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, welcome to today’s conference call. Following today’s presentation, we will have a Q&A session. And 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. So 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. And 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, epcoritamab, 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 Daratumumab and with a higher clinical benefit rate including minimal response and better, it appears that more patients receiving HexaBody-CD38 experienced some level of improvement compared to Daratumumab, and while more patients receiving IV HexaBody-CD38 reports at least 1 adverse events, most are low-grade or manageable with more serious adverse events remain generally manageable and standard supportive care. standard supportive measures. Overall, HexaBody-CD38 delivers deeper responses than Daratumumab in relapsed or refractory multiple myeloma, which maintained safety and tolerability.

However, despite the encouraging nature of this data, given the current market dynamic 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 latest focus on and the investments in our promising late-stage proprietary clinical pipeline, specifically epcoritamab, Rina-S and acasunlimab. Because these three programs are poised to drive very significant revenue growth for Genmab at the end of the decade. As you can see here, there are currently 7 Phase III trials between EPKINLY, Rina-S and acasunlimab.

As a reminder, 3 of the 5 ongoing Phase III Stage IV epcoritamab have been fully recruited [indiscernible] of schedule, and we anticipate three potentially significant pivotal readouts 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 or track record of acceleration and our experience in the Gino space with Tivdak. Based on the exceptionally strong execution of the team post acquisition, we remain [indiscernible] to bring Rina-S to patients by 2027 with its best-in-class profile expected to achieve peak sales exceeding $2 billion. Our 2 Phase IIIs, we plan to have underway by the year-end. We are well on track towards putting into place the building blocks to achieve these targets. There is also a meaningful opportunity for novel treatments like acasunlimab in [indiscernible] second line non-small cell lung cancer to provide not just improved response rate but durability of response.

And here, we anticipate the peak sales opportunity of $1 billion. Beyond these programs, we’ll 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. And 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 the full potential because of the team and the capabilities that we have put into place.

In the next — in the past few years, we are focused on scaling up the development so that we can expand from early page stage developments. We are now doing this with multiple ongoing and planned Phase III clinical trials, you saw already on the previous slides. And we are doing it quickly, as evidenced by both the extremely rapid development of EPKINLY, which advanced from first in-human clinical trial to approve medicine in 5 years. And our ability to progress Rina-S so significantly in less than 1 year. We not only brought forward the start of the first Phase III trial for Rina-S but we have now announced a second Phase III trial in an additional indication. We have also significantly built our technical locations and commercialization functions, enabling us to not just bring products to market but to ensure that right therapies get to the right patients as quickly as possible.

And thanks to our exceptionally strong performance in key markets like [indiscernible] in Japan, we are confident in our ability to [indiscernible] EPKINLY 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 [indiscernible] refractory follicular lymphoma. And with this approval EPKINLY is now the only bispecific antibody approved at a dual indication for the treatment of certain B-cell malignancies in the U.S., the European Union and in Japan.

Looking ahead, we also see opportunities to accelerate the potential of Tivdak in advanced cervical cancer to new markets for patients’ needs remain high. We expect approval in Japan early this year. Genmab will lead full commercialization responsibilities and in Europe later this year following a positive CAP 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 remains 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 priorital investments and expanding market opportunities. as we have the financial foundation, the talented team and the capability in place to continue to do so. We will continue to [indiscernible] accelerating the development of our high-impact late-stage programs EPKINLY Rina-S and acasunlimab, with investment into Phase III clinical trucks. 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 for us by the end of the decade.

We will continue to see 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 developments, and we will continue to be disciplined in our approach to these investments 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 Instructions] Our first question will come from the line of James Gordon with JPMorgan.

James Gordon, JPMorgan. The question with Slide 5, which helpfully lays out the key late stage pipeline news flow. It’s notable that there isn’t anything listed for this year. So is that definitely the case or say, 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?

And then the other part of the question would be, if there isn’t anything happening on the readout front. Now 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, A, get some more late-stage pipeline? Because now you [indiscernible] have 29-30 erosion to address or absolutely no change in [indiscernible] that there is no readouts in the next 12 months?

James, I think I can take both of the questions. So there is definitely potential earlier readouts for sure. We cannot say that for sure because they are value-driven. But there is absolutely a potential for earlier results 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 5. But there’s clearly a potential earlier readout in 2026 for sure.

