Q3 2020 Bristol-Myers Squibb Co Earnings Call
The Evo plus Cabo and first line RCC for which we were granted priority review some things up the teams of executed well commercially and clinically which shows the continue with us for a Vevo in your voice makes this even more confident in our expectations for the annual year-over-year growth in 2021.
Operator: Good day, and welcome to the Bristol-Myers Squibb 2020 Third Quarter Results Conference call. Today's conference is being recorded. At this time, I would like to turn the conference over to Mr. Tim Power, Vice President, Investor Relations. Please go ahead, sir.
Moving on tour in line multiple myeloma, we're fully on 5/12 and palm. Let's continue to perform very well which strong double-digit growth on a performer basis down to 10% primarily driven on increased treatment duration and Tom was grew 17% driven by growth in earlier lines of treatment and increased treatment duration in the US may be experiencing temporary softness to the nudibranch are dumb COVID-19 has now recovering and this is being offset by better adherence and longer duration of therapy for existing patients wage is performing sales for revlimid increase 11% u.s. Performance sales for pomalyst increased 19% This strong performance was driven by increased use of triplets therapy and treatment duration in major European markets.
Tim Power: Thanks, Kevin. And good morning, everyone. Thanks for joining us this morning for our third quarter 2020 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, and also participating in today's call are Chris Boerner, our Chief Commercialization Officer, Nadeem Ahmed, President of Hematology, and Samit Hirawat, our Chief Medical Officer and Head of Global Drug Development. As you'll note, we've posted slides on bms.com that you can follow along with for Giovanni and David's remarks. And before we get going, 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. However, 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 filing, www.youtube.com.au. Reconciliations of those non-GAAP financial measures and those comparable GAAP measures are available at BMS. Thank you, team. And good morning, everyone.
Hold it had a minimal impact on ongoing patient treatment with a small impact observed in new patient starts. We are seeing strong signs of new patients returning to Prior treatment wage right now moving on to a recent Launches on slide 13 has been off to a robust start with the approval of ours positive MBS Associated media Global sales and a quarter were ninety six million dollars representing 75% sequential growth of a quarter to in the US position feedback from me positive significant awareness of the Brand Plus still early. We continue to be pleased with the launch including new patient update and patient protection on the product for the majority of patients of adhered to their treatment as a reminder significant proportion off early update these driven by the initial post the patience waiting for a new treatment option. We remain very encouraged by the underlying demand for the product and patience with beta-thalassemia as well as MDS associated with
Giovanni Caforio: I hope that you and your families are safe and healthy. Q3 was a very strong quarter across the company, adding to great performance over the past. I will go into more details about the quarter in a few moments, but recognizing that it has been almost a year since we established our new company, I would first like to give you my perspective on the company overall. Turning to slide four.
Giovanni Caforio: A year ago, we transformed our company with the goal of positioning us for growth in the near, medium, and long term. I am very pleased with our ability to consistently deliver on that promise across multiple dimensions. Starting with integration, where we continue to make great progress. The strength of our execution as a combined company is a testament to our successful integration so far. The culture of our company is being shaped by our values, including a focus on innovation, collaboration, and a great sense of urgency.
Internationally recent launches in Germany and Austria are going well. Although very early in the lunch. We also receive approval for beta-thalassemia associate anemia in Canada and am to launching the various markets globally of course of twenty Twenty-One as we receive reimbursement.
Trying to suppose you were encouraged by what we're seeing through the first few months. It suppose you have lunch. We are focused on driving demand and establishing suppose the the leading s1p modulator in multiple sclerosis. You secured strong commercial access and our commercial teams are executing. Well, we are pleased with the physician receptivity and prescription initiation. We've seen thus far.
Giovanni Caforio: Our Synergy Capture is ahead of our original expectations. From a commercial perspective, we have driven strong performance from our inline brand. We have launched four new medicines, including InRebEx, Reblozol, Zipozia, and Onaret. We have entered the first-line lung cancer market with Opdivo and Yerba. In the past year, we've also delivered strongly on the potential of our five, starting with immuno-oncology, where we have seen successful trials across both the metastatic and the adjuvant, which further supports the growth opportunity for Optiva. Specifically, in the adjuvant setting, Ob-Divo is well-positioned as a leading medicine with results in four different tumor types.
No moving on to our Newest Lunch on your leg, which is great and approval for first-line AML maintenance by the FDA on September 1st while very early in the launch feedback from positions wage promise it the message that on your egg the first and only medicine to demonstrate overall survival and maintenance settings would be convenient oral route of administration is resonating well.
This is a market that it's largely underdeveloped as they were previously known FDA-approved options for patients in the maintenance setting after intensive chemotherapy and like many other medicines and maintenance that will take some time to educate prescribers about the use of new treatment for patients.
Giovanni Caforio: Beyond immuno-oncology, we are continuing to strengthen our presence in immunology with very encouraging data from a number of assets and programs. These include phase 3 data for zikosia in ulcerative colitis, the decision to move to registrational trials for syndactyma in eosinophilic esophagitis, and phase 2 data for our TIK2 inhibitor, Ducrasatinib, in psori Most importantly, we now have top-line data from our first phase three trial for Ducrava-Satinib in psoriasis. Now, let me take a moment to talk about Dukla Vashat.
An enemy is under review in Europe and we expect approval and twenty twenty-one.
And I'm moving on to our balance sheet and capital location on 514. We continue to generate significant amount of cash flow from operations in the third quarter. We ended the quarter in a strong liquidity position offered me $22 in cash and marketable securities. That's after tax payments approximately 1.7 dollars for Debt Pay down and large cash payments including tax payments associate the gain on a Tesla.
Our Capital allocation priorities remain unchanged delivering and achieving less than 1/2 times debt-to-ebitda issue, which is now expected by the end of 2024. We continue our commitment to our dividends and investing in future Innovation through business development in touch on our business development activities is Giovanni discussed. We have not believed against our priorities. We have executed an important deals over the third quarter including our acquisition of 40th and license agreement with dragon flag as well as our recently announced pending acquisition of myocardium, each of these transactions in line a criteria for business development strategically aligned scientific exam and financially attractive. We will continue to be active the business development searching for additional opportunities further strengthen our growth of the company for the long term and creating value for shareholders.
Giovanni Caforio: Based on the top-line data that we have seen so far, we are very encouraged by the potential for this asset to be the best oral option for patients with psoriasis, with potential broad applicability across multiple diseases including psoriatic arthritis, lupus, ulcerative colitis, and Crohn's. And finally, we strengthened our IP position for Red Limit and Elixir. Delivered strong financial results and continue to invest in the future with a number of important business development transactions, including two early stage assets, Gruffodious and Dragonswine, as well as the announced acquisition of Myokai. Now turning to slide five, through the planned acquisition of Myocardia, we're gaining. A potential first-in-class medicine for the treatment of obstructive hypertrophic cardiomyopathy, which is a chronic heart disease.
Now let's turn the guidance at 5:15 based on the strength of a result here. Today. We're updating our full-year 2020 Outlook. We are narrowing our Revenue range two between 41.5 billion and $42 billion dollars based upon the strong performance year-to-date and we do expect sales to be at the higher end of the range.
Giovanni Caforio: High Morbidity and Patient Income. We believe Mavackhampton has a multi-billion dollar market, with further potential value drivers from additional indications and the myocardial valve. We look forward to closing the transaction during Q4 and welcoming our new colleagues from Myocardia to Bristol-Myers. Turning is life. I am optimistic about the strategic position of our company and how we are well positioned for growth and to navigate through the challenges. Today, Bristol-Myers Squibb has significant strength and breadth in all four of our current therapeutic programs. Across Oncology, Hematology, Immunology, and CV, we have robust inline businesses, exciting near-term launches, as well as long-term pipeline operations. Across all four areas, we are successfully building our portfolio of humanities through a combination of short-term launches, the advancement of significant late-stage pipeline opportunities, and disciplined business development. To be more specific, Eliquis and Ovivo are assets with significant growth potential.
Turning to us.
Pretty expensive we expect total spend to be generally in line with our expectations. We do have some slight shift since and relate to RMS May and R&D logs for m s n a we decide to make additional one time purchase accelerating DPT advertising and support the business as we close out the year, and we now expect to spend approximately six point nine billion dollars. This is being all set by lower our Deep South now expected to be approximately nine $42 billion dollars the same time. We remain very pleased with our Synergy capture, which is Giovanni mentioned is tracking ahead of our original expectations.
We now expect our tax rate to be approximately 16% for the full year and taking all this together. We are increasing our full year adjusted EPS range to be between $6.25 and $6.35 per share.
Our Revenue guidance takes into account the pentacle which continues to affect us in the fourth quarter as I mentioned earlier as well as continued competitive Dynamics associated with some of our established brands.
Now as it relates to our 2021 guidance, we are reaffirming our non-gaap EPS guidance seven dollars and fifteen cents $7.45 which absorbs the dilution associated with the off position. We look forward to providing more color on 2021 during our fourth-quarter cause normally do before we move the question answer and want to thank all of our teams around the office for delivering such outstanding results here date these results. Allow me to rank confident in a long-term outlook for the company.
Giovanni Caforio: We have eight new medicines that are launching now or have the potential to launch over the next few years, and most of these have important expansion opportunities beyond just their initial indications. We have gained clear line of sight to our next set of registrational assets, with seven in or close to registrational development. Including Royal Atlanab, our two multiple myeloma cell mods, Iverdamide and CC9248, as well as Sandakimab and our Factor 11a inhibitor, and our early pipeline will continue to evolve, with more than 20 assets with the potential to transition to full development over the next three years. Given the strength of our portfolio and pipeline, together with the talent of our people, we are focused on delivering on our Within that context, let me turn briefly to the strength of the quarter on slide seven.
