Genmab A/S (GMAB) Earnings Call Transcript

Hello, and welcome to Genmab's Investor Event. [Operator Instructions] As a reminder, this conference is being recorded today. If you have any objections, please disconnect at this time. I would now like to pass the call to Jan van de Winkel, Genmab's CEO. Please proceed.

Hello, everyone, and welcome to our investor event. I can tell you this has been a really exciting month for Genmab and more importantly, for patients. We delivered 3 positive Phase III clinical readouts in 3 different cancers: diffuse large B-cell lymphoma, platinum-resistant ovarian cancer and head and neck cancer. And at ESMO, new data that support taking bitusentamab further into colorectal cancer. There are 3 things I want you to take away today. First, we believe the 3 Phase III readouts have the potential to change how patients are treated. Second, data at ESMO on petosemtamab support expansion into colorectal cancer. And third, what this means for Genmab, multiple potential launches starting in 2027 and a growth trajectory increasingly driven by our own medicines. So with me today is our Chief Medical Officer, Tahi Ahmadi, who will walk you through the data. And for our Q&A, we will be joined by our Chief Financial Officer, Anthony Pagano; and our Chief Commercial Officer, Brad Bailey. Next slide. As always, we will be making forward-looking statements, so please keep that in mind during the call. Actual results may differ materially, and please refer to the statement on this slide and to our filings. As we are in a quiet period, today's discussion is limited to information already in the public domain. We will cover the broader business on our Q3 call on November 5. Next slide. At JPMorgan in January, I said 2026 would be a defining year for Genmab. We have been clear about what we set out to do. We told you that EPKINLY, Rina-S anditcentamab, we are on track to Phase III readouts in the second half of this year, setting up potential approvals and launches in 2027. And that is exactly what we have done. In unprecedented month for Genmab, we have reported 3 Phase III data sets that each have the potential to establish a new standard in their respective indications. EPKINLY for R-CHOP plus R-CHOP in first-line diffuse large B-cell lymphoma, reducing the risk of progression or death by 51% Rina-S in platinum-resistant ovarian cancer demonstrated a 71% reduction in the risk of disease progression and a 57% reduction in the risk of death in the ITT population. And petosemtamab plus pembrolizumab in first-line head and neck cancer showed both a statistically significant improvement in response rate and in overall survival. Each is in a setting where patients need better options and each has the potential to change the standard of care. And the Phase II data at ESMO showed that petosemtamab can go further into colorectal cancer. Next slide. This slide shows how we got there. Over the past 10 months, we had 3 Phase III readouts for APkILi in January, June and October. Both Phase II and Phase III data for Rina-S and the first Phase III readout foritcentamab, each on the time line we guided. And there is more to come with the Phase III LIGAHN2 readout in previously treated head and neck cancer expected in the first quarter of 2027. Together, these data support potential approvals and launches beginning in 2027. And this is what we have been building towards. It reflects our focused execution and the strategic choices we made with Rina-S and petosemtamab. In January, I told you that we deliver on our promises. This month, we have shown it. And what sets Genmab apart is not just a great science, but our consistent ability to execute with speed, agility and a focus on patients. Tahi, the floor is yours now.