Then as it relates to data, we will have multiple data readouts this year also for already, I think, next week for second line plus [indiscernible] to look at the Rina-S data actually in the trial you have already have seen data from last year at ESMO. There’s definitely an oral presentation on one of the [indiscernible]. There will be a data on [indiscernible] cancer in the first half of this year at a major cancer conference also for Rina-S. So there will be multiple data readouts.

And 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 time will be of potential deals. And I think we have shown you already last year with the very efficient, not only execution but also integration of Profound Bio. We’re really very well on track to actually execute one or more M&A deals. And that will be important for the — 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 end of the decade. But we are — I think all engines are running at full speed, James. So you don’t have to be worried there.

Our next question will come from the line of Jonathan Chang with Leerink Partners.

This is [ Jinder Lee ] on for Jonathan Chang. So 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 DARVALEX. Could you share your take on why this is the case? And can you discuss the potential implication of this data to the other body HexaBody programs such as GEN1055?

Thanks for the question. I will hand it over to Tahi who is our multiple myeloma expert. Maybe you can give us a bit of color there?

Yes, sure. Thank you for. I mean, as you see in a comparison — the comparing this intravenous to subcutaneous you see comparing a drug that has almost a doubling of the depth of response and there’s also a higher discontinuation rate partially related to the fact that, certainly, there’s significantly more experience in managing Daratumumab in the subcutaneous version that is on the HexaBody-CD38, to some degree, it was treated as a novel IND. And there’s also a difference in the safety profile, for example, the IRRS in Neutropenia.

Thanks, Tahi. Handing it back to the operator.

Our next question will come from the line of Xian Deng with UBS.

So 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 ORR seems to be broadly comparable. Do you think that might, by any signals I don’t know, maybe higher potency by any chance. So any follow-up HexaBody program needs to be [indiscernible] clean in terms of the targets or any insights that would be great. That’s the first question.

Second question is — just wondering, looking at your major Phase III trials, acasunlimab is kind of lung cancer, EPKINLY frontline 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?

Thanks, Xian, for the questions. And I will start with the first and then hand over to Tahi to also handle — the next part of the first question and then also the second question, the rank ordering. It will be quite interesting.

I can tell you that we feel that the data of this trial really clinically validates the HexaBody platform and we are pursuing a number of programs, both in the clinic as well as in the pre-clinical setting getting ready for the clinic, especially the enhancement of complement the [indiscernible] toxicity was really clearly shown clinically to [indiscernible] benefit here in this [indiscernible] trial. So we’re very excited about the potential of HexaBody about 10% of our product that’s in the whole pipeline are based on the HexaBody, Xian. So we — you will see more candidates coming to the clinic. And I think this bodes quite well actually for a number of those candidates. But then I’ll now hand it over to Tahi to give further color and also to the challenging rank ordering here.

On the first part, I think, yes, absolutely, the question is a great question and when Xian was always saying to the fact, which we have always flagged up that in part, this is also validation around the HexaBody mutation, which is a single point mutation, to enhance CDC. And so what you saw on this trial and when the data is in the public domain also relates to the [indiscernible], sure I appreciate this, that the efficacy signal [indiscernible] we are profound. It’s more of the doubling of the depth of response in the context of the imbalances and risk factors today, it will become even more important. So to us, this is a strong validation of the [ Hexa-atomization ] 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 observations. So — it validates the technology and it validates, for sure gives us a toolbox that we are exploring for other targets and other diseases.

On the rank order I actually don’t really think this is a helpful exercise. We don’t really tend to start studies that we don’t believe and are committed and of course, to some degree, probability of successes and mathematical exercise in the [indiscernible] study is positive or negative, and partially informed, of course, by what additional data you are generating or the robust of the understanding of the drug that you have, certainly, you have certainly better understanding of [indiscernible] than, for example, acasunlimab because there’s just more data there. But this, we cannot think this is a good exercise to rank all in this.

Thanks, Tahi. I think you have to do with the rank ordering by yourself. It sounds like, Xian. 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.

Can I ask, will you provide — can you provide any feedback on the reason for opting out? I mean, when you look at the data that we presented, certainly, the better response seem to be in favor in the GEN3014. With it more to do with overall response rate or was the toxicity profile that made them want to back out?

And then Tahi, it sounds like from your comments that maybe the IV formulation may have made it a little bit harder to balance the AEs — that made a little bit more pronounced. So does a subcutaneous version of the HexaBody parent makes sense? And then lastly, when do you plan on actually providing us with the data from this head-to-head study?

