This conference call transcript was computer generated and almost certianly contains errors. This transcript is provided for information purposes only.EarningsCall, LLC makes no representation about the accuracy of the aforementioned transcript, and you are cautioned not to place undue reliance on the information provided by the transcript.
spk05: 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, Investor Relations. Please go ahead, sir.
spk18: 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 Coforio, our Board Chair and Chief Executive Officer, and David Elkins, our Chief Financial Officer. Also participating in today's call are Chris Berner, our Chief Commercialization Officer, and Sumon 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. And before we get started, I'll read our forward-looking statement. During 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. 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. We specifically disclaim any 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. Reconciliations of certain non-GAAP financial measures to the most comparable GAAP measures
spk17: available on bms.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 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 Obdivo, as well as continued demand growth for our new products. The launch of Ziposia 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 Reblozil in ESA refractory MDS and transfusion-dependent Betafal, and our cell therapies, Prianzina-Becma, continue to see significant demand while we remain focused on broadening supply and expanding indications over time. We are advancing our strategy and delivered key pipeline milestones in the fourth quarter. This enables us to help more patients, accelerate the renewal of our portfolio, and support our growth outlook. Let me highlight some key achievements. We submitted applications for Ducarvacitinib in the US, EU and Japan, which position us well to grow our presence in immunology. We are excited about the potential of Duclavacitinib as the oral standard of care in moderate to severe psoriasis and various other autoimmune diseases. We are expanding our cardiovascular portfolio and presented exciting data at AHA for Milvexian, which we see as a next-generation antithrombotic with a $5 billion-plus non-risk-adjusted revenue opportunity. We presented important updates at ASH on our hematology pipeline. This includes encouraging data for iberdomide and 480, our exciting new multiple meloma cell mod agents. These have the potential to replace red limit and pulmonary stover time. Importantly, the transformed data for Brianzi in second-line B-cell lymphoma showed practice-changing benefit compared to the current standard of care. We continue to see Brianzi as 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. 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 let David speak to the details in a moment. What's important is that we're guiding to growth this year with low double-digit growth from our continuing business, more than offsetting the revenue impact from generics in the US and internationally. Turning to our 2021 execution scorecard on slide five. At the beginning of last year, 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. We returned of divorce growth, successfully launched multiple new products and produced key expansion data sets 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. And on slide six, you can see there are multiple catalysts ahead during 2022. The 2022 milestones include expected approvals and launches for three exciting first-in-class medicines, Navacantin, Ducrevacitinib, and Relatlanab. 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. We look forward to keeping you updated on our progress throughout the year. 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 2025. With continued growth of our inline brands, and 10 to 13 billion of additional sales expected from our new product portfolio. 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've said, we expect more than 25 billion in non-risk adjusted revenue potential from the current new product portfolio in 2029. with additional contributions coming from our pipeline, including assets like Milvexion and our exciting Selmon agents. As we continue our journey to renew our business and grow through the impact of LOEs starting this year, I'm increasingly excited about the future of Bristol-Myers Squibb. With that, I'll turn it over to David to walk you through the financials.
