Bristol Myers Squibb Company's BMY CEO Giovanni Caforio on Early Pipeline and Immuno Oncology

Ladies and gentlemen, thank you for standing by and welcome to the Bristol-Myers Squibb Early Pipeline and Immuno-Oncology Call. At this time all participants are in a listen-only mode. After the speaker presentation there will be a question-and-answer session. To ask a question during the session you will need to press star 1 on your telephone. Please be advised that today's conference may be recorded. If you require any further assistance please press star 0. I would now like to hand the conference over to your speakers, Tim Powers, please go ahead.

Thanks Latisse and good morning everyone. Thanks for joining us today for the first of our three-part investor series. The plan for today is that we'll have a presentation followed by a Q&A session, and so if you're not participating via the webcast you can always go ahead and download the materials from bms.com. Joining me today for the presentation are Giovanni Caforio, Chairman and Chief Executive Officer; Rupert Vesey, Executive Vice President, Research and Early Development; Sumit Chakravarty, Chief Medical Officer, Global Drug Development; and Chris Boerner, Chief Commercialization Officer. And also with me today for the Q&A session are Anna DeMuth, President, Hematology; David Elkins, Chief Financial Officer; as well as some folks from our research and clinical teams for Q&A as well. Before we get started I'll read our forward-looking statement. During today's call we'll make statements about the company's future plans and prospects that constitute forward-looking statements. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors including those discussed in the company's SEC filings. These forward-looking statements represent our estimates as of today and should not be relied upon as representing our estimates as of any future date. We specifically disclaim any obligation to update forward-looking statements even if our estimates change. We may also discuss certain non-GAAP financial measures which are adjusted to exclude certain specified items. Reconciliations of these non-GAAP financial measures to the most comparable GAAP measures are available on bms.com. With that let's turn to Slide 3 and I'll hand over to Giovanni to start the leadoff.

Thank you very much Giovanni. In this next section I will cover Research and Early Development at the new BMS. I'm going to describe our organization and approach to drug discovery and early development, and I'll also provide insights into proprietary data sets and platforms and give you a summary of our robust early pipeline. Here you can see the members of my leadership team in Research and Early Development. This is a truly outstanding group drawn from both heritage organizations. They share many decades of drug discovery and development experience and have contributed in a wide range of venues including numerous small biotech companies as well as large-scale biopharma. This makes for a great blend of entrepreneurial spirit and outstanding execution. The new BMS has been fortunate enough to inherit a diverse set of research centers located in hubs of innovation across the United States. Each center has a specific area of focus and the ability to undertake integrated drug discovery, translational research, and early development. This creates a strong local identity and sense of purpose. They also have critical cross-site collaboration and are supported by a broad range of capabilities that makes them much more than the sum of their parts. In addition to our network of internal research centers we're bringing together the best of both heritage companies to create a leading external research model that will be a central part of our long-term future. This includes a broad range of activities including participation in VC funds, enabling academic incubators, equity investments in strategically important new companies, and industry-leading deal structures. We're further empowered by our geographical locations which place us close to most of our key partners. Evidence of the success of this approach can be seen in our emerging neuroscience pipeline where we have constructed a network of partnerships over just two years that has already yielded our first clinical program with the endocannabinoid enhancer. Research and Early Development at BMS is responsible for bringing forward the next generation of assets and demonstrating their initial clinical utility. We partner closely with our colleagues in Global Drug Development who have the size and scale to take the most promising assets and build them into products for our patients. In the next few slides I'd like to move on and describe how we think about our drug discovery and early development activities at BMS. We believe it's critical to start with the patient in mind, and that has driven major investments in foundational patient data sets that we can cull from our trials and numerous other strategic relationships. The application of molecular profiling technologies and cutting-edge computational research allows us to define both subsets of patients and the molecular pathology that matches that patient group. We can then utilize our array of innovative drug discovery platforms to identify the best approach to targeting the pathology and rapidly move to test the concept in the clinic. Programs that deliver