Hello, and welcome to Genmab's 2025 Post-ASCO Virtual R&D 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 beliefs, 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 over the call to your first speaker for today, Jan van de Winkel.
Please go ahead.
Hello and welcome to a brief review of the energizing data that has recently been presented for Rinatabart Sesutecan, 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 Rinatabart Sesutecan, 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, Rinatabart Sesutecan looks more and more like a potentially best-in-class treatment for gynecologic cancers, but it also holds promise more broadly in folate receptor alpha expressing solid tumors.
We have with us today our Chief Medical Officer, Tahamtan Ahmadi, who will both review this data and provide you with an update to our robust development plan for Rinatabart Sesutecan. 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, and Tahi, the floor is yours.
Thank you, Jan, and thank you, everyone, to join us for today's call. Next slide, please. In the data we will review today, you will see why that Rinatabart Sesutecan 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 Rinatabart Sesutecan. Rinatabart Sesutecan consists of a human monoclonal antibody, F131, that selectively binds to folate receptor alpha, a novel cleavable hydrophilic linker, and a second-generation topoisomerase I inhibitor payload, exatecan. The hydrophilic linker is designed to mask the hydrophobicity of the conjugated exatecan on the ADC, enabling a high drug-to-antibody ratio, DAR, of eight, and the efficient delivery of the exatecan payloads 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 showed that Rinatabart Sesutecan dosed at 120 mg/m² every three weeks led to a confirmed objective response rate of 55.6%. This includes four women with complete responses. This encouraging anti-tumor activity was durable. With a median on-study follow-up of 48 weeks, the median duration of response has not been reached, as only one of the 10 patients so far experienced disease progression. Rinatabart Sesutecan 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 Rinatabart Sesutecan 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 covers the entire patient population, that is, with 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. It is here my pleasure to present the first results for single-agent Rinatabart Sesutecan in patients with advanced endometrial cancer from the dose expansion cohort B2, which is part of the phase I/II RAINFOL-01 study. 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 therapeutic target that is overexpressed in multiple solid tumors, including endometrial cancer. Next slide.
We conducted a study evaluating single-agent Rinatabart Sesutecan administered once every three weeks for the treatment of women or patients with advanced solid tumors, regardless of folate receptor alpha expression. In the dose escalation, just to recap, presented by Dr. Lee at ASCO in 2024, Rinatabart Sesutecan 100 mg/m² and 120 mg/m² Q3 weeks showed encouraging single-agent anti-tumor activity in heavily treated 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 one-to-one to receive either Rinatabart Sesutecan at 100 mg/m² or 120 mg/m² . Next slide.
As I said, a total of 64 women were randomized with metastatic or unresectable EC, and all had received 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 three lines of therapy. Patients primarily had endometrial carcinoma followed by serous carcinoma. In efficacy evaluable patients, the confirmed ORR was 50%, including two complete responses with Rinatabart Sesutecan at a dose level of 100 mg per m². This includes 22 patients and 47.1% with a 120 mg per m² dosing for the 34 patients. Disease control was 100% and 85% respectively with 100 mg and 120 mg, and anti-tumor activity was observed regardless of exploratory folate receptor alpha expression. Next slide.
As I mentioned, the treatment with Rinatabart Sesutecan at 100 mg/m² led to an encouraging confirmed and objective response rate of 50%, including two complete responses, while treatment with Rinatabart Sesutecan 120 mg led to an objective response rate of 47.1%. In addition to the superior response rate, treatment with Rinatabart Sesutecan at 100 mg led to deeper, more meaningful tumor size reductions as seen on the waterfall plots on the left. For both those 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, eight of the 11 confirmed responses with 100 mg/m² are still ongoing. Shown in the small plot, responses with Rinatabart Sesutecan were observed early, with a median time to response of six weeks in both cohorts. Next slide. The safety profile was similar between the two dose levels.
