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I woipt uld now like to hand over the call to your first speaker for today, Jan G.J. de Winkel. Please go ahead.

Hello, and welcome to a brief review of the energizing data that has recently been presented for Rina-S, including today at the 2025 ASCO Annual Meeting.

Next slide. Before we begin, as a reminder, this presentation may contain forward-looking statements and may contain certain risks and uncertainties. Let’s move to the next slide.

Now to our agenda for today’s call. We are encouraged by the recent compelling data that we have seen for Rina-S, both the updated data in PROC that was presented at SGO and the highly anticipated data in endometrial cancer that was presented just today at ASCO in Chicago. When viewed together, Rina-S looks more and more like a potentially best-in-class treatment for gynecologic cancers but it also holds promise more broadly in other folate receptor alpha expressing solid tumors. We have with us today our Chief Medical Officer, Tahi Ahmadi who will both review this data and provide you with an update to our robust development plan for Rina-S.

I will conclude today’s call with a reminder of the strength of our overall late-stage development program, and we will then open the call for what I’m sure will be an engaging Q&A. I would like to get right into the data. So let’s move to the next slide.

Thank you, Jan, and thank you, everyone, to join us for today’s call. Next slide, please. The data we will review today, you will see why that Rina-S is differentiated from the first generation of folate receptor alpha approaches, both in efficacy and safety. This differentiation is a direct result of the proprietary hydrophilic linker technology that was used to create Rina-S. Rina-S consists of a human monoclonal antibody, S131 that selectively binds to receptor alpha, a novel cleavable hydrophilic linker and a second-generation topoisomerase 1 inhibitor payload exatecan. The Sesutecan linker designed to mask the hydrophobicity of conjugated exatecan on the ADC, enabling a high drug-to-antibody ratio, DAR of 8 and the efficient delivery of the exatecan payload to tumors. Now let’s briefly review the meaningful follow-up data from the expansion cohort with PROC that we presented at SGO on the next slide.

As a reminder, these were women that were very heavily pretreated with ovarian cancer regardless of folate receptor alpha expression results also showed that Rina-S dosed at 120 milligram per meter square every 3 weeks led to a confirmed objective response rate of 55.6%. This includes 4 women with complete responses. And this encouraging antitumor activity was durable. With a median on-study follow-up of 48 weeks, the median duration of response has not been reached as only 1 of the 10 patients so far experienced disease progression.

Rina-S was well tolerated. And once again, so far, no signs of ocular toxicity or interstitial lung disease have been observed. Altogether, this data reinforces the potential of Rina-S to become a best-in-class treatment for ovarian cancer, benefiting a broader patient population than currently approved therapies with a differentiated efficacy signal, it cross the entire patient population that is with a no need for selection based on folate receptor alpha expression, a better and differentiated safety profile that is without ocular toxicity or ILD and an unprecedented durability. I would now like to outline the deep and durable responses and manageable safety that we saw in endometrial cancers equally across all levels of folate receptor alpha expression.

Next slide, please. This is my pleasure to present the first results for a single-agent Rina-S in patients with advanced endometrial cancer from the dose expansion cohort B2, which is part of the Phase I/II RAINFOL-01study.

Next slide. There continues to be a significant unmet need for the treatment of patients with endometrial cancer. And folate receptor alpha is indeed a validated third party target that is overexpressed in multiple solid tumors, including endometrial cancer.

Next slide. We conducted a study evaluating single-agent Rina-S administered once every 3 weeks for the treatment of women or patients with advanced solid tumors regardless of folate receptor alpha expression. And the dose — A dose escalation, just to recap presented by Dr. Lee at ESMO in 2024. Rina-S 100 milligram and 120 milligram per meter square Q3 weeks showed encouraging single-agent antitumor activity in heavily mutated patients with endometrial cancer and was selected for further evaluation in the so-called Cohort B2. Cohort B2 of the dose expansion involved 64 patients with heavily pretreated endometrial cancer who were randomized 1:1 to receive either Rina-S at 100 milligram per meter square or 120 milligram per meter square.

Next slide. As I said, a total of 64 women were randomized with metastatic or unresectable AEC and all had received prior platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor, thus representing the current standard of care. Most patients had ECOG Performance Status 1, approximately half were aged over 70, and patients had received a median 3 prior lines of therapy. Patients primarily had endometrial carcinoma followed by serous carcinoma. In the efficacy evaluable patients, the confirmed ORR was 50%, including 2 complete responses with Rina-S at a dose level of 100 milligram per meter square. This includes 22 patients and 47.1% with a 120-milligram per meter square dosing for the 34 patients. Disease control was 100% and 85%, respectively, with 100 milligram and 120 milligram, and antitumor activity was observed regardless of exploratory folate receptor alpha expression.

