Hello, and welcome to Genmab's ASH 2025 update. As a reminder, this webcast is being recorded. During this webcast, you may be presented with forward-looking statements that include words such as believes, anticipates, plans, or expects. Actual results may differ materially, for example, as a result of delayed or unsuccessful development projects. Genmab is not under any obligation to update statements regarding the future, nor to confirm such statements in relation to actual results unless it is required by law. Please also note that Genmab may hold your personal data as indicated by you as part of our investor relations outreach activities in order to update you on Genmab moving forward. Please refer to our website for more information on Genmab and our privacy policy. I would now like to hand over to your first speaker today, Jan van de Winkel. Please go ahead.
Hello, and welcome to Genmab's 2025 R&D update and ASH data review. I'm Jan van de Winkel, President and CEO of Genmab. I'm delighted to share with you some of the highlights for Genmab in 2025, as well as exciting upcoming data from this year's ASH meeting. Next slide, please. As a reminder, this presentation may contain forward-looking statements, and the statements may contain certain risks and uncertainties, so let's move to slide three. We will begin with a review of the progress we made this year as we advance towards our 2030 vision. Next, we will review some of the encouraging hematologic data presented at this year's ASH meeting, and for this, we are pleased to have Dr. Lorenzo Falchi, then looking ahead, I will provide a brief overview of some of the key events we are anticipating for 2026.
To conclude, I will open the floor for a lively Q&A session. And for this, Dr. Falchi and I will be joined by Genmab's Chief Medical Officer, Dr. Tahamtan Ahmadi, and our Chief Development Officer, Dr. Judith Klimovsky. But first, let's explore some of the highlights from the past year. Next slide, please. I'm pleased to say that we have successfully delivered on the commitments that we made at the beginning of the year. With the proposed acquisition of Mirus and the addition of Pathosentomab to our portfolio, we saw an opportunity that will position us for sustained growth and long-term value creation. And our other commitments this year support our conviction that we will be able to rapidly maximize Pathosentomab's potential. We significantly accelerated the development of RINA-S, and together with our partners, we expanded the reach of both EPKINLY and TIVDAK.
These strategic investments, in addition to our high-quality recurring revenue, have set us up for success in 2026 and beyond, so let's look at some of the specific progress we have made this year on the next slides. Since 2013, we have been executing a strategic shift from our royalty-depending earnings to a diversified, fully integrated, 100%-owned model. The addition of Pathosentomab to our already compelling late-stage pipeline significantly accelerates the shift. The totality of data that we have seen for Pathosentomab underscores its potential as a best-in-class EGFR-directed bispecific across head and neck cancer indications, as well as other EGFR-expressing tumors. We anticipate the transaction will close by early in the first quarter of next year, and the integration of Mirus will be a key priority for us in 2026.
For RINA-S, we have presented compelling data in both second-line endometrial cancer, where RINA-S has also received breakthrough therapy designation, as well as in platinum-resistant ovarian cancer, or PROC. What emerges from these data sets is a highly compelling product profile across efficacy, durability, safety, and through the whole spectrum of folate receptor alpha expression, and we are investing to maximize the potential we see in RINA-S with an accelerated and comprehensive development plan. We are ending this year with three phase III trials and two phase II potentially registrational trials. For Arkasunimab, hopefully you have seen the updated data presented at ESMO- IO just yesterday, showing promising overall survival and durable benefits with manageable safety. Turning to our already commercialized medicines, TIVDAK was approved in both Japan and Europe, providing us with the opportunity for the first independent product launches in Genmab's history.
With these launches, we are building a foundation in the oncology community that will set us up for future success with the potential future launch of RINA-S. EPKINLY expanded with additional approvals, including the approval from the FDA just last month in combination with R-squared in second-line follicular lymphoma. The unprecedented phase III data in this indication was simultaneously published in the prestigious journal The Lancet and highlighted during an oral presentation at ASH, one of seven oral presentations and over 30 total accepted abstracts for Genmab this year. Now let's review this data along with two other key data sets presented this year at this year's ASH Annual Meeting. Let's move to the next slide. To present this exciting data, I'm delighted to introduce to you Dr. Lorenzo Falchi of the Memorial Sloan Kettering Cancer Center in New York.
Lorenzo is a medical oncologist and hematologist and an expert in the treatment of lymphoma. As an investigator, he is intimately involved in the development of epcoritamab. Lorenzo, please go ahead.
Thank you. Thank you so much, and it's a great pleasure to be here with you and to share some of the exciting reports that Genmab has presented at this year's ASH. I was very honored to be part of several of those. I'll begin with this slide, which is an overview of the accomplishments that have been made at this year's ASH through epcoritamab, with 31 abstracts accepted and seven of them being an oral presentation. You see them highlighted here in three particular disease domains: follicular lymphoma, diffuse large B-cell lymphoma, and Richter's transformation, which is a specific complication of chronic lymphocytic leukemia and a very severe one. For follicular lymphoma, you can see three abstracts were presented in the frontline setting.
The first, EPCORE NHL-2, arm six and seven, were presented combined in one oral presentation with a three-year follow-up update of this triplet combination of epcoritamab plus rituximab and lenalidomide, or R-squared. epcore NHL-2, arm three was also presented as a three-year update in this particular study. Epcoritamab was combined with the chemoimmunotherapy standard bendamustine and rituximab. Then finally, in an academic study from the Dana-Farber Group, epcoritamab combined with rituximab was also tested for patients with newly diagnosed follicular lymphoma and presented as an oral talk. In the relapse refractory setting is where we really were happy to share for the first time the primary analysis of the randomized controlled phase III trial named EPCORE FL-1, which tested rituximab and lenalidomide with or without epcoritamab. I'll talk a little bit more about the study that I was honored to be presenting at this meeting.
