Genmab A/S

NASDAQ:GMAB

Earnings Call Analysis

Q1 2024 Performance and Future Outlook of Genmab

In Q1 2024, Genmab delivered robust financial results with a net profit exceeding DKK 1.3 billion. Key revenue drivers were DARZALEX, which grew 19% year-over-year with $2.7 billion in net sales, and Kesimpta, which achieved 66% growth. The company anticipates a 19% increase in revenue for 2024, driven by EPKINLY and Tivdak, expected to contribute DKK 1.2 billion. The proposed acquisition of ProfoundBio aims to strengthen the clinical pipeline, with significant investments slated for late-stage R&D. Despite increased expenditures, Genmab remains focused on profitability and growth, targeting blockbuster potential for Rina-S by 2027.

Strong Revenue Growth

In the first quarter of 2024, the company reported strong financial performance with total revenue exceeding DKK 4.1 billion, a 46% increase from the previous year. This growth was driven predominantly by a 42% rise in recurring revenues, fueled by robust royalties from key products like DARZALEX and Kesimpta, alongside net product sales for new entrants like EPKINLY and Tivdak .

Operational Investments

Operating expenses also grew significantly by 31% as the company continued to invest in research and development, focusing particularly on advancing mid- to late-stage pipelines such as EPKINLY, Tivdak, GEN1046, and GEN1042. The emphasis remains on securing successful launches, especially in major markets like the U.S. and Japan .

Product Performance

EPKINLY delivered USD 54 million in net sales for Q1, with over 90% of this arising from strong launch performance in the U.S. and Japan. Tivdak also showed promise with USD 27 million in net sales, marking its tenth consecutive quarter of demand growth, driven by positive feedback from gynecology and medical oncology customers .

Financial Position and Profitability

Even with increased investments, the company managed to deliver over DKK 800 million in operating profit, representing a 90% rise year over year. The effective tax rate stood at 22.8%, leading to a net profit exceeding DKK 1.3 billion for the quarter .

Future Guidance

The company has set ambitious goals for 2024, anticipating a 19% increase in revenue at the midpoint, largely driven by EPKINLY and Tivdak, which are expected to contribute over DKK 1.2 billion in growth. The proposed acquisition of ProfoundBio is expected to influence operational expenses pushing them toward the upper end of the guidance range of DKK 12.4 billion to DKK 13.4 billion .

Strategic Acquisitions

The proposed acquisition of ProfoundBio is considered highly synergistic with the company's strategic vision. The acquisition will strengthen the company’s portfolio, especially with Rina-S, which is regarded as a potential best-in-class ADC and is projected to achieve blockbuster peak sales upon regulatory approval expected by 2027 .

Regulatory Approvals and Pipeline Expansion

There have been significant regulatory developments, including the FDA approval of Tivdak for treating recurrent or metastatic cervical cancer. Additional filings and approvals for EPKINLY in various regions are ongoing, with emphasis on follicular lymphoma. The company also anticipates starting multiple Phase III trials for their pipeline products throughout the year .

R&D and Innovation

As a part of its innovation strategy, the company presented new data for several products at major conferences. Upcoming presentations include rapid oral presentations on EPKINLY and Tivdak, as well as a pivotal trial design for acasunlimab in second-line non-small cell lung cancer. Efforts are underway to engage with health authorities for developing these pivotal trials .

Closing Remarks and Outlook

The leadership emphasized their satisfaction with the year’s strong start and reiterated their focus on seizing significant growth opportunities through disciplined investments. Continued success in regulatory approvals, strategic acquisitions, and pipeline advancements are expected to propel the company forward in achieving its 2024 goals .

Earnings Call Transcript 2024-Q1

[Operator]

Hello, and welcome to the Genmab First Quarter 2024 Conference Call. As a reminder, this conference call is being recorded.

During this telephone conference, you may be presented with forward-looking statements that 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 actual results, unless this is required by law.

Please also 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.

[Jan van de Winkel, executive]

Hello, and welcome to Genmab's conference call to discuss the company's financial results for the period ending March 31, 2024. With me today to present these results is our CFO, Anthony Pagano; and our Chief Operating Officer, Anthony Mancini. For the Q&A, we will be joined by our Chief Medical Officer, Tahi Ahmadi, and Chief Development Officer, Judith Klimovsky.

As already said, we will be making forward-looking statements, so please keep that in mind as we go through this call. During today's presentation, we will reference products being developed under some of our strategic collaborations, and this slide acknowledges those relationships.

Before we look at our first quarter results, I want to remind you of our consistent track record of success. Our proprietary technologies fuel our robust product pipeline which is both expanding and maturing and our growing revenue streams allow us to continue to invest in our people and in our pipeline. These are investments that will further accelerate our evolution into a fully integrated biotech innovation powerhouse.

In addition to our existing technologies and mid-to late-stage pipeline, a key investment that will enhance our long-term growth profile is the exciting proposed acquisition of ProfoundBio. So let us turn to that briefly now.

The proposed acquisition of ProfoundBio firmly aligns with our core vision and strategy of transforming the lives of people with cancer and other serious diseases. It is highly complementary to our business. And the addition of ProfoundBio's next-generation ADCs, including Rina-S, plus its novel ADC technology will further strengthen our already very strong and innovative mid- to late-stage clinical pipeline. This will also strengthen and accelerate our capabilities in the ADC space. In addition to helping to propel us towards a 100% owned model with more value captures.