Next slide. As I mentioned, the treatment with Rina-S with 100 milligram per meter square led to an encouraging confirmed and objective response rate of 50%, including 2 complete responses, while treatment with Rina-S 120 milligram led to an objective response rate of 47.1%. In addition to the superior response rate, treatment with Rina-S at 100 milligram led to deeper, more meaningful tumor size reductions as seen on the waterfall plots on the left. For both dose cohorts at the time of data cut, the median duration of response was not yet reached. With a median follow-up of 7.7 months, 8 of the 11 confirmed responses with 100-milligram per meter square are still ongoing. And shown in the small plot responses with Rina-S were observed early with a median time to response of 6 weeks in both cohorts.

Next slide. The safety profile was similar between the 2 dose levels. The most common treatment emergent were cytopenias in grade 1 and 2 gastrointestinal events. Grade 3 or 4 cytopenia included neutropenia, anemia and thrombocytopenia. Treatment-emergent AEs needed the dose reduction or treatment discontinuation were similarly low and prophylactic G-CSF according to ASCO guidelines was used in 77% and 55% of the patients treated at both dose levels, respectively. There were 2 fatal TAEs in the 120-milligram cohort and none in the 100-milligram meter per square cohort. There were no signals of ocular toxicities, interstitial lung disease or neuropathy observed in this reported patient cohort.

Next slide. In conclusion, single-agent Rina-S given once every 3 weeks showed encouraging antitumor activity in heavily pretreated patients with endometrial cancer. In the dose expansion, treatment with Rina-S at 100 milligram per meter square resulted in 2 confirmed responses and an objective response rate of 50% and a median follow-up of 7.7 months for the 100 milligram per meter square cohort, 73% of the responses were ongoing, suggesting durable responses. Rina-S had a manageable safety profile consistent with previous reports, and there were no signals of ocular toxicity, interstitial lung disease or neuropathy observed in these reported patient cohorts.

Based on the totality of evidence, Rina-S 100 milligram per meter square every 3 weeks was selected for further evaluation, both as monotherapy in patients with advanced recurrent or metastatic EC after 1 to 3 prior lines of therapy, including platinum chemotherapy and PD-1 or PD-L1 inhibitor in the Part F of the RAINFOL-01 study, which is a single-arm Phase II study intended for registration, which is currently ongoing and enrolling patients.

Next slide. Now I would like to walk you through the near-term development plans for Rina-S.

Next slide, please. While the primary opportunity for Rina-S is ovarian cancer and endometrial, the data we have seen both in ovarian and especially endometrial cancer, which is known to have a lower expression of folate receptor alpha support and hypothesis that Rina-S has a potential to work irrespective of the level of folate receptor alpha expression. As folate receptor alpha is known to be expressed across a broad range of solid tumors, this presents a broad potential opportunity across a diverse area of tumor types, opening multiple avenues for therapeutic expansion.

Our ambition is to expand both within the gynecological cancers and beyond, targeting additional solid tumors such as but not restricted to non-small cell lung cancer.Now let’s take a look at our existing and near-term plans for Rina-S.

Next slide, please. First, we are strategically broadening our scope in ovarian cancer. In addition to the already actively enrolling pivotal Phase III trial in PROC, we are now planning a Phase III trial in second-line platinum-sensitive ovarian cancer maintenance to start dosing before the end of this year. Complementing this is our ongoing Phase I/II trial, which has an explorative cohort with a combination of carboplatin as well as bevacizumab. This includes a pivotal second-line plus PROC cohort as well, which is now in Phase II. And this is based on the Phase II data presented at ASCO earlier this year.

So in ovarian, we have a Phase II study intended for registration accelerated approval, one Phase III ongoing in PROC and now a Phase III in [ESOP] maintenance that is to be dosed patients before the end of this year.

Next slide, please. As we have noted before, based on the data that we now presented to you at ASCO, we had already articulated near-term plans to expand our focus in the endometrial with a Phase III trial that is also planned to start before the end of this year. Equally, there is an ongoing expansion of a Phase II intended for registration similar to our PROC strategy, which is equally already enrolling patients. Lastly, there is an ongoing Phase I trial for the combination of Rina-S with immune checkpoint inhibitors in endometrial cancer.