As a corollary to that study, we also presented in the form of a poster patient-reported outcomes from the same study showing how the addition of epcoritamab really preserved the patient's quality of life while improving the results, as I'll mention. In diffuse large B-cell lymphoma in the frontline setting, three studies were presented, two of them as an oral talk. The first is the arm one of EPCORE NHL-2. This is the flagship study, if you will, for patients who are fit to receive full-dose chemotherapy, and in the study, patients receive R-CHOP plus epcoritamab. Here, we gave an updated three-year follow-up or longer than three-year follow-up, and we showed really encouraging results, and I'll talk about this in a subsequent slide. The arm eight of the same study, EPCORE NHL-2, looking at dose-reduced chemotherapy for patients who are a little bit more elderly and cannot receive a full-dose chemotherapy.
And then EPCORE DLBCL-3, which is looking at epcoritamab monotherapy, meaning epcoritamab given alone for patients who are really more frail or very elderly and really cannot take any chemotherapy at all. And this is really going to fill a really important unmet need in that space. In the relapse refractory setting, a four-year update of the EPCORE NHL-1 study, the original trial that led to the approval of epcoritamab for recurrent large cell lymphoma. This four-year update gives essentially the longest update for a bispecific in diffuse large B-cell lymphoma in the market. And these data were also very exciting and very confirmatory in a good way. EPCORE NHL-6 study was looking at epcoritamab in the same indication that it's approved for, but including a diversity cohort in the U.S., including Puerto Rico, and kind of testing epcoritamab a little bit more in the real world.
And then the NHL2 arm five study also was presented as a two-year update. In this particular trial, epcoritamab was combined with GemOx. Also exciting news from the Richter's transformation space, as I mentioned, both epcoritamab as monotherapy and in combination with either lenalidomide or R-CHOP were tested and reported both as oral presentations. Of note, the epcoritamab monotherapy study eventually led to the NCCN recognition. And so this treatment, this drug, is now included in the NCCN compendium for patients with recurrent chronic lymphocytic leukemia. And so you see here how you have a phase III readout. You have first reveal of data in a niche, but very important disease such as Richter's transformation. And you have a lot of long-term updates, in particular for the frontline follicular lymphoma and large cell lymphoma setting in combination, but also in the relapse setting as epcoritamab monotherapy.
A little bit more about the EPCORE FL-1 study. This has been really our pride. Certainly, it has been my honor and my pride to present this study on behalf of all our co-authors. This was a randomized phase III trial comparing in a one-to-one fashion epcoritamab plus R- squared versus R- squared alone. You can see it's a large study for 188 patients equally distributed in the two arms. These were patients with follicular lymphoma who had received at least one systemic therapy, including chemotherapy, and in need of subsequent treatment. The study was designed to demonstrate the dual primary endpoints of overall response rate and progression-free survival. It was conducted at 189 sites across the globe. We presented this particular analysis with a median follow-up of 14.8 months. This was the second interim analysis where we were able to analyze both primary endpoints.
Here is a look at the patient's characteristics at baseline by treatment arm. Obviously, this being a randomized control trial, the characteristics were well-balanced in general. But I invite you to look at the bottom part of the chart where you can see the treatment history of these patients. And although just over half of the patients had received one line of therapy only prior to entering the study, there were a large number of patients with heavily pretreated disease, but more importantly, patients with high-risk features, including POD24, which means an earlier relapse after frontline chemotherapy, and also patients that were refractory to the first-line therapy, meaning they never achieved a satisfactory response, or patients who were double refractory, meaning that neither rituximab nor chemotherapy has succeeded. So a particularly difficult-to-treat patient subgroup. So here's the study of first co-primary endpoint.
The addition of epcoritamab to R- squared led to a massive 79% risk reduction in the risk of progression or death, and this was with a hazard ratio of 0.21, which at least in my experience is unprecedented. I don't recall seeing a hazard ratio this favorable, obviously highly statistically significant, but it's important to emphasize also that when we did the subgroup analysis of progression-free survival, what we found is that the benefit in terms of progression-free survival was preserved across patient subsets, including the higher risk, but also the lower-risk patients across ages, obviously sex, regions of the world, et cetera, so this really demonstrates that the benefits of adding epcoritamab to R- squared are really maintained across a broad population of patients with recurrent follicular lymphoma, and here's a second co-primary endpoint, which is overall response rate. This was an earlier endpoint that we looked at.
This was also met. The overall response rate was 95% for epcoritamab R- squared and 79% for R-squared alone. The complete response rate, perhaps even more compellingly, was 83% for epcoritamab R-squared and 50% for R-squared alone. It's a large difference. We know that the value of complete response is very significant in follicular lymphoma, where the complete response really translates almost in a one-to-one fashion into better progression-free survival and eventually better outcomes. We also looked at a number of secondary endpoints. Perhaps an important one is a duration of response. That is how long the response that is achieved can last. Here again, we saw a very large difference with a very significant improvement in the duration of response with the addition of epcoritamab to R-squared.
Again, here, an incredibly favorable hazard ratio of 0.19, highly statistically significant, really suggesting that once that response is achieved, it tends to be maintained for a long time. This was true for epcoritamab alone, and it's even more pronounced with the addition of epcoritamab and R-squared. We also took an early look at overall survival. Now, I don't want you to over-interpret this curve because the follow-up of the study, as I mentioned, is too short, and this is, as we know, follicular lymphoma, where overall survival analysis can take a long time, but with this very early time point, we started to see a little separation in those curves with a hazard ratio of 0.38 and a significant p-value. This does not mean that epcoritamab R-squared results in a longer progression overall survival than R-squared.
But it's possible that with longer follow-up, we may be able to see that difference. This would be, I would say, unprecedented that a new treatment improves overall survival over an established real second-line therapy like R-squared, that it's an internationally accepted standard of care. And then finally, we looked at safety because obviously, we were very happy to see the efficacy results, but we didn't want to neglect safety. And obviously, we want to make sure that this is not only an effective treatment and a superior treatment, but it's also well-tolerated with adverse events that are manageable. This was indeed the case. Obviously, adding a drug that's very powerful is not going to go without any side effects. There were a little bit more adverse events in the patients treated with epcoritamab plus R-squared. But these were not adverse events that were unexpected.
