Welcome to the Bristol Myers Squibb Hematology Drug Development Update conference call. All participants will be in a listen-only mode. Should you need assistance, please signal a conference specialist by pressing the star key followed by zero. After today's presentation, there will be an opportunity to ask questions. To ask a question, you may press star, then one, on your touch telephone keypad. To withdraw your question, please press star, then two. Please note this event is being recorded. I would now like to turn the conference over to Kate Bender, Investor Relations. Please go ahead.
Good morning. This is Kate Bender from Bristol Myers Squibb Investor Relations, and I'd like to thank you for joining us today to discuss our progress across key programs that are expected to shape the future of hematology treatments. It's exciting news for patients and the company, and we have a lot to talk about. I'm joined by Christian Massacesi, our Chief Medical Officer and Head of Global Drug Development, who will take you through our slide presentation. Following the presentation, three of our leaders will join Christian for Q&A: Lynelle Hoch, President of our Cell Therapy Organization; Monica Shaw, Senior Vice President of Oncology Commercialization; and Rosanna Ricafort, Vice President of Hematology and Cell Therapy Global Drug Development. On slide two, please note that 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 those forward-looking statements as a result of various important factors, including those discussed in our SEC filings, and we specifically disclaim any obligation to update forward-looking statements even if our estimates change, and with that, I'll hand it over to Christian to begin our presentation.
Thank you, Kate. Good morning, everyone. It's great to be here with you in my new role at BMS. I was drawn to the company because of the strong science, broad portfolio, and innovative pipeline across high-growth therapeutic areas. In the four months since I joined the company, I've also been impressed by all the people I've met and their dedication to our mission to discover, to develop, and to deliver innovative and life-changing medicines to patients. Turning to today's agenda on slide four, the purpose of bringing you here for this event is to share our strategic approach to drug development, with an emphasis on our hematology therapeutic area. We are excited to highlight the strength and innovation of our research platforms, which are driving advances across targeted protein degradation and cell therapy.
Today, I will highlight and contextualize some of our newest data presentations from the International Myeloma Society and ASH Congresses, as well as touch upon some early-stage assets to watch. This data not only showcases the progress of our assets but also reinforces our confidence as we look forward to many pivotal results next year. Our goal is to provide you with a clear understanding of how these developments reinforce our leadership position in hematology and why they represent significant opportunities for Bristol's future growth. Moving to slide five, success in our Global Drug Development Organization is grounded in three key priorities: science, execution, and value. Everything we do is rooted in science. We are leveraging our deep scientific expertise to develop assets that we believe can provide a clinically meaningful benefit and set new standards of care. Our approach to science and pipeline is dynamic.
We assess each of our opportunities on an ongoing basis to ensure we are allocating our time, people, and capital behind the most promising growth opportunities. At the same time, we are laser-focused on achieving best-in-class execution. We are operating with urgency and precision across the entire development organization, and execution is not only delivering clinical trials but also being highly disciplined to ensure each study has the highest probability of success. In this process, we are also utilizing AI and machine learning to power our R&D engine and bring treatments to patients faster. Our third key priority is value. We are developing medicines that address higher met needs, creating value for patients by providing innovative treatments with the goal of improving upon current standards of care and striving for cure, while at the same time delivering value to Bristol Myers Squibb and our shareholders.
We are being more deliberate in how we prioritize programs, pursuing assets where the science is highly differentiated and where we believe we have the ability to create value. These priorities and portfolio discipline in what we pursue and where we allocate our resources are applied across all therapeutic areas. Ultimately, the goal of this strategy is to ensure that we are investing in the best science with the highest probability of success so that we can deliver more value to all of our stakeholders. On slide six, it's important to highlight BMS's strong legacy and decades of experience in hematology, which is a true differentiator. We have been at the forefront of this area for decades with a rich portfolio and pipeline of truly transformative treatments across hematological diseases.
More recently, BMS is proud to be the first and only company with two approved CAR-T cell therapies in two distinct disease areas, with Abecma and Breyanzi. Reflecting on where we are today, we have the first and only CELMoD in late-stage development with six ongoing phase three studies, bolstering our leadership in targeted protein degradation, as well as arlo-cel, the first GPRC5D- targeting CAR-T assessed in pivotal trials, which expands our leadership position in cell therapy. Last week, we announced Breyanzi's approval as the first and only Cell Therapy Marginal Zone Lymphoma, marking its approval across five cancer types, more than any other CD19-directed CAR-T. Looking ahead, we will continue to advance scientific discovery and maximize our late-stage portfolio value by investing in these platforms that have the potential to transform the treatment paradigm for hematological diseases and further extend BMS's leadership.
On slide seven, you can see our next chapter in hematology is driven by two complementary platforms: targeted protein degradation and cell therapy. Starting with targeted protein degradation, we are building on our legacy with a new wave of innovative science across therapeutic areas, with multiple assets in development. Our researchers are leveraging three different modalities for targeted protein degraders: CELMoDs, ligand-directed degraders, and degrader antibody conjugates. This three-pronged approach allows us to match the right modality to a mechanism of action to target what have previously been considered undruggable targets. One of the most exciting qualities of these assets is that they are highly combinable with other approaches, such as targeted therapies, immune modulators, CAR- T cell therapies, and also complex biologics.
