Hello, and welcome to the Genmab third quarter 2026 financial results conference call. As a reminder, this conference call is being recorded. During this telephone conference, you may be presented with forward-looking statements that include words such as beliefs, anticipates, plans, or expects. Actual results may differ materially, for example, as a result of delayed or unsuccessful development projects. Genmab is not under any obligation to update statements regarding the future, nor to confirm such statements in relations to actual results, unless this is required by law. Today's presentation will also include comments on certain non-IFRS financial measures, which management uses to describe the company's baseline performance, and which supplement but do not substitute for the comparable IFRS measures. We encourage you to review our full financial statements and publicly filed reports, and not to rely on any single financial measure.
Please also note that Genmab may hold your personal data as indicated by you as a part of our investor relations outreach activities in order to update you on Genmab going forward. Please refer to our website for more information on Genmab and our privacy policy. I would now like to hand the conference over to our first speaker today, Jan van de Winkel. Please go ahead.
Good to have you all with us, and welcome to Genmab's results call for the first nine months of 2026. Joining me are our Chief Financial Officer, Anthony Pagano, and our Chief Commercial Officer, Brad Bailey. Our Chief Medical Officer, Tahi Ahmadi, and Chief Development Officer, Judith Klimovsky, will both join us for the Q&A. As the operator said, we will be making forward-looking statements, so please keep that in mind during the call. This has been a landmark stretch for Genmab, and I'm delighted to share it with you. Let's start with the numbers. Our total revenue is up 22%, with growth coming from across our portfolio. We have continued to manage our investments thoughtfully and strategically, allowing us to grow our adjusted operating profit by 9%. Growth and profitability together are certainly a sign of a healthy, high-quality business.
But the product development news is what has me most energized. October was a truly unprecedented month in our history, with three milestone phase III readouts, all with the potential to change how patients are treated. Three strengths stand behind these results: our expertise in antibody science and oncology, our ability to evaluate innovation, and our speed of execution. You can see all three in these programs. We acquired Rina-S in May 2024 when it was a single phase I/II trial. Two and a half years later, it has a positive phase III and a broad phase III program across ovarian and endometrial cancers. We acquired petosemtamab last December, and less than 11 months after closing, it too has a positive phase III and a growing phase III program. Epkinly, an antibody created by Genmab and co-developed with AbbVie, has delivered three phase III readouts this year.
We said these therapies had substantial promise, and the phase III data have now confirmed it. In each case, the phase III result is consistent with the phase II data that led us there. Let me turn to the next slide to remind you of this remarkable phase III data and what it means for us going forward. Last week, we held a call summarizing the important phase III datasets that we announced in October. You can listen to a replay of that call through our website, so I will keep this brief and focus on what it means for us. First, EPKINLY. The EPCORE DLBCL-2 trial, which met its progression-free survival endpoint with a hazard ratio of 0.49, demonstrated that EPKINLY has the potential to change how frontline diffuse large B-cell lymphoma is treated after more than two decades of R-CHOP as the standard.
Expanding into frontline supports EPKINLY's potential to become the core therapy in B-cell malignancies. Second, Rina-S. Our ambition is for Rina-S to be the best, first, and broadest in class. The RAINFOL-02 trial, which met both its primary endpoint of progression-free survival with a hazard ratio of 0.29 in the intent-to-treat population and the key secondary endpoint of overall survival, supports that ambition with efficacy irrespective of folate receptor alpha expression level or previous mirvetuximab. Platinum-resistant ovarian cancer is just our first potential launch. With our established global presence in recurrent or metastatic cervical cancer, the breadth of our Rina-S program across ovarian and endometrial cancers positions us well to lead innovation in the gyn-onc space. Third, petosemtamab.
The LiGeR-HN1 trial, which met its dual endpoints of overall survival with a hazard ratio of 0.5, as well as objective response rate, anchors the program in first-line head and neck cancer. This will be followed by our next milestone, the LiGeR-HN2 trial in the second and third-line setting, which we expect in the first quarter of 2027. With two phase III trials underway, we are already expanding into colorectal cancer, which is another area of significant unmet need. Given the global capabilities that we have built, I have no doubt that we are well-prepared to continue to maximize the potential of all three of these programs with successful commercialization if approved. Now let me pass on to Brad to talk more about this and how our currently commercialized medicines, EPKINLY and TIVDAK, are doing in the market. Brad, the floor is yours.
Thanks, Jan. Our proprietary medicines continue to perform extremely well, with EPKINLY and TIVDAK reaching more patients around the world. These results reflect the strength of our antibody science and effective execution by our teams to increase treatment adoption, broaden access, and expand into new markets. Together with the late-stage progress Jan shared earlier, this performance puts us in a strong position to close out 2026 and deliver on our next phase of growth. EPKINLY is the most prescribed bispecific antibody in lymphoma globally, and we are building on that leadership. Sales grew to $491 million in the first nine months, representing a 47% increase year-over-year. In the U.S., EPKINLY continues to grow across indications and sites of care, particularly in the community, where its differentiated dual indication profile is resonating with physicians.
