Hello, and welcome to Genmab's investor update. As a reminder, this conference call is being recorded. During this telephone conference, 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 this 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 going forward. Please refer to our website for more information on Genmab and our privacy policy. I would now like to hand the conference over to your speaker today, Jan van de Winkel . Please go ahead.
Hello and welcome to today's conference call. Following today's presentation, we will have a Q&A session. For this, I will be joined by our Chief Medical Officer, Tahamtan Ahmadi , our Chief Development Officer, Judith Klimovsky , our Chief Financial Officer, Anthony Pagano, and our Chief Commercial Officer, Brad Bailey. Now let's get started. Next slide, please. Before we continue, just a reminder that we will be making forward-looking statements, so please keep that in mind as we go through the rest of the call. Next slide. To begin, thank you for joining us to discuss this highly anticipated decision. While we are disappointed that J&J decided not to advance HexaBody-CD38, the data we will present to you today confirms and validates the clinical potential of the HexaBody platform, reinforcing its value for future applications.
While the initial clinical data looks promising and shows robust clinical efficacy, following a thorough evaluation of the data, the market landscape, and the principle of rigorous portfolio prioritization, we have made the decision to not pursue further clinical development of HexaBody-CD38. That said, what is important to emphasize here is that this decision has no impact on our long-term strategy. Genmab remains well-positioned for future growth, and our strong balance sheet will allow us to continue to invest and advance our high-value late-stage assets at EPKINLY, Rina-S, and Acasunlimab as we evolve into a fully integrated biotech innovation powerhouse. Let's now turn to the data on the next slide. As you can see, in a head-to-head trial, HexaBody-CD38 delivered both higher and deeper clinical responses compared to DARZALEX.
With the higher clinical benefit rates, including minimal response and better, it appears that more patients receiving HexaBody-CD38 experienced some level of improvement compared to DARZALEX. While more patients receiving intravenous HexaBody-CD38 reported at least one adverse event, most are low-grade or manageable, with more serious adverse events remaining generally manageable with standard supportive measures. Overall, HexaBody-CD38 delivers deeper responses than Darzalex in relapsed or refractory multiple myeloma, with maintained safety and tolerability. However, despite the encouraging nature of this data, given the current market dynamics and potential for commercial viability, as I noted, we will not be continuing the development of the HexaBody-CD38 program. Next slide, please. As we stated during our Q4 financial results call, regardless of J&J's decision, our strategic priorities in 2025 and beyond would remain unchanged.
We intend to maintain our laser-sharp focus on and investments in our promising late-stage proprietary clinical pipeline, specifically at Epcoritamab, Rina-S, and Acasunlimab, because these three programs are poised to drive very significant revenue growth for Genmab by the end of the decade. As you can see here, there are currently seven phase three trials between EPKINLY, Rina-S, and Acasunlimab. As a reminder, three of the five ongoing phase three studies for Epcoritamab have been fully recruited well ahead of schedule, and we anticipate three potentially significant pivotal results by the end of 2026. Our commitment to advancing EPKINLY across multiple indications in B-cell cancers underscores its potential as a best-in-class treatment, with a peak sales opportunity exceeding $3 billion. For Rina-S, we are exceptionally well-positioned to maximize its potential, given our proven clinical development capabilities, our track record of acceleration, and our experience in the guiding space with Tivdak.
Based on the exceptionally strong execution of the team post-acquisition, we remain on track to bring Rina-S to patients by 2027, with its best-in-class profile expected to achieve peak sales exceeding $2 billion. With two phase threes we plan to have underway by the year end, we are well on track to putting into place the building blocks to achieve this target. There is also a meaningful opportunity for novel treatments like Acasunlimab in non-driver-mutated second-line plus non-small cell lung cancer to provide not just improved response rates, but durability of response. Here we anticipate a peak sales opportunity of $1 billion. Beyond these programs, we will continue to actively look for opportunities to grow our pipeline both organically, with the development of a promising early-stage pipeline, and inorganically. This will position us for sustained growth and long-term value creation for our shareholders.
We will continue to execute against our capital allocation framework, ensuring future growth. Next slide. We are confident that our high-impact programs will reach their full potential because of the team and the capabilities that we have put into place. In the past few years, we have focused on scaling up the development so that we can expand from early to late-stage development. We are now doing this with multiple ongoing and planned phase three clinical trials you saw already on the previous slides. We are doing it quickly, as evidenced by both the extremely rapid development of EPKINLY, which advanced from first in-human clinical trial to approved medicine in five years, and our ability to progress Rina-S so significantly in less than a year.