A male friend call back over to Tim and Jean volume for Geodon.
Great. Thanks very much. David, Kevin. Can we go to our first question, please?
Certainly, ladies and gentlemen, if you would like to ask a question, please take me by pressing one. Our first question today comes from Chris. Thanks very much for the club. I can drop them all the progress you've made this year. I guess I said to hear may be first on the tick to can you elaborate a little bit more on the safety profile? I think there's still some lingering questions outbreak of what we see any of maybe some of the Jack like safety issues. I know you've talked a lot about that in the past, but just to confirm that you see any imbalance at all, you know, the smaller not on the robotic events from the public study and just help us a little bit in terms of the profile of shaping up like on the safety there and then my second question was on Vevo you're watching a number of adjuvant indications next year off on those. Do you expect people have fast uptake? Like we've seen in some of the metastatic settings or these indications that maybe take a little bit longer to build over time. Thanks so much.
Giovanni Caforio: David will provide more details, but let me discuss a few highlights from my presentation. First, we continue to perform very well in highly competitive markets, with sales increasing 6% compared to the same period last year. In addition, we are making good progress across our market, and during the quarter, we have seen significant clinical progress, including multiple positive trials in IOP, as well as the first phase three trial for Ducravacetamol. Based on the strength of the business, we are increasing our EPS guidance for this year and continue to be very encouraged about the Earnings Growth Opportunity Act, as captured by our non-GAP EPS guidance for next, which we are reaffirming. Before I hand it over to David, I want to reiterate that I'm more encouraged today than ever before about our future prospects. I can say with confidence that our company has never been stronger.
Chris thank you. I think I'll start off again Christian possible to you four people David a question. First of all, you're very happy with what we've seen from. The results respective is the first of the two free free trials for the one that has read out and we have seen not only statistical as well as clinical meaningfulness wage. But also the the superiority versus Apprentice or Tesla in moderate-to-severe psoriasis from what we have seen before that indicates do studies and you talked about basic profile you continue to believe in that it was a differentiated mechanism of action that we believe in you do think that that fixed two in condition which has a specific down stream effect on our 12:23 as well as interferon. Alpha has played out and we continue to believe in that of course, I can't go into the specifics of the data. They will be presented in the future.
David V. Elkins: Bristol-Myers Squibb is well positioned to launch multiple new medicines, new indications, and benefit more patients in the very short term. And as we look to the future, our pipeline and financial flexibility, combined with the strength and critical mass we have built across all key areas, provide us with tremendous opportunity. I'm extremely optimistic about what is to come, and with that, I'll hand it over. Thank you, Giovanni. Hello, everyone.
Two in the medical meeting or overall. You're very happy.
David V. Elkins: And thanks again for joining our call today. I'm very pleased with the execution of our teams, delivering very strong quarterly and year-to-date results while operating in this global pandemic. Let's turn to slide nine and discuss our top-line performance. Third quarter and year-to-date revenues continue to reflect our strong execution, growing 6% versus prior year on a performance basis. As you can see, a vast majority of our brands demonstrate robust
Baby out and I look forward to what I read out the second phase three in the first quarter of 2021. So hopefully that answer your question and let me also on the Chris to talk about our Beetle from here. I'm sure thanks for the question Chris. We do have a number of exciting opportunities in the adjuvant setting I'll give you just highlight gastric and bladder specifically as we talked about a few months ago with respect to uh, gastric cancer. We're excited about the opportunity coming out of check made 577. This is the space where there's significant unmet need is very little in the way of life therapy that's used here. And it's Amit is previously talked about those patients who are getting neoadjuvant chemo radiotherapy about three-quarters of those patients. Don't get a patsy are so naturally there are no great options for those patients and we've seen very good efficacy coming out of 577 with a w d f s at a manageable safety profile and there's relative clean are here from a competitive standpoint.
David V. Elkins: Let me provide additional commentary on the underlying performance of our key brands and new launches. Starting with Eloquist on slide 10, demand trends continue to be robust with double-digit TRS growth of 18% in the U.S. versus prior year. This demonstrates strong execution of our teams and best in class profile. As we discussed previously, we accrue our liability related to the coverage gap as patients enter it, so the effects are second-half gross-to-
David V. Elkins: This is more pronounced this year as the size of the coverage gap per patient increased in 2020 and the Medicare component is a larger component of our net. This impact is in line with our expectations for Q3, and you should expect this to be a factor in the fourth quarter. International, Tales Made Strong with revenue growth of approximately $1 billion, growing 22% versus prior year.
This will be the first I owe in the setting for a number of years with respect to Bladder again happy with the results that we saw with 274. This is a space with about six to 7,000 treated treated patients in the US again, not a lot in the way of great systemic therapies here and as we've said we met them and point for a Betta and very much look forward to launching in the space. And this is again another space where there's relative clean air. So we would expect a reasonably aggressive of both of these indications.
David V. Elkins: Hellequist continues to be the number one NOAC in many key markets in our nation, including Germany, France, and the United Kingdom. Both in the U.S. and globally, we continue to see very strong outlook for eloquence resulting from the strength of its profile, enabling increasing share within a growing class. Turning to upkeep on slide 11, in the US, the teams have been executing very well. We continue to see strong shares across key indications. We now have a high single-digit share in first-line lung cancer with more patients benefiting from the approvals of 227 and 908. And you can see that the adoption of first-line lung cancer is reflected in the acceleration of the airway. What we're really encouraged by is the return to sequential underlying growth for up to. Underlying demand growth from Q2 to Q3 was approximately 2%, and sales grew 6% versus quarter two, driven by growing underlying demand, as well as a favorable customer buying pattern.
Thanks, Chris can let me go to the next question, please.
The next question today comes from Seamus Fernandez of Guggenheim.
Oh great. Thanks so much, everybody, you know congrats on the quarter and all the projects as well. My question is actually on the higher wage 12 milligram dose that we're going to see next week in psoriatic arthritis. You just give us you know, that's really where we see problems with other jacks off trying to get your sense of you know, what we should be looking for in those data. Obviously, they're about to be presented but I think that's something that investors were interested in home and then incremental to that as we think about the
David V. Elkins: Expect the impact from these buying patterns to reverse in the fourth quarter, but sequential demand growth to continue supporting our return to annual year-over-year growth for EVO in 2021. Internationally, we've seen strong commercial execution across the board with sales up 5% versus the prior year. Eventually, we saw a rebound to stronger demand driven primarily by the European and Japanese markets.
Have you think about the opportunity in areas, like ulcerative colitis? You've really empathize this dial 23 1223 profile is that your enthusiasm for the product is in and also the collider in particular. Thanks so much.
David V. Elkins: Markets Continued Gain Reimbursement for New Indications, and Firstline RCC in Melanoma There continues to be some softness in new patient starts across tumors, but most notably in melanoma. We generally saw good recovery of the impact of COVID in Q3. And we also look forward to bringing our FEVA plus Urovoid and limited chemotherapy to first-line lung cancer patients in Europe this quarter. We expect several additional near-term launches in 2021, including the potential for first-line gastric and several adjuvant indications such as esophageal and muscle-invasive bladder, and Upviva Plus Cabo and Firstline RCC, for which we will grant priority review. To sum things up, the teams have executed well, both commercially and clinically, which shows the continued promise for Avivo and Uruguay and makes us even more confident in our expectations for annual year-over-year growth in 2021.
Thank you. Tim's for the question. Then quite quite appropriate. In fact, when we look at the critic one read out as we send the bill used in the month free trial with fixing other Grande's and what do you have in the abstract in the poster at the APR course already calculated that you mentioned that both shows at 6 and the problem of the Panthers. We do offer via profile from a safety perspective of the 6 milligram. We talked about also in in looking at the older place to study generally very good at that those and that's the choice you have now seen the face place that you as well and the twelve uragan those we do see those response, but then we have to keep in mind as you very correctly said the overall Safety Management is. So, we'll continue to dig deeper into the data as we plan phase three studies in the Sahara car. It's great. But overall, we are very happy with the goals that we have tested in the pastry study. And of course we had said earlier we look at it off.
David V. Elkins: Moving on to our inline multiple myeloma portfolio on slide 12, Revlimid and POMELIS continue to perform very well, with strong double-digit growth on a performance basis; Revlimid grew 10% primarily driven by increased treatment duration, and Palmless grew 17% driven by growth in earlier lines of treatment and increased treatment duration in the U.S. We experienced some temporary softness in the nudibranchia during CO And this is being offset by better adherence and longer duration of therapy for existing patients. Ex-US performance sales for Revlimid increased 11%, while Ex-US performance sales for Promilus increased 19%. This strong performance was driven by increased use of triplet-based therapies and treatment duration in major European markets. COVID had a minimal impact on ongoing treatment, with a small impact observed in new patient SART.
And in the phase 3 the second beat out in the first quarter of next year as you move forward, so that's I think that the depreciation.
That it's not just about efficacy. We have to balance the benefit-risk and that's why the the the customer example seems quite reasonable for us, you know safety and efficacy combined and participation in that relates to the ultra-quiet the mechanism as you very well said, I think the differentiation the old Administration the convenience of treatment we talked about our sale required is is the browser already life. Now, we are looking towards a readout in the future for the victory program and bringing that differentiated mechanism once again, and hopefully be able to show the efficacy and safety for patience with all she has predicted will be important and yet I 12 and 23 in addition mechanism is going to play a big role of boat and also the collages and then in the future and Crohn's disease as well.