During the quarter, we increased the number of sites ordering EPKINLY and expanded adoption among existing accounts, with more than 97% of key customers now ordering from two or more sites. We are especially pleased with the uptake of chemo-free, fixed-duration EPKINLY plus R² in second-line FL, which is now considered the standard of care in this setting. This uptake is broadening physician experience with EPKINLY, driving increased utilization across both FL and DLBCL, and bringing bispecific-based treatment to sites closer to where patients live. Outside the U.S., EPKINLY continues to perform very well. In Japan, the launch of EPKINLY plus R² in second-line FL is off to an encouraging start, building on EPKINLY's established presence in the market. Through our partner AbbVie, this combination is also approved in more than 40 countries, creating opportunities to reach more eligible patients.
For the rest of this year, our focus is on maximizing these opportunities, particularly in the U.S. and Japan, where we book sales, while preparing for anticipated launches in early lines of DLBCL as soon as next year. Moving to TIVDAK, sales totaled $131 million in the first nine months, which is an increase of 9% year-over-year. This reflects strong, stable performance in the U.S. and continued growth in our launch markets in Japan and Europe, driven by effective field execution and expanding site activation. TIVDAK is now approved and reimbursed in multiple countries, with additional reimbursement discussions underway. This expansion is bringing TIVDAK to more patients while strengthening the local market knowledge, customer relationships, and access capabilities that will help drive our success with Rina-S and petosemtamab in the future.
Looking ahead, our focus is on translating progress in our late-stage portfolio into well-executed launches and access for patients. For EPKINLY, first-line DLBCL represents a substantial opportunity to reach patients at the start of treatment and potentially advance the standard of care. The broad physician network and treatment experience we are building today in EPKINLY's approved indications across sites of care serves as strong foundation as we prepare to expand into earlier lines of DLBCL. If approved, EPKINLY plus R-CHOP would significantly expand EPKINLY's role in lymphoma treatment and move us closer to our ambition of establishing EPKINLY as the core therapy in B-cell malignancies. For Rina-S, the positive RAINFOL-02 results represent an important step forward for patients with platinum-resistant ovarian cancer who face limited options and poor outcomes.
If approved, Rina-S would become our second medicine in gynecologic cancer and advance our ambition to become the recognized leader in this space. Our proven experience with TIVDAK gives us an established understanding of gynecologic cancer care and longstanding relationships with physicians and care teams to set a strong foundation for our work with Rina-S in the future. Lastly, as Jan shared, LiGeR-HN1 was the first positive phase III trial in first-line head and neck cancer in nearly a decade. If approved, petosemtamab will broaden our solid tumor portfolio and could offer an important new treatment option for patients in a setting where progress has been long overdue.
Over the last several years, we've built a commercialization engine across key markets designed to scale with our portfolio and support the growth ahead, pairing deep antibody and oncology expertise with local market insights and data to differentiate our medicines, secure broad access, and drive successful launches. Our field teams bring these capabilities together with a highly coordinated and seamless engagement plan for care teams and customers, supporting broad uptake and utilization. As we close out 2026 and look towards 2027, we're in a strong position, driving growth from our approved medicines, advancing readiness for anticipated launches next year, and turning the strength of our science into sustained growth and meaningful impact for more patients. With that, I'll turn it over to Anthony to walk you through the financials.
Thanks, Brad. The first nine months of 2026 demonstrated the continued strength of our business, with revenue growing 22% year-over-year. I'd highlight two characteristics of our performance. First, the high level of the growth, and second, the broad-based nature of that growth. Starting with the high growth, DARZALEX increased 19% year- over-y ear, while worldwide EPKINLY net product sales increased 47%, reflecting continued commercial momentum and strong execution. Beyond these two brands, the remainder of our portfolio increased 30% year- over- year. Turning to broad-based growth, approximately half of our year-over-year revenue growth came from DARZALEX. Impressively, the other half was generated by EPKINLY and the remainder of our portfolio. Taken together, these results demonstrate that our business is becoming more diversified and more durable.
That evolution continues to strengthen the quality of our revenue base, and this strength provides us with the financial flexibility to continue investing behind our highest value growth opportunities. This includes launch readiness for EPKINLY, Rina-S, and petosemtamab, as well as the ability to broaden the development for both of our wholly owned programs. As you know, we currently have nine ongoing phase III trials for Rina-S and petosemtamab, with more announced or in development. Even with this investment, we grew adjusted operating profit by 9%. So together, our results demonstrate that Genmab can increase investment while continuing to expand profitability. Now, let me briefly comment on tax. Our effective tax rate for the first nine months was 3.4%, primarily reflecting the ongoing integration of Merus and related recognition and utilization of deferred tax assets.
As we previously discussed, our effective tax rate may continue to fluctuate as those integration activities progress. We expect our effective tax rate will normalize over the next 12- 18 months. With that, let me turn to our 2026 financial guidance. We remain on track to achieve our 2026 guidance, which we are maintaining, with strong revenue growth and strong profitability. We expect our revenue to be in the range of around $4.325 billion-$4.525 billion, delivering a robust 19% growth at the midpoint. It's EPKINLY and the continued momentum in our royalty portfolio that's driving that growth. Given our performance through the first nine months, we now expect revenue to be in the upper part of that range.
