Genmab - Earnings Call - Q2 2025

Transcript

Speaker 3

Hello and welcome to the Genmab first half 2025 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 believes, 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 relation to the actual results unless this is required by law. Please note that Genmab may hold your personal data as indicated by you as 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 your first speaker today, Jan van de Winkel.

Please go ahead.

Speaker 1

Hello and welcome to our financial results for the first half of 2025. With me today is our Chief Financial Officer, Anthony Pagano, our Chief Commercial Officer, Brad Bailey, and our Chief Medical Officer, Tahamtan Ahmadi. For the Q&A, we will be joined by our Chief Development Officer, Judith Klimovsky. As we have already said, we will be making forward-looking statements, so please keep that in mind during the call. During today's presentation, we will reference products being developed and the sum of our strategic collaborations. This slide acknowledges those relationships. I would like to start with a reminder of our commitments for 2025. In February, we said that we would accelerate the development of our high-impact, late-stage pipeline, that we would maximize the potential of our commercialized medicines, and that we would deliver on our capital allocation priorities, supporting our continued growth and long-term value creation.

Let's review how we have delivered on these commitments in the first half. Over the past six months, our total revenue grew by 19%, fueled by increased recurring revenue, and we have invested fully in line with our capital allocation priority, focusing on our high-impact programs. More on that in a moment. Importantly, we have grown our operating profit by 56%, even while making these strategic investments. In addition, in June, we completed share buyback, underscoring both our confidence in Genmab's future and our commitment to delivering value to our shareholders. We ended the first half with around $3 billion in cash, and that not only reinforces the strength of our financial foundation, but importantly, it gives us the flexibility for continued growth and expansion. Now, let's turn to some of the recent advancements for our late-stage programs, as well as a reminder of the overall potential.

ApgaritaMab, RINA-S, and AkasuniMab are all poised to drive significant revenue growth for Genmab by the end of this decade. All three programs made progress towards this potential over the past few months. Excitingly, for ApgaritaMab, in May, we submitted an FPLA to the FDA for ApgaritaMab in second-line follicular lymphoma in combination with Rituximab and lenalidomide, or R-square, based on a statistical and clinically significant improvement in overall response rates. In July, the FDA accepted this PLA for priority review with a target action date of November 30, 2025. If approved, ApgaritaMab plus R-square has the potential to be the first bispecific antibody combination regimen available as a second-line treatment option for patients with relapsed or refractory follicular lymphoma. Even more excitingly, today, we announced that the Apgar FL1 study met its dual endpoints of progression-free survival and overall response rate in a pre-planned interim analysis.

These unprecedented positive results will be the basis for global regulatory submissions. Taha will share some of the details of this promising data with you in just a moment. These important phase 3 results support our goal to move ApgaritaMab into earlier lines of therapy in order to benefit more cancer patients. Also supporting this goal, in recent months, we and ApgaritaMab have presented data highlighting the depth, breadth, and strength of the comprehensive ApgaritaMab development program. This includes 14 abstracts at EHA, including two oral presentations, and 28 abstracts, including one oral at ICML. ApgaritaMab, with its rapid clinical development and over 40 active clinical trials, remains positioned to become the core therapy in B-cell lymphomas, with anticipated peak sales exceeding $3 billion.

Turning to RINA-S, the first disclosure for single-agent RINA-S in patients with advanced endometrial cancer from a dose expansion cohort of the phase 1-2 RAINFALL-01 study was unveiled at ESCO. Today, Taha will provide a brief reminder of this exciting data. During our post-ESCO event, we also announced our plans to broaden the reach of RINA-S, and we anticipate that we will have three phase 3 trials underway by the end of the year. In addition to our ongoing trial in platinum-resistant ovarian cancer, we plan to initiate a phase 3 in endometrial cancer and a phase 3 trial in platinum-sensitive ovarian cancer. Beyond gynecologic cancers, we also announced our intent to begin a phase 2 trial in non-small cell lung cancer. You can see our track record of being able to accelerate the clinical development of key programs continues.