The most common treatment-emergent AE were cytopenias and grade one and two gastrointestinal events. Grade three or four cytopenias included neutropenia, anemia, and thrombocytopenia. Treatment-emergent AEs leading to dose reduction or treatment discontinuation were similarly low, and prophylactic G-CSF, according to ASCO guidance, was used in 77% and 55% of the patients treated at both dose levels, respectively. There were two fatal TEAEs in the 120 mg cohort and none in the 100 mg/m² 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 Rinatabart Sesutecan given once every three weeks showed encouraging anti-tumor activity in heavily pretreated patients with endometrial cancer. In a dose expansion, treatment with Rinatabart Sesutecan at 100 mg/m² resulted in two confirmed responses and an objective response rate of 50%.
At a median follow-up of 7.7 months for the 100 mg/m² 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 mg/m² every three weeks was selected for further evaluation, both as monotherapy in patients with advanced recurrent or metastatic EC after one to three pipelines 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 in 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 Rinatabart Sesutecan is ovarian cancer and endometrial, the data we've seen both in ovarian and especially endometrial cancer, which is known to have a lower expression of folate receptor alpha, support the hypothesis that Rinatabart Sesutecan 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 gynecologic 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 Rinatabart Sesutecan. 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 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 I. This is based on the phase II data I presented at SGO earlier this year. 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 PSOC maintenance that is to be dosed to 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 into 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 Rinatabart Sesutecan with immune checkpoint inhibitors in endometrial cancer. Next slide. Looking beyond gynecologic malignancies, our next significant step in our plans for Rinatabart Sesutecan 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 Rinatabart Sesutecan and other indications, which demonstrates our confidence in Rinatabart Sesutecan 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 Rinatabart Sesutecan as energizing as we do. As you can see, Rinatabart Sesutecan 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 Rinatabart Sesutecan to ovarian cancer patients in 2027. Given its best-in-class profile, we expect to achieve peak sales exceeding $2 billion.
Beyond Rinatabart Sesutecan, 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. 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. 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.
We firmly believe this continues with Rinatabart Sesutecan. 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. We are prepared to maximize its potential with a robust development plan. We very much look forward to sharing our progress with you as Rinatabart Sesutecan 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.
For the Q&A session, we'll be utilizing the raise hand feature. If you'd like to ask a question, click on the raise hand button at the bottom of your screen. Once prompted, please unmute yourself and begin with your question. We'll now pause for a moment to assemble the queue.
Okay, our first question will come from Jonathan Chang with Leerink Partners. Your line is now open. Please unmute and ask your question.
Hi guys, congrats on the data, and thanks for taking my questions. First question, do these data change your level of confidence in the ability of Rinatabart Sesutecan 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 Rinatabart Sesutecan? And then third question, if I may, how do you view the competitive landscape for Rinatabart Sesutecan in endometrial, specifically the TROP2 ADCs, which seem to be ahead? How could part F of RAINFOL-01 help expedite Rinatabart Sesutecan timelines? Thank you.
Thanks, Jonathan, for the questions.
I'm going to hand them all three over to Tahi, who is at ASCO, and I think can give you perfect answers for all three. Tahi.
Thank you for the question. Let's start with the first one. I think we've said it before many times, and it's true in this cohort as well. If you just take the PROC dataset and the endometrial dataset 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 who, in the case of PROC, are exposed to MIRV. We have expression responses 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 have 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 folate receptor alpha expression is more relevant for us in the context of stratification than it is in selection. That is the first part. The second question was on endometrial and say what?
I think it is myelosuppression.
Sorry. Oh, myelosuppression, sorry. Myelosuppression. Myelosuppression predominantly is neutropenia, very well manageable if you follow the ASCO guidelines on secondary prophylaxis.
In the endometrial dataset, I did not 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 a PROC PK level, the exatecan-free exatecan level is for 100 mg endometrial overlayer with 120 mg in ovarian. If you use 100 mg, it is essentially the same dose exposure as it is for 120 mg in PROC. That is a dose level for which we feel very comfortable that it is manageable and tolerable, and that with appropriate secondary prophylaxis, which is G-CSF, as evidenced by the fact that we have a very low discontinuation rate, is quite tolerable. This low discontinuation rate, even in endometrial for 100 mg, was 4%, then translates into a very long duration of response.