For operating expenses, our full-year investment plan has not changed, so we still expect to be in a range around $2.81 billion-$2.95 billion, and we expect to be around that midpoint of $2.88 billion. We expect Q4 OpEx to step up significantly because we have substantial activity planned in the fourth quarter, including manufacturing, clinical development, and launch readiness for Rina-S and petosemtamab. I would caution against taking down your 2026 OpEx figures as a result of our first nine months. Putting all this together, we are planning for adjusted operating profit in a range between $1.065 billion- $1.35 billion, with the midpoint of our guidance amounting to over $1.2 billion. With revenue in the upper part of the range and OpEx around the midpoint, we expect our operating profit to end above that midpoint.
Our guidance highlights our continued strategic discipline, with revenue growth funding targeted investments in petosemtamab, Rina-S, and launch readiness, all while maintaining strong profitability. Finally, before I conclude, I would like to take a minute to look ahead to 2027. While, of course, our guidance will be given in February next year, as I stand here today, 2027 consensus expectations for OpEx on Bloomberg and FactSet appear to be in a reasonable place, capturing our investment priorities. Importantly, we remain confident that Genmab will deliver strong profitability both in 2026 and continued growth in 2027. In summary, our performance in the first nine months of 2026 underscores our ability to produce high-quality revenue growth, advance our late-stage pipeline, and maintain strong profitability through disciplined execution. Together, this positions us well to deliver sustained growth and long-term value creation. Jan, back over to you.
Thank you, Anthony. This brings us to our final slide. It has already been a remarkable year for Genmab, both for our science and our financials. I can summarize this with three themes. The first is our sustained financial growth based on revenue from our portfolio, including significant contributions from EPKINLY. The second is our high-potential late-stage pipeline, where we have had unprecedented phase III readouts across EPKINLY, Rina-S, and petosemtamab, setting up potential launches in 2027 and multi-billion dollar peak sales potential. Finally, our disciplined capital allocation. We are investing in our high-impact late-stage programs with broad clinical development and launch readiness, all while sticking to our goal of gross leverage below 3x by the end of next year. In short, we have three high-quality late-stage programs, a broadening revenue base, and more catalysts still to come.
All of this gives us real momentum as we head into the next decade. As we move forward to the end of the year, I could not be more energized about our future, both in 2027 and beyond. That concludes our prepared remarks. Before we move to Q&A, I am pleased to announce that we will hold our annual virtual R&D update and ASH data review event on December 16. Details will be available on our website, and with over 20 accepted abstracts, including six oral presentations, we look forward to a lively event. With that, thank you for listening. Operator, we are now ready for questions.
Thank you. Dear participants, as a reminder, if you wish to ask a question, please press star, one on your telephone keypad and wait for your name to be announced. To withdraw a question, please press star, one, and one again. Please stand by while we compile the Q&A roster. This will take a few moments. Now we are going to take our first question, and it comes to the line of Benjamin Jackson from Jefferies. Your line is open. Please ask your question.
Brilliant. Thanks for the question, guys. Can I just start on the ASH abstract for DLBCL4, please? Just interested if there is any color you can add around what you are seeing or thinking about with regards to that OS hazard ratio that obviously shows no detriment to the patients. But is this something similar to what we saw in and around the DLBCL1 trial, where we need to adjust for any COVID-related deaths or subsequent therapies? How do you see this reading across to the first-line trial? Is it just a factor of the short or very short follow-up compared to the other trials that we see in this space? Is this something that ultimately you will need to show a statistically significant OS benefit in one of these two trials to be confirmatory across the board?
So, any thoughts in and around the OS side of that as well? Then also, just as a follow-up, on the safety side, slight increase in that trial in and around grade 5 events. Is there any color you can add here? Is this COVID-related again, or is something else at play? Thank you.
Thanks, Ben. You very cleverly, I think, put three questions under the first one. That is the ASH abstracts, and then the safety one is an extra question. So, we will ask Tahi to start, and then Judith can chip in, and you can add further color. Tahi?
Yeah, thank you, Jan, and thank you, Benjamin. There are probably five questions in there, so we're going to take them one at a time. As it relates to the OS for the 04 trial, I think you already alluded to it. The median follow-up on that trial, driven by the impressive hazard ratio on the PFS side that triggered the readout, was 10 months. If you just think about the cross-comparison to 05 or the Glofit GemOx study, the follow-up there was more like towards 28- 30 months. From that, you can just already appreciate that this is totally immature, so very few events. As it relates to COVID is not necessarily an issue anymore. These trials were run post the COVID phase.
But of course, the availability of bispecifics and CARs, so the next available lymphoma treatment, does, to a degree, play a role. We're still very confident that this hazard ratio will continue to actually improve and actually show a benefit for EPKINLY. So, we'll have to just wait for that follow-up. As it relates to confirmatory trial, I think it's fair to say at this point that the frontline epcoritamab phase III, with an overwhelming positive PFS, will function as our regulatory, from a regulatory point, as our confirmatory trial. That was the second question that you had. The third one was on safety. You correctly noted that there were a few death events on the EPKINLY arm, also on the control arm. But there's really no isolated signal. This is really multifactorial, and it's a relatively small number of patients.
There are all kinds of different factors that play a role there. So, we stand behind the conclusion that really the trial didn't show any new safety signals, and I think it will be better appreciated when the data is actually presented in its totality at ASH. I hope I touched on all of the questions.
Yes, that's brilliant. Thank you very much.