Based on this exceptionally strong execution, we remain on track to bring RINA-S to ovarian cancer patients in 2027. Given its best-in-class profile, we expect to achieve peak sales in ovarian and endometrial cancers exceeding $2 billion. We're also launching a phase 2 study for AkasuniMab as we evaluate its potential in advanced melanoma. As we continue to look forward to additional data for this program in non-small cell lung cancer in the second half of the year, now over to Taha, who will provide a brief review of our recent company announcement on ApgaritaMab, followed by an overview of the promising RINA-S data from ESCO. Taha, the floor is yours.

Speaker 2

Thank you, Jan. We are, of course, extremely pleased to announce today the results of the phase 3 Apgar FL1 trial, which met its two primary endpoints of overall response rate and progression-free survival, demonstrating statistically significant and remarkable clinical data and differences in both endpoints, reducing the risk of disease progression or death by 79%. In other words, a hazard ratio of 0.21. These results, which were derived from a pre-planned interim analysis, will be submitted for presentation at this year's ASH meeting, and they will serve as the basis for global regulatory submissions. Here I would like to note that the supplemental BLA submission that Jan mentioned earlier with the FDA was actually based on data from an earlier interim analysis in the beginning of this year.

These results also demonstrated comparable, consistent, statistically significant improvements in OR and PFS, and the details you can see on this slide. For both interim analyses, the safety profile of ApgaritaMab in combination with R-square was consistent with the known safety profile of the individual regimens, and no new safety signals have been observed. Patients with relapsed and refractory follicular lymphoma do have therapeutic options available. However, responses become progressively shorter and less durable with each subsequent line of therapy, and this is accompanied by an increased risk of transformation into aggressive large cell lymphoma. What the data we shared today for ApgaritaMab highlights is the potential to completely transform and disrupt this current treatment paradigm. This is really also reflected in the collaboration with the FDA as we were able to accelerate the submission in the United States.

Both the recent sBLA submission and these data, which will support the planned global regulatory submissions, as mentioned, bring us closer to being able to offer ApgaritaMab to patients in need of innovative therapies earlier in their treatment journey, where they can have a much larger impact. Now, let's move on to the recent RINA-S data that was shared at ASCO. Previously, we discussed the medical need for patients with ovarian cancer. There also continues to be a significant unmet medical need for the treatment of women with endometrial cancer. At ASCO, we presented the first results for single-agent RINA-S in women with advanced endometrial cancer from the dose expansion cohort B2 of the ongoing phase 1-2 RAINFALL-01 study.

This cohort included 64 patients with heavily pretreated endometrial cancer who were randomized one to one to receive either RINA-S at 100 milligrams per meter squared or RINA-S at 120 milligrams per meter squared. In the efficacy evaluation of patients, the confirmed ORR was 50%, including two complete responses with RINA-S 100 milligrams per meter squared, and the disease control rate at that dose was 100%. Antitumor activity was observed regardless of exploratory folate receptor alpha expression levels. In addition to a superior response rate, treatment with RINA-S at 100 milligrams per meter squared led to deeper and more meaningful tumor size reductions. At the time of the data cutoff for the presentation, the median duration of response was not yet reached, and with a median follow-up of 7.7 months, 8 of the 11 confirmed responses were still ongoing.

As shown in the swimmer plot, responses with RINA-S were observed early, with a median time to response of six weeks for both groups, that is de facto at the first response assessment. RINA-S also had a manageable safety profile consistent with previous reports, and the safety profile was broadly similar between the two dose levels. The most common treatment-emergent AEs were cytopenias and grade 1 and 2 gastrointestinal events. Notably, there were no signals of ocular toxicity, interstitial lung disease, or neuropathy observed in these reported patient cohorts. The data we've now seen in both ovarian and especially endometrial cancer, which is known to actually have a much lower expression of folate receptor alpha, support the important hypothesis that RINA-S potentially works irrespective of the level of folate receptor alpha expression.

As folate receptor alpha is expressed across a broad range of solid tumors, this, of course, presents an opportunity to broaden the potential across a diverse array of tumor types, opening multiple avenues for therapeutic expansion. Our ambition is to expand both within gynecological cancers across the lines and move RINA-S into the earlier lines as fast and efficient as possible, but also beyond targeting additional solid tumors, such as in the first step, non-small cell lung cancer. To that end, a proof of concept phase 2 study is indeed planned to start dosing patients in the fourth quarter of this year. As Jan mentioned, we are accelerating and expanding the development of RINA-S into additional trials, which already announced three phase 3s to dose the first patient in 2025, one of them already ongoing.

