Merck at ASCO: Expanding Beyond Keytruda

On Monday, 02 June 2025, Merck & Co. (NYSE:MRK) presented its strategic vision at the American Society of Clinical Oncology Annual Meeting 2025. The event highlighted Merck’s efforts to diversify its oncology portfolio beyond Keytruda and expand into other therapeutic areas. While the company showcased promising advancements, challenges remain as it aims to sustain its leadership in oncology.

Key Takeaways

• Merck is focused on diversifying its oncology portfolio beyond Keytruda and expanding into HIV, vaccines, immunology, cardiovascular, and ophthalmology.
• Keytruda has been a significant contributor, with 35 phase three trials showing positive results and 56 FDA-approved indications.
• Merck anticipates a 30-40% uptake of subcutaneous pembrolizumab in the U.S. within 18-24 months post-launch.
• The company plans to launch 20 new growth drivers, with 13 in oncology, over the next several years.
• Merck’s late-stage pipeline presents a commercial opportunity exceeding $25 billion.

Financial Results

• Merck’s oncology products have reached over 3.4 million patients globally.
• The company has 56 U.S. approved indications, with 41 for Keytruda alone.
• Merck foresees a significant commercial opportunity from its late-stage pipeline, valued at over $25 billion.

Operational Updates

• Development is underway for a subcutaneous fixed-dose combination of pembrolizumab and barahyaluronidase alfa.
• Keynote-689 showed that neoadjuvant pembrolizumab improved event-free survival in certain head and neck cancers.
• MK-1084 is being developed as a potent, combinable daily treatment.
• Data from MK-2140 in diffuse large B cell lymphoma was presented.

Future Outlook

• Subcutaneous pembrolizumab is under review by the FDA and EMA.
• A phase III study of MK1084 combined with Keytruda is planned for high TPS score tumors.
• The CANDOLET-12 study in colorectal cancer is set to begin.
• Global phase three studies for Sac TMT in EGFR mutated non-small cell lung cancer are ongoing.

Q&A Highlights

• Analysts inquired about the market evolution of PD-1/PD-L1/VEGF bispecifics and plans for MK-2010.
• Questions were raised about the adoption rate of subcutaneous Keytruda and differentiation of TROP-2 ADCs.
• Discussions included the impact of Most Favored Nation clauses and Medicare Part D draft guidance.

Readers are encouraged to refer to the full transcript for more detailed insights into Merck’s strategic plans and developments.

Full transcript - American Society of Clinical Oncology Annual Meeting 2025:

Operator: Thank you for standing by. Welcome to the Merck and Company Incorporated, New Jersey, USA Investor Event at the American Society of Clinical Oncology Annual Meeting. At this time, all participants are on a listen only mode until the question and answer session of today’s conference. At that time, to ask a question, press star one on your phone and record your name at the prompt. This call is being recorded.

If you have any objections, you may disconnect at this time. I would now like to turn the call over to Mr. Peter Dannenbaum, Senior Vice President, Investor Relations. Sir, you may begin.

Peter Dannenbaum, Senior Vice President, Investor Relations, Merck: Thank you very much, Denise, and good evening, everyone. Thank you very much for making the effort to be with us here in Chicago, and welcome to our investor event at ASCO. Thank you also to everyone tuning in via the webcast. So we’re very excited obviously to have this opportunity to speak to you about our oncology program. During today’s call, a slide presentation will accompany our speakers’ prepared remarks and has been posted to the Investor Relations section of Merck’s website.

But before we get started, we’d like to remind you that some of the statements that we make during today’s call may be considered forward looking statements within the meaning of the Safe Harbor provision of The U. S. Private Securities Litigation Reform Act of 1995. Such statements are made based on the current beliefs of our company’s management and are subject to significant risks and uncertainties. If our underlying assumptions prove inaccurate or uncertainties materialize, actual results may differ materially from those set forth in the forward looking statements.

Please reference this slide in our presentation and our twenty twenty four ten ks, which identifies certain risk factors and cautionary statements. I’d now like to introduce Doctor. Dean Lee, President, Merck Research Laboratories, who will open with a few remarks and outline our agenda and speaker lineup. Dean.

Dean Lee, President, Merck Research Laboratories, Merck: Thank you, Peter, and good evening and welcome. We’re pleased to host this annual event, focused on oncology. What I would say that I’ve said to many of you is that since 2021, what Rob Davis, the COI, and I have done since we took our roles is that we’ve said that there’s two major goals. One is first to diversify across oncology using the power of Keytruda. And the second is to expand in additional therapeutic areas such as HIV vaccines, immunology, cardiovascular and ophthalmology.