In other words, it's what we call in jargon, there was no safety signal. We didn't see anything surprising. There was no strange toxicity coming out of the combination by putting together these two components. So certainly, nothing that we were not able to manage. CRS or cytokine release syndrome has been a major theme in terms of adverse events when talking about bispecific antibodies. With the addition of rituximab, with the particularly modified step-up dosing schedule during the first month of therapy, we were able to bring down not only the incidence of CRS, but also the severity. There were no cases of severe CRS. No patient was hospitalized for this treatment. So this treatment really is a fully outpatient therapy that can be applicable even in community settings across the country and beyond the U.S. One brief comment about infections. Obviously, epcoritamab is an immunosuppressive therapy.
It's not surprising that these patients had a little bit of an excess in infections. I would note that most of these infections were mild respiratory infections that we were able to monitor in an outpatient setting. Sometimes, patients had to be admitted for infections. This was in part true also for the control arm of the R-squared. Clearly, these data point towards an attention that needs to be paid to prophylaxis and proactive management of infections. We don't want to start patients on this treatment without adequate antibiotic prophylaxis and adequate monitoring. I think after a brief learning curve, what we've learned ourselves is that it's really easy to do that frequent monitoring and just really treating proactively these infections. Ultimately, at least in our center, we didn't have to hospitalize anyone.
And so here, you really have an essentially practice-changing study that shows that the addition of a highly potent bispecific antibody like epcoritamab in patients with relapsed follicular lymphoma leads to a massive reduction in the risk of progression or death, has a positive trend in overall survival. It is chemotherapy-free. It is fixed duration. I should mention this. You might remember in the epcoritamab monotherapy cohort, treatment was given until progression, so indefinitely. Here, we fixed the duration to 12 months or 12 cycles. So this was really a transformative treatment in a transformative study. This was recognized by prestigious journal like The Lancet that we were honored to be accepted in.
But it also, importantly, was recognized by healthcare authorities, in particular the FDA, that, as you know, on November 18th, granted approval to this combination for the treatment of patients with follicular lymphoma after at least one line of therapy. And it also secured traditional approval for epcoritamab monotherapy in its present indication in follicular lymphoma. Other regulatory submissions are ongoing globally. And I would expect them to be positively received. Now, moving on to other follicular lymphoma settings, as I mentioned, in the frontline space, things are moving. Here are three studies that were presented: results of EPCORE NHL2 study, classic frontline study, patients with high-burden disease in need of therapy, two years of treatment with epcoritamab, rituximab, and lenalidomide, same combination as in EPCORE FL1, but given for a little bit longer. Very impressive overall and complete response rates, 95% and 88%, respectively.
And at 33 months, a pretty impressive 90% of patients remain progression-free. These data, if confirmed, would compare favorably with what we typically see with chemotherapy. Similarly impressive, a smaller study, epcoritamab combined with classic chemoimmunotherapy, BR, same patient population. Almost every patient here had a complete response. And these were also preserved at three years, another very powerful combination. And I would note the study led by my good friend and colleague, Dr. Reid Merryman at Dana-Farber. This was an investigator-initiated study looking at chemo-free but also lenalidomide-free combination of epcoritamab and rituximab. Very impressive overall response rate, 97%, complete response rate, 91%. It's a little bit early. The follow-up is still short, but certainly very promising results. So you can see how epcoritamab-based combinations are really bringing a serious challenge to standard chemotherapy for the first-line treatment of follicular lymphoma.
So moving on to diffuse large B-cell lymphoma, particularly talking about the frontline setting. There are three studies that I'm going to briefly cover: the Arm 1 of EPCORE NHL-2, Arm 8 of the same study, and then EPCORE DLBCL-3. The first study, Arm 1 of EPCORE NHL-2, it was dedicated to patients fit for full-dose chemotherapy and with high-risk diffuse large B-cell lymphoma, with R-CHOP given for six cycles and epcoritamab extended to one year. In these patients, we saw an impressive overall response rate of 98% and a complete response rate of 85%. And at this three-year follow-up update, we also observed that 83% of patients remained alive and 74% in complete response. If we think about a comparator for this, for example, the control arm of the POLARIX study, that three-year mark has a probably lower progression-free survival.
It makes us have high hopes for this particular combination in this setting. In Arm 8, we tested lower dose of chemoimmunotherapy with epcoritumab. Again, here, there was a three-year follow-up update that was presented. This is for patients who are not able to tolerate full-dose chemotherapy. Look at the responses. Again, high overall response rate, 93%, and 86% complete response rate, very similar to patients who had a full-dose chemoimmunotherapy. At two years, which is the update presented here, 82% of the patients remained alive and 79% in response. Then finally, EPCORE DLBCL3, looking at epcoritumab monotherapy, that is epcoritumab alone, in patients who are elderly or very frail and unable to tolerate any chemotherapy. These patients are really a highly unmet need because they would not be treated other than palliatively, and they don't really have viable options.
Having a chemo-free treatment that results in a very encouraging 73% overall response rate and 62% complete response rate, with the vast majority of patients completing treatment remaining in remission, is certainly very encouraging news for these patients who will really have very few, if any, options. The collection of this data really strongly supports the versatility of epcoritamab and the ongoing phase III registration-directed EPCORE DLBCL-2 trial, comparing epcoritamab plus R-CHOP versus R-CHOP in patients with newly diagnosed diffuse large B-cell lymphoma. And the study will read out in 2026. So I'm very eager to really discover the results of that study. And I'm very hopeful to celebrate those results as well. So in summary, we dedicated a little more time to the EPCORE FL1 study because it really is a transformative study.
It really exemplifies the power of epcoritamab and how it can really reshape treatment paradigms, just really displace current treatment standards. Really unprecedented progression-free survival and, more importantly, massive reduction of that risk of progression or death, almost 80%. There certainly is momentum for the drug. This is the first positive phase III study, not for just epcoritamab, for any bispecific in follicular lymphoma. In fact, it's the only randomized trial published for bispecifics in follicular lymphoma. Got FDA approved. Got published in a highly resonant journal. Basically, we have the trifecta here. I couldn't be prouder of the team, and I couldn't be more grateful to be part of this project, really, but more importantly, I couldn't be happier for our patients that now have a really substantial improvement in their outcomes when treated with this combination.
