Earnings Call Transcript - GMAB 2026-11-05

Operator

Welcome to the GenMAP 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. GEDMAP is not under any obligation to update statements regarding the future, nor to confirm such statements in relation to actual results, unless this is required by law. Today's presentation will also include comments on certain non-IFIS financial measures which management uses to describe the company's baseline performance. and which supplements but do not substitute for the comparable IFIS 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 GenMap may hold your personal data as indicated by you as a part of our investor relations outreach activities in order to update you on GenMap going forward. Please refer to our website for more information on GenMap and our privacy policy. I would like to hand the conference over to our first speaker today, Jan van der Winkel. Please go ahead.

Jan van de Winkel, CEO

Good to have you all with us, and welcome to GenMap'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. And our Chief Medical Officer, Tai Yamadi, and Chief Development Officer, Judith Kulimovsky, you 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 GenMob, 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 three 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 RENA-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 Pitocentumab last December, and less than 11 months after closing, it too has a positive Phase III and a growing Phase III program. And that Kinley, an antibody created by Genmob 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. And 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 3 data and what it means for us going forward. Last week, we held a call summarizing the important Phase 3 data sets that we announced in October. You can listen to a replay of that call to our website, so I will keep this brief and focus on what it means for us. First, at Kinley. The EPCOR-DLBCL2 trial, which met its progression-free survival endpoint with a hazard ratio of 0.49, demonstrated that Epkinli has the potential to change how Fondline diffused last B-cell lymphoma is treated after more than two decades of our job as the standard. And expanding into Fondline supports Epkinli's potential to become D-Core therapy in B-cell malignancies. Second, RINA-S. Our ambition is for RINA as to be the best, first, and broadest in class. The RAINFOL02 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 4-litreceptor alpha expression level or previous nilvotuximab. And 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 RNA-S program across ovarian and endometrial cancers positions us well to lead innovation in the gyno-oncology section. And third, p2-centamol. 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. And with two Phase III trials on the way, we are already expanding into colorectal cancer, which is another area of significant unmet need. And 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, Epkidly and Tivdac, are doing in the market. Brad, the floor is yours.

Brad Bailey, Other

Thanks, Jan. Our proprietary medicines continue to perform extremely well, with Epkidly and Tivdac 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 the 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. F. Kinley is the most prescribed bispecific antibody in lymphoma globally, and we're 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., Epkinlee 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 Epkinlee and expanded adoption among existing accounts, with more than 97% of key customers now ordering from two or more sites. We're especially pleased with the uptake of chemo-free, fixed-duration Epkinlee plus R-squared and second-line FL. This uptake is broadening physician experience with Epkinle, driving increased utilization across both FL and DOBCL, and bringing bispecific base treatment to sites closer to where patients live. Outside the U.S., Epkinle continues to perform very well. In Japan, the launch of Epkinle plus R-squared and second-line FL is off to an encouraging start. Building on McKinley'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 TIBDAC. 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. TIBDAC is now approved and reimbursed in multiple countries, with additional reimbursement discussions underway. This expansion is bringing TIFFDAC to more patients while strengthening the local market knowledge, customer relationships, and access capabilities that will help drive our success with Rhena-S and Pitocimtumab in the future. Looking ahead, our focus is on translating progress in our late-stage portfolio into well-executed launches and access for patients. From Kinley. First-line DOBCL 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're building today and at Kinley's approved indications across sites of care serves as strong foundations we prepare to expand into earlier lines of DOBCL. If approved, Epkinle plus RCHOP would significantly expand Epkinle's role in lymphoma treatment and move us closer to our ambition of establishing Epkinle as the core therapy in B-cell malignancies. For Rhena S, the positive rainfall O2 results represent an important step forward for patients with platinum-resistant ovarian cancer who face limited options and poor outcomes. If approved, RENA-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 TIBDAC gives us an established understanding of gynecologic cancer care and longstanding relationships with physicians and care teams set a strong foundation for our work with RENA-S in the future. Lastly, as John shared, Liger HN1 was the first positive Phase III trial in first-line head and neck cancer in nearly a decade. If approved, PETA-Symptomab 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. We're 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.