But the focus today at ASCO will be on the substantial progress of oncology programs. And Keytruda has been a source of extraordinary impact to the world and for medicine and for Merck. It’s been such an important medicine with a remarkable impact for patients and provider. It’s been a driver, as you’ve seen here, of many of the important contributions made across our entire oncology portfolio. To date, our portfolio has yielded 35 phase three oncology trials with statistically significant overall survival, 56 FDA approved indications and a significant impact to patients with more than three point four million treated globally.

And what we intend to do is to leverage our proven track record advancing the standards of care to sustain our leadership in oncology beyond the LOEs of Keytruda in 2028, in 02/1931, and in 02/1932. And so here’s a graph of the evolution of Keytruda approval. Since 2020, there’s been a continuing expansion of Keytruda from 26 to 41 indications and growing across 18 tumor types and tumor agnostic, two tumor agnostic indications, and essentially Keytruda has laid a roadmap across solid tumors and increasingly in the earlier stage and curative intense setting. So in the light green, you can see nine approvals in the earlier stage and as Marjorie and Eli will suggest is we hope to have that turn into 10. And four of the current approvals are based on studies that have already shown overall survival and recognize that we have many more opportunities brewing in the earlier stage.

The power and the broad impact of KEYTRUDA provides us a roadmap for the future as we diversify our portfolio in oncology, and we listed the four sort of major topics that we’ll be talking about here. First, the progress made in curative intense setting, including more accessible options and new treatment paradigms. And what do I mean by that? In terms of more accessible options, it’s a subQ administration has a potential to be an important option in earlier stage settings, can enable access in healthcare settings closer to, the patient’s home, doesn’t always require a highly skilled oncology nurse to access support, you could provide, access to sub cutaneous pembrolizumab and non infusion center, such as a physician’s office. And Marjorie will touch on subcu pembro.

This injection was specifically designed to be administered within two minutes, so very easy and very fast. We are also defining in the earlier stage, defining new populations such as pathologic complete responders and non responders following surgical resection And we think that separation of those populations create a platform for us to, for example, really think about how we can do more good for those who are non responders. And in our collaboration with Moderna in developing INT and individualized neoantigen therapy, which essentially, for the last thirty years is making the promise of a cancer vaccine go from impossible and improbable to possible. We are also studying in earlier stages, which we’re also studying in earlier stages of melanoma in a non small cell lung cancer and those that are PD-one and oncology sensitive. The second is the combination of KEYTRUDA with chemotherapy that has absolutely been transformative.

Often people throughout the words of being, you know, keynote 189 in the stage of cancer and KEYNOTE-six 71, but it’s actually true in many other cancers than just lung cancers. And we now ask how can KEYTRUDA amplify the impact of next generation chemo? And so we have antibody drug conjugates, and we’re advancing next generation chemo with a broad ADC program. We’ll outline this is, we have nine ADCs clearly in the public domain, five which we will touch on today, but we will really give a context around one, which is Sac TMT, which is probably the furthest along, but the other ones are right behind it. And in that one, we have 14 studies that’s publicly acknowledged.

And of those fourteen, nine of them are in indications where we believe that we’re clearly gonna be first. And then the other ones where we will be clearly differentiated. Third, we also understand the power of KEYTRUDA to potentially think about opportunities for chemo free regimens. And we’ll touch on this. We’ll focus on doing this with MK1084, our KRAS C12C, which is designed to be highly potent and highly combinable with potential benefit in both earlier and late stages of cancer.

And Marjorie and Elliot will speak more about it momentarily. And finally, we also have learned where PD-one or Keytruda has not been as effective and it has taught us ways and mechanisms and avenues for us to tackle these areas such as small cell lung cancer, MSS CRC, and in heme. And this has led us to go into other agents, including KRAS, G12C, but also T cell engagers, ADCs, and combinations amongst them. So today, we hope to just give you a flavor of our broad efforts across oncology, across early and late phase, across multiple mechanism of actions, and across multiple modalities. And by focusing on a subset of our robust registrational clinical trial portfolio, hope to give you an insight into the strategic context and importantly, the timing of these readouts.

So first, Marjorie Green will provide recent notable data updates from ASCO, AACR, and the European Lung Cancer Congress. Then Doctor. Elliot Barr will take a more expansive view of our oncology development strategy, providing compelling exemplars of our strategy and action, including how we are leveraging our foundational position in immuno oncology and advancing combinations to improve standard of care. And finally, Chirpy Gwindow will provide an update on the commercial landscape and the opportunity that we have to positively impact patients with cancer. I’ll end with brief closing remarks prior to opening the session for Q and A.

And now I’ll turn the podium over to Marjorie.