We can go to the next slide. Thank you, Jan. Let me start with EPKINLY in first-line diffuse large B-cell lymphoma, the largest opportunity in B-cell lymphoma and in a setting where R-CHOP has been the gold standard for more than a decade and where way too many patients still relapse after frontline therapy. If you can go to the next slide. Epcor diffuse large B-cell -2 is the first Phase III trial to show that adding a bispecific antibody to frontline chemoimmunotherapy significantly improves progression-free survival in diffuse large B-cell lymphoma. In patients with an IPI score of 2 to 5, EPKINLY plus R-CHOP reduced the risk of progression or death by 51%, a hazard ratio of 0.49 with a p-value below 0.0001. To put that into context, the landmark trial that established R-CHOP as a standard of care was almost 25 years ago. And in a disease where a segment of patients is cured, the addition of rituximab to R-CHOP with a hazard ratio of around 0.58 back then was considered to be the ceiling of what one could reasonably expect. Cost trial comparisons always have their limits, but even with the most recent positive Phase III trials, a hazard ratio of 0.49 speaks for itself. It did so with a fixed duration subcutaneous regimen and with the safety consistent with the known profiles of epcoritamab and R-CHOP. And this is a pattern we've now seen multiple times with EPKINLY. Efficacy and safety are very predictable. The Phase II combination data are highly consistent with the larger Phase III data sets. We saw that in combination with denalidomide in June, and we see it here again. In our view, these results have the potential to change frontline practice in diffuse large B-cell lymphoma, and we look very much forward to presenting the full data at a future medical meeting, together with AbbVie, we will engage with the global health authorities. Next slide, please. Now here is why this matters. Today, EPKINLY's approved indication, third line plus diffuse large B-cell and follicular lymphoma and more recently, second line plus follicular lymphoma address around 27,000 patients. With potential 2027 launches in second-line plus and first-line diffuse large B-cell lymphoma and first-line follicular lymphoma to follow soon, EPIi can address around 146,000 patients across the U.S., EU5 and Japan, more than 5x where we are today. First-line diffuse large B-cell alone represents around 70,000 of these patients, by far the largest population where we can have the greatest impact for these patients. And we are prepared for this moment. Frontline patients are primarily treated close to home in their community. Our work to date with EPKINLY has built strong momentum among community sites with broaden treatment experience across both diffuse large B-cell lymphoma and follicular lymphoma. And this will be important as we look ahead to a potential launch in frontline diffuse large B-cell lymphoma. In fact, we shared during our last earnings call that the majority of new adoption for EPKINLY in the U.S. came from community centers, exactly where these first-line patients are treated. If we can go to the next slide, please. The Phase III readouts this year put EPKINY on a path to spend diffuse large B-cell follicular lymphoma from first-line onwards with data in first-line follicular lymphoma still to come in the future. With a differentiated dual indication profile and demonstrated versatility across lines of therapy and histologies as a monotherapy or in the various combinations, EPKINY has the potential to become the core therapy in B-cell malignancies. And we see a peak sales opportunity of more than $3 billion for this program. And with the frontline data in hand, we believe we are around 1 to 1.5 years ahead of the main competitors in this setting. Now let's turn to Rina-S. Next slide, please. Rina-S is the first of our 2 wholly owned late-stage medicines we will talk about today. And we have 2 data sets to cover here. The positive Phase III WANE402 top line and the Phase II WAIN401 data presented at IGCS. Next slide, please. The Phase II data at IGCS show why we had such high conviction going into the Phase III readout. In heavily pretreated patients, Rina-S delivered a confirmed response rate of 45.9% and a median duration of response of 12.1 months. And these responses were seen across the folate receptor alpha expression levels. The safety profile supports long-term use. There are no ocular events, neuropathy and no ILD signal. And only 1.8% of patients discontinued due to treatment-related adverse events. As I said on our call in the second quarter in August. Put these together, and you could already get a sense of the direction of the PFS and what BAIN-402 has now shown. Next slide, please. RAIN 402 marks a significant milestone for Genmab and for women with platinum-resistant ovarian cancer who today have limited treatment options. The study met its primary endpoint of progression-free survival versus investigator choice therapy in both populations we analyzed. In the intent-to-treat population, which comprised of all randomized patients with PARC regardless of the folate receptor alpha expression, Rina-S demonstrated a 71% reduction in the risk of progression or death with an unprecedented hazard ratio of 0.29. In the primary analysis, which mandated that patients with a folate receptor alpha expression above 75% PS2 positivity had to be treated with minlituximab, Rina-S demonstrated a 67% reduction in the risk of progression or death with a hazard ratio of 0.33. Importantly, RAIE-402 also met its key secondary endpoint of over survival in both populations. Safety was consistent with what we have seen before with no new safety signal. And these results support the phenomenon we have routinely described with VNS that is the efficacy irrespective of folate receptor alpha expression level or prior treatment with mirvetuximab. And this gives Rina-S the potential to reach a much broader group of patients. Our ambition for Rina-S has been from the beginning to be the best first and broadest in class, and we plan to file as soon as possible with a potential launch in 2027, and we will present the full data at a future medical meeting. If we now go to the next slide, please. When we acquired ProfoundBio in May 2024, there was Phase I/II trial ongoing. Today, there are 6 Phase III trials that have been announced and initiated across ovarian and endometrial cancers, addressing around 79,000 patients. TRC is the first potential launch. With possibility of endometrial and platinum-sensitive disease in the future, we are building a franchise we own entirely with a peak sales opportunity of more than $2 billion. With the Phase III data now in our hands, Rina-S has the potential to become best-in-class ADC. Combined with our established global presence in recurrent or metastatic cervical cancer, the breadth of our programs in ovarian and endometrial cancer positions us well to lead innovation in the gynecological cancer space. Next slide. Now finally, let's move on to poilamab, our second wholly owned late-stage medicine that we believe has the potential to redefine how epithelial cancers are treated. I'll offer 3 updates here. The Phase III LIGAR-HN-1 top line in first-line head and neck cancer and the updated Phase II data at ESMO in both head and neck and in colorectal data. If we go to the next slide, please. In August, we said ESMO would show why we are so enthusiastic about petosemtamab. First, let's focus on head and neck cancer. In first-line head and neck, the Phase II data that underpinned LIGOR-HN-1 have held up with a longer follow-up, a 63% confirmed response rate and a median overall survival of 28.2 months. This data is support of the Phase III data we announced just this morning, as you will see on the next slide. LIGAR-HN-1 enrolled around 700 patients with first-line PD-L1 positive recurrent or metastatic head and neck cancer, comparing petosemtamab plus pembrolizumab with pembrolizumab alone with a dual primary endpoint of response rate and overall survival. At the first interim analysis conducted by an independent data monitoring committee, the combination delivered a statistically significant and clinically meaningful improvement in response rate regardless of HPV status. It also significantly improved overall survival, reducing the risk of death by 50%, meeting both primary endpoints. Petosemtamab was generally well tolerated with no new safety signals. Let me put this into context. Today, patients with first-line head and neck cancer face some of the most dismal outcomes of any frontline cancer. Pembrolizumab alone delivers response rate in the high teens to low 20s and an overall survival of roughly a year. When you combine pembrolizumab with chemo, the results aren't much better. The overall response rate increases to approximately 36% with a moderate improvement in over survival to 13 months. Going back to what I said that if the Phase III came anywhere in the ballpark of our Phase II data, there would be no question this would be the new standard. This makes petosemtamab the first bispecific antibody with positive Phase III data in first-line head and neck cancer, the largest population in this disease and in a setting where currently pembrolizumab alone or in combination with chemo is the standard of care. And we believe this has the potential to change that standard, bringing us closer to potentially delivering the first EGFR targeting bispecific antibody approved for first-line head and neck cancer. And this enforces our conviction that bitrozab is not only potentially the first, but also the best-in-class second-generation bispecific as an EGFR LGR5 bispecific antibody. And we will present the full data at a future meeting and engage with regulatory authorities on a potential filing here as well. Next slide. Also at ESMO, we presented updated data in colorectal cancer. Colorectal cancer gives petosemtamab a second path for growth beyond head and neck cancer. And so here, petosemtamab plus chemotherapy delivered response rates of 81% in left-sided first-line tumors and 67% in second-line disease control in both above 90% with no new safety signals. And these data supported 2 Phase III trials in colorectal, addressing a patient population around 3x the size of head and neck. If you go to the next slide. When we acquired MS, we said we would pursue a broad focused development. Today, we have a positive Phase III in first-line head and neck LIGAR-HN2 will read out in Q1 2027 and 2 Phase III trials in colorectal cancer, a program addressing already around 315,000 patients with multibillion-dollar peak sales potential. So to sum it all up, 3 Phase III trials, 3 positive results in 3 cancers where patients need better options. And in each case, the Phase III results are consistent with the Phase II data that led us here. With that, I'll give it back to you, Jan.