Anthony Pagano, CFO

Thanks, Brad. The first nine months of 2026 demonstrated the continued strength of our business, with revenue growing 22% year over year. And 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. Darzilex increased 19% year-over-year, 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 Darzilex. Impressively, the other half was generated by Abkinli 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 Epkinlee, Rhena-S, and Pitocentumab, as well as the ability to broaden the development for both of our wholly-owned programs. And as you know, We currently have nine ongoing Phase III trials for RENA-S and Pitocentumab, with more announced or in development. And even with this investment, we grew adjusted operating profit by 9%. So, together, our results demonstrate that GEMMAP 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 merits and related recognition and utilization of deferred tax assets. As we've 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 to 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 to $4.525 billion, delivering a robust 19% growth at the midpoint. And it's at Kinley 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 of around $2.81 billion to $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 RENA-S and Pedocentumab. So I would caution against taking down your 2026 OPEX figures as a result of our first nine months. Putting all this together, we're planning for adjusted operating profit in a range between $1.065 billion to $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 Pitocentumab, RENA-S, and launch readiness, all while maintaining strong profitability. Now, Finally, before I conclude, I'd 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 GenMAD will deliver strong profitability both in 2026 and continued growth in 2027. So, 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 van de Winkel, CEO

Jan, back over to you. Thank you, Anthony. This brings us to our final slide. It has already been a remarkable year for GenMob, 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 AppKinley. The second is a high-potential late-stage pipeline, where we have had unprecedented Phase 3 readouts across AppKinley, RINA-S, and P2Centremop, 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 three times 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. So, 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'm 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.

Operator

Thank you. Dear participants, as a reminder, if you wish to ask a question, please press star 1-1 on your telephone keypad and wait for your name to be announced. To withdraw a question, please press star 1-1 again. Please stand by or we'll compile the queue in the roster. This will take a few moments. And now we're 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.

Benjamin Jackson, Analyst — Jefferies

Brilliant. Thank you for the question, guys. Can I just start on the ASH abstract for DLBCL4, please? Just interested if there's any color you can add around what you're 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? And 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? And 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? And then also, just as a follow-up, on the safety side, slight increase in that trial in and around grade five events. Is there any clue you can add here? Is this COVID related again, or is something else at play? Thank you.

Jan van de Winkel, CEO

Thanks, Ben. You very cleverly, I think, put three questions under the first one. That is the S-abstracts, and then the safety one is an extra question. So we'll ask Thay to start, and then Judith can chip in where you can add further caller. Thay?

Tahamtan Ahmadi, Other

Yeah, thank you, Jan. Thank you, Benjamin. There are probably five questions in there. So I'm going to take them one at a time. As it relates to the U.S. for the O4 trial, I think you already alluded to a medium follow-up on that trial driven by the impressive hazard ratio on the PFS side. That triggered the readout was 10 months. And if you just think about the cost comparison to 05 or the GLOFI-GEMOX study, the follow-up there was more like towards 28 to 30 months. And so from that, you can just already appreciate that this is totally immature to very few events. As it relates to COVID, COVID is not necessarily an issue anymore. These trials were run post the COVID phase. But, of course, the availability of biospecifics in CARDS, 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 hep kidney. 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 Diffus HB7 Phase 3 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. And the third one was on safety. You correctly noted that there were a few death events on the kidney arm, also on the control arm. But there's really no isolated signal, there's a really multifactorial and it's a relatively small number of patients. So 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 what would be better appreciated when the data is actually presented in its totality at ASH. I hope I touched on all of the questions.

Jan van de Winkel, CEO

Yes, that's brilliant. Thank you very much. Thanks, Ty. Thanks, Ben, for the question. Let's move to the next question.

