Bristol-Myers Squibb Company (NYSE:BMY) Early Pipeline and Immuno-Oncology Call June 22, 2020 11:30 AM ET
Tim Power – VP IR
Giovanni Caforio – Chairman and CEO
Rupert Vessey – Executive Vice President Research and Early Development
Samit Hirawat – Chief Medical Officer and Global Drug Development
Chris Boerner – Chief Commercialization Officer
Nadim Ahmed – President Hematology
David Elkins – Chief Financial Officer
Conference Call Participants
Geoff Meacham – Bank of America Merrill Lynch
Andrew Baum – Citi
Chris Schott – JPMorgan
Terence Flynn – Goldman Sachs
Seamus Fernandez – Guggenheim
Steve Scala – Cowen
David Risinger – Morgan Stanley
Matthew Phipps – William Blair
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. [Operator Instructions] Please be advised that today’s conference may be recorded. [Operator Instructions]
I would now like to hand the conference over to your speaker, Tim Power. Sir, please go ahead.
Thanks Matisse [ph] and good morning everyone. Thanks for joining us today for the first of our three parts investor series. The plan for today is that we will have a presentation followed by Q&A session and so if you are not participating via the webcast you can always go ahead and download the materials on bms.com.
Joining me today for the presentation are Giovanni Caforio, Chairman and Chief Executive Officer; Rupert Vessey, Executive Vice President Research and Early Development; Samit Hirawat, Chief Medical Officer and Global Drug Development; and Chris Boerner, Chief Commercialization Officer. And also with me today for the Q&A session are Nadim Ahmed, 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 statements. During today’s call, we will 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 will hand over to Giovanni to start the meeting.
Thank you, Tim, and good morning, afternoon or evening to all of you wherever you are in the world. I hope that you and your families are continuing to stay safe and healthy. Welcome to the first of our investor series. As you know we had hoped to meet with you all in person in April, but unfortunately the circumstances didn’t allow for that.
With that said, we are extremely excited about the promise of our portfolio. So we’ve decided to go ahead now with a series of three virtual events over the course of this week.
Turning now to Slide 4. Let me start with who we are as a company today. Our strength has become apparent, as we started operating as one company since November. On this slide you can see the strength of our company across the commercial portfolio, the depth of the pipeline and our financial flexibility.
From a commercial perspective, we are the number one company in oncology. We are continuing to grow the #1 cardiovascular brand with Eliquis and we have a growing immunology franchise, starting with our blockbuster ORENCIA, expanding with Zeposia with the potential of further broadening with TYK2i, and a new asset, cendakimab, our anti-IL-13 asset for eosinophilic esophagitis. Samit will talk more about this asset in detail on Friday.
Over the short and medium team we are excited with our deep and broad late-stage portfolio with 8 near-term launches, 3 Phase 3 assets, and greater than 20 lifecycle management opportunities scenario. And for the longer-term we have a robust early-stage pipeline with about 15 [ph] Phase 1/2 assets that will help future opportunities. Importantly, we remain very strong financially with significant flexibility. This enables us to aggressively invest in innovation, internal and external.
Moving to Slide 5. Since the close of the acquisition, I’ve been very proud of our execution as a combined company. We have delivered very strong execution across the board. In commercial we continued topline growth and in R&D with outstanding pipeline progress, clinically and from a regulatory perspective.
And we delivered excellent financial performance while continuing to successfully integrate the company. We are on track with integration and with obtaining 2.5 billion in synergies. I couldn’t be prouder of the performance of our teams and the progress that we’ve made. I was encouraged when we first announced the deal, but I see even more promise today than before.
Now, moving to Slide 6. Looking forward I am very encouraged about our future as a company. We have strong inline businesses that continue to grow and we are now accelerating the renewal of our portfolio through an unprecedented number of launches. Additionally, these are assets that all have important lifecycle management opportunities ahead, important for growth in the medium term. We feel good about our long-term sustainability enabled by our R&D strategy which is focused on leveraging the combination of internal and external innovation.
Let me take a minute to walk you through how I view the company through each of these lenses. On Slide 7, you can see the strength of our in-line portfolio of key medicines. Opdivo and Yervoy continue to perform well and have a broad set of expansion opportunities, which Samit and Chris will discuss shortly. I feel good about growth in 2021 and beyond.
Revlimid and Pomalyst are established and growing backbone multiple myeloma therapies. Following the progress made last year with Revlimid IP situation and given where we are today, we remain confident in our assumptions regarding LOE [ph]. Samit and Nadim will highlight how we plan to sustain and reinforce our strong presence in myeloma while expanding into other hematologic diseases.
And lastly, Eliquis continues to be the #1, with additional room to grow in an expanding market/. Samit and Chris will discuss how we plan to continue to advance our position in TB [ph] through the Factor XIa program.
Now, moving to Slide 8, we are executing an unprecedented number of new launches. On this slide, you can see the 8 near-term launch opportunities. These include our recently launched Reblozyl for MDS associated anemia, Zeposia in multiple sclerosis, as well as our dual I-O combo Opdivo plus Yervoy in personal lung. Although it is early for these launches, we are pleased with execution and we are encouraged by the feedback we have received from prescribers so far.
A lot is happening on the regulatory front. We are continuing to work with regulators on liso-cel, ide-cel and CC-486. Importantly, we have a potential best-in-class oral asset with our TYK2 inhibitor and we are expecting results from the first of our Phase 3 trials by year end. These launches provide significant opportunities for growth and they lay the foundation for the renewal of our portfolio. This is strengthened further by the significant LCM plans for these assets which are described on Slide 9.
I continue to be very encouraged by the breadth of opportunities I see to expand the use of these medicines. Across almost every one of our new products we have the potential to build on our initial launch success with new indications, benefiting more patients and growing our business. Over the next few days you will hear more details about these programs, but let me take a minute to provide my perspective.