In large cell lymphoma, I think we continue to build momentum around epcoritamab-based combinations and really support very strongly the phase III study that's ongoing, comparing R-CHOP plus epcoritamab versus R-CHOP alone. And I think the collection of this data, including the ones in Richter's and some others that I didn't have time to mention or that were unpresented this year at ASH, really speak collectively to really the broad versatility of epcoritamab as a combination partner and as a drug that can really make a big dent in many disease settings in B-cell non-Hodgkin lymphoma. Because it's administered subcutaneously, it doesn't have really significant chair time. It doesn't have overlapping toxicity with most treatments that we commonly use for B-cell non-Hodgkin lymphoma. It really has its position in the best way to really make a difference in every existing treatment paradigm for these patients.
So really, all the data that I went over really support epcoritamab as almost shifting the narrative as a backbone therapy as opposed to considering chemotherapy as the backbone for patients with B-cell non-Hodgkin lymphoma. So I'm very excited to look forward to 2026 when more data will read out. And I'm just really going to be there and watch as the data unfold and probably, and hopefully, at least celebrate many of this data. I'm just really thankful to be a part of several of these efforts. It's been so rewarding to use this drug in the clinic and see really the patients' outcomes under our eyes improve so significantly. And I thank you all for your attention. I'm happy to take any questions you might have.
For the Q&A session.
Thank you, Lorenzo, for that inspirational presentation.
So now let's move to some of the key pipeline events that we are anticipating in 2026. Next slide. Yes. 2026 will be a year of important catalysts for Genmab. A key focus will be the rapid integration of Merus following the close of the proposed acquisition. As a reminder, we integrated ProfoundBio in less than a year. And we are confident that we will replicate that success with Merus. As part of this integration, we will keep a laser-sharp focus on our investments in order to position the company for optimal growth. This includes investments to maximize the potential of our commercialized medicines and in our promising late-stage portfolio. In 2026, we expect multiple potential registrational data sets for EPCORE, Rina-S, and beta centromere. If successful, we envision a 2027 with four KYSO products on the market. Half of which will be entirely Genmab-owned.
So in summary, in 2025, we significantly strengthened the foundation of our business. We did this through targeted M&A and strategic investments in the expansion of our key late-stage and commercial programs. In 2026, we will take the next pivotal steps in our shift into a diversified, fully integrated, 100%-owned model, advancing our evolution into a global biotech leader and positioning us for durable growth. So let's move to the next slide. Yes. And now it's time for our Q&A session. And I'm pleased to note that in addition to Lorenzo and I, we also have members of our executive committee to answer your questions: our Chief Development Officer, Judith Klimovsky, and our Chief Medical Officer, Tahamtan Ahmadi.
And before we begin, a quick note that as Lorenzo is very busy with the important work of caring for patients in New York, he will not be able to join us for the entire Q&A. So please now open the line for questions.
For the Q&A section of today's session, we'll be utilizing the raise hand feature. If you would like to ask a question, please click on the raise hand button at the bottom of the screen. Once prompted, please unmute yourself and begin with your question. We'll now pause a moment to assemble the queue. Our first question comes from Jonathan Chang with Leerink Partners. Your line is open. Please feel free to ask your question.
Hi, guys. Congrats on the data. And thanks for taking my question. On EPKINLY, what is the strategy for increasing adoption in community settings for both FL and DLBCL?
Thanks, Jonathan, for that question. I'll hand it over to Tahamtan to give you a perspective.
Yeah. Again, Jonathan, thanks for the question. Generally speaking, and just to go back a little bit, I mean, from the very beginning, we've been very clear that we thought a key component of the differentiated profile of epcoritamab was the subQ administration, the efficacy, the safety, and the convenience that comes with that. And that has translated into the relatively low grade two CRS rates, which we have further been able to improve in follicular form with the three-step updosing and diffuse large B-cell with a modified steroid regimen that we have already presented to health authorities.
To come to your question, I think, A, the sub-Q administration in and of itself is an important differentiator as we enter the community, which is where a lot of these patients, particularly in follicular form, are going to be, are being treated today, but also in diffuse HBC, in particular, if we get into frontline. The documented safety and the ease of administration, together with clinical trials that we are conducting and have been conducting to generate data that this is actually that community physicians are able to administer EPKINLY alone or in combination safely and confidently. That's another added differentiator.
And so also the updated label that comes with this particular study and that we also are looking for diffuse HBC. All of these components changed in the label, sub-Q administration, safety, experience in the community that then gets communicated are components of a strategy to increase adoption in the community where most of these patients are being treated. And so we're looking forward to seeing this 26 play out.
Thanks, Tahamtan . Thanks, Jonathan, for the question. Let's move on to the next one.
Our next question comes from Matt Phipps with William Blair. Your line is now open. Please feel free to ask your question.
Hi. Thanks for having me and doing this. For Dr. Falchi, how do you think about the infection risk for EPKINLY and bispecifics? Is there any additional prophylaxis that needs to be done, particularly as these move into those community settings, maybe making sure they're familiar with that, and if I can, just ask the company on the epcoritamab update. The OS did. Median OS did come down to about 12 months in the six-week dosing regimen. How do you think about odds of success there when some docetaxel arms have shown maybe an 11-12-month median OS in recent phase III studies? Thank you.
Thanks, Matt, for the questions. I think I don't know whether Dr. Falchi is already on the line. Otherwise, Tai can answer the first question, and Judith can definitely handle the epcoritamab question, Matt, but let's wait for a sec whether Dr. Falchi is on board. Otherwise, he may join later, Matt. I will ask Tahamtan to address the first question on prophylaxis.