We not only brought forward the start of the first phase three trial for Rina-S, but we have now announced a second phase three trial in an additional indication. We have also significantly built our technical operations and commercialization functions, enabling us to not just bring our own products to market, but to ensure that the right therapies get to the right patients as quickly as possible. Thanks to our exceptionally strong performance in key markets like the US and Japan, we are confident in our ability to expand EPKINLY's reach even further. Our prioritization of the Japanese market has been especially successful, and we are now well-positioned to build on our leadership position in this market with the recent approval for third-line plus relapsed or refractory follicular lymphoma.
With this approval, EPKINLY is now the only bispecific antibody approved in a dual indication for the treatment of certain B-cell malignancies in the U.S., in the European Union, and in Japan. Looking ahead, we also see opportunities to expand the potential of Tivdak in advanced cervical cancer to new markets where patients' needs remain high. We expect approval in Japan early this year, where Genmab will lead full commercialization responsibilities, and in Europe later this year, following a positive CHMP opinion issued in January. Importantly, the anticipated launch in Europe provides a catalyst to enter the next phase of our commercialization strategy as we expand our work to new markets in a strategic and financially disciplined manner, just as we have successfully done in the U.S. and Japan to date. Next slide.
In summary, while we are disappointed in J&J's decision not to develop HexaBody-CD38, the fundamentals of our business remain strong, and our long-term strategy remains unchanged. At Genmab, we have a proven track record of creating innovative antibody medicines. We will continue to build on the momentum provided by our previous successes by further prioritizing our investments and expanding market opportunities. We have the financial foundation, the talented team, and the capabilities in place to continue to do so. We will continue to invest in accelerating the development of high-impact late-stage programs at EPKINLY, Rina-S, and Acasunlimab, with investment into phase three clinical trials. We will also continue to maximize the success of our commercialized medicines because it's our investment in these programs now that will potentially generate meaningful revenue by us by the end of the decade.
We will continue to seek our business development and M&A opportunities that fit within our core focus areas: mid to late-stage development and commercial stage product opportunities, where, just as we have done with Rina-S, we have the ability to accelerate development. We will continue to be disciplined in our approach to this investment to deliver on our capital allocation priorities, positioning us for sustained growth and long-term value creation for our shareholders. We are confident that as we look into the future, our long-term strategy will ensure that we will see the realization of our 2030 vision of transforming the lives of patients through innovative antibody medicines. Next slide. That ends our formal presentation. Operator, please open the call for questions.
[Operator's Instruction] Thank you. Our first question will come from the line of James Gordon with J.P. Morgan. Your line is open. Please feel free to unmute and ask your question.
Hello, James Gordon, J.P. Morgan. Thanks for taking the question or questions. The question, if I look at slide five, which hopefully lays out the key late-stage pipeline news flow, it's notable that there isn't anything listed for this year. Is that definitely the case? For EPKINLY in the first-line trial, is there any chance that there could be an interim that means we could get some data ahead of next year, or is it definitely nothing until next year? The other part of the question would be, if there isn't anything happening on the readout front, that doesn't mean there's not lots going on for you to be doing.
With clarity on HexaBody now, could that mean there is a bit more urgency to do some more M&A, get some more late-stage pipeline, because now you definitely do have a 29-30 erosion to address, or absolutely no change, and it's fine if there is no readouts in the next 12 months?
James, I think I can take both of the questions. There was definitely potential for earlier readouts, for sure. We cannot say that for sure because they are event-driven, but there is absolutely potential for earlier readouts, and even in this year for EPKINLY, albeit that we are not certain about that, and that's the reason, James, that they are not on slide five. There is clearly a potential earlier readout in 2026, for sure. As it relates to data, we will have multiple data readouts this year also for already, I think, next week for second-line plus POC to look at the Rina-S data. Actually, in the trial you already have seen data from last year at ESMO, there is definitely an oral presentation on Monday the 17th at SGO on data.
There will be data on endometrial cancer in the first half of this year at a major cancer conference also for Rina-S. There will be multiple data readouts. Yes, James, we are very busy also at the BD front. We have multiple target companies on the radar screen, albeit that we cannot estimate what the timing will be of potential deals. I think we have shown you already last year with the very efficient, not only execution, but also integration of ProfoundBio that we're really very well on track to actually execute one or more M&A deals.
That will be important to fill the income at the end of this decade, early next decade, albeit that we are very, very confident that the key assets, the three key assets, EPKINLY, Rina-S, and Acasunlimab will contribute in a meaningful way to income by the end of the decade. I think all engines are running at full speed, James, so you do not have to be worried there.