Thanks, Asthika. Let me start here and then ask to step in. What we actually heard from J&J is that basically the data not maintained — it’s a very high bar for both on clinical differentiation and also market potential. And that’s also to a certain degree, as we heard a consequence of the change in the treatment landscape for multiple myeloma. It’s actually more and more difficult to develop new medicines there because it’s getting more product in the market. But I will pause here and see whether Tahi can give further color and then also go into the IV versus subcu formulation, AEs potential for HexaBody. Tahi?

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 the profound change has happened in the last couple of years and how much standard of care has improved already. So leave it at that.

And then on the subcu versus IV, and I would probably answer the question historically, if you look at the subcu versus IV studies that were on with Daratumumab, you get a sense of 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 [indiscernible] the HexaBody story. And so there’s no need to worry about subcu versus IV, generally speaking, in future, there might be another story for another target.

Our next question will come from the line of Michael Schmidt with Guggenheim Securities.

This is Paul on for Michael Schmidt. 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 and focus — for instance, is it largely a solid tumor focus or [indiscernible] as well evaluating the potential to go into autoimmune?

Thanks, Paul. I think I can handle that question. So we are looking for Phase II or Phase III ready program for — as the targets for potential acquisition and oncology is a key focus right now. But of course, we also keep our wide open for I&I targets because that is our second core focus area, Paul.

But 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 Profound Bio acquisition where we heard actually that other companies were looking at the company, but we were simply too quick. And I think we were very quickly in doing the due diligence because of our experience and antibody medicine. So oncology is likely going to be the key target, and we are looking very broad, both solid tumors as well as hematological cancers. And yes, we have things on the radar screen. So things look quite good from that perspective, albeit that it’s difficult to give you a further estimate all of timing because they tend to have the own [indiscernible] some of these processes. Let’s move to the next question, operator?

Our next question will come from Yifeng Liu with HSBC.

Just one clarification question. Since that — I’m assuming that your agreement with J&J 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 being — could be applied potentially coming with your agreement with J&J?

I mean 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 developed out in other areas, that is per contract. And so it has a more limited span of use, I think, in the future for us as well as for other parties.

But the asset is back in our own hands, but we are definitely restricted that it is also only possible to in DARZALEX-resist patients and other indications except those where DARZALEX is on the market. So I think it is a much more limited scope.

Just to clarify, thanks first of all, even if we were to transfer it to list licensing out that sort of restriction still 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.

Our next question will come from the line of Vikram Purohit with Morgan Stanley. [Operator Instructions].

Yes. So first, on HexaBody-CD38, we were just curious when you all made the decision to kind of see internal development here, did that take into consideration the potential for the molecule in autoimmune conditions? And kind of when you think about the future for autoimmune development in your pipeline is HexaBody-CD38 something that could resurface?

And then secondly, we had a housekeeping question. Just wanted to make sure on time line that for acasunlimab, Phase II data update in second line and CLC that’s still on track for this year? And then 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?

Thanks, Vikram, for the questions. I’m going to move over to say a bit about the potential for autoimmune diseases. For the second one, I can answer that with a Yes. We are absolutely on track in the second half of the year to come with further data on acasunlimab, not only survival and duration of response, but also of Hexa patients of atleast an extra 20 patients of the every 6-week dosing, which is the dosing which is used in the Phase III trial, which is progressing well. So absolutely on track Vikram. And then Anthony Pagano can probably handle the expense on the — expense question, the operating expense question after Tahi gives his color on IMI — I mean, autoimmune diseases. Tahi?

Yes. Yes, thanks for the question. And the answer is very simple as said in the beginning, we will not continue development of HexaBody-CD38, not in oncology, not in immunology. Generally speaking, CD-38 is a challenging target in immunology because of the requirement for solid animal [indiscernible] that have some long-term survival.

Thanks, Tahi. That’s clear. Anthony Pagano, on the operating expenses as a consequence of this.

Yes, 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 number one, in terms of the expansion and acceleration of core clinical development with 5 Phase III trials ongoing and expansion of EPCORE into two key markets. So that’s number one.

Secondly, we really continue to expand put our foot on the gas pedal for Rina-S with the start of the Phase III and really the continuation of the first Phase III in [indiscernible] and then also the start of the first Phase III in second-line plus and endometrial cancer by the end of the year, then, 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 III. Moving forward, we’ll continue to really be focused and are taking 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’ve really paid off. But we’re now in a position where we expect 3 Phase III readouts for EPKINLY by the 2026 and we continue to expect the first approval for Rina-S in 2027 with more to come. And really, from a commercialization settings, we’re really pleased with the investments we’ve made and the successful launches of EPKINLY and Tivdak. To come back to your specific question, today’s news does not impact our 2025 financial guidance.