David V. Elkins: We are seeing strong signs of new patients returning to prior treatment. Now moving on to our recent launches on slide 13, Revazel has been off to a robust start with the approval of RS-positive MDS-associated meaning. Global sales in the quarter were $96 million, representing 75% sequential growth over quarter two.
Let me go to our next question, please.
Next question comes from Jeff Meacham of Bank of America.
Thanks a lot guys for the the questions just had a couple I think both of them both of them for Chris. So when you look at the first sign lung transfer you guys have a guy from Cher I think 5% or so in the US, but I don't see much of a trend break this quarter was there already reasonable share in first-line long before the label expansion and maybe just help us as well and the feedback from the ground so far and the second one on my GloZell the sequential Trends have been really strong. I know obviously it's early but what can you say about the distribution between wage and maybe just the Cadence of uptick between the two indications? Thanks a lot guys.
David V. Elkins: In the U.S., physician feedback remains positive, with significant awareness of the brand. While still early, we continue to be pleased with the launch, including new patient uptake and patient retention on the product, where the majority of patients have adhered to their treatment. As a reminder, a significant proportion of early uptick is driven by the initial bolus of patients waiting for a new treatment option. However, we remain very encouraged by the underlying demand for the product in patients with beta thalassemia, as well as MBS-related anemia. Internationally, recent launches in Germany and Austria are going well, although very early. We also received approval for beta thalassemia associated anemia in Canada and look forward to launching in various markets globally over the course of 2021 as we receive reimbursement. Turning to Sepposia, we're encouraged by what we're seeing through the first few months of Sepposia's launch. We are focused on driving demand and establishing Suposio as the leading S1P modulator in multiple sclerosis.
Maybe I'll start and then I'll turn it over to Nadine to drop the second part of your question. So with respect to let me just first give you the Dynamics for the quarter. So obviously happy with the schools will grow that we saw for the quarter page that um in the is a function of favorable demand and we'll talk about first line lungs specifically in a second. We also as David noted saw some inventory build this was off upset by the impact that we'd seen with the decline in Iowa eligibility that we've been discussing previously that means in the second line drastic indications and that still is a drug on a Divo currently that said we were happy to see that we got sequential growth for the quarter and that was in part as a a function of first-line lung and would respect personally one. You're very happy with what we're seeing with the launches so far in the the update continues to increase steadily as we noted earlier the market share is currently in the high single digits.
David V. Elkins: We have secured strong commercial access, and our commercial teams are executing well. We are pleased with the physician receptivity and prescription initiation we've seen thus far. Now moving on to our newest launch, IME-REG, which was granted approval for first-line AML maintenance by the FDA on September 1st. While very early in the launch, feedback from physicians has been promising. The message that On Your Egg is the first and only medicine to demonstrate overall survival in a maintenance setting with a convenient oral route of administration is resonating well.
Um, the execution here continues to be very good. So for example, we have a leading share of voice in in person lying lung and importantly at this phase of the launch. We're seeing a nice steady growth in the number of new trials took over week. So overall, we're happy with the update that we've seen. We we knew as we discussed previously that this was going to be a different set of launches. Just getting the insurance Dynamics from a competitive point, unfortunately, but we continue to be very pleased with the team's performance here. So maybe I'll turn it over to Nadine for the second part of your question.
David V. Elkins: This is a market that is largely underdeveloped as there were previously no FDA-approved options for patients in the maintenance setting after intensive chemotherapy. And like many other medicines in the maintenance setting, it will take some time to educate prescribers about the use of new treatment for a patient. NMA is under review in Europe, and we expect approval in 2021. And I'm moving on to our balance sheet and capital allocation on slide 14. We continue to generate a significant amount of cash flow from operations in the third quarter. We ended the quarter in a strong liquidity position with approximately $22 billion in cash and marketable security. That's after tax payments of approximately $1.7 billion for debt paydown and large cash payments, including tax payments associated with the gain on the test.
Great. Thanks, Jesse.
Question. So regarding the rebels launched maybe I'll just make a couple of points. So as David said very pleased with the launch so far and high demand very good brand awareness fuel team is doing really well. And if you remember we had always said that the predominant use at least in the would be and it's playing out exactly that same way. So today the majority you age in the US is on a patient and the interesting thing is we've all we've seen a little bit of a halo effect computer failing that we've seen a little bit more uptake with beat ourselves instead of lunch, but the predominant use is still MBS now globally as we launch across the world, there'd be different regions where you see a different fragments profile beta thalassemia where it's higher for example in Asia off the Mediterranean, but today in the US the predominant use is still envious exactly as we had anticipated questions,
David V. Elkins: For capital allocation priorities, we may deliver and achieve less than one and a half times that EBITDA ratio, which is now expected by the end of 2024. We continue our commitment to our dividends and investing in future innovation through business development. Touching on our business development activities, as Giovanni discussed, we have not wavered against our priorities.
David V. Elkins: We have executed some important deals in the third quarter, including our acquisition of Forbius, a license agreement with Dragonfly, as well as our recently announced pending acquisition of Myocardium. Each of these transactions is in line with our criteria for business development: Strategically Aligned, Scientifically Sound, and Financially Attractive.
And thanks Kevin. Can we go to the next question, please?
the next question comes from Terrence Flynn of Goldman Sachs
David V. Elkins: We will continue to be active in business development, searching for additional opportunities to further strengthen our growth profile of the company for the long term and creating value for our shareholders. Now, let's turn to guidance on slide six. Based on the strength of our results here today, we're updating our full year 2020 outlook. We are narrowing our revenue range to between $41.5 billion and $42 billion based upon our strong performance year-to-date.
All right. Thanks for taking the questions. I was just wondering first time for lung if you can give us any update on the regulatory path and when you might know more they're not confident that you could get approval on the the PCR endpoint alone. And then the second question you mentioned that this energy is our tracking ahead of your expectations. I guess just trying to understand how much of money to spend is synergies and how much is kind of, you know from a COVID-19 forward into the 20 21. Thank you.
David V. Elkins: And we do expect sales to be at the higher end of the range. According to operating expenses, we expect total spend to be generally in line with our. We do have some slight shifts in scope related to our MS&A and R&D lines. For MSNA, we decided to make additional one-time investments, such as accelerating DPC advertising to support the business as we close out the year, and we now expect to spend approximately $6.9 billion. This is being offset by lower R&D, which is now expected to be approximately $9.2 billion.
Thank you Terrance for the question Thomas here. Chris mentioned earlier. There is still obviously a much required need for new medicines in patients with early disease to be able to get into a technological complete response because that may signal for the long-term benefits to these stations. Now, of course, this is not a validated regulatory in point of view very often. So what we're looking forward to now of course continuing our dialogue with regulatory agency, especially with the FDA as we also continue to qualifications for the first day of 4 a.m. Please survival as well. So we will obviously keep you posted in the future as we make progress at the current time. We continue our dialogue and continue with the the patient follow-up break mobile. I don't think we can give clear guidance today in terms of approve ability based on the employment.
David V. Elkins: At the same time, we remain very pleased with our Synergy Capture, which, as Giovanni mentioned, Tracking Ahead of Original Estimatations. We now expect our tax rate to be approximately 16% for the full year. In taking all this together, we are increasing our full year adjusted EPS range to be between $6.25 and $6.35. Our revenue guidance takes into account the donut hole, which continues to affect eloquence in the fourth quarter, as I mentioned earlier, as well as continued competitive dynamics associated with some of our established grants.
Jeez, I think David or Thursday so far this year and we're really encouraged to see that our Synergy captures actually tracking ahead of our original expectations for for for this year. So we'll provide further insight to that on our expectations of the overall syndrome treatment. You don't have to we close the year, but you know things are going very well.
David V. Elkins: Now as it relates to our 2021 guidance, we are reaffirming our non-GAAP EPS guidance of $7.15 to $7.45, which absorbs the dilution associated with the myocardia acquisition. We look forward to providing more color on 2021 during our fourth quarter call, as we normally do. Before we move to question and answer, I want to thank all of our teams around the world for delivering such outstanding results here today
We go to our next question, please.
The next question comes from Tim Anderson of wolf research.
Thank you. I have a question on going back to take too. So I think most investors use it a value proposition and psoriasis relative of Tesla even better athlete to see but we've wondered if better tolerability can also be a differentiator because it has levers GI side effects that required drug titration and your drug doesn't require to estate relation to the remotes you had side effects. So when we see the full face he resolves my we also see better tolerable another area of differentiation Beyond just oral dosing and Beyond better ethnicity.
David V. Elkins: These results allow me to remain confident in a long-term outlook for the company. I'll now turn the call back over to Tim and Giovanni for Q&A.
Operator: Thanks very much, David. Kevin, can we go to our first question, please? Certainly. Ladies and gentlemen, if you would like to ask a question, please signal by pressing star 1.
Chris Schott: Our first question today comes from Chris Schott of J.P. Morgan. Great, thanks very much for the questions and congratulations on all the progress you've made this year. I guess I said two here, maybe first on the TIC-2. Can you just elaborate a little bit more on the safety profile?
Thank you Tim with a question. He said if you look at the overall trial design for this one as well as for the next 30 to be followed. The good news is that there is a comparable model need the table, but also the comparison versus the Tesla and so there will certainly be an opportunity to contrast and compare not only the efficacy but also the possibility our safety as we talk and those are going to be very important from a patient perspective and position perspective from a convenience perspective. Certainly. These will have implications from a commercial perspective and then we pass on to Chris to comment on that.