spk06: David? 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 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 inline and new product portfolios. Now, let's turn to some product specifics starting with Eloquist 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 U.S., fourth quarter sales increased 22% versus prior year, driven primarily by total prescription growth of 13%. Internationally, Eliquis 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 Eliquis 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 one-time favorable true-up in the U.S. of approximately $160 million that will not repeat in Q1 of 22. Moving to Optiva's 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. 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, 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 prior year, driven largely by demand for new indications and expanded access, primarily in emerging markets. More broadly, we continue to see uptake of our new launches in lung and renal cancer in Germany and Japan. And we secured reimbursement in Italy and Spain in the fourth quarter. As we look forward, we continue to expect further growth for Updivo as we secure additional reimbursement for recent approvals. We're in a strong position to continue to grow Updivo and look forward to additional approvals this year and in the years ahead. Now, let's turn to our IMMA portfolio on slide 12, starting with RevelMed. Fourth quarter revenues grew 1% globally versus prior year and grew 6% for the full year with sales of approximately $12.8 billion. 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 ex-U.S. markets. 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 volumes. For the first quarter, our best projection for global revenue sales is approximately $2.5 billion. Beyond 2022 through 2025, although they're still uncertainly due to ongoing litigation, we view an annual step down of roughly $2 to $2.5 billion per year as a reasonable projection. Now onto Pomalyst. Global sales in the fourth quarter were up 2%. Sales were primarily driven by demand for triplet-based therapies in ex-US markets and fewer selling days in the US. We continue to expect growth for Pomalyst 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 Pomalyst, we are 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. We are very pleased with the momentum and feedback we're 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 me provide some color on each launch individually, starting with Reblazel, 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 in ESA refractory MDS patients. Demand continued to grow in the fourth quarter. Sequentially, revenue was impacted by one-time favorable inventory build in the third quarter of approximately $20 to $25 million. Our 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 at Beckman and Brianzi. Beckman generated revenues of $164 million since its launch in May of last year. 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 capacity. We expect first quarter revenues to be largely similar to fourth quarter. Turning to our CD19 cell therapy, Brianzi, Physicians continue to recognize Brianzi's best-in-class profile for relapsed refractory patients. We look forward to moving Brianzi 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 U.S. this year. Now moving to Supposia, global sales for the year were $134 million, primarily driven by our multiple sclerosis indication. In the U.S., 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. We continue to be pleased with the progress we have made on patient conversion, with significant decrease in time to commercial therapy. Our early UC launch is continuing to gain traction with a leading share of voice and increased overall volume. Physicians are responding well to the profile, and we encourage by their intent to prescribe. We are working on building volume and growing access and reimbursement. We expect to have increased contribution from UC in the second half of this year and expanding in 2023. Internationally, Zoposia continues to gain momentum in MS as the product gets additional reimbursement in more markets and benefited from some near-end stocking. 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. Our focus remains on shaping the maintenance segment and increasing adoption and patient adherence. 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 RELATMAB and Mavicampton with PDUFA dates in March and April. And we're on track for Ducrevacitinib'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-GAAP key line items. Operating expenses increased versus prior quarter due to timing of MS&A investments that shifted to the fourth quarter as noted in October. MS&A decreased versus prior year due to some incremental and accelerated investments to support our business in 2020. The fourth quarter effective tax rate was impacted by earnings mix. 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. We have 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 science and mid-size bolt-on deals. 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 plan to execute a $5 billion ASR this quarter. Now turning to our 2022 non-GAAP guidance at current exchange rates on slide 16. As announced last month, we expect 2022 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 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%. Finally, also communicated earlier this year, we expect non-GAAP EPS to grow faster in 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. 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 RevelMed, 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 RevelMed 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. 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.
spk18: Thanks, David. Alan, can we go to our first question, please?
spk05: Certainly, sir. We'll go first to Seamus Fernandez with Guggenheim.
spk04: Oh, thanks so much for the questions. So, first question is just on your Factor 11. I just wanted to, you know, check in on timing of a potential update from your Phase 2 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 dosing 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 put with your expectations? And can you guys help us understand a little bit better the opportunity for 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 second, just on your, we just had the filing of the cytokinetics competitor compound. Can you just talk a little bit about the competitive landscape as you think about the opportunity you know, flumavacantin versus other competitor compounds. Thanks so much.
spk01: Thank you, Seamus. This is Samit. I'll take both of those questions. So for FECTA-11a, as we have talked about, the second phase two 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'll 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 Maldixine. As 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. 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 therapies of anti-platelet agents. as well as to then progress them further into appropriate indications, either as a single agent or as combinations. So we just have to wait for the data. But as we saw in the TKR study, there was no increase in the bleeds, but we certainly saw increase 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 of that. Coming on to Mavacampton and the competitor compound, we remain very focused and very confident in the data for Mavacampton. As you know, we are launch ready, as David spoke earlier, for the PDUFA date coming up soon. And as it relates to then additional data, we are waiting for the readout of the VALOR trial as well in the short timeframe. 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 isoparamide. 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 patients who are going to be receiving the background therapy of disopramide 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.