Thank you.
Our next question will come from the line of Jonathan Chang with Leerink Partners. Please go ahead.
Hello, this is Ying Li for Jonathan Chang. Thanks for taking my question. We have a question about looking at the head-to-head data, there seems to be a higher adverse event and discontinuation for GEN3014 compared to Darzalex. Could you share your take on why this is the case, and can you discuss the potential implication of this data to the other HexaBody programs such as GEN1055? Thank you.
Thanks, Jon, for the question. I will hand it over to Tahamtan, with our multiple myeloma expert, Tahamtan. Maybe you can give a bit of color there?
Thank you for the question. I mean, as you see in the comparison, you're comparing a drug that is intravenous to subcutaneous. You see a drug that has almost a doubling of the depth of response, and there's also a higher discontinuation. Partially related to the fact that certainly there's significantly more experience in managing daratumumab in the subcutaneous version than there is on the HexaBody-CD38. To some degree, it was treated as a novel IND. That there's also a difference in the safety profile, for example, the IRRs neutropenia.
Thanks, Tahamtan. Handing it back to the operator.
Our next question will come from the line of Xian Deng with UBS. Your line is now open, Xian. Please go ahead.
Hi, thank you for taking my question. Two, please. Maybe the first one, just to follow up on the previous questions. Other than the IV versus subcu difference, do you think this kind of tells you much about the HexaBody technology? Just wondering, do you think the fact that you have higher AEs, but then the ORRs seem to be broadly comparable, do you think that might, by any chance, signal, I do not know, maybe higher potency by any chance? Any follow-up HexaBody program needs to be extremely clean in terms of the targets. Any insights, that would be great. That is the first question.
Second question is just wondering, looking at your major phase three trials, Acasunlimab in second-line lung cancer, EPKINLY in front-line DLBCL, and Rina-S in second-line ovarian cancers, just wondering, if I were to ask you to force rank those three trials in terms of probability of success, just wondering, how do you view that? Thank you very much.
Thanks, Xian, for the questions. I will start with the first one and then hand over to Tahamtan to also handle the next part of the first question and then also the second question, the rank ordering. This will be quite interesting. I can tell you that we feel that the data of this trial, Xian, really clinically validates the HexaBody platform. We are pursuing a number of programs, both in the clinic as well as in the preclinical setting, getting ready for the clinic. Especially the enhancement of complement-dependent cytotoxicity was really clearly shown clinically to lead to benefit here in this head-to-head trial. We are very excited about the potential of HexaBody. About 10% of our product candidates in the whole pipeline are based on the HexaBody platform, Xian.
You will see more candidates coming to the clinic, and I think this bodes quite well, actually, for a number of those candidates. I'll now hand it over to Tahamtan to give further color and also do the challenging rank ordering here.
Thank you for the question. On the first part, I think, yeah, absolutely, the question is a great question. The points that Sion was obviously saying to the fact, which we have always flagged up, that in part, this was also validation around the HexaBody mutation, which is a single-point mutation to enhance CDC. What you saw in this trial, when the data is in the public domain, also relates to the demographics. What you will, I'm sure, appreciate is that the efficacy signal is actually real and profound. It's more of the doubling of the depth of response and in the context of the imbalances on risk factors to the degree it will become even more important. To us, this is a strong validation of the hexamization as a mechanism to unlock further CDC.
It's also supported by a deep dive into the biomarker data that kind of lights up from a scientific point of view with the clinical observation. It validates the technology and it validates this approach and it for sure gives us a toolbox that we are exploring for other targets and other diseases. On the rank ordering, I actually don't really think this is a helpful exercise. We don't really tend to start studies that we don't believe in or are committed.
Of course, to some degree, probability of success is a mathematical exercise in the end if a study is positive or negative, and partially informed, of course, by what additional data you are generating or the robustness of the understanding of the drug that you have. Certainly, we have a certainly better understanding of Epco and Nowrena than, for example, Acasunlimab, because there's just more data there. Broadly speaking, I don't think this is a good exercise to rank all this.
Thanks, thanks, Tahamtan . I think you have to do the rank ordering by yourself, it sounds like, Xian.
Thank you.
All right, thank you very much. Let's move back to the operator for the next question.
Our next question comes from the line of Asthika Goonewardene with Truist Securities. Please go ahead.
