All right, well, good afternoon, everybody, and thank you once again for joining us for the 45th Annual TD Cowen Healthcare Conference. I'm Yaron Werber from the Biotech team, and it's a great pleasure to moderate with my colleague, Jeanna Han, and it's a great pleasure to have Genmab with us today. With us, we have Anthony Pagano, EVP and Chief Financial Officer, and to my left is Judith Klimovsky, EVP and Chief Development Officer. Ladies and gentlemen, thank you for joining us. We appreciate it.
Yes, absolutely. A pleasure to be here.
So we have lots to talk about, Anthony. I think we're going to start with you, and we'll cover some of the BD questions and some finance questions and a little bit of strategy. And Judith, we have a lot of questions for you. Just to be ready. So, Anthony, maybe for you, as you're thinking about, you've talked a lot about P&L and the strategy about how you invest in the pipeline, how you grow the top line. You have a lot of pipelines also in early development, and I think you're also looking still for maybe external innovation as well. So, as you're thinking about it, balancing earnings growth or margins versus investment, what comes to mind?
Yeah, so again, first of all, it's great to be here today. It's a great chance to sort of reengage with all of our investors and have a nice chat here with you. Look, our capital allocation priorities are super clear. About a year ago, in February of 2024, we outlined our capital allocation framework, and we've been executing against that in a very diligent and focused way for the last year or so. Just to summarize for everybody, priority number one is investing back into our business. This gets to the heart of your question here. What do we mean by that? It's really meaningfully and purposefully reallocating our R&D investments in particular towards the late stage. Here, we now have 55% of our R&D spend being directed to our three most advanced programs. That's EPKINLY, Rina-S, and then also Acasunlimab.
This is absolutely from an R&D perspective to invest in these three phase three programs. Now here, what's important to think about in terms of the growth opportunities moving forward, there are seven ongoing phase three trials for these three programs. As we look at the opportunity set here today, we see there's absolutely more potential for each one of these to do a fair amount more moving forward. This will be absolutely our priority from an investment perspective, particularly around R&D. In terms of the earlier stage, we've scaled up our investment in research, discovery, and phase one/phase two over the last number of years. That's now in a reasonable place. Really, as we move forward, we're prioritizing more of the late-stage programs, particularly as it relates to any growth in terms of total R&D.
In terms of the other side of the coin and investment in SG&A, really, we've invested quite a bit over the last number of years to scale up here. We're increasingly focused on realizing scale opportunities, and you can see that really pull through in our 2024 numbers and our 2025 numbers, how we were able to deliver on our financial commitments. G&A is increasingly at scale, so we have limited growth there. Our growth and our investment is really focused on sales and marketing, continuing to support our brands, EPKINLY and TIVDAK, that are in the market today, but really now focusing on moving forward, laying the groundwork for Rina-S in particular in the next period of time, so if I really zoom out and really think about managing our investments is really geared towards investments that are successful, can generate meaningful revenues.
Now, to sort of round this off, really, we're really focused on making these investments to generate revenue, but also having a mind towards an eye towards the bottom line. And here you can see the very significant operating profit levels, 26% operating profit growth in 2024, followed by 16% operating growth in 2025 at the midpoint.
And do you have room to bring in another externally derived asset into late stage, the P&L room?
So the short answer is yes. We would have to clear a very high bar, but if we find the right opportunity, we're certainly not going to shy away from acting. We're not going to chase deals, to be clear. But again, if something clears our very high bar, we have both from a demonstrated track record now with how we've acquired Profound Bio, accelerated Rina-S, operational capacity, and certainly a fair amount of financial bandwidth to take on board the right late-stage program.
And you just renegotiated your agreement or you changed a little bit of the primary responsibility in TIVDAK. How does that tie into also strategically to EPKINLY in your co-marketing with Anthony?
So in terms of TIVDAK, that was the question.
Yeah, TIVDAK and co-marketing.