Well, I mean, I'm going to try to do my best impression of Lorenzo. Thanks, Matt, for the questions. From our point of view, and then obviously, you wanted to hear the external point of view, with the instructions in the protocol that then also translated into the label instructions, which is general guidance on using GCSF when appropriate, but not mandating it. We don't think there is a priori need to include antibiotic prophylaxis. I think what's going to happen is, generally speaking, that physicians and the community will get increasingly more sophisticated in individualizing this a little bit. I would remind everybody that this is kind of like an interesting phenomenon. The more you deplete B-cells, the more you end up with neutropenia. But there was really infectious neutropenia, neutropenia fever, or the likes of was really not an issue on the study.
And you mentioned that most, actually, all of the patients were managed really in the outpatient setting. So anyway, from my point of view, from the company's point of view, we feel like we have given the community sufficient instructions to administer EPKINLY very safely. And I'm pretty sure that as a community, they are going to continue to fine-tune this and individualize this a little bit. There might be patients who are at a higher risk who may get some prophylaxis. This is the way it's always been handled in oncology, also with chemotherapies.
Thanks, Tahamtan . Judith, maybe you can address the new data, the updated data, I would say, on epcoritamab.
Yeah, of course. Thank you for the questions. And we were delighted to have this data in the public domain.
So I want to call to your attention that the subset phase III eligible is the one that matters for the comparison. And this encompasses patients that PD-L1 positive, as per central, and all of them exhausted PD-1 inhibitor and chemotherapy. In that subset, which is numerically 32 patients, the median OS is 14 months. But what I want to call to your attention is that the median overall survival is not predictive as much as milestone survival analysis. And here, for the ITT population, the 12 months is 51%, which is considerably higher than docetaxel, even if you go to ITT. And the population of interest, which is the 32 patients that were subset that phase III eligible, the 12-month OS is 64%. And when you compare with docetaxel, you see that the delta is meaningful. And most importantly, this study has follow-up to really see the tail.
You see the 24 months, which is 30% with some censoring. The tail is real. This is totally different with the curve of docetaxel. We are pretty confident that these results support the strategy that is being implemented in ABILITY 06.
Thanks. Thanks, Judith. Thanks, Matt, for the questions. Let's move on to the next question.
Our next question comes from Judah Frommer with Morgan Stanley. Please unmute your line and ask your question.
Yeah. Hi. Thanks for the presentation, guys. Thanks for taking the questions. Maybe I'm not sure if Dr. Falchi is on, but maybe one just high-level on CAR-T versus bispecific. Hey, doctor. Maybe just high-level thoughts on sequencing CAR-T versus bispecifics in lymphoma, where we sit after ASH. Certainly, it was a big debate in multiple myeloma, but curious how you're thinking about sequencing in lymphoma. And then just on DLBCL specifically, with Polivy approved in the frontline, but not seeing necessarily an OS benefit over R-CHOP, how do we think about predicting OS and the benefit there in first-line DLBCL for other assets? Thanks.
Please go ahead, Lorenzo. Why don't you?
Oh, I'm sorry. Yes, I'm sorry. Yeah. So in terms of the sequencing, that's a very different question in the setting of follicular lymphoma and large-cell lymphoma. I think in large-cell lymphoma, it's a little more straightforward because, at least at the moment, outside of a context of a clinical trial, you don't really have a label conflict because CAR-T cell therapies are proven in the second line, and APCOM monotherapies are proven in the third line.
However, particularly in the United States, some of these boundaries can be pushed through compendium indications and just by virtue of the sheer fact that a third-party payer system sometimes allows for earlier use of bispecific-based therapies in the second line. What I will say is that there's data for both the bispecific-to-CAR sequence and the CAR-to-bispecific sequence. And I would say the overall takeaway is that in the first case, there's not clear evidence that the performance of CAR-T cell therapy is affected by prior bispecifics. In the second case, as we know from the pivotal trial, the complete response rates remain high or higher than pretty much any other alternative for bispecifics after CAR-T cell therapy. And so I think that bispecifics do remain the go-to therapy after CAR-T.
But I think that bispecifics pre-CAR-T is a more important question in 2025 because, as I said, more and more people are using them. And so some of the questions are, if you use bispecific therapy as a holding therapy, meaning before CAR-T cell collection, does that affect the collection? We're actually trying to answer that question here at MSK as we speak. And we presented also data as a bispecifics consortium at this ASH, showing that really the performance of CAR-T doesn't seem to be affected, whether you use bispecifics as holding or bridging therapy. In follicular lymphoma, the question is a lot more nuanced because when the goal is remission rather than cure, it comes down a lot more to patient's preference and to the specific context where that patient is being treated.
If you focus for a second on bispecifics monotherapy, the clear advantage of bispecifics over CAR-T is their off-the-shelf nature and ability to be accessed outside centers that practice CAR-T cell therapy. Let's not forget that out of 6,000 healthcare facilities in the United States, 5,100 are community hospitals, and out of those 6,000 facilities, only 300 offer CAR-T cell therapy, so when you scale this discourse up nationwide, you immediately see how having an off-the-shelf therapy that has excellent tolerance or tolerability and good, if not very good, long-term outcomes is a huge value. The longest-lasting bispecific study in that space shows that if you have a response, you have about a 40% chance of being disease-free at five years. I mean, that's not something we've ever seen before this era, so I don't think that the sequencing matters too much in terms of efficacy.
I also don't think the sequencing matters too much in terms of burning bridges, so to speak. The whole discussion that I had about whether CAR-T cell could be affected by prior bispecifics, I think here is a little less relevant in follicular lymphoma, where you always have more time between one treatment and another, with few exceptions. So that ability of T cells to regain their fitness is much more likely in the setting of follicular lymphoma. But I would say now, with the results of APCOR, AFL1, this whole discussion acquires a whole new different light because when you're looking at patients in the second line, first of all, there's an additional indication that CAR-T currently doesn't have, which is second line.