Starting in I-O where we see multiple opportunities including in the adjuvant settings to support future growth of this franchise. With respect to Reblozyl we are working to expand the use of this first in class medicine to first-line patients regardless of RS status with commands and potentially the myelofibrosis patients in the future.
For Zeposia we have already announced that our UC trial met its primary endpoints and we continue to recruit patients in our Crohn’s disease study. For our two lead cell therapy programs we have opportunities to increase the addressable patient populations removing into other lines of therapies. And for example, with liso-cel moving into adjacent malignancies such as CLL. And for TYK2i Samit will describe on Friday based on the mechanism we believe we have the potential to develop this agent as a medicine for a broad set of autoimmune diseases beyond the initial in the potential indication in psoriasis. There is a significant potential for us to broaden and strengthen our portfolio of new medicines going forward.
Let’s move on to our long-term outlook starting on Page 10. Investing in innovation is central to our strategy and as you will hear in a few minutes from Rupert, we have set up an organization with strong balance and capabilities. We are advancing a very exciting pipeline with the next set of registrational opportunities already in the house. At the same time, as we’ve done for many years, we remain very focused on ensuring we can source external opportunities that complement our portfolio. And business development remains the central pillar of our capital allocation strategy.
On Slide 11 you can see the strength and breadth of our entire portfolio. While Samit and Rupert will cover a lot they will not be able to cover everything. However, we are very encouraged by the opportunities we see in the pipeline and I’m looking forward to discussing those with you over the next few days.
Before I close, I would like to provide my perspective on our future outlook on Slide 12. I’ve said a number of times, I feel more confident in our company today than I was a year ago when the deals was announced. There are good reasons for this. Over the last 18 months the pipeline has advanced and a number of opportunities have been somewhat derisked. These includes the positive results for Zeposia in UC as an example. New programs have emerged such as CC-486 in AML. We feel strongly about the value of our late-stage assets. When we project known risk-adjusted peak revenues by the end of the decade, they are expected to be at approximately $20 billion, which is above where we were before.
I am also encouraged by the progress with the next wave of medicines that are emerging, including the data on CELMoDs and our BCMA T-Cell Engager presented at recent meetings. Even this week, we will introduce our perspective on a new asset, cendakimab. Most importantly, we continue to have the financial flexibility needed to continue to aggressively invest in future innovation internally and through business development, which remains as important as ever. Taken together, we are in a strong position to own our future and drive a successful renewal of our portfolio which we’ve done before and we are committed to doing again.
With that, I would like to start the meeting. Rupert, the floor is yours.
Thank you, very much, Giovanni. In this next session, I will cover research and early development in BMS. I’m going to describe our organization and approach to drug discovery and early development and I’ll also provide insights into our 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 areas across site collaboration and are supported by a range of capabilities that makes them much more than the sum of their parts.
In addition to our network of internal research centers, we are 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 enable academic incubators, equity investments in strategically important new companies, and industry-leading deal structures.
We have further empowered by our geographical locations which places 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 forth 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.
On 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 call 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 apology 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 have assembled some of the largest hematology data sets throughout our network of partners. Deep 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 are 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.
On the next slide you’ll see that 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 are focused on the role of human genetics and 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 prove 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, JNK-1 as an antifibrotic, and BTK as an antiinflammatory just as a few examples.
In some instances we need to take a robust 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 the compounds bind to the E3 ligase cereblon and then lead to the tagging and destruction of specific proteins such as aiolos and ikaros, 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 have also taken this effort one step further by investing in large-scale proteomics to try and capture the 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 dataset with other confirmatory datasets, we are 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 datasets our 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 pre-clinical 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 of the power of CELMoD technology, I’d like to remind you of the data, we shared at ASH for CC-90009. This CELMoD degrades a completely novel substrate, GSPT1, that is a translation of the termination factor.
Disruption of this target were 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 has also enabled us to develop another class of compound that we term Ligand Directed Degraders or LDD.
In this case we 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 tank 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 graph on the bottom left is from skip mouse BCaP model and shows exposures in both plasma and tumor after oral administration and in the purple bars the androgen receptor degradation of the tumor. And the graph on the right we show that this translates to efficacy, same mouse model that is resistant to standard of care shown by tumor growth inhibition in the green line as compared with enzalutamide in the red line. We’ve recently had our IND approved for this molecule and dosing is imminent. Behind this molecule there is 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 side of antibodies until they reach the tumor microenvironment, immune cell engages 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 at 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 Engager molecule with an 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 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 is 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. For our own efforts we see this evolving in several stages. In the near term we are invested in moving our best-in-class programs forward and ensuring that we capitalize on lifecycle management. In the mid-term we are working to optimize our manufacturing and looking forward to bringing our next generation CAR-T therapy forward known as NEX-T.
Lastly, looking to the longer-term, we are 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 optimize patient selection, rational combinations for platform studies and process improvements that have given rise to our NEX-T products that are now in the clinic. The NEX-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 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 persistence, fuel targeting CAR-T to mitigate escape through antigen loss and the engineering of allogeneic CAR-T to create off the shelf product.
In closing, I’d like to give you an overview of our early pipeline. The highlighted programs have been mentioned I’ll briefly describe through the course of my presentation. However, as you can see there are many programs we didn’t have time to discuss today to give us the opportunity for numerous proof-of-concept decisions over the coming few years. In addition, we are 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 datasets with leading platforms, so that we can address the most important biological targets. And 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, Samit Hirawat.
Thank you, Rupert for that wonderful overview of 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 lead development portfolio.
If you can go to the next slide, as Rupert just showed you the pipeline, we have more than 50 medicines in developed in the Phase 1 and 2 clinical trials at this time. Today of course as Giovanni mentioned earlier, we will focus on the oncology development pipeline, but there is a continuous evolution of data in the late-stage programs.