So we are investing to unlock meaningful value by the end of the decade with significant upside into the 2030s. We expect to close the acquisition in the first half of 2024, subject to the receipt of regulatory clearances. So now let us turn to other important recent events.

Epcoritamab continues to receive regulatory approvals and relapsed or refractory diffuse large B-cell lymphoma in various territories with additional filings underway. We and our partner AbbVie, have a robust development plan for epcoritamab. And in the first quarter of the year, we took significant steps to move into follicular lymphoma. In March, we, along with AbbVie, initiated the first of multiple Phase III trials anticipated to start this year.

Epcoritamab in combination with rituximab and lenalidomide for the treatment of patients with previously untreated follicular lymphoma. Looking at relapsed or refractory follicular lymphoma, in addition to the J-NDA submission in Japan, the FDA granted priority review to a supplemental biologic license application for EPKINLY as a treatment for relapsed or refractory follicular lymphoma following at least 2 prior lines of therapy with a PDUFA date of June 28.

If approved, EPKINLY will be the first and only subcutaneous bispecific antibody approved to treat this indication. And these were not the only regulatory events.

Excitingly, the FDA has now approved the supplemental biologics license application for Tivdak for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. And this converts the 2021 accelerated approval of Tivdak to a full approval, making Tivdak the first ADC with demonstrated overall survival data to be granted full approval in this patient population.

This approval represents a significant achievement for women with recurrent or metastatic -- and metastatic cervical cancer as it reinforces Tivdak as a survival extending treatment option in patients whose disease has advanced after initial treatment.

In addition to this approval, I'm very excited to share that at the end of April, we filed a J-NDA requesting approval for Tivdak for patients with advanced or recurrent cervical cancer in Japan. And this is excellent news for patients in Japan in need of this potential therapy and a milestone for Genmab as we continue to build our presence in Japan.

I would like to thank the patient and investigators who took part in the clinical trials that form the basis of the U.S. approval and Japanese submission or partners at Pfizer for the collaboration and the passionate and determined teams at Genmab whose hard work and commitments made these events possible.

Before moving on, I would also like to note that we were very pleased to hear that in March, Tivdak was added to the NCCN Clinical Practice Guidelines in Oncology for Vaginal cancer under Other Recommended Regimens.

In the first quarter, there were several data presentations across our programs, including an oral presentation for Tivdak at the SGO Annual Meeting on women's cancer. And presentations for EPKINLY at conferences, including the Annual Meeting of the Japanese Society of Medical Oncology and the AACR Annual meetings.

We are also looking forward to multiple upcoming data presentations at ASCO. These include 2 rapid oral presentations for EPKINLY of new data in both relapsed or refractory and untreated follicular lymphoma. A rapid oral presentation on Tivdak in head and neck cancer and a poster presentation for acasunlimab or GEN1046 in second-line non-small cell lung cancer. And this is, of course, the data that we and our partner, BioNTech, anticipated presenting in the first half of this year. And we are currently engaging with health authorities on the design of a pivotal trial in this patient population with an aim to start this trial in late 2024.

Finally, turning to medicines powered by our innovation. In March, Janssen announced that the FDA approved RYBREVANT in combination with chemotherapy for the first-line treatment of patients with non-small cell lung cancer with EGFR exon 20 insertion mutations, converting to May 2021, accelerated approval to a full approval.

In addition, in Q1, Janssen submitted applications for approval in both the U.S. and Europe for subcutaneous daratumumab based on data from the Phase III PERSEUS study.

I'm pleased to now hand over the call to Anthony Mancini to take you through our first quarter 2024 net product sales, including for DARZALEX, Anthony, the floor is yours.

[Anthony Mancini, executive]

Thank you, Jan. In Q1, product performance across our 2 key revenue streams, royalty Medicines and Genmab commercialized medicines showed very strong growth. Our portfolio includes royalty medicines: DARZALEX, Kesimpta, TEPEZZA, TECVAYLI, RYBREVANT and TALVEY.

DARZALEX demonstrated strong demand growth in Q1 with just under USD 2.7 billion in net sales, a 19% year-over-year growth driven predominantly from share gains in frontline multiple myeloma.

With the recent filing of PERSEUS, there are continued growth opportunities ahead with DARZALEX subcutaneous based therapies in the frontline transplant-eligible multiple myeloma space, including maintenance.

DARZALEX is also being combined with both newer and older therapies in multiple myeloma, including with 2 of our recently approved DuoBody medicines TECVAYLI and TALVEY. We expect continued growth and use of DARZALEX as a backbone in later line settings as well.

Kesimpta achieved continued strong demand growth with $637 million in Q1, a 66% year-on-year growth. Kesimpta demand growth is not only progressing well in the United States, but also outside the United States. It continues to be the new to brand share leader in 7 of 10 major markets outside the U.S.

The performance across our other recently launched royalty medicines, TECVAYLI, TALVEY and RYBREVANT all bispecifics based on our DuoBody technology, each delivered strong growth in the quarter.

