Brilliant. Thank you all, and welcome to day two of the Jefferies Healthcare Conference. My name is Ben Jackson. I'm from the European Biopharma team here at Jefferies. Pleasure to be joined today by Genmab. We've got a lot to chat through. We're here with Judith, the Chief Development Officer, as well as Andrew Carlsen, IR. Look, I'll hand it over to you guys just to say a couple of words, introduction about your background and the Genmab story at the moment, and then we'll dive right in with Q&A.
Sure. Thank you.
Thank you, Ben. It's a pleasure to be here. Yeah, so 2025, I would say, is characterized with a year of significant development. We're just coming off the back of ASCO, where we presented new data on one of our important late-stage assets called Rina-S. Rina-S is a wholly owned asset that we got access to from the acquisition of ProfoundBio last year. Now, you could say, essentially, the data we presented at ASCO confirms that we have a potential opportunity within endometrial cancer in addition to ovarian cancer. This fits nicely within our, you could say, gynecological suite, where we already now have Tivdak launched in cervical cancer. It aligns well with the overall strategy where, you could say, going forward, it's always been Genmab's ambition to forward integrate, to become an end-to-end biotech.
With now Rina-S and the positive data supporting that, we have an additional asset that will complement EPKINLY, which is our second important medicine, where you could say we are pleased to announce that we had positive data in second-line follicular lymphoma. We are on track to submit here in the first half on that, and more to come on EPKINLY. In Genmab's evolution, we have EPKINLY, we have Rina-S, and then thirdly, we have our important asset, acasunlimab, where we later this year will provide an update. Putting that all together, more and more of our own medicines are making significant progress. Our existing royalty business is performing strongly. Most of you have likely seen our Q1 results with Darzalex continuing to grow nicely, Kesimpta, etc.
We're in a really good position where we have a solid financial foundation with growing royalty streams, which we're reinvesting back into the business, more specifically EPKINLY, Rina-S, acasunlimab. Yeah, overall, making significant progress, which is what it's all about in drug development. With that, I'll hand it back to you, Ben.
Awesome. Yeah, lots to go through. I think we go through that order of the drugs that you've highlighted. We'll start with Rina-S. It's very topical. Before we jump into the ASCO data, do you want to tell us a little bit about the rationale behind the original ProfoundBio acquisition? What is it with regards to that ADC that draws you to it and draws to the acquisition, especially considering that there are several folate receptor alpha ADCs out there?
Thank you for the question and for the opportunity to be here. The acquisition of ProfoundBio was after a lot of digging on what could be the best ADC platform to make a meaningful difference for patients. The beautiful approach and decision that we made to acquire ProfoundBio was in these hydrophilic linkers. If we talk about hydrophilic linkers, and particularly [inaudible], which is the linker and payload that has Rina-S, it allows to mask the hydrophobicity of Exatecan, which is a very potent payload. When the drug-to-antibody ratio is 8, we see an optimal PK and physiochemical properties, which is a PK that overlaps with a parental antibody. We have great optimal delivery to the tumor, where the DAR8 and the Exatecan hydrophobicity allows for very good bystander effect.
These hydrophilic linkers, which is a suite that allows to combine even with many payloads. And as we all know, we are an antibody expert with other technologies such as DuoBody for bispecific. So the ADC was a perfect strategic fit to increase our opportunities. And we are unleashing the benefit for patients now with the initial data that we presented on Rina, but more to come on these hydrophilic linkers and more payloads in the future for patients.
That makes sense. If we think about the data so far, what is it that underpins the confidence when we compare it to the likes of [Abluzelahab], for example, that they got from the acquisition of ImmunoGen? What drives that confidence?
Yeah, no, so thank you. Let's start with the comparison. The data that we showed at SGO in a set of around 40 patients with platinum-resistant ovarian cancer is that Rina-S works across the board of folate receptor expression intensity. Different to Elahere or Mirvetuximab, which is restricted to the 75+%, we showed unprecedented efficacy, 50% overall response rate, unprecedented durability, which, you know, 48 weeks follow-up, which is almost one year, only one patient out of 10 progressed with very good tolerability. When I say very good tolerability, I said only one patient of those 10 discontinued before because of AEs. Basically, different reach across the whole spectrum of folate receptor alpha expression, different efficacy.
