Welcome to day three of the Jefferies London Healthcare conference. My name is Ben Jackson. I'm one of the analysts here on the European Biopharma team. It's a pleasure today to be joined by the team from Genmab. We've got both CEO Jan van de Winkel and also Anthony Pagano, who is CFO. Look, we're going to jump straight into the Q&A. I guess if you could just set the scene for us a little bit. There's been a lot going on with the development of the products, but if you could put the lay of the land out there, what drugs are we focusing on at the moment and what are the opportunities? And then we'll dig into the individual assets.
Absolutely. I'm delighted. So good to see you all. I'm delighted to be here. We're really focusing on the late-stage programs now: Epkinly, Rina-S , Acasunlimab, and also hopefully soon petosemtamab or Peto, which we intend to bring in via the acquisition of Merus. That is the late-stage development medicines. Of course, also we have Darzalex as a commercial molecule, which we are now rolling out commercially in different European key countries in order to create a foothold for the Rina-S , 1.5 years from now in the future in the Genmab area.
Perfect. Look, let's start with Peto then, because I think that's probably what's been debated most as of late. Could you give us a little bit of an overview? What attracted you towards the asset and why did you make that move?
Absolutely. Peto is a fantastic EGFR-targeted bispecific antibody with a unique profile. We've never seen that with any other EGFR-targeted antibody up to now. It actually removes the epidermal growth factor receptor, which is a key target from the surface of cancer cells. It actually allows this molecule to shrink tumors very, very quickly. That is also what is seen in the clinical trials. The data from Merus is absolutely impressive in both the frontline head and neck cancer setting, where they see more than a tripling of the responses versus the benchmark with pembrolizumab. Also in the second, third line setting, unprecedented data with only petosemtamab . We believe it has a unique profile. We actually have a lot of experience at Genmab in EGFR targeting.
We actually worked on a naked EGFR-targeting antibody many, many years ago, also in the head and neck cancer setting. We worked actually on creating, we helped J&J create Amivantamab also by giving them access to an EGFR antibody and a CMET antibody with our bispecific technology. We know exactly what these molecules need to look at. We think Petosemtamab is uniquely positioned there. On top of that, Genmab has a lot of knowledge on head and neck cancer. We had actually two molecules in clinical development in head and neck cancer. We knew exactly what to look for in Petosemtamab and what to focus on. One of the molecules in head and neck cancer was Tivdak, our product for cervical cancer, second, third line cervical cancer. It created very good data in head and neck cancer, I can assure you all.
Despite that, we decided not to progress it to phase III development because of the evolving landscape. I even mentioned, perfectly mentioned Petosemtamab as one of the molecules now really shaping and reshaping the second, third line setting in a very dramatic way. Another molecule we had in development until recently in head and neck cancer was 1042. It's a 41B targeted bispecific antibody we created together with BioNTech, which we were testing together with Pembrolizumab and chemo in the frontline head and neck cancer setting. We actually realized that that molecule was not potent enough to really deal with the evolving landscape in head and neck. We feel that we are the appropriate owners of Petosemtamab . We actually screened the landscape really, really carefully.
We think it's an ideal molecule, not only for treatment of head and neck cancer and bring really progress that to the absolute new level, but also in other EGFR-positive tumors. We think the potential is actually a lot bigger for Petosemtamab . I should stop there probably, but I can go on for like half an hour if you want me to.
Perhaps can you reference some of the recent data you've seen that's got you particularly excited about the biology?
Yes, absolutely. I mean, the data and the biology, I need to be careful here because I need to only be speaking about the perfectly available data because we have done deep due diligence on Petosemtamab . I think it's probably better for me to stick with the clinical data here than with the preclinical data because I'm not sure that all of that is in the public domain. Given that we still need antitrust clearance from the relevant authorities, we need to be very, very careful in talking only about what is in the public domain and not what we have seen under due diligence. What I can tell you is that in the frontline head and neck cancer setting, Merus has seen a 63% overall response rate combining Petosemtamab with Pembrolizumab.