Marjorie Green, Doctor, Merck: Thank you, Dean, and hello, everybody. We’re excited about the data that we presented earlier this year as well as at ASCO, and we continue to make significant progress in our portfolio. One advance has been the development of subcutaneous fixed dose combination of pembrolizumab with barahyaluronidase alfa. We presented the results of D77 at ELCC, evaluating the combination of pembrolizumab and barahyaluronidase alfa with chemotherapy compared with IV Keytruda combined with chemotherapy in non small cell metastatic lung cancer. The study met its primary endpoint showing comparability of PK between the two different treatments when you’re looking at the subQ formulation compared to IV and demonstrating non inferiority.

Important secondary efficacy endpoints which were descriptive show that response rate, progression free survival, duration of response were all consistent between treatment arms. Median overall survival was not reached in either arm. The median injection time for subcutaneous pembrolizumab in D77 given on an every six week schedule was two minutes. Clinicians can have confidence that the subcutaneous co formulation of pembrolizumab, which is currently under FDA and EMA review, can provide the same benefit they’ve seen with IV Keytruda but with the patient benefit of immediate injection time of two minutes. Moving on to more Keytruda news, Dean spoke about our ambition of moving Keytruda as well as other agents in our portfolio into earlier lines of therapy, whether it’s in the first line of metastatic cancer or into the curative setting.

We have the biggest opportunity to impact public health and cancer by treating people when they’re either first diagnosed or in the curative or in the metastatic setting. Key note six eighty nine, which was initially presented at AACR and subsequently updated at ASCO, evaluated patients with resectable, locally advanced head and neck squamous cell carcinoma and demonstrated that the use of two cycles of neoadjuvant pembrolizumab followed by surgery and then adjuvant therapy with pembrolizumab combined with either radiation or chemoradiation improved event free survival when compared to the standard of care control arm. This has been the first advance in this population in more than twenty years. The data demonstrates that improvement in event free survival was seen in ITT as well as in the populations whose tumors express EDL1. At the time of this interim analysis, which is the first interim analysis, a trend towards improvement in overall survival was observed for those whose tumors have a CPS score greater than 10.

These results did not reach statistical significance and will be evaluated at the next interim analysis. We also shared data from MK1084, our oral KRAS G12C inhibitor, which we believe is an improvement on the previous generations of KRAS G12C inhibitors. This asset was designed to be highly potent, combinable, as Dean said. It’s also given once a day. Therefore, we can combine it well with therapies such as Keytruda as well as chemotherapy.

At ASCO, we presented data from the Phase I CANDOLET one study of MK1084, One data set looking at non small cell lung cancer, looking at its monotherapy as well as in combination with pembrolizumab, and that combination showed that for people who have PD L1 positive non small cell lung cancer, the overall response rate is seventy seven percent. It’s really rare and nice to see a waterfall where everything is sort of pointing in the downward the right direction, showing benefit for patients. And that’s something that’s really exciting about this. In colorectal cancer, we also presented data looking at MK1084 as monotherapy as well as combined with cetuximab, and then finally, the triplet of MK1084, cetuximab, and FOLFOX, also demonstrating very robust responses. Both of these showed manageable safety and tolerability and, again, promising anti tumor activity.

So we have Phase III studies ongoing both in non small cell lung cancer as well as in colorectal cancer. In non small cell lung cancer, we have a study looking at MK1084 combined with Keytruda for patients who have tumors that have a TPS score greater than 50%. We are also going to be initiating, based upon the very promising results of MK1084 combined with pembrolizumab shown in this study, a trial comparing the combination of MK1084 with subcutaneous pembrolizumab compared to the KEYNOTE-one hundred eighty nine regimen of chemotherapy combined with Keytruda. So that’s going be something that’s going to be essentially a chemotherapy free, IV free regimen for patients with non small cell lung cancer. We have initiated the CANDOLET-twelve study in colorectal cancer, and first patient enrollment is imminent.

So we’re really excited about the host suite of studies that we have, and we’re looking forward to sharing more data in the future. Moving on to hematologic malignancies, we have a growing portfolio of agents that we think are very active across multiple different hematologic malignancies and are excited about our opportunity for patients who have these different diseases. At ASCO this year, presented data from MK two one four zero, otherwise known as zilobirtamazdotin, which is a ROR1 ADC with the payload as a microtubule inhibitor. We presented data last year at ASH with ZV. I’m going to call this MK2140.

In the frontline setting, ZV with RCHP as frontline therapy for patients who have diffuse large B cell lymphoma. At ASCO, we presented data from the second line plus setting in diffuse large B cell lymphoma, looking at the first part of a Phase IIIII study of different dose levels of ZV combined with rituximab and gemcitabine oxaliplatin. It was not only dose finding, but also demonstrated that this is an active combination that potentially will help further unlock potential for ZV in diffuse large B cell lymphoma. In this study, the combination of ZV with rGemox showed a response rate of the mid-fifty percent range, and historical control data shows that that response rate is estimated at thirty five percent to forty percent. So we’re excited about the combination data.