Operator

Yes, of course. And now we're 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, Analyst — Bank of America

Charlie Haywood, Bank of America. Thanks for taking the question. I have two, please. So the first one is just looking ahead to potential launches for these assets and how... And on Pitot specifically, I think your prior commentary was a billion dollar sales by 29. And so just wondering, obviously, you've hit OS at interim, which I imagine was more of an upside scenario. So how has that informed confidence to reach that status by 29? And then the second question, just on your two phase three readout or your filable readouts coming next year, so PETO, second, third line, head and neck, and then RUNER-S, second line, endometrial. I guess both optically smaller ops than the recent anchor readouts you've had, but both a broader halo potential for the assets you've got. So, you know, OS benefit for PETA across potentially first line, second line, and third line, and then renal S, ovarian, and endometrial. So, how do you view the commercial importance and the potential halo effect of those two indications? Thank you.

Jan van de Winkel, CEO

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 29 to provide further color if needed? Brad, maybe you can start.

Brad Bailey, Other

Thanks, John, and thank you for the question. And, you know, as we look ahead, obviously, the oncology in general is a data-driven market and a very competitive market, but also extremely data-driven, and we're confident in the data. That we've seen to date for all the assets, as you mentioned across this, your questions, and, you know, we're confident also in the capabilities we've built at this point to bring our medicines to market. We've 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've provided thus far. And as we get into the data further with the presentations, as we've stated at an upcoming Medical Congress next year, we'll be able to provide further color on that as we move forward.

Jan van de Winkel, CEO

Thanks, Brad. Anthony, you want to give further call on?

Anthony Pagano, CFO

Yeah. Yeah. Thanks, Charlie. We've been super clear. We had high conviction. I was only zooming in on Pitocentumab. We had high conviction in Pitocentumab in October. We backed it up with the really super strong phase three results, including the OS that you referenced. So, we stand fully behind the peak year sales estimate for PO Centimap at multi-billion, and we stand fully behind that $1 billion number for 2029. So, I really feel like on the heels of this data, Charlie, we're well positioned here moving forward.

Charlie Haywood, Analyst — Bank of America

Great.

Anthony Pagano, CFO

Thank you.

Jan van de Winkel, CEO

Thanks, Charlie.

Operator

Now we're going to take our next question. And the question comes from line of Zane Abraham from J.P. Morgan. Your line is open. Please ask a question.

Zane Abraham, Analyst — J.P. Morgan

Hello, thanks for taking the question. Zane, everyone, Jason 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 two, you showed medium progression-free survival of about nine months, but based on the phase three results, you're basically, you're effectively doubling overall survival, so could we see potentially longer duration of therapy than that progression-free survival nine-month point? And my second question is on Kinley 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 Epkinlee next year?

Jan van de Winkel, CEO

Thanks, Tain, for the questions. So maybe, Tain, you can start with the PITO, duration of response question. I don't know how much detail we can give here, but you can potentially give some perspective. And then Brad, maybe you can talk about the launches and the rollout of APCO in Frontline, DLBCL, and further.

Tahamtan Ahmadi, Other

Yeah, thank you, Jan, and thank you for the question. Now, of course, as I'm sure you 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 any questions, to remind ourselves that, you know, from a pure... The 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 we're involved. And then we can have these nuanced discussions around modeling, duration of treatment, and these things.

Jan van de Winkel, CEO

Thanks, Ty. And Brad, maybe a bit on the rollout of Abkinli in the different settings.

Brad Bailey, Other

You know, thanks. Thank you for the question. And, you know, we've said for quite some time the largest opportunities, 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's already moving, I think, as we know, from R-CHOP to these R-CHOP combinations. And it's also long stated that we believe Biospecifics can really build on this R-CHOP and emerge as the new standard. The top-line data at this point validate this position and the roll-up Kenley plus R-CHOP can play. And we feel extremely confident, again, in the data for Epkinlee. We've 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're already seeing, and a bit of a proof point with a second-line FL launch from around the same time last year. That's driven the primary part of our uptake thus far. So, we expect strong uptake, and I look forward to sharing more as we move further.