I'll hand it over to Brad for a review of the solid recent commercial performance for ApgaritaMab and Tivdak.

Speaker 0

Hey, thanks, Taha. We delivered strong performance across our commercial business in the first half of 2025. This is driven by our innovative antibody science, our proven launch capabilities, and execution by our field teams. We've maintained leading positions for our commercialized brands and have achieved critical milestones that will support our long-term growth. This performance reinforces the solid foundation we've built as we strategically scale our operations, accelerate adoption of our medicines, and positively impact treatment paradigms for patients around the world. Overall, sales for ApgaritaMab and Tivdak in the first half of 2025 were up 60% year over year. This accounted for 31% of our total revenue growth. We expect to see our commercialized medicines increasingly contribute to our overall revenue growth over time. In the second quarter, we achieved significant milestones for ApgaritaMab and Tivdak that will be important catalysts for our future growth.

Following regulatory approvals for Tivdak in Japan and Europe last quarter, we've now entered into the next phase of our commercialization strategy focused on long-term value creation through our wholly owned launches. We also made important progress in our work to reach more patients and deliver on ApgaritaMab's growth potential. As Jan noted, we presented data at ASCO, EHA, and ICML that together emphasize the strength of the ApgaritaMab clinical development program across histologies and treatment settings. Importantly, as we announced earlier today, we've accelerated our work to move ApgaritaMab into earlier lines of therapy with the launch in second-line follicular lymphoma expected later this year. Turning now to ApgaritaMab's first half performance, ApgaritaMab posted $211 million in global sales. This is a 74% year-over-year increase.

We're highly encouraged by ApgaritaMab's performance and steady growth across geographies to date as we work to bring ApgaritaMab to as many appropriate patients as possible. Performance in the U.S. continues to demonstrate the value of ApgaritaMab as an off-the-shelf, dual indication option for both DLBCL and FL, as we're seeing accelerated adoption across sites of care and increases in new patient starts. As we continue executing on our launches and prepare to enter earlier lines of therapy, we remain focused on increasing adoption and rapidly identifying patients, particularly in the community setting where most patients seek treatment. In Japan, ApgaritaMab launched in third-line plus follicular lymphoma in May. The launch is off to an encouraging start, building on the uptake we've seen in large B-cell lymphoma and also driven by the national and field-level activities and account activation.

Across all other markets, through our partner AbbVie, we've also seen solid growth for ApgaritaMab and Tivdak. This is driven by an increasing number of countries gaining access and reimbursement, along with a rapid uptake by physicians following reimbursement decisions. Globally, ApgaritaMab has received the most regulatory approvals for bispecific in DLBCL and FL, with approvals in more than 60 countries worldwide. This includes nearly 50 countries with approvals in both indications. Today, ApgaritaMab is uniquely positioned as the only bispecific approved as an off-the-shelf, dual indication option in DLBCL and FL. With encouraging utilization across markets, consistently positive feedback from physicians on ApgaritaMab's profile, and our progress moving into earlier lines of therapy, we're confident that we have the commercial and clinical foundation in place for ApgaritaMab to become the core therapy across B-cell lymphomas. Moving now to Tivdak.

Tivdak has proven to be a significant advancement for women with recurrent or metastatic cervical cancer in the U.S. It has changed the treatment paradigm, serving as a model for a new standard of care around the world. In the first half of this year, we built on this progress to bring Tivdak to more women and deliver on our commitment to contribute to the gynecologic cancer community in a meaningful way. Global sales for Tivdak in the first half of 2025 totaled $78 million. This is up 30% compared to the same time last year. Of note, commercial sales now reflect our launch of Tivdak in Japan in May. This was the first medicine launched independently by Genmab, and we're seeing encouraging uptake. In the U.S., performance continues to be strong and stable across sites of care.