We have Phase III study that’s ongoing in the first line setting, looking at a combination of ZV with RCHP that I referenced that was presented the data from ASH. This is Waveline 10. We also have a Phase II study that is looking at ZV versus polatuzumab vedotin in the GCV subtype in Waveline 11. I’d like to touch on additional data from our ADC portfolio, looking at data that our partners at Kulin Biotech generated with Sac TMT for patients in China who have EGFR mutated non small cell lung cancer. We are very fortunate to advance Sac TMT in close coordination with Balloon Biotech.

They’ve been a really remarkable partner to work with. The data that they’ve generated provides key insights and clinical signals in their studies that enables Merck to optimally design registration studies for Sac TMT in The United States and globally. This is a Phase II study called Ophi Trop Lung03 comparing Sac TMT versus standard of care chemotherapy in patients who have EGFR mutated non small cell lung cancer, showing a statistically significant and clinically meaningful improvement in progression free survival as well as overall survival. The safety profile of SAT TMT is very manageable, and we believe that it is a differentiated ADC in the Trope-two space. This is the first Trope-two ADC approved for lung cancer in China, and two global phase three studies are ongoing in this specific EGFR mutated non small cell cancer population.

Finally, with Sac TMT, data from studies being conducted in China have been presented by our partner in triple receptor negative breast cancer. At this ASCO, the data is from a Phase II Optitrop breast O5, demonstrating in the first line setting very promising anti tumor activity for patients who either received adjuvant therapy and had relapse or had de novo newly diagnosed triple receptor negative breast cancer. The response rate is very robust at seventy percent, and consistent results were observed across PD L1 expression levels. The median duration of response is approximately twelve months, showing the promise of this asset in triple receptor negative breast cancer. As with the data that Kallun has generated in China in lung cancer, the data they’ve generated has helped engage us initiating studies globally in triple receptor negative breast cancer.

The data continues to demonstrate a manageable safety profile. And the phase three studies we have underway include TROFUSE eleven, which is in the first line triple receptor negative breast cancer for patients whose tumors have low levels of PD L1 expression. We have not only a monotherapy arm in the study compared to standard of care, but we are also looking at the ability of Keytruda with Sac TMT to give benefit for patients whose tumors have lower PD L1 expression, as we’ve seen quite robust activity of the combination of Keytruda with ADCs across a range of PD L1 expression. We also have TROFUSE twelve in the setting of residual disease for patients who do not have a pathologic complete response with the KEYNOTE-five twenty two regimen. And very recently, we have started TROFUSE thirty two.

This is a neoadjuvant study of Sac TMT as a replacement for anthracycline based therapy as part of the KEYNOTE-five twenty two regimen in the neoadjuvant setting. We’re very excited about our growing portfolio of Sac TMT. You heard about the number of studies that we have underway and the opportunity we have for patients globally. And we look forward, again, to sharing more results with you at future meetings. As you see, we continue to generate compelling data, which gives us increased confidence in our differentiated late stage development program.

You’ll hear more about from Elliot. So I’m gonna hand it over to Elliot now.

Dean Lee, President, Merck Research Laboratories, Merck: Thank you, Marjorie, and again thanks all of you for making it at the end of here at the end of ASCO. So as you’ve heard, we have a broad and deep pipeline. That’s divided into three groups. Our immuno oncology medicines are designed to stimulate anti cancer immune responses and they include the subcutaneous pembrolizumab with bari hyaluronidase alpha, INT and the bispecifics. Our precision targeted agents are designed to impact pathways that can drive cancer growth.

You’ve seen the early data with MK1084 that Marjorie just pointed to. We anticipate important readouts for belzutafan, abovastat and nipibrutinib over the next year or so. Finally, our ADCs and TCs are designed to target chemotherapy and immune cell activation to tumors while mitigating the effects of normal tissue. You’ve heard about Sac TMT and Zolverb, famotidotin from Marjorie. And we’re also excited about our other DXD assets.

And I wanna particularly point to our highly active Rising Star, again, from Killeen Biotech MK 3,120 and Actin-four ADC as well as our early pipeline. These are really exciting molecules. You’ll hear more about them as the year progresses, but I did wanna touch on 03/2020. Now we’re deploying these assets with a goal of maximizing benefit risk and convenience to patients while providing exceptional value for payers. We anticipate developing novel rationally selected combinations of highly active medicines that are targeted to specific patient populations.

What I’d like to do in my talk is just to give you examples of that so it doesn’t become isn’t just so generic and you can’t grab onto specific examples to give you an understanding of how we’re deploying our pipeline. So we’re also working hard on biomarker selection and I’ll talk a little bit more about that. Where feasible, we think that’s gonna be very important for patients to get the right medicine at the right time. Note that our team at Merck has developed a strong presence in biomarkers, starting with a PD L1 biomarker of course, and we have extensive work going on for all of our ADCs with immunohistochemistry, digital pathology, imaging markers, AI, and so on. These are in a fairly advanced stage and we’re looking forward to presenting those in due course as our phase three studies read out.