Hey, guys, thanks for taking my questions. Can I ask, will you provide, will Genmab provide any feedback on the reason for opting out? I mean, when you look at the data that's presented, certainly the depth of response seemed to be favored in the GEN3014. Was it more to do with overall response rate or was it the toxicity profile that made them want to back out? Tahamtan, it sounds like from your comments that maybe the IV formulation may have made it a little bit harder to balance the AEs, made it a little bit more pronounced. Does a subcutaneous version of a HexaBody product make sense? Lastly, when do you plan on actually providing us with the data from this head-to-head study? Thanks, guys.
Thanks, Asthika . Let me start here and then ask Tahamtan to step in. What we actually heard from J&J is that basically the data do not meet J&J's very high bar for both showing clinical differentiation and also market potential. That is also to a certain degree, as we heard, a consequence of the change in the treatment landscape for multiple myeloma. It is actually more and more difficult to develop new medicines there because it is getting more crowded in the market. I will pause here and see whether Tahamtan can give further color and then also go into the IV versus subcu formulation and AEs potentially for HexaBody. Tahamtan? Tahamtan, you are on mute, Tahamtan.
Yeah, there's not much to add to the decision on J&J. If you look at the evolution of the multiple myeloma landscape, I think it's quite apparent already what a profound change has happened in the last couple of years and how much standard of care has improved already. We can leave it at that. On the subcu versus IV, I would probably answer the question historically. If you look at the subcu versus IV studies that were run with Darzalex, you get a sense that subcu administration does mitigate some of the AEs related to this particular target. As Jan said in the beginning, I think this is important to reiterate. For us, this is the end of the CD38 HexaBody story, and there is no need to worry about subcu versus IV.
Generally speaking, in the future, that might be another story for another target.
Thanks, thanks, Tahamtan . Thanks, Asthika, for the questions. Let's move on to the next one.
Our next question will come from the line of Michael Schmidt with Guggenheim Securities. Please go ahead.
Hi, this is Paul on for Michael Schmidt. Thanks for taking our question. I was hoping just to expand on your M&A strategy comments from earlier. You mentioned mid to late-stage programs. Are there any specific modalities or indications in focus? For instance, is it largely a solid tumor focus or heme as well? Are you still evaluating the potential to go into autoimmune? Thanks very much.
Thanks, Paul. I think I can handle that question. We are looking for phase three or phase three ready programs as the top targets for potential acquisition. Oncology is a key focus right now, but of course, we also keep our eyes wide open for I&I targets because that is our second core focus area, Paul. Realistically, I think we will probably end up with oncology targets because we feel that we are really well equipped to evaluate them earlier, quicker, and more effectively than some other companies can. I think we showed it with the ProfoundBio acquisition where we heard actually that other companies were looking at that company, but we were simply too quick. I think we were very quickly in doing the due diligence because of our experience in antibody medicine.
Oncology is likely going to be the key target, and we are looking very broad, both solid tumors as well as hematological cancers. Yeah, we have things on the radar screen. Things look quite good from that perspective, albeit that it's difficult to give you a further estimate, Paul, of timing because they tend to have their own rhythm, some of these processes.
Let's move to the next question, operator.
Our next question will come from Yifeng Liu with HSBC. Please go ahead. Yifeng, your line is open. Please feel free to unmute.
Thanks for taking my question. Just one clarification question. Since I'm assuming that your agreement with Genmab on HexaBody-CD38 is terminated, any chance this asset is still transferable? If that's the case, and whether there's any sort of restriction could be applied potentially coming from your agreement with Genmab? Thanks.
The contract, Yifeng, specifies that this molecule cannot be developed in areas where Darzalex is actually in late-stage development or on the market, but it can be developed in other areas. That is per contract. It has a more limited span of use, I think, in the future for us as well as for other parties. The asset is now back in our own hands, but we are definitely restricted that it is also only possible in Darzalex-resistant patients and other indications, except those where Darzalex is on the market. I think it has a much more limited scope.
Just to clarify that, thanks very much, first of all. Even if you were to transfer it to licensing out, that sort of restriction still will apply. Am I correct in understanding that?
Yes, the restrictions still apply because that part of the contract is still intact, and we are not considering any partnering or out-licensing opportunities for HexaBody-CD38 for that reason.
Clear. Thank you very much.
Thank you.
Our next question will come from the line of Vikram Purohit with Morgan Stanley. Vikram, it appears you're on a phone. Star 6 will allow you to unmute.
Great, thank you. Can you hear me now?
Yes.