Next slide. Looking beyond gynecological malignancies, our next significant step in our plans for Rina-S is the start of a Phase II trial in non-small cell lung cancer equally before the end of the year with data to be expected to read out in 2026. We have future plans that we will announce in the next few months to investigate the potential of Rina-S in other indications, which demonstrates our confidence in Rina-S as a potential therapeutic across folate receptor alpha expression and our commitment to diversifying our therapeutic impact across multiple challenging tumor types. With this, I would like to hand back to Jan. Thank you.

Thank you, Tahi. We hope that you find the data we reviewed today and our development plans for Rina-S as energizing as we do. As you can see, Rina-S is a key part of our overall very strong late-stage pipeline, and we are excited to expand its potential with the additional clinical trials that Tahi highlighted. We remain on track to bring Rina-S to ovarian cancer patients in 2027. And given its best-in-class profile, we expect to achieve peak sales exceeding $2 billion. Beyond Rina-S, epcoritamab and acasunlimab are also poised to drive significant revenue growth for Genmab by the end of the decade. EPKINLY with its rapid clinical development is positioned to become the core therapy in B-cell lymphomas with anticipated peak sales exceeding $3 billion.

And 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 both improved response rate and durability of response. In addition, we are also moving into advanced melanoma with a Phase II trial anticipated to start in the coming months. And as you know, beyond these programs, we are continuing to actively look for opportunities to further grow our pipeline, both organically and inorganically, positioning us for long-term growth and value creation.

In conclusion, in our over 25-year history, we have demonstrated a proven track record of creating and developing innovative antibody medicines, and we firmly believe this continues with Rina-S. From the data we have seen and presented to you today, we believe it has the potential to be a best-in-class therapy for patients regardless of folate receptor alpha expression level. And we are prepared to maximize its potential with a robust development plan. We very much look forward to sharing our progress with you as Rina-S moves rapidly forward into these new trials.

Next slide. We would now be pleased to take any questions you have. So operator, please open the call for questions.

[Operator Instructions] Our first question will come from Yiwen Zhang with Leerink Partners.

Congrats on the data. First question, do these data change your level of confidence in the ability of Rina-S to address lower expressing FR alpha patients? Any color on the biomarker expression levels of the patients in the study specifically or endometrial cancer broadly would be very helpful. Second question, how concerning or not is the myelosuppression observed with Rina-S? And then third question, if I may, how do you view the competitive landscape for Rina-S in endometrial, specifically to ADCs, which seem to be ahead? How could Part F of RAINFOL-01 help expedite Rina-S time lines?

Thanks, Jonathan, for the questions. I’m going to hand them all 3 over to Tahi, who is at ASCO, and I think can give you perfect answers for all 3. Tahi?.

Yes. Thank you for the question. Let’s start with the first one. I think we said it before many times, and it’s true in this cohort as well. If you just take the PROC data set and the endometrial data set that is in the public domain, we are now having roughly 100 patients worth of data, probably a little bit more, where we can confidently say that we have responses in patients who have high expression in the case of PROC are exposed to MIRV. We have expression in patients who have moderate expression of folate receptor or low or even those who by the assay are determined to be negative. This is why we are confidently and repeatedly said Rina-S in our hands is a drug that has across the entire spectrum, unselected efficacy in each one of these subgroups, if you will, that is meaningful and superior to anything that is out there, which is at that point, it becomes a little bit an all-comers drug and the fully receptor alpha expression is more relevant for us in the context of stratification than it is in selection. So that’s the first part. The second question was on endometrial and what?

I think it’s myelosuppression.

Myelosuppression, sorry. So myelosuppression predominantly is neutropenia, very well manageable if you follow the ASCO guidelines on secondary prophylaxis. In the endometrial data set, I didn’t really speak too much in the presentation, but if you actually look at the slide, you can see that the BMI of these women is significantly different. Actually, on the PopPK level, the exatecan levels for 100-milligram endometrial overlay with 120 in ovarian. So if you use 100 milligram, it’s essentially the same dose exposure as it is 120 in PROC. That is a dose level for which we feel very comfortable that it’s manageable and tolerable and that with appropriate secondary prophylaxis with G-CSF as evidenced by the fact that we have a very low discontinuation rate as quite tolerable.

