Q4 2021 Bristol-Myers Squibb Co Earnings Call

Please standby we're about to begin.

Good day, everyone and welcome to the Bristol Myers Squibb 2021 fourth quarter results Conference call. Today's conference is being recorded at this time I would like to turn the call over to Mr. Tim Power Vice President Investor Relations. Please go ahead Sir.

Operator: Please stand by; we're about to begin. Good day, everyone, and welcome to the Bristol Myers Squibb 2021 fourth quarter results conference call. Today's conference is being recorded. At this time, I'd like to turn the call over to Mr. Tim Power, Vice President of Investor Relations. Please go ahead.

Thank you Alan and good morning, everyone. Thanks for joining us this morning for our fourth quarter 2021 earnings call.

Tim Power: Thank you, Alan. And good morning, everyone. Thanks for joining us this morning for our fourth quarter 2021 earnings call. Joining me this morning with prepared remarks are Giovanni Caforio, our Board Chair and Chief Executive Officer, and David Elkins, our Chief Financial Officer. Also participating in today's call are Chris Boerner, our Chief Commercialization Officer, and Samit Hirawat, our Chief Medical Officer and Head of Global Drug Development. As you'll note, we've posted slides to bms.com that you can follow along with for Giovanni and David's remarks.

Joining me this morning with prepared remarks are do you have any cause for you our board chair and Chief Executive Officer, and David Elkins, Our Chief Financial Officer.

Also participating in today's call are Chris burner, our chief commercialization officer and someone here a lot our chief Medical officer, and head of global drug development.

As you'll note we've posted slides to be M. S. Dot com that you can follow along with Giovanni on David's remarks, and before we get started I will read our forward looking statements.

Tim Power: And before we get started, I'll read our forward-looking statement. During this call, we will make statements about the company's future plans and prospects that constitute forward-looking statements. However, actual results may differ materially from those indicated by these forward-looking statements.

This call, we'll make statements about the company's future plans and prospects that constitute forward looking statements actual results may differ materially from those indicated by these forward looking statements as a result of various important factors, including those discussed in the company's SEC filings.

Tim Power: Very important factors, including those discussed in the company's SEC filing. These forward-looking statements represent our estimates as of today and should not be relied upon as representing our estimates as of any future date. Josephically Disclaim, Any Obligate, Obligation, Update Forward-looking Statements, Dr. Prima, Dr. Prima, We'll also focus our comments on our non-GAAP financial measures, which were adjusted to exclude certain specified items. Reconciliations of certain non-GAAP financial measures to the most comparable GAAP measures are available on BMS.gov. With that, I'll hand over to Geoff. Thank you, Tim. And good morning, everyone.

Are we looking statements represent our estimates as of today and should not be relied upon as representing our estimates as of any future date, we specifically disclaim any obligation obligation to update forward looking statements, even if our estimates change.

We'll also focus our comments on our non-GAAP financial measures, which are adjusted to exclude certain specified items.

Conciliation of certain non-GAAP financial measures to the most comparable GAAP measures are available on BMS dot com and with that I'll hand over to Giovanni.

Thank you Tim and good morning, everyone, let's start with our fourth quarter performance on slide four I'm.

Giovanni Caforio: Let's start with our fourth quarter performance on slide four. I'm pleased to report we delivered another strong quarter, building on our very good performance throughout 2021. Our commercial results were strong across the portfolio, with robust performance in our continuing business, driven by eloquence and accelerated growth for a, as well as continued demand growth for our new product. The launch of Zipozia in Ulcerative Colliders is progressing well in the US, and we obtained European approval during the... We are pleased with continued demand growth for Reblozil in ESA refractory MDS and transfusion-

I'm pleased to report we delivered another strong quarter building on our very good performance throughout 2021.

Our commercial results were strong across the portfolio with a robust performance in our continuing business driven by <unk> and accelerated growth for Opdivo as well as continued demand growth what I wasn't your products.

The launch of depots, yet in ulcerative colitis is progressing well in the U S and we obtained European approval during the quarter.

We are pleased with continued demand growth for <unk> in Esa refractory Mds and transfusion dependent beta thal.

Giovanni Caforio: And our cell therapies, Brianzina Beckma, continue to see significant demand, while we remain focused on broadening supply and expanding indications or... We are advancing our strategy and delivered key pipeline milestones in the fourth quarter. This enables us to have more patients. Accelerate the Renewal of Our Portfolio and Support Our Growth Opportunities. Let me highlight some key... We submitted applications for the Kravitz Sydney between the US, EU, and Japan, which positions us well to grow our presence in Europe. We're excited about the potential of the Kravassidinim as the oral standard of care in moderate to severe psoriasis and various other polymunities.

And our cell therapies reacting at Beckman continued to see significant demand why did we remain focused on broadening supply and expanding indications all the time.

We are advancing our strategy and delivered key pipeline milestones in the fourth quarter.

This enables us to help more patients accelerated are you all of our portfolio and support our growth outlook.

Let me highlight like yesterday.

Which would meet those obligations will do privacy than had been the U S EU, and Japan, which position us well to grow our presence and you got knowledge.

We are excited about the potential of the scrubber citizen as the oral standard of care in moderate to severe psoriasis and various other autoimmune diseases.

Giovanni Caforio: We are expanding our cardiovascular portfolio and presented exciting data at AHA for Milvex, which we see as the next generation antithrombotic with a $5 billion plus non-risk adjusted revenue. We presented important updates on Ash for our hematology pipeline, including encouraging data for iverdomyte and phloridin, our exciting new multiple myeloma cell model.

We are expanding our cardiovascular portfolio presented exciting data at IHA for mill vaccine, which we see as the next generation Antithrombotic with a 5 billion dollar plus no risk adjusted revenue opportunity.

We presented important update at ash on our hematology pipeline.

These includes encouraging data I've learned tonight and for JD, our exciting new multiple myeloma cell Mod agents.

Giovanni Caforio: These have the potential to replace Red Limit and Pomodestore. Importantly, the TRANSFORM data for Brianzi in second-line B-cell insomnia showed practice-changing benefits compared to the current standard of care. We continue to see Brayanzi as one of the key growth drivers for the company, with over 3 billion in non-risk adjusted revenue for them. Our strong execution, health drive, and solid financial performance in the fourth course. [inaudible] We reported 8% sales growth and double-digit non-GAAP EPS growth.

These have the potential to replace Revlimid and pulmonary store thing.

Importantly, the transform data for brands in second line B cell lymphoma.

Rockies changing benefit compared to the current standard of care.

We continue to see reality is one of the key growth drivers for the company with over $3 billion in non risk adjusted revenue potential.

Our strong execution helped drive solid financial performance in the fourth quarter.

We reported 8% sales growth and double digit non-GAAP EPS growth.

Giovanni Caforio: Our strong cash flow and financial strength provide us with significant financial resources. This enables us to continue prioritizing disciplined business development opportunities while paying down debt and expanding shareholder distribution. We also introduced our 2022 guidance, and I will let David speak to the details in a moment.

Our strong cash flow and financial strength provide us with significant financial flexibility.

This enables us to continue prioritizing disciplined business development opportunities, while paying down debt and expanding shareholder distributions.

We also introduced our 2022 guidance last month.

And I'll, let David speak to the details in a moment.

Giovanni Caforio: What's important is that we are guiding to growth, with low double-digit growth from our continuing business more than offsetting the revenue impact from generics in the U.S. and internationally. Turning to our 2021 Executious Scorecard on slide, at the beginning of last year.

What's important is that we are guiding to growth this year with low double digit growth from our continuing business more than offsetting the revlimid revenue impact from generics in the U S and internationally.

Turning to our 2021 execution scorecard on slide five.

At the beginning of last year.

Giovanni Caforio: I outlined a number of milestones that we believed would be important to us, including opportunities to renew our portfolio and grow our business during the decade. I am pleased to report that we have made great progress. We have returned to Devar's growth, successfully launched multiple new products, and produced key expansion datasets for several months. This record of execution across the company further strengthens my confidence in our ability to continue to renew our portfolio and grow it.

I outlined a number of milestones that we believed would be important to our future.

Including opportunities to renew our portfolio and grow our business during the decade.

I am pleased to report we've made great progress.

Would he turned opdivo to growth.

That's what he launched multiple new products and produced key expansion datasets for several assets.

This record of execution across the company further strengthens my confidence in our ability to continue to renew our portfolio and grow in the future.

We know we must remain focused on advancing our pipeline to accelerate the renewal of our portfolio.

Giovanni Caforio: We know we must remain focused on advancing our pipeline to accelerate the renewal of our... And on slide six, you can see there are multiple catalysts ahead during 2020. The 2022 milestones include expected approvals and launches for three exciting first-in-class medicines, Mavakampton, Lucreva Sittinib, and we're last. We believe that all of these assets have the potential to further strengthen the commercial opportunity for our new product portfolio and support our growth. We expect that each of these assets will have at least $4 billion in revenue potential at the end of the decade on a non-risk adjustment.

And on slide six you can see that our multiple catalysts ahead during 2022.

The 2022 milestones include expected approvals and launches or three exciting first in class medicines Novack Hampton to cross citizen Henry last time as.

We believe that all of these have the potential to further strengthen the commercial opportunity for our new product portfolio and support our growth outlook.

We expect that each of these assets has at least 4 billion revenue potential at the end of the decade on a non risk adjusted basis.

Giovanni Caforio: We look forward to keeping you updated on our progress throughout. Looking to the future, slide 7 summarizes our perspective of how all of this comes together to support the growth of the company moving forward. We expect the growth in our continuing business will enable us to more than offset key LOEs through 2020, with continued growth of our inline brands and $10 to $13 billion of additional sales expected from our new product line.

Look forward to keeping you updated on our progress throughout the year.

Looking to the future slide seven summarizes our perspective, all that how all of this comes together to support the growth of the company moving forward.

We expect the growth in our continuing business will enable us to more than offset T alloys through 2025.

With continued growth, although our inline brands and $10 billion to $13 billion of additional sales expected from our new product portfolio.

Giovanni Caforio: In the second half of the decade, with a broad and expanding product portfolio, we will have multiple paths to achieving our growth objective from 2025 to 2029. As we said, we expect more than $25 billion, and not risk-adjusted revenue potential, from the Current New Brother Portfolio in 29, with additional contributions coming from our pipeline, including assets like Milvexian and our exciting Selma.

In the second half of the decade, with a broad and expanding product portfolio, we would have multiple paths to achieving our growth objectives from 2025 to 2029.

As we've said, we expect more than 25 billion and non risk adjusted revenue potential from the current new blogger portfolio in 29 with.

With additional contributions coming from our pipeline, including assets like meal vaccine and how exciting settlement agents.

As we continue our journey to renew our business and growth of the impact of Eloise starting this year I'm increasingly excited about the future of Bristol Myers Squibb.

David Elkins: As we continue our journey to renew our business and grow through the impact of Eloise, starting this year, I'm increasingly excited about the future of Bristol Myers. With that, I'll turn it over to David to walk you through the financials.

With that I'll turn it over to David to walk you through the financials David.

Thank you Giovanni and thank you all for joining our call today I'd like to start with our strong topline performance on slide nine we closed out the year with another great quarter across our key franchises revenues grew high single digits versus prior year, which was driven primarily by increased demand for our in line and new product portfolios.

David Elkins: Thank you, Giovanni, and thank you all for joining our call today. I'd like to start with our strong top line performance on Slide 9. We closed out the year with another great quarter across our key franchises.

David Elkins: Revenues grew high single digits versus prior year, which was driven primarily by increased demand for an inline and new product portfolio. Now, let's turn to some product specifics, starting with Eliquis on slide 10. Eloquist continues to deliver extraordinary growth with global sales up 20% for both the fourth quarter and the full year. In the US, fourth quarter sales increased 22% versus prior year, driven primarily by total prescription growth of 1

Now, let's turn to some product specific starting with the earlier question on slide 10.

