ESMO Investor Event Transcript

The following is excerpted from the question-and-answer section of the transcript.

Question: Evan Seigerman - BMO Capital Markets - Analyst : Hi, Samit, and Tim. Thank you for the presentation. Two for me. While I appreciate the comparison to the PD-1 chemo in the real world in the non-small cell lung cancer setting, can you just walk me through what gives you the confidence to move into this large Phase 2 program based on a small subset of patients? And then just a follow-up there, taking a step back, how do you see this combination of Opdualag plus chemo fitting in with a rapidly developing non-small cell lung cancer space. And I'm specifically referring to some of the bispecific data we saw at World Lung and then today as well at ESMO. Samit Hirawat - Bristol-Myers Squibb Co - Executive Vice President, Chief Medical Officer, Global Drug Development, Member of the Leadership Team Thank you for your questions, Evan. For the first question, what gives us the confidence? Remember, this is our Phase 2 signal-seeking trial, which set out to ask two very important questions. First, to look if rela added on top of the I-O plus chemotherapy backbone and very systematically then explore that if it did, what is the next subgroup of patients where the drug works versus where it doesn't work. And there are three ways to look at this area. Number one, within the trial is that consistency of the data. And you may not have noticed it, but on slide 10 of the presentation this morning by Dr. Gerard, we saw the data in the part one of the study. That data then carries through in the randomized portion of the study. So, two parts. We saw the efficacy in PD-1-positive non-squamous cell lung cancer in part one that carried through in the randomized portion of that same study. Number two, in the randomized portion, we clearly saw the efficacy of rela on top of the I-O plus chemo backbone that was superior to what was present in the control arm. Number three, when we look at this data in the real world now, how the range of data for the control arm that is the standard of care today has evolved from the days of KEYNOTE-189 to what today we have seen in the real world, is somewhere around 6 months or so. These data bodes fairly well. And we believe that now there is a hypothesis that we need to test in the Phase 3 study, and we are confident these data put us in that position to be able to test the hypothesis of comparing rela plus nivo plus chemo versus pembro plus chemo. One important thing that the Phase 2 study allowed us to demonstrate already the contribution of components, meaning rela addition to the IO plus chemo backbone. So therefore, we can now avoid having a third arm in the Phase 3 trial. So that's for the first part of your question. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. SEPTEMBER 14, 2024 / 6:00PM, BMY.N - ESMO Investor Event The second about the landscape evolution in non-small cell lung cancer, especially the bispecifics that you talked about, I think, yes, we acknowledge there is a huge movement and that's great for patients that we are moving the non-small cell lung cancer treatment from target therapies to naked antibodies, to ADCs, bispecifics, and beyond. And every one of them will add to the ultimate outcome for patients. It's important to note -- it will be important to understand these data from a geographical application. And especially if you think about the bispecific data that you refer to PD-1 plus VEGF versus PD-1 alone, how that data will evolve and the global studies are conducted because remember, VEGF showed a differential activity when you look at Caucasian population versus the Asian population. And secondly, in population of non-small cell lung cancer below 50% expression of PD-1, the standard of care is not a single agent I-O. So I think it will be important to understand all of that. Then of course, we have to keep on thinking about what the durability is. And we saw very importantly what the control arm performance was, of course, of pembro as well as what the durability will be, we will continue to watch out for. So I think it's great, the portfolio is evolving. But as you also saw that what I showed, our portfolio is also evolving. So we are very competitive in the target therapy space, in radioligand space, evolution