Turning to cell therapy, this is an area where we are a proven industry leader with two approved CAR-Ts in two distinct targets: Breyanzi across the broadest array of B-cell malignancies and Abecma, the first approved CAR-T multiple myeloma. While we are focused on delivering the first and best-in-class treatments across blood cancers, we are also exploring opportunities to increase accessibility of cell therapy for more patients. The focus of today's event is on hematology, but let's not forget that both of these platforms will enable our leadership across multiple therapeutic areas, including solid tumors and autoimmune diseases. Taken together, our deep knowledge in targeted protein degradation and proven track record in cell therapy execution gives us multiple shots on goal to deliver the next wave of hematology assets.
Turning to slide eight, we have a broad hematology portfolio and pipeline diversified across various diseases, including multiple myeloma, leukemias, lymphomas, and anemia. We have critical assets spanning both late and early stages. So we strongly believe our diverse hematology pipeline is differentiated and positioned to contribute meaningfully to our growth in the years ahead. While I would love to speak in detail on each of our assets, today I will be focusing on a subset of assets you see starred here, where we expect to have key data readouts in the next 12-24 months. Let's transition now, beginning with multiple myeloma, where I will walk you through our vision, recent data, and portfolio. On slide 11, you see our exciting next wave of assets in multiple myeloma that I will be covering today.
We are well-positioned to leverage our research platforms with two pivotal-stage CELMoDs, iberdomide and mezigdomide, and our next generation of first-in-class CAR- T assets, arlo-cel , and our BCMA and GPRC5D dual-targeting CAR- T. Moving to slide 12, our vision for iberdomide and mezigdomide is to become the first novel CELMoD protein degraders approved in multiple myeloma. These agents are well-positioned to be essential foundations across the multiple myeloma treatment landscape, based on their enhanced potency and immune stimulation. CELMoDs are combinable oral agents with the potential to displace the IMiDs, Revlimid and Pomalyst, across patient segments and be the combination partner of choice for other T-cell redirecting therapies.
Turning to slide 13, we know the IMiDs, Revlimid and Pomalyst, have been a cornerstone of multiple myeloma treatment for decades, but this disease remains incurable, with highly heterogeneous patients requiring novel and convenient therapies to optimize outcomes over current standards of care. Iberdomide and mezigdomide are potent oral CELMoDs that evolved from the IMiDs. The CELMoDs are not just incremental improvements. They represent a potential new foundation for multiple myeloma treatment by inducing even greater and faster targeted protein degradation. Based on their pharmacological and clinical profiles, they each address distinct patient populations and combination regimens across four ongoing phase III trials. We envision iberdomide replacing Revlimid in newly diagnosed post-transplant maintenance. The head-to-head phase III study of iberdomide versus Revlimid is ongoing, with data expected in 2029.
In early relapsed refractory patients, our intention is for iberdomide to be combined with daratumumab because iberdomide and anti-CD38 monoclonal antibodies have a synergistic activity. Our second CELMoD, mezigdomide, induces maximal protein degradation, and we plan to use it in combination with proteasome inhibitors in patients who are anti-CD38 exposed or refractory. I will dive deeper into our CELMoDs data in the next slides. Slide 14 shows the recent early phase data we presented at IMS Congress in September for iberdomide in combination with daratumumab and dexamethasone. In this population of newly diagnosed patients not receiving stem cell transplant, this data set demonstrated deep and durable responses. Patients achieved an overall response rate of 95%, with 68% of patients achieving a complete response at 22 months. Additionally, we tested minimal residual disease, or MRD.
MRD negativity is important as it correlates with PFS/OS and is an indicator of clinical benefit and improved outcomes. In this trial, Iber-Dara-Dex induced MRD negativity in over two-thirds of patients. These results are very encouraging. When you look at historical results for standard regimens in the MAIA and BENEFIT trials, less than one-third of the same population of patients achieved MRD negativity. Turning to slide 15, the Iber-Dara-Dex regimen demonstrated a manageable safety profile consistent with prior data, with no new safety signals observed. There were overall low rates of grade three or four non-hematological events, and hematologists are well accustomed to managing neutropenia and infections in these patients. In summary, Iber-Dara-Dex is the regimen we are currently studying in the ongoing pivotal EXCALIBER-RRMM study.
In September, we announced that this study evaluating iberdomide in combination with standard therapies, daratumumab and dexamethasone, demonstrated a significant improvement in MRD negativity rates in a second- to third-line multiple myeloma patient population. We expect to have the PFS data next year. Let's switch focus to our second CELMoD in multiple myeloma, mezigdomide, on slide 16. At IMS, we presented early phase pooled data for mezigdomide in combination with both proteasome inhibitors, bortezomib and carfilzomib, plus dexamethasone. Across a population of pretreated patients ranging from one to four prior lines of therapy, the combination of Mezi PI and dex demonstrated deep responses. Overall response rates were over 80% in patients who received one or two prior lines, with responses above 70% in more heavily pretreated patients. Notably, in patients who had received one or two prior lines, complete response rates were over 25%.
These results are encouraging as all of these patients had received prior lenalidomide, with a subset of patients being refractory to PI or anti-CD38 agents. These results show that mezigdomide, plus a PI and dex, provided benefit in patients regardless of the number of prior lines of therapy. Turning to slide 17, the safety profile for mezigdomide plus PI and dex regimen showed Grade 3 or 4 adverse events were mostly hematological and were manageable with supportive care across this largely triple-class exposed population. These data support our ongoing pivotal trials for mezigdomide, SUCCESSOR-1 and SUCCESSOR-2, which are studying mezigdomide plus a proteasome inhibitor in later relapsed multiple myeloma populations. We anticipate seeing the PFS top-line data for both successor studies next year and look forward to sharing it with you.