Thank you, Tahi. Very clear. Let me bring it all together. Next slide, please. Over the past decade, we have taken Genmab from a royalty-based company to a fully integrated biotech with its own medicines and a powerful late-stage pipeline. This month is the proof point for that strategy. So what does this all mean for Genmab? To me, it comes down to 3 things. First, 3 positive Phase III readouts in first-line diffuse large B-cell lymphoma, platinum-resistant ovarian cancer and first-line head and neck cancer, each with the potential to change clinical practice. Second, new data at ESMO on petosemtamab that support expansion beyond head and neck into colorectal cancer. And third, a development plan and clinical evidence that combined support supports a growth trajectory you can now see very clearly, multiple potential launches beginning in 2027 with peak sales potential of more than $3 billion for EPKINLY, more than $2 billion for Rolinas and multibillion dollars for petosemtamab. And 2 of these 3 medicines are wholly owned. Together, these 3 programs carry 5 FDA breakthrough therapy designations and with 6 new Phase III trials launch this year, each one is still expanding. In August, at our Q2 call, I said that with 3 super important Phase III studies reading out, we are well on track to deliver sustainable growth well into the next decade. Together, today, with 3 positive results in hand, I can say with great confidence that growth will increasingly be driven by our own medicines. None of this would be possible without the patients and caregivers who take part in our trials, the investigators and our talented and passionate colleagues across Genmab. Thank you. Our purpose is to transform lives with pioneering antibody science. And this month brought us closer to doing that for many more cancer patients. Next slide. That now ends our formal presentation. Operator, please open the call for questions, and thank you.