If we go to the next slide, as you’ve just heard from Rupert, the focus of Research and Early Development Organization is to drive innovation and using novel platforms continue to bring the next generation assets into development. 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 barring the capabilities from early developments 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 significant number of first-in-class or best-in-class assets in late-stage development, many of which have registrational or lifecycle management trials already underway. Today we will discuss the breadth of opportunities in immuno-oncology, both through our existing franchise in addition to potential new medicines as we are studying.
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, if you can click our focus on the early stage setting that is highlighted on the right hand side of this slide. If we go to the next slide, I won’t take a minute to talk about why I believe that immuno-oncology has a 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 early-stage disease. On the top portion of this slide you can see the data for Yervoy and for Opdivo versus 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 and two tumor types already and if you go to the next slide, we have a very broad registrational program for Opdivo and Yervoy which you see over here. We are 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 option for treatment is only surgery, they say is significant amount of morbidity. So it’s especially important to prevent recurrence for these patients.
What we are looking at is a program that considers both the adjuvant setting as well as the periadjuvant opportunity for patients who are eligible for chemotherapy. We expect to start seeing data from CheckMate-274 later this year or early next year, with more to follow from CheckMate-078 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 periadjuvant setting as we would say and we are also looking at the unresectable stage 3 population.
First of all, we have the potential to see the data as early as this year from the neoadjuvant trial with CheckMate-816. Of course this will depend whether the pathological complete response data is unblinded to us by the Data Monitoring Committee this year. Secondly, the CheckMate-73L trial is a very interesting trial because it will answer the question whether dual I-O is better than single agent PDL-1 therapy in Stage 3 unresectable population where durvalumab is the current standard of care.
Now 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 this slide that if 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 are hoping to see the 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 registrational data, this clinical trial will also provide us with data we need to truly understand whether LAG-3 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, would also help inform potential lifecycle management plans for Relatlimab.
If you go to the next slide, now beyond the Relatlimab, we continue to study our IL-2 asset partnered with NEKTAR, where all the time we are doing the right experiment to learn what the potential role of adding this agent to Opdivo can be in terms of melanoma and then several of the other indications that you can see on this slide. So the journey in immuno-oncology, it doesn’t end with lifecycle management of Opdivo and Yervoy. With both of these agents that I just talked about, there is the potential for future therapeutic options for patients through next generation immuno-oncology medicines.
On 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 am excited to see what the potential of the next generation I-O therapies could be when we get the data, starting this year and into next year and beyond. We are 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 Samit, and good day everyone. I’m going to pick up where Samit left off and talk a bit about where we are commercially with the I-O business today and how we see that business evolving in the near to medium term.
Clicking 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 I-O just shy of $9 billion globally last year. In doing so we solidified BMS as not only a scientific leader as the company that first launched I-O 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’ve built a very strong track record of launch success.
Second, we worked to quickly establish BMS I-O 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.
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 and our approved indication. In fact, we’ve seen some growth in share of the first few months of this year.
This performance reflects very good commercial execution and importantly the impressive depth and durability of response as we see with dual I-O therapy. This latter point was amplified with the impressive update to CheckMate-214 OS data that we saw at ASCO GU earlier this year and 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 Samit mentioned from CheckMate-9ER for Opdivo plus cabozantinib gives us real opportunity to grow this position. As Samit mentioned, 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 I-O plus 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 I think as many of you know 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 ship additional TKI monotherapy to Opdivo plus cabo, most of the share that exists in I-O for 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 I-O 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 I-O 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 227 and 9LA, but I’d highlight a few things as to where we are.
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 is 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 response that is seen with 227, especially in light of the three-year update provided at ASCO. And while there’s acknowledgment that the 9LA data are still relatively immature, customers like the early separation of the curves and the consistency of benefit seen across PDL-1 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. Those customers we speak with see a role for dual I-O therapy. This is particularly true among customers who have experience with the regimen in other tumors, which I’ll remind you is roughly about half of lung cancer treatments, and we have very strong commercial and medical teams that are in the field and actively engaging on these data.
Next slide please. The two tumors that we just reviewed along with the strength of our base business provide an important foundation for our I-O business going forward. As we discussed on my first slide, another area in which we have a number of studies that will also be important for this franchise or the early stage in adjuvant settings. Let me try to frame how we think about these commercially. I think there are three things to keep in mind. First, early stage tumors represent an area of significant unmet need.
These are large tumors with a significant percent of incident patients diagnosed in the early stage setting as you can see on the left hand side of this slide. Importantly, the standard of care in the early stage settings is often either not particularly affective or carry significant toxicities. So there is great opportunity for I-O to penetrate these settings and have significant impact for patients.
In fact that’s what we’ve done in melanoma, first with Yervoy then with Opdivo. As noted in the middle of this slide with the introduction of I-O we’ve seen more than a doubling of treatment rates in this setting. As we’ve discussed previously, we would expect that with successful I-O studies we would see a similar increase in treatment rates in other tumors. Finally, and importantly from a commercial standpoint, the opportunity in adjuvant is largely complementary to that in the metastatic setting as you see on the far right of this slide.
In melanoma, we’ve been able to substantially grow our adjuvant business without negatively impacting our metastatic business and again this is something we’d expect to play out in other tumors. As Samit mentioned, we have a very large set of programs in the adjuvant setting across a range of tumors with studies reading out later this year and into 2021. These studies are going to be very important as we think about the shape of our I-O growth trajectory starting next year and beyond.
Going to the next slide, so what I would leave you with is that our current business is performing very much in line with expectation and provides a nice platform for future growth. The data that you’ve seen from CheckMate-9ER kidney cancer and the recent launches of lung in the U.S. based on 227 and 9LA are important catalysts for near-term growth in the metastatic settings in two very important tumors. Beyond these metastatic programs, we have a very large set of studies in early and adjuvant disease that we believe hold great promise both for patients as well as the future growth of our I-O business.
And with that, I’ll turn it back over to Giovanni.