Question: Chris Schott - J.P. Morgan Securities LLC - Analyst : Great. Thanks so much. Just two for me. Just can you talk a little bit about nivo and LAG-3 in the greater-than-50% population, is that something we should expect to move directly into Phase 3? Or is there more Phase 2 work to be done there? And should we think about chemo as a piece of that program? Just any additional color there. And my second question -- I know it wasn't part of the discussion, but we're approaching the Opdivo subcu PDUFA. So just talk a little bit about just -- how do you think about how quickly we should anticipate that new format ramping? Is that something that could go quickly? Or will that take some time to convert over the franchise? Thank you. Samit Hirawat - Bristol-Myers Squibb Co - Executive Vice President, Chief Medical Officer, Global Drug Development, Member of the Leadership Team Sure. Thank you, Chris. As always, great questions. So on the first question of nivo plus LAG-3 in the more than 50%, we are actively working on that design of the study. And while today, I'm not ready to provide you the specifics of the population as well as the control arm, but soon we will be able to share that information with you. We are excited about the data that has been generated and looking forward to discussing that very, very soon. In terms of the Opdivo subcu, as we have discussed before, truly excited by the PDUFA date coming up in December towards the end. We look forward to bringing that into the I-O franchise beginning of very early next year and extend that benefit to patients all the way through into the next decade. As Adam has spoken about before, we look forward to conversion of patients, about 30% to 40% of the US business to the subcu franchise. And certainly, we have about four years to accomplish that or looking forward to that conversion as well.

Question: Mohit Bansal - Wells Fargo Securities, LLC - Analyst : Great. Thank you very much for taking my question. Two for me, if I can. Samit, could you please help us understand why -- like we understand the subgroups it worked in, but in the subgroups such as squamous and then PD-1 expression less than 1% where the combination of rela did not work, could you -- what could be the rationale behind that? And the second part is, is it reasonable to think about combining rela with pembro plus chemo combination given that nivo plus chemo combination also did not fare well in the prospective trial? So just trying to get your thoughts on those two precaution. Samit Hirawat - Bristol-Myers Squibb Co - Executive Vice President, Chief Medical Officer, Global Drug Development, Member of the Leadership Team Thank you very much for that. So for the first question about why the drug did not work in less than 1% PD-1 expressors or in squamous histology, look, I think in the previous trials or in the past trials, actually there was a symposia today where Dr. Louis presented some of the data of I-O plus chemo in less than 1% expressors of PD-1 as well as in the squamous histologies, and the continuous evolution of the data has shown that PD-1 plus chemotherapy generally has had lower activity in squamous population as well as in the less than 1% expressors. Here, we actually -- when we look at the multi-weighted analysis, we see similarly. If you combine the two, less than 1% expression and the squamous histology, we do not see that activity. And therefore, we are focusing on the non-squamous and greater than 1% expression, that's where the best efficacy has been observed. I think the biology is quite interesting. And I think the Darwinian expression as we say, the tumors evolve and we'll have to continue to find new ways of treatment of these cancers as we understand and learn what we are going to gather from there. From the perspective of the control arm and the combination arm, certainly, there are opportunities of combining -- or there was an opportunity to combining rela, pembro, chemo, but we have our own PD-1 and chemo. And we did show within the trial that the investigational arm certainly performed better than the control arm in the subgroup of interest that we have shown over here. We do believe that these data are very comparable as we have seen within the trial, and then we take that beyond from both the range of data sets that have been available from KEYNOTE-189 and then beyond in the real-world setting. For the control arm, If you think about what nivo plus chemo has shown, and then if you take that data and look at it as it relates to the pembro plus chemo data, I think it fares pretty well in their compatibility. So we are confident in terms of conducting our study with nivo plus rela plus chemo and comparing that versus pembro plus chemo, and that hypothesis is now being tested in the Phase 3.

Question: Matt Phipps - William Blair & Company, L.L.C. - Analyst : Hi. Thanks for taking my question. Just curious what was the rationale for evaluating this higher dose of relatlimab in lung cancer versus what you -- it's approved in melanoma and also going with the Q3 week regimen, which does not point that Opdivo is, I believe, currently approved for now. Thank you REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. SEPTEMBER 14, 2024 / 6:00PM, BMY.N - ESMO Investor Event Samit Hirawat - Bristol-Myers Squibb Co - Executive Vice President, Chief Medical Officer, Global Drug Development, Member of the Leadership Team Yeah. Thank you for those questions, Matt. So on the high dose, that's very much based on what we have done in the pre-clinical space, looking at occupancy and certainly degradation as well as looking at the overall immune cell impact when we combine relatlimab and nivolumab. So we have to look at that data and try to achieve concentrations that are best. And in non-small cell lung cancer, we feel that -- we found that higher doses would be required to achieve an effect as opposed to what we had observed in melanoma. And that's why we did the Phase 1 study also to look at the safety of the combination of relatlimab. And there, as you saw from the presentation this morning, we did test out even a further higher dose of 720, but settled at the 360-milligram dose over here. We went with a Q3 week regimen over here, because the chemotherapy is given every Q3 weeks, so it matches very well with the dual chemotherapy or platinum doublet that is normally used in non-small cell lung cancer. And therefore, nivo, rela will be given along with the chemotherapy within the same regimen. Thank you.