Now our investment in treating early stage cancers in new medicine like INT or now it’s called Intismaran AutoGene is based on our goal of effectively treating cancer in the curative intense setting before it metastasizes. KEYTRUDA continues to provide important data and of course KEYNOTE-six eighty nine, which you just heard about, is one of those things, but also I’d point you to a large cluster of six studies, that are going to, read out across the spectrum of bladder cancer, which is a really important part of our portfolio. And again, make reference to NK-three 120. We’re also gonna have some readouts of KEYNOTE-seven 56 in HR positive breast cancer, and I think that’s gonna be a really exciting study. Now to give you again, as I mentioned, a little bit more flavor about how all of these molecules come together, I wanna show you how the combination of industry leading foundation of Keytruda and a rich pipeline can enable us to provide unique opportunities to advance cancer care.

So I show you four examples here and we’ll go through I’ll give you a little quick highlight and then we’ll go through each one of these in detail. This is not the only thing that we have in the pipeline, but we thought it’d be an emblematic demonstration or a demonstration of what we’re heading to. So we’ll start with the first one. Keytruda and KEYNOTE-six seventy one have demonstrated that perioperative treatment with pembrolizumab improved outcomes in patients in six seventy one case with non small cell lung cancer, but there’s a whole series of studies as Marjorie pointed out and Dean, where we’ve shown that perioperative therapy with Keytruda can really improve outcomes in especially OS. The patients with detectable viable tumor at the time of surgery remain at high risk for recurrence.

So as an example, the percentage of patients in Keynote six seventy one who do not achieve pathologic complete response is eighty percent. So there’s quite a bit of patients who still are at residual risk even after getting neoadjuvant therapy. Now, adjuvant pembrolizumab helps them but they’re still at risk. And so we’re keen on adding to the platforms that things like KEYNOTE-five twenty two in triple negative breast cancer or KEYNOTE-six seventy one in non small cell lung cancer using those platforms to improve outcomes for patients in particular populations that are at high risk. Now we just announced the results of keynote B96 in ovarian cancer.

This is the very first demonstration of the value of IO in the ovarian cancer space. And so Keynote B96 provides us with a pole position to create combinations with RDXD, which is highly active in this setting. And then finally, a last example, or within the as a third example, should say, keynote 189 set a very high standard for benefits in patients with newly diagnosed locally advanced metastatic non small cell lung cancer. And as Marjorie notes, we can now define segments of the populations with the potential for even better outcomes using MP1084, which has really quite exceptional duration of response and objective response rates. And then the last example is Academig and IDXD.

These are two agents, that are being developed in partnership with Beichi Sankyo and these are orthogonal, mechanisms of action and high activity in small cell lung cancer. And in all of these settings, in each one of these settings, we’re very excited about the potential for MK2010, which is our PD-one VEGF bispecific to enhance the foundation that pembrolizumab gives us. As promised, I’m gonna take each of these four examples and give you a little bit more of a deep dive. So as you can see, these are a suites of KEYTRUDA studies, in the early stage cancers. You can see that each one of them has really made a difference in patients outcomes when KEYTRUDA is used either in the context of neoadjuvant adjuvant or adjuvant therapies.

Are more than 30,000 patients in over 30 active phase three trials in early disease across 10 tumor types and this is really a large effort. Now, with that foundation, we can use our suite of medicines to use this platform to advance care in selected patient segments. So again, you can look at Keynote six seventy one as an example, we’ve mentioned already a couple of times the importance of P671 as improving overall survival in patients with stage two, three non small cell lung cancer. However, patients with detectable viable tumor at the time of surgery remain at high risk for recurrence and in these patients we’re evaluating both INT, you can see, in that second line in Tysmorin Autogene, as well as Sac TMT. Now these are drugs with very different profiles and we don’t think that they’re gonna be overlapping.

So these are distinct benefit, distinct populations where these drugs will be used and so distinct offerings to really broaden our ability to help patients who don’t get the optimal result in the neoadjuvant state. We’ve got similar approaches in other settings, and we’ve already had studies planned to add settings where readouts with pembrolizumab in the perioperative settings are imminent. So, stay tuned for that. I’ve talked a little bit already about keynote B96, and this is, really exciting for us because this is, the first time where you can see that addition of pembrolizumab to standard of care chemotherapy resulted in potentially practice changing OS benefits in certain patients with platinum resistant refractory ovarian cancer. So now we and Daechi Sankyo have shown the outstanding activity of relinitatogue durexdakin or RDXD, in later lines of therapy in ovarian cancer.