<unk> continues to deliver extraordinary growth with global sales up 20% for both the fourth quarter and the full year.

In the U S fourth quarter sales increased 22% versus prior year, driven primarily by total prescription growth of 13%.

David Elkins: Internationally, electric sales growth continues to be driven by increased share across all key markets, and the brand remains the number one OAC in multiple countries. Looking forward, the growth outlook for Eliclister is strong as we continue to grow the oral anticoagulant class and increase our share within the class. As a reminder, the first quarter of 2021 did experience a one-time favorable true-up in the U.S. of approximately $160 million that will not repeat in Q1 of 2022. Moving to Updiva's performance on slide 11.

Internationally with sales growth continues to be driven by increased share across all key markets and the brand remains the number one <unk> in multiple countries.

Looking forward the growth outlook for eloquence remains strong as we continue to grow the oral anticoagulant class and increase our share within the class.

As a reminder, the first quarter of 2021 did experience a onetime favorable true up in the U S of approximately $160 million that will not repeat in Q1 of 'twenty two.

Moving to Opdivo performance on Slide 11, we are very pleased with the accelerated momentum growing 11% globally versus prior year. This is driven by strong demand, particularly for our new launch indications.

David Elkins: We are very pleased with the accelerated momentum, growing 11% globally versus prior year. This is driven by strong demand, particularly for our new launch indication. In the U.S., fourth quarter revenues were strong, up 16% versus prior year.

In the U S fourth quarter revenues were strong up 16% versus prior year growth was primarily attributable to demand in metastatic indications, including first line lung first line renal in first line gastric cancers as well as adjuvant indications with the approvals of adjuvant esophageal and adjuvant bladder cancers in too.

David Elkins: Growth was primarily attributable to demand for metastatic indications, including first-line lung, first-line renal, and first-line gastric cancers, as well as adjuvant indications with the approvals of adjuvant esophageal and adjuvant bladder cancers in 2021. Internationally, fourth quarter revenues grew 5% versus the prior year, driven largely by demand for new indications and expanded access, primarily in More broadly, we continue to see uptake of our new launches for lung and renal cancer in Germany and Japan, and we secured reimbursement in Italy and Spain in the fourth quarter.

'twenty one.

Internationally fourth quarter revenues grew 5% versus prior year, driven largely by demand for new indications and expanded access primarily in emerging market.

More broadly we continue to see uptake of our new launches in lung and renal cancer in Germany and Japan.

David Elkins: As we look forward, we continue to expect further growth for Updivos, and we secure additional reimbursement for recent approval. We're in a strong position to continue to grow Updevo and look forward to additional approvals this year and in the years ahead. Now let's turn to our image portfolio on slide 12, starting with Revolman. Fourth quarter revenues grew 1% globally versus the prior year and grew 6% for the full year with sales of approximately $12.8 billion.

And we secured reimbursement, Italy, and Spain in the fourth quarter as we look forward. We continue to expect further growth for Opdivo as we secure additional reimbursement for recent approvals.

We're in a strong position to continue to grow up to Evo and look forward to additional approvals this year and in the years ahead.

Now, let's turn to our entire portfolio on slide 12, starting with Revlimid fourth quarter revenues grew 1% globally versus prior year and grew 6% for the full year with sales of approximately $12 8 billion.

David Elkins: As we enter into the first year of generic entry for Revlimid, I want to remind you of our expectations for Revlimid sales in 2022 and beyond. We expect Revlimid sales of $9.5 to $10 billion in 2022. Of these sales, we expect roughly 75% to come from the U.S., and the remaining from non-U.S. markets.

As we enter into the first year of generic entry for Revlimid I want to remind you of our expectations for Revlimid sales in 2022 and beyond.

We expect Revlimid sales of nine and a half to $10 billion in 2022.

These sales, we expect roughly 75% come from the U S and the remaining from ex U S markets.

David Elkins: As we think about generic entry this year, we expect sales variability quarter to quarter based on the timing of how generic competitors fulfill their annual volume. For the first quarter, our best projection for global revenue and sales is approximately $2.5 billion. Beyond 22 through 2025, although there is still uncertainty due to ongoing litigation, we view an annual step-down of roughly $2 to $2.5 billion per year as a reasonable projected. Now on to Pomalyst. Global sales in the fourth quarter were up 2%.

We think about generic entry this year, we expect sales variability quarter to quarter based on the timing of how generic competitors to fill their annual volumes for the first quarter, our best projection for global Revlimid sales is approximately $2 5 billion.

Beyond 'twenty two through 2025, although there is still uncertainty due to ongoing litigation, we view an annual step down of roughly two to $2 $5 billion per year is a reasonable projection.

Now on to <unk> global sales in the fourth quarter were up 2% sales were primarily driven by demand for triplet based therapies in ex U S markets and fewer selling days in the U S. We continue to expect growth for promise as treatments move to earlier lines of therapy and more triplet based therapies are approved with longer duration of treatment.

David Elkins: Sales were primarily driven by demand for triplet-based therapies in ex-U.S. markets and fewer selling days in the U.S. We continue to expect growth for pomelos as treatments move to earlier lines of therapy, and more triplet-based therapies are approved with longer duration of treatment. As it relates to USIP for POMELUS, we are pleased that there is now no outstanding litigation. At this point, we don't expect generic entry into the U.S. market prior to the first quarter of 2026.

As it relates to U S. IP for Palm list. We're pleased that there is now no outstanding litigation.

At this point, we don't expect generic entry in the U S market prior to the first quarter of 2026.

Now, let's move on to our new product portfolio on slide 13.

David Elkins: Now let's move on to our new product portfolio on slide three. [Inaudible] We are very pleased with the momentum and feedback we are receiving on our new product portfolio. These products contributed over $350 million in the fourth quarter and $1.1 billion for the full year.

We are very pleased with the momentum and feedback were receiving on our new product portfolio. These products contributed over $350 million in the fourth quarter and $1 1 billion for the full year let.

David Elkins: Let me provide some color on each launch individually, starting with Rebozo, which generated global revenues of just over $550 million in 2021, more than doubling its revenues over last year. In the US, full-year sales grew 87% versus the prior year, primarily due to continued demand in ESA refractory MDS patients. The company continued to grow in the fourth quarter.

Let me provide some color on each launched individually starting with rebels, which generated global revenues of just over $550 million in 2021.

More than doubling its revenues over last year.

In the U S full year sales grew 87% versus prior year, primarily due to continued demand and Esa refractory Mds patients demand continued to grow in the fourth quarter.

David Elkins: sequentially, revenue was impacted by one-time favorable inventory billed in the third quarter of approximately $20 to $25 million. The focus remains on treating new patients earlier in their treatment journey upon ESA failure, as well as ensuring physicians titrate their patients up to receive the appropriate dose for sustained benefit. Internationally, we continue to launch in additional countries and expect to continue to do so in 2022, helping more patients and driving additional growth for the brand. Now, moving to our cell therapy launches of Becma and Brianzi. Becma has generated revenues of $164 million since its launch in May of last year.

Sequentially revenue was impacted by one time favorable inventory build in the third quarter of approximately $20 to $25 million.

Focus remains on treating new patients earlier in their treatment journey upon Esa failure, as well ensuring physicians titrate the patients up.

To receive the appropriate dose for sustained benefit.

Internationally, we continue to launch in additional countries and expect to continue to do so in 2020 to helping more patients and driving additional growth for the brand.

Now moving to our cell therapy launches at Beckman Brianti Beckman generated revenues of $164 million since its launch <unk> launch in may of last year.

David Elkins: Revenues reflect very strong demand for the first ever BCMA cell therapy. As noted in the past, demand continues to be very robust, and we're working hard to expand. We expect first quarter revenues to be largely similar to fourth quarter. Turning to our CD19 cell therapy, Brionzi.

Revenues reflect very strong demand for the first ever be CMA cell therapy as noted in the past demand continues to be very robust and we're working hard to expand capacity, we expect first quarter revenues to be largely similar to fourth quarter.

Turning to our CD 19 cell therapy Brianti physicians continue to recognize beyond these best in class profile for relapsed refractory patients.

David Elkins: Physicians continue to recognize Brionzi's best-in-class profile for relapsed refractory patients. We look forward to moving Brionzi up the treatment paradigm in the second-line setting with remarkable EFS data presented from our TRANSFORM study at ASH. And we look forward to bringing this treatment to second-line patients in the US this year. Now moving to Symposia, global sales for the year were $134 million, primarily driven by our multiple sclerosis indication.

We look forward to moving.

The treatment paradigm in the second line setting with remarkable Uff's data presented from our transform study at Ash and we look forward to bring this treatment to second line patients in the U S. This year.

Now moving to suppose your global sales for the year were $134 million, primarily driven by our multiple sclerosis indication.

David Elkins: In the US, the MS launch continues to go well. Supposio remains the leading S1P in written prescriptions, and we remain focused on establishing Supposio not only as the S1P of choice, but also the oral treatment of choice.

In the U S. M. S launch continues to go well.

<unk> remains the leading <unk> and written prescriptions and we remained focus on establishing supposedly and not only is the <unk> of choice, but also the oral treatment of choice. We continue to be pleased with the progress. We have made on patient conversion with significant decrease in time to commercial therapy.

David Elkins: We continue to be pleased with the progress we have made on patient conversion, with a significant decrease in time to commercial therapy. Our early UC launches are continuing to gain traction with a leading share of voice and increased overall violence. Physicians are responding well to the profile, and we are encouraged by their intent to prescribe.

Our early UC launches continuing to gain traction with our leading share of voice and increased overall volume.

Physicians are responding well to the profile and we are encouraged by their intent to prescribe.

David Elkins: We are working on building volume and growing access and reimbursement. We expect to have increased contribution from you in the second half of this year and to expand in 2023. Internationally, Zapposia continues to gain momentum in MS as the product gets additional reimbursement in more markets and benefits from year-end stock.

We're working on building volume and growing access and reimbursement we expect to have an increased contribution from you see in the second half of this year and expanding in 2023.

Internationally as opposed to you continues to gain momentum in MFS as the product gets additional reimbursement in more markets and benefited from some year end stocking. We're very pleased with the recent EMEA approval of UC in December and look forward to securing access and reimbursement for this indication to drive further growth for the brand.

David Elkins: We are very pleased with the recent EMA approval of UC in December and look forward to securing access and reimbursement for this indication to drive further growth for the brand. Lastly, on Onurag in the U.S., we continue to make progress on establishing the product for patients in complete remission following intensive chemotherapy. Focus remains on shaping the maintenance segment and increasing adoption and patient adherence.

Lastly on <unk> in the U S. We continue to make progress on establishing the product for patients in complete remission following intensive chemotherapy.

Our focus remains on shaping the maintenance segment, and increasing adoption and patient adherence.

David Elkins: Overall, I'm pleased with our new product portfolio performance and look forward to three additional approvals expected this year. We are launch ready for Relat Mab and Mavicampton, with Padufa Dayton in March and April. And we're on track for Dukrevacit Nibb's launch in September. Now, switching gears to our fourth quarter P&L on slide 14. Having just covered sales performance, let me walk you through a few non-gap key liners. Operating expenses increased versus the prior quarter due to timing of MS&A investments that shifted to the fourth quarter, as noted in October. MS&A decreased versus the prior year due to some incremental and accelerated investments to support our business in 2020. Force Quarter Effective Tax Rate was impacted by Ernie Smith.

Overall, I'm pleased with our new product portfolio performance and look forward to three additional approvals expected. This year, we are launch ready for rollout Mab and Maverick Hampton with <unk> dates in March and April and we're on track for <unk> sitting there was launched in September .

Now switching gears to our fourth quarter P&L on slide 14.

Having just covered sales performance, let me walk you through a few non-GAAP key line items.