spk08: 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's entirely competitive. consistent with what would be expected from a myosin inhibitor. And so we feel very good about the competitive position for this agent and look forward to launching.
spk18: Thanks, Chris. Alan, can we go to our next question, please?
spk05: Certainly, sir. Next, we'll go to Chris Schott with J.P. Morgan.
spk02: Great. Thanks so much. Just to maybe 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 should we 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. Just walk through a little bit about how you're 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.
spk08: Sure, Chris. I'll take both of those questions. With respect to MAVA 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 of excellence where these patients are being treated today. That's going to be the initial focus. Beyond this, 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 other thing 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. The good news is we have a very strong team with an established presence in this space. We have a very good drug, so we feel very good about the long-term potential for the asset. And that stepwise approach that I articulated really is in line with the overall opportunity of $4 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 ABECMA. And our efforts are really focused on working with CMOs 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, increasing our operational efficiency, and increasing site capacity. On a BECMA, we would anticipate being in a much better position for supply as we get into the middle of this year. And then as it relates to Breonzi, Breonzi, the big focus there is on vector supply, 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 would have any label expansions for that product.
spk18: Thanks, Chris. Can we go to our next question, please?
spk05: Yes, sir. Next we'll go to Jeff Meacham with Bank of America.
spk07: Morning, guys. Thanks for taking the question. For some of the new launches, are there any metrics you guys can provide, you know, that show, you know, the wins and access and reimbursement, mostly talking about, you know, cell therapies and Ziposia? The bigger picture is just trying to assess, you know, you know, 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 on kind of a sequential basis. And then the second question, real quick on Ducravisit, and I know there's been a lot of angst about the, you know, potential for differentiating labels versus JAX. And just now that we have clarity on the latter, just wanted to get maybe an updated view from you guys on that.
spk08: Thank you. Sure. Maybe I'll start, 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. We'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 an 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 concerns. And I would say largely 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 mentioned Ziposia, 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 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 Ziposia. 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 drug and do 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. What I can say, though, in any case, is that on Zapposia, we're 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 Zapposia into an earlier access position as we head into 2023, and we're very much on track to do that.
spk01: And, Jeff, I'll take on the question around Ducrella. 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're looking forward to the PDUFA date in September.
spk18: Thanks so much. Colin, can we go to our next question, please?
spk05: Yes, sir. Next, we'll go to Steve Scala with Common.
spk03: Thank you. I have a couple questions. Updivo 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-related shutdowns. Are there any other reasons for 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 Novexian 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.
spk08: Maybe I'll start, Steve. With respect to, let me just say at the outset, with respect to Avdevo, we're actually very happy with the performance we saw for Avdevo in the quarter. As David and Giovanni mentioned, we saw a return to growth for Avdevo and actually saw an acceleration of Avdevo 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. As it relates to IO specifically, new patient volume has been gradually recovering, though I would say 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. Our hope in terms of the outlook is that we'll continue to see an improvement over the course of the year. As 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 resilient in 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.
spk01: 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 conference. Really looking forward to it, though. Thank you.
spk18: Thanks so much. So, Alan, can we go to our next question, please?
spk05: Yes, sir. Next we'll go to Chris Shibutani with Goldman Sachs.
spk03: Thank you. If I could ask a question about the immuno-oncology franchise, maybe more medium to longer term. There's a couple of dynamics that are happening. One, I think we have a PDUFA coming up in March for the LAG3 combination fixed dose. Anything that you could share in terms of How are you 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 Tidget? Could you also comment with a combination of data from Dempeg, plus Opdivo, which I believe could be in the second quarter 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-1s. Can you share with us your initial thoughts at this stage about how you see that influencing the market dynamics for checkpoint inhibitors and IO? Thank you.