successful evidence of clinical activity move into late-phase development with our GDD colleagues and we provide ongoing support through our translational medicine teams that continue to deliver scientific insights and in some cases complementary or companion diagnostics. I'll now give you an overview of how we're applying some of these critical data sets to our drug discovery work. In this example we've assembled some of the largest hematology data sets through a network of partners. The molecular profiling of these samples has yielded important insights both in terms of novel myeloma drug targets and newly defined high-risk myeloma patient subsets that are being evaluated as part of our late-phase clinical trials. Similar work is ongoing in lymphoma and CLL. In solid tumors we're also assembling very substantial data sets from a wide range of tumor types and this is allowing us to understand the molecular basis of checkpoint inhibitor resistance. In turn we're using these insights to focus on particular drug targets for internal discovery and external licensing as well as incorporating biomarkers into our ongoing clinical trials to look for responder populations. This approach is not limited to hematology and oncology. We're also applying similar strategies to our other disease areas of interest. In particular we're focused on the role of human genetics in predisposition to disease. We've established partnerships that allow us to look for genetically defined drug targets in certain disease areas and then deploy our leading discovery platforms to address those targets. Our TYK2 program is a particularly strong example of this. TYK2 is a highly validated genetic target in numerous immune disorders but selective drugs proved hard to find until BMS identified a class of novel allosteric inhibitors to create one of the most promising programs in our portfolio. Similar strategies have been applied to other genetically validated targets including Factor XIa as an anticoagulant, JNK1 as an anti-fibrotic, and BTK as an anti-inflammatory, just as a few examples. In some instances we need to take a reverse pharmacology approach to matching our discovery platforms to targets and patient populations, and this is particularly the case with our industry-leading CELMoD platform. Over the last several years we've created a large library of CELMoD compounds that can degrade novel protein targets that are inaccessible to conventional drug discovery approaches. Knowing the target protein substrate we can then undertake reverse matching to our molecular patient data sets and initiate new drug discovery and development programs. In the next few slides I'll describe this approach in more detail. For those of you unfamiliar with the CELMoD platform, this is a unique branch of drug discovery based on our insights into the mechanism of action of lenalidomide and pomalidomide. Over several years our scientists have elucidated the mechanism of action of these drugs demonstrating that the compounds bind to the cereblon E3 ligase and then lead to the tagging and destruction of specific proteins such as Ikaros and Aiolos, the key mediators of efficacy in myeloma. By building our library of these compounds and comparing the proteins degraded by different members of the library we've been able to establish published insights into the structural features of proteins that render them CELMoD substrates. And we now have several novel drug development programs targeting a range of different proteins and indications. We've also taken this effort one step further by investing in large-scale proteomics to try and capture the universe of potential protein substrates. This strategy has now yielded literally hundreds of potential novel target substrates that we can degrade through our CELMoD compound collections. By combining the data from our proteomics data set with other confirmatory data sets we're now creating an inventory of addressable target proteins. Some of these have obvious utility for specific disease conditions and can move rapidly into development, but many others have relatively little biological information associated with them. However by using our foundational patient data sets, computational research teams are now working to match novel targets to biological information across a range of disease areas. This work is translating to a significant pipeline of CELMoD compounds that is beginning to be appreciated externally. I would point to the recent data shared around iberdomide and CC-92480, both of which have shown very exciting data in relapsed/refractory multiple myeloma. Iberdomide is also in Phase 2 for SLE following promising Phase 1b data. Beyond that we have CC-99282 in development for lymphoma and two completely novel agents that are now moving ahead for refractory AML. Looking to the preclinical stage pipeline, we're very excited about an emerging set of solid tumor programs that are moving rapidly towards selection of development candidates. As evidence for the power of CELMoD technology I'd like to remind you of the data we shared for CC-90091. This CELMoD degrades a completely novel substrate GSPT1, which is a translation termination factor. Disruption of this target was shown to have significant preclinical activity in AML cell lines and we've now been able to demonstrate activity in the clinic. Dose and schedule optimization continues along with