The TECVAYLI launch is continuing to go very well and delivered $133 million in the quarter with strong uptake and rapid adoption in the U.S. and other key markets, reflecting a best-in-class off-the-shelf BCMA bispecific therapy that's offering deep and durable responses in relapsed or refractory multiple myeloma. We expect to see continued strong Genmab revenue growth from our diverse royalty medicines portfolio in 2024 and beyond.

Turning to our Genmab commercialized medicines on Slide 8. EPKINLY delivered USD 54 million in net sales for Q1. With over 90% coming from strong launch performance in both the U.S. and Japan. We are very pleased with the EPKINLY launch performance across geographies. In the U.S., we continue to see robust uptake across key accounts. EPKINLY was launched in Japan late last year, and we're highly encouraged by the early launch update, an overall positive response from our customers there.

EPKINLY is the first and only approved bispecific antibody in the U.S., the EU and Japan, for patients with third line plus diffuse large B-cell lymphoma. And we are preparing for potential approvals for EPKINLY in third-line plus follicular lymphoma with U.S. PDUFA date of June 28.

We're also pleased to announce that earlier this week, the NCCN has included EPKINLY monotherapy as a preferred regimen with a 2a designation in follicular lymphoma after 2 prior lines of therapy. Our first indication in third-line plus DLBCL, an area of significant unmet need is the first step to establishing EPKINLY as the core therapy across B-cell malignancies including follicular lymphoma and in earlier lines of treatment.

Tivdak delivered $27 million in net sales for Q1, representing the tenth consecutive quarter of demand growth. We're pleased with Tivdak performance which was primarily driven by an increasing breadth of ordering accounts. Gyno and Med Onc customers continue to provide positive feedback on the impact Tivdak is making on the lives of women with cervical cancer.

As Jan mentioned, the Japan New Drug Application for Tivdak was submitted in late April. And the FDA approval on April 29 based on the innovative 301 study, which demonstrated a 30% improvement in overall survival and a 33% improvement in progression-free survival will help establish Tivdak as the clear standard of care in second line plus recurrent or metastatic cervical cancer.

We're enthusiastic about the proposed acquisition of Profound Bio, whose lead asset Rina-S is a potential best-in-class ADC in ovarian cancer that would add a second ADC in gynecologic oncology to our portfolio in addition to Tivdak.

As an end-to-end biotech company, we're very pleased with the performance of our Genmab commercialized medicines and look forward to carrying this momentum through 2024 and beyond. Thanks to our partners and thanks to the entire cross-functional Genmab team for all they do every day to deliver for the patients we serve.

With that, let me hand it off to Anthony Pagano to provide additional perspective on our Q1 financials. Anthony?

[Anthony Pagano, executive]

Great. Thanks, Anthony. We continue to strengthen our foundation in Q1. Having reached our goal of successful regulatory approvals and launches for EPKINLY in the U.S., Europe and Japan in 2023. We are pleased with how the launches are progressing into Q1. Now we're looking forward to the potential for additional approvals in these territories for late line follicular lymphoma, and continuing to expand and accelerate EPCORE's clinical development. And as we see, our financials remain strong.

Recurring revenues grew by 42% in Q1. This was principally driven by strong royalties from DARZALEX, Kesimpta and other approved medicines as well as net product sales for EPKINLY. Our solid balance sheet, growing recurring revenues and significant underlying profitability allow us to continue to invest in our business and our pipeline at a very focused and disciplined way. And an important part of this has been to continue to build the team and capabilities that we need to succeed.

So let's take a look at those revenues in a bit more detail. We grew total revenue to over DKK 4.1 billion in Q1. And as I've already highlighted, that included a 42% increase in our recurring revenue.

This strong growth was driven by higher DARZALEX and Kesimpta royalties as well as royalties from other products, and we're really pleased with how EPKINLY and Tivdak are performing. Taken together, these 2 products contributed 27% of the total growth in revenue that we realized in Q1. And this really illustrates the power of our recurring revenue. And overall, this strong recurring revenue growth enables our continued highly focused investment, as you can see on the next slide.

In line with our significant growth opportunities, total OpEx grew 31% in Q1. In R&D, we've accelerated our investment into our product portfolio, especially the advancement of our mid- to late-stage pipeline. Here, we're expanding the development for EPKINLY, Tivdak, GEN1046 and GEN1042, and we continue to invest to secure a successful EPKINLY launch in our 2 key markets. the U.S. and Japan.

Now let's take a look at our financials as a whole. Here, you can see our summary P&L for Q1. Revenue came in at over DKK 4.1 billion, and that's up 46% on last year. Total expenses were just under DKK 3.2 billion with 73% being R&D and 27% SG&A. And even with the increased investment, we're still delivering over DKK 800 million of operating profit, and that's up more than 90%.

Moving now to our net financial items. Here, we have a gain of DKK 915 million. This gain was driven by the strengthening of the dollar against the Krona in Q1 as well as by an increase in interest income. Then we have tax expense of just over DKK 390 million, which equates to an effective tax rate of 22.8%. And that brings us to our net profit of over DKK 1.3 billion. So as you can see, continued strong underlying financial performance.

With that, let's take a minute to revisit our robust financial framework. First off, our revenue profile on the left. There are now 8 products in the market that are generating recurring revenues for us. Three of these are already blockbusters and the remaining 5 all have significant potential for future revenue growth. So for this year, we're anticipating 25% recurring revenue growth at the midpoint and we expect significant cash inflows in the years to come.