In Europe, we've made important progress establishing our infrastructure and operations to support commercial markets in the region. Our teams are ready to launch Tivdak with the first launch anticipated in Germany soon. Other countries are expected to follow based on regulatory and reimbursement timelines. This progress marks a strong entrance into the next phase of our commercialization strategy as we launch our medicines independently, enter new markets, and broaden our impact for patients in the gynecologic cancer community. With continued solid performance of our commercialized medicines and proven launch execution, we're confident in our path for growth. We believe we have the right pieces in place to drive long-term value creation and maximize our opportunities ahead for ApgaritaMab and our emerging Gynoc portfolio.

As we continue executing the next phase of our commercialization strategy, we're focused on expanding utilization of our medicines and bringing them to as many patients as possible around the world. The work we've done to transform our commercialization business and accelerate our pipeline is paying off. As we progress through this new and exciting chapter for Genmab, we look forward to all that is to come for Tivdak and ApgaritaMab in the back half of the year. With that, I'll hand the call over to Anthony to discuss our financials. Thanks, Brad. In the first half of 2025, we delivered solid revenue growth, driven by sustained recurring revenues and the solid market performance of our products. We've also significantly enhanced our long-term growth potential as we continue to gather promising clinical data for both ApgaritaMab and RINA-S. As we're going to see, our financials remain strong.

We achieved 19% total revenue growth and 27% recurring revenue growth. This was driven by very strong royalties from Darzalex and Kesimpta. Importantly, this growth was also driven by product sales from ApgaritaMab and Tivdak, which together represented around 31% of our total revenue growth. Looking at Darzalex, we continue to see strong growth. Overall, net sales grew by nearly 22%. That's $6.8 billion for the first half of the year, which translates to over $1 billion in royalty revenue for us. This growth was driven by continued share gains and strong performance in the frontline setting. You can see that the quality of our revenue profile continues to improve. In fact, in the first half of this year, recurring revenues represented 97% of our total revenue. That compares favorably to 90% in the first half of last year.

Stepping back, what's really clear is that the investments we've made in building out our commercialization teams and capabilities are paying off. This sets us up well as we prepare for potential expansion into earlier lines for ApgaritaMab, including second-line FL, and the potential launch of RINA-S in 2027. We continue to take a disciplined approach to these investments. Total OpEx in the first half of 2025 was slightly less than $1 billion, up 6% over the first half of last year. That excludes the impact of the Profound Bio acquisition. We're managing our investments strategically, prioritizing our high-impact phase 3 programs and focused investments in our commercialization capabilities. Our operational discipline contributed to our operating profit growth of an impressive 56% in the first half. Here you can see that we're really continuing to deliver on our commitments.

Next, looking at our net financial items, we have a net gain of $119 million. Moving on to tax, we have tax expense of $136 million, which equates to an effective tax rate of about 20%. Taken together, our net profit amounts to $531 million. You can see continued strong underlying financial performance. Let's move to our 2025 financial guidance. I'm pleased to note that we're improving our guidance based on projected higher revenues and operating profit, even as we continue to expand the development of our late-stage programs. We now expect our revenue to be in the range of around $3.5 to $3.7 billion, delivering a robust 15% growth at the midpoint. That compares to 12% growth under our previous guidance. We're increasing the midpoint of our total revenue guidance by $100 million. This is driven by the strong performance of Darzalex and positive ApgaritaMab sales momentum.

That's partially offset by a slight impact from lower TEPEZZA royalties and milestone revenue. We now anticipate that our recurring revenues for the year will grow 22%, compared to 18% under our previous guidance. For OpEx, due to our continued focus and disciplined approach to our investments, we still expect to be in a range of around $2.1 to $2.2 billion. Putting this all together, we're planning for operating profit in a range between around $1.1 to $1.4 billion, with the midpoint of guidance amounting to over $1.2 billion of operating profit and strong year-over-year growth of 26%. Our improved guidance highlights our continued strategic discipline, targeted investments, and operational efficiency, all while advancing our pipeline. Now, finally, to give you just a bit of color on FX.