Moving to slide 18, I want to highlight the potential opportunities we see for novel combinations with CELMoDs in multiple myeloma, which extend beyond the regimens being investigated in ongoing pivotal studies. We have a broad research program combining CELMoDs with BCMA targeting bispecifics, as well as exploring optimal sequencing of CELMoDs as pre-CAR-T conditioning agents or as maintenance therapy to enhance responses following CAR-T infusions. First disclosures of combination data for CELMoDs and the T-cell engager, elranatamab, were just presented at ASH. In the MagnetisMM study, we explored iberdomide plus Elra, and in the MELT investigator-sponsored study, mezigdomide plus Elra. We have a compelling preclinical scientific rationale demonstrating synergistic activity of these agents, with CELMoDs potentially enhancing T-cell engager function.
Early phase safety and efficacy data are encouraging, and studies are ongoing to optimize the CELMoDs and T-cell engager regimens in larger patient sets. Early data also suggests CELMoDs may play a role in optimal sequencing strategies with CAR-T therapies. The CELMoDs may enhance CAR-T cell expansion and subsequent potency when used as preconditioning agents. It may enhance CAR-T cell persistence when used as maintenance therapies post-CAR-T infusion. Exploration of novel CELMoD approaches are ongoing in early phase studies, and the data highlights the potential roles CELMoDs may play to combine or enhance other growing modalities to drive better outcomes for multiple myeloma patients. Moving to slide 19, as pioneers in the field of cell therapy, we are committed to a future where more eligible patients with multiple myeloma are treated with the promise of CAR-T.
Our vision is to offer patients a durable path toward a potential cure. While current therapeutic options have significantly advanced in recent years, there remains a need for new treatments to further improve outcomes. GPRC5D is a promising target for patients with multiple myeloma, both sequentially and in combination with BCMA. Our next generation assets, arlo-cel and the dual-targeting BCMA and GPRC5D CAR-T, have the potential to address their unmet needs for these patients with the hope of putting more patients on a path toward cure. On slide 20, you can see the latest arlo-cel data we presented at IMS. Arlo-cel, our GPRC5D targeting CAR-T, is a potential first-in-class cell therapy for relapsed and refractory multiple myeloma. In this phase I update, heavily pretreated patients have received a median of five prior lines of therapy, with nearly half receiving a prior BCMA targeting therapy.
We recognize the post-BCMA setting is a growing segment with a higher unmet need as more patients are receiving BCMA targeted therapies earlier in their treatment journey. At a median follow-up time of nearly two years, arlo-cel showed continued deep and durable responses with overall response rates of over 90% and achieved MRD negative complete responses in over 40% of patients. These efficacy results are highly encouraging in this difficult-to-treat late-line population. Turning to safety results on slide 21, arlo-cel demonstrated a manageable tolerability profile. Rates of CRS, ICANS, and on-target off-tumor adverse events were low-grade and all resolved. There were no Grade 3 or 4 events. Hematological adverse events were manageable and in line with what we have shown previously.
In summary, following a one-time infusion of arlo-cel these safety and efficacy outcomes in a late-line population, including patients with prior BCMA exposure, show a preliminary favorable benefit-risk profile. This compelling data supports the ongoing pivotal arlo-cel studies. QUINTESSENTIAL, that is run in a heavily pretreated population, the data are expected next year, and QUINTESSENTIAL-2 , the pivotal study in a BCMA-naïve population with data that are expected in 2028. Turning to slide 22, our dual-targeting BCMA and GPRC5D CAR-T is a potential first-in-class cell therapy in multiple myeloma. This asset capitalizes on the proven activity of these two clinically validated and independently expressed targets. We believe that targeting BCMA and GPRC5D simultaneously with a single infusion CAR-T may be beneficial in preventing relapse that is driven by the loss of a single target.
In taking a dual-targeting approach, there is the potential to lead to a more durable and potent activity than what can be achieved with a single-targeting approach. phase I studies are ongoing in newly diagnosed and late-line patient populations, and we anticipate presenting the first clinical data for this asset next year. On slide 23, you see that our broad and diverse portfolio is well-positioned to address the full continuum of multiple myeloma care, from newly diagnosed patients to those with late-stage refractory disease. Our first and best-in-class agents, whether our novel one-time infusion cell therapy agents or our combinable or CELMoDs, have the potential to offer new therapies for myeloma patients across treatment settings. We recognize that each patient is unique, and our commitment is to ensure that no patient segment is left behind.
We look forward to sharing important data readouts beginning next year for these assets that will shape the future growth of the company. Let's switch gears now, moving on to discuss our exciting updates across our lymphoma assets. Turning to slide 25, I'm excited to discuss two of our novel lymphoma assets from our targeted protein degradation platform, golcadomide, our CELMoD, which has two ongoing phase III trials in LBCL and FL, and our earlier stage BCL6 targeting ligand-directed degrader. As highlighted on slide 26, our protein degraders have the potential to disrupt current standards of care across non-Hodgkin lymphoma, providing patients with combination regimens that are chemo-free, all-oral, or that can improve upon outcomes of the standard chemotherapy regimens offered today. Both golcadomide and our BCL6 degrader are first-in-class agents that we envision becoming therapeutic partners of choice for current or newly emerging therapies.