Operating expenses increased versus prior quarter due to timing of M. S. N a investments that shifted from the fourth quarter as noted in October Emerson, a decrease versus prior year due to some incremental and accelerated investments to support our business in 2020.

Our fourth quarter effective tax rate was impacted by earnings mix.

David Elkins: And as a result of the strong performance in the quarter, non-gap EPS increased approximately 25% year-over-year. Moving to the balance sheet and capital allocation on slide 15, we continue to generate a significant amount of cash from operations, with approximately $4 billion in the fourth quarter. We ended the quarter in a strong liquidity position with approximately $17 billion in cash and market votes to secure. Arcafato Allocation Priorities Remain Munching Business Development remains our top priority to further renew and diversify our portfolio.

And as a result, the strong performance in the quarter non-GAAP EPS increased approximately 25% year over year.

Moving to the balance sheet and capital allocation on slide 15, we continue to generate a significant amount of cash from operations with approximately $4 billion in the fourth quarter. We ended the quarter in a strong liquidity position with approximately $17 billion in cash and marketable securities.

Our capital allocation priorities remain unchanged business development remains our top priority to further renew and diversify our portfolio and we are also focused on reducing debt and returning capital to shareholders.

David Elkins: And we are also focused on reducing debt and returning capital to shareholders. We executed several business development deals last year, bringing in differentiated early-stage assets. We have the financial strength to be size agnostic, but we are particularly interested in early stage and mid-size bolt-ons.

We have executed several business development deals last year, bringing differentiated early stage assets, we have the financial strength to be size agnostic, but we are particularly interested in early science and mid sized bolt on deals.

David Elkins: As it relates to debt, in 2021, we reduced gross debt by over $6 billion and remain committed to maintaining a strong investment grade credit rating. Lastly, as it relates to returning capital to shareholders, we recently grew the dividend by over 10%, which was our 13th consecutive increase. Additionally, we increased our share repurchase authorization by $15 billion and planned to execute a $5 billion ASR this quarter. Now turning to our 2022 non-GAAP guidance at current exchange rates on slide 16.

As it relates to that in 2021, we reduced gross debt by over $6 billion and remain committed to maintaining a strong investment grade credit rating.

Lastly, as it relates to returning capital to shareholders. We recently grew the dividend by over 10%, which was our 13th consecutive increase. Additionally, we increased our share repurchase authorization by $15 billion and plan to execute a $5 billion ASR this quarter.

Now turning to our 2022 non-GAAP guidance at current exchange rates on slide 16.

David Elkins: As announced last month, we expect 22 revenues to be approximately $47 billion, representing low single-digit growth over 2021. Growth from our continuing business will more than offset the revenue impact from Revlimid and Abraxane LOEs. We expect key LOE brand sales to be approximately $10.5 billion, and our continuing business, which represents our in-line and new product portfolios, is expected to grow at a low double-digit rate and contribute approximately $36.5 billion. As it relates to our line item guidance for the year, we expect our gross margin to be approximately 78%, and our total operating expenses to be in line with 2021 expenses. And we project our tax rate to be approximately 16.5%.

As announced last month, we expect 22 revenues to be approximately $47 billion.

Representing low single digit growth over 2020 one.

Growth from our continuing business will more than offset the revenue impact from revlimid and practicing Louise.

We expect key low brand sales to be approximately $10 5 billion and our continuing business, which represents our in line and new product portfolios is expected to grow low double digit and contribute approximately $36 5 billion.

As it relates to our line item guidance for the year, we expect our gross margin to be approximately 78% and our total operating expenses to be in line with 2021 expenses and we project our tax rate to be approximately 16, 5%.

David Elkins: Finally, as communicated earlier this year, we expect non-GAAP EPS to grow faster with sales and be between $7.65 and $7.95. As it relates to our share count, I'd like to provide a little color as we plan to execute the $5 billion ASR. We ended the year with approximately 2.2 billion diluted shares outstanding.

Finally also communicated earlier this year, we expect non-GAAP EPS to grow faster than sales and be between $7 65 and.

$7 95.

As it relates to our share count I'd like to provide a little color as we plan to execute the $5 billion ASR. We ended the year with approximately $2 2 billion diluted shares outstanding.

David Elkins: We'll be executing the ASR later this quarter, which means we will get a majority, but not all of the benefit, on the Luke Share count this year. Lastly, given this is the first quarter of generic entry for Revolmed, we thought it would be helpful to provide some perspective on revenue for the first quarter. In addition to the approximately $2.5 billion of Revolved Sales I mentioned previously, we are projecting total global first quarter sales to range from 11 to $11.5 billion.

We will be executing the ASR later this quarter, which means we will get a majority, but not all of the benefit on diluted share count this year.

Lastly, given this is the first quarter of generic entry for Revlimid, we thought it'd be helpful to provide some perspective on revenue for the first quarter. In addition to the approximately $2 $5 billion of Revlimid sales I mentioned previously we are projecting total global first quarter sales to range from 11 to 11 5 billion.

So before I turn it over to question and answer I just want to thank our teams around the world for delivering these remarkable results in 2021.

David Elkins: So before I turn to a question and answer, I just want to thank our teams around the world for delivering these remarkable results in 2021. These results and our guidance for 2022 demonstrate the financial strength of the business and the renewal of our portfolio, which positions us well for long-term growth. I'll now turn the call back over to Tim and Giovanni for Q&A. David Allen, could we go to our first question, please? [inaudible] Certainly, sir. We'll go first to Seamus Fernandez with Guggenheim.

These results and our guidance for 2020 to demonstrate the financial strength of the business and the renewal of our portfolio, which positions us well for long term growth.

I'll now turn the call back over to Tim and Giovanni for Q&A.

Thanks, David Allen can we go to our first question. Please.

Certainly Sir well go first to Seamus Fernandez with Guggenheim.

Oh, thanks, so much for the question.

Samit Hirawat: Oh, thanks so much for the questions. Um, so, uh, the first question is just on your factor 11. I just wanted to, um, check in on timing of a potential update from your phase two study and just wanted to get a sense of where your expectations are, as we've spoken with thought leaders in the space. The hope is that the increase in the dose or the stepped-up dose would result in no bleeding increase but with roughly a 15 to potentially 20% benefit on stroke.

Our first question is just on your factor 11, I just wanted to.

Check in on timing of a potential update from your from your Phase III study.

And just wanted to get a sense of where your expectations are as we spoken with thought leaders in the space.

Samit Hirawat: How does that sort of put you guys in the expectations, and can you guys help us understand a little bit better the opportunity to open up this potentially new market and how you see the size of the opportunity should that profile be achieved, and do you agree with those views? And then, secondly, just on your own that we just had the filing of the site of kinetics competitor compound. You just talk a little bit about the competitive landscape as you think about the opportunity. You know, form out of camp and versus other competitor compounds. Thanks so much. Thank you, Seamus. This is Samit.

The hope is that the increase in the in the dosing or the or the stepped up dosing would result in no bleeding increase but with roughly a 15 to potentially 20% benefit on stroke, how does that sort of foot with your expectations and can you guys help us understand a little bit better.

The opportunity.

Two to open up.

It's potentially new market and how you see the size of the opportunity should that profile be achieved and do you agree with with those those views.

And then second just on.

Your your debt that we just had the filing of the cider kinetics competitor compound can you just talk a little bit about the competitive landscape as you think about the opportunity.

Format of Camden versus other competitor compound. Thanks, so much.

Thank you Shannon this is summit.

Samit Hirawat: I'll take both of those questions. So for Factor XI-A, as we have talked about, the second Phase II study, which is in secondary stroke prevention, we expect to have the data in-house around the middle of the year. And at the appropriate conference, we will be able to share that data beyond that. And we are continuing to work with our partners, Jensen, to really execute on the future development of Melvixian. As for your question related to what the data would show and what the acceptance and availability would be and applicability would be from a bleed perspective or efficacy perspective, I think we just have to wait to see the data.

I'll take both of those questions. So far factor 11 day as we have talked about the second phase III study, which is in secondary stroke prevention, we expect to have the data in house on the middle of the year and at the appropriate conference, we will be able to share that data beyond that and we're continuing to work with our partners Janssen to really a X.

<unk> on the future development of <unk> as your question related to what the data would show and what the acceptance and availability would be and applicability would be from a lead perspective, what efficacy perspective, I think we just have to wait to see the data.

Samit Hirawat: The primary goal for these studies is to be able to isolate what the impact is on the bleed as we look to combine it with the background therapy of antiplatelet agents, as well as to then progress them further into appropriate indications, either as a single agent or as combinations.

Primary goal for these studies is to be able to isolate what the impact is on the bleed as we look to combine it with the background therapies of adaptive.

Patrick let agents as well as to then progress them further into appropriate indications either as a single agent dose combinations. So we just have to wait for the data, but as we saw in the <unk> study there was no increase in the bleeds, but we certainly saw increase as a dose dependent and it always has been in a matter from the efficacy perspective, so let's wait for the middle of the year.

Samit Hirawat: So we just have to wait for the data. But as we saw in the TKR study, there was no increase in bleeds, but we certainly saw an increase as a dose-dependent, in a dose-dependent manner from the efficacy perspective. So let's wait for the middle of the year to see the data, and then we'll define the future trajectory for the development. Coming on to Maverkampton and the competitor compound, we remain very focused and very confident in the data for Maverkampton.

See the data and then we will define the future trajectory for the development of that.

Coming on to the tomb ever Camden, and the competitor compound we remain very focused and very confident in the data from Maverick Anthony as you know we are launch ready as David spoke earlier for the <unk> date coming up soon and as it relates to then additional data we are waiting for the readout of the valor trial as well and.

Samit Hirawat: As you know, we are launch ready, as David spoke earlier, for the PDUFA date coming up soon. And as it relates to additional data, we are waiting for the readout of the Valor trial as well in the short time frame. Now, of course, we've seen the small amount of data that has been talked about from, I think, 13 patients looking now at a different cohort in combination with disopiramide. Certainly, we, in our EXPLORER trial, have looked at the commonly used background therapies of beta blockers and calcium channel blockers.

The short timeframe.

Now of course, we've seen a small amount of data that has been talked about from I think 13 patients looking now at a different cohort in combination with Disopyramide certainly we in our explorer trial have looked at the commonly used background therapies of beta blockers and calcium channel blockers in the valor trial, we do have pace.

Samit Hirawat: In the VALOR trial, we do have patients who are going to be receiving the background therapy of disopiramide as well. So, we do not see a differentiated profile at this time from a competitor perspective. We certainly are confident that we already have a phase 3 trial that has been submitted and a second phase 3 trial that is going to be read out in the fall. The only thing I would add, Seamus, is just on MAVA. As we've discussed previously, the current standards of care for these patients really aren't focused on targeting the underlying nature of the disease, so we feel good about the competitive environment when we launch. And, as Samit mentioned, we don't see any differentiated competition on the horizon, and certainly based on the public data that we've seen thus far from competitors, it' For more information, visit www. FEMA.gov, Chris, and Ellen, can we go to our next question, please? Certainly, sir. Next, we'll go to Chris Schott with J.P. Morgan. Great, thanks so much.

<unk>, who are either going to be receiving the background therapy of dice with automated as well. So we do not see a differentiated profile at this time from a competitor perspective, we certainly are confident that we already have a phase III trial that has been submitted and the second phase III trial that is going to read out in the short term.

Yes, the only thing I would add Seamus is just on mamba as we've discussed previously the current standards of care for these patients really aren't focused on targeting the underlying nature of the disease. So we feel good about the competitive environment, when we launch and as Amit mentioned, we don't see any differentiated competition on the horizon and certainly based on the public data that we've seen thus far from.

<unk>, it's entirely consistent with what would be expected from a milestone inhibitor and and so we feel very good about the competitive position for this agent and look forward to launching.

Thanks, Chris Allen can we go to our next question. Please.