spk08: Sure. Maybe I'll start and I'll hit your first and third question. We're very pleased with the opportunity to potentially launch RelatLimib. 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's 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 Opdivo and Keytruda 50-50, and then you have a third of the market, which is really focused on targeted therapies. We see the opportunity for Rolatilamib 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. Remember that Rilatilamib 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 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. 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 put a finer point on it, we shouldn't underestimate the barriers to sort of broad-based commoditization in oncology, particularly for a product like Avdevo, given the breadth of our data and indications.
spk01: And, Chris, on the BEMPEG 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, as you very well pointed out, is in melanoma. We are anticipating the data within the first half of this year. With that said, we are certainly very pleased to have three IO mechanisms already, as in PD-1 as well as CTLA-4, and then anticipating the PDUFA and launch for elaclimab, as you also mentioned earlier. And we're looking forward to continuing work with Nectar in progressing the program as the data continues to evolve.
spk18: Thanks so much. Alan, can we go to the next question, please?
spk05: Next we'll go to Tim Anderson with Wolf Research.
spk12: Hi. Thanks so much. This is Adam on behalf of Tim. On Mavacantin, 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. 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.
spk08: Sure, maybe I'll take both of those questions, or at least the first two questions. So, Adam, with respect to how we've thought about NAVA, 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 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 are symptomatic and diagnosed and where there's a real urgency to treat. 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%. 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 is an obstructive disease, but certainly we are looking forward to potentially seeing data in non-obstructive as well.
spk01: Yeah, and on the adcom question, we have not been notified of a potential adcom. We do believe in the strong profile of Mavacantin and 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 Chris said.
spk18: Thanks so much. Helen, can we go to our next question, please?
spk05: Yes, sir. Next, we'll go to Andrew Baum with Citi.
spk16: Thank you. A couple of questions. So first on norvexin, 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 norvexin. Perhaps you could comment on level of reassurance in terms of either interaction with antiplatelets or commonly administered drugs in this patient population. And then second, you already highlighted the Q1 inflation in 2021 for Eloquist. Perhaps you could talk more generally to the trends, particularly the U.S. Eloquist growth for 2022. 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 to whether we expect to be slowing, that would be helpful.
spk01: So I will start off, Andrew. Thank you for your questions. And for Melvixian, as you know, that we have, first of all, the study ongoing already with anti-placar agents in the SSP. So we'll get to see that data when that reads out. In terms of the other drug-drug interaction studies, that is partly parcel of the usual clinical pharmacology package that we prepare in anticipation of future filings in NDA. At the current time, we do not see any major impact or anything major in terms of EDI.
spk08: 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 then this year, we expect continued strong growth for Eloquist. Eloquist is likely going to be the key driver of the overall OAC market. 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 eloquent NBRX 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. 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. What we know in this space is that there's significant risk for non-medical switching of patients who are on Eloquus. We know also 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 gross to nets and how we manage those, and this is part of that story.
spk18: Thanks, Chris. Alan, can we go to the next question, please?
spk05: Yes, sir. Next we'll go to Ronnie Gall with Bernstein.
spk13: Good morning, and thank you for taking my question. First, just following up on Andrew's question, can you talk a little bit about a benefit from 340 switch, especially from Eloquence? It seems to the net prices, Eloquence and 340B was close to nothing. 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, Orencia, it seems to be growing together with the RA market. It seems to be in position to grow better given the JAK inhibitor safety issues. Can you talk a little bit about what you're seeing and what's your projection for 2022?
spk08: Sure. Let me – Jibani, do you want to start? Go ahead, Chris. Sure. So on 340B, let me just say at a macro level, we remain committed to ensuring the eligibility of patients for 340B, those patients who can directly benefit from the program. And what 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. First, BMS and Celgene having different policies. around the recognition of contract pharmacies and needing to align those as part of integration. And then 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 for how we think about the 340B program. And then do you mind repeating your second question again?
spk13: It would be great if you can quantify the 340B impact. And the second question was around Orencia trends and the potential for benefit from the JAK inhibitor's black box label.