And this low discontinuation rate, even in endometrial 100 milligram was 4%, then translate into a very long duration of response. And that brings me to the last part, which is your question on the TROP-2. I think it’s probably fair to say now that the data is a public domain that if you look at the 60-plus women with endometrial cancer, this is a best-in-class signal with a response rate of 50% confirmed unprecedented with the durability that also is beyond what is in the public domain. We are accelerating. As I said, we already have an ongoing Phase II that is intended for registration and accelerated approval. And we are already announced and we’re going to very soon start dosing patients on the Phase III. And we’re also starting to move into front line. I mentioned that we have a cohort and so there’s more to come. We feel very comfortable where we are positioned, and we believe that when everything is said and done, Rina-S is going to be the top ADC in the gyn-onc space, both in ovarian across multiple lines as well in endometrial.

Let’s move on to the next analyst. Operator?

Our next question will come from the line of Yaron Werber with TD Cowen.

Congrats on a really nice data. So maybe the first one, Tahi, for endometrial in second line, what would be the Phase II trial design? Should we assume sort of head-to-head against chemo — and can you get approval with a response rate in PFS? Or is it a PFS and sort of you really need a secondary trend at least on survival? And then secondly, for the maintenance, again, as you think about the maintenance study, and I’m kind of getting ahead of things in the platinum sensitive, this is going to be, I assume, all comers regardless of homologous recombination. So what would be the control in that setting?

Yes. Thank you for the question. So the first part is on endometrial, just to clarify, there are 2 studies. There’s a Phase II study, classical accelerated approval strategy in the U.S. where the key endpoints are response and durability of response. And then there is a Phase III where we randomized against investigator choice chemotherapy. I think at this point, there’s also maybe an opportunity to reemphasize, which I should probably have emphasized at the last question that this is the first data set actually generated in patients who had exhausted both checkpoints and chemotherapy, basically reflected of the current standard of care, which has been changed with the checkpoints.

So that’s the endometrial study, and that is a PFS, OS endpoint. So we have this dual strategy, the same that we have in PROC, if you will. On the maintenance study, it’s a Phase III that is if you end up choosing Bev maintenance, then it is Bev versus Bev plus Rina-S. And if you are not having any maintenance because some women don’t get any Bev maintenance in the second line because they have Bev in frontline, then it’s nothing against Rina-S if that design makes sense.

Our next question will come from Vikram Purohit with Morgan Stanley.

We’ll actually move on to the next question. We lost Vikram. So our next question will come from Xian Deng with UBS.

Just actually 2, please. The first one on Rina-S, the endometrial data you just presented. So just wondering, it seems that between the 100 milligram and 120 milligram, there doesn’t seem to be a bit of a difference. I think you alluded to something with BMI, but I didn’t quite catch that. So just wondering, because if I remember correctly, in ovarian cancer, there’s actually quite a bit of difference between the 2 doses. But here, you don’t seem to have a difference and you actually selected the 100 milligram for Phase III. So just wondering any thoughts on that, please? That’s the first one.

And the second one, just wondering for the Phase II non-small cell lung cancer. So just wondering, is that — is that still planned for EGFR mutant only? Or is that for all comers?

Thanks, Deng for the question. Tahi, can you handle both of them?

Of course, sure. Thank you for the question. So let’s get to the first part. So yes, so just to clarify and be precise about this, women with endometrial cancer tend to have a larger body mass index, BMI, than women with ovarian. And that’s relevant, of course, because we dose by surface area. So you end up giving more drug and that at some point ends up getting into levels of [indiscernible] that probably are not giving us a favorable safety profile where the combination of efficacy and safety makes sense. So that’s why for endometrial, we chose 100 milligram.

Now you’re absolutely correct. In ovarian, there was a steep dose response curve between 100 and 120. And in endometrial, that is not the case. The both of them actually have a very high efficacy. And then what does tell us is that endometrial probably the sensitivity of the tumor to this ADC is actually higher to a degree, at least that you have already at 100 milligram. But all things being equal, we’re very comfortable with our dose. This has already been discussed with regulators across the globe and has been endorsed and the efficacy signal speaks for itself. And as I said, we already are enrolling women in registration and intended studies on that dose. On the non-small cell lung cancer question, that study will have multiple cohorts actually in EGFR mutated, both as monotherapy as well as combination. But in that study, we will also explore broadly adenocarcinoma outside of the EGFR mutated space.

Thanks, Tahi. Thanks, Deng, for the questions. Let’s move on to the next analyst.

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

This is Paul on for Michael. So just on endometrial, following up on the prior questions on the control for the pivotal studies. So how should we think about sort of what the right bar is given the range of standard of care options and also factoring the sort of subgroups like MMR and impact there, is there a benchmark that you’d like to clear for both ORR and PFS for this registration-enabling strategy you’re having?