Jan van de Winkel, CEO

Thank you, Brad. And as you said before, data is the currency in oncology design, and what we hope is that we can actually present the data of the frontline study with Apcoritimab quite quickly and show how fantastic that data is so that that launch will be even quicker once it's on the market.

Zane Abraham, Analyst — J.P. Morgan

Okay, thanks a lot.

Jan van de Winkel, CEO

Let's move to the next question, operator.

Operator

Yes, of course. And the question comes line of Romy O'Connor from Van Lanschotkampen. Your line is open. Please ask your question.

Romy O'Connor, Analyst — Van Lanschot Kempen

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 pedacentumab, just wondering how you're thinking of the subcutaneous formulation and how advanced along is that? And looking at the frontline DLBCL space, so following the positive data that we saw, how should we be thinking about the positioning of Epkenly and RCHOP against, for example, PolarRCHIP? So do you anticipate more of a broad adoption, or could treatment decisions be dependent on risk characteristics, for example? Thank you.

Jan van de Winkel, CEO

Thanks, Romy. The first question can be on the sub-Q. Maybe Tai can start with that and then also handle the second question on the competition and the positioning versus polar archip and frontline diffused as B-celliforma. Tai, maybe you can start.

Tahamtan Ahmadi, Other

Yeah, so on the PITO questions first, look, when we obviously started, I think the deal with Helozyme was announced in the middle, in the midst of... The closure period of the acquisition of mail, so we've been working on sub-Q. We have always understood sub-Q 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 Epkinly question, this question comes up a lot, and I think they're going to step back for a moment. So first off, Archop Epkinly has at least 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 Diffusas Pisa for a quarter of a century. 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 you can tell the difference between hazard ratio between 3 to 5 to 2 to 5 was non-existent, which basically means that the hazard ratio of 2 mimics the hazard ratio of the 3 to 5 population. That in and of itself is already a significant differentiator. And then there are other subgroup populations that you could think about as As it relates to the original polar RCHP 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 while we're here today, while we have a phase three, the Glophie Polar RCUHP study is going to read out sometime in the future. I think Russia's guided 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, ARCHOP is the standard of care. That's something that physicians in the community are comfortable with for 25 years plus. The sub-cure 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 plays a role 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 WASH. 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-Sharp, Glowfee, and R-CHP, Glowfee. So I think that kind of summarizes how we think about it. We feel very comfortable with the positioning of where we are. Super excited. to share this data as soon as we get the opportunity to, and then we'll have more detailed conversations.

Jan van de Winkel, CEO

Thank you, Taya. Thank you. Thanks, Homi.

Operator

Thank you. Now we're going to take our next question. And the question comes line of Aztika Gunnubardine from Learink. Your line is open. Please ask your question.

Karina, Analyst — Leerink

Hi, everyone. This is Karina for Aztika. Congrats on all the data. I had a question for Reena S. So SAC-TMT, their Phase III data and endometrial showed meaningful PFS and ALS benefit, but they also had 35% response rate and considerable traumatitis. So with SAC-TMT filed now, does Reena S still have an accelerated approval and I have a follow-up.

Jan van de Winkel, CEO

Thank you, Karina. Judith, can you take this question?

Judith Klimovsky, Other

Yes, thank you for the question. So, as you know, for RINA-ES in endometria, we have a dual strategy. We started with a single arm, and in parallel, we opened a phase three randomized study. So, basically, aligned with what we did with Piroc. So, the more likely scenario now is that the filing will be based on the phase three result.

Jan van de Winkel, CEO

Thanks, you. That's very clear. Thanks, Corina.