Okay, thank you. I appreciate your taking our questions. First, on HexaBody-CD38, we were just curious, when you all made the decision to kind of cease internal development here, did that take into consideration the potential for the molecule in autoimmune conditions? When you think about the future for autoimmune development in your pipeline, is HexaBody-CD38 something that could resurface? Secondly, we had a housekeeping question. Just wanted to make sure on timeline that for Acasunlimab, phase two, a data update in second line and NSCLC, that's still on track for this year. Actually, a final housekeeping question.
I know that you mentioned that for 2025 guidance, there's no changes, but is there anything we should keep in mind on the OpEx side now that HexaBody-CD38 is being rolled back, either for 2025 or 2026, anything that we should be mindful of? Thank you.
Thanks, Vikram, for the question. The first one, I'm going to move over to Tahamtan to say a bit about the potential for autoimmune diseases. For the second one, I can answer that with a clear yes. We are absolutely on track in the second half of the year to combat further data on Acasunlimab, not only survival and duration of response data, but also of extra patients, of at least an extra 20 patients of the every six-week dosing, which is the dosing which is used in the phase three trial, which is progressing well. Absolutely on track, Vikram. Anthony Pagano can probably handle the expense question, the operating expense question after Tahamtan gives us color on AI, I mean, autoimmune diseases. Tahamtan?
Yeah, yeah, thanks for the question. The answer is very simple. I mean, as Jan said in the beginning, we will not continue development of HexaBody-CD38, not in oncology, not in immunology. Generally speaking, CD38 is a challenging target in immunology because of the requirement for surrogate animal data that have some long-term survival.
Thanks, Tahamtan. That's clear. Anthony Pagano on the operating expenses as a consequence of this?
Yeah, Vikram, to be clear, and it's in our company announcement, this decision does not impact our 2025 financial guidance. Maybe just a reminder for you and those listening in today, our investments here in 2025 in terms of our top three investment priorities really focused at number one in terms of the expansion and acceleration of Epcor clinical development with five phase three trials ongoing and expansion of Epcor into two key markets. That is number one. Secondly, really continuing to expand and to put our foot on the gas pedal for Rina-S with the start of the phase three and really the continuation of the first phase three in PROC, and then also the start of the first phase three in second line plus endometrial cancer by the end of the year.
Of course, picking up on the part of your question around Acasunlimab as well, investing back into that program in terms of the ongoing phase three. Moving forward, we'll continue to really be focused and take a disciplined approach to our OpEx and do more of the same. I think you'd agree, and you've seen with the recent investments we've made, they really paid off. We're now in a position where we expect three phase three readouts for EPKINLY by the end of 2026, and we continue to expect the first approval for Rina-S in 2027 with more to come. Really, from a commercialization side of things, we're really pleased with the investments we've made and the successful recent launches of EPKINLY and Tivdak. To come back to your specific question, today's news does not impact our 2025 financial guidance.
Thanks, Anthony. Thanks, Vikram, for the questions. Let's move on to the next question.
Our next question will come from Matthew Phipps with William Blair. Please go ahead.
Thanks for taking my question. I realize you're not going to pursue these, but just wondering if you have data from the AML or DLBCL arms of the trial and how that might, if that looked any kind of different versus any data that you had from Darzalex historically. Then thinking about this program for the OX-40 target, I'm just wondering, I guess you get clustering of the OX-40 receptor, but do you not get depletion of OX-40 positive T cells from the enhanced complement pathway activation? Thank you.
Thanks, Matt, for the questions. Tahamtan, I'm handing both of them to you. Maybe a bit on AML and diffuse large B-cell lymphoma and then OX-40. You're on mute, Tahamtan.
Thank you. There will be no data on diffuse large B-cell lymphoma and AML because we actually focused very early on the generation of the comparison data. That was that to CD38 HexaBody. On OX-40, there are two different biologies. One is CDC enhancement here, and the other one is the outside-inside signaling. Without getting into the specifics of how these approaches are also different and how we construct these antibody concepts, we do not get depletion of OX-40 positive cells. We will be able to provide some data on the OX-40 program at some point in the future, but that is a different question.
It is basically clustering and agonistic effects for the OX-40 target in a way that does not deplete the OX-40 positive cells.
Correct.
All right. Thanks, Matt. Let's move on to the next question.
Our next question will come from the line of Yaron Werber with TD Cowen. Please go ahead.
Great. Thanks for taking my question. I have a question actually on EPKINLY. EPCORE DLBCL- 1 has a primary of survival, and the EPCORE DLBCL-2 has a primary of PFS. It sounds like we're going to get data from both of them next year. I guess my question, do you think we're going to have PFS data from those studies? For DLBCL1, do you think you're going to hit survival already next year? For DLBCL2, would you also have some survival data when you read out the PFS next year? Thank you.