[Operator Instructions] Our first question will come from the line of Yaron Werber with TD Cowen.

Terrific. Congrats on really landmark results. Really great to see this. So I guess the big question is, it looks like this data is relatively immature for the HPV-positive population. Would you agree with that? And should we assume that roughly 20% of patients were HPV positive, in which case most of the effect was -- must have been driven a lot of it by the HPV-negative population.

Thanks, Yaron, for the question. I will hand it over to Tahi to give potentially more color there. Tahi?

Thank you for the question. So first thing I would say this, study population, broadly speaking, and that's not only true for HPV positive, but for local regional versus metastatic and for the various subtypes of head and neck is almost on point reflective of the epidemiology of the disease. That's the first point. The second point is, I'm not sure where this idea comes from that there is a difference between the subgroups in terms of maturity. The data met its statistical significance because the hazard ratio is so profound. That's just the way statistics work. Obviously, there is a follow-up, but it tells you a little bit what the scale of the OS difference was with that follow-up. Just to basically get to the point, broadly speaking, regardless of HPV positive or negativity or any of the subgroups, I think it's fair to say that all subgroups in one way or the other had a positive outcome on this trial and benefited from the combination.

Thanks, Tahi. I think we should leave it with this, Yaron, and then we will give further color at a medical conference, hopefully soon.

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

Really, really congratulations to your really extraordinary data and all of them. So maybe if I could ask a maybe bigger picture question, please. Just looking at your peak sales guidance, you still kept your $3 billion for EPKINLY, $2 billion for Rina-S, even including frontline endometrial, right? I mean now you have your own Phase III data, and you've probably also seen the latest updates from the ESMO from your competitors. So just wondering, I mean, I would say your peak sales guidance are probably vastly, vastly below what the Street is actually expecting now. I'm just wondering how do you think about this guidance? And yes, any color on the thoughts behind, please?

Thanks, Xian, for the compliments. And I hand this question over to Anthony, who can give you a bit further color on the thinking on peak sales guidance. Anthony?