And further exciting data are gonna be released in the upcoming months. It’s really a great drug. We’ll now combine pembro and RDXB with the potential to further improve outcomes in these cancers, as well as in earlier lines of therapy within ovarian cancer. Now I’ll remind you that bevacizumab plays an important role in the treatment of certain ovarian cancer settings. With our unique insights from keynote B96, we are confident that we can consider MK2010 with RDXD in the future.

We’ve talked a lot about MK ten eighty four, but I wanna emphasize that keynote 189 set a very high standard for benefit of Keytruda in combination with pemetrexed and platinum chemotherapy in certain patients with newly diagnosed non small cell lung cancer. As Marjorie explained, we’ve shown the co administration of MK1084 with pembrolizumab is generally well tolerated and results in a very high rate of extremely durable responses up to twenty four months and counting. The reason why it’s just twenty four months is because that’s pretty much when we started the study. So it’s a it’s a really quite remarkable, drug. I’m particularly excited about the imminent, start of CANDOLET seven.

This study is a phase three study. We’ll compare MK1084 plus subcutaneous pembrolizumab with beryllium arsenide alpha and the KEYNOTE-one hundred eighty nine pembro chemo regimen in patients with newly diagnosed locally advanced or metastatic KRAS G12C positive non small cell lung cancer. So on the one side, we’ll have subcu pembro and a oral tablet administered once a day. And then the other side, we’ll have Keynote 189. And you can imagine how that combination of a pill and a subcutaneous injection that can be given over one to two minutes is gonna be really a revolution for patients if you can see that the efficacy is as we expect.

So if the study is successful, we’ll have an opportunity to really make a meaningful difference in patients’ lives, not only improve outcomes for the patients but also improve their experience as they go through something as bad as, advanced metastatic non small cell lung cancer. Now small cell lung cancer is our next, frontier that we’ll tackle and have chosen small cell lung cancer because this is not an area where pembrolizumab has been a foundational drug. In The US, there are about thirty four thousand patients per year. They’re diagnosed with small cell lung cancer and that represents about fifteen percent of all lung cancers. And you all know that the prognosis is quite dismal.

Gucatinib, MK6070 and IDXC, we call them MK2400, have orthogonal mechanisms of action and each has shown high activity in small cell. And you can see the two waterfall plots here that are really quite impressive. We’ve already quite along the way in evaluating these two drugs together. And

Marjorie Green, Doctor, Merck: I

Dean Lee, President, Merck Research Laboratories, Merck: think this is where we are really differentiating. The results of those studies will present in due course, but suffice it to say that we’re thrilled by the results and we’re looking forward to being able to advance this combination. So these four examples are just the tip of the iceberg in our ambitious plans. We have one of the largest and broadest ADC portfolios in late development covering important cancers. I think our early pipeline will bring diversity and targets by specifics and new payloads, as well as other opportunities to improve outcomes for patients and create unique combinations.

And you can see all of the different ADCs here, some with our colleagues at Kolutin Biotech and some with our colleagues at Daiichi Sankyo, which really a group that really has done enormous amount of benefit in advancing the field of ADCs. Sac TMT is our most advanced ADC. Kallun studies in China have provided us with confidence in this asset as well as important data to aid in the designs for Sac TMT studies. Now we recognize that there are other trope to directed ADCs with different antibodies, linkers, and payloads, but our foundation with Keytruda and the strength of this particular asset in our execution teams has led us to a multifaceted and unique program that displayed here. The publicly announced studies are shown here as you can see, we’re potentially first in class in most indications, we’re testing unique combinations or we’re evaluating biomarker defined populations.

Not shown here is the intensive biomarker development strategy that’s bearing fruit and will be disclosed in the future and of course, there’ll be other studies that will present it in due course. So how does this huge pipeline and our overarching strategy translate into phase two registration trial? In this slide and the next, I’ll show protocol completion dates for over 60 registrational trials across 16 mechanisms of action. Of course, each study has interim analysis implying that in some cases earlier readouts may occur. The pembrolizumab studies shown here will provide critical data to improve patient outcomes, but these can be imputed to subcutaneous pembrolizumab or MK3475A with the potential to meaningfully lower the barriers to access for patients and providers.

The studies will also enable combination strategies. And I’m excited about the WellerReg studies that are finally getting close to being ready for readouts they have the great potential to advance therapy in RCC where there’s significant unmet need. And then here’s our new pipeline programs and you can see in the bright green, the Sac TMT program, which is really a huge effort in our part. We also have studies of MK1084. We have studies of upavacostat, our CYT11A lyase inhibitor for prostate cancer, bomadenstat, our LSD one inhibitor for essential thrombocythemia, and emtibrutinib, our non covalent BTK inhibitor.