Our goals for these assets are to improve upon the cure rates in large B-cell lymphoma that are achievable with R-CHOP treatment today and to pursue a functional cure in follicular lymphoma. On the next slides, I will highlight the latest data for both of these assets we presented this past weekend at ASH. Moving to slide 27, you see long-term two-year results from our early phase study of front-line golcadomide in combination with R-CHOP in patients with aggressive B-cell lymphoma. All responses at the end of treatment were complete responses, with MRD negativity rates of 90% or greater. These efficacy results showed that adding golcadomide on top of standard R-CHOP led to early responses with high rates of durable remissions, with a 24-month rate of duration of response of over 90% in the overall NHL risk patient populations.
Taken together, these results demonstrated impressive 24-month progression-free survival rates of 79%. On slide 28, you can see that the adverse events for this combination were similar to what is seen with R-CHOP alone, with mainly hematologic events observed. The non-hematologic adverse events were infrequent and mainly low-grade. Importantly, adding golcadomide to R-CHOP did not compromise the delivery of the chemotherapy regimen. Overall, these long-term efficacy and safety results support the ongoing phase III GOLSEEK-1 study, where we are investigating golcadomide plus R-CHOP head-to-head versus R-CHOP in first-line LBCL. We anticipate seeing this phase III data in 2028, and while not covering today's events, our second phase III trial for golcadomide, GOLSEEK-4, is ongoing, also with data expected in 2028.
This study is evaluating golcadomide plus rituximab versus R-chemo or R-s quared in second-line plus follicular lymphoma and offers a potential chemo-free regimen which is meaningful to these patients. Shifting to slide 29, I'm excited to share the ASH data for our first-in-class BCL6 ligand-directed degrader, a new asset we are studying in diffuse large B-cell lymphoma and follicular lymphoma, also developed through our protein degradation platform. BCL6 is a key genetic driver of lymphomas. Most types of DLBCL and FL require BCL6 to maintain their cell proliferation and survival, making BCL6 a broadly relevant therapeutic target for lymphoid malignancies. The BCL6 transcription factor has historically been considered undraggable, as opposed to kinases and other targeted enzymes. However, ligand-directed protein degraders can potentially target any type of protein, including transcription factors.
Data demonstrated that in heavily pretreated patients, our BCL6 degrader has promising efficacy results with overall response rates of 65% in both DLBCL and FL. The safety profile consisted of mainly low-grade adverse events, with no Grade 4 cytopenias observed. We are encouraged by these preliminary results, and we continue to evaluate this asset both as a monotherapy and in combination with bispecifics or rituximab across non-Hodgkin lymphomas. Slide 30 shows our broad portfolio across both aggressive and indolent lymphomas. It is worth mentioning the latest Breyanzi data just presented at ASH. Long-term follow-up data from our phase III TRANSFORM study in second-line relapsed refractory LBCL showed the highest rates of 40-month median PFS and median OS seen so far in a randomized CAR-T clinical trial in this setting. This data underscores Breyanzi as the best-in-class CD19-directed cell therapy.
Then, looking at our next wave of protein degraders, golcadomide and BCL6, we may have agents with transformational potential because these drugs are highly combinable oral options. We envision they may become new standards of care across DLBCL, FL, and the other histologies we are studying through the early phase studies. Let's conclude today's discussion before moving to Q&A. Turning to slide 32, we have covered a lot of information today, but what I'd like you to take away is how we are uniquely positioned to transform how hematological diseases are treated. We are on the cusp of a new wave of hematology assets across our differentiated protein degradation and cell therapy platforms. As we head into 2026, I'm excited for the many pivotal and early-stage data readouts anticipated across our hematology portfolio.
The near and long-term growth of the company will be fueled by new asset launches, the expansion of indications, and our investment behind our innovative research platforms to change the lives of patients. I'm energized by our next wave of assets with their high commercial potential to solidify our leadership in hematology and help drive BMS into the future. I'll now turn the discussion back over to Kate.
Thank you, Christian. We will now begin the Q&A portion of today's event. Operator, let's begin with our first question.
We will now begin the question and answer session. To ask a question, you may press star, then one on your telephone keypad. If you are using a speakerphone, please pick up your handset before pressing the keys. We ask that you please limit yourself to one question. To withdraw your question, please press star, then two.
The first question today comes from Evan Seigerman with BMO. Please go ahead.
Hi, this is Malcolm Hoffman on for Evan. Thanks for taking our question. I was wondering if you can talk about how new comments from the FDA preferring randomized controlled trials with a comparator for new CAR-T agents may impact your planned GPRC5D development and regulatory plans. Appreciate it. Thank you.
Thank you. Thank you for the question, Malcolm. This is an important one. Lynelle, do you want to give it a try?
Absolutely. Great question, Evan. And we've certainly anticipated that that would be a question based on the article most recently in JAMA.
First thing I would say overarching is while they have presented in that article as a new framework and a higher bar for CAR-T, ironically, in every discussion we all have as a field with the FDA, they really encourage randomized controlled trials, and where we can do those, we do perform those as follow-on trials. But we also are able to negotiate with the FDA, and most recently, marginal zone was a perfect example of that, where we got approval on a single-arm trial with no requirement of a randomized controlled trial. Now, the good news with our arlo-cel, we, as you know, QUINTESSENTIAL, the initial trial in relapsed refractory, is a single-arm trial. But we also have already in flight a randomized controlled trial known as QUINTESSENTIAL-2 , so we are encouraged and will pursue an approval on our later-line trial, just as we have previously.
And we'll look forward to the negotiations with the FDA, but are confident that we'll pursue an approval on that later-line trial because we have in flight a randomized controlled trial.