Yes. Thanks, Xian. Look, I think as a starting point, and you all know this, we had high conviction around our 3 very strong products. Of course, that's EPKINLY, Rina-S and petosemtamab. And now what you've seen here during the month of October is that we've backed up that high conviction with these very strong Phase III data sets across all 3 products, and Ty has done a wonderful job really elucidating that point. And then that takes us to the next point. And that gives us high conviction in the peak year sales estimates that we've previously communicated, again, across EPKINLY, Rina-S and petosemtamab. And I think here's an important point, and we stand fully behind those estimates. This conviction not only comes from that strong data that we presented, but it also comes from the very strong capabilities that we've intentionally built out here at Genmab over the last number of years. That's the capabilities to develop these products. It's also the very strong commercialization capabilities and the strong performance we've seen for TIVDAK and EPKINLY. And of course, in addition to that, all of the prelaunch work that we've done across all 3 brands here moving forward. So Xian, what I want to leave you with is that we stand fully behind the estimates that we've previously provided and are super excited about the data we've been able to present here and deliver to the market during the course of October.

Next question will come from Michael Schmidt with Guggenheim.

Congrats on this amazing execution on these Phase III studies and also very smart business development. Any comments on how the pembrolizumab control arm performed in the head and neck cancer study relative to historic studies? Just curious. And then as you have this very impressive data now in hand that clearly derisks petosemtamab as a product candidate. How do you think about expanding that opportunity into other cancer types? I did see you had the collaboration announcement with Incyte recently, obviously, on the KRAS inhibitor, but I'm curious if there are other opportunities that you could now evaluate with this validation in hand.

Michael, thanks very much for the compliments. And then I hand this over again to Tahi control arm Tahi and then the expansion plan for petosemtamab because we are super excited, as you can imagine, Michael, about what you are seeing here. Tahi?

Yes. Look, without getting into a nuanced discussion on the data of the trial, which I think you will appreciate will probably more appropriately happen in the context of a medical conference. I think it's probably fair to say that the pembro arm behaved exactly the way a pembro arm has behaved in the past. On future plans, I think we have been very clear in our ambition, I think, from the day when we announced our intent to acquire Mos that we're going to anchor petosemtamab in head and neck and really think of it as the best-in-class bispecific EGFR bispecific in the entire space. And now recently also have put a little bit more emphasis on the very exciting opportunity in colorectal cancer. As it goes to the concrete studies that we're going to initiate, I think we're going to stick to what we've been practicing now for, I think, the last 12 months or so, where we are going to be very disciplined in announcing new trials right around the time when they are actually open. I keep saying this it's a very competitive field. everybody is watching. But if you followed how this has translated for VAS, I hope you have to trust in us that we are going to expand this program appropriately with all the conviction that we have in petosemtamab as a drug to bring this innovation, which we really think is a transformative innovation to as many patients with head and neck as possible.

Thanks, Tahi. Michael, it comes down to execution, execution, execution from here, I think, on multiple fronts, both in the clinical trials as well as in the filing and bringing it to the market for [indiscernible] and for petosemtamab. So we're very focused on execution in the coming time.

Next up will be James Gordon with Barclays.

James Gordon from Barclays. My question is on regulatory and commercial. So planned time lines for global filings, not just the U.S., but Europe, Japan and China. Can you get all 3 of these done, say, in the next 6 months? Or are any further things needed you need more mature data in other places? And the commercial part of that, does it now make sense for Genmab to build a truly global sales force in, say, head and neck and Gyne? Or could we actually see some partnering announcements in some regions, part outside the West? Is there a reason a larger company couldn't make even more of these products or hope to make even more of these products, which look like very, very strong clinical data?

Thanks, James, for the questions. I will ask Tahi on the first one, the regulatory process in the different territories. And then Brad can comment on the expansive commercialization plans we are putting into gear at this moment. Maybe Tahi, you can start on the sequence of the regulatory filings and the timing roughly.

Sure, James. And unfortunately, I won't do that. So I will just say that with the profound OS benefits, I think it's very clear that we will engage globally with all the relevant health authorities in the most expeditious time possible.

Thanks, Tahi. Brad, a bit of color on the commercialization.