Moving to the right. We remain focused on our investments as we evolve our organization for continued success. And at the top of the list is accelerating and expanding [ EPCORE ], but that's just one of the exciting opportunities that provide us with a compelling rationale for investing back into our business. As we've told you before, if we want to seize these meaningful opportunities, we've got to invest. And that's exactly what we're doing. With the Phase III trials we anticipate will start in 2024.

And on top of this, we also have the proposed acquisition of ProfoundBio, including its most advanced program, Rina-S. Rina-S is potentially best-in-class and registration trial ready. We anticipate the first potential approval for Rina-S in 2027. And importantly, we are anticipating blockbuster peak sales potential.

So with that background, let's now take a look at our guidance. Here, you can see our existing guidance, which we announced in February. We're currently on track to meet these financial targets, excluding the impact of the proposed ProfoundBio acquisition and related deal costs. We continue to anticipate strong growth in revenue for 2024 of 19% at the midpoint, driven by both our royalty medicines and importantly, we anticipate that we will have over DKK 1.2 billion of growth from EPKINLY and Tivdak. In fact, EPKINLY and Tivdak are driving nearly 40% of our total revenue growth in 2024.

Now as I told you back in April, we anticipate that the proposed acquisition of ProfoundBio will impact our guidance.

Pending closing of the deal, OpEx before transaction expenses are now anticipated to be at or moderately above the upper end of the guidance range of DKK 12.4 billion to DKK 13.4 billion. The anticipated increase reflects the incremental R&D investment to support the advancement of ProfoundBio's clinical programs, primarily Rina-S. This potential incremental investment is fully in line with our previously communicated priority of increasingly focusing our investment on mid- to late-stage R&D programs with high potential. And finally, as a reminder, we plan to update our overall guidance no later than our second quarter 2024 earnings.

Now let me provide a few closing remarks. In summary, we've had a very solid start to the year. We have growing recurring revenue streams, increasingly from our proprietary products. And that gives us a strong backbone of significant underlying profitability. And we're investing those revenues in a highly focused way to realize our vision and to capitalize on the very significant growth opportunities in front of us.

And on that note, I'm going to hand you back over to Jan.

[Jan van de Winkel, executive]

Thanks, Anthony. Let's move to our final slide. Over the past few months, we have made significant progress towards our 2024 goals especially for EPKINLY, we made strides towards both goals you see here with the initiation of a new Phase III trial as well as priority review from the FDA for relapsed or refractory follicular lymphoma. We look forward to the PDUFA date and potential approval of this new indication in June. And of course, we are extremely pleased with the recent approval for Tivdak. We're also very much looking forward to presenting the Phase II acasunlimab data at ASCO next month.

We continue to have a lot to look forward to in 2024, and we look forward to providing you with additional updates. That ends our presentation of Genmab's financial results for the first quarter of 2024. Operator, please open the call for questions.

[Operator]

[Operator Instructions]. And your first question comes from the line of James Gordon.

[Jan van de Winkel, executive]

Maybe move on to the next one, operator, and then take James back when he is back online. .

[Operator]

Of course, Yes, of course. The next question comes from the line of Sachin Jain.

[Sachin Jain, analyst]

Just 2 pipeline questions, if I may. Firstly, just post recent FDA, MRD negativity in first-line myeloma. Just wondered on your headline thoughts as to how that may change development and whether you sense any shift in J&Js? Whether this is a key decision metric for them as part of the HexaBody decision I expect at the end of this year, early into next year.

And then secondly, on GEN1046, just 2 quick questions. One at ASCO, should we be thinking about potential OS data in addition to the PFS you flagged before? And then on the Phase III trial design discussions with the regulators, just wondering if that's taking a little bit longer than expected and if there any specific aspects of the design that are holding us up at this moment.

[Jan van de Winkel, executive]

Thanks, Sachin, for the questions. So I think I'm going to hand over both of the questions to Tahi, and then maybe Judith can add to that. Tahi, why don't you start with the MRD-negative molecular endpoints.

[Tahamtan Ahmadi, executive]

Sure. Thank you for the question. So the first question, MRD-negative, I think the reaction generally to this is that this is a good thing for patients with multiple myeloma because it's frankly allows the opportunity to the development of novel mechanisms in front line, which otherwise would have been extremely challenging.

And I think as it relates to J&J they also in their own call recognized the opportunity that MRD negativity as a surrogate endpoint provides for the development of novel mechanisms in multiple myeloma. I think we can leave it at that.

As it relates to 1046, where we actually had all of our health authority interactions. So we met with the FDA and the European and Japanese Health Authorities and have gotten the feedback incorporating as we speak. And are continually operationalizing towards activating the study by the end of the year. So there's nothing really to hold up.

Your other question around the specifics of the abstract. We've done this many times. I try to avoid getting into the details of the abstract or the presentation. But I would, again, emphasize that OS is the appropriate endpoint in that space. And of course, an important data point -- probably the most important data point in the decision-making process for us.

[Jan van de Winkel, executive]

Thanks. Tahi, I think, Sachin, we probably need to keep it to that.

Thanks, Sachin, for the questions. So maybe, operator, let's see whether we can get James Gordon back.

[Operator]

One moment please. At the moment he's not in the queue, would you like to move on to the next question?