Certainly Sir next we'll go to Chris Schott with J P. Morgan.

Chris Boerner: Just to follow up on Mavacampton, can you help set some expectations about how we should be thinking about the launch here? I guess this is a product given the current standard of care where there could be kind of a bolus of already identified patients you could go after, or you should be thinking about maybe a more gradual ramp as you need to get, we think about reimbursement and familiarizing physicians with whatever REMS program ends up coming out of this one. And then my second question was just an update on car key capacity.

Hi, great. Thanks, so much just to follow up on Nava Campton can you just help set some expectations about how we should be thinking about the launch here.

This is a product given the current standard of care, where there could be kind of a bolus of already identified patients you could go after or should we be thinking about maybe a more gradual ramp as you to get when you think about reimbursement and familiarizing physicians with whatever Rems program ends up coming out of this one and.

And then my second question was just an update on car T capacity I just walk through a little bit about how you are expecting capacity to ramp as we move through 2022, and I guess when will you be in a position where capacity is not the rate limiting factor for the growth of these products. Thanks, so much.

Chris Boerner: I just walked through a little bit about how you're expecting capacities to ramp up as we move forward. That is, through 2022. And I guess when will you be in a position where capacity is not the right limiting factor for the growth of these products? Thanks so much.

Chris Boerner: Sure, Chris, I'll take both of those questions with respect to Maven and how we think about the shape of the opportunity. I would think about it as more of a gradual opportunity. When we look at the way this launch will likely progress, it's very much going to be in a stepwise fashion. We expect that there will be strong interest in treating the most severe patients, particularly in centers of excellence where these patients are being treated today.

Sure Chris I'll take both of those questions with respect to <unk> and how we think about the shape of the opportunity I would think about it as more of a gradual opportunity. When we look at the way. This launch will likely progress, it's very much going to be in a stepwise fashion. We expect that there will be strong interest in treating the most severe patients, particularly in the centers.

Excellence, where these patients are being treated today, that's going to be the initial focus beyond this will expand our focus to cardiology specialists and then to the broader cardiology community, where uptake is just going to be more gradual and one other thing I would say about as we think about.

Chris Boerner: That's going to be the initial focus. Beyond that, we'll expand our focus to cardiology specialists and then to the broader cardiology community, where uptake is just going to be more gradual. One of the things I would say about, as we think about really all of these segments, we have an educational effort that will be initiated at launch as to how physicians should initiate and treat these patients, and certainly there will be a focused effort to get patients on therapy quickly. But just those efforts, in and of themselves, will take some amount of time.

Really all of these segments, we have an educational effort on that will be initiated at launches to help position should initiate and treat these patients and certainly there will be a focused effort to get patients on therapy quickly, but but just those efforts in and of themselves will will take some amount of time. The good news is we have a very strong team with an established presence in this space we have a very good day.

So we feel very good about the long term potential for the asset.

Chris Boerner: The good news is we have a very strong team with an established presence in the space. We have a very good drug, so we feel very good about this. The long-term potential for the asset

And that step wise approach that I articulated really is in line with the overall opportunity of four plus billion that we see for this asset moving to cell therapy supply constraints.

As we've said previously the supply constraints that we're seeing right now are mainly related to a back.

Chris Boerner: That stepwise approach that I articulated really is in line with the overall opportunity of 4 plus billion that we see for this asset. Moving to cell therapy supply constraints, as we've said previously, the supply constraints that we're seeing right now are mainly related to Beckmont. In our efforts, we are really focused on working with CMOs to accelerate capacity for a vector, and then internally, we're focused on slot capacity. There are a number of things across both of these efforts that we're focused on, including training and qualifying new staff, increasing our operational efficiency, and increasing site capacity. On a Beckmont basis, we would anticipate being in a much better position for supply as we get into the middle of this year.

Our efforts are really focused on working with CMS to accelerate capacity for vector and then internally we're focused on slot capacity and there are a number of things across both of these efforts that we're focused on including training and qualifying new staff increase increasing our operational efficiency and increasing site capacity on our back.

We would anticipate being in a much better position for supply as we get into the middle of this year.

Then as it relates to <unk>.

Honestly, the big focus areas on vector supply and something that we've continued to stay focused on.

We fully expect to be in a position to support.

Demand as we get later into this year and certainly by the time that we would have any label expansions for that product.

Thanks, Chris.

Chris Boerner: And then as it relates to Breonzi, the big focus there is on vector supply. It's something we continue to stay focused on, and we fully expect to be in a position to support demand as we get later into this year and certainly by the time that we have any label expansions for that product. Chris, can we go to our next question, please? Sir, next we'll go to Geoff Meacham with Bank of America. Morning, guys.

Can we go to our next question please.

Yes, Sir next we'll go to Geoff Meacham with Bank of America.

Good morning, guys. Thanks for taking my question.

Chris Boerner: Thanks for taking the question. For some of the new launches, are there any metrics you guys can provide that show the wins and access and reimbursement, mostly talking about self-therapy? and Zapposia.

For some of the new launches are there any metrics you guys can provide that show the wins in access and reimbursement, mostly you're talking about cell therapies and and as opposed to you. The bigger picture is just trying to assess.

Chris Boerner: The bigger picture is just trying to assess the tipping point for this year, potentially, for the launches collectively versus what we saw last year, which was a lot of lumpiness on a kind of sequential basis. And then the second question, real quick on Ducravacitinib, I know there's been a lot of angst about the potential for differentiating labels versus Jax and just wanted, now that we have clarity on the latter, just wanted to get maybe an updated view from you guys on that. Thank you. Sure, maybe I'll start.

No.

The tipping point for this year potentially for the launches collectively you know versus what we saw last year, which was a lot of lumpiness.

Kind of a sequential basis.

And then the second question real quick on <unk> sitting there, but I know there's been a lot of angst about the potential for a differentiated label versus Jackson. Just wanted now that now that we have clarity on the ladder just wanted to get maybe an updated view from you guys.

On that thank you.

Sure maybe I'll start.

Chris Boerner: Geoff, thanks for the question. So as we look at access really across all of these launches, we feel very good about where we are from an access standpoint. I'll start with cell therapy. Cell therapy, actually, I think is a very, very good story.

Jeff Thanks for the question. So as we look at access really across all of these launches we feel very good about where we are from an access standpoint, I'll start with cell therapy cell therapy actually I think is a very very good story, we have seen no issues with respect to access constraints for our cell therapy launches.

We've discussed the supply constraints, but the launches have gone off really without a hitch from a supply from a access standpoint and in fact, if you look at the class of agents more generally if you go back a couple of years as you well know.

Chris Boerner: We have seen no issues with respect to access constraints for our cell therapy launches. You know, we've discussed the supply constraints, but the launches have gone off really without a hitch from a supply and access standpoint. And in fact, if you look at the class of agents more generally, if you go back a couple of years, as you well know, access and reimbursement were significant areas of concern. And I would say, largely for the class of agents, we've been trending in the right direction. But we see no issues with our cell therapy assets.

Access and reimbursement were significant areas of concerns and I would say largely for.

For the class of agents, we've been trending in the right direction, but we see no issues on our cell therapy assets as we switch gears and you'd mentioned as oppose yet obviously the focus is on UC, but very quickly on the MFS feel very good about the access position there we have very broad coverage in MFS.

Chris Boerner: As we switch gears, and you mentioned Zeposia, obviously, the focus is on UC, but very quickly on MS, I feel very good about the access position there. We have very broad coverage in MS, so really not a significant concern on the MS side. In UC, we've been very clear that we have to make a diligent effort around access over the course of this year.

So really not a not a significant concern on the EMS side and you see we've we've been very clear that we have to execute a diligent effort around access over the course of this year, what I can say coming into 2022 is we have very broad formulary coverage for as oppose yet.

Chris Boerner: What I can say coming into 2022 is that we have very broad formulary coverage for Zeposia. Now, how restrictive that formulary coverage is varies by plan, and for the course of this year, for those patients with less restricted access, the focus is going to be on converting those patients from starter or bridge programs to commercial drugs and doing so very quickly. For patients with more restricted access, which, unsurprisingly, for our first full year in the market, most patients have multiple step edits, the focus is going to be on working through those restrictions, and that's going to take more time.

How restrictive that formulary coverage is varies by plan and for the person for the course of this year for those patients with less restricted access the focus is going to be on converting those patients from starter or bridge programs to commercial drug and do so very quickly for patients with more restricted access which unsurprisingly for our <unk>.

First full year in the market most patients have multiple step that adds the focus is going to be on working through those restrictions and that's going to take more time, what I can say, though in any case is that on suppose you were continuing to build volume over the course of this year. The plan has been and continues to be to then leverage that volume to move symposia into an earlier access position.

Chris Boerner: What I can say, though, in any case, is that on Zaposia, we're continuing to build volume over the course of this year, and the plan has been and continues to be to then leverage that volume to move Zaposia into an earlier access position as we head into 2023, and we're very much on track to do that. And Geoff, I'll take on the question around Ducrella-Citrinib. So let me start by saying that we're obviously not going to speculate on the label for what we'll see, but we certainly remain very confident in the efficacy and the safety profile that we've talked about before. And we are looking forward to the PDUFA date in September. Thanks so much.

As we head into 2023, and we're very much on track to do that.

And Jeff I'll take on the question around do Carlos it in them. So let me start by saying that we are obviously not going to speculate on the label.

But what we will see but we certainly remain very confident in the efficacy and the safety profile that we've talked about before and we're looking forward to the <unk> date in September .

Thanks, Amit Alan can we go to our next question. Please.

Operator: Alan, can we go to our next question, please? Thank you, sir. Next, we'll go to Steve Scala with Cali. Thank you. I have a couple questions. Updevo was a bit weak in Q4, similar to what we've seen from some of your competitors. However, diagnoses still appear to be pressured despite fewer COVID-related shutdowns. Are there any other reasons for the weak oncology numbers? And what is the outlook for recovery? So that's the first question. The second question is for Samit. Samit, do you or anyone else at Bristol know the total number of stroke and bleeding events in the Milvexian Stroke Study to date? So both arms combined, not just each one.

Yes, Sir next we'll go to Steve Scala with Cowen.

Thank you I have a couple of questions Opdivo was a bit weak in Q4 similar to what we've seen from some of your competitors diagnoses still appear to be pressured despite fewer COVID-19 related shutdowns are there any other reasons for week oncology numbers.

And what is the outlook for recovery. So that's the first question. The second question is for summit.

Summit do you or anyone else at Bristol No. The total number of stroke and bleeding events in the no vaccine stroke study to date. So both arms combined not each one and if yes, how are those total stroke and bleeding events trending to what you expected. Thank you.

Maybe I'll start Steve.

Chris Boerner: And if yes, how are those total stroke and bleeding events trending to what you expected? Thank you. Maybe I'll start, Steve. With respect to, let me just say at the outset, with respect to Obdivo. As David and Giovanni mentioned, we saw a return to growth for Obdivo and actually saw an acceleration in growth in the latter half of the year. As it relates to COVID, we have generally seen some improvement in a number of markets. But, as you would imagine, the situation remains quite dynamic.

With respect to let me just say at the outset with respect to Opdivo, we're actually very happy with the performance we saw for Opdivo in the quarter as David and Giovanni mentioned, we saw a return to growth for Opdivo and actually saw an acceleration of opdivo.

In the latter half of the year as it relates to Covid, we have generally seen some improvement in a number of markets, but as you would imagine the situation remains quite.

Dramatic dynamic.

As it relates to Io, specifically new patient volume.

Chris Boerner: As it relates to IOs specifically, new patient volume has been gradually recovering, though I would say we're, where we sit today, we're roughly 5% to 10% below pre-COVID levels in terms of patient volume. There's just a considerable amount of variability across tumor types, as well as in academic versus community. But on net, it's about 5% to 10% below where we were pre-COVID.

<unk> been gradually recovering, though I would say.