Thank you, Chris, and thank you Rupert, Samit, and Chris for your presentation.
If we could go to the next slide, please. We’re on Slide 59. So today, you’ve seen a summary of our research and early development strategy and pipeline. We’ve also had an opportunity to discuss the totality of our approach in immuno-oncology, specifically discuss the performance of our in-line brands, the focus on new launches, the LCM opportunities we are working on, and the next medicines that are emerging. This is the same format that we’re planning on leveraging for the second and the third of our series of calls on our pipeline and we’re confident that it shows the real depth and breadth of our pipeline.
So going to Slide 60, the next meeting will happen on June 25 and it will be focused on hematology, but obviously, right now we are going to be opening the meeting for the Q&A. And so on the next Slide 61, you can see who will be joining me for the Q&A. As a reminder, it is not only Rupert Vessey, Samit Hirawat, and Chris Boerner who have presented, but also our CFO David Elkins and our Head of Hematology Nadim Ahmed together with me and the number of members of our team will be here to answer any questions.
So with that, operator, we’re ready to start the Q&A. Thank you.
[Operator Instructions] Our first question comes from the line of Geoff Meacham of Bank of America. Your line is open.
Okay, great, thanks. Good afternoon guys. Thanks a lot of the question and for hosting the call series. I just had a few, one for Chris on the early response to 227 and 9LA then label expansion, what’s been the common theme is it mostly lung patients who are looking for a chemo free or chemo led option? I wasn’t sure what you’re getting specifically from the field.
And then for Rupert or Samit, when you think about ide-cel upstream in myeloma, in the past we’ve talked about MRD negativity being an endpoint, I wasn’t sure if there is an update on how that’s playing out as you think about moving upstream to a third or the second line from an FDA perspective? Thanks guys.
Thanks. Maybe I’ll start and then I’ll turn it over to Sumit. So based on the feedback we’ve had so far coming out of ASCO, I think there isn’t really one specific customer type that patients are focused on and in fact what we hear most consistently is that given the depth and durability of responses that we’ve seen, particularly with the updated 227 data that we have presented at ASCO, physicians are willing to consider the dual I-O regimen across a range of patients.
Now having said that, there are a number of patient types that do come up in these conversations, so notably PDL-1 expression levels, less than 50% as well as non-expressers, I think that’s as much a function of the fact that PD-1 monotherapy is pretty much ingrained in the 50% and above PDL-1 expression levels. Customers have consistently going back to ASMO been very impressed with the squamous cell histology data that we’ve seen coming out of 227.
Obviously as you noted in your question there, patients who don’t want or can’t tolerate chemotherapy or patients who may want to get the benefit of dual I-O therapy but may need a limited amount of chemotherapy to get their disease under control and that’s very much going to be a patient by patient discussion that takes place with the physician.
So the way I would summarize it is, there is no one specific niche that dual I-O therapy has been pegged to physicians who are willing to consider it across a broad range of patients including the ones that I just mentioned. And again, I think the focus really has been on what’s that conversation that’s going to take place between the physician in his or her patient. So that’s basically what we’re hearing coming out of ASCO. Samit?
Thanks, Chris. Geoff, thanks for the question on the MRD part of multiple myeloma and certainly let me start by saying, Chris of all of course you know that MRD as such MRD negativity is not acceptable endpoint from a registration perspective by the FDA. Having said that, it’s very important and I can understand the point behind your question is, if one were to follow the conventional endpoints in the early stage setting it will take a while before any new drugs are approved in the first or second line, so it becomes important to evaluate new endpoint that will lead to faster approvals and getting the drugs out to patients in a meaningful way and as quickly as possible.
So that is one of the reasons why we continue to evaluate MRD in all patient populations and every single trial that we are conducting to be able to generate that data and to provide continuous validation how to manage MRD in terms of measurement, what test to use, which tissue to use and what the correlation of MRD negative to durability PFS and OS is.
And when the time is right, when we have adequate amount of data and we are ready to go into late-stage trials for ide-cel or any other molecules, as you will hear more in the next series and hematology, we will be discussing that endpoint with regulators and try to come to a conclusion, how to use it, whether is a primary key secondary or secondary or tertiary endpoint, but that part is yet to be discussed, but certainly on top of our minds.
Thank you. Our next question comes from Andrew Baum of Citi. Your line is open.
Thank you. Couple of questions, firstly for Samit, historically Bristol development history in immuno-oncology may be as currently described is mixed. When you think about tackling the clinical development of the new generation of immuno-oncology products, how are you thinking differently about trial design, patient selection in order to reduce some of the risks, which may have affected the recent history?
Second for Rupert and I guess Samit as well, COVID-19 would seem to open the door to potentially adopting the novel development programs embracing master protocols beyond oncology particularly in autoimmune and other areas in order to expedite and explore whether individual drugs have activity across multiple diseases at the same time and to find where they sit. I’m just interested in your view, whether this opens the door to a new development paradigm? And then finally, just on your early stage pipe, could you just comment on when you expect to see or when we will see the Phase 2 data on the Factor XIa and when we anticipate Phase 3 potentially to begin? Thank you.
Thank you, Andrew for your questions. Let me start off and then I’ll pass it on to Rupert to tackle some other points. So first of all about tackling new medicines and how we will make progress as we look towards BMS and its ability to execute on clinical trials in a different way.
As I mentioned in one of my slides, early on and Rupert also mentioned in terms of how we now envision utilizing a plethora of data that has been collected internally from clinical trials. So, to be able to investigate that we have a platform, applying machine learning, artificial intelligence, and of course the neuronal knowledge that we’ve gathered over the time to now be able to be more specific in terms of utilization of either Synthetic arms historical controls, as well as conduct of Phase 2 a powered study that will lead us into thinking about what the best approach would be to Phase 3 development for example or to take actions in terms of not doing further research in the Phase 3 setting to be able to do that early decision making early on.