And allow me a more general comment. Everything is very much dependent on the quality of the drug and the product that you bring to the agency. Because if you have a product with a transformational potential, this is independent of the modality. I think there is always willingness to bring it to the patient as soon as possible. And we also want and continue to collaborate with the agency with the fastest way. And you can go with an assertive approval and eventually confirmatory trial like we do in many of these with these promising drugs.
Thank you.
Thank you, Lynelle and Christian. Let's move to the next question, please.
The next question comes from Geoff Meacham with Citi. Please go ahead.
Good morning. This is Mary Kate for Jeff. Thanks for taking our question. Just one on cell therapy here. So you walked us through the positioning of arlo-cel in multiple myeloma. Maybe what feedback have you received from physicians regarding placing arlo-cel in the treatment paradigm upon approval? Where do you think physicians fancy this treatment? Thank you.
Thank you. Thank you for the question. Lynelle, I think you field it.
Yes. Yes, absolutely. So great question. And let me just start off by saying we were really excited about the opportunity to continue to share data at the ASH meeting. And the excitement continues to grow on our arlo-cel particularly as we see the BCMA field continue to expand. So patients are going to be exposed to BCMA and earlier lines at a greater degree.
And so that really does present a great opportunity for our arlo-cel. But you also pointed out the other point. A lot of physicians have been talking to us and are happy that we're showing data both in BCMA- exposed and BCMA- naïve. The efficacy, as you have seen on data that we presented, looks very similar, both on depth of durability, duration of durability, and depth of response. So while the data looks very similar, we are pursuing this as a post-BCMA asset. We do feel that the unmet need is very high and, as I said earlier, growing. And the field is certainly looking forward to having a CAR-T as an option there. Because as you know, the disadvantage right now is they have one agent to be able to provide patients that have been exposed to BCMA. And it's teclistamab. It's a BCMA targeting TCE.
That agent, while it has efficacy benefits, it also carries some liabilities when it comes to on-target, off-tumor side effects that have proven to be very difficult for patients to tolerate. And so for us, with a CAR-T, where you're putting pressure on that target once, you're seeing those efficacy benefits you'd like to see and even greater depths with a CAR-T, but not seeing some of those off-target or, sorry, on-target, off-tumor liabilities that you've seen with the TC. So we're quite excited about our arlo-cel . And the field is eager for us to get this asset onto market.
Thank you, Lynelle. Let's take our next question.
The next question comes from Matt Phipps with William Blair. Please go ahead.
Thanks for taking my question and all the updates here.
I was wondering if you still plan to file iberdomide for accelerated approval based on the MRD results of EXCALIBER. And then for the dual BCMA and GPRC5D, what, I guess, do you think you need to see to move that program forward? Is it higher initial CR rates, trying to beat the 70-75 rates we've seen so far with BCMA? Or do you really need to see more durable CRs from the dual targeting? Thank you.
Thanks. Thanks for the questions. Maybe, Lynelle, I want to give an update of where we are with iberdomide and the registrational discussions ongoing.
Sure. So as you've seen from the press release that we issued, we were pleased to announce that the EXCALIBER Relapsed Refractory Study did achieve a positive MRD negative CR readout.
And as you know, that's an important milestone for this program coming from the FDA ODAC last year, where they voted unanimously on the utility of MRD negativity as an accelerated endpoint for regulatory action. We intend to discuss with the health authorities the potential to bring this asset forward. You've seen from the clinical data from our phase one study that the combination of iberdomide with daratumumab and dexamethasone is highly active. And compared to historical Len, it has improved the outcomes with faster and deeper MRD. And so we're very excited about the data. And we'll see how negotiations go.
So as you know, we will guide on filing acceptance. At the moment, we will have a filing acceptance. What I want to add is we didn't present these results at ASH. Have you noticed that?
Because PFS, that is the second dual endpoint, is so important also in the context of any regulatory interaction that we are having, that, of course, we don't want to jeopardize that endpoint rushing into presenting the data. We are very excited by this first readout, and we'll keep you posted on this. Let's move to the second part, to your second question. Lynelle, you want to maybe explain the value of a dual CAR-T?
Yes. As you probably know, obviously, we first started really pursuing this when we started pursuing GPRC5D. We wanted to first prove that that target, we could actually effectively hit that target with the anticipation that if we could, we would actually move into a dual targeting approach.
And since that time, there has been clinical data that has shown different modality that hitting those two targets does create greater durability and duration of that durability. So that is an exciting place to be when you think about multi-targets. Now, the question you have is, what will a one-time infusion hitting a GPRC5D and a BCMA need to be for us to continue to pursue this? For us right now, what we're looking at is two things. One, the efficacy, which you articulated. We are going to need to see high CRs and high OR rates to clear the hurdles of what we see today on single-targeting agents. And certainly, we also are watching the field from other modalities. And what we need to say to ourselves, what does the field need?
What we hear from physicians and why this is one of the fastest accruing trials that we have in our cell portfolio is because they want a curative intent modality to move into earlier lines. They do not feel in the field today they have that. There are liabilities with some of the other agents. What they would like to be able to provide a patient in earlier lines is something that provides them that curative intent without some of the permanent liabilities, especially knowing that patients with multiple myeloma live for years. They go through multiple lines of therapies. When they think about CARs moving into earlier lines, they want one that they feel is going to give them the efficacy without all the liabilities. We certainly have a high TPP for this asset across efficacy and safety.
But I can tell you indications of our clinical trial recruitment is one of great exuberance and excitement. So we're looking forward to be able to share data as Christian shared earlier in the presentation next year.