That is roughly 3x higher than what you see only with Pembrolizumab in the frontline head and neck cancer setting. The median overall survival has not been reached even with very, very good indicators that this will be a very long median overall survival. In the second line setting with monotherapy of Petosemtamab , they have seen a 36% overall response rate, whereas the benchmark is between 6% and 19% depending on whether you look at chemo or an antibody targeting EGFR, Cetuximab, a first-generation EGFR-targeting antibody. There, with very, very impressive median progression-free survival and overall survival of 11.4 months, which is hugely impressive. I think I better stick with the clinically available data in head and neck cancer. Peto has actually set a new bar there which I think will be a focus point, I think, for other companies to focus on in the coming time.
That makes sense on efficacy, but we also have to probably touch on safety and tolerability as well. One of the things that we debate often with the EGFR-targeting drugs is often the severe rash. What can you tell us about that within the context of the profile? Is there anything that's been dne to mitigate that that you've seen?
Absolutely. Merus has tested a new schedule for dosing with Peto. Since the implementation of that new schedule, the infusion-related reactions have farther managed versus the original schedule. On top of that, what Merus announced this week is that they have agreed with Halozyme to actually create a subcutaneous version. Many times subcutaneous applications of antibodies also against EGFR actually really help to mitigate infusion-related reactions. As life cycle management, that is also what we have already confirmed a week ago in our conference call. We said, you know, subQ development is an integral part of our proposed development for Petosemtamab . That will likely further improve infusion-related reactions. It is already very well under control with the new administration's regimen, very much better than the original regimen.
Very clear. I guess not only is the drug being studied in head and neck cancer, but there's also, as you referenced, some interest in other cancers as well. One of those is colorectal cancer. Perhaps could you add some additional color about where else this could be of interest and what you've seen so far?
The answer is yes, I can, but I will not do that because of several reasons. One is that we need to be very careful with what I can say at this moment about our plans for Peto because we still need to finalize the transaction. The second reason is competition. I mean, there are other companies moving into this area. We do not want to give them good ideas. We want to keep the good ideas for ourselves, actually. After we finalize the transaction, I am happy to speak about it much more openly. We see a lot of potential.
That's very fair. Anthony, perhaps one for you on financials. What are the key considerations that we need to be thinking about as this deal progresses? What have you pointed to in terms of accretion in the long term?
Yeah, so thanks for the question, Ben. Maybe you sort of start off and think about our investment priorities are super clear at Genmab. We're going to be investing in our late-stage pipeline, particularly Rina-S , Epkinly, Acasunlimab, and now moving forward Peto. This is not only in late-stage development, but it's also important investments in commercialization capabilities to prepare for Epkinly line extensions, as well as upcoming launches for both Peto and Rina-S , hopefully in 2027. Now, to reiterate some of the guidance we provided when we announced the deal, then more recently reaffirmed on our Q3 earnings call for everybody, 2026 invariably is going to be an investment year. These are important investments that are 100% in line with our investment priorities, but are also going to be driving a number of important registration trial readouts in 2026, as well as some important launches here in 2027.
In 2026, it will be an investment year. Now, we did say on our Q3 call that we feel that consensus, both from a Genmab investment level perspective as well as a Merus investment level perspective, is in a reasonable place. The other thing you should be thinking about, Genmab investment priorities are clear. Just highlighted that. On the other side of the coin, if you like, we're absolutely focused on realizing scale benefits as we move forward. Our business is fundamentally in a different place now in terms of the size and scale of our operations. That means we can be very focused now on realizing these productivity measures and scale benefits. This has been a major driver for how we landed 2024 in terms of the overall financial performance and also our year-to-date financial performance in terms of, let's call it, OpEx management.
