definitely helps make it a very strategic product for us, a very important product for the growth of the company. And, you know, the fit is just perfect.

And obviously, we had to make a certain set of assumptions about how that product would evolve in our ownership.

So far I have to say I'm, even more pleased with the with the strength.

The product brings to Amgen, we've been successful as you highlight in.

Demonstrating the product's efficacy and safety in the mild to moderate patient setting, which is a perfect sweet spot for this product given the convenience of its oral dosing given the.

Well demonstrated safety and efficacy of the product.

We also recently.

Murdo: You know, we have integrated the legacy Celgene team fully into Amgen. We've got both Enbrel and Otezla now being promoted in rheumatology and dermatology, and we've seen volume growth improve, and most markedly in the last part of Q3. But that continues into Q4.

Had a decision on the patent.

For <unk>, which definitely helps make it a very strategic product for us a very important product for the growth of the company and the.

The fit is just perfect.

We've integrated the legacy Celgene team fully into Amgen, we've got.

Murdo: You know, we didn't plan on a pandemic when we did the transaction, obviously, but we've weathered it well. The team is staying focused, and we are well prepared for a mild to moderate launch. We're anticipating a decision on that soon from the FDA. We have the resources available. We have the teams trained. We have an increased footprint in dermatology and anticipation of the approval, and we expect to be able to execute very effectively.

Both Enbrel Ando Tesla now being promoted in rheumatology and dermatology and we've seen we've seen volume growth improve in most most markedly in the last part of.

Q3, but that continues into Q4.

We didn't plan on a pandemic when we did the transaction, obviously, but we've weathered it well the team is staying focused and we are well prepared for the mild to moderate launch youre anticipating.

<unk> on that soon from the FDA, we have the resources available. We have the teams trained we have an increased footprint in dermatology in anticipation of the approval.

And we expect to be able to execute very effectively. We also have very very strong payer coverage here and we think that the majority of these mild to moderate patients and we're targeting a specific subset we're targeting those patients that have larger body surface area or very difficult to treat areas.

With topical so thats about a one 5 million patient population. So it is a large opportunity, but we think that the.

Murdo: The other thing I would add is that we expect to benefit from it somewhat more in the PSA area versus psoriasis, but the safety concerns of the jacks right now are helping Otesla and the overall perception of our safety and our efficacy. And I think that might bode well for future competition that's currently in the process, I guess, of being filed with the FDA.

The profile of the product the price point of the product versus biologics puts us in a very very strong position.

Two to treat these patients the other thing I would add that.

We expect to benefit from somewhat more so than the PSA area versus psoriasis, but the safety concerns of the Jack's right now quite frankly are helping with Tesla and the overall perception of our safety and our efficacy and I think that might bode well for future competition.

Operator: Your next question comes from the line of Carter Gould with Barclays. Great. Good evening. Thanks for taking the call.

Carter Gould: Great. Good evening.

Currently.

Carter Gould: Thanks for taking the question. Maybe to change it up a little bit, I wanted to ask you about the line extension strategy for tezapelumab into EOE, how you think about the attractiveness of EOE, given that it's increasingly caught the attention of larger biopharma, and I guess alongside that, when your partner disclosed the orphan drug designation, they talked about a planned phase three. Should that be the expectation, that you'll move straight into phase three versus doing some phase two work here? Thank you. Thanks, Carter.

In the process I guess are being filed with the FDA.

Your next question comes from the line of Carter Gould with Barclays.

Great. Good evening, Thanks for taking the question maybe to change it up a little bit I wanted to ask around the debt.

The line extension strategy for <unk> how.

How do you think about the attractiveness of Eo given that its increasingly caught the attention of larger biopharma and I guess alongside that when your partner disclosed the orphan drug designation. They talked about a planned phase III should that be the expectation that youll move straight into phase III versus doing some phase II work here. Thank you.