All of these studies are well underway, enthusiastically enrolled and will read out as noted in the PCD dates. Finally, we’re advancing NK2010 in China where we have highly efficient operational capability. This PD-one VEGF bispecific has potential across many tumor types. And as you see from our presentations, we have unique assets and a highly experienced operations engine that in aggregate will enable rapid evaluation of MK2010 alone or with other agents in large number of patients. And our unique pipeline provides us with important insights as well as opportunities to develop this drug for patients across the spectrum of cancer.

So in closing, I hope I’ve shown you that we’ve moved with urgency to execute a tremendous strategic pivot for beyond KEYTRUDA to a more diversified multifaceted pipeline of innovative candidates, not just with signal generation phase one studies, which is mostly what you saw with exception of Sac TMT in this ASCO, but with a tremendous cascade of phase three studies that over the next few years will read out and I think will make a tremendous impact on cancer care going forward. And we really think that this pipeline will help us write the next chapter in the book of cancer therapeutics for Merck. And with that, I’ll turn it over to Chirfi.

Chirfi Gwindow, Merck: Thank you, Eliav, and, pleasure to be here. Thank you for coming at the end of this very long and exhausting ASCO. I’m proud to speak on behalf of our industry leading oncology commercial organization, which continues to drive patient access and impact to our important medicines for the treatment of cancer. We have reached to date over three point four million patients around the world with our medicines, in part thanks to our strong commercial execution. Our suite of oncology products is approved in a total of 56 indications in The US, Forty Four in The EU, and 41 in Japan.

Of those, Keytruda is approved in unparalleled 41 indications in The US, Thirty One in The EU, helping us drive strong growth and IO leadership. Our success is underpinned by a talented team that has built a robust commercial engine globally. This includes, among others, our market access efforts where we have achieved positive HTA approvals around the world. We continue to execute with excellence across all tumor types and across all markets, and we’re proud of the progress we’re making. But we got a lot more opportunities ahead.

As you’ve heard from my colleagues, we’re driving impact in earlier stage disease. We continue to be excited about the opportunity for Keytruda specifically. Keytruda is the one and only IO to demonstrate a significant overall survival benefit in four studies and to have received nine approvals across six tumor types. We await, as Dean indicated, we await FDA action on our application in resectable locally advanced head and neck cancer based on the compelling results of the KEYNOTE-six ’89 study. This is the first positive trial in twenty years for patients with resectable locally advanced head and neck cancer.

For context, in The US, there were fifty eight thousand new cases of head and neck cancers diagnosed last year, and sadly twelve thousand deaths from the disease, which speaks to the large unmet medical need in this space. Approximately sixty percent of these cases are diagnosed at the locally advanced stage, and a portion of those would be addressable by KEYNOTE-six 89. We look forward to bringing this treatment option to appropriate patients. If approved, 80 9 would mark the tenth earlier stage approval for KEYTRUDA. Unprecedented.

Our commitment to innovation and addressing the unique needs of patients and health care providers and systems extends to the development of subcutaneous pembrolizumab in combination with beta hyaluronidase alpha. We hope to bring this innovation to patients in The US later this year. Subcutaneous pembro pairs well the clinical strength of Keytruda with meaningful patient and customer benefits. These include the potential for the fastest injection time of approximately one minute for the q three week injection, two minutes for the q six week injection, and the lowest volume injected. We’re seeking all adults for the tumor indications where KEYTRUDA is current currently approved.

Sub q pembro could be particularly appealing for patients receiving monotherapy or oral combinations, especially those in earlier stages of disease, where time and setting of administration may be a concern for patients. We believe that the potential benefits of this subcu will extend beyond patients to health care systems as well. By optimizing health care resource utilization, particularly in settings where infusion capacity is limited, we believe we can help contribute to overall efficiency. In terms of adoption, we anticipate that peak uptake in The United States will reach between 3040% within eighteen to twenty four months. We expect initial update to reflect potential delays in reimbursement by payers until a permanent J code is assigned by CMS.

Having said that, based on insights we’ve received, we continue to receive from customers and patients, we believe there is a keen interest in the adoption of this formulation. Outside of The United States, we also anticipate strong adoption of subcutaneous pembro, varying rates depending on specific country market archetypes. As we look to the future, we’re confident that our oncology commercial engine puts us in a strong position to maximize the impact of the broad and deep pipeline that my colleagues presented earlier. We have communicated a greater than $25,000,000,000 non risk adjusted commercial opportunity from our late stage pipeline. Of note, this number does not include innovations with currently marketed products, subcu pembro, earlier stage pipeline compounds such as the PD-one VEGF bispecific, or additional business development.

This revenue opportunity will result in our company maintaining one of the most diverse footprints across tumors, as well as driving into new areas, such as small cell lung cancer, prostate cancer, and hematologic malignancies. More than half of this commercial opportunity is driven by ADCs. We have a multitude of ADCs, as you saw in Eliot’s presentation a moment ago. We have a multitude of ADC candidates that are really, really exciting. In the next slide, I’ll I’ll give you an example of market opportunities specifically focusing on Sac TMT or Trop-two ADC.