Where we sit today, we're roughly 5% to 10% below pre COVID-19 levels in terms of patient volume.

Theres, just a considerable amount of variability across tumor types as well as in academic versus community on net it's about 5% to 10% below where we were pre COVID-19 . Our hope in terms of the outlook is that we will continue to see an improvement over the course of the year.

Chris Boerner: Our hope in terms of the outlook is that we'll continue to see improvement over the course of the year. If the pandemic has taught us anything, it's that we're going to have to continue to be flexible and agile. What I can say definitively is that the impact will likely vary by product and market. From our standpoint, I think we've shown our businesses are resilient and our ability to grow really through the pandemic. And I think we've demonstrated an ability to execute. But, sort of, if you level it up, it's still a dynamic situation and one we'll watch carefully.

As the pandemic has taught us anything it's that we're gonna have to continue to be flexible and agile what I can say definitively is that the impact will likely vary by product and market.

From our standpoint, I think we've we've shown our business is resilient and our ability to grow really through the pandemic and I think we've demonstrated an ability to execute but but sort of if you level. It up it's still a dynamic situation and we'll watch carefully.

Samit Hirawat: And on the Melvixian trial, Steve, the study is ongoing, and we will not be talking about data, whether it's a pooled analysis or unblinded. We'll just have to wait for the data, and as I said earlier, we'll be presenting the data at the appropriate time. So Alan, can we go to our next question, please? Next we'll go to Chris Shibutani with Goldman Sachs.

And on the <unk> trial, Steve of the study is ongoing and we will not be talking about data, whether it's a pooled analysis or unblinded.

Have to wait for the data and as I said earlier, we will be presenting the data at the appropriate conference really looking forward to it though.

Thank you.

Thanks, so much so how long can we go to our next question. Please.

Yes, Sir next we'll go to Christopher <unk> with Goldman Sachs.

Thank you if I could ask a question about the immuno oncology franchise, making more medium to longer term couple of dynamics that are happening. One I think we have a producer coming up in March for the lag three combination ticks down anything.

Chris Boerner: Thank you. If I could ask a question about the immuno-oncology franchise, maybe more in the medium to longer term. There are a couple of dynamics that are happening. One, I think we have a PDUFA coming up in March for the LAG-3 combination fixed dose. Anything that you could share in terms of how you're thinking about positioning this so that you have success commercially, given the anticipation for competition, not just from other players but also from other regimens like TGIT? Could you also comment on a combination of data from BEMPEG plus Opdivo, which I believe could be in the second quarter timeframe? The economics are distinct there.

Anything that you could share in terms of how you're thinking about positioning. This so that you have success commercially given the anticipation for competition not just from other players, but also from other regimens like T. J could you also comment with a combination of data from them Peg plus opdivo, which I believe could be in the second quarter.

[noise] timeframe. The economics are distinct there however, help us at all with progress and timelines that would be appreciated and then finally on the Io, we see potential for the entry of lower cost checkpoint inhibitors PD. One can you share with US your initial thoughts at this stage about how you see that influencing the market dynamics for check.

Chris Boerner: However, if you could help us at all with progress and timelines, that would be appreciated. And then finally, on the I.O., we see potential for the entry of lower-cost checkpoint inhibitors, PD-1s. Can you share with us your initial thoughts at this stage about how you see that affecting the market dynamics for checkpoint inhibitors and PD-1s? Thank you. Thank you. Sure, maybe I'll start, and I'll answer your first and third question.

<unk> inhibitors in IL. Thank you.

Sure, maybe I'll start and I'll hit your first and third question.

Chris Boerner: We're very pleased with the opportunity to potentially launch RELATLAMIB. As we've said, if you look at the first line metastatic melanoma market, it's really divided into thirds. You've got a third of patients who are treated with Dual IO, that is, Optivo plus Urovoid. That's a very strong position given the sustained OS benefit that we have with that population. You have about a third of patients who are treated with IO monotherapy, roughly split between Optivo and Keytruda 5050, and then you have a third of the market which is really focused on targeted therapies. We see the opportunity for RELATLAMIB to really go after that third of the market, which is single agent PD-1 therapy. We think that the data are very compelling relative to that population.

Pleased with the opportunity to potentially launch rollout.

As we've said if you look at the first line metastatic melanoma market, it's really divided into thirds, you've got a third of patients who are treated with dual I O. That's opdivo plus you avoid that has a very strong position given the sustained OS benefit that we have with that population you have about a third of patients who are treated with <unk>.

I L mono therapy roughly split between.

Opdivo and Keytruda 50 50.

And.

And then you have a third of the market, which is really focused on targeted therapies, we see the opportunity for <unk>.

To really go after that third of the market, which is a single agent PD. One therapy, we think that the data are very compelling relative to that population remember that rollout limit is two products in one vial and so we think the opportunity to offer those patients dual I O therapy.

Chris Boerner: Remember that RELATLAMIB is two products in one vial, and so we think the opportunity to offer those patients Dual IO therapy in a fixed dose combination offers a significant improvement over single agent monotherapy, and that's going to be the initial focus at launch. As it relates to your question on low-cost entries of PD-1 agents, we don't see a significant threat to our business in the near-to-medium term from In larger markets like the U.S., evidence continues to be the most important dimension of choice.

In a fixed dose combination offers a significant improvement over over single agent monotherapy and that's going to be the initial focus at launch as it relates to your question on <unk>.

Low cost entries of PD, one agents, we don't see a significant threat to our business in the near to medium term from these products.

In our larger markets like the U S.

Evidence continues to be the most important dimension of choice physicians want to see data in a specific tumor and patient type.

Chris Boerner: Physicians want to see data on a specific tumor and patient type, and so there may be markets where these sort of low-cost me-too drugs are able to piggyback on innovation and drive use, but those historically have not been our larger markets. Obviously, things can evolve, and we'll continue to monitor and adjust as necessary, but I think, as a sort of finer point on it, we shouldn't underestimate the barriers to sort of broad-based commoditization in oncology, particularly for a product like Opdivo given the breadth of our data and indications.

And so there may be markets, where these sort of low cost me two drugs are able to piggyback on innovation and drive us, but those historically have not been our larger markets, obviously things can evolve and we'll continue to monitor and adjust as necessary, but I think as a sort of put a finer point on it we shouldnt underestimate the barriers to sort of <unk>.

<unk> based commoditization oncology, particularly for our potash product like Opdivo, given the breadth of our data and indications.

Chris Boerner: And Chris, on the BEMPEC side, just as a reminder, there are three readouts that we anticipate this year, one in melanoma, one in renal cancer, and one in bladder cancer. The first study, as you very well pointed out, is in melanoma.

And Chris on the <unk> side, just as a reminder, there are three readouts that we anticipate this year, one in melanoma and renal cancer and one in bladder cancer. The first prophage as you very well pointed out is in melanoma, we are anticipating the data within the first half of this year.

Samit Hirawat: We are anticipating data within the first half. With that said, we are certainly very pleased to have three I.O. mechanisms already, as in PD-1, as well as CTLA-4, and then anticipating the PDUFA and launch for ELATLIMAB, as you also mentioned earlier, and we are looking forward to continuing work with NECTAR in progressing the program as the data So Ellen, can we go to the next question, please? Next we'll go to Tim Anderson with Wolf Research. Hi, thanks for taking the question. This is Adam on behalf of Tim.

But that said we are certainly very pleased to have three io mechanisms already.

PD, one as well as <unk> four and then anticipating the Purdue planned launch for laterally map as you also mentioned earlier and we're looking forward to continuing work with Nektar and progressing the program as the data continues to evolve.

Thanks, a lot Alan can we go to the next question. Please.

Next we'll go to Tim Anderson with Wolfe Research.

Hi, Thanks.

This is Adam on behalf of Tim.

Chris Boerner: On Mavikanton, you've described this as being a $4 billion plus product by 2029. It seems that there are two main drivers of this, one of which is that the forecast assumes a tripling of diagnosis rates for OHCM going from about 25% today to 75% in the future. And the second is a mention of NHCM and other indications. My question is twofold.

Now they can't then you've described this as being a $4 billion plus product by 2029.

Seems that there are two main drivers of this one of.

Which is that the forecast assumes a tripling of diagnosis rates for <unk> going from about 25% today to 75% in the future.

And the second as I mentioned of NH cm and other indications.

Chris Boerner: How realistic is it to expect a tripling of diagnosis rates? And second, what portion of the $4 billion is due to NHCM and other indications that you have not talked about as much? Separately, can we assume that an FDA advisory committee meeting is unlikely with this drug before approval happens? Thanks. Sure, maybe I'll take both of those questions, or at least the first two questions.

Western is twofold, how realistic is it to expect a tripling of diagnosis rates and second what portion of the $4 billion is due to an HCM and other indications that you have not talked about as much.

Secondly, can we assume that an FDA Advisory Committee meeting is unlikely with district before approval happens. Thanks.

Sure maybe I'll I'll tee.

Take both of those questions in there or at least the first two questions.

Chris Boerner: So Adam, with respect to how we've thought about MAPA, first of all, this is a market where we see a fairly well-defined patient population. There are about 80,000 to 100,000 patients in the U.S., and roughly a comparable number outside the U.S. We see significant unmet need for this patient population, and the initial focus at launch is going to be focused on treating those patients who are symptomatic, diagnosed, and where there's a real urgency to treat.

So Adam with respect to how we thought about now but first of all.

This is a this is a market where we see a fairly well defined patient population. There are about 80 to 100000 patients in the U S and a roughly a comparable number ex U S. We see significant unmet need for this patient population and the initial focus at launch is going to be focused on treating those patients who were symptomatic diagnosed and where there is a real urgency to treat and what we.

Chris Boerner: Now, what we have said is that, over the longer term, with obstructive HCM, the focus will be on increasing the diagnosis rate. What we have said is that we plan on, or we think it's feasible to double that diagnosis rate. It is currently, as you note, about 25 percent, and we think with significant effort, which we certainly have the skill set in the field to do, we can double that over time.

<unk> said is that over the longer term with obstructive HCM the focus will be on increasing the diagnosis rate. What we have said is that we plan on where we think it's feasible to double that diagnosis rate. It is currently as you know about 25% and we think with significant efforts, which we certainly have the.

Skill set in the field to do we think we can double that over time. So that's how we're looking at it in terms of the overall opportunity. The majority of the opportunity that we see as an obstructive disease, but certainly we are looking forward to potentially seeing data in non obstructive as well, yes and on the AD Comm question.

Chris Boerner: So that's how we're looking at it. In terms of the overall opportunity, the majority of the opportunity that we see is in obstructive disease, but certainly we are looking forward to potentially seeing data in non-obstructive. Yeah, and on the adcom question, we have not been notified of any potential adcom. We do believe in the strong profile of Mavacampton and the benefit it provides in patients that we have enrolled in clinical trials for obstructive hypertrophic cardiomyopathy. And we're now looking to launch, as you know, in April of 2022 as Alan, could we go to our next question, please? Next, we'll go to Andrew Baum with Citi.

We have not been notified of a potential outcome. We do believe in the strong profile of Maverick Camden and benefits. It provides innovations that we have enrolled in clinical trials, but obstructive hypertrophic cardiomyopathy and we're now looking to launch as you know.

In April of 2022, as Chris said.

Thanks Summit, how long can we go to our next question. Please.

Yes, Sir next we'll go to Andrew Baum with Citi.

Thank you couple of questions on no vaccine I'm mindful the dose dependent interaction of aspirin with.

Samit Hirawat: Thank you. I have a couple of questions. So first on Norvexian, I'm mindful of the dose-dependent interaction of aspirin with Plavix. You have a number of trials ongoing and completed looking at potential drug interactions with Norvexian. Perhaps you could comment on the level of reassurance in terms of either interaction with antiplatelets or commonly administered drugs in this patient population. And then, second, you've already highlighted the Q1 inflation in 2021 for Eliquis. Perhaps you could talk more generally about the trends, particularly for U.S. Eliquis growth for 2022.