That brings me to the last part, which is your question on the TROP2. I think it's probably fair to say now that the data is in the public domain that if you look at these 60+ women with endometrial cancer, this is a best-in-class signal with a response rate of 50% confirmed, unprecedented, with a 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. We are already announcing we're going to very soon start dosing patients on the phase III. We are also starting to move into frontline. 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, Rinatabart Sesutecan is going to be the ADC, topo ADC in the gynecological space, both in ovarian across multiple lines as well in endometrial.
Thanks, Tahi.
Thanks for taking the questions.
Thanks, Jonathan, for the questions. Let's move on to the next analyst operator.
Our next question will come from the line of Yaron Werber with TD Cowen. Your line is now open. Please unmute and ask your question.
Great. Thanks so much for asking my question and congrats on really nice data. Maybe the first one, Tahi, for endometrial in second line, what would be the phase III trial design? Should we assume sort of head-to-head against chemo? Can you get approval with a response rate and PFS?
Is it a PFS and you really need a secondary trinity on survival? Secondly, for the maintenance, as you think about the maintenance study, and I'm kind of getting ahead of things a little bit in the platinum-sensitive, this is going to be, I assume, all-comers regardless of homologous recombination. What would be the control in that setting? Thank you.
Thank you for the question. The first part is on the endometrial. Just to clarify, there are two studies. There is a phase II study, classical accelerated approval strategy in the U.S., where the key endpoints are response and durability of response. Then there is a phase III where we randomize 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 dataset actually generated in patients who had exhausted both checkpoints and chemotherapy, basically reflected off the current standard of care, which has been changed with the checkpoints. That is the endometrial study, and that is a PFS OS endpoint. We have these dual strategies, 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. If you are not having any maintenance because some women do not get any BEV maintenance in the second line because they had BEV in frontline, then it's nothing against Rina-S, if that design makes sense.
Thanks, Tahi.
I think we can move to the next question.
Our next question will come from Vikram Purohit with Morgan Stanley. Your line is now open. Please unmute and ask your question.
Vikram?
We'll actually move on to the next question. We lost Vikram. So our next question will come from Xian Deng with UBS. Your line is now open. Please go ahead.
Hi, thank you for taking my question. Just actually two, please. The first one, Rinatabart Sesutecan, the endometrial data you just presented. So just wondering, it seems that between the 100 mg, 120 mg, there does not seem to be a bit of a difference. I think you alluded to something with BMI, but I did not quite catch that.
Just wondering, because if I remember correctly, ovarian cancer, there's actually quite a bit of difference between the two doses, but here you do not seem to have a difference, and then you actually selected the 100 mg for phase III. Just wondering, any thought on that, please? That is the first one. The second one, just wondering for the phase II, non-small cell lung cancer. Just wondering, is that trial, is that still planned for EGFR mutant only, or is that for all-comers? Thank you very much.
Thanks, Xian, for the question. Tahi, can you handle both of them?
Of course, sure. Thank you for the question. Let's get to the first part. Yeah, 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.
That is relevant, of course, because we dose by surface area. You end up giving more drug, and that at some point ends up getting into levels of free sesutecan that probably are not giving us a favorable safety profile where the combination of efficacy and safety makes sense. That is why for endometrial, we chose 100 mg. Now, you're absolutely correct. In ovarian, there was a steep dose response curve between 100 mg and 120 mg. In endometrial, that is not the case. Both of them actually have a very high efficacy. What this tells us is that in endometrial, probably the sensitivity of the tumor to this ADC is actually higher to a degree, at least that you have already a plateau at 100 mg. 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. The efficacy signal speaks for itself. As I said, we already are involving 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. In that study, we will also explore broadly adenocarcinoma outside of the EGFR mutated space.