Question: Trung Huynh - UBS Limited - Analyst : Hi, guys. Thanks for putting this together and answering my questions. Just two from me. So first, and perhaps a somewhat unfair question, but you pointed out the real-world setting for Keytruda plus chemo has evolved to be around six months versus the KEYNOTE-189 where we see a median PFS of nine months. So what is actually evolving here? Is it just simply people discontinuing earlier? Is there a discrepancy in the baseline population versus the real world setting? Or is there any other reason that you've concluded? And then just second, in the Phase II, you mandated GCSF administration prophylactically to address the neutropenia. You're also going to do that in the Phase 3. Just wondering how much of a burden is this for patients and prescribers and how common is it to administer GCSF in the first line with the standard of care? Thank you. Samit Hirawat - Bristol-Myers Squibb Co - Executive Vice President, Chief Medical Officer, Global Drug Development, Member of the Leadership Team Thank you for those questions. Look, as I said, over time, treatment of patients with non-small cell lung cancer continues to evolve. And I think as we think about the data, there's a range of data for I-O plus chemotherapy. And what we are seeing now in the real world, and again, this data -- this similar data for OS was also presented earlier today, where I-O plus chemo OS data in the real world does not look same at this time compared to what was shown in KEYNOTE-189. So this range of data, as we look at them -- and again large populations from the data that have been collected in the real world -- really support our own data within the trial and our hypothesis that the progression-free survival at this time is somewhere around 6 to 6.5 months. And that's what we're taking as a hypothesis that we are going to be testing in the clinical trials as well. From the growth factor perspective, truly based on the emergence of the data in the Phase 1 portion of the part one of the clinical trial, where we notice neutropenia and the best way to manage that was by allowing the use and then mandating the use in patients who are greater than 60 years of age, and that's what is based on the guidelines and that is very commonly done in this particular patient population. So this is not a burden -- at least we don't believe it's a burden and the physicians tell us and investigators tell us the same. And so we are carrying that forward in the Phase 3 trial as well and looking forward to readout of those trials and data. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. SEPTEMBER 14, 2024 / 6:00PM, BMY.N - ESMO Investor Event

Question: Steve Scala - TD Cowen - Analyst : Thank you so much. What is Bristol's best case scenario for filing rela plus nivo in first-line non-small cell lung cancer, and do you think you ultimately need to show overall survival benefit to see substantial uptake? So that's the first question. Second question is Bristol is confident in EGFR HER3 bispecific ADC based on China-only data. Just generally speaking, how would you characterize the reliability of data generated in China and your level of confidence in it being replicated globally? Thank you. Samit Hirawat - Bristol-Myers Squibb Co - Executive Vice President, Chief Medical Officer, Global Drug Development, Member of the Leadership Team Thank you, Steve. As is always the case, great questions. For the first one, look, it's an event-driven trial. We are just initiating the centers and beginning the enrollment of the clinical trial. We have not yet said what the filing date would look like but certainly over time, we will be able to commit and confirm those dates for you. And overall survival is the primary endpoint. So we are certainly looking forward to showing superiority on overall survival for appropriateness in this particular patient population. For your second question on EGFRxHER3 patient population data, we totally acknowledge that the primary data right now that we have are certainly from China-only clinical trials, and certainly, we are doing the global study right now has a Phase 1 to identify the right dose, if the dose is comparable to what we have seen in China as well. And that emergence of the data is going to continue to dictate how we are proceeding further. Now, having said that, it's substantial amount of data across multiple tumor types, showing single-agent activity in those multiple tumor types. So we do have to take that along. And certainly as we have learned, many of these ADCs are coming through now that have shown efficacy in the Chinese patient population. And now that efficacy is also translating into global settings when done appropriately. So we will continue to evaluate that. But certainly we're looking forward to taking this now into the global trials and registration trials with more than 850 patients already treated with this drug in China. So we are very confident with the emergence of these data.