[Jan van de Winkel, executive]

Absolutely, Operator, please move on to the next one. He may have lost the line.

[Operator]

Your next question comes from the line of Vikram Purohit.

[Vikram Purohit, analyst]

So we had 2, one on GEN3014, and then one on just your thoughts on business development broadly. So on 3014, I just wanted to see if there's any updated thoughts from your side on time lines to the next data update? And then also how much of a time lapse there may be between the release of the data and the potential decision from J&J regarding potential next steps.

And then on business development, moving forward, how are you thinking about prioritizing between opportunities in oncology and potential efforts in immunology?

[Jan van de Winkel, executive]

Thanks for the question. So I will pass the first one to Tahi. So let me start with the second one on BD.

I mean we are going to be very, very focused on oncology. I mean, currently, the dominant focus is on oncology. And priority one is to actually as it relates to the opportunities is closing ProfoundBio acquisition, which we hope to do after getting a regulatory clearance in the coming months and then integrate and execute the development plan for Rina-S.

And then beyond that, we continue to look for opportunities such as bringing in tools and components for the R&D engine. And oncology is getting a lot of attention, but also I&I because we are increasingly also looking at immunology and inflammation. But the dominant focus is oncology for the time being.

So let me move to Tahi now for the Gen3014 data and the decision timing for J&J. Tahi?

[Tahamtan Ahmadi, executive]

Yes. I think on this particular question, I think we have been very clear and consistent. There's a pre-agreed data set with J&J that includes a number of patients and the number of months follow-up for these patients and also I have in previous calls repeatedly reiterated that the -- there's a predefined time window and that is relatively confined for J&J to make that decision. And if you take this all together, you can imagine that -- we said we are continuing to operations towards providing that data by the end of the year and the time window probably between that data becoming public and a decision is not that long. We should probably leave it at that. I don't think we can be more specific on this. But it's a very clearly laid out timetable window actually.

[Jan van de Winkel, executive]

Thanks Tahi. Thanks Vikram for the questions. So let's move back to the operator.

[Operator]

Your next question comes from the line of Xian Deng.

[Xian Deng, analyst]

Could you hear me all right?

[Jan van de Winkel, executive]

Yes, we can hear you. .

[Xian Deng, analyst]

Yes. Perfect. Yes, 3 questions, please, if I may, all on 1046, please. The first one is your data so far on liver tox seems to be quite manageable. But just wondering what are your thoughts on the long-term safety profile on that side, any potential for accumulated liver tox for the patient who you use it for longer? Have you seen any accumulated sort of liver tox data? That's the first one.

And the second question is -- so just wondering, I mean, I understand the 1046 for ASCO, this is a poster presentation, not an oral presentation. So just wondering whether it's possible to disclose the data cutoff for the abstract you submitted? And what is the data cutoff for -- roughly for the actual data to be presented, please? Just wondering whether the data has evolved a lot since that.

And then the third one is, given the feedback you had from the FDA on Phase III trial design, just wondering whether you could disclose that you will focus on PD-1 positive only? Or is going to be more defined such as PD-1 high only.

[Jan van de Winkel, executive]

Thanks, Xian. These are very good questions. I will again hand them over to Tahi, and then maybe Judith can step in there. Tahi, on liver Tox maybe to start off with. Tahi, are you there?

[Tahamtan Ahmadi, executive]

I was on mute. Thank you for the question. On liver tox you're absolutely correct, and we have now a substantial amount of experience with the asset also in combination with PD-1 and also a decent follow-up. It seems manageable, in our hands. Patients can get reexposed after a recovery period. And broadly speaking, tolerate the reexposure really well. And we have absolutely no evidence with accumulation of liver toxicity with a, as I said, a substantial amount of patients across many trials with a relatively long follow-up. So that was the first question.

The second question was on cutoff. I'm not really going to go into the specifics, but previous calls already indicated that there is a cutoff use for the abstract and then there is an updated, more timely cutoff use for the presentation. So there will be updated data at the presentation that will follow up, obviously and more data as in the abstract.

And then the last question was on the trial is on the population, and I think we've also been very clear on this. The intent is -- and then there's nothing changed on this to explore the combination of 1046 plus pembro in control against the current standard of care which is [ docetaxel ] in patients who are PD-L1 positive and PD-L1 positivity here, predominantly is necessary because the drug is PDL1x4-1BB and it requires PD-L1 in tumor cells to activate 4-1BB on T cells.

[Jan van de Winkel, executive]

Thank you, Tahi, very clear. Thanks, Xian. Move on to the next operator.

[Operator]

Your next question comes from the line of Etzer Darout.

[Etzer Darout, analyst]

Just a couple of questions, if you can, on sort of Phase III design. First, around Tivdak. In head and neck, your -- sort of thoughts around sort of the patient population, control arm for that study as well as sort of your -- sort of expectations around sort of the initial indication for Rina-S for the 2027 potential launch that you highlight in terms of sort of what population you would go into today in sort of the line of treatment as well? Just a little bit more color on those Phase III designs, if you can?

[Jan van de Winkel, executive]

Thanks, Etzer, for the question. So Judith, why don't you take the first one on head and neck design for Phase III for Tivdak. And then Tahi can potentially give a bit more color on the Rina-S first trial.

We hope to actually put into place several trials, but the one leading to the potential 2027 initial approval. Judith, maybe you can start.