Chris Schott: I think there's still some lingering questions out there about whether we'll see any of the maybe some of the Jack-like safety issues. I know you've talked a lot about that in the past, but just to confirm, did you see any imbalance at all, you know, small or not, on thrombotic events from the poetic study and just help us a little bit in terms of what the profile is shaping up like. On the safety there,
Samit Hirawat: And then my second question was on DIVO. You're launching a number of adjuvant indications next year. Just remind us about those, do you expect these will have fast uptake like we've seen in some of the metastatic settings, or are these indications that maybe take a little bit longer to build out over time? Thanks so much.
Yeah, thanks for the question Tim. I mean, I think as we said previously we're excited with the opportunity that we have here based on the data that we see coming out of poetic. I think we have a real opportunity to establish as the front line break toys for these moderate to severe patients would I would say just to build on what solid mentioned is that? This is a market where in spite of new biologics coming into the space during just continue to believe in an ascending treatment algorithm. So they typically start with topicals they move to world then they go to injectables and it is also a market if they think you point out where patient preference right away. So you do see a very strong focus on safety concerns needle phobias and issues here and you think these Dynamics really play to the profile that we have with chick to very strong ethical in and formulation a novel limo a and a favorable tolerability and safety profile. And so we we think we've got real opportunity here to to establish kick as as the Leading Edge.
Samit Hirawat: Chris, thank you. I think I'll start off and then, Chris, I'll pass it on to you for the related question. From a TIC-2 perspective, first of all, we are very happy with what we've seen from the results. This is the first of the two phase three trials for TIC-1 that I've read out. And we have seen not only statistical as well as clinical meaningfulness versus placebo, but also superiority versus epinephritis or TESLA in moderate to severe psoriasis. From what we have seen before from the phase 2 studies, and we've talked about the safety profile, we continue to believe in that. There is a differentiated mechanism of action that we believe in.
space
having to be good for next question, please.
The next question comes from Andrew Baum up City questions, please first on a Tesla is you think about marketing. Is it position to judge this place a Tesla as the oral agent a choice given the efficacy tolerability or to what extent can you actually seek to slow or defer the initiation of therapy with biologics then second perhaps you could just give us the market shares in non small-cell 42279 aley in the u.s. In the first line setting. Thank you.
Samit Hirawat: We do think that the TIC-2 inhibition, which has a specific downstream effect on R12, R23, as well as interferon alpha, has played out. And we continue to believe in that. Of course, I can't go into the specifics of the data. They will be presented in the future at a medical meeting. But overall, we are very happy where we are, and I look forward to the readout of phase 3 in the first quarter of 2021. So hopefully, that answers your question, and let me pass it on to Chris to talk about MDRO from here on.
Sure. Sure Andrew. Thanks for the question with respect to Tesla and how we are looking at the opportunity arises. I mean, I think the way I answered the previous question is probably what I would go back to we take based on these data that Tech has the opportunity to to be the Branded full of choice for for moderate-to-severe patients at large in the space. And we think that's a reflection of the fact that this is a market where dermatologist typically are going to try to treat with lessburg routes of administration. They're going to go for the activity that that the best activity that can find however safety is a prominent concern here. And so I think that we have a great opportunity to displace existing therapy with respect to orals pre biologic and we also believe that we have the opportunity to potentially provide more of an opportunity before patients move onto Biolage.
Chris Boerner: Sure, thanks for the question, Chris. We do have a number of exciting opportunities in the adjuvant setting. I'll maybe just highlight gastric and bladder specifically.
Chris Boerner: As we talked about a few months ago with respect to gastric cancer, we're excited about the opportunity coming out of Checkmate 577. This is a space where there is significant unmet need. There's very little in the way of systemic therapy that's used here, and as Samit has previously talked about, those patients who are getting neoadjuvant chemoradiotherapy, about three-quarters of those patients don't get PATH-CR. So really, there are no great options for those patients.
Chris Boerner: And we've seen very good efficacy coming out of 577 with a doubling of DFS at a manageable safety profile. And there's relatively clean air here from a competitive standpoint, as this will be the first IO in the setting for a number of years. With respect to bladder, again, happy with the results that we saw with 274. This is a space with about six to 7,000 treated patients in the U.S. Again, not a lot in the way of great systemic therapies here. And as we've said, we met the primary endpoint for Obdivo and very much look forward to launching in this space. And this is again, another space where there's relatively clean air.
And remember this is the space. We're only about 15% of patients ultimately ever get to biologics and that's in spite of a number of new biologics coming into into the market. So we may actually have an opportunity to do both as it relates to the first line lung market share as we said previously in his David mentioned we have current first-line market share in the High Council digits. The 227 regimen is mainly being used in the PDL one 249 as expected and then received recent uptake of the 9th regiment and that's mainly in a PDL one less than one in pdl1 negatives.
Excuse me, Kevin. Could we go to the next question, please? Wait, the next question comes from Louisa Hector of berenberg.
Oh, hello. I wondering now we have to ask abstract. Was it anything you'd like to point out from the various places that you're presenting and particular update from home ability of response. And then uh, I decide to sell any update you can give up for me. Thank you.
Chris Boerner: So we would expect reasonably aggressive uptake in both of these indicators. Thanks, Chris. Can we go to the next question, please? The next question today comes from Seamus Fernandez of Guggenheim. Oh, great. Thanks so much, everybody.
Seamus Christopher Fernandez: You know, congrats on the quarter and all the progress as well. Samit, my question is actually, on the higher dose, the 12 milligram dose that we're going to see next week in Suryatica Slated. You just give us, you know, that's really where we've seen problems with other jacks. I'm just trying to get your sense of what we should be looking for in these data, obviously, they're about to be presented, but I think that's something that investors were interested in. And then, incremental to that, as we think about the opportunity in areas like ulcerative colitis, you've really emphasized this aisle 23 1223 profile. Is that really where you are? Thank you, Tim, for the question. And quite, quite appropriate. In fact, when we look at the POETIC-1 readout, as we said in the preface, the dose used in the phase three trial is the six milligram dose. And what you have in the abstract in the poster at the ACR for psoriatic arthritis, as you mentioned, are both doses, 6 and the 12 milligram dose.
Sure, thank you. So let me start with Ash first and then I'll go to the license. I just tell and then certainly if you want to comment also took Ash the sector over the last few years certainly both sides and who keeps our demons demons have had dated presents and based on the data that have been presented in the past. So obviously these medicines are now moved it states developing and we are continuing to gather more data having said that there are a few abstracts that are very important that are being presented. So number one the activity of life itself the single month credit. The account has been combination where the group had been patients will receive another class both in CLL are quite important and interesting. If you look at the overall response rate eligibility check eligibility in these patients that continue to evolve especially as you think of the future where the population with the elevation to see how they have been treated with the business and another class there.
Will be a need for subsequent therapy that they rescue them disease as occurrence or relapse another dataset will be presented as you might have seen the abstracts will be the triple combination with the premium app as well as his own and then they didn't text messages own and those are revolutions in the data set and we will continue to see how that that comes through. But certainly respond athletes are going to be important as we look forward to.
Samit Hirawat: We do see a profile from a safety perspective of the six milligram dose, as we talked about. Also, in looking at the older phase two study, generally very good at that dose, and that's the efficacy we have now seen in the phase three study as well. At the 12 milligram dose, we do see a dose response, but then we have to keep in mind, as you very correctly said, the overall safety management is up. So we'll continue to dig deeper into the data as we plan phase three studies in the psoriatic arthritis phase. But overall, we are very happy with the dose that we tested in the phase two study. And, of course, as I said earlier, we will look at it again in phase three, the second readout in the first quarter of next year as we move forward.
Using I. Am I going to be earlier settings as these data will then start dictating how we proceed further? So very happy with these will continue to look deeper into it and next year will be big from a chrome as you look through the completion of the trials rather than I and then of course progressing other settlements as you heard from Germany and is opening comes from a prospective. Not much to share, uh, except for the fact that we've already communicated. We continue our dialogue with the Regulatory Agencies. We've had the the inspection done for the facility in Washington, and as you communicated earlier that we don't have any any schedules inspections for the second squared away just double-check, which is independent of the other facility for lifestyle. We do have a particular date on 16th of November to either sell same thing. We are continuing our dialogue and if you have a phone number
Samit Hirawat: So that's, I think, the differentiation, that it's not just about efficacy. We have to balance the benefit-risk, and that's why the six milligram dose seems quite reasonable for us from a safety and efficacy combined benefit-risk ratio. As it relates to ulcerative colitis, the mechanism, as you very well said, I think the differentiation, the overall administration, the convenience of treatment, we've talked about ulcerative colitis with diposia already, and now we are looking towards a readout in the future for the TIK2 program, and bringing that differentiated mechanism once again, and hopefully being able to show the efficacy and safety for patients with ulcerative colitis with And yes, the IL-12 and IL-23 inhibition mechanism is going to play a big role both in ulcerative colitis and then in the future in chronic disease as well.
The date of March 27th of 2021. That's where we are other one again if you want to add something or you're right.
I think you covered it well stomach. Thanks. The only thing I would ask what what time it mentioned with respect them. As always. Obviously. We we will update you as our discussion with the regulatory authorities progress.
Thanks, Giovanni, Kevin. Can we go to the next question, please?
Next question comes from De Leon of Raymond James.