And those are the things that we are working hand-in-hand Rupert and I with our organizations, with the translational medicine group which now has the ability to do a very deep look into the biomarkers and genetics and be able to correlate that with the clinical outcomes of patients. So those are attributes that we continue to strengthen in the overall development portfolio.
The second part of your question was around COVID-19 and what that will be used for in terms of knowledge generated there to then further our research. So certainly platform trials that we learn from oncology, we will continue to think about how we can bring that into the immunology portfolio, for example, where we are going to be thinking about multiple indications and how do we read out the new signals versus discontinue the places where we may not have a signal, but we have not applied that yet to be honest.
And we are going to think about it with the advent of new molecules coming from the early development pipeline as we go forward, but certainly we have learned a lot of other lessons in terms of continuing the clinical research in the field for example, use of EMRs, use of remote data monitoring, as well as how to conduct clinical trials in the time of COVID-19. The regulators have provided wonderful guidelines to us as well, as well as the sites have given us new ways of thinking about enrollment of patients and monitoring of that data.
And the third question, from my perspective and then I’ll pass it on to Rupert to comment more for Factor XIa, the Phase 2 trials are ongoing as you know, both in the secondary stroke prevention and total knee replacement. And we anticipate readout of the data for the secondary stroke prevention that BMS is conducting towards the very end of 2021 maybe early 2022, you can imagine the complexity of that study in these times, where the healthcare system is flooded unfortunately because of the increased number of cases of COVID-19 and we come back to that study require not only the emergency room, but also very well run machinery around radiologist, neurologist, ER physicians, et cetera. So that trial is going to take a little bit more time than previously communicated in terms of the conduct, but the total knee replacement trial might be able to finish earlier. And then that will lead to further communication around next trials. Let me pass it on to Rupert if you want to add something Rupert. Thank you.
Yes, thanks, Samit. Thanks for the question. So as we tried to outline in the first part of the presentation we do have access to a lot of information, some of it derived from our own clinical program, some from networks of collaborators and then of course there are public data available that we can also into digital with all that information.
And so, for many of our clinical programs we actually have pre-defined biomarkers that look at different subsets of patients. It’s true in many of our myeloma programs where we’ve published new biomarkers of high risk. Some of those were in the slide, it’s definitely true in solid tumor oncology and actually it’s also true in our immuno-inflammatory diseases as well.
So we are really trying to identify those groups of patients that we think are most likely to respond and be prepared to look at that information in Phase 2 so that we can use it in Phase 3 and I think we’re doing quite well in terms of doing that type of work.
As far as platform studies go I think Samit is right. COVID will accelerate all sorts of things and drug discovery and development from some perspectives including novel trial designs, different ways of monitoring clinical trials. It is having impact even on how we think about drug discovery from the perspective of using more artificial intelligence type approaches for optimizing compounds for example.
So it’s accelerating some of our efforts and in that space, but we were already doing platform trials. Our BTK program is in the platform trial across multiple immune indications and our cell therapies are set up as platform trials, so that we can evaluate multiple add-on therapies to look at their effects on persistence and durability of CAR-T responses. So lots going on and COVID is definitely a disrupter as you point out. Thanks.
Great. Can we go to the next question please Matisse [ph]?
Yes, sir. Next question comes from the line of Chris Schott of JPMorgan. Your line is open.
Great, thanks so much for the questions. First one from me was Opdivo in adjuvant. Can you just elaborate a little bit more on your confidence in the bladder cancer setting given the competitor setback earlier this year and so that’s one of the next we are also going to be watching here? And maybe more broadly on adjuvant, How do derisked do you see these opportunities? I think there’s some debate across the street of how risky these clinical studies are relative to we saw in the metastatic settings.
And then my second question was, when I look at the various modalities you’re developing and thinking specifically here about kind of the T-cell enhancers versus cell therapy versus some of the CELMoD platform, how do you prioritize those? And when you reach a point in development where you’ll start to make kind of bets, I guess on one approach versus the other, or do you feel you’ve got large enough R&D budget here you can kind of broadly push forward with these various modalities? Thanks so much.
Thank you for the question, Chris. Let me start off and then I’ll pass it on to Chris. And then maybe Nadim can chime in, also for the multiple myeloma side of things. So for Opdivo, as I spoke up earlier, certainly we know the melanoma setting. So we’ve done the studies with Yervoy followed by nivolumab compared to Yervoy, nivolumab single agent being superior to Yervoy. We have the study ongoing of nivolumab-Yervoy in melanoma and we’ll see how that study reads out. Now in non-small cell lung cancer with single agent nivolumab we did see there was no impact on surgery, but 20 of the 21 patients did undergo complete resection with 45% major pathological responses.
Now beyond that we have to wait for the data as I said it will start to read out this year. The overall principles remain the same, overall principles of intact community and the drugs being able to work better we’ve seen earlier line settings immuno-oncology agents or checkpoint inhibitors do better as opposed to late-line setting.
So there is enough science I think and enough belief from that data that has been generated in various commissions, that lead us or that led us to design the overall program. Certainly bladder cancer and non-small cell lung cancer trials and melanoma trials that will read out this year will give us even more to be able to then construct further hypotheses as we look forward and then bringing in the new mechanisms of actions that I talked about. So that means it is all data based. So I do feel pretty good about what is to come in the future.
Now from the BCMA side and then I’ll pass it on to Chris, so that we don’t have to go back and forth, but from a BCMA targeting perspective, certainly, we’ve taken a holistic approach and we’ll talk in greater detail on the next call on Thursday, when we talk about hematology, but suffice it to say it’s a holistic approach to treatment of multiple myeloma, because not all patients can be treated with a singular modality.
So we have to see where T-cell engagers would be better utilized versus where the cell therapies may be better utilized or where the CELMoDs will come in, but more importantly, how these modalities can actually be combined to give the best outcome for patients as we move them forward in the earlier settings.