Karina, Analyst — Leerink

And I have a follow-up. For Rina, as the ovarian cancer data, they had, you guys showed a strong OS hazard ratio, and there has been, like, a lot of buzz generated at ESMO. Are you seeing, like, any preliminary impact on patient recruitment to the other ongoing phase 3 studies and also The basket studies.

Jan van de Winkel, CEO

Judith, can you handle this one as well?

Judith Klimovsky, Other

Yeah, no, and thank you for the question. As you can appreciate the unprecedented results of RINA in Piroc are creating what we call a halo effect. So we expect recruitment on the other studies to be even more encouraged by these results being already making public.

Jan van de Winkel, CEO

Thanks, Judith. Thanks, Corina. We move on to the next question. Thanks.

Operator

Thank you. And now we're going to take our next question, and it comes to the line of Gregorio Ranza from TWIST. Your line is open. Please ask a question.

Gregorio Ranza, Analyst — TWIST

Hi. Thanks so much for taking our question. This is support on for Greg. Another one on Rina asks, 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.

Jan van de Winkel, CEO

Thanks, Gregory, for the question. Anthony, you can handle this one for sure.

Anthony Pagano, CFO

Yeah, thanks. Thanks, Greg. Really, I come back to the high conviction we've had in RENA-S, and again, now we've backed this up with the Phase 3 data that was released in October and really showing that strong OS data. So, really, our conviction is really backed up now based upon this data. So, again, we stand fully behind that peak year sales estimate. And just remind everybody, for RENA-S, that's greater than $2 billion. That conviction comes from the data, but it also comes from the capabilities we've deliberately built, how we develop the medicines, how we commercialize them, and you've seen, again, to remind everybody, that strong execution with TIBDAC and F. Kinley, and that same engine is already doing the appropriate pre-launch work, particularly now zooming in on green acid and really leveraging all of the capabilities we've also built out in the gynecological oncology space. So I think we're very, very well positioned to deliver against that greater than $2 billion estimate for RENA-S. Gregory, at this stage, we're not breaking it down any further than that in terms of, you know, further breaking down ovarian or endometrial to split. Really, 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 RENA-S.

Jan van de Winkel, CEO

Thanks, Anthony. And as a reminder, Gregory, we also have trials in lung cancer as well as in gastrointestinal cancers with RNA, so it may have far broader potential than just ovarian and endometrial. Let's move to the next question, operator.

Operator

Yes, of course. And now we're going to take the question from Rajan Sharma from Goldman Sachs. Your line is open. Please ask a question.

Rajan Sharma, Analyst — Goldman Sachs

Hi, thanks for taking my questions. I've got two as well. First one, just on Epkinly dynamics, it looks like sequential growth between 2Q and Q3 was relatively flat, so could you just maybe talk about what you're seeing there, and is that sort of the run rate we should be expecting until the frontline approval comes through? And 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 Dazalex patent expiration, or sorry, your royalty expiration? Are you confident that there's ability to grow through that or at least be flat? Thank you.

Jan van de Winkel, CEO

Thanks, Rajan. Very good questions. Brad, can you handle the first one? Kindly growth dynamics and how to think of that going forward. And then, Anthony, maybe you can start on the top line versus bottom line, and I can potentially jump in there as well. Brad?

Brad Bailey, Other

Yeah, 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 F. Kinley, and as we look globally, expecting, as mentioned, we just launched in Japan with SecondLineFL as well, and so I think you'll see that continue to, you know, we expect continued growth there also, but we said all along, you know, the earlier lines of therapy is for the value is, and as we I 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'll leave it there.

Jan van de Winkel, CEO

Thanks. Thanks, Brad. And maybe Anthony on the top line versus bottom line going forward?