And I'll just add to what Lynelle said and describe the dual targeting construct and how we feel this differentiates. We optimize this by specific construct so that it overcomes variability in patients' antigen expression. It is leveraging the binders that we have with our arlo-cel and orva-cel, so not Abecma. And it's a tandem loop design that has advantages in product uniformity, potency, and persistence. So as we move this into newly diagnosed, we do have a treat to cure intent.
Thank you.
Matt, I hope that you feel how excited we are with this second CAR-T that we want to bring into the clinic and how differentiated potentially it can be. It's at the beginning of the journey. But we will see how he's delivering the expectation.
Thank you. Let's move on to the next question.
The next question comes from Luisa Hector from Berenberg. Please go ahead.
Thank you for taking my questions. And hi, Christian. Good to hear from you. I wonder if you could just expand a little on your vision, particularly of the first-line myeloma treatment paradigm. Because it's become pretty complex. And there's a lot of studies ongoing that we'll read out. So how do you think about that front line? Will it become simplified? What is your level of confidence that Bristol Myers therapies will participate here?
Or should we be thinking about your franchise perhaps as more second-line plus? And then if I could just check on the CELMoDs , you talk here about being the backbone, potential new backbone therapy. Is there anything we should think about in terms of overlapping toxicities with partner drugs or even with the BCMA T-cell engagers? Anything to think about there if the CELMoDs are going to join other products? Thank you.
Hi, Luisa. Very nice hearing from you. Very complex question. We'll not expect anything less from you. So first of all, let me start with the front line. You're right. The front line in myeloma is becoming a very incredibly complex space. And I think it's a good thing. It's a good thing because it means that everybody of us can bring to patients novel and different treatment options.
I want to link back a little bit to what Lynelle was telling. As a company, BMS would like to bring a cure to these patients. Today, the myeloma has been incremental, first of all, an incredibly successful story. If you think where myeloma was a few decades ago, the patients today are surviving almost normal times because all the advancement has been done in this disease but it's a sequence of one treatment after the other, after the other, after the other. The question that everybody's asking is, can we bring something curative upfront and ultimately solve the problem since the beginning and this has been done in other diseases. You need probably something more than what you have today so this is why I believe everything we are doing in the development of the next generation of CAR-T cells, I think, is very relevant here.
Because this is one way to bring cure, probably. And we have seen in other indications. So it is one thing. And CAR-T not necessarily can be delivered by itself. And here I want to link a little bit with our CELMoD strategy. Because what we are doing with Iber is adding Iber after a CAR-T. Because we know that this can bring benefit in or after a transplant. But the concept is the same. We want to integrate other modalities to what can be potentially curative, but not necessarily can be in every patient. This is where we believe integrating a portfolio like ours with multiple shots on goal can give us this opportunity. For the role of CELMoDs, I am absolutely excited by this drug. First of all, Luisa, protein degradation has always been a very important aim in research and in development.
I think BMS has a platform that put the company, in all honesty, up front there. Because it's something that is in research and since many years, there is the highest level of knowledge. We have currently 11 drugs in clinic between hematology and oncology with targeted protein degradation. And it's not only CELMoDs. We have ligand degraders. We have antibody conjugate degraders. So it's really a platform that can deliver. The great thing of this thing is that these are oral drugs. These are pills that you can combine very nicely with other treatment. Of course, there is some toxicity associated with some of them. But this is why we have such a large portfolio. Because, for instance, we know that Mezi is a very potent CELMoD and more difficult to be combined with anti-CD38. This is why we are using Mezi with PIs.
And we use Iber that is more combinable with Dara in that space. This allows us to position these drugs across the spectrum of treatment. So to wrap up, what I would say is first line, absolutely, we want to play them. We want to bring cure to this patient and newly diagnosed is the space to be. But there will be inevitably some patients that will need further treatments. And this is where we believe building regimens with our portfolio will help us to deliver this.
And maybe building, Christian, this is exactly an exciting time for patients with multiple myeloma. And the BMS portfolio is extremely well positioned, as you've heard, with CAR-T and also with our CELMoDs.
Coming off ASH, what we've really heard from clinicians is they see that Iber and Mezi are now going to be the partner of choice, whether you're talking triplets, quadruplets, whether you're talking combination with TCEs. We also already have, as part of our registrational program for iber, maintenance study, which is, of course, a highly important segment for these patients, and what our clinicians tell us, and this is a study that's recruiting very well, is that they can tell when patients are on ibers and CELMoDs because the number of GI side effects and fatigue, which are particularly important when you think about our previous IMiD therapies, they're seeing this is very much lower, so this is definitely a group of products that show broad applicability, high quality of life for patients, not only in academia but also in community.
And as the field starts to evolve with TCEs coming in earlier, we are also ideally placed as a partner of choice there. You saw MagnetisMM and MELT data coming out of ASH that showed, to your point, a reassuring safety profile in combo. And we're seeing from our clinicians that this is probably an ideal combo in a setting where people may have already had Dara early on.
Thank you. Thank you, Monica.
Thank you, Christian and Monica. Operator, let's move to the next question.
The next question comes from Steve Scala with TD Cowen. Please go ahead.
Oh, thank you so much. As a follow-up to Luisa's question, how has the approval of BLENREP changed Bristol's view on how the multiple myeloma treatment landscape will evolve in the U.S.?
Does Bristol view BLENREP as an important potential combination partner, or do you not expect significant use of BLENREP in multiple myeloma? Thank you.