Thank you for the question, Yon. Tahamtan, can you address those?
Sure. Yeah, you correctly noted that the primary endpoint for DLBCL1 is OS, and so that's what's driving the timelines, and that's what's driving the readout. For the second study in the relapse refractory setting, this time in combination with lenalidomide, the primary endpoint is PFS, but OS still remains a very important secondary endpoint. I think this is probably all we can say at this point.
All right, thanks. It's very fun drifting, Jan, so we have to wait, huh? Let's move to the next question, operator.
Our next question will come from Suzanne van Voorthuizen with VLK. Please go ahead.
Hi, this is Suzanne from VLK. Thanks for taking my questions. I was wondering, looking ahead into the 2030s, can you elaborate how confident you are that your current assets and pipeline as this can make up for the Darzalex cliff? Considering the different profit splits here and there, which assets do you see as the most valuable for Genmab by that time? Allow me also a follow-up for EPKINLY specifically. For the frontline and relapsed or refractory studies in DLBCL, how do you foresee the data from the phase three trials to position EPKINLY in those treatment paradigms and to help further adoption there? Thank you.
Thanks, Suzanne, for two. We have very easy questions. I will ask Anthony to give his perspective on the contribution to our income for the different key products by the 2030s. Tahamtan, maybe you can help with the second question on EPKINLY and the positioning in the landscape. Anthony, why don't you start?
Yeah, I mean, as we think about our business overall, I really think it's useful to start with some important fundamentals. The fundamentals of our business are strong and continue to be very strong here. As a reminder, we have absolutely an unquestioned, proven track record, a very, very strong foundation across our entire business. That's our technology, our pipeline, our team members, our products, and our financials. It's really the strong foundation that has put some very meaningful growth opportunities in front of us. Let's unpack those growth opportunities that are in front of us today and how we are going to create some more growth opportunities here moving forward. As we've outlined our three late-stage programs, EPKINLY, Rina-S, and Acasunlimab, right now here in today, we have seven ongoing phase three trials.
We have gone through these in lots of detail in terms of the market opportunities, potential trial readouts, etc. Now, we think about those three products with the seven ongoing phase threes. I really think the first major future growth driver is our ability, based upon the very strong product profiles for each of these programs, to do more with each of these three programs, whether it be EPKINLY, Rina-S, or Acasunlimab. I think there is a lot more potential or more potential for each of these three existing phase three programs. The second way we are going to create future growth opportunities is really the power of our research and discovery engine and our early-stage pipeline. This is really useful to go back and think about our proven track record here.
I really can't tell you which program will come from our preclinical pipeline or our early-stage pipeline, but as we sit here today, I think we can all agree, and we're very confident that we'll have one or more programs in hopefully the near future that can transition from early-stage development to mid or late-stage development. That will be the second area for future growth opportunities. Third is really looking at external opportunities. Here, very clearly, we've outlined within our capital allocation framework what we'd be looking for in terms of external opportunities. Very clearly, to sort of summarize it for you, it would be a late-stage opportunity that is either phase three or phase three ready or beyond.
I think if we put that all together, Suzanne, it really starts to create an overall financial picture as we exit this decade, get into the early part of the next decade, a really appealing high-growth company with lots of opportunities in front of us. Importantly, not only the financial profile, but also what our late-stage pipeline will look like as we exit the decade. Very strong foundations and very exciting growth opportunities. Let's remind ourselves, in addition to the Genmab business, we currently have six royalty-bearing medicines. Now, one of those, of course, is Darzalex. There are five additional products that have lots of growth opportunities there as well.
There are three additional potential royalty-bearing programs that are either in phase three or beyond. There's a program with Novo, a program with Pfizer, and a program with Lundbeck. The totality of our business is really strong. The fundamentals are strong, and we have lots of growth opportunities moving forward.
Thanks, Anthony. Let's move to Tahamtan for the positioning.
Sure. Let me take a similar approach and step back a little bit on EPKINLY and diffuse large B-cell lymphoma. I think from the very beginning, we were very clear that in our mind, this novel mechanism of action of B-cell redirection towards CD20 was going to be transformative for the space of B-cell malignancies. That EPKINLY, based on its documented efficacy signal, its safety as well as the subcutaneous administration, which is part of the safety, but also in the convenience both for the patient as well as for the provider, was going to be the market leader, is the market leader.