Anthony Pagano, CFO

Yeah, happy to do so. And really, it's going to be reiterating some key messages we've been sharing with the markets here now for really the last year. It really starts. With the strength, the quality, and the high conviction that we had and continue to have really across Epkinle, RINA-S, and Pitocentumab. Again, now we've backed this up with this phase three data here during the course of October. And again, we stand fully behind the peak sales estimates that we've previously communicated. And just to remind everybody, that's greater than $3 billion for Epkinlee, greater than $2 billion for RENA-S, and multi-billion for P-O-centimab. 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-Darzolex, Epkinlee, Epkinlee. 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 a overall very nice revenue growth trajectory here moving forward. And 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 Maris. And Q4 of last year, or very late Q3. And 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 three times gross leverage. And 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 commitment. 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 GenMap. 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 GemMap from both a product perspective as well as a capability perspective.

Jan van de Winkel, CEO

Thanks, Anthony. I think very little to add. It comes down to execution, execution, execution here, Rajan, and that's what we are pretty good at.

Operator

Thank you. Now we're going to take our next question. And the question comes line of Shan Deng from UBS. Your line is open. Please ask a question.

Shan Deng, Analyst — UBS

Hi, thank you very much for taking my questions. Two, please. One on P2 symptomap in colorectal. So just looking at the ASMO data you presented, so just wondering, you know, the ORR, of course, looks very high, but the current center of care in this particular, sorry, in the frontline setting also looks pretty high, and my understanding is the duration is what really matters. So just wondering, given the public data we've seen is relatively early stage, and you've already started stage three, so just wondering, you know, what are your thoughts in terms of, you know, duration, and especially considering amivantimab, it's actually a lot ahead in terms of timeline, so just wondering your confidence on duration, especially also versus amivantimab on that. So that's the first question. Second one is on Reina F. So you are announcing the phase three trial in frontline PMMR, endometrial. So just wondering, you know, is that, you know, trying to replace chemo induction or more sort of to add during maintenance? And sorry, this is a long second question. So it's kind of a broader one on renax is that you are also starting phase three on maintenance and on PSOC as well as induction in proc. So, historically, the maintenance in those settings, whether it's endometrial or ovarian, it tends to be monotherapy and no chemo. I'm just wondering, you know, given 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 peak sales. So thank you very much.

Jan van de Winkel, CEO

Thanks, Sion. Very good question. The first one, I think, can be handled by Thay. And then, Judith, you can take the Rina-ask question, and then Thay can potentially step in there as well.

Tahamtan Ahmadi, Other

Yeah, let me start with the question and then, you know, between Drew and me. We can certainly also answer the real questions. Let's start with the colorectal. Yeah, so, I mean, you're absolutely right that the follow-up for the frontline data set that we presented was relatively short. I think it was five months. But in the end, there are two data sets. There's also a second-line data set with a slightly longer follow-up. Which is the same combination with chemotherapy, 4-Fox or 4-Fury. And so you can, to a degree, extrapolate from... The second line, durability, that is already, I think, better appreciated to the frontline durability. And 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. So we look at these data sets 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 data set that is described before, a response rate in that data set, in frontline, obviously, in the left side, and then in the second line, in the totality of patients, these data points give us confidence, and then the durability that we've seen on the second line emerge confirms that conviction. And then, of course, by now, I think we are, broadly speaking, a pretty robust understanding of the safety. And that's particularly relevant also as you start getting into these thought exercises and comparing it to ambivantamab. And I think we've talked about this also in the last call. There is a very clear distinction in the safety profile and the tolerability of PETO versus ambivantamab. Um, it's, in Terms in the system organ class, obviously, as an EGFR class, there are skin-related toxicities, but the numerical, the degree, the greater and higher, and the complexity, and even like the locality of the affected skin areas is drastically different between these two acids. And so if you then compare... The safety that we have generated now repeatedly, and it also is in the phase three, obviously, to the available data sets with AMI, and then you know that AMI-Vantamat achieves that safety profile with a very complex and involved mitigation strategy, then I think it's pretty obvious that there's a massive differentiation on safety, and that definitely, in our mind, translates into our ability. So I think that's my answer on the core rectal, so we feel super excited about core rectal. And I think the data that we presented just at ASMO underwrites that excitement that, of course, already had motivated us to start these two phase threes. And then I would say this would not be the first phase three that we have started after the competition that ran out before the competition. And then I give it to...