All right. Thank you for taking my question. Congratulations on all the progress just some quick runs from May. When do you think you would be able to disclose the actual logic complete response rate for the 816 study? And if that would still be non non disclosure item for you until regular discussions complete. Could you at least give us how the study was powered on that end point so we can make our own assumptions on how to chemo farm would perform and then how the condo arm probably would have bought that Sig and then in terms of either divided do you have a longer timeline now in terms of path to pivotal studies and and when that could happen gets Market, I think a lot of us in the kind of community as well or thinking about this as an offset to revlimid in the patent expiration there. So any kind of long
Samit Hirawat: Thanks, Samit. Kevin, can we go to our next question, please? The next question comes from Geoff Meacham of Bank of America. Great. Thanks a lot, guys, for the questions. I just had a couple, both of them for Chris.
Geoff Meacham: So when you look at the First Line Lung Trends for Optiva, Chris, you guys have gained some share, I think 5% or so in the U.S., but I don't see much of a trend break this quarter. Was there already a reasonable share in First Line Lung before the label expansion? And maybe just help us with what's been the feedback from the ground so far? And the second one on ribosomes, the sequential trends have been really strong. I know, obviously, it's early.
Chris Boerner: But what can you say about the distribution between MDS and beta-thal and maybe just the cadence of the uptick between the two indications? Thanks a lot, guys. Maybe I'll start and then I'll turn it over to Nadim to address the second part of your question. So, with respect to Avdivo, let me first give you the dynamics for the quarter. So obviously, happy with the sequential growth that we saw for the quarter. On that, in the US, it is a function of favorable demand, and I'll talk about first line long, specifically in a second.
Their term Insight you might be able to give them the development path would be super helpful. Thank you.
Thank you for the question. So let me talk with the PTR part. So certainly going to look for an opportunity for proper presentation of the data at a future medical meeting that is not dependent on the regulatory aspect because it's an independent and point that can certainly be discussed. So you look into that. I think the the trial details we have not shared the statistical analysis plan per se in terms of the the assumptions made for for example calculation on this time. So will we will not be able to share that but certainly there is a previous data may have been presented and published for chemotherapy needed to keep the responses. So you can assume with that. Now what differences did the important in terms of the Delta between chemotherapy and then the, the map those are the types of discussions you need to continue to have the regulatory agency as to what becomes meaningful so as as the dialogue involved and once the decisions are made wage.
Chris Boerner: We also, as David noted, saw some inventory build. However, this was partially offset by the impact that we've seen with the decline in IO eligibility that we've been discussing previously. That's mainly in the second line thoracic indications, and that still is a drag on Avdivo. Currently, that said, we were happy to see that we got consequential growth for the quarter, and that was in part as a function of first line long. And with respect to first line long, we're very happy with what we're seeing with the launches so far in the US. The uptake continues to increase steadily. As we noted earlier, the market share is currently in the high single digits. The execution here continues to be very good. So, for example, we have a leading share of voice in the first line long.
Certainly communicate back with you from the adult microstructure the 4th Line + 30 is already from growing as we said and as I just mentioned previously as the data continues to evolve and we'll have that.
Chris Boerner: And importantly, at this stage of the launch, we're seeing a nice steady growth in the number of new trialists week over week. So overall, we're happy with the uptake that we've seen. We knew, as we discussed previously, that this was going to be a different set of launches just given the entrenched dynamics from a competitive standpoint in first line long, but we continue to be very pleased with the team's performance here. So maybe I'll turn it over to Nadine for the second part of your question. Great
Without or sometime next year those will be a trigger points for us to discuss that similar similar combinations dexamethasone discussions with regulatory agencies wage. If the data would suffice for the regulatory dialogue and the full-time job of setting and then as the data involved for the double up in the triplets in the earlier setting then you launched the later line trying to redeem. Do you want to add something to that sure I would just add a couple of points maybe so thanks for your question the point that took it had made our plans had always been to move from the doublet to the triplet which is as you know, very important, especially in relapse a newly diagnosed disease. So having these dates are Ash will be an important foundation how we moved the treatment up from the lateline setting then to the early relapse setting and then ultimately newly diagnosed settings since she would ask the question about reveling made an impact on the future. So so we have a game
Nadeem Ahmed: Thanks, Geoff, for your question. So regarding the Reblazil launch, I'll just make a couple of points. So, as David said, we are very pleased with the launch so far. High demand, and very good brand awareness. The Fuel Team is doing really well. And if you remember, we had always said that the predominant use, at least in the U.S., would be MBS, and it's playing out exactly that same way. So today, the majority of use in the U.S. is in MBS patients. And the interesting thing is we've seen a little bit of a halo effect on beta-thal and that we've seen a little bit more uptake with beta-thal since the MBS launch, but the predominant use is still MBS. Now globally, as we launch across the world, there'll be different regions where you see a different prevalence profile, beta-thalassemia, where it's higher, for example, in Asia and the Mediterranean. But today in the U.S., Geoff, the predominant use is still MBS, exactly as we had anticipated.
Play development plan at Summit says of. The past all the clinical Gates as we go through but the starting point is the triplet data that we're seeing. So we're excited about the opportunity moving forward. Thank a question.
Let me go to the next question, please. Next question comes from David Risinger of Morgan Stanley.
Yes. Thank you very much. So I have two questions, please first. Could you provide more color on what you need to discuss with? The FDA on life itself would seem to me that discussion should be over by this point and a follow-on to that is are there any issues with the recent manufacturing inspections or your confidence following those managers inspections? And then the second question is other b c m a c s has been associated with ocular talks in multiple myeloma. Do you expect a differentiated profile for your BCM? Acc9 902 and when should we expect to see data? Thank you.
Nadeem Ahmed: Thanks for your question. Again, thanks. Kevin, can we go to the next question, please?
Terence C. Flynn: The next question comes from Terence Flynn of Goldman Sachs. Hi, thanks for taking the questions. I was just wondering, first of all, on OpDivo for neoadjuvant lung, if you can give us any update on the regulatory path and when you might know more there and if you're confident that you could get approval on the PCR endpoint alone. And then on the second question, you mentioned that the synergies are tracking ahead of your expectations. I guess just trying to understand how much of the spend is synergies and how much is kind of, you know, from a COVID environment. And so how much of that should we expect to carry forward into 2021?
Thank you for the question for Life as we mentioned earlier as we disclosed in the past you have informed the company that both are plants in washing as well as the one in Texas need to be inspected. They've been able to inspect the plant in Iraq Washington at this time, but have not scheduled any inspection on a second class. As you know, after you are doing what they can to ensure the staff are kept safe and it's called the pandemic and because of the travel restrictions, you have to obviously honor their desires to wage and then they go as we said in the past that the conversations with the agency that brings out and we look forward to seeing the the hopefully the wage at some point to be able to bring it to the patients as soon as possible. Obviously let you know as soon as we get the decision. We are not very common obviously specifically about the dialogue around
Samit Hirawat: Thank you. Thank you, Terence, for the question. Samit here. As Chris mentioned earlier, there's still obviously a much needed need for new medicines in patients with early disease to be able to get into a pathological complete response because that may signal a long-term benefit for these patients. Now, of course, this is not a validated regulatory endpoint, as you very well said. So what we're looking forward to now, of course, continuing our dialogue with the regulatory agencies, especially the FDA, as we also continue to follow these patients for the first data on event-free survival as well. And we will obviously keep you posted in the future as we make progress. At this time, we continue our dialogue and continue with patient follow-up to generate more data.
Inspections Etc. You're generally very happy with the dialogue that has been happening on the 80s.
Nissan for multiple myeloma here in the states. It's only time to comment whether we'll be able to differentiate or not. But we absolutely are aware of the ocular toxicity and certainly will keep that in mind as we go along. We continue to evaluate the patience for that. I think the First Data we would see would be Sometime Late next year because we are still in the build escalation paid and so that's certainly as soon as the data I've matured enough to be presented will be able to bring it to the medical conference and share that view.
Samit Hirawat: I don't think we can give clear guidance today in terms of approvability based on the, And for Synergies, I think David or... David, why don't you go ahead? Thanks for the question. Look, we've been very pleased with our ability to capture Synergy so far this year, and we're really encouraged to see that our Synergy capture is actually tracking ahead of our original expectations for this year. So we'll provide further insight into our expectations of the overall Synergy achievement after we close the year, but things are going very well. Thanks, David.
We get your next question, please.
next question comes from Greg Gilbert of truest
All right. Thank you for the questions Giovanni. You've made it very clear that cardiovascular is a core franchise for the company on Factor. Eleven a what do you think you have to deliver in terms of clinical profile to enable that asset to add value in what will eventually be a generic environment and then maybe more strategically and cardiovascular looks like you have at one end of the spectrum kind of a mass-market wage in fact or 11 a approach and on the other hand a more specialized approach with myocardial. I assume your strategic vision and cardiovascular spans across that I am a curious if you want to be more focused in one end or the other as you consider additional be being cardiovascular and then a follow-up for David. How would you describe the l o e step down for reveling in the coming years? And do you think this street has that right at least in general in terms of how it's being modeled? We obviously have an imperfect information. Thank you.
David V. Elkins: Kevin, can we go to our next question, please? The next question comes from Tim Anderson of Wolf Research. So I think most investors, Value Proposition, and Teriasis Relative.
Tim Anderson: But we've wondered if better tolerability could also be a differentiator because with a Tesla, there's a GI side. The Bulletproof Executive 2013, When we see the full Phase 3 results, might we also see better tolerance? Thank you, Tim, for the question. As we said, if you look at the overall trial design for this one, as well as for the next study to be followed, the good news is that there is a comparison not only versus placebo but also versus the Tesla. And so there will certainly be an opportunity to contrast and compare not only the efficacy but also the tolerability or safety, as we talked about. And those are going to be very important from a patient perspective and from a physician perspective, from a convenience perspective. Certainly, these will have implications from a commercial perspective. And let me pass it on to Chris to comment on, Yeah, thanks for the question, Tim.