This was a wonderful opportunity to sit down with our partner and us to essentially reacquire or acquire the commercialization rights outside of the U.S. and in China, something that we really were proactive in and wanted to do. This was an excellent foundation and opportunity to bring TIVDAK to patients, assuming all the approvals and everything, to patients in Europe and Japan in a very kind of thoughtful, stepwise focused manner. And really what this does for us more strategically, of course, the first order is to help patients, but strategically what this will do is provide an excellent, excellent foundation for Rina-S should that be approved moving forward. There's significant synergies and significant learnings that we can apply from what we're going to be doing with TIVDAK in the next year or two that can apply to Rina-S as we move forward.
What I would give you in terms of context, remember what we said when we did the deal is that the first approval, at least in the U.S., could come in 2027. So you would expect approvals in other markets subsequent to that. So these are investments that we'd have to be making anyway to build out these markets and do some preparation work for Rina-S in any event for us. So in summary, this was really a no-brainer for Genmab to take this next step.
As you lay down commercial ops in Europe, I imagine you're going to do it in a scaled kind of version, right, based on upcoming approvals and upcoming launches and reimbursements.
Yeah, we're going to look at this in a very focused way, country by country, market by market, do what's right for patients, but also be mindful about how we're investing in terms of building out the team and the capabilities. Again, these were investments we would be making anyway for Rina-S. So this is a wonderful opportunity, again, not only to build out Europe from scratch. We've demonstrated our ability to do that successfully in the United States, in Japan. Now we get a chance to do this in Europe. And then in Japan, in terms of TIVDAK, we'll be able to leverage to a very significant degree some of the investments we've made in our commercialization capabilities there. So something we're really excited about here as we get into 2025 and beyond.
Maybe there's a lot of talk about on the pipeline, but I do want to maybe ask one question on 3014. I think J&J has, I think it was 60 days from when they accepted. So essentially this week or next week to hear a decision. Is my timing sort of correct? And then secondly, from everything you've said, and I think some of the things they've said, it sounds like increasingly likely that you're obviously designing your business with the assumption that they're probably not going to, that's upside to your plan. Is that sort of fair? And the writing on the wall is that we're all expecting that they're probably not going to bring that forward. I don't know if you can comment at all.
I think as everybody knows who's followed the company, we outlined the overall process and timeline in a fair amount of detail. What I can say is we're on track to execute against that. Certainly, we expect, and there will be a decision here in Q1. All I can leave you with today is that we're absolutely on track against that overall Q1 timeline. Once the decision is made, we'll have more to say at this point. I can't really add anything else. I certainly appreciate the interest in the question, but at this point, nothing else I can add.
No matter what the decision is at that point, you will release the data and outline next steps? Or they will release the data and outline next steps?
So once the decision is made, we will have a company announcement/press release where we'll outline the top line data and look to provide as much information we can at that point in time.
Actually, maybe I'll proceed next and I'll turn it over to Jeanna on EPKINLY. Judith, maybe a couple of questions for you. There's going to be a lot of data coming next year, right? Three phase three studies with EPKINLY across both DLBCL and FL. Maybe do you have a sense how that data is going to come out? Which study might you think might come first just based on enrollment and your expectations?
Yeah, so what we say is that by the end of 2026, three major phase three studies will be rolled out in addition to the confirmatory study. We didn't give more color, and so we'll stay with what we said. But I want to elaborate on the data sets as they are relevant for patients. So in addition to the confirmatory study, we expect two studies, phase three, in the second line, one in DLBCL in combination with lenalidomide and one in FL in combination with R2. And in addition, the first line in DLBCL in combination with R-CHOP, where we presented the two years follow-up of the proof of concept in ASH this year. So we are excited of the opportunity to expand on the potential for EPKINLY to earlier lines in FL and DLBCL.
And when you think, Judith, on the cadence, I mean, the second line follicular, that's EPKINLY plus or minus R squared, right? Maybe just to orient everybody. There's a first line DLBCL study, EPKINLY with R-CHOP, and then there's a second line DLBCL study, EPKINLY head-to-head against standard of care. The primary is PFS.