Thanks, Tahi. Thanks, Ben, for the question. Let's move to the next question.
Yes, of course. Now we are going to take the question from the line of Charlie Haywood from Bank of America. Your line is open. Please ask your question.
Charlie Haywood, Bank of America. Thanks for taking the question. I have two, please. The first one is just looking ahead to potential launches for these assets and how, on peto specifically, I think your prior commentary was a billion-dollar sales by 2029. I was just wondering, obviously, you have hit OS at interim, which I imagine was more of an upside scenario. So how has that informed confidence to reach that status by 2029? Then the second question, just on your two phase III readout or your fileable readouts coming next year. So peto second, third line head and neck, and then Rina-S second line endometrial. I guess both optically smaller ops than the recent anchor readouts you have had, but both broader halo potential for the assets you have got.
So, OS benefit for peto across potentially first line, second line, and third line, and then Rina-S ovarian and endometrial. How do you view the commercial importance and the potential halo effect of those two indications? Thank you.
Thanks, Charlie. Brad, can you start off with both questions, and then Anthony can potentially chip in also as it relates to the sales in 2029 to provide further color if needed. Brad, maybe you can start.
Yeah, no, thanks, Jan, and thank you for the question. As we look ahead, obviously, oncology in general is a data-driven market and a very competitive market, but also extremely data-driven. We are confident in the data that we have seen to date for all the assets, as you mentioned across your questions. We are confident also in the capabilities we have built at this point to bring our medicines to market. We really built our commercialization capabilities with all of this in mind over the last few years, and certainly with this level of growth and expansion, looking to differentiate in these spaces. We evaluate the markets with multiple sources overall and feel confident in the guidance we have provided thus far.
As we get into the data further with the presentations, as we have stated, upcoming medical congress next year, we will be able to provide further color on that as we move forward.
Thanks, Brad. Anthony, you want to give further color?
Yeah. Yeah, thanks, Charlie. Look, we've been super clear. We had high conviction. I was really zooming in on petosem, that's petosemtamab. We had high conviction in petosemtamab in October. We backed it up with the really super strong phase III results, including the OS that you referenced. We stand fully behind the peak year sales estimate for petosemtamab at multi-billion, and we stand fully behind that $1 billion number for 2029. Yeah, really feel like on the heels of this data, Charlie, we're well-positioned here moving forward.
Great. Thank you.
Thanks, Charlie.
Now we're going to take our next question. The question comes from the line of Zain Ebrahim from JP Morgan. Your line is open. Please ask your question.
Hello. Thanks for taking the question. Zain Ebrahim, JP Morgan. Two from me as well. First question is on peto and just how we should think about the duration of treatment that you're expecting to see from a modeling perspective. I think in the phase II, you showed median progression-free survival of about nine months, but based on the phase III results, you're effectively doubling overall survival. Could we see potentially longer duration of therapy than that progression-free survival nine-month point? My second question is on EPKINLY and how we should think about the pace of the rollout in first-line DLBCL and second-line DLBCL pending approval next year. Given the strength of the data, particularly in first line, could you see blockbuster sales for EPKINLY next year?
Thanks, Zain, for the questions. Maybe, Tahi, you can start with the peto duration of response question. I don't know how much detail we can give here, but you can potentially give some perspective. Then Brad, maybe you can talk about the launches and the rollout of epco in the frontline DLBCL and further.
Yeah. Thank you, Jan, and thank you, Zain, for the question. Now, of course, as I'm sure you all understand, we're not going to be able to get at this point into a nuanced discussion around duration of treatment and any kind of detailed discussion on the data until we have it in the public domain. I think it's important to step back, though, as you also were alluding to in the question, to remind ourselves that from a pure odds ratio on response, and then particularly on the OS hazard ratio, what we're looking at is really like a transformative study, and we're really excited to show the totality of the data in the context of the patients that were enrolled. Then we can have these nuanced discussions around modeling, duration of treatment, and these things.
Thanks, Tahi. Brad, maybe a bit on the rollout of EPKINLY in the different settings.
Yeah, no, thanks. Thank you for the question. We have said for quite some time, the largest opportunity is obviously as we move into earlier lines of therapy, specifically in frontline, and where the majority of the patients we know are treated in the community, and intent of treatment is curative. The market is already moving, I think, as we know, from R-CHOP to these R-CHOP combinations. It is also long-stated that we believe bispecifics can really build on this R-CHOP and emerge as the new standard. The top-line data at this point validate this position in the rollout of EPKINLY plus R-CHOP could play. We feel extremely confident again in the data for EPKINLY.
We have built the capabilities all along to prepare for earlier lines of therapy as it relates to our infrastructure, and we expect strong uptake at launch, primarily with academics, and then certainly moving into the community as more sites gain experience, as we are already seeing, and a bit of a proof point with the second-line FL launch from around this same time last year. That has driven the primary part of our uptake thus far. So, we expect strong uptake and look forward to sharing more as we move further.
Thank you, Brad. As you said before, data is the currency in oncology, Zain, and what we hope is that we can actually present the data of the frontline study with epcoritamab quite quickly and show how fantastic that data is so that launch will be even quicker once it is on the market.
Very okay. Thanks a lot.
Let's move to the next question, operator.