Our next question will come from Matthew Phipps with William Blair.

I realize you’re not going to pursue these, but just wondering if you have data from the AML or DLBC arms of the trial and how that might — if that looked any kind of differentiated versus which you had some — there like historically — I’m thinking about this program for the OX-40 target. I’m just wondering, I guess, you get clustering in the [indiscernible] receptor, but do you not get depletion of OX-40 positive T-cells from the enhanced complement pathway activation?

Thanks, Matt, for the questions. Tahi I’m handing both of them to you. You’ve been on AML and diffuse last B-cell lymphoma and then OX-40.

So there will be no data on the [indiscernible] in AML because we actually focus very early on the generation of the comparison data. So that will start to see the 38 HexaBody. And on OX-40, so there’s two different biologies, one CDC enhancement here. And the other one is the outside-inside signaling, without getting into the specifics of how these approaches are also different in how we construct these antibody concepts. We do not get depletion of OX-40 positive cells. And so we’ll be able to provide some data on the OX-40 program at some point in the future, but that’s a different question.

It’s basically clustering and agonistic effect or the OX-40 target and in a way that doesn’t deplete the Ox-40 positive sounds. 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.

I have a question on EPKINLY. So EPCORE DLBCL-1 has a primary survival and EPCORE DLBC-2 has primary of PFS. And it sounds like we’re going to get data from both next year. So my question, do you think we’re going to have PFS data from those studies? Or for DLBCL-1, do you think you’re going to hit survival already next year? And then for DLBCL-2, would you also have some survival data when you read out the PFS next year?

Thank you for the question, John. Tahi, can you address those?

Yes, you correctly noted that the primary endpoint for DLBCL-1 is OS. And so that was driving the time lines, and that’s what’s driving the readout. And for the [indiscernible] study in the [indiscernible] refactory setting this time in combination with [indiscernible], the primary endpoint is PFS, but OS so remains a very important secondary endpoint. And I think this is probably all we can say at this point.

Our next question will come from Suzanne van Voorthuizen with VLK.

I was wondering, looking ahead into the 2030s. Can you elaborate how confident you are that your current assets and pipeline as is can make up for the DARZALEX cliff and considering the different profit splits in there, which assets do you see, the most valuable for Genmab that time? And allow me also a follow-up for EPKINLY specifically for the frontline and relapsed/refractory studies in DLBCL. How foresee data from the Phase III trials to position EPKINLY in those treatment paradigms and to help further adoption there?

Thanks, Suzanne, for two very easy questions. So I will ask Anthony to give his perspective on the — on the contribution to our income for the different key products by the 2030s. And Tahi, maybe you can help with the second question on EPKINLY and the positioning in the landscape, Anthony, why don’t you start?

Yes. I mean as we think about our business overall, I really think it’s useful to start with some important fundamentals. And 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. And it’s really the strong foundation that has put some very meaningful growth opportunities in front of us. So lets unpack those growth opportunities that are in front of us today and how we can — 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 and today, we have 7 ongoing phase trials. And we’ve gone through these in lots of details in terms of the market opportunities, potential trial readouts, et cetera. Now we think about those — those 3 products with 7 ongoing Phase IIIs, 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 at EPKINLY, Rina-S or acasunlimab. So I think there’s a lot more potential or more potential for each of these three existing Phase III programs.

The second way, we’re going to create future growth opportunities is really the power of our research and discovery engine and our early-stage pipeline. Now this is really [indiscernible] sort of 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 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 and hopefully in the near future that can transition from early-stage development to mid- or late-stage development. So that’ll be the second area for future growth opportunities.

And then third is really looking at external opportunities. And here, very clearly, we’ve outlined within our capital allocation framework, what we’d be looking for in terms of external opportunities but it’s very clearly to sort of size it for you. It wouldn’t be a late-stage opportunity that is either Phase II or Phase III ready for or beyond. So 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. and importantly, not only the financial profile, but also what our late-stage pipeline will look like as we exit the decade. So very strong foundations and very exciting growth opportunities. And just to remind ourselves, in addition to the Genmab business, we currently have 6 royalty-bearing medicines.