All right. Thank you Greg. Let me start and then maybe I'll ask on specifically on cardiovascular factor in the increase to add and then they did more cover your question about the l e. So first of all, let me say yes to answer your question. Can you ask you a reason a strategic importance to us? And it has been consistently month for the company and when you look at what we've done with Eliquis, I'm really proud of our ability to develop differentiated assets in in cardiovascular take a very different approach to establishing the value of those assets in the case of Eliquis used to reload evidence as an example in maximize the value of the medicine. And so whether you look at Alec with you look at our camp in and talk to him and he better we feel really good about uh our ability to execute and cardiovascular and our commitment. I think the approaches are different between month.
Chris Boerner: I mean, I think, as we've said previously, we're excited about the opportunity that we have here based on the data that we see coming out of poetic. I think we have a real opportunity to establish tick as the frontline branded oral choice for these moderate to severe patients. What I would say, just to build on what Samit mentioned, is that this is a market where, in spite of new biologics coming into the space, dermatologists continue to believe in an ascending treatment algorithm. So they typically start with topical, then move to oral, then go to injectables.
Chris Boerner: And it is also a market, as I think you point out, where patient preference drives choice. So you do see a very strong focus on safety concerns; needle phobia is an issue here. And we think these dynamics really play to the profile that we have with Tick-2, very strong efficacy in an oral formulation, a novel MOA, and a favorable tolerability and safety profile. And so we think we've got a real opportunity here to establish Tick as the leading oral in the space. Kevin, can we go to our next question, please?
I said like Eliquis or factory could be in those cases as you know, we made a choice to partner those assets because we want to be working with another company that offers together enables us to have a broader reach into a primary care market and support the development of assets that require very large investments in the divorce settlement, uh on the asset across multiple indications. I think when when you look at my accountant, uh, it's much more about a Precision approach to cardiovascular which feeds a really nicely with our with our strategy actually very consistent with the early guideline. We have in heart failure in calculus cure. So I don't think it's necessarily one one approach versus the other but it's really looking at cardiovascular is one of the areas where the underneath continues to be really high. The company has demonstrated ability to execute which is excellent and then we take wage
Andrew Baum: The next question comes from Andrew Baum of City. Thank you. A couple of questions, please. First, on Tesla, as you think about marketing, is the position to replace Tesla as the oral agent of choice, given the efficacy and tolerability? Or to what extent can you actually seek to slow or defer the initiation of therapy with biologics?
Chris Boerner: And then second, perhaps you could just give us the market shares in non-small cell for 227, 9LA in the US in the first line setting. Thank you. Sure, sure. Andrew, thanks for the question. With respect to Tesla and how we are looking at the tick opportunity in psoriasis, I mean, I think the way I answered the previous question is probably what I would go back to. We think, based on these data, that tick has the opportunity to be the branded oral of choice for moderate to severe patients writ large in this space. And we think that's a reflection of the fact that this is a market where dermatologists typically are going to try to treat with less burdensome routes of administration. They're going to go for the activity that, the best activity they can find.
different approach, uh, depending on what it needs in order for its value to be maximized and when we spms had the best at
The best capability so you know, that's what we think about it. And actually my reality is a really really interesting asset because uh and acquisition because uh, the Precision approach is really consistent with you when you look at things and let me just ask Summit if you wants to add anything on on fact eleven a specifically differentiation in our development strategy and then back to your question about limit.
Thank you. Do I need one thing that I would also have never can remember patience with obstructive hypertrophic cardiomyopathy the ones that are symptomatic the ones that we are talking about life in perspective also have it with me especially if you could relation that they experience so eloquently use that as well and many are cardiologists are very well aware of of using actors and certainly in the future when camping my potentially might be available would be very helpful for these patients coming back again, then uh onto the anticoagulation then try to eleven a I think certainly very happy that we are in that space and developers what we have done two things that are going to be important to remember is number one. There are still leading this and Paige promised to get seated with Google get up off the currently available in this and some patients are not even treated because the reading lists the second uh-uh unmet medical need is that
Chris Boerner: However, safety is a prominent concern here, and so I think that we have the opportunity to displace existing therapy with respect to oral prebiologic therapy. And we also believe that we have the opportunity to potentially provide more of an opportunity before patients move on to biologics. And remember, this is a space where only about 15% of patients ultimately ever get to biologics. And that's in spite of a number of new biologics coming into the market. So we think we actually have an opportunity to do both.
Chris Boerner: As it relates to the first line lung market share, as we said previously, and as David mentioned, we have current first line market share in the high single digits. The 227 regimen is mainly being used in the PDL1 to 49, as expected, and then we're seeing recent uptake of the 9LA regimen, which is mainly in the PDL1 less than one and PDL1 negative.
Patients cannot be treated on top of their background and that lately therapies for for indications such as the secondary Spokes and that is a very high and the medical need and and patients who have had a choice robot very high risk of experience in the second row of maybe even fifty to sixty percent probability. And therefore what we're looking for in the factory lemonade Welby program as we look at the places that are correct I'm doing is the is number one the decrease in the reading ability and second is a combined ability that that background. We haven't updated agents in the same direction. It's got to be ongoing and in terms of its enrollment. So those are the the important aspects that will make us go into the safety development program. Once the data are available any possible David and two comments later and have you have you beside
Operator: Kevin, can we go to the next question, please? Certainly. The next question comes from Luisa Hector of Barenburg. Oh, hello.
Luisa Caroline Hector: I wonder now that we have the ASH abstract. Was there anything you'd like to point out from the various data sets you're presenting and any particular updates on durability of response? and then Ida Sell and Liza Sell.
Samit Hirawat: Any updates you can give us on the FDA review? Thank you. Sure, thank you. So, let me start with Ash first, and then I'll go to the life of cell, either cell, and then certainly if Nadine wants to comment also, that would be wonderful.
Yeah, thank you, sir. Thank you. For the question. We made great progress this year on the front both with revlimid as well as with Eliquis. And as you know settled with dr. Reddy's we we have the settlement with nacho, which just to remind you. Remember your natural agreement is a single-digit volume entry in 20 22, which grows to about a third of like twenty twenty-five and we have other settlements which aren't public with. Dr. Reddy's in and allergen but as you know, we clearly see it more as a month not as Cliff starting in twenty-two with full generic entry coming in 26th. And you have the time you did. The acquisition I would say is that we took a more conservative view on Rebel met them outside Equity Analyst at that time. So, you know with that said you still believe recommend will at potential, you know, significant cashier for the business over that
Samit Hirawat: So for Ash's perspective, over the last few years, certainly both Celgene and, I think, Celgene as well as BMS have had basic, And based on the data that has been presented in the past, obviously, these medicines have now moved on to late stage development, and we are continuing to gather more, Having said that, there are a few abstracts that are very important that are being presented. So number one, the activity of lysocele as a single therapy, as well as in combination with abrutinib in patients who have received prior abrutinib and venetoclax, both in CLL, are quite important and interesting if you look at the overall response rate, tolerability, as well as durability in these patients that continue to evolve, especially as we think of the future where the population with CLL, where patients with CLL will have been treated with abrutinib and venetoclax, there will be a need for subsequent therapy that will rescue them if the disease has a recurrence or relapse.
. From 20 to 3:25
Yeah, thank you David. Let me just let me just irate irate. I think specifically to your question when we look at the period during which you know over time the slope of credit limit will take place between 2022 to 2000. Sorry 2020 to 2026. First of all, I think you know, I think they displaying out the way we had told it to be a slope that starts at a point where the overall performance of the brand has been really strong in our view of Ip and strength of Ip has been validated by you know, the idea is that we're not granted and and and with the settlements that uh that David mentioned at the same time, you know the strength on our business. Let me ask you to be a really really good the progress we've made with a pipeline has given us a real confidence in our ability as a company wage.
Samit Hirawat: Another data set will be presented, as you might have seen in the abstracts, will be the triplet combination of arbutamide, daratumumab, as well as dexamethasone, and then valcade and dexamethasone. And those are evolutions in the data sets, and we'll continue to see how that comes through, but certainly, response rates are going to be important as we look forward to moving arbutamide into earlier settings, as these data will then start dictating how we proceed further. So I am very happy with these.
Samit Hirawat: We'll continue to look deeper into it, and next year will be big from a cell mods perspective, as we look to the completion of the trials for arbutamide and then, of course, progressing other cell mods, as you heard from Giovanni in his opening comments. From a LysaCell perspective, not much to share, except for the fact that we've already communicated, and we continue our dialogue with the regulatory agencies. We've had the inspection done for the facility in Washington. And, as we communicated earlier, we don't have any scheduled inspections for the second facility, which is independent of the other facility.
Continue to redo the portfolio. So as I mentioned at the beginning, I feel really good about our ability to continue to perform very strongly as we renew our money per folio during the time in which over time are limited will lose exclusivity. That's what we set up to do from the very beginning and I think execution so far has been really strong with which makes me confident in our ability to continue to be successful during that time.
Samit Hirawat: For LysaCell, we do have a PDUCA date on the 16th of November. For IDSL, same thing, we are continuing our dialogue, and we have a PDUCA date of March 27 in 2021. That's where we are. I don't know, Nadim, if you want to add something or Giovanni?
Giovanni have we met have time for one or two more than just the next question.
the next question comes from Matt V of William Blair
You want to thank the next quarter wondering if after the mafia thought it was study. If you're going to look at moving this effort into a more mild fish and setting off similar to the recent study. And then also I think a quick question on how much for the attractiveness and just wondering if you could compare and contrast maybe moving a tgf-beta and monochrome plus something like that via versus a buy specific molecule like, uh in traffic Alpha that has the tgf-beta Trap kind of combined with antibiotics month.