[Judith Klimovsky, executive]

Yes. So with the Phase III, we are engaging with head authorities as we speak, to finalize the details of the study design, but it's based on the initial data presented at ASTRO and the updated data that will be presented in an oral this year at ASCO. So more to come so -- but the population that we presented at ASTRO consistent with what we will present the second third line after checkpoint inhibitors, platinum and we allow for cetuximab as well. And as you know, the 3 of them are given almost in the majority of patient in ASTRO. And with regard to the Phase III design, more to come based on the interaction that we are currently having.

[Jan van de Winkel, executive]

Thanks. Thanks Judith, and maybe we can move to Rina-S and then maybe, Tahi, you can start and potential, Judith, you can add to that. Tahi?

[Tahamtan Ahmadi, executive]

Yes, I want to be very careful what I'm going to say because we're still in the HOS period. And so I'm going to stay with what ProfoundBio has publicly already stated on their end, which is that they are planning to initiate a Phase III in [indiscernible]. And that they are planning to initiate a study that looks at folate receptor expression across the spectrum.

[Jan van de Winkel, executive]

Thanks, Tahi. I think that's very wise to stay on the right side of the line because we still need regulatory clearance for that proposed acquisition We could probably also not be [indiscernible] further details at this moment. We will do that after we hopefully execute successfully.

Thanks. Let's move on to the next analyst.

[Operator]

Your next question comes from the line of Yaron Werber.

[Unknown Analyst]

This is [ Jana ] on for Yaron. Congrats on the quarter. I have 2, one on DARZALEX and one on EPKINLY. You mentioned on the call that DARZALEX you expect it to continue to have some presence in the relapsed refractory setting. Can you actually give us a breakdown of DARZALEX share across lines of therapy. And then for EPKINLY, how are you thinking about advantage of kind of subcutaneous administration versus [indiscernible] advantage of fixed-duration dosing? And do you think that EPKINLY is also going to have fixed-duration dosing over time?

[Jan van de Winkel, executive]

Thanks very much for the questions. And Anthony Mancini, I think best go into the first question and then Tahi can give further color on subcu of EPKINLY and then -- and fixed-duration of dosing in the newer studies. Maybe, Anthony Mancini, you can start .

[Anthony Mancini, executive]

Yes. So thanks for the question. I'll just start by summarizing what I said earlier, which is the DARZALEX share gains are really driven by a frontline continued growth in frontline. So if you look at the frontline new patient share, it's now 53%, which is a over 14% absolute growth versus same time last year, which is really the key driver. And I would just -- the other -- the other key number is overall, DARZALEX patient share was about 43%. This is based on IQVIA brand ImpactRx data. And the new patient share overall is exceeding the total patient share with a year-on-year 4-point uptake versus last year on an absolute basis.

So we continue to see that leading indicator being really important to predict continued growth of DARZALEX. Front line and second line were where the majority of the growth came and at the expense of third and fourth line. I think I'll leave it there and pass it to Tahi to talk a little bit about duration. I'm happy to add in on that one, too. Tahi?

[Tahamtan Ahmadi, executive]

Yes, sure. So I'll take the first question and also answer the second question. So generally, I think this discussion, this messaging around duration of treatment is a very academic one in my mind. As you noted, in combination, EPKINLY will also be given in a fixed duration because in combination the efficacy is, of course, enhanced and the CR rates are higher. So potential to achieve long-term durable emissions is higher.

I would say like the final judgment on whether it is wise to stop treatment in the relapsed refractory setting with a single agent will probably come from the updated longer-term follow-up data and then people can cost compare anyhow they can swap if they would like so. But they can probably not start if they are forced to stop by label. So that's my first thing.

I think this is a less of an important differentiator, frankly, as you can hear from my commentary, then IV versus subcu because fundamentally subcu route together with the also optimized safety profile gives us the opportunity to reach the patients with completely different health care settings then, I think [indiscernible] whether it is IV administration.

[Jan van de Winkel, executive]

Thanks, Tahi. Maybe you can give a bit more color on the more recent studies and earlier lines of treatment, where we don't use fixed -- where we also use a fixed duration.

[Tahamtan Ahmadi, executive]

Yes. So all ASCO studies that are in combination [indiscernible] and diffuse large B-cell or in follicular lymphoma, in combination have a fixed duration treatment. And that, as I kind of alluded to in the earlier commentary, is a function of our belief that in combination, we have seen increase significantly in times increased CR rates, and this is fundamentally all about CR. The durability of the remission, which is driven by the CR, a potential to give these patients the benefit of a very long, sometimes maybe possibly a curative response to EPKINLY is significantly enhanced when it comes to combination and then it makes sense to think about stopping treatment vis-a-vis a similar therapy, at least in the refractory to diffuse large B-cell setting.

[Jan van de Winkel, executive]

Thanks, Tahi. I think that should be -- hopefully, it's clear now Jana. All right. Thanks.

Let's move on to the next.

[Operator]

Your next question comes from the line of Asthika Goonewardene.

[Asthika Goonewardene, analyst]

So I've got a couple on EPKINLY, please. How much of your sales are coming from academic centers versus community? And then are you getting any pushback from the community practitioners about having to send the patient to the academic center to get -- to be admitted for the monitoring required on just the 1 dose?