Thanks, Tahi. Thanks, Xian, for the questions. Let's move on to the next analyst.
Our next question will come from Michael Schmidt with Guggenheim Securities. Your line is now open. Please unmute and ask your question.
Hey, guys, this is Paul for Michael. Thanks for taking our question.
Just on endometrial, following up on the prior questions on the control for the pivotal studies, 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 and enabling strategy you're having? Thank you.
Thanks, Paul. Tahi.
Sorry, yes, thanks for the question. I think this is a question that we have been asked a couple of times. There's actually really no good data to point to in this novel population. If you look at historical data prior to that change in standard of care, chemotherapy, roughly at best case, has a response of 10%-15%.
Now that actually women are already getting checkpoint inhibition in frontline, it will be 10 or 15 minus X, whatever X may be. That is 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.
Thanks, Tahi.
Thank you very much.
Thanks, Paul. Let's move on.
Our next question will come from Matt Phipps with William Blair. Your line is now open. Please unmute and ask your question.
Thanks for taking my questions. Congrats on the endometrial update here. Why was there less prophylactic G-CSF use at the 120 mg cohort versus 100 mg cohort? Has that confounded any of the results?
Why not just try to evaluate maybe some body mass index adjustments to your dose across maybe all studies if you're seeing this maybe issue with higher BMI?
Yeah. Tahi. Go ahead.
Sorry, yeah. 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 mg cohort as the expansion of the trial before we went into randomization. What happens is this is an expansion cohort after phase I. There 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 it a little bit more. This is where the disparity comes from.
On the idea of capping it, it is actually capped moving forward in the sense that there is a cap for the body surface area, at which point you do not dose beyond that, which is quite common usually for ADCs. As the question before alluded to, just look at if we look at the data, what you see is that you essentially already have a plateau. It does not really make sense to push the dose. I think it is then equally important to think about long-term durability. I kind of alluded to the PopPK data, which actually gave us the evidence that the 120 mg dose in endometrium might be a little bit higher than what was modeled for PROC, in fact, 100 mg/m² free exatecan.
I'm going to repeat this again, over lays, more or less, almost to a point where you cannot differentiate the curves with 120 mg in PROC. 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. It's important to understand this with ADCs, tolerability drives duration of treatment, duration of treatment drives duration of response.
Thanks, Tahi. That's very clear. Let's move on.
Before we take our next question, I'd like to remind everyone, in order to ask a question, please use the raise hand feature. Our next question will come from Qize Ding with Redburn Atlantic. Your line is now open. Please unmute and ask your question.
Thanks for taking my questions. Two, if I may.
These two 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 to give you the confidence to move forward to the phase II stage. 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? Probably just one last one. Just to clarify, you mentioned about you're going to test the Rinatabart Sesutecan in combination. Can you elaborate a little bit more? Is it in combination with bispecific antibody, or is it in combination with checkpoint inhibitor, please? Thank you.
Thanks for the questions. Tahi, can you handle all three, starting with the lung cancer one?
Yeah, I can start with the beginning, but then I would ask for clarification on the last question. This is for the non-small cell lung cancer study. You were asking about combination with checkpoint or bispecifics. I was not really clear in what indication the question was focusing on.
Qize?
Yeah, the key question, I mean, all three questions are related to the non-small cell lung cancer program.
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 seems to have an even higher folate receptor alpha expression. Now, it is not to the degree that it is as high as the highest level of folate receptor alpha expression that has been observed in PROC.
The entire scientific argument that we've made for a while was that once we get confidence on the fact that Rinatabart Sesutecan actually has efficacy in lower levels of folate receptor alpha expression, it really becomes a question whether the tumor is sensitive to topo as a mechanism. I think there's already evidence in the public domain that EGFR-mutated lung cancers are sensitive to topo. We do also have a cohort already enrolling patients. We have already a cohort enrolling patients as an expansion cohort of the phase I. 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 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 van de Winkel for closing remarks.
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.