2026 investment year, 2026 consensus from an OpEx perspective in a reasonable place. For 2027, we expect to return to meaningful growth on the EBITDA line. Now, you might be asking, why are you talking about EBITDA? Here, it's important to note, assuming successful launches or launches of both Peto and Rina-S in 2027, we will start to see some purchase price amortization in 2027. However, we expect meaningful growth on the EBITDA line of 2027. Looking at the Merus transaction, we expect to be approaching break-even on the EBITDA line. In 2029, having the transaction being highly accretive, again, on that EBITDA line, funded or fueled in part by what we expect is to be a pretty significant ramp for Peto. Here we've guided to around $1 billion or more than $1 billion of sales already in 2029.
What you have in the Genmab team really is very clear investment priorities, super focused on driving productivity measures and a really nice growth profile, both from the existing inline business as well as new potential launches starting in 2027.
Super clear. If we park Peto then and we move on to Epkinly, I want to chat a little bit on this. Perhaps set the scene, could you just touch on the commercial differentiation in the landscape that we see with Roche's bispecifics as well? Maybe if you could reference the recent outpatient study as well and how that helps the profile.
Anthony?
Yeah, so overall, we're very pleased with the Epkinly launch performance. If you think about where we're at overall, we've set the scene for Epkinly potentially being a $3 billion+ global brand. Right now, the brand has been performing very well since its launch in May of 2023 in the US. The initial approval today is in the late line setting in both third line DLBCL and third line FL. Now, we think about the recent positive data in second line follicular lymphoma and are very encouraged by the approval by the U.S. FDA. Now, it's important to note that this second line FL opportunity is an important one for the brand. It's the first positive phase III for Epkinly, now also in combination.
This is an important sort of, let's call it, qualitative aspect for the brand to get into earlier lines, to get further in towards the community. At the same time, we should be mindful that this will not be a hockey stick in terms of the sales performance in 2026, given the size of the total addressable market in second line follicular lymphoma. It's around 9,000 patients across the U.S., E.U.-5 , and Japan. We are very encouraged with what we've seen. We have a nice stepping stone here with the second line FL. We are very much looking forward to the front line diffuse large B-cell lymphoma readout in 2026. If I think about the brand overall, when we think about the target product profile, what continues to stand out, number one is Epkinly being a single option across FL and DLBCL.
Number two, the subQ delivery and really uncompromising balance of safety and efficacy. It's really that combination that really sets it up for having a very strong competitive target product profile. Moving forward, it's going to be important for us to continue to compete from a development perspective. Let's try to get those trials read out and onto market as quickly as possible, but also leverage the investments we've made commercially to continue to drive commercial performance. Overall, we're pleased with performance and look forward to some of the potential launch here in second line FL and then the front line DLBCL data next year.
If we stick on the last point then, to what extent does the later line studies read across to the earlier line studies in terms of the profile that we should be expecting? Is it fairly de-risking or is there still more to learn?
I can take that. What is very, very good for Epkinly is that actually the phase II data actually translate really, really well to the phase III data. That's what we have seen now with the second line follicular lymphoma data. The data is just stunning in second line follicular lymphoma. A hazard ratio of 0.21 means a 79% decrease in the presence of Epkinly and R² in risk reduction, risk for disease progression. That is a hazard ratio which has simply never been seen before with any other combination of medicines in that setting. It was already preluded by data presented last year at ASH in the phase II setting. It really translated really well from phase II to phase III. That is what antibodies tend to do. They tend to be very predictable.
We have very sizable phase II studies also in the frontline setting. The very important study Anthony referred to, where we combine Epkinly with R-CHOP, we have very strong phase II data last year already at ASH and also this year at ASH. We have over 20 presentations, seven oral presentations, and some of them are frontline combining with R-CHOP. We believe that there is a very good likelihood that these data will translate well into robust phase III data. Of course, you never know for sure until you've seen the data. We very much look forward to hopefully seeing this data and share them with all of you next year.