Yes, of course. The question comes line of Romy O'Connor from Van Lanschot Kempen. Your line is open. Please ask your question.
Hi, this is Romy. Thank you for taking my questions. Maybe just following on to the previous one. So, with the potential long treatment duration that we might see with petosemtamab, just wondering how you're thinking of the subcutaneous formulation and how advanced along is that? Looking at the frontline DLBCL space, so following the positive data that we saw, how should we be thinking about the positioning of EPKINLY and R-CHOP against, for example, Pola-R-CHP? Do you anticipate more of a broad adoption, or could treatment decisions be dependent on risk characteristics, for example? Thank you.
Thanks, Romy. The first question can be on the subcu. Maybe Tahi can start with that, and then also handle the second question on the competition and the positioning versus Pola-R-CHP in frontline diffuse large B-cell lymphoma. Tahi, maybe you can start.
Yeah. So, on the peto question first, look, I mean, we obviously started, I think the deal with Halozyme was announced in the midst of the closure period of the acquisition of Merus. So we've been working on subcu. We have always understood subcu to be an important lifecycle management component. And that's probably where we have to leave it at this point for a variety of reasons. On the epcoritamab question, this question comes up a lot, and I think that it's good to step back for a moment. So first off, R-CHOP EPKINLY has a ratio of 0.49. This word unprecedented, that gets sometimes overused, but this is literally a trial at a scale of positivity that has not been seen in diffuse large B-cell for a quarter of a century.
So what that also means, even without having a discussion on the nuanced data, is that when you have an effect size of that scale, that it probably will have an impact on a number of populations. So where you can tell the difference in hazard ratio between three to five to two to five was nonexistent, which basically means that the hazard ratio of two mimics the hazard ratio of the three to five population. That in and of itself is already a significant differentiator. And then there are other subgroup populations that you could think about as it relates to the original Pola-R-CHP dataset from POLARIX that led to the approval. So I think that's the first differentiator that's important. The second part that is important is, well, we're here today, right. We have a phase III.
The Glofit Pola-R-CHP study is going to read out sometime in the future. I think Roche guides towards the end of next year. So there is a significant time advantage, and that is an important one. I think the third part that sometimes gets also not really appreciated is that from the beginning, what we discussed, and Brad touched on this, the vast majority of these patients get treated in the community. And in the community, R-CHOP is the standard of care. That's something that physicians in the community are comfortable with for 25+ years . The subcu administration is a differentiator for the community. Dual indication is a differentiator in the community. And so these things all are important aspects. Not to have two marketed products within a regimen, plausible in certain cost-conscious markets.
And then the last part is, if you actually look at the most recent ASH abstract that just got released by Roche, that's something that we also talked many, many years ago already. There might be actually a ceiling that is determined by CD3, CD20, that is then determining how high you can go in the efficacy in terms of CR, because there is really no difference between R-CHOP, Glofit, and R-CHP, Glofit. So I think that kind of summarizes how we think about it. We feel very comfortable with the positioning of where we are. We're super excited to share this data as soon as we get the opportunity to, and then we'll have more detailed conversations.
Thank you, Tahi.
Thank you.
Thanks, Romy.
Thank you. Now we're going to take our next question. The question comes line of Asthika Goonewardene from Leerink. Your line is open. Please ask your question.
Hi, everyone. This is Karina for Asthika. Congrats on all the data. I had a question for Rina-S. SAC-TMT, their phase III data in the endometrial showed meaningful PFS and OS benefit, but they also had 35% response rate and considerable stomatitis. With SAC-TMT filed now, does Rina-S still have a shot at accelerated approval? And I have a follow-up.
Thank you, Karina. Judith, can you take this question?
Yes. Thank you for the question. As you know, for Rina-S in endometrial, we have a dual strategy. We started with a single arm, and in parallel, we opened a phase III randomized study. Basically, align with what we did with PROC. The more likely scenario now is that the filing will be based on the phase III results.
Thanks, Judith. Very clear. Thanks, Karina.
I have a follow-up. For Rina-S, the ovarian cancer data you guys showed a strong OS hazard ratio, and there has been a lot of buzz generated at ESMO. Are you seeing any preliminary impact on patient recruitment to the other ongoing phase III studies and also basket studies?
Judith, can you handle this one as well?
Yeah, thank you for the question. As you can appreciate, the unprecedented results of Rina-S in PROC are creating what we call a halo effect. We expect recruitment on the other studies to be even more encouraged by these results being already made public.
Thanks, Judith. Thanks, Karina.
Thank you.
We move on to the next question. Thanks.
Thank you. Now we are going to take our next question, and it comes from the line of Gregory Renza from Truist. Your line is open. Please ask your question.
Hi. Thanks so much for taking our question. This is support on for Greg. Another one on Rina-S. On the greater than $2 billion peak sales, how does that number split across platinum-resistant, platinum-sensitive, and endometrial cancers? What setting drives most of the value? Thanks so much.
Thanks, Gregory, for the question. Anthony, you can handle this one for sure.