Now one of those, of course, is DARZALEX. There are 5 additional products that have lots of growth opportunities there as well. And there are three additional potential royalty bearing programs that are either in — that are in Phase III or beyond. There’s a program with Novo, a program with Pfizer in a program with [indiscernible] the totality of our business is really strong, and the fundamentals are strong, and we have lots of growth opportunities moving forward.

Thanks, Anthony. Let’s move to Tahi for the for repositioning.

Sure. And let me take similar approach and take a step back a little bit on EPKINLY and the [indiscernible]. I think from the very beginning, we were very clear that in our mind, this is novel mechanism of action of Hexa towards [indiscernible] — it was going to be transformative for the space of B-cell malignancies and that at EPKINLY based on its documented efficacy signal, it’s safety as well as the subcutaneous administration, which is part of the safety, but it’s also in the convenience both for the patient as well as for the provider. What’s going to be the market leader is the market leader.

And if you just look at how this class in particular EPKINLY now is already kind of impacted the lives of patients in third line — three [indiscernible] of therapy such [indiscernible], I think it’s very clear that a significant amount of patients already are getting this approach. And so that’s the first part. The second part is — if you then look at the Phase II data that we had presented on the commission with [indiscernible] patients who had a [indiscernible] of IPI-3 to 5. So really those patients who actually have the highest chance of not getting cured with [indiscernible] because there is a roughly 50% to 60% probability [indiscernible] cured. The data was broadly speaking, without the president, 100% response rate in [indiscernible] purposes, 100% CR rate. There was one patient who didn’t have a CR basically [indiscernible]. So that gives us the confidence and the belief that once the data reads out in frontline, that’s going to fundamentally transform frontline[indiscernible] data set that is without the [indiscernible]. And we’ll very certain from our end with a significant positive impact for patients with the [indiscernible] in frontline.

Our next question will come from Alistair Campbell with RBC.

Yes. Just a very brief follow-up, actually, just thinking about the HexaBody platform. So not just not CD-38, but outside of CD-38. I mean given the data you’ve seen from this trial, which is sort of indicates very good target engagement, but a step-up in side effect as well. If you think about HexaBod as a platform outside of oncology in I — does this give you pause for thought? Or do you think it’s actually simply about choosing the right target at the right dose?

So the short answer is Alistair absolutely no pause of thought because we are actually working preclinically with HexaBody problems for I&I. And we think that this is actually an excellent technology platform. which is validated here quickly. And we don’t think that the safety aspects will be very much impacted by the HexaBody modification. So no, I think this trial and this data shows that there is a clear advantage in potentiating the killing activity of anti-HexaBody mutation.

But also we are testing agonist OX-40 concept, we already answered to a previous analyst that this doesn’t lead to depletion of OX-40 positive cells. So we think this is a very promising platform, Alistair. And then more to come in the coming years. We have a number of very exciting preclinical program which are slotted to move to the clinic we actually hope to break paradigms, basically moving into new areas where antibodies are not very successful in tumor therapy. But with this modification, I think, could be very successful. So more to come.

Our next question will come from the line of Qize Ding with Redburn Atlantic.

Okay. I only have one. So following today’s news, am I right to assume that your level of confidence in your HexaBody technology platform remains unchanged going forward, right? And so what have you learned from the HexaBody-CD38 for the future development of other HexaBody pipeline assets?

Thank you for the question. I don’t think that is actually unchanged, actually much higher because we think that this rate shows that the HexaBody platform is clinically validated to lead to a more effective therapeutic. But what it has learned is actually a number of things, but I will hand it over to Tahi who is overseeing a lot of the development of new concepts based on HexaBody, Tahi, you can speak a little bit about what it has learned us for future development of the HexaBody platform?

Yes. I will do that and gladly do so. Number one, just like remind ourselves of what the challenge and what the objective was. The objective was with a single point mutation to create an asset that with [indiscernible] and through the hexomization with enhanced CDC and as we talked about, what that would do is it will lower the threshold of CD-38 required on the cells to then be sensitive to CDC. And it would overcome to a degree, biologically existence mechanism that prevent this otherwise, which is the expression of complement inhibitory proteins CD-55, CD-59. And what the data clearly shows is that with the single point mutation, you get — and I mentioned the imbalance, and you will see the imbalance when the data is presented. [indiscernible], significantly meaningful enhancement of the depth of response, meaning we captured a large portion of tumor cells CD-38 because there is an inter-patient variability of CD38, next version on the myeloma cells.