If you just look at how this class, in particular EPKINLY, now has already kind of impacted the lives of patients in third-line, three pipelines of therapy and diffuse large B-cell lymphoma, I think it's very clear that a significant amount of patients already are getting this approach.
That's the first part. The second part is, if you then look at the phase two data that we had presented on the combination with R-CHOP in patients who had a high-risk feature of IPR 3-5, so really those patients who actually have the highest chance of not getting cured with R-CHOP because there's a roughly 50-60% probability of getting cured. The data was, broadly speaking, without a precedent. 100% response rate in all practical purposes, 100% CR rate. There was one patient who didn't have a CR, basically dropped off.
That gives us the confidence and the belief that once the data reads out in frontline, this is going to fundamentally transform frontline diffuse large B-cell lymphoma with a data set that is without a precedent and will, with very certain from our end, provide a significant positive impact for patients with diffuse large B-cell lymphoma in frontline.
Thanks, Tahamtan. I hope that you're okay with this answer, Suzanne. Let's move on to the next question, operator.
Our next question will come from Alastair Campbell with RBC. Please go ahead.
Hi, they can hear me, okay now?
Yes.
Yes.
Great. Yeah, sorry, just a very brief follow-up, actually, just thinking about the HexaBody platform. Not just not CD38, but outside of CD38. I mean, given the data you've seen from this trial, which sort of indicates very good target engagement, but a step up in side effects as well. If you think about HexaBody as a platform outside of oncology, so in I&I, does this give you pause for thought, or do you think it's actually simply about choosing the right target and the right dose? Thank you.
The short answer is, Alistair, absolutely no pause for thought because we are actually working preclinically with HexaBody programs for I&I. We think that this is actually an excellent technology platform, which is validated here clinically. We do not think that the safety aspects will be very much impacted by the HexaBody modification. I think this trial and this data show that there is a clear advantage in potentiating the killing activity of antibodies via the HexaBody mutation. Also, we are testing agonism with the OX-40 concept. We already answered to a previous analyst that this does not lead to depletion of OX-40 positive cells. We think this is a very promising platform, Alistair, and more to come in the coming years.
We have a number of very exciting preclinical programs which are slotted to move to the clinic, where we actually hope to break paradigms, basically, and moving into new areas where antibodies are not very successful in tumor therapy. With this modification, I think could be very successful. More to come.
Thanks, Jan.
Our next question will come from the line of Qize Ding with Redburn Atlantic. Please go ahead.
Hi, can you hear me okay?
Yes.
Okay, great. Thanks for taking my question. I only have one. Following today's news, am I right to assume that your level of confidence in your HexaBody technology platform remains unchanged going forward, right? Also, what have you learned from the HexaBody-CD38 for the future development of other HexaBody pipeline assets? Thank you.
Thank you for the question. I don't think that it is actually unchanged. It's actually much higher because we think that this data shows that the HexaBody platform is clinically validated to lead to a more effective therapeutic. What it has learned us is actually a number of things. I will hand it over to Tahamtan, who's overseeing a lot of the development of new concepts based on HexaBody. Tahamtan, maybe you can speak a little bit about what it has learned us for future development of the HexaBody platform.
Yeah, thank you. I will do that. I'll gladly do so. Number one, let's just remind ourselves of what the challenge and what the objective was. The objective was, with a single point mutation, to create an asset that then would hexamerize, and through the hexamerization would enhance CDC. As we talked about, what that would do, it would lower the threshold of CD38 required on the cells to then be sensitive to CDC. It would overcome to a degree biologically existing mechanisms that prevent this otherwise, which is the expression of complement inhibitory proteins, particularly CD55 and CD59.
What the data clearly shows is that with a single point mutation, you get—I mentioned the imbalance, and you will see the imbalance when the data is presented—even with the imbalance, a significantly meaningful enhancement of the depth of response, meaning we captured a larger portion of tumor cells with CD38 because there is an interpatient variability of CD38 expression on the myeloma cells. CD38, to remind everyone, is arguably one of the dirtiest targets out there. It's expressed in a lot of cells. There are tumors, it's kind of like the Goldilocks phenomenon. It doesn't really touch all of these CD38 positive cells.
There is a little bit of a higher neutropenia rate that is arguably related to the mechanism, but also arguably related to the increased efficacy because this phenomenon of neutropenia and B-cell depletion, while ill-understood, has been observed in every single B-cell redirected therapy. The more modifications to B-cell depletion is, the more enhanced is the neutropenia. I think that's the main safety observation on HexaBody-CD38. What is the readout for us, as Jan was saying? Actually, I agree. What it has given us is a higher degree of confidence that this technology, with a single point mutation, is able to enhance complement-mediated cell cytotoxicity and is able to overcome to a degree the expression of complement inhibitory proteins. This is very important as we think about other disease areas and other targets.