the initiation of combination trials. Our knowledge of cereblon binding has also enabled us to develop another class of compound that we term Linker-directed degraders or LDD. In this case we've discovered inert cereblon binders, in contrast to the active CELMoDs, and these binders can then be connected by a linker to a second target-binding moiety. Heterobifunctional molecules such as these can be used to tag protein targets in the cell without having to exhibit the structural motifs required by CELMoD substrates. This approach further extends our ability to go after difficult-to-drug protein targets. Our first LDD program is an androgen receptor degrader that will be used to target castration-resistant prostate cancer. The data from a xenograft mouse model shows exposures in both plasma and tumor after oral administration, and the androgen receptor degradation in the tumor. This translates to efficacy in the same mouse model that is resistant to standard of care, shown by tumor growth inhibition compared with enzalutamide. We've recently had our IND filing for this molecule and dosing is imminent. Behind this molecule there's an emerging pipeline of LDD programs across a broad range of therapeutic areas. Okay, so moving away from small molecules I'd like to discuss our biologics capabilities and highlight a few more early programs. As you're aware there have been significant advances in protein engineering that have enabled molecules to be designed for both validated and novel drug targets. These approaches include pro-bodies that can mask the active site of antibodies until they reach the tumor microenvironment, immune cell engagers that can bring the power of a range of immune cells to tumors, bispecifics that can optimize targeting of antibodies to an environment where both targets of the bispecific are expressed, and optimized antibody-drug conjugates that have an improved therapeutic index. Just to briefly highlight a couple of our programs. CC-93269 is a BCMA T-cell engaging molecule with a unique two-to-one binding configuration. In our early clinical trials presented at ASH last year we were able to show very promising activity in highly refractory multiple myeloma patients. CC-99712 is a BCMA-specific antibody-drug conjugate that uses site-specific conjugation technology. This approach controls the drug-to-antibody ratio with the aim of improving the therapeutic index. We're currently dose-escalating this molecule to see if we can retain efficacy while mitigating the troublesome ocular toxicity that has been observed with first-in-class BCMA ADCs. Finally I'd like to discuss our cell therapy platform. Cell therapy is an emerging modality that will continue to evolve and mature for years as we have observed with both biologics and RNA-based therapeutics in the past. Our own efforts we see this evolving in several stages. In the near term we're invested in moving our best-in-class programs forward and ensuring that we capitalize on lifecycle management. In the mid-term we're working to optimize our manufacturing and looking forward to bringing our next-generation CAR-T therapy forward, known as next-T. Lastly, looking to the longer term with deploying technologies for overcoming resistance to CAR-T therapy, expanding into solid tumors, and creating off-the-shelf solutions for patients. As with so much of our research we believe that our translational data sets represent a competitive advantage. The BMS cell therapy team has the largest number of patients treated across indications and manufacturing processes. Using a proprietary data integration platform we've been able to deploy machine learning approaches to develop critical insights for our programs including optimized patient selection, rationale combinations for platform studies, and process improvements that have given rise to our next-T products that are now in the clinic. Next-T has the potential to markedly impact turnaround time and cost of goods for autologous cell therapy. Through a series of strategic collaborations we continue to build the next generation of cell therapies including engineered T-cell receptors targeting solid tumors, CAR-T cells that are armed with a tunable payload that can overcome tumor microenvironment resistance, dual-targeting CAR-T to mitigate escape through antigen loss, and the engineering of allogeneic CAR-T to create an off-the-shelf product. Closing, I'd like to give you an overview of our early pipeline. The highlighted programs have been mentioned or briefly described through the course of my presentation. However as you can see there are many programs we didn't have time to discuss today that give us the opportunity for numerous proof-of-concept decisions over the coming few years. In addition we're actively adding to this pipeline through our ongoing business development efforts. So in summary I've described our Research and Early Development organization, in particular the outstanding talent, geographical location, and external research strategy. We've discussed our approach to research whereby we match foundational data sets with leading platforms so that we can address the most important biological targets. Finally I've given you an insight into a number of our early programs and shown you the extent of our very exciting early development pipeline. Thank you very much and with that I'll hand over to my colleague Sumit Chakravarty.