And CD-38 to remind everybody is arguably one of the dirtiest targets out there. It’s expressed on a lot of cells, but there are [indiscernible] kind of like the [indiscernible], — it doesn’t touch all of these CD-38 positives. So there is a little bit of a high-end neutropenia rate that is arguably related to the mechanism, but also arguably related to the increased efficacy because the phenomenon of neutropenia and B-cell depletion, while in understood has been observed in every single B-cell-directed therapy. The more modifications to B-cell depletions the more enhanced in Neutropenia. And that’s, I think, 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 comments that this technology, where a single point mutation is able to enhance complement-mediated cell toxicity and is able to overcome to a degree the expression of complement inhibitory proteins. And this is very important as we think about other disease areas and other targets.

Our next question will come from the line of Rajan Sharma with Goldman Sachs.

Just noted in the kind of the comments that you’ve made on the high bar set by [indiscernible] 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’re going forward, whether that’s through the internal pipeline or external? If it’s not — that the case. What do you need to see in early stage trials to give you confidence that there is a benefit beyond [indiscernible] and other current therapy? And then 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 atonal PD-L1 activity?

Thanks, Rajan, for the questions. I will hand the first one over to Tahi to ask a bit more about multiple myeloma as a target for new approaches. And then you can take the acasunlimab questions and the describe the covenants we have and the conditional activation [indiscernible] for 4-1BB to be definitely differentiated versus the blockade of the PD-L1 access [indiscernible].

Let us start with Tahi and the multiple myeloma changing landscape again.

I think the answer for us asrelated to multiple myeloma is very clear. Multiple myeloma is not really an area that we are focusing on internally cost 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 look at the quadruple therapy in multiple myeloma and frontline. It is very hard if there is such a thing as relapse refractory multiple myeloma as some foreseeable future. So for us, this is not an area that we are focusing on.

Thanks. Let’s move to Judith and acasunlimab and the confidence level that the 4-1BB agonist arm really matters.

For the question. Just I would like to remind you that the population that was enrolled in the study was patients that progress on checkpoint inhibition, PD-1 or PD-L1 and most of them progress on pembro. On the patient population, pembro doesn’t have activity. So it’s not the inhibition of PD-1, but the agonist, the combination of total abrogation of the PD-1, PD-L1 access through the PD-L1 arm of the do-able the offer acasunlimab plus pembro and the agonistic effect of 4-1BB. And in the literature — and as we saw in the post that presented in ASCO we saw not just stable disease but some peers like 17% partial response. This is inhertu of patients with a checkpoint innovation after checkpoint inhibition. So definitely is the combination of the agonist 4-1BB plus checkpoint inhibition — need both.

Thanks, Judith. And Rajan we will get more data in the second half of the year, and that will make it even clearer. Now let us move to the next slide, operator.

Our last question will come from Yaron Werber with TD Cowen.

So Tahi, just for you, I wanted to follow up on your comment earlier about CD38 is a target for INI. 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 INI studies. Can you just maybe highlight that again and maybe share a little more information?

Sure. Very simplistically, most patients with immunological diseases are [indiscernible] most case patients with cancer patients that includes particular women of [indiscernible] bearing age. What that generally does is in oncology, we sometimes don’t do long-term safety studies. Sometimes we do, sometimes we don’t. If we don’t and the inclusion, exclusion criteria and the label has something like women of [indiscernible] age should not take the respective medicine in the knowledge that, of course, is a little bit challenging because, as I said, the patient population tends to be more in that age group. CD-38 does have a slightly different biology in [indiscernible] which if you go all the way back to the old Daratumumab studies — require back then actually the conduct of [indiscernible] studies. And so it’s really difficult to get long-term exposure. Save long term exposure for surrogate animal models with the CD-38 antibody.

Thanks, Tahi. So Yaron, we think there are better targets actually for INI and one of the targets we are likely going to pursue together with EPKINLY is ofcourse CD-20 with the EPKINLY, we really think that, that has a molecule with great potential for INI in addition to B-cell cancer. So Hopefully, we can progress that in the coming months, and you’ll hear more about that. Let’s move to the next question, operator.

Well, this concludes the Q&A section of the call. I will turn the call back to you, Jan van de Winkel for closing remarks.

All right. Thank you for calling in today. If you have additional questions, please reach out to our Investor Relations team. We hope that you’re all safe and keep optimistic, and we very much look forward to speaking with you again soon.