Yeah, so there are different endpoints. So let's start with the Epco second line in FL. The primary is PFS. There are two studies in the second, third line in DLBCL, one in combination with LEN and the other one as a single agent vis-à-vis standard of care with GemOx. The primary is PFS and OS because it's just more advanced. And in first line, DLBCL, the primary is PFS.
To file on the primary that's co-primary and PFS and survival, do you need mature survival data or can you file with a trend on OS?
Yeah, it's in the first line you are talking about. So survival takes much more longer. So PFS with a reasonable trend could be enough. And like the last approval in the first line met PFS and it didn't meet OS, which is the POLARIX for POLIVY. So in the first line, DLBCL, the primary is PFS. Of course, if you have OS in the other direction, you have a problem.
Do you have sufficient power in the second line setting for OS?
We have. Our studies are powered for primary and then you carry on the alpha for secondary as well.
Are patients allowed to do crossover once they hit PFS?
Sorry?
In the second line setting, if once you hit the PFS, is there a crossover?
No, we don't allow to crossover. The studies don't allow for the crossover because it's not approved. So the studies don't have crossover built in.
Patients will go on to next best supportive care at that point.
Correct.
Theoretically, they can go into a CAR-T at that point?
They can go to bispecific, they can go to a CAR-T, but there is no crossover built in the studies.
Okay. Got it. And maybe just a quick question about commercially right now, how has the uptake been in follicular since the approval?
So as we know, we're co-commercializing with AbbVie, in particular in the U.S. where it was approved last summer. We're very pleased with the uptake in FL post-approval. What really seems to be resonating in the marketplace is a single option across FL and DLBCL. And for the FL label, as you know, there's no hospitalization requirement. So this has been, I think, overall an opportunity to kind of re-engage with the healthcare professionals around this new data set. And this is, as we think about the revenue trajectory for 2025, the annualization of the FL in the U.S. is a driver of the revenue growth. And likewise now in Japan, with the recent approval, having Japan FL as a label as well, which is really important.
Are most physicians following the label and treating through progressions, or are they doing fixed duration, or is it going to be a combination?
I can take it, so the label is treatment till progression in this very setting, which is second line plus FL or DLBCL. We show data at ASH. It's posted by Dr. Liao, which clearly, like doing modeling on simulation, portrays the case where treatment till progression is meaningful, particularly for a subset of patients with certain characteristics like bulky disease or that they don't have a very rapid tumor shrinkage or have positive CT DNA at the end of treatment, so those patients, and we model, it's very beautiful that you see that if you stop, the patients will progress, so I think that in talking with physicians that treat those patients, they are using a fit for purpose approach and they are really satisfied with the label that allows them to choose a kind of more personalized approach.
And we show this data as well, even in DLBCL, like patients that decide to go to transplant, so they stop, or patients that decide to take like a pause and then they can start and we show data. So, I think that the label as it is gives versatility to make decisions in a personalized fashion.
I think that maybe last question on EPKINLY, you're also studying outpatient dosing. Can you talk about what those studies? I mean, I think outpatient is now your standard, right, in all future studies and ongoing studies?
So we have an ongoing study that focuses in community centers. So by design, chose community sites and we call it outpatient study because it doesn't require patients to be hospitalized like after the initial indication with a single day on day 15. We will expect to present data of this study later this year. And this could be the basis for potentially modifying the label just to remove the day 15, but just as a clarification, the ongoing phase three studies don't mandate hospitalization.
Okay. Jane, over to you.
Great. Thanks, Jerome. I want to ask a little bit more on RINA-S. I know that as you've mentioned, you've really accelerated this program since you had the ProfoundBio acquisition. Right now, you have a phase three trial that's already ongoing in second-line PROC. It's enrolling all comers regardless of FR alpha expression, even kind of Elahere exposed patients, and you're going to have a second trial in second-line endometrial cancer starting at the end of this year, so for the first trial in PROC, PFS is the primary endpoint, but I was wondering if it's possible to kind of accelerate the approval process with ORR or DOR as an endpoint.