I would like to say that the SORAYA study, which is the phase II for Mirvetuximab in the preselected, had an ORR of 32% and Mirasol 40, which had durability median of 6.9. We are one year, and we did not reach the median. You know, who knows what will be the median? But we know for sure it will be more than 12 months. Very good efficacy, GI and hematologic, you know, which are manageable, no ocular toxicity, no ILD. Overall, you know, super differentiated in terms of patient reach, safety, and efficacy.
That makes sense. You are hot off the press from ASCO, I think, with the presentation of the dose expansion for endometrial cancer. What would be the key takeaways from that data? What did you learn, and what confidence does that build?
Yeah, so let's talk about the disease first. You know, endometrial cancer treatment paradigm evolved. And now, for the last year, the first-line treatment is checkpoint inhibitor plus chemo. Patients that fail checkpoints, inhibitors, and chemo have no standard. You know, the only treatment will be single-agent chemo, doxorubicin or Taxol, with an ORR around 15%, a median PFS of 3.9, and median OS of around 11 months. This is the sad situation. The reason for optimism and hope is what we presented at ASCO, whereas in patients heavily pretreated, all of them prior PD-1 pretreated, all of them chemo pretreated, median prior lines three, the overall response rate with the recommended phase II dose, 50%, 55.0. Again, ORR is important, but duration of response is as important.
What we showed is that with a median follow-up of 7.9 months for the 100, 73% are still on response. What we saw, you know, is compelling in terms of efficacy. In terms of tolerability, as I said, no ILD, no ocular, again, aligned with ovarian, minor GI, and cytopenias, which were well managed. We are overall, you know, very excited about this data to the point that we have a registration plan potentially in motion, which is composed of a phase II study that will enroll up to 100 patients with an endpoint of ORR and DOR, duration of response, and a phase III confirmatory plan to start by the end of the year in this very setting. Very excited and just leveraging on the opportunity to move fast and seamless.
That makes sense on endometrial cancer, but how should we be thinking about the relative opportunities between endometrial cancer and then also ovarian cancer as well, which you're also having a look at, Genmab?
I can start. So we signal that we envision Rina-S as an opportunity of $2 billion+ , you know, driven by the opportunities in PRSOC, a PSOC, which is platinum-sensitive ovarian, where we have a phase III study planned by the end of the year, and endometrial. So both of indications compose our, you know, modeling for the $2 billion.
That makes sense. Good. I think at the investor event the other day, we also started talking about the other cancers as well. What underpins the hopes that it's also going to be efficacious in the likes of lung cancer, which you're also looking at? What is the strategy to bringing that to market as well?
Yeah, so thank you for the question. The totality of the data that we have today in ovarian and endometrial for folate receptor expression and response allows us to say that the data has demonstrated that there is activity. Rina-S has activity across the board of different expression ranges of folate receptor. This compels us to go to other diseases where folate receptor expression is prevalent, but maybe with lower intensity. To that end, you know, we are starting a phase II totally devoted to non-small cell lung cancer, which will be a signal-seeking study in adenocarcinoma of the lung, EGFR mutated and EGFR wild, to assess the potential of Rina in non-small cell, which is, you know, a disease where the prevalence of folate receptor expression is high.
We are embarking on this looking at other indications, and there are more to come, but the first one outside GynONC is non-small cell lung cancer.
That's very clear. Look, we'll chat briefly about the second asset then that we touched on, so EPKINLY. I'm quite interested to know your thoughts about the timeline for earlier line readouts for EPKINLY that could increase the eligible population, perhaps to more of a blockbuster sales potential as well, and particularly considering the fact that your competitor, Roche, has had several readouts recently and a couple more upcoming. Tell us a little bit about the strategy in the earlier line setting there.
Yeah, so we already communicated at the beginning of May the positive results based off one of the dual endpoints for EPKINLY plus R2 versus R2 in second, third line follicular lymphoma. We already announced that the ORR, which was one of the dual primary endpoints, was met with a P significant value of below 0.0001. Based on that, you know, the filing H1 2025. We also announced that there are two phase III studies that are fully accrued where we expect readouts by 2026. These are in DLBCL, the second, third line DLBCL of Epcor versus R-GemOx, which is standard of care. Most importantly, the first line DLBCL of Epcor R-CHOP as compared to R-CHOP, which completed enrollment, and we envision, you know, having results by end of 2026.