Question: Chris Shibutani - Goldman Sachs & Co. LLC - Analyst : Thank you very much. Perhaps if I could ask a question about the MK cooperative PRMT5 inhibitor, you will have some updated data in the second half of this year at this meeting, ESMO. A competitor had some data, and there are several other players there. Maybe just around that particular approach, talk about your confidence in monotherapy. Perhaps is there something that you can help us understand that characterizes the potential differentiation either with your molecule and approach and which particular tumor types might we be expecting the updated data to come when you present it later this year. Thank you. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. SEPTEMBER 14, 2024 / 6:00PM, BMY.N - ESMO Investor Event Samit Hirawat - Bristol-Myers Squibb Co - Executive Vice President, Chief Medical Officer, Global Drug Development, Member of the Leadership Team Thank you, Chris, for the question. For PRMT5, we are not presenting our data here, but soon to be hopefully and within this year, another conference. We have seen the competitor data. One thing that we can say is what is going to be important is to observe what the duration of response is because stability of that response would be important and the duration of response is going to be important as well as the disease control rate beyond just the overall response rate. And so continue to watch out for that. And I think our data set is going to be much larger than what you have seen or you will be seeing from the competitors. So we're really looking forward to that. Will this drug have a very high response rate as a single agent? I think that is still to be confirmed. But certainly, both approaches will be very important, and I think are interesting, not only as a single agent but also starting to think about combinations, and we are already thinking about those. And soon, we will be initiating combination trials with this agent as well.

Question: Billal Jahangiri - Truist Securities - Analyst : Hi. This is Billal on for Kripa. I had a couple of questions. Do you think the RELATIVITY control arm is more representative today's real-world population than the KN-189. And also what did you see in the 720-milligram arm in part one that got you to go down to the lower dose and finalize on that? And then, I guess, for future combinations, what do you think is more prevalent to address here? How big of a concern is T-cell exhaustion with these I-O therapy? Would it make more sense to combine with PD-L1x4-1BB like agonistic type thing? Or do you think targeted cytotoxic agents is more of a priority? Thanks. Samit Hirawat - Bristol-Myers Squibb Co - Executive Vice President, Chief Medical Officer, Global Drug Development, Member of the Leadership Team Thank you very much. So I've said earlier, I think that we do believe that this control arm that we used and the data that we've seen within the trial is truly representative of what you see in the real world. By the way, if you look at other I-O plus chemo combinations in this space, repeatedly we are seeing a PFS similar to what we have seen in the control arm for nivo plus chemo within RELATIVITY-104. In terms of the dose, we tested both 360 and 720 dose in part one of the study. The 720 dose ultimately ended up being more toxic, and we saw that safety that you saw in the presentations today of the triplet of nivo, rela, chemo was very comparable to nivo plus chemo, and that's why we have taken the 360-milligram forward. And there, we've seen the efficacy already in the subgroup. So now we have the Phase 3 on hold. For future combinations, I think that one will need to be tested out that beyond the chemotherapy, can we go to chemo-free regimens or not? Jury is still out. We continue to see the evolution of that data. Some would say that while ADCs are a different way to approach it, but the payload is still chemotherapy. So that would be one approach, whether 4-1BB on top of PD-1s and then attaching them to another PD-1 or another I-O therapy will work or not. I think we just have to do the trials and understand if the efficacy stands or not. Thus far, we are far away from that.