Hi, Steve. Nice hearing from you. Let me start. I see this approval as a positive thing for patients, like always. Of course, we know what are the strength and potential some liability with ADCs in this space. So I want to, Rosanna, maybe give a little bit of your view on this approval.
Sure. Now, the BLENREP approval in third-line plus relapsed refractory myeloma was with BVD post and IMiD PI. It is limited. It rejected the second-line use. But it's a good option for patients in late lines when other drugs have failed. The ocular toxicity will be a logistical and practical burden. Using BLENREP early, we have heard from physicians and investigators, can limit the effectiveness of TCEs and CAR-Ts.
Actually, the International Myeloma Working Group recommends using ADCs after TCEs and CAR-T. If we look at our CELMoD programs, as Monica was talking about, these are orally convenient drugs that can be used across a wide range of treatment settings across patient populations, easy to use and administer with side effect profiles that clinicians are used to managing from IMiDs. I think we are well positioned with our myeloma strategy.
Steve, all in all, it's a positive that BLENREP was approved because it's another option for the patients. But also because it gave us the confidence that there is still the space to bring potentially even better drugs there and building better regimens. The agency is open to this approach.
Thank you, Christian and Rosanna. Let's move to our next question.
The next question comes from Courtney Breen with Bernstein. Please go ahead.
Thank you so much for taking our question today. I actually wanted to follow up a little bit on Luisa's question about the first-line multiple myeloma crowding context. And particularly as we think about kind of Iber and Mezi perhaps replacing some of your older agents, can you talk a little bit about how we should think about the potential size and scope of the TAM for these CELMoDs relative to kind of that replacement opportunity for Revlimid and Pom, given kind of this evolving landscape and perhaps greater competition and different options available to physicians?
Thank you, Courtney, for the question. I would ask maybe Rosanna try to give an overview of where we are playing with the different studies and the view. And maybe Monica can take the second part of your question, Courtney.
Sure. Absolutely. Multiple myeloma has always been a rapidly evolving treatment landscape.
That has not changed. Our portfolio is built for a future treatment paradigm. If we look at how treatment has changed over the decades, IMiD has been the consistent backbone of therapy. CELMoDs were deliberately designed with a deep understanding of the biology of IMiD. They offer a more tailored approach of potency, tolerability, and combinability. Aside from the scientific rationale, we now have compelling data that shows the improvement that CELMoDs can bring. Christian reviewed the EMN26 data of Iber replacing lenalidomide. It doubles the MRD conversion rate in the post-transplant setting compared to Len in modern trials. We're excited about the EXCALIBER maintenance readout. The other thing that we saw is from our MM-001 study, Iber-Dara-Dex in newly diagnosed transplant non-intended. We saw faster and deeper MRD compared to historical Len, more than double the MRD rate.
And so that, along with our ambition with our dual-targeting CAR-T in newly diagnosed, we feel that we have a portfolio that is built for the future of treatment paradigms.
Yeah, absolutely. And from a commercial perspective, Rev and Pom have been extremely popular for very good reasons. They are extremely easy to use. The majority of patients still sit today in community where having an oral accessible treatment for patients is highly appreciated. And in Iber and Mezi, you basically have the next generation, or as some people have called them, super IMiDs, where you have even more potency from an efficacy standpoint. But also this improved side effect profile, which many patients, particularly when you're thinking of a maintenance therapy, which is, again, a large segment of the population, is extremely valuable to patients.
We really do see Iber and Mezi replacing the backbone being the partner of choice for all of these new therapies coming along. And the emerging data that we're seeing in these combination treatments is extremely reassuring from a safety perspective.
Thank you, Monica. And Rosanna, let's take the next question.
The next question comes from David Amsellem with Piper Sandler. Please go ahead.
Thanks. So sticking with the commercial landscape for Iber and Mezi, can you talk to access and affordability for those two, particularly earlier lines of therapy in multiple myeloma, in the context of a world where the IMiDs are going to get a whole lot cheaper over the next few years just in terms of generic competition? How do you think about that? Thank you.
So of course, I can't talk specifically about price.
But what I can say is that we believe that we have a product that shows significant value for patients. This is a regimen that's going to be able to be used both in community and academia. And as the multiple myeloma landscape evolves, we believe that these products represent value for patients and for the physicians that serve them.
Thank you. Let's move on to the next question.
The next question comes from Zack Dunn with Guggenheim Securities. Please go ahead.
Thank you for the question. This is Zack Dunn on for Seamus Fernandez. So firstly, we've been encouraged by the growth of Breyanzi. I'm wondering, can you elaborate on what is driving this growth and where do you see market share ultimately ending up? And if you can address U.S. and OUS, that would be greatly appreciated.
And moving to your BCL6 degrader, it seemed at ASH there were some questions on the correlation between BCL6 expression at baseline versus response and how there doesn't seem to be a clear correlation at this moment in time. I guess, can you provide a little more guidance on how you're selecting the right patients, or do you think that this drug will be more reserved for follicular lymphoma given the higher CR and ORs in this population? Thank you.
Thank you, Zack. Very good question. Let's start, Lynelle, with the Breyanzi.
Yes. Thank you so much, Zack. And thank you also for noticing Breyanzi's significant growth this year. You are right. We became the number one CD19 CAR-T in worldwide sales last quarter, which was a great milestone to achieve, particularly since we launched third to market and spent our first three years vector constrained.