Here, every 10-point move in the exchange rate relative to our guidance rate for the dollar to kroner of 7.2 is worth around $5 million in operating profit or loss at the midpoint. In summary, our performance in the first half of 2025 underscores our ability to deliver solid, high-quality revenue growth, advance key pipeline assets, and maintain strong profitability through disciplined execution. Looking ahead to the second half of 2025, we will continue to build on this momentum by further prioritizing our investments and expanding market opportunities. We are, of course, continuing to monitor the geopolitical situation and the potential impact on our business. At this stage, we do not anticipate a significant impact on our 2025 financial guidance.

What's important to note is our very strong financial foundation, sustained profitability, and disciplined capital allocation strategy will really enable us to position Genmab for growth and expansion, as well as create value for shareholders and patients. On that note, I'm going to hand you back over to Jan.

Speaker 1

Thank you, Anthony. Let's move on to our final slide. We have strengthened the foundations of our business in the first half of 2025. We have expanded the reach of both ApgaritaMab and Tivdak to more patients, and we anticipate even further growth for ApgaritaMab before the end of the year. For RINA-S, we have presented additional supportive clinical data showing its potential beyond ovarian cancer, and we are prepared to maximize that potential with additional phase 3 clinical trials. We continue to anticipate further AkasuniMab data this year. In addition to these priorities, we will continue to actively look for opportunities to grow our pipeline, both organically and inorganically, positioning us for sustainable long-term growth and value creation. In summary, in the first half of 2025, our solid financial performance, including our own products, ApgaritaMab and Tivdak, reinforced the strength of our financial foundation.

This strong foundation is coupled with a disciplined capital allocation strategy that prioritizes investment in our high-impact phase 3 programs, allowing us to unleash the full potential of our late-stage pipeline while maximizing the success of our commercialized medicines. Together with our demonstrated track record of execution, we are set up for long-term success and continued outperformance through 2030 and beyond. That ends our formal presentation. Thank you for listening. Operator, please open the call for questions.

Speaker 3

Thank you, sir. As a reminder to ask a question, please press star one and one on your telephone and wait for your name to be announced. To withdraw your question, please press star one and one again. Once again, please press star one and one on your telephone and wait for your name to be announced. To withdraw your question, please press star one and one again. For the benefit of all participants on the call today, please limit yourself to one question per person. If you have any further questions, please rejoin the queue. Thank you. We are now going to proceed with our first question. The questions come from the line of Jonathan Chang from LIRINC. Please ask your question.

Hi guys, thanks for taking my questions, and congrats on the positive phase 3 ApgaritaMab FL1 results. What is your latest thinking on the positioning of ApgaritaMab versus other CD20 bispecifics in the competitive landscape, both in terms of clinical development and your commercial experience? Thank you.

Speaker 1

Thanks, Jonathan, for the question. Excellent question. I'm going to hand it over to Taha first, and then Brad will certainly add to that. Taha, why don't you start?

Speaker 2

Yes, Jonathan, thank you for the question. As it relates to the position, I think we feel, and we've been saying this for a while, very comfortable where we are. We have a very broad and aggressive development plan. This is the first phase 3 to read out now for ApgaritaMab, but there are more to come in the next six to nine months. As you just look at the breadth of the development and also the accrual, as well as the times when these studies were initiated, I think we have a head start now in second-line follicular lymphoma for sure, even though we started one and a half years later. We announced that our frontline diffuse HB cell studies fully accrued a year ahead of initial projections, so we are very anxiously awaiting those results coming. We announced that we expect them to come in 2026.

The phase 3 is both in monotherapy as well as in combination with lenalidomide, also results that we're looking forward to. The frontline follicular lymphoma study is accruing extremely well. From a positioning, from a data generation point of view, we feel very strong on the utilization. I think Brad can also talk about this, the fact that we very early on started to generate data that was informing physicians in the outpatient setting how to utilize ApgaritaMab is also paying off quite well. There is more to come on that end as well. As it relates to how the market reacts, I probably should hand this over to Brad. Broadly speaking, we feel that we have the broadest, most ambitious program in the bispecific space, and we've also been consistently showing that we're executing successfully on these studies.

That is equally important, not only on the clinical execution, but also on the regulatory execution if you look at some of the competitive news. Brad.