Question: Charlie Yang - BofA Global Reasearch - Analyst : Great. Thanks for taking my question. My first one is, I'm just wondering like whether the -- the real-world how data set for the NSCLC that performed worse than the trial -- is that partly due to the fact that they are how in the real-world setting the outperformance score to patients who are on

Question: Sean McCutcheon - Raymond James & Associates, Inc. - Analyst : All right. Thanks for taking the questions. Just a couple for me. Can you speak to the dose flexibility or how you're thinking about the go-forward dose with AR LDD moving into a Phase 3 program, just given the cardiotoxicity you saw at the 900 mg BID dose? And how critical do you think getting to that higher dose or some intermediate dose above 600 mg BID will be to get sufficient degradation? REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. SEPTEMBER 14, 2024 / 6:00PM, BMY.N - ESMO Investor Event And then second question, I would be interested in getting your thoughts on what seems to be a general lack of PFS benefit for the anti-fucosyl-GM1, but a signal on overall survival, what your interpretation on the underlying mechanism is there and maybe why we're seeing this dynamic, and if we should expect to see that be replicated in our Phase 3? Thanks. Samit Hirawat - Bristol-Myers Squibb Co - Executive Vice President, Chief Medical Officer, Global Drug Development, Member of the Leadership Team Yeah. Thank you for both the questions, Sean. On the first one on the dose for AR LDD, very well said. I think there is a QTc signal that we have to be aware of. But that QTc signal is primarily Grade 1 and Grade 2, non-symptomatic, well managed with those interruptions or those decrease. We did not have any dose discontinuation due to QTc prolongation. With that said, though, it's an important one, and we'll keep an eye on it. As we look towards late-phase development of this particular molecule, we are changing the formulation, and the formulation will then bring our very manageable Cmax and AUC smoothening of the curves. So hopefully, we will be able to better manage the QTc signal over there as well as we look to initiation of these trials next year. For the anti-fucosyl-GM1, as I said earlier, across the board in small cell lung cancer, it has been very difficult to show a progression-free survival benefit. So I think what happens is the biology of the tumor changes with every treatment, and therefore, they add to the overall survival benefit that we have seen even in the earlier trials as we think about the evolution of this landscape. So we have a very strong hypothesis emerging from a randomized trial in the first-line setting that we have now got to do and prove in a Phase 3 study. Then that's what we are starting now, and I think it's an encouraging signal in terms of this disease, which has a very high unmet medical need.

Question: James Shin - Deutsche Bank Securities, Inc. - Analyst : Hi, guys. Thanks for squeezing me in. Seems LAG-3 was assessed at baseline in RELA-104. Did the BMY team do any exploratory look at LAG-3 expression levels and outcomes? And then secondly, Samit, there is some OS data from part one of RELA-104. It seems pretty in line with 189. Any concerns PD-L1 may not be the best biomarker? Thank you. Samit Hirawat - Bristol-Myers Squibb Co - Executive Vice President, Chief Medical Officer, Global Drug Development, Member of the Leadership Team Yeah, sure. Thank you very much. James, for the first question on LAG-3 expression, we did look at LAG-3 expression. And interestingly enough, the driver really is the PD-1 expression, not necessarily differentiating based on the LAG-3 expression. So we have to continue to monitor it. But within this trial, LAG-3 did not turn out to be a marker of great differentiation in terms of the activity of the drugs that have been used. So we have to understand that even better going forward. So we'll continue to collect that data, and let's see where it takes us. In terms of the data, I think part one data is very consistent that we have seen over to part one. In part one, we did see an overall survival also. But again, these are continuing collection of the data. We had a longer follow-up in part one. So we have an overall survival of about 22 months and approaching higher, but we again have to follow these patients longer. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. SEPTEMBER 14, 2024 / 6:00PM, BMY.N - ESMO Investor Event For part two, we only have a 10.7-month follow-up thus far. So we don't have enough information on the overall survival. And as that data matures and becomes available, we'll certainly be sharing that. And overall survival remains the primary goal and endpoint that one has to follow in the Phase 3 study. So we are conducting that study with that intention in mind. What I would say overall, with the portfolio that we have in non-small cell lung cancer, we have multiple opportunities to impact the outcomes for these patients. And that is a truly exciting part of conducting drug development at BMS and looking forward to bringing many, many of these updates in 2025 to you.