Yeah. So of course, it's data dependent, but an example that you can think about it, just to give context, is mirvetuximab. So Elahere was based on accelerated approval based on a study called Soraya that was a phase two with 100 patients with a response rate of 32% and a median duration of response of 6.9 months. So there is still an unmet medical need in PROC. So there could be an opportunity data dependent if the ORR and the duration is meaningful and we meet with the criteria of having a phase three underway for potential accelerated. So our commitment is to launch on 2027 and we have the PCs in place to launch in 2027.
Yeah, it makes a lot of sense. You referenced some of the previous data, obviously from Elahere. What do you think is the efficacy bar for success in PROC in light of competition, obviously from existing agents and also from a lot of other FR alpha targeting agents in development right now?
So for RINA, we don't preselect based on expression on folate receptor. So let's start just to level the ground. In PROC, more than 90% of patients have some level of folate receptor expression. From them, 30% are what we call high, which is above 75 to plus IHC. Around 40% are what we call medium, which is from 25 to 75, and around 25% below 25%, which is the low. What we have seen in our data and showed in the medical conference is that RINA-S works regardless of 75 above and below, and we saw activity even in the below 25%. So we are very comfortable with the activity across the board, and you will understand the activity vis-à-vis expression when we share the data in endometrial, where in endometrial, the presence of folate receptor is quite prevalent, around 70%, although the expression is lower.
And you saw this from data, for example, from Sutro, which is another folate receptor, but the ORR is 25%. But we don't preselect because we don't need to. And we don't need to because of our ADC, RINA-S, which has a linker that allows for a very high DAR 8, which is a very good bystander effect. And we saw it not just in folate receptor, but in a model of HER2, very compelling preclinical data that talks that this is a sort that can work across the whole spectrum of expression.
Right. And then you said that we'll be seeing data in endometrial cancer in the first half of this year. Can you give us any insight into how many patients, how much follow-up we're going to have with this data cut, and then kind of what about this data that you've seen already drove your enthusiasm to start this or to go ahead with a phase 3?
Yeah, so the data that you will see, I mean, I cannot provide numbers because we haven't shared, but it's the data set that allowed us to select the recommended phase two, three dose, so we follow the FDA requirement as per Optimus, and we enrolled into a subset of different doses, and this is the data set that you will see. I cannot share the data, but we are very encouraged of the data, and just for you to know a benchmark, all the patients in the study were after receiving a checkpoint inhibitor and chemotherapy. In that very setting, the standard of care is single agent chemotherapy, and the overall response rate is 15%, 15% with a median PFS 3.9. This is the standard of care, and you will see our data when we present it in a public medical conference.
Great, and I know you're also pursuing a couple of combination strategies here. You have some cohorts ongoing with carboplatin, with bevacizumab, with also PD-1. When can we start to see these kind of combo data emerge?
Yeah, so we have three combination cohorts with bevacizumab in PSOC and PROC, with Carbo in PSOC, and with Pembro in endometrial. Those are actively accruing, and usually, when we get to the number of patients and we have ORR, we put this data in the public domain. We don't have clarity on when it will be, so we didn't share, but we will share as soon as we have this data.
Got it. And if you look at indications, obviously you're looking in PROC, you're looking in PSOC, you're looking in endometrial. Kind of beyond that, I know that there's a lot of tumors that express folate receptor alpha. Where are you thinking of kind of next steps in terms of tumor type?
Yeah. So at PROC, and we mentioned already, we will present the ORR at the recommended phase 2, 50%. In the very next conference, we will present durability, which is critical as well. For endometrial, we talk. We are also actively enrolling in non-small-cell lung cancer, EGFR-positive, and this cohort is ongoing. And potential additional opportunities for us to open additional cohorts are non-small-cell lung cancer, non-EGFR, where the expression is not as high, but very prevalent, and triple-negative breast cancer, where the expression is around 70%.