Speaker 0

Yeah, Jonathan, thanks for the question. Just kind of building on what Taha had said, we're certainly encouraged by our current leading sales position globally, and also being the only off-the-shelf dual indication bispecific. We're just receiving tremendous feedback from our physicians and customers. As we've said all along, starting to move into earlier lines of therapy with larger markets is proving beneficial, as mentioned, with the 60+ countries where we're approved, 50 within a dual indication. Certainly, this most recent FL data can continue to help us expand into the community where we've seen accelerating uptake already. It has been a differentiator in the marketplace.

Speaker 1

Thanks, Tah.

Speaker 2

Thanks for taking the question.

Speaker 1

Thanks. To top it off, Jonathan, we just submitted close to 30 abstracts on ApgaritaMab for ASH. There will be a lot of data, hopefully, at the end of the year. Let us move to the next question, operator.

Speaker 3

Sure, sure. We are now going to take our next question. The questions come from the line of Asthika Goonewardene from Truist. Please ask your question.

Hi guys, thanks for taking my question. There's a lot of chaos at the FDA right now, or calamity, whatever you want to call it. We think about some of the regulatory filings you have coming up. I have a two-part question on that. One, how confident do you feel that you can file RAINFALL-01 Part C, which is the single-arm cohort? How confident do you feel you can file that for accelerated approval? Secondly, is there any risk of pushback from the FDA on Epcore, FL1 to wait until OS is more mature? Thanks.

Speaker 1

Thanks, Asthika, for the questions. I will ask you to start off with the RAINFALL study, and then maybe you can also take the FL1 study units.

Speaker 3

Thank you, Jan, and thank you, Asthika. I start with RAINFALL. The accelerated approval, of course, is predicated on strong data on ORR and duration of response. At this moment, we don't have any reason to believe that the FDA will have any pushback provided the data supports and we are aligned with the regulations in terms of the phase 3 well underway. At this moment, we don't perceive any risk on that. As we committed to launch in 2027, we reinforce our commitment to launch RINA-S in 2027. With regard to EPKINLY, FL01, as you know, that indication got BTD in September 2024. We are engaging with the FDA in a very active and positive manner. As we announced publicly today, the sBLA was accepted with the PDUFA date in November. We feel very confident that we have a path forward ahead of us.

Speaker 1

Thank you, Judith. Thanks, Asthika, for the question.

Speaker 3

We are now going to proceed with our next question. The questions come from the line of Rajan Sharma from Goldman Sachs. Please ask your question.

Hi, and thanks for taking the question. Firstly, on ApgaritaMab, assuming you get the approval in November, could you just outline your initial launch strategy? Is there a specific patient group that you might be targeting? How should we think about revenue contribution in 2025 and 2026? On the label there, do you expect that there'll be no requirement for hospitalization? The second question was on the pipeline. I noticed that the Hexabody OX40 or Gen 1055 has been discontinued in solid tumors. Could you talk to the rationale here? I think that's the second Hexabody asset now that's not being progressed this year. It'd be great to hear your confidence in that platform. Could that OX40 asset be used in immunology potentially? Thank you.

Speaker 1

Thanks, Rajan, for the questions. I will ask first Brad to comment on the ApgaritaMab questions, and then Taha, you can probably speak a bit more on Hexabody OX40. What I can tell you before they start, Rajan, is that we're very excited about the Hexabody platform. We will actually bring a new one into the clinic, we hope, between now and the end of the year. We are certainly very confident in the platform, but we also are rigorous in prioritizing our portfolio, focusing more and more on late-stage programs. That requires tough decisions. I will let Taha give you some further color there. Brad, why don't you start on ApgaritaMab and the launch strategy for in the follicular lymphoma setting?

Speaker 0

Thank you for the question. I think, as we've stated for quite some time, the larger opportunity is in these earlier lines of therapy. We're certainly pleased with the potential for ApgaritaMab to pave the way in this indication, specifically in second-line FL. In the U.S., as we've discussed, FL is a really important opportunity as we expand into the community where we've already seen accelerating uptake and see this as a meaningful opportunity for patients, but also for the brand moving forward.

Speaker 1

Thanks, thanks, Brad.