We look forward to it too. Moving on to Rina-S then. If we take a step back and think a little bit more about ADCs in general, what's important around ADCs in terms of the payload, the linker, the target? Which are the most important in terms of delivering a better efficacy and tolerability profile? How does that read across to what you're developing?
Yeah, what is super important with an ADC is that they actually, while you attach toxic payloads, that is what happens in an ADC to an antibody molecule, that you do not really change the half-life and the pharmacodynamics of the molecule. That is what is absolutely unique with Rina-S . What ProfoundBio, the company which we acquired last year in May, did with Rina-S is they combined a very good antibody with a hydrophilic linker, allowing them to attach up to eight toxin molecules per antibody molecule and then have an antibody which really had a very good half-life and very good PK/PD characteristics. What it does translate to with that molecule is it actually gives you very, very good data in the clinic efficacy-wise, but also safety-wise. It is a very clean safety profile, no ocular toxicity, no interstitial lung disease observed with Rina-S .
That is that you can actually treat patients for a very prolonged period of time because patients can actually tolerate that medicine for a much longer time, leading to deeper and more long-lasting responses. It is actually a unique molecule with perfect characteristics. I think that is, I think, leading to Rina-S becoming a potential best in class and very likely also a first in class in a much broader group of patients and tumors than the first generation of folate receptor alpha ADCs earlier here have been able to demonstrate. Another aspect of Rina-S is that it has very good what is called bystander killing activity. When it is near a tumor and the payloads are cleaved off from the antibody, they can kill bystander cells with an antigen negative. That is super important because tumors tend to be heterogeneous. They are never 100% homogeneous.
You want to kill all the cells from the cancer locally with a toxic molecule. That is what Rina-S also does really, really well. This combination is very difficult to get actually in an ADC. I think we should really be all keenly aware of, yes, there is competition building up. There are several other molecules now targeting folate receptor alpha with a toxin and a linker. They have all very different characteristics from what Rina-S is showing already at this time. That is, I think, something to be aware of, that they will not all be the same. There will be different categories for sure. I think time will tell which molecule will be the dominant medicine in a category of cancer. I think Rina-S has a very good chance now.
We already have a Breakthrough Therapy Designation in the meteoral cancer, which we got this year from the U.S. FDA. That is a type of cancer which has too low expression of folate receptor alpha. It cannot be hit by the first generation of folate receptor alpha ADCs. I think up to now, the data is just unparalleled with Rina-S. What is important for the company, Ben, is that we actually keep the momentum, that we keep executing and keep in the forefront basically of this development because other competitors are potentially moving in. I think it's too early to really categorize them in different categories at this moment.
That's very fair. Perhaps, Anthony, one for you as well. You've provided some peak sales guidance for the asset. How do you see that in terms of the balance between endometrial and ovarian? What are the key signposts we should be watching for to de-risk that and unlock that potential?
Yeah, so I guess maybe sort of starting point for Rina-S is we're very excited about the brand, what we've seen so far, and the prospects here moving forward. To just remind everybody, when we announced the deal in April of 2024, we provided kind of two pieces of guidance relevant to your question, Ben. One was that we expect a launch in 2027. And number two, that we expect peak year sales of north of $1 billion. Now, as we fast forward to today, we stand behind the 2027 potential launch date, number one. Secondly, earlier this year in January, we've upgraded that peak year sales guidance to $2 billion. That's underwritten by the data we've seen, but also underwritten by the rapid progress and expansion of the clinical data development program. Here, when we essentially bought the program, we had around 50 patients' worth of data.
We're going to exit 2025 with two registrational phase IIs and three registrational phase IIIs. Now, what is that $2 billion underwritten by? It's really underwritten by sort of four subsegments or four sub-indications. That's going to be the PROC indication. That's going to be the PSOC or platinum sensitive ovarian indication. That's going to be front line and second line endometrial cancer. Now, in terms of major events, you'd be looking forward to 2026, where we have potentially the first phase II registrational readout in the PROC indication. That's what you should really be focused on. Obviously, it will de-risk that particular opportunity. I think it'll be nice to see the data in a registrational setting and see the activity across folate receptor alpha expression level. Certainly looking forward to that in 2026.