Yeah. Thanks, Greg. I come back to the high conviction we've had in Rina-S, and again, now we back this up with the phase III data that was released in October and really showing that strong OS data. Our conviction is really backed up now based upon this data. Again, we stand fully behind that peak year sales estimate, and just to remind everybody, for Rina-S, that's greater than $2 billion. That conviction comes from the data, but it also comes from the capabilities we've deliberately built, again, how we develop the medicines, how we commercialize them. You've seen, again, to remind everybody, that strong execution with TIVDAK and EPKINLY, and that same engine is already doing the appropriate pre-launch work, particularly now zooming in on Rina-S, and really leveraging all of the capabilities we've also built out in the gynecological oncology space.
I think we're very, very well-positioned to deliver against that greater than $2 billion estimate for Rina-S. Gregory, at this stage, we're not breaking it down any further than that in terms of further breaking down ovarian or endometrial to split. I just have you focused on the capabilities in place, the data in place for us to now deliver against that greater than $2 billion target for Rina-S.
Thanks, Anthony. As a reminder, Gregory, we also have trials in lung cancer as well as in gastrointestinal cancers with Rina-S, so it may have far broader potential than just ovarian and endometrial. Let's move to the next question, operator.
Yes, of course. Now we are going to take the question from Rajan Sharma from Goldman Sachs. Your line is open. Please ask your question.
Hi. Thanks for taking my questions. I have two as well. First one just on EPKINLY dynamics. It looks like sequential growth between 2Q and Q3 was relatively flat. Could you just maybe talk about what you are seeing there, and is that sort of the run rate we should be expecting until the frontline approval comes through? Then secondly, maybe just following up on a question from the call last week. Just now that you have the data in hand, how are you thinking about the shape of the top line and the bottom line of the company through the DARZALEX patent expiration, or sorry, your royalty expiration? Are you confident that there is ability to grow through that or at least be flat? Thank you.
Thanks, Rajan. Very good questions. Brad, can you handle the first one, EPKINLY growth dynamics, and how to think of that going forward? Then Anthony, maybe you can start on the top line versus bottom line, and I can potentially jump in there as well. Brad?
Yeah, no, thank you for the question, and we certainly continue to see kind of post the second line FL launch, as well as removal of hospitalization, strong growth, specifically in the U.S. with EPKINLY. As we look globally, expecting, as mentioned, we just launched in Japan with second line FL as well. I think you will see that continue to We expect continued growth there also. But we have said all along, the earlier lines of therapy is where the value is. As we have just seen the data with frontline, looking to continue to build on this strength that we have with our infrastructure, both our field teams, our market access, patient service teams in the field are ready to deliver from that perspective as well. So, I will leave it there.
Thanks, Brad. Maybe Anthony, on the top line versus bottom line going forward?
Yeah, happy to do so. It really starts with the strength, the quality, and the high conviction that we had and continue to have really across EPKINLY, Rina-S, and p etosemtamab . Again, now we back this up with this phase III data here during the course of October. Again, we stand fully behind the peak sales estimates that we've previously communicated. Just to remind everybody, that's greater than $3 billion for EPKINLY, greater than $2 billion for Rina-S, and multi-billion for petosemtamab. I would also then look to something we highlighted during our call today when I talked about the characteristics of the growth that we're seeing ex-DARZALEX. EPKINLY up 47% compared to last year. The rest of the portfolio up 30%.
So putting that all together from a revenue perspective, we absolutely have the building blocks in place to see an overall very nice revenue growth trajectory here moving forward. Then sort of thinking about the investment and ultimately the bottom line, Rajan, I would really anchor you back to the important financial commitments that we've made to the market, most recently when we acquired Merus in Q4 of last year, or very late Q3. Really three things that we said to you all. We said, number one, we would deliver strong operating profit in 2026. Here, we're up year to date 9% on adjusted operating profit. We also said when we thought about 2027, we committed to deliver operating profit growth and to delever to below 3x gross leverage.
Based upon the strong performance of our brands, coupled with focused and disciplined investment, we are very well positioned to deliver these important 2027 financial commitments. So if you sort of zoom out, Rajan, it's really thinking we have it from a revenue perspective, the building blocks in place, very high-quality data we've seen here in October, and that real focus in leveraging that revenue to the extent possible to drive profits for Genmab. So we're not in a position today to give you any real specific medium-term guidance, but you really should take away from this that the building blocks are really in place here at Genmab from both a product perspective as well as a capability perspective.
Thanks, Anthony. I think very little to add. Comes down to execution, execution here, Rajan, and that's what we are pretty good at.
Thank you. Now we're going to take our next question. The question comes from Xian Deng from UBS. The line is open, please ask the question.
Hi. Thank you very much for taking my questions. Two, please. One on petosemtamab in colorectal. Just looking at the ESMO data you presented, just wondering, the ORR of course looks very high, but the current standard of care in this particular, sorry, in the frontline setting also looks pretty high, and my understanding is the duration is what really matters. Just wondering, given the public data we've seen, it's relatively early stage, and you've already started phase III, so just wondering, what are your thoughts in terms of the duration and especially considering amivantamab? It's actually a lot ahead in terms of timeline, so just wondering your confidence on duration especially also versus amivantamab on that. That's the first question. Second one is on Rina-S. You are announcing the phase III trial in frontline pMMR endometrial.