Yes. Thanks for the question. And as we know, oncology is an extremely competitive and data-driven market, and this data gives us extreme confidence. As you've mentioned, as we've said all along, we've built our capabilities from a commercialization perspective with this level of growth and portfolio expansion in mind. And the differentiated focus that we've currently brought, both U.S., Japan and now in Europe around scientific engagement, customer engagement as well as our market access and patient support services really puts us in a position to be extremely confident to execute moving forward, and we can certainly update more as we move along the progress here.

Your next question will come from the line of Benjamin Jackson with Jefferies.

Just quick ones from my side. The first is on Rina-S, I think it's becoming clear in the PROP space that a big driver of the efficacy or the clinical efficacy that we're seeing is actually the duration of response. Are you able to comment or give any color in and around how duration of response varies between the folate receptor alpha different subgroups given that could be a better predictor of the actual clinical efficacy we're seeing between those groups? And then secondly, just interested to hear your thoughts going forward in and around EPKINLY combinations in the earlier line of cancer. So specifically around DLBCL here. You've obviously shown previously early-stage data in and around the combination with [ Polivy ]. Is this something that you could pursue? And how would you pursue that? Do they need full-blown Phase III randomized controlled trials? Or could you do it in a simpler and quicker fashion to enhance the label earlier?

Thanks, Ben, for the questions. I think they both go to Tahi first on the Rina-S and duration of response. And then EPKINLY, we think that EPKINLY is very, very good for combinations with different other medicines as we already have shown now with several combination partners. Maybe Tahi can give a bit of color on that as well on the plans for EPKINLY together with AbbVie. But Tahi, why don't you start with Rina-S?

Sure. Thank you for the question. Now let's start in the beginning. I mean, I think we said this for a while, and you touched on this, that one of the many differentiating aspects about Rina-S, its safety profile, its tolerability, its lack of neurotoxicity or b toxicity or for that matter of interstitial lung disease. And this tolerability with a very, very low rate of discontinuation due to AEs mainly related to neutropenia that's really almost restricted to the first cycle is leading to long duration of treatment, and that is beyond the overall response that's driving the duration of response. I'm not going to get into a discussion on how these different subgroups behave specifically because I think you will appreciate like to the answer I gave to the Pet question, that this is probably best done in the context of a full disclosure of the data and the whole demographics and all of this. But I would say with a hazard ratio of 0.29 on the PFS, it's really not that hard to imagine that essentially, which whatever way you were going to look at the data, slice the data, there was an unprecedented benefit for patients. On the EPKINLY question frontline, you're right. We also generated data with R-HPV poly in combination with EPKINLY and had an opportunity to present that in the future, and then we'll have a conversation about that. Look, given the fact that we have such a profound positive trial with R-CHOP, I think our focus is on R-CHOP. Globally, it is still for the totality of patients, the standard of care. HP Poly has made some inroads, I think, predominantly for patients with ABC, if you really look into it. Now with a completely new standard of care, the way we think, I think a lot of this is going to fall into the hands of EPKINLY, R-CHOP, which really honestly with an unprecedented hazard ratio for [indiscernible], I think what reasonably could have been expected before the emergence of bispecifics. I think that's where the focus is. This data is, of course, important. That's why we're generating it, and we will continue to engage with the respective ways of engaging with health authorities or other methods of making this combination also available for patients. But I don't foresee us having another Phase III of that scale and size. That's probably not the best resource spend for us. The focus is on the transformative data that we have generated and the significant time advantage that we have over [ Roche ].

Your next question will come from the line of Victor Floch with BNP Paribas.

First, congrats on all the fantastic data, incredible job across the board. Maybe first question on peto, to try here. Any chance you could share a bit more on how consistent the OS benefit was across the different PD-L1 CPS subgroups? And do you believe peto could become a new standard of care across the entire PD-L1 positive population? And a quick follow-up on locally advanced head and neck cancer. To what extent do you think these results have further derisked the opportunity in that setting? Does the magnitude of the survival benefit give you greater confidence in moving into earlier stage of the disease?