Secondly, when you look at that performance, which is the same in second and third line, you're looking at complete response rate in the mid-80s% that are deep and durable. When you achieve that response, the duration, we don't even know what it is yet because it wasn't reached, but I wouldn't be surprised if it's in the order of years, progression-free survival that are very long, and more impressively, the time-to-next lymphoma therapy being essentially 93% next lymphoma therapy free at 16 months with no sign of the curve dropping, I think that's pretty impressive, and I think that makes a strong case to prefer a treatment like EPCORE R-squared in follicular lymphoma after frontline treatment and leave CAR-T cell therapy as a third line. With regard to your DLBCL question, I think that's very important.
And the short answer is we don't really have great tools to predict overall survival during chemotherapy, but I think we're starting to have great tools to predict long-term survival after induction chemotherapy. R-CHOP polatuzumab is the best treatment for non-GCB large-cell lymphoma. And I think not using that treatment for non-GCB large-cell lymphoma patients is, I'm not afraid to say, it's an error. For GCB large-cell lymphoma, I think it's much less clear. I don't think that polatuzumab adds what it adds in non-GCB. But in either case, the measurement of minimal residual disease at the end of induction therapy seems to currently be the most powerful predictor of cure, not just remission or progression-free survival. We know that if you have clearance of MRD, regardless of the results of PET, granted that most of those patients are PET negative, you have an almost 100% chance of being cured.
So I think we're getting to a point where we're very, very precise in predicting overall survival after induction therapy. Before induction therapy, that is, at baseline, we don't have that ability at the moment. And I think that we're really all very eager to await the results of studies like EPCORE DLBCL2, that if positive, may have an advantage and may have an advantage not only in progression-free survival because the results that we had seen in the phase II experience were just so good in patients who were otherwise higher risk. So to answer your question, I think that right now, there are tools to predict survival, none of which is readily applicable in clinical practice.
And we're waiting to see the results of these randomized trials, chiefly EPCORE DLBCL-2, to see if we can improve overall survival across the board and perhaps not even need too many tools to predict overall survival after induction is done.
Thanks, Lorenzo. Thanks, Judith, for the questions. Let's move on to the next question.
Our next question comes from Jieun Han with TD Cowen. Your line's unmuted. Please go ahead.
Jane?
Hi. Sorry. Yeah. My other question for Dr. Falchi also on kind of the first-line DLBCL opportunity. So EPCORE DLBCL-2 is versus R-CHOP, and we know that's glofitamab with Columvi versus Pola-R-CHP. I was curious, for you and for your colleagues, what degree of PFS benefit do you want to see with the EPCO combination over R-CHOP to drive usage of this regimen over both R-CHOP and also over Pola-R-CHP? And also, if you could give us some context about kind of the current uptake of Pola-R-CHP in the real-world setting. Thanks so much.
Yeah. Thank you. You couldn't have picked a more difficult question to answer, but I'll do my best. I think that it's important to understand there's a big distinction that it's important to understand, and that speaks to both of your questions. One thing is what the FDA is asking of a clinical trial, and one thing is what the community is going to do with those results. What the FDA is asking is a progression-free survival advantage that is statistically significant per the study design. If that happens, the study is positive. Now, obviously, there's a phase IV where you have to see what happens if and when the community picks up the new standard.
I think if there's even a strong suggestion of overall survival advantage, there's no question. That's going to just become the new standard across the board. If there is a progression-free survival-only advantage, it's not going to be at 2%. If it is an advantage, it's probably going to be more substantial. As you know, POLARIX had a 6%-7% advantage in progression-free survival. That was enough to give it whatever it is, 30%, I believe, uptake in the community. And as always happens, well, not people. The investigators, they present usually subgroup analysis that have the limitations that they have, but then people interpret those subgroup analysis. And if there are subgroups that have a bigger advantage, it's possible that colleagues in the community might be more, yeah, attracted towards using the combination in one subset versus another.
But I would say, again, the study is designed to answer a question in patients IPI 2-5 and, in particular, 3-5 all-comers. If the study is positive, and you're empowered as a physician to use epcoritamab in association with R-CHOP for those patients, in patients with non-GCB large-cell lymphoma, where epcoritamab R-CHP Pola really is delivering very good results, it's going to come down to the always unwarranted practice of cross-trial comparison and, frankly, familiarity of the specific physician with one regimen or another. That's very hard to control, certainly even harder to predict now, but I would wait and see. It's not just about the progression-free survival advantage, the magnitude of it. Obviously, if you have a 10%-12% advantage, that's plenty, and if possible, frankly, based on the EPCORE NHL-2 results.
But if the advantage is a little bit thinner, then it depends on the specific estimate of progression-free survival in that particular non-GCB population.
Thanks, Lorenzo. Thanks, Jieun, for the questions. Let's move on to the next one.
The next question comes from Alek Ebbeling with UBS. Please unmute your line and ask your question.
Great. Thanks for taking my questions. Two, please. First, on EPKINLY and R-CHOP in first-line DLBCL. So it's nice to see sustained high PFS and OS rate at the three-year follow-up. I'm just wondering if the duration data are similar in the GCB and ABC subtypes and if their duration curves are largely driven by one subtype. And second question on Rina-S in ovarian cancer. I was just wondering if you could share anything on the potential filing strategy there. Do you think you can file based on pivotal phase II data, or will you have to wait for the confirmatory phase III trial? Thank you.
Thanks, Alec, for the questions. I think Dr. Falchi can probably best address the first one, and then Judith can address the second one.
Yeah. Thank you. Yes. I don't believe we have curves by subtype. The response rates are very similar, and the representation of those patients in the clinical trial is fairly similar to real life with about 60/40 GCB, non-GCB. It's perhaps not surprising because bispecific antibodies were never really shown to work differently in GCB, non-GCB. And so, again, you might have that in high-risk patients that is IPI 3 and above. With non-GCB, you may have excellent survival curves. And I always recommend caution in comparing and in doing cross-trial comparison.
But what we have seen in our experience is really sustained responses at three years plus, which is plenty of follow-up for large-cell lymphoma in all patients that we treated.