Just wondering, is that trying to replace chemo induction or more sort of to add during maintenance? Sorry, this is a long second question. It's kind of a broader one on Rina-S, is that you are also starting phase III on maintenance and on PSOC as well as induction in PROC. Historically, the maintenance in those settings, whether it's endometrial or ovarian, it tend to be monotherapy and no chemo. Just wondering, giving the toxicity of chemo, but then of course this is ADC, so just wondering what are your overall thoughts on potentially using ADCs in maintenance setting? I'm asking because whether you can use it in maintenance setting actually matters a lot in PSOC. Thank you very much.
Thanks, Xian. Very good questions. The first one I think can be handled by Tahi, and then Judith, you can take the Rina-S question, and then Tahi can potentially step in there as well.
Yeah. Let me just start with the peto question, and then, between Judith and me, we can certainly also answer the Rina-S questions. Let's start with the colorectal. Yeah. You are absolutely right that the follow-up for the frontline dataset that we presented was relatively short. I think it was five months. But in the end, there are two datasets. There is also a second-line dataset with a slightly longer follow-up, which is the same combination with chemotherapy, FOLFOX or FOLFIRI. So you can, to a degree, extrapolate from the second-line durability that is already, I think, better appreciated to the frontline durability. And then in the end, durability is a function of the mechanism, of course, the safety profile, and the treatment duration, and then of course the sensitivity of the disease. And so this is at least how we think about it.
We look at these datasets not in complete isolation. They also inform each other. And if you take them in totality, both with point estimates, higher response rate that have been described than any dataset that has described before, a response rate in that dataset in frontline, obviously in the left side, and then in the second line and in the totality of patients, these data points give us a confidence. And then the durability that we have seen on the second-line merge confirms that conviction. And then of course, by now, I think we have, broadly speaking, a pretty robust understanding of the safety of petosemtamab. And that's particularly relevant also as you start getting into these thought exercises and comparing it to amivantamab. And I think we have talked about this also on the last call.
There is a very clear distinction in the safety profile and the tolerability of peto versus amivantamab. In terms of the system organ class, obviously, as an EGFR class, there are skin-related toxicities. But the numerical, or the degree, the greatly and higher, and the complexity, and even the locality of the affected skin areas is drastically different between these two assets. So if you then compare the safety that we have generated now repeatedly, and that also is in the phase III, obviously, to the available data sets with ami, and then you know that amivantamab achieves that safety profile with a very complex and involved mitigation strategy, then I think it's pretty obvious that there is a massive differentiation on safety. And that definitely, in our mind, translates into ability. So I think that's my answer on the colorectal. So we feel super excited about colorectal.
I think the data that we presented just at ESMO underwrites that excitement that, of course, already had motivated us to start these two phase IIIs. I would say this, Xian, this would not be the first phase III that we have started after the competition that read out before the competition. I give it to Judith on the Rina questions.
Yeah. Thank you for your questions. For Rina, the endometrial cancer study that is in the public domain is the phase III in the second, third line. The first line is planned, so we haven't provided specifics about the design or comparator. As you well alluded to, the standard of care is induction chemo plus IO, followed by maintenance IO. So we haven't shared the specifics of the trial, but stay tuned. We'll be shortly posting. With regard to PSOC, we have the one strategy, in fact, like triple strategy. So in PSOC second, third line, we have two studies, study 04 and 07. One is maintenance post doublet chemo plus minus Bev, and the other one is what we call replacement strategy.
We have the first line PSOC posted recently in ClinicalTrials.gov, which is not PSOC, but first line maintenance, which is doublet chemo followed by Bev versus doublet chemo followed by Bev plus Rina. So basically, what we are doing is covering all the aspects to potentially unleash the full potential of Rina in the whole spectrum of the disease. Tahi, do you want to add anything?
Well, the only other thing is, like in your question, you alluded to the idea of whether or not an ADC at all is a maintenance drug.
Yeah.
I think there, again, nuances matter. I think we've talked a lot about what we consider to be differentiation for Rina-S, and that is that it is mainly in toxicity. They are mainly restricted to the first or second cycle, and then thereafter, it is actually a very well-tolerated drug with an extremely low discontinuation rate. Then if you have a drug that has a safety profile that is truly tolerable, meaning it doesn't have this discontinuation due to eye toxicity, neurotoxicity, interstitial lung disease, or any other form of cumulative toxicity, then it is actually indeed a very good maintenance drug.
Yeah. We presented data on Rina-S-Bev last year that speaks about that, the good tolerability in terms of patients staying on both drugs, Bev and Rina, for a long period of time.
Thank you. Thank you, Judith and Tahi. That, I think, is really, really a very good response to the question from Xian.
Thank you.
Let's move to the next question, operator.
Yes, of course. The next question comes from the line of Yaron Werber from TD Securities. Your line is open. Please ask your question.
Great. Thank you so much. I have a couple of questions. The first one is on peto. Would you file based on the first-line survival data that you just got, or would you wait to file and include the second-line survival data, which you're expecting early next year? Secondly, I think it's maybe a nuanced question relative to what was asked before. I think when many of us look at the guidance now, $3 billion and higher for EPKINLY, $2 billion for Rina-S, and billions for peto, they all look fairly conservative. What would it take to update them? Thank you.
Thanks, Yaron, for the question. The first one, Judith and Tahi can take that one. Maybe Judith, Anthony, you can give more perspective on the guidance.
Yeah. As we guided the street, when we shared the top-line results of LiGeR-HN1, we are actively planning, engaging with health authorities for the potential filing based on the results that we already communicated.