spk08: 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 Orincia, look, Orincia 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 Orincia or, frankly, any of our products is that those changes will likely continue to push Jax into later lines of therapy as labels are updated and their position continues to evolve. So we think there's 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 obviously, we'll allow the situation with Jax to evolve as they do.
spk18: Can we go to our next question, please?
spk05: Certainly. Next, we'll go to Louisa Hector with Barenberg.
spk00: Hello, thank you for taking my question. Just wanted to discuss a little bit more on 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? Anything of note? I guess really to confirm the pace of the Revlimid erosion is pretty predictable. So just checking on levels of uncertainty. And then specifically around how you are adapting to 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 of it. Thank you.
spk06: Yes. Thanks for the question, Lisa. As we think about Revlimid, we thought it was important this year, number one, to provide guidance on the full year. Secondly, we thought it was really important to provide guidance on the quarter. I'd say one thing is that the contracts are annual volume limitations. 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 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 quarter. And then the remainder of the generics will come usually about 180 days later. It's pretty typical in a generic entry scenario. So that would be in the September timeframe. But for the full year, we feel very confident in the guidance that we provided for the full year as it relates to revenue. As far as the expense base is concerned, I mean, this is a really fortunate thing for us in the standpoint, 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 the launch brands. So as you think about our hematology sales force, you know, being able to move those resources out of Revlimed and into, like, cell therapy with the Breonzy 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.
spk17: Luis, this is Giovanni. Let me just make another comment there. You mentioned about our level of confidence there. 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 generics of Revlimid. And what I'm really pleased of is the fact that we've got strong momentum with inline business. We are making great progress with the launch plans that are already on the market. We are looking forward to three important approvals. And this year, as you know, we've guided the growth both in terms of our revenue base, but also in terms of earnings per share. 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.
spk18: Thanks, Giovanni. Alan, could we go to the next question, please?
spk05: Yes, sir. Next we'll go to Evan Siegerman with BMO. Hey, guys, thank you so much for taking my question.
spk09: I'd like to dive a little bit more on 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 Pomeloid 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.
spk01: Sure. Thank you for the question. From a CellMod perspective, the way we are thinking about development and as we continue forward, we've generated the data in the late lines looking at a combination of Iberdomyte 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 Ibertamide plus Valcade plus dexamethasone, comparing to, sorry, Ibertamide, Daratumumab, dexamethasone, comparing to dexamethasone, as well as Valcade and CD38 antibodies. So that's a first foray into the second line plus patient population for the cell model. The other trials that you will see in the short while coming up will be the phase three trials of CC480, looking to replace pomalidomide, and that would be a head-to-head comparison versus pomalidomide combinations. And in 2023 and beyond, you will see trials of ibertamide looking into the post-transplant maintenance, head-to-head comparison versus Revlimid, as well as the newly diagnosed patients who are transplant non-eligible to again replace Revlimid in the first line or front 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.
spk08: 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 IMIDs. There's obviously going to be a focus to address areas of IMID unmet need, whether it's renal impairment or look at potentially other populations where IMIDs underperform. And then ultimately, from a commercial standpoint, we're going to need to establish a strong value proposition versus generic IMIDs. But all of that will be part of the plan.
spk18: Chris, let's go to our next question, please, Alan.
spk05: Yes, sir. Next we'll go to Carter Gold with Barclays.
spk19: Great. Good morning. Thanks for taking the questions. I wanted to focus a little bit on the GI immunology portfolio. You know, last year after the Phase II 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 23 and 22 and 23, just any additional thoughts on that front? And now 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. And then maybe a little bit off the radar, syndacumab, we've seen you sort of expand the development program there, and then recently add sort of a phase three study in Japan, so in eosinophilic gastroenteritis. 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 the recent history kind of maybe has shaped that viewpoint. Thank you.
spk01: Sure. Thanks, Carter. To sum it again, for Ducrevacidinib, UC, as well as Crohn's disease, 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 with ducrava 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 those and take that program forward once we have a proof of concept so it is not off the charts but more about looking uh 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. 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, that we have a study ongoing in atopic dermatitis is a 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?
spk05: Yes, sir. Next, we'll go to Matt Phipps with William Blair.