Speaker 2

I'll take the question on OX40. The first thing I would say is that just to correct the impression that hexamerization asset is used for this particular target, or also how it was used for C27 in order to increase outside-inside signaling by improving clustering. That hypothesis definitely helped through. The Hexabody OX40 program did show all the things that we were anticipating and hoping for, both in terms of a much, much stronger signal in terms of the biology, but also in terms of overcoming the bell-shaped curve. The decision to discontinue, as Jan was already indicating, was primarily around the fact that it's from a profile not really differentiated from some of the other assets that we have. From a development path vis-à-vis other opportunities that exist, it's really not as promising as some of the other opportunities.

We're investing, as you've been hearing for a while now from us, our resources or money where we can see the most return on our investment. That was the OX40 question. Maybe I'll take the labeling question that we still owe you. The follicular lymphoma label already does not include any hospitalization. That's true for monotherapy ApgaritaMab and follicular lymphoma in third line. That's also going to be true in combination with elsewhere.

Speaker 1

Thanks, Taha. Let's move on to the next question.

Speaker 3

We are now going to take our next question. The questions come from the line of Yaron Werber from TD Securities. Please ask your question.

Hey, good afternoon, Dr. McClure, and thanks for taking my question. This is Jane on for Yaron. Now that follicular lymphoma is really a growing part of the conversation for ApgaritaMab, how are you thinking about ApgaritaMab's opportunity and differentiation versus leukemia specifically? Thanks so much.

Speaker 1

Thank you very much for the question. I'm handing it over to you, Tahamtan.

Speaker 2

Thank you for the question. First things first, we have a positive phase 3 in second line, and they don't yet have a report of the results. I think they have publicly said that they expect the results to come in by the end of the year. That's the first differentiation. We will have a significant head start, and I think that has played out well for us. In terms of the signal, consistently, although maybe not as dramatic, ApgaritaMab has shown better efficacy, higher CR rates, both in follicular lymphoma and then definitely also diffuse use of B cells. It's the more efficacious of the two bispecifics. The subcutaneous administration has been a disadvantage for us, and you know Lush is trying to bridge towards that, but not yet. That's another differentiation that currently is playing out.

I think in terms of safety, with the subsequent optimization, our CRS rates are as low as they are with MUSUL. Broadly speaking, we feel now very, very good about our position. I don't know if Brad has anything to say to that.

Speaker 1

Thanks, Taha. That is plenty. Let's move on to the next question.

Speaker 3

We are now going to take our next question. The questions come from the line of Michael Schmidt from Guggenheim Partners. Please ask your question.

Oh, hey, thanks for taking my question. I had another one on RINA-S, and specifically around your plans for development outside ovarian cancer. You did talk about this new phase 2 study in non-small cell lung cancer. Just wondering if you could expand upon that opportunity. Do you have any data in-house, phase 1 data in-house, or supporting this? What do we know about the follicular alpha expression in lung cancer? Thanks so much.

Speaker 1

Thanks, Michael, for the question. I'm going to hand it over to Taha, and he can give you an excellent rationale, Michael.

Speaker 2

Thank you for the question. I'll start at the beginning. Yes, I think the way we have been talking about this is, as we have increasingly learned that RINA-S is able to generate efficacy even in patients who have lower levels of folate receptor alpha expression. That, of course, then raises interest in disease areas where folate receptor alpha is expressed but at lower levels. That was what I was mentioning and referring to. EGFR-mutated non-small cell lung cancer, that's the indication we are looking at as the next step, is one that is slightly different. Adenocarcinoma non-small cell lung cancer is known to have folate receptor alpha expression really broadly, but not as high as it is, for example, in ovarian, but somewhat similar to endometrial, actually. EGFR-mutated non-small cell lung cancer does actually have an increase in folate receptor alpha expression.

This is the first case study for us to then explore additional solid tumor indications, not the last but the first, in a sequence that is very much driven by preclinical data and scientific rationale. We do have, as you were pointing to already, a small cohort that is very well enrolled now for its size. Initially, we meant to just generate some safety data, and we do have some signals, and they continue to be encouraging. We continue to generate that data. The intent of this study is really to give us now a dedicated vehicle with multiple different arms so that we can really strategically explore the opportunity for RINA-S initially in EGFR-mutated, but not restricted necessarily to EGFR-mutated non-small cell lung cancer. Very excited about that study, and we're going to be very much looking forward to the data this study will generate.