You have a number of trials ongoing and completed.

The tenant for drop interactions were no vaccine, perhaps you could comment on that and the reassurance in terms of either interaction rocky platelets or commonly administered drugs in this patient population and then second.

Woody highlighted the Q1 inflation in 2021 .

Samit Hirawat: I seem to remember that you've been excluded from one of the big three formularies. I'm assuming that pricing will offset volume, but if you could talk about whether we expect to be slowing, that would be helpful. So I will start off, Andrew.

Illiquid.

Perhaps you could talk more generally to the trends, particularly the U S liquids growth.

2022.

I seem to remember that.

And you've been excluded from one of the big three formularies I'm, assuming that pricing will offset volume, but if you could talk to whether we expect to be slightly and that would be helpful.

So I will start off Andrew Thank you for your questions and for <unk>. As you know that we have first of all the study ongoing already with anti platelet agents and the SSP. So we've got to see that data when that reads out in terms of the other drug drug interaction studies that is part and parcel of the usual clinical pharmacology package that we put.

Samit Hirawat: Thank you for your questions. And for Melvixian, as you know, we have, first of all, the study ongoing already with antiplatelet. In terms of the other drug-drug interaction studies, that is part and parcel of the usual clinical pharmacology package that we prepare in anticipation of future filings in an NDA. At this time, we do not see any major impact or anything major in terms of DDS. On the Eloquist questions, first of all, we're very happy with the performance that we saw with Eloquist, obviously, coming out of the fourth quarter. And for this year, we expect continued strong growth for Eloquist. Eloquist is likely going to be the key driver of the overall OAC market.

Bear in anticipation of future filings and the NDA at the current time, we do not see any major impact or anything major in terms of VDI.

Chris Boerner: We're seeing a nice delta in share between our new-to-brand share and total brand share, which is roughly around 7% now. That gives us confidence in the near-term growth trajectory. And we really do expect to see Eloquist in BRX and TRX share grow this year, both at the expense of Warfarin and Xarelto. As it relates to the zinc situation, we see no meaningful impact on revenue.

Yeah on the <unk> questions first of all we're very happy with the performance that we saw with eloquence, obviously coming out of the fourth quarter and this year. We expect continued strong growth for <unk> <unk> is going to likely going to be the key driver of over of the overall <unk> market, we're seeing a nice delta in share between our new to brand share.

In total brand share, which is roughly around 7% now that gives us confidence in the near term growth trajectory and we really do expect to see <unk> N V. Rx in Trs share grow this year, both at the expense of warfarin and Sorel toe as it relates to the zinc situation, we see no meaningful impact on revenue and there are few things too.

Chris Boerner: There are a few things to consider here. First, it's a relatively small part of our overall business. You certainly won't lose all of the volume.

Consider here first it's a relatively small part of our overall business.

You certainly won't lose all of the volume what we know in this space is that there is significant risk for nonmedical switching of patients who are on <unk>.

We know also that downstream accounts in light of that many of them will not adhere to the.

Chris Boerner: What we know in this space is that there's a significant risk for non-medical switching of patients who are on Eloquist. We also know that downstream accounts, in light of that, many of them will not adhere to the change that's been proposed at a macro level. And so we're actually very confident that the impact of revenue will be non-material, if any. And the last thing I would say, just related to that situation, is we've said consistently that we're going to continue to be disciplined on growth in NETs and how we manage those. And this is part of that story.

The change that's been proposed at a macro level and so so we're actually very confident that the impact of revenue will be non material if any.

And then the last thing I would say just related to that situation. As we've said consistently that we're going to continue to be disciplined on gross to nets in how we manage those and this is part of that story.

Thanks, Chris Allen could go to the next question. Please.

Yes, Sir next we'll go to Ronny Gal with Bernstein.

Chris Boerner: Chris, Alan, can we go to the next question please? Next we'll go to Ronnie Gall with Bernstein. Good morning, and thank you for taking my questions. First, just following up on Andrew's question, can you talk a little bit about a benefit from the 340 switch, especially from Eloquist? It seems that the net price of Eloquist and 340B was close to nothing.

Chris Boerner: And given the volume estimate that we're seeing, it should be a pretty good benefit for them this year. Can you talk about that? And second, Aurentia, it seems to be growing together with the RA market. It seems to be in a position to grow better, given the JAK inhibitors safety issues. Can you talk a little bit about what you're seeing and your projection for 2022? Schoer, let me, Geoff, what do you want to start? [inaudible] Go ahead, Chris.

Good morning, and thank you for taking my question.

First just following up on Andrew's question can you talk a little bit about the benefit from $3 40 switch, especially from adequate.

Two the net price is adequate and safe would you be able to close to nothing and given the volume estimate that we are saying it should be a pretty good benefit for them. This year can you talk about that and second of all rents, yes. It seems to be growing together with the market. It seems to be in position to grow better given the JAK inhibitors safety issues can you talk a little bit about.

What are you seeing and what you're projecting for 2022.

Sure sure let me.

Giovanni you wont start.

Go ahead, Chris.

Chris Boerner: Sure. So on 340B, let me just say at a macro level that we remain committed to ensuring the eligibility of patients for 340B, those patients who can directly benefit from the program. And I would say, there's really no change in our stance with respect to 340B as it relates to the program. We're committed to it, and we're committed to patients maintaining access to our medicine. The change that we announced really was reflective of two things.

Sure. So on 340 <unk>, let me just say at a macro level, we remain committed to ensuring the eligibility of patients for 340 B.

Those patients who can directly benefit from the program and and what I would say theres really no change in our stance with respect to 340 b as it relates to the program. We're committed to it and we were committed to patients maintaining access to our medicine. The change that we announced really was reflective of two things first BMS and celgene having different policies.

Chris Boerner: First, BMS and Celgene have different policies around the recognition of contract pharmacies and needing to align those as part of integration. And second, wanting to ensure that the 340B discounts that we pay are valid and appropriate, and we feel this change in policy allows us to do that. And so that's really been the focus of how we think about the 340B program. And then, do you mind repeating your second question again? It would be great if you could quantify the 340B impact.

The recognition of contract pharmacies and needing to align those as part of integration and then second wanting to ensure that.

The $3 40 would be discounts that we pay are valid and appropriate and we feel this change in policy.

It allows us to do that and so that's really been the focus for <unk>.

For how we think about the 340 B program.

And then do you mind repeating your second question again.

It was a great. If you can quantify hello, okay. It will be great. If you didn't quantify the 340 being back and the second question was around <unk> trends and the potential to benefit from the JAK inhibitors are black box label.

Chris Boerner: And the second question was around Orencia trends and the potential for benefit from the JAK inhibitors, Black Box. Sure, we're not going to comment on any impact of 340B. Again, I think we've given the rationale for having made that change. As it relates to Aurensia, look, Aurensia continues to perform well in the RA market. The way we've thought about any potential change from a label update on Jack, as it relates to Aurensia, or frankly, any of our products, is that those changes will likely continue to push Jacks into later lines of therapy, as labels are updated and their position continues to evolve.

Sure, we're not going to comment on any impact of 340, <unk> again, I think we've given the rationale for having made that change.

As it relates to <unk> look as <unk> continues to perform well in the in the or a market.

The way, we've thought about any potential change from a label update on Jack as it relates to rent or frankly any of our products is that those changes will likely continue to push jacks into later lines of therapy as they are.

Chris Boerner: So we think there's potentially an opportunity. That said, I think our focus on really all of our products continues to execute against the strategy that we have for those assets to continue to compete effectively in those markets. And obviously, we'll allow the situation with Jacks to evolve as they do.

Labels are updated and.

Their position continues to evolve. So we think there is potentially opportunity that said I think our focus on really all of our products continues to execute against the strategy that we have for those assets to continue to compete effectively in those markets and <unk>.

And obviously, we will allow the the situation with JAKKS to evolve as they do.

We go to our next question please.

Operator: Can we go to our next question, please? Certainly. Next, we'll go to Luisa Hector with Barenberg.

Certainly next we'll go to Luisa Hector with Bahrenburg.

Hello, and thank you for taking my question.

David Elkins: Hello, thank you for taking my question. I just wanted to discuss a little bit more about the 22 outlook and the impact of Revlimid. So I just wondered if there are any particular risks you would highlight around the delivery of your sales target, just anything of note.

Just wanted to discuss a little bit more on the 'twenty outlook.

And the impact.

I just wanted to get there any particular risks you would highlight around the delivery of your sales targets.

Just anything of note.

Yes.

I guess really comes on the pace of the rapid maturation is it's pretty predictable.

Just checking on a level.

Okay.

And then specifically around how you are adapting to.

David Elkins: And I guess really to confirm that the pace of the Revlimid erosion is pretty predictable. So just checking on levels of uncertainty and then specifically around how you are adapting. Revlimid generic entry in terms of your cost base, any color around that given that you have the ongoing presence of multiple myeloma, so just trying to understand kind of the cost side of it. Thank you. Thanks for the question, Lisa. As we think about Revlimid, we thought it was important this year, number one, to provide guidance for the full year. And secondly, we thought it was really important to provide guidance for the quarter. And I'd say one thing is that these are, the contracts are annual volume limitations.

Revlimid generic entry in terms of your cost base any color around that given that you have the ongoing presence in multiple myeloma. So just trying to understand kind of the cost side.

Thank you.

David Elkins: So as generics enter the market, there could be quarter to quarter variability based upon how quickly the product makes it to the marketplace. So that's why we thought it was important to provide that. The first generic entry is occurring in March, so there could be variability between the first and second quarters. And then the remainder of the generics will come usually about 180 days later. It is pretty typical in a generic entry scenario. So that would be in the September timeframe.

Yeah. Thanks for the question listen.

We think about Revlimid, we thought it was important this year number one to provide guidance on the full year.

And secondly, we thought it was really important.

To provide guidance on the quarter and I'd say one thing is that.

The contracts are annual volume limitations, so as the generic center.

There could be quarter to quarter variability based upon how quickly the product makes it to the marketplace.

So that's why we felt it was important to provide that the first generic entry is occurring in March so there's could be variability between the first and second quarter and then the rest of the remainder of the generics will come usually about 180 days later, it's pretty typical in a generic entry scenario. So that'd be in the September timeframe, but for the full year, we feel.

David Elkins: But for the full year, we feel very confident in the guidance that we provided for the full year as it relates to Revlimid. As far as the expense space is concerned, I mean, this is a really fortunate thing for us in the standpoint that, if you think about the nine products that we're bringing to the marketplace, the six that are on the market, and the three that we're launching this year, we're able to move resources within our therapeutic areas and reallocate resources to the launch brands.

Very confident.

The guidance that we provided for the full year as it relates to Revlimid.

As far as the expense base is concerned I mean, this is really fortunate thing for us in the standpoint of if you think about the nine products that we're bringing to the marketplace. The six that are on the market and the three that we're launching this year, we're able to move resources within our therapeutic areas and reallocate the resources to launch brands. So as you think about our hematology sales force.

David Elkins: So as you think about our hematology sales force, you know, being able to move those resources out of Revlimid and into cell therapy with Briandia and Becma, we're able to use existing resources to support those launch brands and maintain our call space where we are. So, you know, and that's why we provide the guidance on operating expenses as we did.

Being able to move those resources out of out of Revlimid and into like cell therapy with the <unk>, we're able to use existing resources to support those launch brands and maintain our cost base, where we are so.

That's why we provided the guidance on operating expenses as we did.

Giovanni Caforio: Luisa, this is Giovanni. Let me just make another comment there. You mentioned our level of confidence, David referenced Revlimid, and let me just say this is an important year for us because, obviously, it's the first year in which there will be generics of Revlimid and what I'm really pleased about is the fact that we've got strong momentum with inline. We are making great progress with the launch plans that are already on We are looking forward to three important approvals, and this year, as you know, we've guided to growth both in terms of our revenue base and also in terms of earnings per share.