Thank you Rupert for that wonderful overview of the research and early development portfolio. And good morning, good afternoon, good evening to you all. It's a pleasure to be with you to walk you through the late-stage development portfolio. If we can go to the next slide, as Rupert just showed you the pipeline, we have more than 50 medicines in development in Phase 1 and 2 clinical trials at this time. Today of course, as Giovanni mentioned earlier, we will focus on the oncology development pipeline where there is a continuous evolution of data in the late-stage programs. As you go to the next slide, as you've just heard from Rupert, the focus of the research and early development organization is to drive innovation and using novel platforms continue to bring the next generation of assets into development. Now working hand-in-hand, the late development part of the organization looks to accelerate the development and maximize the potential for these innovations. This maximization occurs by deep and strong collaborations internally and borrowing the capabilities from early development such as the expertise in translational sciences and companion diagnostics development, as well as through external collaborations not only for discovery but also for development. Global Drug Development utilizes a global footprint of approximately 20,000 clinical sites around the world and the capabilities and data and computational sciences to design innovative trials and to bring these medicines to patients as quickly as possible. If you move to the next slide, now looking at our assets collectively, we have a significant number of first-in-class or best-in-class assets in late-stage development, many of which have registration or lifecycle management trials already underway. Today we will discuss the breadth of opportunities in human oncology both through our existing franchise as well as potential new medicines as Giovanni mentioned. We will share our hematology, cell therapy, immunology, and cardiovascular insights in our follow-up presentations later in the week on Thursday and Friday. So if you go to the next slide you can see the breadth of registration trials that are still underway. We will not have time to talk about them all of course. So today I'll focus on the early-stage setting that is highlighted on the right-hand side of this slide. Going to the next slide, I want to take a minute to talk about why I believe that immuno-oncology has potential in early-stage disease. The first thing to be aware of is that early-stage disease from the patient perspective is the point where one can intervene and potentially cure the disease. The second thing is that we already know that checkpoint inhibitors work in adjuvant melanoma, so we believe that immuno-oncology could play an important role more broadly because we know that the immune system is more intact in patients with early-stage disease. So if you go to the next slide, let me just take a moment to remind you of what we know about Opdivo and Yervoy in early-stage disease. On the top portion of this slide you can see the data for Yervoy and for Opdivo plus Yervoy as it relates to melanoma. Here we've clearly proven that these checkpoint inhibitors are active and are benefiting patients with melanoma in the long term. On the bottom you can see data that was published in the New England Journal of Medicine showing how Opdivo as a single agent has demonstrated activity in neoadjuvant non-small cell lung cancer as well. So we've been seeing clinical data supporting the potential for Opdivo and/or Yervoy in early-stage disease in two tumor types already. And if you go to the next slide we have a very broad registration program for Opdivo and Yervoy which you see here. We're going to start to see data this year and over the next few years in these additional indications. And I want to take a moment to talk about two tumor types where we have a fairly broad approach to treating early-stage disease. So on the next slide, starting with bladder cancer. This is a disease impacting a significant number of patients, and for those patients whose only option for treatment is surgery, they face a significant amount of morbidity. So it's especially important to prevent recurrence for these patients. What we're looking at is a program that considers both the adjuvant setting as well as the peri-adjuvant opportunity for patients who are eligible for chemotherapy. We expect to start seeing data from CheckMate -274 later this year or early next year, but more to follow from CheckMate PRO-7/8 in 2022 and beyond. If we go to the next slide, in lung cancer we have a very broad approach. We are looking at multiple ways of treating patients before surgery, after surgery, both before and after, or the peri-adjuvant setting. And we're also looking at the unresectable Stage 3 population. First of all we have the potential to see data as early as this year from the neoadjuvant trial with CheckMate -816. Of course this will depend on whether the pathological complete response data is unblinded to us by the data monitoring committee this year. Secondly, the CheckMate -73L trial looks like a very interesting trial because it will answer the question whether dual IO is better than single-agent PD-L1 therapy in Stage 3 unresectable population where durvalumab is a common standard of care. Turning to the next slide, to a different mechanism of action that we are pursuing in immuno-oncology with our LAG-3 inhibitor relatlimab. The hypothesis behind this agent is that LAG-3 expression is associated with T-cell exhaustion and therefore could be a form of primary or possibly secondary resistance to PD-1 blockade. That means, as you can see on the picture on the left side of the slide, that if that hypothesis is accurate, dual inhibition of the PD-1/PD-L1 pathway combined with the LAG-3 blockade could allow for T-cell activation in situations where T-cell exhaustion is causing a lack of response. We are now testing this hypothesis in a randomized Phase 2/3 trial looking at what added benefit relatlimab might demonstrate on top of Opdivo. As you can see on the right-hand side, we're hoping to see data from this trial later this year. We are anticipating completion of enrollment quite readily and then of course the readout will depend on the number of events. In addition to providing us with potentially registration data, this clinical trial will also provide us with data we need to truly understand whether relatlimab could be a next-generation immuno-oncology mechanism that we need to pursue. And it doesn't end there, because the data from this study, if successful of course, will also help inform potential lifecycle management plans for relatlimab. If you go to the next slide, now beyond relatlimab we continue to study our IL-2 asset, nafodekimab. Over time we are doing the right experiment to learn what the potential role of adding this agent to Opdivo can be in melanoma and then several of the other indications that you can see on the slide. So the journey in immuno-oncology doesn't end with lifecycle management of Opdivo and Yervoy. With both of these agents that I just talked about there is a potential for future therapeutic options for patients through next-generation immuno-oncology medicines. Going to our next slide, to conclude, when I look at the program in general I believe we have a lot of opportunities for Opdivo and Yervoy both in the advanced and early-stage disease and I'm excited to see what the potential of the next-generation IO therapies could be when we get the data starting this year and into next year and beyond. They're also going to continue to see the data evolving from the early-stage pipeline that Rupert shared earlier. All in all we have an exciting portfolio and opportunities to look forward to in the coming years. With that let me pass it over to Chris to give his perspective from a commercial point of view. Thank you so much.