Speaker 1

Thanks, Tahamtan. Thanks, Michael.

Speaker 3

We are now going to proceed with our next question. The questions come from the line of Matthew Phipps from William Blair. Please ask your question.

Thanks for your question. Congrats on the strong EpgaritaMab, FL1 data. Maybe a question for Taha. You mentioned the broad development plan with EpgaritaMab as being a strength. I was wondering what you think about ADC combinations, and do you see a role for those longer term in lymphoma? Maybe how you will continue to explore those. Quickly, EpgaritaMab in melanoma, will that use the same q6 week dosing, or do you need to explore additional dosing regimens in melanoma? Thank you.

Speaker 1

Thanks, Matthew. I can take the second question. AkasuniMab, we will stick with this every six week dosing because we think it's optimal for that compound. We don't need to do further dose frequency combinations, we believe. I'll let Judith add to that if there are any further things to add. Taha, why don't you start with the Epco development plans in the context of ADC combinations?

Speaker 2

Yeah, thank you for the question. Maybe the way I start this is, you know, what I laid out was the regulatory strategy that was following a very clear outline strategy, which we actually really talked about five years ago, that we were going to enter monotherapy in the relapsed refractory setting and then very rapidly move down the lines into the front line both in diffuse HB cell and follicular lymphoma, and these are the studies that are yet to read out. That was the development plan. Once we had the development plan, we would then focus on complementary data that would drive or inform how physicians can use the drug in different settings. A combination with an ADC is a very interesting one in that regard, in that place.

Jan already mentioned that there's a lot of data generation, up to a little bit more than 30 abstracts that are being submitted to ASH. There's actually an ISD that's going to open up in combination with LONCA, which is, I think, where you're heading towards too. There are other ADCs that are coming, MERKAS one, where there are discussions ongoing. I think ADCs very well will have a role in diffuse HB cell as well if they are able to improve the outcomes. I do think that with increasing data, what is our ambition, what is also becoming a reality is that bispecifics in particular, ApgaritaMab, are going to become a backbone of these novel combinations in the future.

Speaker 1

Thanks, Taha. Especially combinability seems to be really, really good with ApgaritaMab. We can combine it with literally all different types of different agents, Matthew. I think that may be a big advantage of the bispecific format like the one we use for ApgaritaMab. Judith, are you able to add anything more to the AkasuniMab every six week dosing question?

Speaker 3

No, thank you. As you said, we explored the every six weeks because it showed the best in terms of efficacy and safety.

Speaker 1

Thanks, Judith. I think that's it, Matthew. Thank you very much for the questions.

Speaker 3

We are now going to proceed with the last question. The questions come from the line of Keir Sting from Rayburn Atlantic. Please ask your question.

Oh, hi. Thanks for taking my question. I just have one follow-up question on the RINA-S in non-small cell lung cancer. Is the phase 2 trial going to test RINA-S in patients in the first line or second line setting of the non-small cell lung cancer, or both? Just a quick follow-up, is the RINA-S going to be tested as monotherapy or in combination with other checkpoint inhibitors? Thank you.

Speaker 1

Thank you for the question. Tahamtan, can you address this one?

Speaker 2

Yes, I will try to address it, although I do think we are now entering into spaces where we have to be careful because it's a competitive landscape and we may not necessarily want to show our hands as we are moving into this field. This study, as I mentioned, is intended to give us the optionality to interrogate RINA-S both in monotherapy as well as in combination. If you look a little bit at how our philosophy is in drug development as it played out in ApgaritaMab or in RINA-S in ovarian and in endometrial, then I think you can get an idea of how this study is going to be set up without going into the details of what combinations we're going to test and which line of therapy. Clearly, it is going to interrogate mono and combination therapy.

Speaker 1

Thanks, Taha. Very clear. This is the last question, operator.

Speaker 3

Yes, this is the last question showing. I hand back to you for closing remarks. Thank you.

Speaker 1

Thank you for calling in today. If you have additional questions, please reach out to our investor relations team. We very much look forward to speaking with you again soon.

Speaker 3

This concludes today's conference call. Thank you all for participating. You may now disconnect your lines. Thank you.