Thanks, Judith. Anthony?
Yeah. Yaron, just at this stage, we're going to stand fully behind the previous peak year sales estimates for the three brands. Again, reminder, it's greater than $3 billion for EPKINLY, greater than $2 billion for Rina-S. And just want to clarify, I think you said a billion for petosemtamab. For petosemtamab, it's multi-billion. We had strong conviction in these estimates coming into the readouts that we saw in October, and we continue to have that high conviction, and that's where I'm going to leave it for now.
Thanks, Anthony. Thanks, Yaron, for the two questions.
Thank you. Now we're going to take our next question, and it comes line of Victor Floc'h from BNP Paribas. Your line is open, please ask your question.
Hi, thanks so much for taking my question. Maybe just first one, a quick follow-up on the subcu formulation. I noticed that you've added a new cohort to the phase II colorectal study. Just wondering whether it would be enough to support a subcu finding across indication, or would you still need a dedicated bridging study? The follow-up is on the commercial opportunity for peto. I was wondering whether the subcu could become as important as a driver for DARZALEX, and whether the subcu launch is already packed toward in your ambition to reach at least $1 billion in sales by 2029. Finally, more broadly, how does KEYTRUDA expected loss of exclusivity towards the end of the decade shape your long-term expectation for peto? Thank you very much.
Thanks, Victor, for the questions. Maybe Judith, you can actually take the peto subcu question.
Yeah, so I-
And Brad can follow through. Yeah.
Thank you. I would echo what Tahi answered with regard to the peto subcutaneous. We already mentioned the partnership with Halozyme to start the development of the subcutaneous. It is part of our life cycle management, so it is pretty mature to highlight details of the specific plans that we will follow.
Thank you, Judith. And Brad, maybe the subcu as a driver, like DARZALEX subcu was driving the DARZALEX sales, maybe you can give a bit of perspective there.
Yeah, no, thank you for the question. As already mentioned, the LiGeR-HN1 data shows the potential for petosemtamab to be both first and best in class in frontline head and neck. We are confident in this potentially practice-changing data that we have just looked into and shared. Any innovations certainly or updates would be assessed in the future, and we will certainly update those as we move forward. But again, an extremely area of high unmet need right now, and very confident in the data we presented at this point.
Thanks, Brad. Thanks, Victor, for the questions. Let's move on to the next one.
Yes, of course. Now we are going to take our final question for today. Just give us a moment. It comes line of Sean Laaman from Morgan Stanley. Your line is open, please ask your question.
Hello, everyone. Congrats on the results. Thanks for taking my number, and hope everyone is well. Two quick ones. First of all, strategic, given the significant strengthening you have observed at the late-stage pipeline, has your appetite for external business development changed, or is execution on internal assets now the highest return use of capital, is the first one. The second one is just on the two CRC programs. What milestone should we expect over, say, next 12-24 months? Given where you could position this in CRC, particularly with the differentiated safety profile you are pointing to, could the opportunity outsize what you observe in or expect in head and neck? Thank you.
Thanks, Sean. I will take this first one myself, then the CRC questions Judith can handle. BD, we are very active, Sean, in looking at interactions with other companies for potential combinations of our drugs. We already announced the Incyte partnership recently. There will be more to come. We are currently focusing on really maximizing the potential of our late-stage programs. Two of the three have been taken in via BD, via acquisitions. We also are working very strongly on our organic pipeline. We do not talk a lot about it because we want you to focus on the late-stage programs. This year, we moved already four new programs, antibody-based programs, into the clinic from our own pipeline, two bispecifics, two ADCs. At least two more programs will be moved into the clinic between now and the end of the year.
We are very actively working on our organic pipeline, but it will be balanced. Right now, the focus is clearly on maximizing the potential of the late stage, what I call winning programs, Sean. We have, of course, a commitment in addition to this expansion of the programs to also lower the leverage by end of next year to less than threefold gross leverage, which we have focused on. We have a very active BD team to really bring the outside landscape into great perspective for us so that we can strike again if needed in the future. Then maybe, Judith, you can talk about the colorectal cancer setting.
Yeah. Thank you. Unfortunately, CRC is a high unmet medical need and a larger opportunity potentially commercially than head and neck. In first-line KRAS wild-type, the treatment paradigm is an EGFR antibody, usually cetuximab or panitumumab, plus FOLFOX or FOLFIRI. Unfortunately, the median PFS is only 12 months and median overall survival around two years. In the second line, the unmet medical need is even more compelling. With best treatment in KRAS wild-type, with cetuximab, panitumumab, or any other EGFR plus chemo, the response rate is only 30%-40%, median PFS 6 months, and median survival of one year. So a compelling unmet medical need, where, as we highlighted or Tahi highlighted in ESMO, we showed very strong, encouraging, although still early preliminary data.
We expect to have longer follow-up of this dataset, which is pretty good for a phase II proof of concept, and we will communicate this when the data is more mature.
Thank you, Judith. Thanks, Sean, for the question. Thank you. I think this will end our Q&A. Thank you all for your questions and for being with us today. As always, if you have additional questions, please reach out to our investor relations team.
This concludes this conference call. Thank you for participating. You may now all disconnect. Have a nice day.