Thanks Sumit. Good day everyone. I want to pick up where Sumit left off and talk a bit about where we are commercially with the IO business today and how we see that business evolving in the near term and medium term. Going on to the next slide, let's start with where we sit today. As you see on the left-hand side of this slide, we've built a very robust business in IO, just shy of 9 billion dollars globally last year. In doing so we've solidified BMS as not only a scientific leader, the company that first launched IO, but also as a commercial leader in this space. And we've done so by focusing on doing a few things exceptionally well. First we put considerable focus on launch execution. We've executed 23 separate launches on a global basis, that translates to over 400 global launches, and we built a very strong track record of launch success. Second, we've worked to quickly establish BMS IO as a standard of care as we've done so in nine separate tumors. And finally we've successfully defended our position in the face of intense competition. You can see that reflected in our competitive shares across promoted tumors. This book of business today provides a very strong foundation for continued growth. As you can see on the right-hand side of this slide, we have a number of opportunities to continue to grow this business across a host of tumors with a robust set of metastatic and adjuvant programs. I'll spend my remaining time today highlighting a few of these opportunities, starting with kidney cancer. Going to the next slide please, as we think about the opportunities for growth in renal cell carcinoma, I think it's helpful to start with where the business is today. Over the last few years we've seen growing competitive intensity in RCC. In spite of that, Opdivo plus Yervoy has remained an important standard of care with over 40% share in our approved indication. In fact we've seen some growth in share in the first few months of this year. This performance reflects very good commercial execution and importantly the impressive depth and durability of responses we see with dual IO therapy. This latter point was amplified with the impressive update to CheckMate -214 data that we saw at ASCO GU earlier this year. You can see that data is highlighted on the right-hand side of this slide. So there continues to be very strong advocacy for Opdivo plus Yervoy in first-line renal cell. As we expected and as we've discussed over the last year or so, the data Sumit mentioned from CheckMate -9ER for Opdivo plus cabozantinib gives us real opportunity to grow this position. This study delivered very strong OS and PFS data with a manageable safety profile across patient risk status. And based on what we've seen we feel we have a profile that is best-in-class relative to other IO-TKI therapies. As a result we see opportunities to grow our business in a few areas. First, data from CheckMate -9ER should enable us to promote in the favorable-risk patient segment, which is currently off-label based on CheckMate -214. You can see that reflected in this slide in the relatively low share we have in favorable-risk patients today. Second, we think we should be able to shift additional TKI monotherapy to Opdivo plus cabozantinib. Most of the share that existing IO-TKI regimens have achieved in first-line renal cell has come from TKI monotherapy. You can see that roughly 20% of first-line is still TKI monotherapy and we should be able to capture some of that share. Finally, we should be able to compete very effectively against existing IO-plus-TKI agents. So we're very excited about the opportunity to bring this regimen to patients and we see growth in kidney cancer as an important catalyst as we get into 2021. Let's go to the next slide. The foundational role that dual IO has played in kidney cancer as well as melanoma is relevant as we talk about lung cancer. In both of these diseases the addition of CTLA-4 to PD-1 has meaningfully extended survival. As a result we've seen physician familiarity with both Yervoy and the regimen increase over time in the community setting. That's important given that the vast majority of lung cancer is treated in the community setting. It's still very early days in the U.S. launch of CheckMate -9LA but I'd highlight a few things. Coming out of ASCO, the feedback from customers has largely been consistent with what we've heard over the last number of months. In spite of advances in first-line lung cancer in recent years there's still significant unmet need here, particularly around the durability of responses. And that point was amplified as we've seen the evolution of competitor data over time, including the most recent updates at ASCO. Customers continue to be impressed with the depth and durability of responses they're seeing with CheckMate -228 and -9LA, especially in light of the three-year update provided at ASCO. And while there is acknowledgment that the -9LA data are still relatively immature, customers like the early separation of the curves and the consistency of benefit seen across PD-L1 status and histology. So while it is still very early days, we're happy with what we're hearing from customers and where we sit with the launches. Most customers we speak with see a role for