Got it. And then I know that Rina-S has been the real focus of your ProfoundBio acquisition, but you have a lot of other kind of pipeline candidates that came into your pipeline. Where are these in development? What are you excited about in terms of these other candidates?
Yeah. So there is some data in the public domain on those ADCs that we acquire with ProfoundBio. They're actively enrolling. So we have PTK7 targeting CD70, LITARK6, and EGFR/c- Met, and all of those are in phase one.
For the CD70, are you looking at, I imagine you're not looking at AML, I imagine you're looking at solid tumors?
Yeah. So still, it's in dose escalation, so we cannot talk, but the target for CD70 is more lymphomas. And again, the study is in dose escalation as we speak.
How do you decide, or back maybe then, how did Profound decide whether to use an MMAE or a topo or a different payload?
Yes. So it's a good question. So the linkers or the family of linkers that we acquired when we acquired ProfoundBio gives the opportunity. It's a cysteine-linked, so you can link not only topo, but other payloads. So based on the indication, the sensitivity to tubulin, it was decided whether to go to an MMAE, and we have an MMAE with PTK7 or topo. But the idea was that with these linkers, you can have a very diverse family of payloads.
Great. And then to hit the last of your trifecta of late-stage assets, I want to ask about acasanlimab. Kind of where are you? You have the phase 2 update that's coming in 2025. Can you give us a little more timeline on granularity where in 2025? What can we expect to see in the data?
Yeah. And it was clear, but I will be more clear. So what we presented at ASCO, when we presented acasunlimab and what encouraged us to start the phase three was the overall survival data particularly in Arm C that was the every six weeks GEN-1046 in combination with Pembro. Subsequently, we presented PKPD data and exposure data where we showed that the every six weeks has a biological reason on why it behaves differently than every three weeks, but was based on that data set. Now, when we presented that data set, the median overall survival was 17 months, but there were 29 patients ongoing. So what we want to assess is the durability, and there was some censoring because around seven or eight patients were below before the median. So what we need to see is the duration of this overall survival as these censored patients mature.
This is the data that we will present in the second half of this year.
Great. I know that you had really, really good overall survival in your initial cut. Even if there's a little decrement to overall survival, as long as you're kind of significantly better than docetaxel, do you think that would still be a success for you?
You are correct. I mean, but data is data. So we will look at the data. We will see how it goes. We know that docetaxel is 10-11 months, so we know what the benchmark is. And of course, we expect the data to validate our hypotheses.
Great. And a couple of kind of other pipeline assets. Do you have any comments on the Mim8 asset in hemophilia, just given that Novo is planning to file in the U.S. and EU in the second half of this year?
No, so what I know is like Mim8 is what is in the public domain, that the FRONTIER two and three were positive and they plan to file. We don't know more than that.
Maybe for Anthony, just remind us what the royalty rate that you do on Mim8?
Yeah, so just to kind of orient everybody, we have a number of royalty medicines come with varying royalty rates, so this one we're talking about is Mim8, which is a royalty license we have with Novo Nordisk, and here it's mid-single digits.
Is it graded or it's fairly flat?
It's graded. I think what's sort of interesting there, though, if you think about the totality of the royalty business, there's obviously DARZALEX, which gets a lot of attention, but in addition to DARZALEX, there's five additional products. Kesimpta is already a very significant product. The three bispecifics with Janssen, and then you also have TEPEZZA with Amgen. There's this product that's had cleared phase three. There's a number of other programs that are also in phase three or beyond. So there is a very nice royalty business, but of course, what we're doing is taking all of those revenues and profits and investing back into our exciting pipeline.
Yeah, well, terrific. Judith, thank you for coming. I owe you an apology. I think I called you Julie. I'm so sorry. It's great to see you. Thank you for joining, and Anthony, thank you for joining. I really appreciate it.
Absolutely. Our pleasure. Thank you. Thank you, and it's great to see Andrew. Thank you for coming.