Got it. If we move on to Acasunlimab as well, near term, we've got some additional data. Could you perhaps outline what we could expect to see in terms of types of data, obviously not the data itself, and how that could help build confidence in the program?
Absolutely, with pleasure. Last year at ASCO, we've seen very, very good data at the every six-week dosing cohort of Acasunlimab plus Pembrolizumab in the second line plus lung cancer setting. You will see more follow-up from that data to see how robust that overall survival difference, which was observed there, is actually at this moment with longer follow-up. We added an extra 20 patients. You get a much bigger cohort also at the every six-week dosing. This is the exact same dosing regimen which is used in the ongoing phase III. That will hopefully give more confidence and reassurance to the markets in believing that Acasunlimab is a very competitive potential medicine for the second line plus lung cancer setting, which is a very important setting. There's a real need for medicines there.
We have actually guided for a peak sales of around $1 billion. I get the question many times, Ben, why is it so low? Because lung cancer is so many patients. This should be a much bigger setting. The reason is we want to really give realistic peak sales guidance to the markets because there is so much competition there with the new very fancy VEGF/ PD-1, VEGF/PD-L1 type bispecifics. There are several ADCs in development in that setting. I cannot really figure out right now or anticipate what the exact distribution will be of the different medicines if they would be approved for that setting. I think it is better to be conservative and realistic at that point than to give fancy projections which everybody will look at with shiny eyes, but cannot really understand.
Very clear. One of the questions that we always have to ask, you've clearly got your hands full at the moment, lots going on in oncology, but we always have to ask about the wider thoughts about pipeline and potentially some movement into immunology and inflammation given the potential applicability of Epkinly, maybe something developing from the Argenx collaboration. What is your thinking around this in the therapeutic area? Is it something you'd like to invest more in?
We have a lot of activity in the preclinical setting and in INI area. We think that our antibody technologies are very well of use in INI, but it takes a longer time. I mean, to develop clinical candidates from scratch preclinically, you need a lot more safety data before you can actually allow to go to the clinic in the INI setting than in cancer. Oncology is a lot faster. Reality is that Genmab's activities are for over 90% in oncology and will remain in oncology because that's where we have most expertise, most track records, most momentum. We probably need to make rigorous choices in rank ordering these programs in the coming time because we have actually a wealth of late-stage programs which can attribute to most value in the shortest possible timeframe, which is, I think, more important now for Genmab. We are progressing.
We have a partnership with Regeneron, which we're really excited about in the INI setting. It is all preclinical. We will report on progress for sure, Ben, but it is actually going to be very minimal compared to what we do in oncology.
Perfect. That makes sense. I guess beyond that, then, final 30 seconds, is there anything else in the portfolio that you think is worth having a look at, or are we covering the main focus areas here?
I think we're covering the main focus areas. We have a very strong organic pipeline, which is also important not to forget because we have now done two acquisitions, one acquisition, one proposed acquisition, two years in a row, bringing in fantastic molecules. Hopefully, Rina-S is just a sensational ADC, which we are very, very impressed by. It does everything which we hoped it would do and more. Then Peto, when we can bring the Merus transaction over the finish line, is also a sensational molecule. We think very differentiated from all each of our targeted antibody molecules. We actually think that we also need to pay attention to our own organic pipeline between now and the end of the year.
We're going to move at least two more bispecifics from our own organic pipeline into the clinic and one ADC, which is a combination of a Genmab antibody and a legacy ProfoundBio payload and linker technology in a new molecule. We believe that we are also very, very capable of generating organically generating the next winners, therapeutic winners. I think that is probably where we should end up with. I see a flashing sign now that means that we need to get out of the room and make place for the next company.
Exciting stuff, lots going on. Thank you so much for your time. Appreciate both of you. Thank you all for coming.
Thank you.