Thanks, T ahamtan. I think we have to move on to the next question.
Our next question will come from the line of Rajan Sharma with Goldman Sachs. Please go ahead.
Hi, thanks for taking the question. Just noting the kind of comments that you made on the high bar set by Dara in multiple myeloma, could you just kind of talk to what this means for your future R&D focus outside of HexaBody-CD38? Is it fair to assume that myeloma may not be an area of focus, but you go forward, whether that's through the internal pipeline or external? If that's not the case, what do you need to see in early-stage trials to give you confidence that there is a benefit beyond Dara and other current therapy? Just a follow-up on Acasunlimab, could you just remind us on what gives you confidence that the 4-1BB part of the mechanism is actually adding anything on top of just additional PD-L1 activity? Thank you.
Thanks, Rajan, for the questions. I will hand the first one over to Tahamtan to speak a bit more about multiple myeloma as a target for new approaches. Judith can take the Acasunlimab questions and describe the confidence we have in the conditional activation concept for 4-1BB to be definitely differentiated versus the blockade of the PD-L1 axis, Rajan. Let us start with Tahamtan and the multiple myeloma changing landscape. Tahamtan, are you on mute?
Sorry, again. I think the answer from our end, as it relates to multiple myeloma, is very clear. Multiple myeloma is not really an area that we are focusing on internally because the opportunity space for anything that you work on today to have any meaningful impact on patients in the future is impossible to imagine with all the novel mechanisms that have entered and have fundamentally changed the landscape. If you just look at the quadruple therapy in multiple myeloma and frontline, it is very hard to imagine if there is such a thing as relapsed/refractory
multiple myeloma in some foreseeable future. For us, this is not an area that we are focusing on.
Thanks, Tahamtan. Let's move to Judith and Acasunlimab, the confidence level that the 4-1BB agonistic arm really matters.
Yeah, thank you for the question. I would like to remind you that the population that was enrolled in the study was patients that progressed on checkpoint inhibition, PD-1 or PDL1, and most of them progressed on Pembro. In this patient population, Pembro doesn't have activity. It is not the inhibition of PD-1, but the agonist, the combination of total abrogation of the PD-1/PD-L1 axis through the PD-1 arm of the DuoBody , offered—this is Acasunlimab plus Pembro—and the agonistic effect of 4-1BB. In the literature, and as we saw in the poster that was presented in ASCO, we saw not just stable disease, but some PRs, like 17% partial response. This is unheard of in patients with a checkpoint inhibition after a checkpoint inhibition. Definitely, it is the combination of the agonist effect of 4-1BB plus checkpoint inhibition. You need both.
Thanks, Judith. Rajan, you will get more data in the second half of the year, and that will make it even clearer. Let us move to the next slide, operator.
Our next question will come from Yaron Werber with TD Cowen. Please go ahead.
Great. Thanks for letting me ask a follow-on. Tahamtan, just for you, I wanted to follow up on your comment earlier about CD38 as a target for I&I. I think you mentioned that there is a requirement to show long-term survival in preclinical animal models, and that makes it a challenge for I&I studies. Can you just maybe highlight that again and maybe share a little bit more information? Thank you.
T ahamtan?
Sure. Very simplistically, most patients with immunological diseases are younger in age, in most cases, patients with cancer patients. That includes particular women of child-bearing age. What that generally does is, in oncology, we sometimes do not do long-term safety studies. Sometimes we do, sometimes we do not. If we do not, then the inclusion-exclusion criteria and the label has something like, you know, women of child-bearing age should not take the prospective medicine.
In immunology, that, of course, is a little bit more challenging because, as I said, the patient population tends to be more in that age group. CD38 does have a slightly different biology in monkeys, which, you know, if you go all the way back to the old Daratumumab studies required back then, actually, the conduct of chimpanzee studies. It's really difficult to get long-term exposure, safe long-term exposure for surrogate animal models with the CD38 antibody.
Thanks, T ahamtan. Yaron, we think there are better targets actually for INI. One of the targets we are likely going to pursue together with AbbVie is, of course, CD20 with EPKINLY. We really think that that has a molecule with great potential for INI in addition to B-cell cancer. Hopefully, we can progress that in the coming months, and you'll hear more about that. Let's move to the next question, operator.
This concludes the Q&A section of the call. I will turn the call back to you, Jan van de Winkel, for closing remarks.
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