Related to that, how are things going with the outpatient study? I'm wondering when we could see that data presented and perhaps filed? And then if I can sneak one in on 1046 on the pivotal trial design that you discussed with regulators. I'm wondering if you had any differential dosing of 1046 based on PD-L1 status, maybe in the 1% to 49%, if you were dosing at a different rate versus patients who had about 50% PD-L1 expression?

[Jan van de Winkel, executive]

Thanks, Asthika, for the questions. So the first 2, I think I want to hand over to Anthony Mancini and Tahi can address the last one, Anthony?

[Anthony Mancini, executive]

Yes. Thanks, Asthika, for the question. So I think it's a great question, academic versus community. I think in the earlier -- in the early part of our launch, we really had a focus on new starts that -- where were heavily pretreated patients were being treated. That was really largely academic focused. We've started to see in recent months now that there's been a modest shift beyond the major academic centers. Of course, our key accounts are primarily major research institutions and health systems that have CAR-T capabilities.

So we have seen a shift of late beyond major academic centers, and we're encouraged by our ability to get to broader sites of care. And we've now seen large physician group practices starting to use EPKINLY, but it's at the early stages Asthika at this point in the community. Of course, that's a U.S. dynamic in Japan. It's really a hospital-based dynamic overall.

But I think this will continue to evolve over time. And as data evolves with outpatient data, as you mentioned and optimization data, both in DLBCL and FL, I think we'll start to see more large physician group practices start to use EPKINLY in a greater way. But again, this is the shift. And with that, maybe I'll pass it to you -- to Tahi to talk about the next 1046 design question.

[Jan van de Winkel, executive]

Maybe Tahi can start with the status of the outpatient study, the Phase II outpatient study. That's one of the questions from Asthika. Any update, Tahi, on the status of that Phase II study?

[Tahamtan Ahmadi, executive]

Well, I mean it's growing quite well. And I think there are also plans to present some of the data towards the end of the year, but that's probably all I can say. It's a happy [indiscernible] study, actually, right. So that's all data.

And on 1046. Well, the simple question is -- the answer is no. So 1 dose on schedule regardless of the PD-L1 status. Also I'm [ not ] sure if I would understand how that would work with the bispecific that wants to engage 4-1BB. But simple answer, one dose, one schedule.

[Operator]

Your next question comes from the line of Emily Field.

[Emily Field, analyst]

I'll just have 2 quick ones. So the first one for acasunlimab, are we going to be seeing the data at ASCO in the poster for both cohort A and cohort B. And then a question on DARZALEX and just sort of the multiple myeloma competitive environment. Obviously, earlier, we saw the DREAMM-7 data for Blenrep, which would test DARZALEX in the comparator arm? I know this is second line plus and the share numbers you gave earlier in first line are super helpful. But are you seeing that assets reentry into the market based on the data you've seen so far as a competitive threat to DARZALEX?

[Jan van de Winkel, executive]

Thanks, Emily for the questions. I think, Tahi, you can probably handle both of the questions. The data at the poster at ASCO for acasunlimab and then the Blenrep, new data from GSK and the impact on the DARZALEX landscape.

[Tahamtan Ahmadi, executive]

While so the first thing, I'll take the 1046 and I'll give my impression on the Blenrep data and maybe Anthony Mancini may also have his own view on this.

But on 1046, what you will see is, the data that we used to make the decision. And obviously, the decision was twofold: one, what is the appropriate dosing schedule and b, overall is there a path forward? What's the proof of concept for this combination. And we'll see essentially the answer to both of these questions. So that means you will see the relevant data from the arms.

On Blenrep, I don't want to sound this way, but it's almost -- it feels like it's a little bit, I think, a little bit too late. As the treatment paradigm has changed and daratumumab has moved into earlier lines, I think the study asked the question. That was certainly relevant at a time when it was designed, but may not be necessarily relevant at the time it was answered. I don't know if Anthony wants to add further to that.

[Anthony Mancini, executive]

No, I think you covered it Tahi.

[Jan van de Winkel, executive]

All right. I think we need to leave it with that, Emily. I think there's now probably better BCMA-targeted molecules like bispecifics and teclistamab is doing really well, as you heard from Anthony Mancini.

All right. Operator, let's move to the next question.

[Operator]

Your next question comes from the line of Peter Verdult.

[Peter Verdult, analyst]

Two questions, please. To Jan and Tahi. I -- and I ask your patience here, but I just want to ask Sachin's question differently. On this GEN1046 data, we're going to see why we're going to Phase III. Can I -- rather than trying to be [indiscernible] I mean it's a big area, huge commercial opportunity but also very competitive. So my simple question is, is there enough data to materially change consensus [indiscernible] in this drug? Do you feel that there could be a pivotal moment in terms of how people view 1046, given how long we've been waiting for this data to come through? So that's question number one.

And then number two, for Anthony Pagano. Just ballpark, when we think about ProFound (sic) [ ProfoundBio ] on an annualized basis, is a good starting point to think over cost base around $100 million, including what might be can you get to prosecute Rina-S? Just anything you can help us with in terms of a run rate in terms of the ProfoundBio cost base?

[Jan van de Winkel, executive]

Thanks, Peter, for the questions. The first one, I will move on to Tahi because he is really on top of that data together with Judith. And we are very excited to present that. And I think it's going to be very clear, Peter. And take -- an underlining the decisions we have taken towards pivotal. But, Tahi, maybe you can give a bit more color for Peter.