Thanks, Lorenzo. Judith, why don't you go on to the registration strategy for Rina? Very exciting.
Yeah. Super exciting. And as you know, we have RMC, which is designed as a potential pivotal arm with more than 100 patients and could potentially meet subpart H accelerated approval requirements. And in addition, we have the O2 study actively enrolling. So the regulatory strategy is including both the potential pivotal for accelerated approval and a phase III for full approval.
Thanks. Thanks, Judith. Thanks, Alek. You should watch out for next year. Very exciting year. Let's move on to the next question.
Our next question comes from Sarah Bai with Guggenheim Securities. Please unmute your line and ask your question.
Hey, this is Sarah. I'm from Michael. Thanks so much for taking my question. Just a really quick one for you. I was wondering if you could speak to the rationale for choosing epcor plus R-Squared to move into frontline follicular over epcor plus bendamustine and rituximab, given that now we've seen positive data for both. Thank you.
I think Tahamtan can probably best address this, and Lorenzo can chip in there as well, because you're very actively involved, Tahamtan.
Yeah, sure, and thanks for the question.
I think you have to just dial a little bit back and look at the data that also Lorenzo talked about, which if you start thinking about when we started to make our decision, the ambition that we articulated for EPKINLY was that it was truly going to change follicular lymphoma and really challenge these paradigms that existed in follicular lymphoma while it's an incurable disease. Eventually, with every kind of relapse, the duration of response to the PFS shortens. If you just look at the second-line data in combination with R-Squared, I think it's probably reasonable to say there's at least a reasonable argument one could make that these assumptions in the past are being challenged as we speak with the data in front of us.
And they're being challenged essentially with what is a regimen of two CD20-directed antibodies, a bispecific and a naked antibody in a pill, which has an enormous amount of convenience, but also safety implications. And so I think it's probably fair to say, and Lorenzo can add his perspective as a treating physician to that, that generally speaking, the toxicity of R-Squared, even in frontline, will probably not be comparable to a regimen that includes any form of chemotherapy, may it be bendamustine or more historical cyclophosphamide combination regimens that have been used in frontline follicular lymphoma.
The idea was to come up with a regimen that can challenge the current standard of care, fundamentally change the outcomes for patients in frontline follicular lymphoma who meet these criteria for intensive care, which is the GELF criteria historically, and provide an option that can be easily administered in the community and that is patient-friendly and better tolerated. That's broadly speaking the idea, the ambition of our frontline study and our general strategy in follicular lymphoma was.
Thanks, Tahamtan . Lorenzo, any further perspective from your side?
Yeah. I echo Tahamtan 's sentiments and an articulation of the rationale. I think having been part of both trials as well as the relapse refractory trial, which is the EPCORE R-squared, I can tell you when we first discussed the study. This was maybe late 2020, and then the Genmab team presented all the five arms we were discussing.
Pretty much after they went through the list, I was like, "That's the one that I want to be part of." That was the R-squared APCOR, just because mechanistically and biologically makes just so much sense. You may be aware, but just to simplify lenalidomide, one of the things it does, it reinvigorates your immune response against the lymphoma. It just kind of made so much sense to say, "Okay, well, on the one hand, you're reinvigorating these T cells, and then on the other, you're just hitting them with a drug that just literally grabs them and brings them in proximity to the target lymphoma cells." That was just kind of a theoretical rationale. You have to prove it. What happened in the first few patients in arm two, which is the relapse setting, was that everybody responded. At our site, everybody responded.
We just got so excited overnight, and so the hope was that it was going to go further and continue like that, and lo and behold, it did, and you can find that it published in Blood earlier this year. Over 100 patients in that arm two had an 88% complete response rate, then the other arm, which is arm six, which is a frontline arm, which has a very similar design, has pretty much the same results, so you're seeing something that has the same very powerful effect in second-line plus or first-line. Almost doesn't matter what line of therapy you are. That's one element. The other element is let's not forget that now you have 108 patients in the second line for arm two, 243 additional patients in second line for arm two, and 40-odd patients in frontline. That's what, like 400 patients treated with R-squared APCOR.
The data for the efficacy and the follow-up are among the most solid in the space, I might say. For bendamustine rituximab epcoritamab, we really have a very low number of patients, and yes, it's powerful, perhaps to no surprise, but there are several reasons to not prefer, at least from my point of view. I'm happy to discuss, but bendamustine is a very immunosuppressive drug, and it tends to kill several of your T cells, some of the ones that you need for epcoritamab to work. That's not to say that epcoritamab didn't add to bendamustine rituximab, but it just doesn't add as much, and on the other hand, you really are compromising the immune system quite severely. We've had a number of pretty severe infections on that arm, and there really is no appetite, I think, in the community to use chemoimmunotherapy as a backbone.
If you take a look across the landscape, all the randomized control trials in frontline follicular lymphoma are against chemo without chemo. So that's really where the field is going. Again, that's not to say that chemotherapy is not working. But we're now in a place where I think Thai mentioned this, where bispecific antibodies, we're flipping the paradigm. It's not that there's a backbone and then you add bispecific antibodies to them. There's bispecific antibodies, which you really can't do without, and then you choose the treatments to add on. So I think of R-squared, for example, as an add-on to EPCORE, not the other way around. If you look at EPCORE FL2, the difference between the curve is so huge, and that's all EPCORE, that you can't help but think, "Okay, well, that's EPCORE that's driving everything.
R-squared is decorating it, but the core therapy is really the bispecific." So if that's true, then in my physician researcher mind, why would I add chemotherapy to that? I think you'd do more harm than good to the APCOR. So to me, it's really the chemo-free rationally conceived therapy that's going to have a better hand. And that's why I think the APCOR FL2 is designed the way that it is.
Thank you, Lorenzo. I think, Sarah, that's an answer you can come back with to Michael. So really clear.
Amazing. Thank you.
Thanks, Sarah.
Our next question comes from Qize Ding with Rothschild & Co. at Redburn. Please go ahead. Hi. Thanks for taking my question.