Judith Klimovsky, Other

Thank you for your questions. For Rina, the endometrial cancer study that is in the public domain is the phase three in the second, third line. The first line is planned, so we haven't provided specifics about the design or comparator, but as you will. Alluded to the standard of care is induction, chemo, plus I.O., followed by maintenance I.O. So we haven't shared the specifics of the trial, but stay tuned. We'll be shortly posted. With regard to PSOC, we have a dual strategy, in fact, like triple strategy. So in PSOC, second, third line, we have two studies, study 04 and 07. One is maintenance post-dablet chemo. Plus, minus, BEV, and the other one is what we call replacement strategy, and we have the first line piece posted recently in clinicaltrial.gov, which is not piece of a first line, maintenance, which is double chemo followed by BEV versus, you know, double chemo followed by BEV plus RINA. So, basically, what we are doing is, you know, covering all the aspects to potentially unleash the full potential of rena in the whole spectrum of the disease. Tai, do you want to add anything?

Tahamtan Ahmadi, Other

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, and I think there, again, nuances matter. I think we have talked a lot about what we consider to be differentiation for VNS, and that is that it is mainly heme 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, and 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.

Judith Klimovsky, Other

And we presented data on Rina Bev last year that speaks about that, you know, the good tolerability in terms of patients staying on both drugs, Bev and Rina, for a long period of time.

Jan van de Winkel, CEO

Thank you. Thank you, Judith and I. I think it's really, really a very good response to the question from Cheon.

Operator

Thank you.

Jan van de Winkel, CEO

Let's move to the next question, operator.

Operator

Yes, of course. And the next question comes from Jaron Weber from TD Securities. Jaron is open. Please ask a question.

Jaron Weber, Analyst — TD Securities

Great. Thank you so much. So I have a couple of questions. The first one is, Ampito, 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? And then secondly, and 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 Kinley, $2 for RENA-S, and billions for PETO, they all look fairly conservative. What would it take to update them? Thank you.

Jan van de Winkel, CEO

Thanks, Jaron, for the question. So, the first one, Judith and Tai can take that one, maybe Judith, and then, Anthony, you can give more perspective on the guidance.

Judith Klimovsky, Other

Yeah. So, as we guided the street, when we shared the top-line results of Liger01, we are actively planning, engaging with health authorities for the potential filing based on the results that we already communicated.

Jan van de Winkel, CEO

Thanks, Judith. Anthony?

Anthony Pagano, CFO

Yeah, Aaron, 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 Epkinlee, greater than $2 billion for Rena S. And just want to clarify, I think you said $1 billion for Pitocentumab. For Pitocentumab, 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.

Jan van de Winkel, CEO

Thanks, Anthony. Thanks, Jaren, for the two questions.

Operator

Thank you. Now we're going to take our next question. And it comes line of Victor Flock from BNP Paribas. Your line is open. Please ask a question.

Victor Flock, Analyst — BNP Paribas

Hi, thanks so much for taking my question. Maybe just first one, a quick follow-up on the subcute formulation. I noticed that you've added a new cohort to the Phase 2 co-director study. Just wondering whether this would be, whether it would be enough to support a subcute finding across indication? Or would you still need a dedicated bridging study? And the follow-up is on the commercial opportunity for PITO. I was wondering whether the subcute could become as important as a driver for PITO than it has been for DARS Annex, and whether the subcute launch is already factored in your ambition to reach at least $1 billion in sales by 2029. And finally, more broadly, how does Keytruda expected loss of exclusivity towards the end of the decade shapes your long-term expectation for VITO. Thank you very much.

Jan van de Winkel, CEO

Thanks, Victor, for the questions. Maybe, Judith, you can actually take the PITO sub-Q question. Yeah, so I... And Brad can take the other too.