Thanks for the question. I think this is a question that we have asked — been asked a couple of times. There’s actually really no good data to point in this novel population. But if you look at historical data, prior to that change in standard of care, chemotherapy roughly at best case has a response of 10 to 15. So now that actually women are already getting checkpoint inhibition in frontline, it will be 10 or 15 minus X, whatever X may be. So that’s basically the benchmark that we modeled the study towards. As it relates to MMR, if you look at the demographics, the vast majority of women were actually PMMR on the study.

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

Congrats on the endometrial update here. Why was there less prophylactic G-CSF use at the 120 mg cohort first 100 mg cohort? And is that confounding of the results? And why not just try to evaluate maybe some body mass index adjustments to your dose across maybe all studies if you’re seeing this issue with larger — with higher BMI.

I think this is a good question. I think if you actually look, there is a disparity in the numbers. There was first a 120-milligram cohort as the expansion of the trial before we went in the randomization. And what happens is this is an expansion cohort of Phase I that was a little bit of a learning curve in educating, frankly, the community on following ASCO guidelines on the use of G-CSF and encouraging this also in the protocol and formalizing a little bit more. This is where the disparity comes from. On the idea of capping it, well, it is actually capped moving forward in the sense that there is a cap for the body surface area, at which point you don’t dose beyond that, which is quite common usually for ADCs.

As the question before alluded to, just look at — if you look at the data, what you see is that you essentially already have a plateau. So it doesn’t really make sense to push the dose. I think it’s equally important to think about long-term durability. And then I kind of alluded to the PopPK data, which actually gave us the evidence that the 120-milligram dose in endometrial might be a little bit higher than what was modeled for PROC. In fact, 100 milligram per meter square [exatecan], I’m going to repeat this again, overlay us more or less almost to a point where you cannot differentiate the curves with 120 milligram in PROC and so all this together, it’s the dose that we feel very comfortable with that gives us a — again, I can only emphasize this unprecedented response rate with a similar to what we’ve seen with PROC, very long durability. And it’s important to understand this with ADCs tolerability, drives duration of treatment, drives duration of response.

[Operator Instructions] Our next question will come from Qize Ding with Redburn Atlantic.

Two, if I may. So these 2 questions are related to the non-small cell lung cancer program. The first one is about what are the key data you have seen so far in the non-small cell lung cancer program that give you the confidence to move forward to the Phase II stage?

And then my second question is, any thoughts on the patient selection such as the folate receptor alpha expression level you’re going to select for the non-small cell lung cancer patient population? And probably just one last one. Just to clarify, you mentioned about you’re going to test the Rina-S in combination. Can you elaborate a little bit more? Is it in combination with bispecific antibody? Or is it in combination with checkpoint either?

Thanks for the question, Tahi, Can you handle all 3, starting with the lung cancer one.

Yes. I can start at the beginning, but then I would ask for clarification on the last question. This is for the non-small cell cancer study, you were asking about combination with checkpoint or bispecifics. I want to be clear and what indication the question was focusing on.

The key question — I mean, all 3 questions are related to the non-small cell lung cancer.

Okay. Okay. Got it. Okay. So let’s start with — I think this is already for a while in the public domain that adenocarcinoma has actually folate receptor alpha expression. And then EGFR mutated non-small cell lung cancer seem to have an even higher folate receptor alpha expression. Now it’s not to the degree that it is as high as the highest level of folate receptor alpha expression that have been observed in PROC. But the entire scientific argument that we’ve made for a while was that once we get confidence on the fact that Rina-S actually has efficacy in lower levels of folate receptor alpha expression, then it really becomes a question whether the tumor is sensitive to topo as a mechanism.

Well, I think there’s already evidence in the public domain that EGFR-mutated lung cancers are sensitive to topo. Now we do also have a cohort already enrolling patients — cohort enrolling patients as an expansion cohort of the Phase I. And so we are now focusing to have a more dedicated lung cancer study with lung cancer experts so that we have the optionality to move this forward as we have done in other indications if the data so supports. The combination that I spoke about is a combination with standard of care in the indications and not any novel-novel therapies.

Thanks, Tahi. Let’s move on to the next question.

There are no further questions. This concludes the Q&A section. I’d now like to turn the call over to Jan G.J. de Winkel for closing remarks.

So thank you all for joining us today. If you have any additional questions, please reach out to our Investor Relations team. We very much look forward to speaking with all of you again soon.

This concludes today’s call. Thank you for joining us.

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