Nadeem Ahmed: I think you covered it well, Samit. Thank you. The only thing I would add is, Giovanni, just to close on what Samit mentioned with respect to license law. As always, obviously, we will update you as our discussion with the regulatory authorities progresses. Thanks, Giovanni.
Giovanni Caforio: Kevin, can we go to the next question please? The next question comes from Dane Leone of Raymond James. Hi, thank you for taking the question. Congratulations on all the progress. Just some quick ones from me.
Dane Leone: When do you think you will be able to disclose the actual pathologic complete response rate for the 816 study? And if that would still be a non-disclosure item for you until regulatory discussions are complete, could you at least give us how the study was powered on that endpoint so we can make our own assumptions on how the chemo arm would perform and then how the combo arm probably would have performed to hit that segment? And then, in terms of Ivertamide, do you have a longer timeline now in terms of a path to pivotal studies and when that could actually get to market? I think a lot of us in the clinical community, as well, are thinking about this as an offset to Revlimid and the patent expirations there. So any kind of longer-term insight you might be able to give on the development path would be super helpful. Thank you for the question. So let me start with the PCR part.
Thank you for the questions that first of all on the object. Well, you know that we are very happy with the results from the Toyota can study. You also know that there's a broad program be under way that we have the the evaluation on growing and so I I try this and Lucas at the beautiful Fridays as well as the inflammatory bowel disease. I said I said we certainly have an eye on it in probably think about this we evolved with the data on the psoriasis. You have to look at the overall efficacy and safety profiles in the second study authors and that will dictate where we go next in terms of evaluation of the equipment in and psoriasis and and other education related to psoriasis on the home front of course aware of the device specifically be afraid of pd-1 that the competitors have when we look at previous data the specificity of dead.
Samit Hirawat: So certainly, we're going to look for an opportunity for a proper presentation of the data at a future medical meeting. That is not dependent on the regulatory aspects, because it's an independent endpoint that can certainly be discussed. So we'll look into that. I think the trial details. We have not shared the statistical analysis plan, per se, in terms of the assumptions made for the sample size calculation. And this time, so we will not be able to share that. But certainly, there is previous data that have been presented and published for chemotherapy leading to PCR responses. So you can assume with that.
In addition cost by this particular antibody is very important and we certainly will look at the combinations with with our own pipeline. Not only with the roadmap that we also have elected members, you know in development team will be looking at all those combinations are
Deceive themselves computer evolved and we kept it see what the bills and the and the schedule will be for it. So during patients had some clarifications and that we paid the way for the combination start looking for I think having the ability to give to that separately will give us more opportunities for combination strategies looking forward.
Samit Hirawat: Now, what differences will be important in terms of the delta between chemotherapy and then the combination with Nivolumab? Those are the types of discussions we'll need to continue to have with the regulatory agencies as to what becomes meaningful. So as the dialogue evolves, and once the decisions are made, there's certainly a need to communicate that with you.
Can we get your last question, please?
Great. Good. Good morning. Thanks for taking the question for asking a quarter. I guess first a competitor in a digit space that was perceived to be most closely related to you with also an fcuk to regen dead discontinued the program recently, you know in the past you've been relatively sort of balance language in on the outlet for this program a change or updates on how you see there any comments on that discontinuation or or differentiation that maybe the street doesn't appreciate between those those two programs and then maybe coming back to the cell mods again wage. We think about the fiber to my decision sort of running independent to 9 to 480 or is there going to be a decision to be made at some point next year where you need to sort of pick a pick a winner or can they co-exist off?
Samit Hirawat: From the abetamide perspective, the fourth line plus study is already ongoing, as we said. And as I just mentioned previously, as the data continues to evolve, and we'll have the data readout sometime next year, those will be the trigger points for us to discuss that single agent or combination of dexamethasone discussions with the regulatory agencies to see if the data would suffice for a regulatory dialogue in the fourth line plus setting. And then, as the data evolves for the doublets and the triplets in the earlier setting, we'll launch the later line trials as well in the earlier setting. Nadeem, do you want to add something to that? Sure. I would just add a couple of points, maybe.
Sure. Thank you Carter. I think great questions. First of all the good side. We certainly have seen the announcement from from the competitor from discontinuation of the program on the website and we don't know the details in the structure of the molecule etcetera. But certainly we have our own module which isn't paid once. We also have been looking at to see where we can go that where the combination very very early on to be able to define the path forward as the data evolves will certainly update you and others in terms of where we go home or what the fate of the program will be but too early to say from our own perspective the specificity of America FC portion or an activity person. I think still needs to be investigated before besides the decision can be made on that side. So more to follow on to get in the future on the settlement and I've read my site as you said both of our town.
Samit Hirawat: So thanks, Dane, for your question. The point that Samit made, our plan had always been to move from the doublet to the triplet, which is, as you know, very important now, especially in relapse and newly diagnosed disease. So having these data, Ash, will be an important foundation for how we move the treatment up from the late-line setting, then to the early relapse setting, and then ultimately to the newly diagnosed setting, since you had asked the question about Revlimid and its impact in the future. So we have a very clear development plan.
And got in development. I brought my drums a little bit further because it started earlier for seating is a very different molecule. We shared the data out fifty plus percent of overall response rate the home for eighty percent of his own in the late lines cutting. Both of those studies are are in the in the developing the food line. Stop selling, but if you recall the overall development of Imaging at regular mail from a little my how they were developed in the heritage in organization how regulate them set up in the option setting and and some little night and became a preferred molecule for the second part of mine fishing population. So we have to keep that in mind as you continue to evolve and we also have the the good position that we have a lot of data available from the bottom of the structural that we can actually investigate to see what is the mechanism where these drugs work with the best what opportunities we may be dead.
Nadeem Ahmed: As Samit says, of course, we have to pass through all the clinical gates as we go through, but the starting point is the triplet data that we're seeing at Ash now. So we're excited about the opportunity moving forward. Can we go to the next question, please? The next question comes from David Risinger of Morgan Stanley. Yes, thank you very much. I have two questions, please.
David R. Risinger: First, could you provide more color on what you need to discuss with the FDA on Lysocel? It does seem to me that the discussion should be over by this point, and a follow-on to that is, are there any issues with the recent manufacturing inspections, or do you have confidence following those manufacturing inspections? And then the second question is, other BCMA ADCs have been associated with ocular tox and multiple myeloma. Do you expect a differentiated profile for your BCMA CC99712?
Prevail in terms of combination strategy development pipeline looking at the platform that you already have. Not only the cell not are also from the detailing behavior from Clarksville therapy as well as involving wage that one so those opportunities because of the principal must be having a hand can certainly before the
Investigators and brought us away rather than limiting ourselves to a singular sign on but let me ask you are needing to add anything. He wants to further elaborate on this. Thank you God. Sure. Thanks so much and thank Scott about your question. So I think right now we're very pleased with the early data. We're seeing for both and as Summit said, you know, we've done the thing the regular minimum wage. Also there are discrete patients segments with very different clinical needs where you could potentially see the coexistence of both. So for example, the maintenance setting so more of a better ability profile in a relapse setting with high-risk disease, you can see a more potent tool mod come through. So I think we're going to continue to look at the data, but we're pleased with how bout a progressing and then if somebody said, you know, one of our key objectives is to come up with this multi-modality combination of pro so you can visit Ur ass Ahmad plus VTOL.
Samit Hirawat: And when should we expect to see the data? Thank you. Thank you for the question. For life, as we mentioned earlier, as we've discussed in the past, FDA has informed the company that both our plants in Washington, as well as the one in Texas, need to be inspected. They've been able to inspect a plant in Washington at this time but have not scheduled any inspection of the second. As you know, our team is doing what they can to ensure that the staff are kept safe in this COVID pandemic. And because of the travel restrictions, we have to obviously honor their desire as to where they go and when they go.
Samit Hirawat: As we said in the past, the conversations with the agencies are going well, and we look forward to hopefully seeing the approval at some point to be able to bring it to the patients as soon as possible. We'll obviously let you know as soon as we get the decision. We are not going to comment, obviously, specifically about the dialogue around inspections, etc. But we're generally very happy with the dialogue that has been happening. On the ABC front for multiple myeloma, we are in phase one. It's early time to comment whether we'll be able to differentiate or not, but we absolutely are aware of the ocular toxicity and certainly will keep that in mind as we go along.
Made three multiple lines of therapy as patients progress from newly diagnosed disease disease and we've already seen the use of sequential treatment through the current cell number or even if I should say we're having a little problem there. So we do think that the combination of btma and Selma's across lines of therapy for different patients segments could be really important both critically and commercially, so thanks for your question. Thank you. Thank you and thanks to all of you for joining our call today. We had a a lucky discuss and I think that speaks to the black and that dead of our business and important to you about pipeline. So if we discuss it's been a really active year and a very very exciting first year for for for a new company and I can say with confidence that we still might be today is, you know, very strong position with significant near-term launch opportunities kind of substantial pipeline to address unmet needs of patients birth.
Samit Hirawat: We continue to evaluate patients for that. I think the first data we'd see would be sometime late next year because we are still in the dose escalation phase. And so certainly, as soon as the data are mature enough to be presented, we'll be able to bring it to the medical conference. Can we go to our next question, please? The next question comes from Greg Gilbert of Truist.