And you will see the overall structure of that talk on Thursday, so I will not belabor that. Suffice it to say we are thinking about it from a holistic point of view. Chris, maybe let me pass it onto your first and then to Nadim.
Sure. Maybe just a couple of comments, Chris. First, with respect to bladder I think that Samit has covered it pretty well. I think the thing that’s true really across adjuvant disease that we’re learning is that you’ve got very distinct patient populations that are going to be relevant as you think about the viability of any given approach to treatment. I mean that’s certainly true of I-O therapies.
What’s interesting about bladder is this is a very large patient population. It is highly fragmented and so, we are pursuing several distinct populations including adjuvant and periadjuvant and that similar approach is being applied in other tumors, like for example, lung cancer, where again we have several opportunities crossing adjuvant, neo-adjuvant, periadjuvant, Stage 3, unrestricted disease.
So I think one of the key things that’s going to be important as I-O agents get into the early stage and adjuvant setting is going to be making sure that you’re applying the right science to the right specific patient populations. And one of the advantages of the program we have is we have not only have a breadth of tumors that we are pursuing but we’re also pursuing breadth of approaches across very distinct patient populations, including monotherapy as well as combination therapy. So I think that helps as we think about our program and the relative risk of that program in the adjuvant setting. And Nadim, anything to add on BCMA?
Sure. Yes, I would just add to what Samit said. So I think multiple myeloma still remains a largely incurable disease. So the unfortunate fact today is that most patients diagnosed in multiple myeloma will die of multiple myeloma. So there is still significant unmet needs in the myeloma space and patients continue to relapse.
So within that context of a larger incurable disease, as we think about BCMA modalities, especially as you think about within a given line of therapy, there may be patient preferences that determine whether a T-cell engager or CAR-T treatment is better for a specific type of patient.
So you could imagine a patient may be younger, once a one and done treatment part, he is going to be much more suitable. Maybe an older patient who lives closer and wants to be treated in the community can benefit from a T-cell engager and the continuous treatment you have there. With the CELMoDs we are now excited of the fact that both CELMoDs have shown activity in image refractory disease and clinicians have told us they do need treatments for patients who are failing both Revlimid and/or Pomalyst.
So there is room for all of these agents to continue to drive efficacy as we seek to prolong remissions and make them more durable and seek cures. I think the most exciting point, I would say that is very unique to BMS is that we also have the opportunity as a company to combine both CELMoD and BCMA approaches, which no other company has. So we’ll talk a lot more about this on Thursday in the hematology session, so I would encourage everyone to dial in there. But thank you for your question.
And let me thank you Nadim. Let me just close out with two additional points. Number one, for the adjuvant side, I think it’s difficult to compare and take away from what others are doing and directly apply to the ongoing trials that we have. Just as a small point for example, the duration of treatment of the PDL-1 applied in the bladder cancer adjuvant trial by our competitors is different than the one we are using in our trial, so and that may play a role of the duration of treatment.
From a BCMA perspective in a similar way, taking into account the fact that how resistance has developed, there is no loss of BCMA antigen per se. So there is a possibility of applying sequential treatment of BCMA directed therapies as well. So I think those are the new answers we have to keep in mind as we look into further development of these assets. Tim?
Okay, thanks Samit. Matisse, can we go to the next question please?
Yes, sir. Our next question comes from the line of Terence Flynn of Goldman Sachs. Your line is open.
Great, thanks for taking the questions. Maybe two from me. First, with respect to the new peak revenue guidance of $20 billion, just wanted to understand, I’m assuming that CC-486 and ozanimod for ulcerative colitis is kind of a key new updates, but was wondering if there was anything else that you’d call out Giovanni? You mentioned increasing confidence here in the forward. And then a question for Rupert, of the 20 proof-of-concept readouts that you cited, how many of those do you have supportive genetic data for and where is your confidence highest among those readouts? Thank you.
Thank you, Terence. Let me start with your first question on the potential of the late-stage pipeline. So you’re right, there are, I guess, there are a couple of different areas that have evolved positively in fact over the last 12 to 18 months. So some of it is new assets like CC-486, in some cases it is a better appreciation for the data and the strength of that data and the potential of an asset. That would be as an example, the maturation of the CARMA trial where we feel really good about the profile of that asset. The third type of consideration is the best-in-class label we received for Zeposia, which we believe positions that asset, extremely well.
And yes you are right, the nature of the positive results for the UC trial for the Zeposia is also an important positive that makes us look maybe in a more informed way at the scope of that opportunity in UC, but I would say more broadly in inflammatory bowel disease. And then of course there are a number of other LCM opportunities that we are now including.
So for example, for Reblozyl the myelofibrosis, the anemia in myelofibrosis is one of the examples of where we have included that opportunity. So I think the pipeline, the late-stage pipeline has developed very positively across the board, and there are multiple drivers of what we feel is a higher potential non-adjusted peak revenue for those assets that we’ve communicated today, all driven by really good events. Rupert, do you want to take the second question?
Sure. Yes, so thanks for the question. So, on the non-oncology side where human genetics mostly plays out, we have, well I already highlighted for you BTK, JNK, TYK2 you know about, the IL-2 programs. Actually Iberdomide in lupus has very good genetic validation because the targets of that asset aiolos and ikaros are both genetic risk factors for lupus and also the same is true for IL-13 cendakimab.
So in that area, it’s a very high proportion. And this is an important part of how we select and bring targets through. Of the programs that will be approaching proof-of-concept, which ones are we most confident about, it tends to be those where we have obviously more evidence of clinical activity.
So all of the BCMA assets, the CELMoDs we’ve already mentioned to you have shown extremely promising data. We’ve got evidence of clinical activity with CC-90009 and obviously we’ve got other assets like the CTLA-4 programs that are designed to have enhanced activity. So I think there is a very strong cluster of programs here that we have a high level of confidence in either because the target is highly validated, pitched genetically validated or we’ve already seen encouraging signals of activity. So I think there’s a lot to be excited about here in the early pipeline. Thanks.