Dave: Eosinophilic esophagitis, or EOE, as it's called in the field, is an increasingly diagnosed condition that, you know, patients with heartburn now, who typically would have been diagnosed with reflux over the previous decade, a fair number of those are now recognized to have eosinophilic esophagitis. Given the mechanism of action of tezapelumab, and given what we've seen in some of our biomarker and tissue acquisition studies in asthma, based on eosinophil depletion in target tissue, this makes a lot of sense.

Yes, Thanks Carter.

Eosinophilic esophagitis or <unk>.

As it's called in the field.

Increasingly diagnosed condition.

Patients with heartburn on now who typically would have been diagnosed with three blocks over the previous decade, a fair number of those are now recognized to have eosinophilic esophagitis, given the mechanism of action of <unk>, given what we've seen in some of our <unk>.

Dave: And that is why, with our partners, we are carrying this forward into phase three based on the phase one data that we have generated. So I think it's the evidence package across the molecule here that supports that. Eric, as we're getting close to the top of the hour, why don't we take one more question, after which I'll answer?

Marker and tissue acquisition.

Studies in asthma based on eosinophil depletion in target tissue.

It makes a lot of sense and that is why with our partners.

We are carrying this forward into phase III based on.

Unknown Executive: Your final question comes from the line of Michael Smith with Guggenheim. Hey, this is Kelsey on behalf of Michael.

The phase one data that we've generated so I think the evidence package across the molecule here that supports that.

Because we are getting close to the top of the hour why don't we take one more question after which I'll ask Bob to make some concluding comments.

Michael Smith: Thanks for taking our question. Could you maybe just discuss kind of your latest thoughts around potential accelerated approval opportunities in the frontline setting for lung cancer, and maybe when you might expect to have kind of a clear path forward one way or the other?

Your final question comes from the line of Michael Schmidt with Guggenheim.

Hey, this is kelsey on for Michael Thanks for taking our question could you maybe just discuss kind of your latest thoughts around potential accelerated approval opportunity in the frontline setting for lung cancer and maybe when you might expect to have kind of a clear.

Unknown Executive: [inaudible]

Unknown Executive: Thanks for the question. The FDA has

Unknown Executive: The FDA has been generally clear that in the first-line setting, randomized data are required. We are, as I indicated, conducting a trial in patients with STK-11 and or PD-L1 negative or low tumors where checkpoint inhibitors are not particularly effective. We've had discussions with regulators, but I think the general expectation is that, you know, barring significant results, one will expect randomized trials in the front line.

<unk>, one way or the other from from the FDA. Thank you.

Yes, thanks for the question.

<unk> has just been generally clear that in the first line setting all randomized data are required.

Okay.

As I indicated conducting a trial in patients with SDK 11 or <unk>.

<unk> PDL one.

Negative or low.

Tumors, where checkpoint inhibitors are not particularly effective.

Unknown Executive: Okay, well, let me... Let me thank all of you again for joining our call, and we'll look forward to having an opportunity to meet with you in the new year when we report on the fourth quarter. We obviously have a lot of exciting things happening between now and then again, starting with the expanded label for Tesla, to be followed by the launch label for Tesla Pelliamab and the beginning of a number of new phase three trial programs, as we indicated on the call. So it is an exciting time for us. I look forward to gathering with you in the new year. Again, thanks for your support.

When we have those phase two data available of course.

<unk>, if we saw interesting data we would have the appropriate.

Discussions with regulators, but I think the general expectation is that.

Barring significant results when we'll expect randomized trials in frontline lung cancer.

Okay, well, let me.

Sure.

Let me. Thank all of you again for your for joining our call and we look forward to having opportunity to meet with you in the new year. When we report on the fourth quarter. We obviously have a lot of exciting things happening between now and then again, starting we'd expect quickly.

Expanded label for hotels loans will be followed by the launch label for <unk> and <unk>.

And this concludes Amgen's third quarter 2021 financial results conference call. You may now disconnect.

Beginnings of a number of new phase III trial programs as we indicated on the call. So exciting time for us to look forward to gathering with you in the new year. Thanks for your support great. Thanks, everybody.

Yes.

And this concludes amgen's third quarter 2021 financial results Conference call you may now disconnect.