[Tahamtan Ahmadi, executive]

Yes. [indiscernible] why. It's not that easy because I don't necessarily know how you guys are going to react. Because it all depends on like what one has in mind in terms of expectations and reality.

The way I look at this and the way I think was in the way we think about this and the reason we are excited is of course something like this. This is going to be a IO option with the similar benefits that immuno-oncology approaches in the past have shown when they were compared against chemotherapy [indiscernible] in that we would be -- what we hope to achieve the study which we hope you will appreciate in the data set is that efficacy is important, durability is probably even more important and over survival is [indiscernible] .

And so it is indeed a competitive space. But I think it's also fair to say that a lot of the approaches have not met the criteria that I just laid out. They've met maybe one, but not all of them. And I think this is how we look at it. This is why we are excited about it. It's in many ways, also validation of a long effort to validate [ 4-1BB ] mechanism. And that enough itself also has some value for us.

[Jan van de Winkel, executive]

Thanks, Tahi. I think we should keep it with that. And then finally, also a question for Anthony Pagano., I was worried that there wouldn't be a question for you, Anthony, but now you can go.

[Anthony Pagano, executive]

I stayed on the line, Jan, don't worry. And thanks, Pete. Yes, maybe to start off with the shorter term, Pete, in terms of our 2024 guidance. And it's what we indicated as part of announcing the proposed acquisition and I reiterated again today that for 2024, we expect to be at or moderately above the upper end of our current guidance range, which is DKK 12.4 million to DKK 13.4 billion. And to be clear, as I sort of think about what the upper band of that could be, it's certainly going to have a 13 handle on it, meaning our OpEx numbers when I start with the 13. We're really focused on, as you would expect, continue to manage our overall investments in a focused and disciplined way as we've done historically.

Now if I kind of zoom out a little bit, Pete, as you'd expect, we have to invest to unlock the full potential particularly around Rina-S, as well as our existing late-stage programs. So as I highlighted on our call to announce the proposed acquisition of Profound, we do expect R&D investments to step up over the near to medium term. What you should be really clear on though is that we fully intend to remain substantially profitable through the -- throughout this investment period. So we're going to manage our expenses accordingly. And that means that moving forward, we're going to continue to be focused and disciplined in our approach to allocate the capital across these mid- to late-stage R&D programs with the most potential.

As we've done in the past, we're not going to shy away from deprioritizing other programs, particularly early-stage programs that won't meet our high bar for continued development. And then finally, and as we talk about Rina-S in a little bit more detail, we expect Rina-S could be accretive to earnings by the first full year of launch, given its potential approval in 2027. And as Jan highlighted, we do anticipate that we're going to unlock meaningful value from this program by the end of the decade with significant further upside into the 2030s.

Maybe one other point, Pete, you might have seen this in the Q1 print. When we gave our guidance for 2024, we're very clear that we're already managing our investments, particularly as it relates to SG&A. You can see the SG&A print here in Q1 is further evidence of that. We're absolutely focused on making the appropriate investments to run our business the right way.

But also, when we have clear investment opportunities, particularly the, let's call it, registration trials. We can't shy away from making these investments. And likewise, when the data aren't clearing the very high bar, we can't shy away from that either.

So I'm not going to give you a precise number. We've highlighted, Pete, that we are anticipating starting Phase III for Rina-S, and you can do some of your normal modeling as you expect what the incremental investment is to run Rina-S. And we'll be back as part of our Q2 earnings to provide some incremental detail, particularly as it relates to 2024 numbers.

[Jan van de Winkel, executive]

Thanks, Anthony. Thanks Peter. Let's see whether there are further questions, operator?

[Operator]

The question comes from the line of [ Suzanne van Voorthuizen ].

[Unknown Analyst]

This is Suzanne from [indiscernible]. I got disconnected for a bit, so apologies if this is maybe a repetitive question. But I wondered if you can elaborate on the tisotumab data set in head and neck cancer that is coming at ASTRO. Could you remind us of the potential that you see for the drug in this setting and expand on what we should expect for next month's update in terms of sample, size, efficacy metrics and follow-ups on.

[Jan van de Winkel, executive]

Thanks, Suzanne, for the question. And I think, yes, you did miss, I think, some of the updates, but I'll ask Judith give you further color on the data set at ASTRO for head and neck and Tivdak, tisotumab vedotin. Judith?

[Judith Klimovsky, executive]

Yes. So the data is based on Phase II study RMC. The initial data was presented at ASTRO. So this is a much more substantial data set with longer follow-up. But data setting is the same. So it's patients with head and neck that fail standard of care, meaning PD-1, chemo and cetuximab.

[Jan van de Winkel, executive]

Thanks, Judith. And only a few weeks, Suzanne, then you will know it all.

Let's see, operator whether there are further questions.

[Operator]

Thank you. In the interest of time, I will hand back for closing remarks.

[Jan van de Winkel, executive]

All right. So thank you all for calling in today to discuss Genmab's Financial Results for the First Quarter of 2024.

If you have additional questions, don't hesitate to reach out to our Investor Relations team. We hope that you all stay safe and keep optimistic, and we very much look forward to speaking with you all again soon.

[Operator]

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