That makes sense. When we think about it, what are the key features of EPKINLY that are being leveraged on the commercial side, so perhaps more so on Andrew's side here, to position it advantageously versus Roche's CD20, CD3?
Sure. One of the key differentiating factors is that EPKINLY is, you say, the only bispecific that has been approved for both indications, so both FL and DLBCL. The fact that we can, you know, with one solution address the two subtypes of indications is a compelling value proposition for prescribers. Of course, it is the clinical evidence, the efficacy, as well as the safety profile. Thirdly, we do have the convenience factor being the fact that it is subcutaneous. Put that all together, of course, we believe we have a highly compelling value proposition compared to our competitors who have two options within the same space.
Yeah, that makes sense. We have about 10 minutes left. Let's shift on to acasunlimab and then talk a little bit about the third asset that you highlighted right at the start. For those that do not know, this is the PD-L1 4-1BB. We got some data this time last year, actually, at ASCO, I believe, the presentation, which was certainly very interesting. It does show the efficacy that exists when in combination with Keytruda. Could you tell us a little bit more about what you saw with the frequency of administration and the mechanistic rationale that you have understood since presenting that initial data that underpins confidence of why that works?
Yeah, so thank you for the question. Just to level the ground, the data that we presented at ASCO last year on aca was for a randomized phase II study where we wanted to test the hypothesis whether acasunlimab every three weeks plus pembro versus acasunlimab every six weeks plus pembro versus acasunlimab alone without pembro. What was clear from the get-go was acasunlimab needs pembro, which was not a surprise by us because the dose was chosen to maximize the agonistic effect of 4-1BB, but the receptor occupancy for the PD-1, PD-L1 axes was around 80%. We knew that, you know, agonistic without blocking PD-1, PD-L1 won't be enough. That data dropped. The other question was whether three or six, what will be better?
The question became because there were these many papers that called to the fact that tonic stimulations of T cells lead to exhaustion. It is like if you press the gas, press the gas, press the gas, you burn the motor, something like that, but for T cells. The whole hypothesis was in order for T cells to stay functional, you need to give them a break. There were started papers like four or five years ago to say you need to do this push-pull, so stimulate the T cells and then let them rest, stimulate. This, from a mechanistic point of view and biology, we had these papers, but we did not have the clinical data. We did this every six weeks versus every three weeks. Let's go to the efficacy first, clinical data.
What we showed is that the median overall survival for the every six weeks was 17.5 months, okay? Because of the censoring, another important parameter is percentage of patients alive by 12 months, which we know docetaxel, the median overall survival is 10-11 months. Twelve months is a very important landmark. What we saw is with the every six weeks was 69%, which was considerably higher than the every three weeks. It became why, whether this hypothesis of T cell exhaustion is confirmed by biomarkers. We presented these biomarkers at CTSI and Well-Lung where very elegantly we showed, the main indicator of T cell exhaustion is TIM-3. When we compare TIM-3 in the every three weeks versus every six weeks, the every six weeks T cells are very functional all across vis-à-vis the every three weeks.
The totality of the data, efficacy, biomarkers plus safety, so one of the potential liabilities of Aca is liver tox. We saw a much better tolerated and less liver tox with every six and every three. The totality of the checks, efficacy, biomarkers, and safety supported the every six weeks. This is what we moved in the clinic with the phase III ongoing.
That makes sense. If we look on a forward-looking basis, when should we anticipate to hear a bit more about overall survival and how confident is management around that?
Yeah, so we will plan another cut of data, data cut, and present this data by the end of the year because as we know, for immuno-oncology, there is not a correlation between response and time to event because the time to event, whether PFS or overall survival, is driven by the tail of the curve, which encompasses durable, stable disease and some durable responses if there are responses. Basically, we think it's very, very relevant to have another cut that shows the sustainability of this tail effect and overall survival because at the end for the phase III, the endpoint is overall survival. This is what we need to give to patients, you know, better overall survival as compared to docetaxel.