And so now, enjoying being unconstrained and manufacturing success rates in the 1990s, it's really allowed the overall profile from efficacy and safety and now manufacturing to really be now the asset of choice. At ASH, in particular, if you didn't have the opportunity to see, there was 2,400 patients' worth of real-world data presented across France and the United States demonstrating the comparison of liso-cel and axi-cel. And in that data set, you got to see that these assets are very similar on efficacy, if not very similar. And then on safety, they're highly differentiated. And this is why we do believe we became the number one CD19 CAR-T. While we are being fueled by our broad set of new indications, that is a differentiator for the asset.
I think the overall profile, if you just clicked in LBCL, we are now the number one asset also in LBCL, which is the largest indication. And that isn't just in the United States. That's in Japan, Germany, and France in the major markets. And the reason for that, again, is because they're enjoying the efficacy of a one-time infusion from Breyanzi, but also not having some of the liabilities that CAR-Ts can bring. And so it really has been a great last year for Breyanzi. And we do anticipate that growth to continue based on the broad indications and its overall profile. Your question about split between international and U.S., we do anticipate the international markets will still accelerate maybe at a faster pace in the United States because they kind of we launched later there. And we were constrained later.
So those we're bringing on an additional market, 12 additional markets, as we move into next year. So with the expansion into new markets, as well as greater penetration into the major markets that we launched into, I do anticipate Breyanzi will continue to grow.
Thank you, Lynelle. Rosanna, let's try to give a little bit of an overview on the BCL6.
Sure. So BCL6 is the ligand degrader, has been shown to induce rapid and sustained BCL6 degradation in both the peripheral blood and in the tumor. Remember, this is a heterobifunctional ligand degrader. So it degrades BCL6 through the Cereblon E3 ligase recruitment, ubiquitination, and subsequent proteolytic processing. And so you not only have degradation of the BCL6, but you also have activity from that CELMoD platform. We have ongoing investigations, of course, in our translational development to look at how BCL6 acts in the tumor.
We know that phenotypically it modulates T follicular helper cells and T regulatory cells without affecting cell viability. And so there's a multi-modality approach to using this asset. And we have ongoing investigations so that we can understand how to best enrich for responses as we move the development forward.
Thank you, Rosanna. Zack, let me add a couple of thoughts. Personally, I'm really excited about this novel degrader. First of all, BCL6 as a target has been chased for decades without success. And now we have a drug because you have seen the monotherapy activity that is very clear. I think your question on can we identify patient can benefit even more is very relevant. And as you can imagine, we are working very hard to understand.
Rosanna gave you some very clear explanation why the drug potentially can still work in most of the patients and all the patients. There is another aspect I want to highlight, and it's the safety profile of the drug. The drug does not induce cytopenias or no severe cytopenias. So the combinability that you can have with the BCL6 maybe is different than the combinability you have with golca that is more on the classical cytopenic toxicity, hematological toxicity. So this is another very relevant drug in our portfolio of lymphoma assets that can give us the flexibility to, again, continue to build another regimen and targeting something that so far has been undruggable. So it's the beginning of the journey again. But actually, we have solid monotherapy data. And as you can imagine, we're starting a very broad combinatorial strategy with the drug across modalities.
Thank you.
Operator, we will now take our last question and then I will ask Christian to make closing remarks.
The last question today comes from Kripa Devarakonda with Truist Securities. Please go ahead.
Hey, guys. Thank you so much for taking my question. Maybe a follow-up on the prior question. As you develop BCL6 combos for second-line LBCL, how do you think about the eligibility of patients for the combinations versus cell therapy and maybe on Breyanzi, as you're seeing increased access and growth, any changes in how you're thinking about pricing and market access? Thank you.
Thank you, Kripa. Maybe Rosanna try to give a little bit of an idea. Of course, we don't guide on the inclusion exclusion criteria directly.
Sure. Sure.
So when we look at our both in myeloma and lymphoma, when we look at our CELMoD portfolio and our cell therapy portfolio, we view them as complementary and not really competing with one another. And so without giving away too much about the inclusion exclusion criteria and how we're moving forward in the pivotal trials, we do see that the oral convenience of BCL6 in patients with non-Hodgkin's lymphoma makes it a nice partner for bispecifics. And we are very much looking forward to the combination strategies that will keep it exploring.
And then Kripa, you actually asked a really good question in reference to Breyanzi and its growth that I didn't mention touching on market access. But its underlying your question is where we're also getting a lot of our growth is into the outpatient and into the community.
Obviously, growing CAR-T as a class is an enormous strategic priority for the industry. And certainly, Bristol Myers Squibb as a leader in this industry is doing a lot to partner with the community and being able to deliver CAR-T at the major community centers. And we're really happy to see multiple CAR-T community practices now come on board and be treating patients in the community. That said, there are no challenges we have faced yet, nor have the treatment centers. That was one of the biggest concerns was how were they going to get reimbursed? Would they be getting reimbursed? And we're really happy to say I think that was a lot of concern and perception. But we've been able to navigate the market access landscape in the United States. And the community physicians are getting reimbursed for CAR-T.
So we have not been facing challenges on pricing and reimbursement with Breyanzi.
Thank you, Lynelle. Operator, let's close.
This concludes our question-and-answer session. I would like to turn the conference back over for any closing remarks.
Thank you for joining today in this hematology drug development update. I really hope that you found this latest data, this pipeline insights, and the strategic perspectives informative but also inspiring because we continue and we wanted to advance these therapies for patients. I'm really looking forward to sharing more progress and especially some of the pivotal milestones next year. Thank you for your question and have a great rest of the day.
The conference is now concluded. Thank you for attending today's presentation. You may now disconnect.