One question from me on EPKINLY. So yeah, I remember you previously talked about the potential indication expansion for EPKINLY in CLL. So after seeing the latest data presentation at ASH this year, can you just talk about your latest thoughts on this potential indication expansion opportunity?
I definitely can. Kishi, but I have a much better colleague to answer that question. That's Thai.
Yeah. Thank you for the question. And so Lorenzo touched on this in the beginning. The data that we presented is in a specific complication of chronic lymphocytic leukemia, essentially a transformation that has been named Richter's transformation. So Richter's transformed large cell lymphoma. That's where we presented the data. It's something that we've had conversations with the health authorities in the past and continue to think about what our strategy is in that particular subset. Equally in CLL, I mean, this has been a topic where we are continuously thinking.
And I think it's probably fair to say that the CLL field is fluid right now with multiple changes. And so I think there's still a little bit of work to be done on our end to establish the most perfect place for EPKINLY to be positioned in that space, and we're continuing to do that.
Thanks, Thai. Thank you, Qize, for the question. Let's move on to the next one.
Our last question comes from Asthika Goonewardene from Truist. Please go ahead. Asthika, go on.
Hi, guys. Sorry, I was on mute there. Thanks for taking my questions. So maybe something quick to Dr. Palchi. And apologies if something similar has been asked already. But in the context, so there are multiple studies in frontline DLBCL, but besides T-cell engagers, that also include BTKs, we saw CELMoD with iberdomide, etc.
All these do have some pretty high CR rates. So maybe to Dr. Palchi here, in the context of having all these options in the future, how will you pick the right therapy? And what do you want to see a T-cell engager plus R-CHOP show to rationalize using this over the other modalities? And maybe related to that, can T-cell engagers be given in the community as easily as the cell mods and BDKs to treat frontline DLBCL?
Yeah. Because the topic would be too huge to address here. But there's something like seven or eight randomized control trials going on now. And when we presented the EPCORE R-CHOP data, I think it was last year at ASH, that session was stellar. Everybody has 100% CR rate. So clearly, CR is an early good surrogate, but you need time-to-event analysis.
That's what we presented this year with the EPCORE R-CHOP at three years with very reassuring and encouraging PFS curves in patients who are, let's not forget, have high-risk disease, many of whom have double or triple hit lymphoma. Obviously, you may have a situation where one or two trials largely stand out from the crowd with progression-free survival advantages that are more sizable in more subgroups. It's going to be a slicing and dicing of data. There's a few factors that are going to help navigate and orient the landscape. One is very simply, who reads out first? Because if you read out early, usually that's a good sign. You also have more time to penetrate the market and the community. We know that familiarity with a certain drug or a certain regimen is key.
I'm very good at using R-squared EPCOR, for example, or EPCOR R-CHOP. My neighbor that's never used it may be less familiar, so that's one other factor, but if you do see a delta that's large enough, frankly, I hope so, from bispecific R-CHOP or epcoritamab, then I think if there is a bispecific that's easy to combine with chemoimmunotherapy, that's EPCOR, and there's multiple reasons for that. One is that it's subcutaneous. Let's not forget logistics are very important. Some of the other intravenous bispecifics you can't give them the same day as R-CHOP or epcoritamab. That means patients have to come another day. Secondly, because your peak of CRS incidence is in cycle one day 15, you have given CHOP two weeks prior, you have debulking enough to dampen some of that CRS. The CRS rates in EPCORE NHL-2 arm one were quite good.
But even more importantly than that, perhaps, the idea that you have a subcutaneously administered bispecific that is quote-unquote gentler or it gets eased a little bit more smoothly into the patient allows you to start that bispecific in cycle one day one. And that's critical for me because most of the resistance that you see, even in patients who end up having a complete response, is born in cycle one. And so having the ability to potentially rescue those patients who are quote-unquote destined to fail later, starting from cycle one, may be a structural advantage of APCOR-based platforms as opposed to others. Again, you're going to have to see the data. You're going to have to compare to the best of your ability the data.
But at least in principle, as of now, the reason that I'm more excited about following those developments with EPCORE DLBCL2 is because of these very plausible advantages that it has over the landscape.
Great. Thank you, Lorenzo.
Yeah, and I was wondering if I can throw one quick one at you here. The R-Pola-Glow data at ASH looked really interesting in the unfit frail population. I was just wondering if that is encouraging Genmab to also consider something like that with an ADC with a chemo-free option. And if you could tell us a little bit more about your thinking. Thanks.
Thanks, Asthika. That's probably a question for Tahamtan , then.
Yeah. I mean, thanks, Asthika. Generally speaking, I would say this. I mean, our strategy on the elderly frail has been to essentially establish an anchor plan.
Hopefully, the study will read out an anchor registration, which would be frontline R-CHOP, and then provide additional data that informs practice within that anchor. Our mini-CHOP where you basically just can dose-reduce and recycle or even immunotherapy where you can basically just drop the chemotherapy if the patient is really not tolerant. That's kind of like how we started to think about this. I mean, I would say there was a lot of debate at ASH actually to who is really frail and how frail is being defined on these trials. There's a little bit of a discussion on each of these trials how frail the frail patients are, something to think about. We don't really actually at this point concretely have any plans to combine with POLIVY. I mean, it is probably from Medicare, fair point, an interesting strategy.
It's not necessarily clear to me why we would engage on that end. But anyway, we'll see. More to come on that end. We feel very happy with where we are with the data that we're generating in elderly and frail. And we're really enthusiastically expecting the result of our frontline study next year.
Thank you, Thai. I think that's a good closing remark. So thank you, Asthika. And thank you all for the very good questions and insightful questions today. Next slide, please. Thank you all for joining us today. And a special bit of thanks goes to Dr. Lorenzo Palchi for his contribution to this year's event. We're very thankful for that. And from all of us at Genmab, we wish you all happy holidays and a healthy, happy, and truly wonderful 2026. Looking forward to speak with you next year. Thank you.