That makes sense. If we stick on oncology for one more and then we'll shift just a little bit broader looking, let's touch on GEN1042. Could you talk to us a little bit about what the early data has told you about that asset and how confident are you that there's a path forward going ahead?
Yeah, so the data that we presented initially was that, so GEN1042 is a 4-1BB CD40. It's basically, you know, it stimulates antigen-presenting cells CD40 and has an agonistic effect 4-1BB. The data showed that it's an asset that has to be combined. The best combination is with chemo and checkpoint inhibitors. Why? Because with chemo, we create immunogenic cell death and neoepitopes that triggers like APC engagement. Then we stimulate these antigen-presenting cells with CD40 and 4-1BB, but we need like the spark, and the spark is the chemo. We learned that this combination is relevant. We showed initial data. Now we will have another look at data later this year to say durability because for IO, you know, time to event, durability is key. Then put this data vis-à-vis potential new standards in head and neck cancer and our internal pipeline.
We will make this decision and we will communicate and we message this clearly.
That makes sense. We shift briefly onto inflammation and immunology. It's somewhere that I think gets probably talked about quite a lot and there's still not much to say. Two parts of the questions. We start in, can you talk a little bit about how the partnership with argenx is progressing on that side of things? Beyond that, what is the timeline that we could start to hear about more broader immunology programs from Genmab in that space?
I can start and maybe my buddy Andrew will help me. No, the collaboration is going very well. We are doing a lot of research activities together for new targets, new modalities based on the synergistic and complementariness of strengths between both companies. As a result of this research, so far, no IND is filed and we communicate publicly not research activities, but IND filings. We are looking internally at our own pipeline and potentially for BD activities as well. Again, our focus now is Aca, Rina, EPKINLY, but we envision to expand with a clinical asset on ANI. I cannot provide firm timelines, but we are actively looking organically and inorganically.
Perfect. Good. There you go. Next further. I guess, look, with the last few minutes, I do want to touch a little bit on business development and M&A because it's something that I think comes up as questions a lot. I guess from your perspective as CDO, is there any areas that you think are particularly interesting at the moment? Secondly on that, perhaps a broader comment from you both. What are you seeing with regards to the current phenotype of deals you're looking for and how amenable is this environment to doing deals? We've heard conflicting things throughout the week from different management teams.
I always start by saying that the acquisition of ProfoundBio provides you a nice representation of what are we looking for when we approach or consider anything for a BD opportunity. It has to be a strategic fit in terms of making a difference for patients. It has to be a strategic fit on being complementary to our area of expertise. It has to be, even if we are thinking about an acquisition, a cultural fit somehow. The integration and acquisition of ProfoundBio have checked every box. Now we are looking for something that can make a difference for patients that in the horizon of timelines is pretty mature potentially and that fits these strategic fit characteristics or making a difference for patients in a nutshell.
Now, in terms of the environment, you know, I would say that oncology is competitive, so is INI. So it's not new. It's competitive, but you know, we have strengths to compete, which is we are very good evaluating potential assets. And when we move, we move fast. And just I want to remind everybody that the first patient enrolled in Rina happened in January two years ago, okay? So in two years, we moved the program from phase I to potentially three registrational studies by the end of the year. I think that we have shown that we can execute well and make decisions for the right reasons. I think we are well positioned, although it's not surprise, it's competitive.
Excellent. Makes a lot of sense. Look, you've got 60 seconds. I'll ask you, looking ahead to the second half of this year and into 2026, what are the key news flow that we should be watching out for here?
Sure. Key news flows in no specific order. Judith highlighted we'll provide an update on Aca or GEN1046. That's the PD-L1 4-1BB. Longer follow-up on the OS curve you saw last year. That's one thing to watch out for. Rina-S, of course, we are continuing to follow the patients in second-line PRSOC. Judith alluded to the, you know, significant duration of responses, which was not met at the cut we presented at SGO. That will be an update on that as well. Of course, EPKINLY continues to generate a lot of data and evidence on that. There will be more updates on EPKINLY in the second half of the year.
That's kind of broadly speaking our three late-stage assets that we'll be continuing to provide news flow in addition to, of course, our quarterly results, which are always exciting given our strong financials.
For sure. Look, very clear story. Really appreciate you both coming and joining us today. It's been fantastic. Thank you all for joining as well. See you again soon.