Judith Klimovsky, Other

Thank you. So, I would echo what I answered with regard to the PETA subcutaneous. You know, we already mentioned the partnership with Allozyme to start the development of the subcutaneous. It's part of our lifecycle management, so it's premature to highlight details of the specific plans that we will follow.

Jan van de Winkel, CEO

Thank you. And Brad, maybe the sub-Q as a driver like Darcellex sub-Q was driving the Darcellex sales, maybe you can say a bit, give a bit of perspective there.

Brad Bailey, Other

Yeah, no, thank you for the question. And as I already mentioned, the Liger HN1 data show the potential for, you know, Peter Symptomab to be both first and best in class in frontline head and neck. And we're confident in this potentially practice-changing data that we've just... Looked into and shared, and, you know, any innovations, certainly, or updates would be assessed in the future, and we'll, you know, certainly update those as we move forward. But again, an extremely area of high-end MET need right now, and I'm very confident in the data that we presented at this point.

Jan van de Winkel, CEO

Thanks, Brad. Thanks, Victor, for the questions. Let's move on to the next one.

Operator

Yes, of course, and now we're going to take our final question for today. Just give us a moment. And it comes to the line of Sean Lahman from Morgan Stanley. Your line is open. Please ask a question.

Sean Lahman, Analyst — Morgan Stanley

Hello, everyone. Congrats on the results. Thanks for taking my number and hope everyone's well. Two quick ones. First of all, strategic, given the significant strengthening you've 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? And the second one is just on the two CRC programs, you know, what milestones should we expect over, say, next 12 to 24 months? Given where you could position this in CRC, particularly with the differentiated safety profile you're pointing to, could the opportunity outsize what you observe or expect in head and neck? Thank you.

Jan van de Winkel, CEO

Thanks, Sean. I will take the first one myself, and then the CRC questions Judith can handle. So BD, we are very active, Sean, in looking at interactions with other companies for potential combinations of our drugs. We already announced the Insight partnership recently. There will be more to come. But 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. But we also are working very strongly on our organic pipeline. We don't talk a lot about it because we want you to focus on the late-stage programs. But this year, we moved already four new programs, antibody-based programs, into the clinic from our own pipeline. And two bispecifics, two ADCs. And at least two more programs will be moved into the clinic between now and the end of the year. So we are very actively working on an organic pipeline, but it will be balanced. But right now, the focus is clearly on maximizing the potential of the late-stage, what I call winning programs, Sean. And also, we have, of course, a commitment in addition to this expansion. of the programs to also lower the leverage, basically, by end of next year to less than three-fold gross leverage, which we have focused on. But 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. And then maybe Judith, you can talk about the colorectal cancer setting.

Judith Klimovsky, Other

Yeah, so thank you. So unfortunately, you know, CRC is a high unmet medical need and a larger opportunity, potentially commercially than head and neck. So in first line, care is wild. The treatment paradigm is an EGFR antibody, usually septicfimab or panitumumab plus Folfox or Folfiti. Unfortunately, the median PFS is only 12 months and median overall survival is around two years. In the second line, the unmet medical need is even more comparing. With best treatment in Care-Rise-Wild, with cetuximab, panitumumab, or any other EGFR plus chemo, the response rate is only 30-40%, median PFS six months, and median survival of one year. So, comparing and met medical needs, where, as we highlighted or as I highlighted in ESMO, we showed very strong encouraging, although still early preliminary data. So, we expect to have longer follow-up of this data set, which is pretty good for a phase two proof of concept, and we will communicate this when the data is more mature.

Jan van de Winkel, CEO

Thank you, Jürgen. Thanks, Sean, for the question. Thank you. I think this will end our Q&A. So thank you all for your questions and for being with us today. And as always, if you have additional questions, please reach out to our investor relations team.

Operator

This concludes this conference call. Thank you for participating. You may now all disconnect. Have a nice day.