Carter Lewis Gould: Hi, thank you for the question. Giovanni, you've made it very clear that cardiovascular is a core franchise for the company. On Factor XI-A, what do you think you have to deliver in terms of clinical profile to enable that asset to add value in what will eventually be a generic environment? And then, maybe more strategically, in cardiovascular, it looks like you have at one end of the spectrum kind of a mass market approach with Eloquist and Factor XI-A, and on the other hand, a more specialized approach with myocardial surgery So I assume your strategic vision in cardiovascular spans across that, but curious if you want to be more focused on one end or the other as you consider additional BD in cardiovascular. And then, a follow-up question for David, how would you describe the LOE step down for Revlimid in the coming years, and do you think the street has that right, at least in general in terms of how it's being modeled? We obviously have imperfect information.
That will position us very strongly very well for the future. So thanks again for joining us. And as always our team will be able to answer further questions. You may could be taped. Thanks, everyone.
And gentlemen that concludes today's conference call. Thank you for your participation. You may know disconnect.
Giovanni Caforio: Thank you. Thank you, Greg. Let me start, and then maybe I'll ask specifically about cardiovascular and factor XI A, Samit and Chris to add, and then David will cover your question about Revlimid LOE.
Giovanni Caforio: So, first of all, let me say, yes, cardiovascular is an area of strategic importance to us, and it has consistently been so. I'm really proud of our ability to develop differentiated assets in cardiovascular, take a very different approach to establishing the value of those assets, in the case of Eliquis, which was through real-world evidence, as an example, and maximize the value of the medicine. And so whether you look at Eliquis, you look at Mavacamten, or a factory-level inhibitor, we feel really good about our ability to execute in cardiovascular and our commitment to cardiovascular. I think the approaches are different between a broader asset like Eliquis and a factory-level inhibitor.
Giovanni Caforio: In those cases, as you know, we made a choice to partner those assets because we want to be working with another company that together enables us to have a broader reach into the primary care market and support the development of assets that require very large investments in the development of the assets across multiple indications. I think when you look at Mavacamten, it's much more about a precision approach to cardiovascular, which fits really nicely with our R&D strategy and actually is very consistent with the early pipeline we have in heart failure and cardiovascular. So I don't think it's necessarily one approach versus the other, but it's really looking at cardiovascular as one of the areas where the unmet need continues to be really high. The company has demonstrated the ability to execute, which is excellent. And then we take a different approach, depending on what an asset needs in order for its value to be maximized and where we as a company are. At the best, at the best of ability.
Samit Hirawat: So, you know, that's what we think about it. And actually, my guardia is a really, really interesting asset for acquisition because the precision approach is really consistent with the way we look at things. Let me just ask Samit if he wants to add anything on factor 11a, specifically differentiation in our development strategy, and then we'll move to your question. Coming back again on to anticoagulation and Tractor 11A, I am certainly very happy that we are in that space and with aliquots what we have done. There are two things that are going to be important to remember. Number one, there are still bleeding risks, and patients don't necessarily get treated with full doses of the currently available agents. And some patients are not even treated because of the bleeding risk. The second unmet medical need is that patients cannot be treated on top of their background in late-life therapies for indications such as secondary strokes.
Samit Hirawat: And that is a very high unmet medical need, and patients who have had a first stroke are at very high risk of experiencing a second stroke, maybe even a 50% to 60% probability. And therefore, what we're looking for in the Factor 11A Development Program as we look at the Phase II studies that are currently ongoing is, number one, a decrease in bleeding probability. And second is the combined ability of that background therapy of anti-platelet agents in the secondary stroke prevention study that is currently ongoing in terms of its enrollment.
Samit Hirawat: So those are the important aspects that will make us go into the Phase III Development Program once the data are available. Any questions for David and to comment further on the review midterm? Yeah, thank you.
David V. Elkins: And Greg, thank you for the question. We made great progress this year on the IP front, both with Revlimed and with Eloquist. And as you know, we've settled with Dr. Reddy's. We have the settlement with NAFTA, which just to remind you, the NAFTA agreement is a single-digit volume entry in 2022, which grows to about a third by 2025. And we have other settlements which aren't public, with Dr. Reddy's and Aldergen.
David V. Elkins: But, as you know, we clearly see it more as a slope, not as a cliff, starting in 2022 with full generic entry coming in 2026. And, you know, at the time we did the acquisition, all I'd say is that we took a more conservative view on Revlimid than the sell-side equity analysts did at that time. So, you know, with that said, we still believe Revlimid will add potential, you know, significant cash flow for the business over that period from 22 through 25. Yeah, thank you, David. Let me just reiterate, specifically to your question, when we look at the period during which, you know, over time, the slope of the red limit will take place between 2022 to 2000.
Giovanni Caforio: First of all, I think that is playing out the way we had modeled it to be a slope that starts at a point where the overall performance of the brand has been really strong. And our view of IP and the strength of IP has been validated by, you know, the IPRs that were not granted and the two settlements that David mentioned. At the same time, you know, the strength of our business beyond the red limit has continued to be really, really good. The progress we've made with the pipeline has given us real confidence in our ability as a company to continue to renew the portfolio. So, as I mentioned at the beginning, I feel really good about our ability to continue to perform very strongly as we renew our portfolio during the time in which, over time, the red limit will lose exclusivity. That's what we set out to do from the very beginning. And I think execution so far has been really strong, which makes me confident in our ability to continue to be successful in doing that.
Giovanni Caforio: Kevin, we might have time for one or two more. Or maybe we can just go to our next question. The next question comes from Matt Phipps of William Blair. And then also, I think, a quick question on amorphobius acquisition. I'm just wondering if you could compare and contrast maybe moving a TGF beta monoclonal antibody plus versus a bispecific molecule like bintrapase alpha that has the TGF beta trap kind of combined with the PGL1 antibody.
Matthew Christopher Phipps: Thank you for the questions, Matt. First of all, on the TIC-2 aspect, you know that we are very happy with the results from the PRODICT-1 study. We also know that there's a broad program already underway where we have the evaluation ongoing in psoriatic arthritis, in lupus, SLE, lupus nephritis, as well as in inflammatory bowel disease. Mild psoriasis, we certainly have our eye on it. We obviously think about this as we evolve with the data on psoriasis. We have to look at the overall efficacy and safety profiles in the second study we did, and that will dictate where we go next in terms of evaluation of the aggressiveness in psoriasis and other indications related to psoriasis.
Samit Hirawat: So we'll be looking at all those combinations as the phase one study data evolves, and we get to see what the dose and the schedule will be for dosing patients with oncologic indications, and that will pave the way for combination strategies looking forward. I think having the ability to give two drugs separately will give us more opportunities for combination strategies looking forward. Kevin, can we go to our last question, please?
Samit Hirawat: Certainly, the last question today comes from Carter Gould of Barclays. Good morning, guys. Thanks for taking the question for us in a quarter. First, a competitor in the tiget space that was perceived to be most closely related to you with also an FC mutated region discontinued its program recently.
Carter Lewis Gould: You know, in the past, you've used relatively sort of balanced language in the outlooks of this program. Any change or updates on what you see there? Any commentary on that discontinuation or differentiation that maybe the street doesn't appreciate between those two programs?
Samit Hirawat: And then maybe coming back to the cell mods again, should we think about the ivertamide decision sort of running independent to 92480, or is there going to be a decision to be made at some point next year where you need to sort of pick a winner, or can they coexist? Thank you. Sure. Thank you, Carter. I think these are great questions. First of all, on the TZIP side, we certainly have seen the announcement from the competitor regarding the discontinuation of the program on the TZIP side. And we don't know the details and the structure of their molecules, etc.
Samit Hirawat: But certainly, we have our own molecule, which is in phase one. We also have been looking to see where we go with the combination very early on to be able to define the path forward for card cell therapy, as well as the evolving ADC platform.
Samit Hirawat: So those opportunities, because of the two Selmods we have in our hands, can certainly be further investigated in a broader way rather than limiting ourselves to a singular Selmod. But let me ask Nadeem to add anything he wants to further elaborate on this. Thank you.
Nadeem Ahmed: Thanks, Samit. And thanks, Carter, for your question. So I think right now we're very pleased with the early data we're seeing for both. And as Samit said, you know, we've done the same with Revlimid and Pomalyst in the past. So there are discrete patient segments with very different clinical needs where you could potentially see the coexistence of both cell mods. So, for example, in the maintenance setting, a cell mod with a better tolerability profile in a relapse setting with high-risk disease, you could see a more potent cell mod come through.
Nadeem Ahmed: So I think we're going to continue to look at the data, but we're pleased with how both are progressing. And then, as Samit said, you know, one of our key objectives is to come up with this multi-modality combination approach. So you can use a cell mod plus BCMA through multiple lines of therapy as patients progress from newly diagnosed disease to late-stage disease. And we've already seen the use of sequential treatment through the current cell mods or in this, I should say, with Revlimid and Pomeli. So we do think that the combination of BCMA and cell mods across lines of therapy for different patient segments could be really important both clinically and commercially.
Giovanni Caforio: So thanks for your question. Thank you. Thank you, Nadim. And thanks to all of you for joining our call today. We had a lot to discuss, and I think that speaks to the breadth and depth of our business and, importantly, our pipeline. So, as we discussed, it's been a really active year and a very, very exciting first year for our new company. And I can say with confidence that Bristol-Myers Squibb today is in a really strong position with significant near-term launch opportunities and a substantial pipeline to address unmet needs of patients that will position us very strongly and very well for the future.
Operator: So thanks again for joining us. And, as always, our team will be able to answer further questions you may have. Have a good day. Thanks, everyone. Ladies and gentlemen, that concludes today's conference call. Thank you for your participation. You may now disconnect.