spk11: Thanks for my questions. You all announced positive transform results in June a couple weeks before a similar announcement from the Ascarta. They have a PDUCA date in April, and we're still kind of waiting on hearing the PDUCA date for Breonzi. Are there any risks to meeting a 2022 approval milestone there? And then Summit, you know, some three phase threes with BIM TAG coming up this year. Do you think those have equal probabilities of success, or is there one indication you think is more likely based on where high dose IL-2 has been more effective?
spk01: 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, we will certainly be able to share more in terms of the filing and the PDUFA dates 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're 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 LBCF. For BEMPEG, certainly it is data dependent. We're 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 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. Can we go to the next question, please?
spk05: Yes, sir. Next, we'll go to Matthew Harrison with Morgan Stanley.
spk14: Hi. This is Charlie. I'm for Matthew. First, on my vaccine, 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 ramps and what that will look like? So, for example, how frequent might patients need to be monitored? And lastly, on a back mind, As you kind of walk through the early lines of therapy, can you talk about in terms of the prioritization of these studies versus commercial supply? And I guess, you know, what are their commercial opportunities relative to kind of current indication? Thank you.
spk01: I'll start off. So first of all, for Melvick CN, in terms of what amount of bleed is acceptable, look, it is all 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 as we look at Melvixian program, but there are no numbers that I can share today with you as to how to start looking at or projecting out those numbers. From the REMS perspective for Mavacampton, 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. The basic mechanism of the drug for Mavacamptan 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, quote-unquote, relax too much and decrease the ejection fraction. And that's the intent and the way the patients are currently managed on a continuous or ongoing basis. is periodic echocardiographies. So more to follow on that as we get to the PDUFA date and final approval and full package of REMS and overall NDA approval. From a BCMA 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 abetment supplies for clinic as well as commercial.
spk08: Sure, and maybe I'll just make one comment on the RIMS program, Charlie. The way that we have approached the RIMS, obviously we knew a RIMS would likely, would be likely with this asset. We've worked very closely from a commercial standpoint with Summit's team to ensure that the nature of that RIMS 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 ABECMA, 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.
spk18: Thanks, Chris. Can we go to the next question, please, Alan?
spk05: Yes, sir. Next, we'll go to Dane Leon with Raymond James.
spk10: Hi, thanks for taking the questions. Two quick ones for me. Firstly, on Mavacampton, we've seen biomarker data from Maverick that suggests the possibility of developing a non-obstructive and HF-MAS. When do you think the team would be able to outline a plan for plausibility of running a compelling clinical strategy in either of those indications? 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.
spk01: I can take both of those, Dane. Thank you. For Mavacamtin, we are looking forward to initiating the first Phase III study in non-obstructive hypertrophic cardiomyopathy within 2022. And for HFPAF, 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 three as well. For Dragonfly, once again, it's an early phase development right now in phase one, looking at single and then combination as well for an IO platform. And as that data evolves, which we currently don't have in hand, and those will be presented at appropriate conferences as we look to the future.
spk18: Thanks, Amit. I think we can maybe go to our last question, please, Alan.
spk05: All right, our last question will be from Mohit Bansal with Wells Fargo Securities.
spk15: Hey, good morning. This is James from Mohit. Just a couple quick questions. For Dukrava, I know there's four new doses, but will you be rerunning the lab safety analysis to differentiate or rule out any JAK-like signals? And then for the S1Ps, how is BMI or BMI expecting the S1Ps to be positioned relative to the JAKs?
spk01: and any thoughts on competitive competitiveness of zircosia relative to trasmod so let me start with duca so we've already got uh two phase three studies that have read out and those uh those safety data all the way with a follow-up of 52 weeks we've already shared and 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 conducted those. 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 S1P perspective, Chris, do you?
spk08: Sure, I'll take that one. 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 from Ziposia, 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. 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 executing 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.
spk17: 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 renewals gain 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 strongly. 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.
spk05: That does conclude today's conference. We thank everyone again for their participation.
Disclaimer