Louis This is Giovanni let me just make another comment there you mentioned about our level of confidence David David referenced Revlimid. Let me just say this is an important year for us because obviously.

It's the first year in which there will be generic silverado.

I'm really pleased up.

Fact that we've got strong momentum with in line business.

We are making great progress with the launch brands that are already on the market.

We are.

Looking forward to three important approvals and D. C are as you know we've guided to growth both in terms of our revenue base, but also in terms of earnings per share. So I think thats a clear.

Giovanni Caforio: So I think that's a clear demonstration that we are confident in the ability to grow through the loss of exclusivity of Revlimid this year and over the next few years just because of the strength and resilience of the underlying business and the fact that we are accelerating the transition of our portfolio to new brands. Thanks, Giovanni.

Demonstration that we are confident in the.

The ability to grow through the loss of exclusivity of traveling in this year and over the next.

A few years, just because of the strength and resilience of the underlying business and the fact that we are accelerating.

Transition of our portfolio through new brands.

Thanks, Giovanni how long could we go to the next question. Please.

Operator: Alan, could we go to the next question please? Yes sir, next we'll go to Evan Seigerman with BMI. Hey guys, thank you so much for taking my question. I'd like to dive a little bit more into the investigational cell mods. Understanding Revlimid, you know, going generic, what do you need to show with these clinical trials to help maybe replace Revlimid and Pomalid in the treatment landscape? And kind of how do you think about progressing those in clinical trials, understanding that you have the standard of care with your current assets? Thank you. Sure.

Yes, Sir next we'll go to Evan <unk> with BMO.

Hey, guys. Thank you so much for taking my question I'd like to dive a little bit more on the investigational cell mod understanding revlimid going generic what do you need to show with these clinical trials to help maybe replace Revlimid <unk> and.

The treatment landscape and kind of how do you think about progressing those in clinical trials understanding that you have the standard of care.

With your current assets. Thank you.

Sure. Thank you Evan for the question from a cell Mod perspective, the way we are thinking about development and as we continue forward we've generated the data in the late lines looking at the combination of fiber at about plus dexamethasone and Cc 480, plus dexamethasone and we have early data and triplets as well looking at.

Samit Hirawat: Thank you, Evan, for the question. From a CellMod perspective, the way we are thinking about development and as we continue forward, we've generated data in late lines looking at a combination of ibridomide plus dexamethasone and CC480 plus dexamethasone. And we have early data in triplets as well looking at combinations with Velcade dexamethasone as well as CD38 antibodies and dexamethasone, et cetera. As you will see later this year, we are initiating a phase three trial of ibridomide plus Velcade plus dexamethasone comparing to, sorry, ibridomide deratumumab dexamethasone compared to dexamethasone as well as Velcade and the CD38 antibody.

<unk>.

Velcade dexamethasone as well as CD 38, antibodies and dexamethasone et cetera. As you will see later this year, we are initiating a phase III trial of <unk>, plus Velcade plus dexamethasone.

Comparing to sorry, I bet my data to Mumbai, dexamethasone, comparing to dexamethasone as well as Medicaid and CD 38 antibody. So that's our first foray into the second line plus patient population for this element. The other trials that you will see in the short while coming up will be the phase III trials of Cc 480 looking to reach.

Samit Hirawat: So that's the first foray into the second line plus patient population for CellMod. The other trials that you will see in the short while coming up will be the phase 3 trials of CC480 looking to replace pomalidomide, and that would be a head-to-head comparison versus pomalidomide and its combination. And in 2023 and beyond, you will see trials of Ibertamide looking into host transplant maintenance, head-to-head comparison versus Revolomit, as well as newly diagnosed patients who are transplant non-eligible to again replace Revolomit in the first line or front setting. Those are the ways we are thinking about as we think about replacement of the current image.

Place formulate it might and that would be a head to head comparison versus pharma that it might combinations and in 2020, I'm, sorry, 2023, and beyond you will see trials, if I britta might looking into the post transplant maintenance head to head comparison versus having them it as well as the newly diagnosed patients who are transplant non eligible to again replace revlimid in.

Chris Boerner: But let me also ask Chris to comment on the commercial perspective. I think you've covered most of it, Samit. It's going to be important, as Samit noted. To generate data that differentiates directly from the image, there's obviously going to be a focus on areas of image need, whether it's renal impairment or look at potentially other populations where images underperform. And then ultimately, from a commercial standpoint, we're going to need to establish a strong value proposition versus generic images. But all of that will be part of the process. Chris, let's go to our next question, please. So next, we'll go to Carter Gould with Mark. Great. Good morning.

The first line or our upfront setting those are the ways. We are thinking about as we think about replacement of the current image, but let me also ask Chris to comment on the commercial perspective, I think you've covered most of it some of it's going to be important as summit noted to generate data that differentiates directly from the image. There is obviously going to be a focus to address areas of it.

The unmet need whether it's renal impairment or look at potentially other populations, where image underperform and then ultimately from a commercial standpoint, we're going to need to establish a strong value proposition versus generic image, but all of that will be part of the plan.

Thanks, Chris Let's go to our next question. Please.

Yes, Sir next we'll go to Carter Gould with Barclays.

Samit Hirawat: Thanks for taking the questions. I wanted to focus a little bit on the GI Immunology Portfolio. You know, last year after the Phase 2 UC data sort of was disappointing, you guys talked about an additional study in UC that's no longer sort of on your slides in terms of catalysts for 22 and 23. Are you, just any additional thoughts on that front now that you think about sort of being able to revisit UC and if we'll be able to get an answer to that question here in 22?

Great. Good morning, Thanks for taking the questions I wanted to focus a little bit on the Gi immunology portfolio.

Last year after the phase two you see data sort of it was disappointing you guys talked about an additional study.

And you see that's no longer sort of on your slides in terms of catalyst for 'twenty three in 'twenty, two and 'twenty three or just any additional thoughts on that front and how you think about sort of being able to revisit you see.

And if we'll be able to get an answer to that question here in 'twenty two and then.

Samit Hirawat: And then maybe a little bit off the radar, Sendakumab, we've seen you sort of expand the development program there and then recently add sort of a Phase 3 study in Japan, so for eosinophilic gastroenteritis. I wanted to see if there were broader plans to run a pivotal study in the U.S. in that indication and maybe how some of the other kind of competitor data in recent history kind of maybe has shaped that viewpoint. Sure. Thanks, Carter. Samit again.

Maybe a little bit.

Off the radar <unk> Mab, we've seen you sort of expand the development program there.

And then recently add sort of a phase III study in Japan. So.

Kinda fill with gastroenteritis I wanted to see if there were broader plans to to run a pivotal study in <unk> in the U S in that indication and maybe how some of the other kind of competitor data in the recent history kind of maybe the shape that that viewpoint. Thank you.

Sure. Thanks Carter to summit again.

Samit Hirawat: For Dukreva-Sidney, UC, as well as Crohn's disease, both of those phase two studies are ongoing. As we said earlier, we do not have a proof of concept based on the first trial that we conducted with Dukreva. But there are two studies that are ongoing, looking at a higher dose in UC in the ongoing study. And when those data are available, we'll certainly be able to analyze them and take that program forward once we have a proof of concept.

For bluegrass.

UC as well as close to these both of those phase II studies are ongoing as we said earlier that we do not have a proof of concept based on the first trial that we conducted that do cover but there are two studies that are ongoing looking at a higher dose.

And you see in the ongoing study in Windows eight out available, we'll certainly be able to analyze those and take that program forward. Once we have a proof of concept. So it is not off the charts, but more about looking to generate the data to make decisions. As we look forward person that came out of the U S study or the global study in Houston Oesophagitis is already.

Samit Hirawat: So it is not off the charts, but more about looking to generate the data to make decisions as we look forward. For Syndacumab, the U.S. study or the global study in eosinophilic esophagitis is already ongoing and enrolling patients as we speak. The Japan part is in addition to that, as you have already noted.

The ongoing and enrolling patients as we speak the Japan part is in addition to do that that's as you have already noted so overall the idea is to get that.

<unk> antibody to iOS 13 into patients with <unk> and look for additional indications as you know that we have a study ongoing in atopic dermatitis is a phase III and that proof of concept can then generate additional indications for further development.

Thanks, Alan we go to our next question. Please.

Samit Hirawat: So overall, the idea is to get that antibody to IL-13 into patients with eosinophilic esophagitis and look for additional indications. As you know, we have a study ongoing in atopic dermatitis as phase two, and that proof of concept can then generate additional indications for further development. Thanks a lot. Can we go to our next question, please, Alan? Yes, sir. Next, we'll go to Matt Phipps with William Blair.

Yes, Sir next we'll go to Matt Phipps with William Blair.

Good morning, Thanks for taking my questions.

Samit Hirawat: Good morning, thanks for taking my questions. You all announced positive transform results in June, a couple weeks before a similar announcement from Yaskarta, yet they have a PDUFA date in April, and we're still kind of waiting to hear the PDUFA date for Beyonce. Are there any risks to meeting a 2022 approval milestone there? And then Samit, you know, three Phase 3's with MTAG coming up this

Our announced private or transform results. Indeed, a couple of weeks before similar to out there from your skirt yet they have a <unk> date in April we're still kind of waiting on that particular day.

Or.

Are there any risks to meeting at 2022 approval milestone there and then summit.

<unk> phase III, but then tag coming up this year do you think those have equal probabilities of success or is there. One indication you think it's more likely based on where high dose IL two has been more effective.

Thanks, Matt for the questions on <unk> as you know we.

Samit Hirawat: Do you think those have equal probabilities of success, or is there one indication you think it's more likely based on where high-dose IL-2 has been more effective? Thanks, Matt, for the questions. On Brianzi, as you know, we don't necessarily declare our filings until we have heard from the FDA from the acceptance perspective. So as time goes by, we will certainly be able to share more in terms of the filing and the PDUFA date, etc., and we are certainly very, very pleased with the data that we have, as well as you know that Brianzi has a large development program, so additional trials are already ongoing in CLL, follicular lymphoma, as well as for additional indications in indolent NHL.

We don't necessarily declare.

Our filings until we have heard from the FDA from the acceptance perspective, so as as time goes we will certainly be able to share more in terms of the filing and the Paducah date etcetera, and we are certainly very very pleased with the data that we have as well as you know that Randy is a large development programs additional trials are already ongoing and <unk> Follicular lymphoma.

As well as as well as for four additional indications and indolent NHL. We are certainly looking forward to launching the second line indication as Chris mentioned earlier during the call in that indication as well in the second line of Bcf for <unk> certainly it is it is data dependent and we are working with <unk> as well to read out these studies.

Samit Hirawat: We are certainly looking forward to launching the second line indication, as Chris mentioned earlier during the call, in that indication as well as in the second line alone. For BEMPEG, certainly, it is data dependent; we are working with NECTAR as well to read out these studies in melanoma as well as in renal cell and bladder cancer. Just as a reminder, these indications were chosen based on those phase 2 data that we had seen early on, but each study stands on its own, and the data will dictate how we proceed further in terms of future development. Can we go to the next question, please? Professor, next we'll go to Matthew Harrison with Morgan Thin. Hi, this is Charlie Ang on behalf of Matthew.

Noma as well as in renal cell and bladder cancer just as a reminder, these indications were chosen based on those phase two data that we had seen early on but each study stand on its own and the data will dictate.

How we proceed further in terms of future development.

When can we go to the next question. Please.

Yes, Sir next we'll go to Matthew Harrison with Morgan Stanley .

Hi.

This is Charlie on for Matthew.