Thanks. Rupert. Matisse, could we go to the next question please?
Yes, sir. Our next question comes from the line of Seamus Fernandez of Guggenheim. Your line is open.
Great, thanks very much for the question, so a couple of here. I noticed the move into neuroscience is building. Can you talk about your commitment to neuroscience and is that an area where business development is also a – these were focus? The second question again on the neuroscience, but also on the M&A side, can you just talk a little bit more about your BTK.
I believe that there was a consideration to move into MS, but then the company decided to move in a slightly different direction in the wake of the BTKI data that we’ve seen from Sanofi’s programs, can you just give us a sense of, if you see an opportunity for your own BTKI in the BMS setting and then if there are other opportunities that you see going forward obviously, the impact on microglia is gaining a lot of attention? Thanks so much.
Yes, thank you, Seamus. This is Giovanni. Let me just start and I’ll ask Rupert to answer both of your questions. And yes you are right, we have, when we looked at the portfolio of the combined company following the close of the transaction, we looked in detail about the presence that Celgene has started developing in neuroscience, which is an area that had not been recent area of focus for BMS, but it’s one where we have historically had significant expertise.
And we felt that the approach was right, that many of the programs were extremely promising, that the unmet medical need in that area was very high and particularly approach of Rupert and his team had started in neuroscience was very attractive to us. So we are committed to continuing that work and I’ll ask Rupert to give you more insights on that and then answer your question on the BTK takeover.
Yes, thanks very much, Giovanni. So we’ve been quite deliberate and thoughtful about the way that we’ve constructed the collaborations that we have in neuroscience and we are very fortunate to have Richard Hargreaves who leads that area for us, who you may know of who is a true expert with a lot of experience in bringing neuroscience drugs all the way through to market. And we’ve accessed some we think very exciting platforms. I’d point to the Skyhawk [ph] platform for example where we’ve got some great programs built around targeting RNA splicing.
We’ve got an exciting relationship actually with Evotec where they had quietly built an outstanding IPSC based screening platform and we are screening both and our compounds and have molecules moving ahead there. But that allows you to go after diseases where there’s a strong genetic element, which we think will increase our probability of success as we’ve already described.
So there is a lot here. We’re moving things forward and they will play out in early clinical development and then we will have the opportunity to decide whether to invest in those further. We are continuing to do business development activities in neuroscience and this has been further spurred actually by the success that we’ve had with Hosanna [ph] with the excellent label that we have that’s opened up other areas of interest for us.
And your question about BTK, we actually have multiple BTK molecules with differing properties and yes, we are actively looking at how to deploy those molecules across a range of indications and having a nice new therapeutic like ozanimod is definitely a stimulus to our thinking in that space, so plenty more to come. Thank you.
Thank you. But we probably have time for two or three more quick questions. Maybe we can go to the next one please Matisse.
Yes, sir. Our next question comes from Steve Scala of Cowen. Your line is open.
Thank you. Giovanni, with all due respect, companies almost always say that an acquisition is better than they thought in terms of pipeline or integration, but not all ultimately are successful. So with Celgene, maybe you can tell us what so far has not worked out as well or been disappointing?
And then second, the $20 billion in risk-adjusted pipeline sales is slightly less than Bristol will be losing from patent expirations during a similar time period. So first, do you agree with the observation and secondly if you agree, then, how does the company grow over the long term in your view? Thank you.
Thank you, Steve. Two very good questions. And first of all, let me say, from our perspective, the acquisition is the integration of the two companies is going extremely well. And the good thing about the bringing together of Celgene and Bristol-Myers Squibb is that, as we’ve said all along that we’re such a strong number of short-term catalysts and proof points that we can now step back and really look at the facts.
And the reality is that the performance of the two businesses remained really strong, which is a testament to our ability to bring the two companies together with minimal disruption to commercial operations. We had a lot of discussion over the last 18 months about the value of the five late-stage assets and if you’ve seen that the clinical data in the regulatory progress is playing out well, there have been new assets that have come to the forefront.
And importantly, we are on track with the synergies. So there are always elements so any large acquisition and integration that goal somewhat differently than you would have expected then as an example, of course, the need to divest Otezla and the three-month delay that we experienced in closing, as a result of that I would point as some of the unexpected and may be more challenging elements, but I am pretty comfortable of how we’ve manage that and so that’s the reason why just based on the concrete events of the last 12 to 18 months, I think I can say that in our case it’s going better then we have plans, just because of the things that have happened already,
Your question regarding losses of exclusivity and portfolio renewal, it’s also a really important question. Obviously as I said in my introduction, this is something that, first of all is sort of the part of the dynamics in our industry it’s also something that our company specific and we have successfully navigated in the past. And at the end, the strategy for renewing our portfolio is a multipronged strategy.
First of all, it starts with our approach to R&D, which is a real combination of internal investment and continued focus on business development. I think we’ve seen even just today in the first session a continued reference to the interplay between internal programs and business development.
Second, we feel really good about the late-stage assets that we have discussed today, not only the first indications that provide a real opportunity for growth in the short term, but also the lifecycle management potential that those assets have and third, I would say, continued productivity of the pipeline. So when we discuss assets beyond those assets the BCMA T-cell engager is a really exciting compound. We’ve made a number of comments today. Rupert has to sell most progressing through the clinical development stages.
Today we have disclosed and discussed for the first time cendakimab as a new agent. So I think the pipeline will mature well beyond the 20 billion in non-risk adjusted sales that we’ve described, just for the current set of late-stage assets. And then of course on Friday, we’ll have an opportunity to discuss with David, the financial strength and flexibility the company has to continue to intelligently invest in business development very much in line with our strategy.
So you have to think about renewing your portfolio with a multipronged approach, which is really the different stages of development for different time periods and the integration of external and internal. And as I’ve said at the beginning, we are very much in a position given our strength to own our future and I can tell you that continuing to successfully renew our portfolio is a high priority for the management team and we will feel really good about the work that we’ve done so far, but of course, we’ll continue to work on it.
Thanks Giovanni. Matisse, can we go to the next question please?
Yes, sir. Next comes from David Risinger of Morgan Stanley. Your line is open.
Yes, thanks very much. So this is very comprehensive, I just had a couple of questions. First, Roche has stated that intact of FC is necessary for a ticket to be active. Since Bristol’s is non-FC binding, could you please comment? And second, regarding the CheckMate-816 non-small cell lung cancer PCR data that’s forthcoming soon, is that potentially fileable or would you have to wait for survival data in 2022? Thank you.
Yes, it’s Rupert here. Thanks for your question about TIGIT. Yes, so there are preclinical data that do support the idea that an active FC may deliver more efficacy than an inactive FC. But there are also data that suggests that an active FC can lead to depletion of TIGIT positive cells. And I don’t think yet that we really know for sure in the clinical setting which of these approaches is absolutely the best because as far as I’m aware there is no direct comparison.
You also have the important question of patient selection and I think Roche’s data point to that question. So that’s got to be factored into any comparison that you might make of different configurations for these antibodies. Our program is still in the early phases of development. We’re obviously digesting the data that we’ve seen in determining what our next step should be. Thanks.
Okay, thank you. Rupert. Maybe I can take on the 816 question by the way on the TIGIT part of course, we also saw the ACR abstract coming out and as a single agent we don’t see activity. So there is a, I think a lot more to be studied for TIGITs and see where it goes. For the 816 part certainly, the primary endpoint one of the primary endpoint is pathological complete response, and beyond the breast cancer side and non-small cell lung cancer right now, it is not up but an endpoint that drugs that approved upon, at least not yet from the FDA perspective and EMA perspective.
So that require some discussions with regulators but the DMC has to first look at the data and if the data are our transformational and meet statistical criteria that have been set in the protocol then certainly they will let us know and we’ll trigger that conversation with the FDA even more in terms of having the dialog around approvability. So I can’t tell you today, is it approvable on PCR or not, but certainly something that will be very important for us to learn if the DMC does share the data with us and if the trial is positive to take it forward. Otherwise, we’ll have to wait for the next 10 point to be readout. Thank you.
Yes, thanks Samit. Matisse, could we go to the last question please?
Yes, sir. Our last question comes from Matt Phipps of William Blair. Your line is open.
Thanks for squeezing me in. I have a couple of slides, focusing here on the CELMoD and then often on my end right integrators, which has been so worked on by searching quite a well and become very house [indiscernible]. So just curious on having both of these sort of platforms and really just trying to extend a number of bio charges for degradation or just disband it, [indiscernible] and then given the pipelines for the first LED program, there is some recent data that [indiscernible] which I think CELMoD content cost ladies and gentlemen credit free [indiscernible] and so just curious as how you think 94676 has any advantages or [indiscernible] point mutations and patients [indiscernible]?
Okay. Unfortunately, there was a lot of breakup on the line, but I’ll do my best to cipher the question and provide some answers. So the CELMoDs are really a revelation actually from our perspective, because we have invested in this big platform effort and it’s been beyond our expectations, the number of proteins that do appear to be addressable, as we continue to expand the library and learn more about the structure activity relationships.
And the nice thing about these molecules small and drug like and once you’ve validated a target and you’ve identified a compound you can actually progressed pretty rapidly to drug candidates. And I think you can see that on slide that I presented. We have a lot of programs that are too early to share right now. But one of the great benefits of the BMS Celgene integration is that we now have a lot more muscle power that we can bring to this. So we’re going to be able to go even faster than we were previously when it was Celgene as a stand-alone. So I think that’s a very exciting area.
The LDD approach is really as you point out an extension in some ways in that we’ve been able to use Cereblon as a way to go after other protein substrates both they don’t have to have structural features that make them a substrate for Cereblon we can just approximate the protein to the E3 ligase and in some cases that’s good enough to get the molecule. In fact, these molecules are harder to optimize and bigger, but we’ve actually had a lot of success in creating compounds for the overly bio-available and we now have a pretty good toolbox for putting in these things forward and interestingly, the larger challenge in many ways actually is now finding binders fourth target subs that protein targets because often that targets that are not represented well in standard compound collections and again having an enormous compound collection in BMS is going to be a great enabler in this regard.
With respect to your question about venous compound, yes we were intrigued to see that of course. We knew about that program, but there is not very much we know about the compound. Yes, we don’t actually I think no what E3 ligase they’re using at the moment, the only preclinical data that we’ve seen there was available in similar models to the ones we’ve targeted is it is suggested that it’s less efficacious, but that’s obviously very difficult to make that comparison between pre-clinical models, but that’s what we’ve seen to date and we’re just about to start those. So we’ll see how they compare when we have a little more data. Thanks.
Thank you, Rupert and thanks everyone. Let me just bring our call to a close and thanks to everyone for participating. I’m happy that we’ve had an opportunity to discuss with you, Our Research and Early Development Organization and approach, as well as some of the really exciting work and programs that are going on in that part of our R&D organization. I’m really proud actually of what Rupert and his team has accomplished since closing and that we have an extraordinary opportunity and research and early development and the team is off to a great start.
We also had an opportunity to give you some insights into the many things happening in immuno-oncology and the next step is for us on Thursday, to have another really important session on one of the broadest segments of our pipeline, which relates to hematology. So we look forward to continuing the series and the dialog on Thursday. Thanks, everyone, and have a good rest of the day.
Thank you. Ladies and gentlemen, this concludes today’s conference call. Thank you for participating. You may now disconnect.