Samit Hirawat: First, on Melvaxian, can you say what amount of incremental bleeding in the stroke prevention study is acceptable clinically? And second, can you provide more details regarding the REMS and what that would look like? So, for example, you know, how often might patients need to be monitored?

First of all no vaccine can you say what amount of incremental bleeding industrial prevention study is sepsis clinical eats and second can you provide more details regarding the rents and what that will look like for example, how frequent my patients need to be monitored.

Samit Hirawat: And lastly, on Abagmay, as you kind of walk through the early lines of therapy, can you talk about the prioritization of these studies versus commercial supply? And I guess, you know, what are the commercial opportunities relative to our current indication? Thank you. Okay, I'll start off. So first of all, for Melvixian, in terms of what amount of bleed is acceptable, look, it is all data-dependent. And certainly, we don't want to see any increase in bleed compared to the control arm. So that's how you have to compare and contrast, and we certainly have historical data from other therapies as well as how patients are treated today. So we'll have to put that into context.

And lastly.

Ah back Mike.

So you kind of walk through the earlier lines of therapy can you talk about in terms of the prioritization of these studies versus commercial supply and I guess no are they accomplish opportunity relative to how current indication. Thank you.

Okay I'll start off.

Samit Hirawat: As we look at the Melvixian program, but there are no numbers that I can share today with you as to how to start looking at or projecting those numbers. From the REMS perspective for Mavacamtin, once again, we are not going to get into specifics, but as we have spoken before, what we are looking forward to is how patients are really managed in the clinic today. We have to go back to what Chris talked about earlier.

So first of all Ford Maldic CN in terms of what amount of lead is acceptable look it is all dependent than and certainly we don't want to see any increase in lead compared to the control arm. So that's how you would have to come.

Compare and contrast, and we certainly have historical data from other therapies as well as our patients are treated today. So we'd have to put that into context as we look at the <unk> program, but there are no numbers that I can share today with you as to.

How to start looking at our <unk>.

Projecting out those numbers from the Rems perspective for Maverick Hampton once again, we're not going to get into specifics, but as we have spoken before.

What we are looking forward to is how patients are really managed in the clinic today, we have to go back to what Chris talked about earlier the basic mechanism of the drug for Maverick Hampton is myosin inhibition and we want to ensure that the patients are treated in a safe way. So that we don't cause the hard to quote unquote relax too much and decrease the ejection fraction and thats the.

Samit Hirawat: The basic mechanism of the drug for Mavacamtin is myosin inhibition, and we want to ensure that the patients are treated in a safe way so that we don't cause the heart to relax too much and decrease the ejection fraction.

Samit Hirawat: That's the intent, and the way the patients are currently managed on a continuous or ongoing basis is through periodic echocardiograms. More to follow on that as we get to the PDUFA date and final approval and the full package of REMS and overall NDA approval. From a BECMA perspective, certainly the continuous progress in looking at the data from CARMA and then CARMA 3 and CARMA 2 proof of concept this year will dictate the further evolution in terms of the overall development program, and studies are going to be as important as commercialization, so certainly from a supply perspective, Chris has spoken before, but certainly I'll ask Chris to comment further on BECMA supplies for clinic as well as commercial. Okay, and The way that we have approached the REMS, obviously, we knew a REMS would be likely with this asset.

We intend in the way the patients are currently managed on a continuous ongoing basis is idiotic echocardiographer. So more to follow on that as we get to the <unk> data and final approval and full package of Rems and overall NDA approval.

Bank My perspective, certainly the continuous progress in looking at the data from <unk>, and then Karma III and Carmike to proof of concept. This year will dictate the further evolution in terms of the overall.

Development program and the studies are going to be as important as commercialization. So certainly from a supply perspective, Chris has spoken before but certainly I'll ask Chris to comment further on our business supplies for clinic as well as commercial sure and maybe I'll just make one comment on the Rems program Charlie the the way that we've approached the rems.

Obviously, we knew <unk> would likely would be likely with this asset we've worked very closely from a commercial standpoint with some its team to ensure that the nature of that room fits very nicely into how physicians treat patients and so we don't anticipate that there will be any particular challenges associated with that as we go into the launch and I think so.

Chris Boerner: We've worked very closely from a commercial standpoint with Samit's team to ensure that the nature of that REMS fits very nicely into how physicians treat patients, and so we don't anticipate that there will be any particular challenges associated with that as we go into the launch. And I think Samit's last point is particularly relevant as it relates to BECMA, which is that the way we've approached looking at clinical and commercial supply is that obviously, commercial supply is critically important, but it is equally important that we continue to prosecute our development program, and we're going to continue to make those tradeoffs with both of those priorities in mind. Chris, can we go to the next question, please Alan? [inaudible] Next, we'll go to Dane Leone with Raymond James.

Last point is is particularly relevant as it relates to a <unk>, which is that the way we've approached looking at clinical and commercial supply is that obviously commercial supply is critically important but it is equally important that we continue to prosecute our development program and we're going to continue to make those tradeoffs with both of those priorities in mind.

Thanks, Chris can we go to the next question. Please darla.

Yes, Sir next we'll go to Dane Leone with Raymond James.

Hi, Thanks for taking the questions two quick ones for me.

Samit Hirawat: Thanks for taking the questions. There are two quick ones for me. Firstly, on Mavicampton, we've seen biomarker data from Maverick that suggests the possibility of developing and non-obstructive and HESPAS. When do you think the team would be able to outline plans for the plausibility of running a compelling clinical strategy in either of those indications? Thank you very much. And then the second question would be, when do you think we might have some emergent data from the Dragonfly collaboration on IL-12 that the oncology community seems to be pretty excited about? Thank you. Sure, I can take both of those, Dane.

Firstly on the campaign.

We've seen biomarker data from.

Maverick that suggests the possibility of developing in non obstructive and has passed when do you think the team would be able to outline.

Plan for plausibility of running a compelling.

<unk> clinical strategy in either of those indications.

And then the second question would be when do you think we might have some emerging data from the dragonfly collaboration on IL 12 that the oncology community seems to be pretty excited about thank you.

Sure I can take both of those day and thank you for <unk>.

Samit Hirawat: Thank you. For Mavacampton, we are looking forward to initiating the first phase three study in non-obstructive hypertrophic cardiomyopathy within 2022. And for HFPEF, the phase two trial is now ongoing, and we're looking forward to that proof of concept readout over time, and then that will dictate the future development for Dragonfly. Once again, it's an early phase development right now in phase one, looking at single and then combination as well for the IO platform.

Looking forward to initiating the first phase III study in non obstructive hypertrophic cardiomyopathy within.

Within 2022, and four have passed the phase two trial is now ongoing and looking forward to that proof of concept readout over time, and then that will dictate the future development phase III as well or dragonfly. Once again, it's an early phase development right done phase one looking at single and then combination as well for Io platform and as that data evolves.

Currently don't have in hand, and those will be presented at appropriate conferences as we look to the future.

I think some of it I think we can maybe go to our last question. Please Anna.

All right. Our last question will be from Mohit Bansal with Wells Fargo Securities.

Samit Hirawat: And as that data evolves, which we currently don't have in hand, and these will be presented at appropriate conferences, as we, I think we can maybe go to our last question, please. All right, our last question will be from Mohit Bansal with Wells Fargo. Good morning, this is James Johnson. Mohit, just a couple of quick questions. For Ducrava, I know we're sporting new doses, but will you be rerunning the lab safety analysis to differentiate or rule out any jack-like signals? And then for the S1Ps, how is BMI or BMI expecting the SMPs to be positioned relative to the JACs? And any thoughts on the competitiveness of the COSIA relative to the Trizomod?

Hey, Good morning. This is James on for Mohit just.

Couple of quick questions.

Or do you cover I never exploring doses, but will you be running the lab safety analysis to differentiate or rule out any Jack like signals and then four that's one piece.

BMI or BMI expecting.

That's one piece to be positioned relative to the jacks and any thoughts on competitive.

Competitiveness as opposed to a relative size amount.

So let me start with Newco asset so we've already got.

Samit Hirawat: So let me start with Duke-Ravassat-Nibb. So we've already got two phase three studies that have read out, and those safety data all the way with a follow-up of 52 weeks we've already shared and will continue to evolve as we look forward. We've also looked at the data and will be part of the submissions in China and Japan for studies that have been conducted in China and Japan with longer-term, one-year follow-ups. So those are all in line with the safety profiles that we have added. So we certainly do not look forward to doing additional analyses on the same data because we've already conducted those.

Two phase III studies that have read out and those are those safety data all the way with a follow up of 52 weeks, we've already shared in and will continue to evolve as we look forward. We've also.

Looked at the data and will be part of the submissions in China and Japan for studies that have been conducted in China, and Japan, but longer term one year follow up. So those are all in line with the safety profile that we have added. So we certainly do not look forward to doing additional analyses on the same data because we've conducted those long term follow.

Ups will continue and see it.

So evolution and certainly those similar sorts of exercises of continuing to generate data at higher doses for other indications that we're studying will be evaluated when data out available from an Epsilon perspective, Chris do you sure I'll take that one so James as I said earlier, we do expect that theres going to continue to be an evolution of Jack labor.

Samit Hirawat: Long-term follow-ups will continue and see additional evolution. And certainly those similar sorts of exercises of continuing to generate data at higher doses for other indications that we are studying will be evaluated when data are available. From an SLMP perspective, Chris, do you want to? Sure, I'll take that one.

Chris Boerner: So, James, as I said earlier, we do expect that there's going to continue to be an evolution of JAK labeling that could continue to push those assets into later lines of therapy, if you will. From our perspective, we continue to be very happy with the profile of Ziposia, both from an efficacy perspective, given the strong clinical remissions, as well as the clean safety profile. Our focus continues to be driving awareness and overall volume.

<unk>.

That could continue to push those assets.

Into later lines of therapy, if you will from our perspective, we continue to be very happy with the profile for from symposia of both from an efficacy given the strong clinical remissions as well as the clean safety profile. Our focus continues to be drive awareness and overall volume, but there may be opportunities longer term given the evolving Jack situation.

Chris Boerner: There may be opportunities longer term, given the evolving JAK situation, but we're going to continue to be disciplined in how we approach this launch and execute against what we need to do in order to build volume. And with respect to differentiation against other future S1Ps in that space, again, I would just say that we're very confident in the profile that we have, and it's important that we execute effectively with the launch in UC, and that's where our commercial focus is.

But we're going to continue to be disciplined in how we approach this launch and executing against what we need to do in order to build volume and with respect to differentiation against other future <unk> in that space.

I would just say that we're very confident in the profile that we have and it's important that we execute effectively with the launch in UC and Thats, where our commercial focuses.

Yes.

Chris Boerner: Thank you. Thank you, Chris. Thanks, everyone, and I appreciate you participating in the call. Let me just close by saying we're really pleased with our performance in the quarter, and, much more broadly, our performance in 2021 positions us really well to deliver growth this year in 2022 and beyond. We have built a solid foundation, and I'm confident that as our portfolio renewal gains traction this year, our company is well-positioned to reach new heights, both for patients and shareholders, and I want to thank our employees for supporting very strong growth.

Thank you.

Alright, thanks, everyone and I appreciate you participating in the call let me just.

Close by saying, we're really pleased with our performance in the quarter and much more broadly our performance in 2021 positions us really well to deliver growth this year in 2022 and <unk>.

Chris Boerner: Thanks for being with us for the call. Our team remains available to answer any additional questions you may have, and I wish all of you a good day. Thank you. That does conclude today's conference. We thank everyone again for their participation. Thanks for watching! Do you want to start a business?

And beyond we have built a solid foundation.

I'm confident that as our portfolio renewal gains traction this year.

Company is well positioned to reach new highs both.

For patients and shareholders and I want to thank our employees for supporting very strong growth thanks for being with us.

For the call our team remains available to answer any additional questions. You may have and I wish all of you a good day. Thank you.

That does conclude today's conference we thank everyone again for their participation.

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