Now this slide depicts the 14 ongoing registrational studies evaluating Sac TMT in multiple tumor types and stages of disease. In the dark teal boxes, you will see the nine potential indications for which we would be first in class. Nine out of the 14, we would be first in class. In the blue, we have the potential for meaningful differentiation. The dotted outline boxes reflect the progress we’ve made since last year’s ASCO.

Significant progress. You can also see on this slide the estimated addressable patient opportunity for each of the indications. So in aggregate, we have significant opportunities to advance standard of care for patients across a range of tumor types. Beyond Sac TMT, we have an extensive ADC portfolio. When considering those, with our collaboration with Daiichi Sankyo, PDXD, RDXD and IDXD, as well as our internal candidate, ZV, each of these ADCs is well positioned with opportunities across various tumor types and the potential to be first in class, each one of them.

More broadly, a company has the potential to launch 20 new growth drivers, and that includes WinRevare and Capraxiv, which are still in the launch phase in many countries, over the next number of years. So 20 new launches over the next number of years. 13 out of those are in the oncology space. So in closing, we’re committed to leveraging our innovative portfolio and our leading commercial engine to sustain our leadership position in oncology and create significant value for patients. With that, I’ll turn it back to Dean.

Dean Lee, President, Merck Research Laboratories, Merck: Thank you, Chorfi. You know, what I hope to do is effort today is to just give a framework in how we’re seeking to diversify in oncology. You know, we have more than 60 phase three trials across 16 candidates. We didn’t cover 60 phase three trials or 16 candidates, but essentially the broad impact of KEYTRUDA writes a roadmap for us to go in the future as we develop molecules spanning three pillars of biology, immuno oncology, tissue targeting, chemo with ADCs and next gen precision targeting, and across earlier and late stage cancers. And hopefully today’s presentation gives some context of our strategy and how we prosecute clinical trials.

And I promise you, you will see more trials posted by the end of the year. We’re in an advantaged position to improve patient outcomes and we look forward to further improving efficacy, treating patients optimally and treating them earlier. And with that, I’ll turn it over to Peter for Q and A.

Peter Dannenbaum, Senior Vice President, Investor Relations, Merck: Thank you, Dean. We look forward to taking your questions. So you’re all aware, Joanne Monaghan, who leads our US Oncology commercial business, is with us and can answer, questions pertaining to her areas of expertise. We’ll start here in the room. But before we do so, Denise, on the line, will you please provide instructions for those who are on the webcast to enter the queue for questions?

Operator: Absolutely.

Operator: You may withdraw your question at any time by pressing star 2. If you are using a speakerphone, please pick up a handset before pressing the numbers. Once again, if you have a question, you may press 1. 1 moment, please, for our first audio question.

Peter Dannenbaum, Senior Vice President, Investor Relations, Merck: So, Denise, we’re gonna hold off on the questions. Just wanna make sure they are aware how to enter the queue. We’re gonna start here in the room. Domini and Steve from the IR team are here with microphones. So please wait for them to get to you with the mic and state your name and firm name before asking your questions.

So we’ll start with questions. Vamil.

Vamil Devan, Guggenheim: Yeah. Vamil Devan from Guggenheim. So maybe a couple of questions. One on 2010. Obviously a lot of focus on the sort of market evolution with PD-one, PD L1, VEGF bispecifics.

Maybe if you can just comment, I think we saw some news from Summit a couple of days ago, what’s your perspective on how the markets are evolving? And you mentioned you have an ongoing trial, Phase III trial in China. I’m just curious what your latest thoughts are when you’d be starting any sort of development work in The U. S? And then my second question was just on June.

And

Dean Lee, President, Merck Research Laboratories, Merck: you mentioned sort of the number

Vamil Devan, Guggenheim: of patients that are diagnosed with head and neck cancer every year. Some of the KOLs we’ve spoken to just had mentioned that was locally advanced that they may not want to wait for surgery. Just if you could maybe sort of quantify a little more just your thought in the market opportunity there, going down further from that sixty percent, they’re diagnosed early. What percentage do think would be interested in?

Dean Lee, President, Merck Research Laboratories, Merck: So why don’t we have Marjorie just talk a little bit about the p d one VEGF space in relationship to the molecules and some of the data and ours, and then Elliot can give a broader sort of view as to how we think about advancing m k twenty ten and also what we believe is our advantage position?

Marjorie Green, Doctor, Merck: Thanks for the question. I I think that we all are watching the emerging data with with interest, and and I I think that we see this as an opportunity. We’ve got a robust portfolio and the ability to combine and make additional benefit for patients is really attractive to us. When you look at the totality of data that’s been generated to date, you’re seeing very consistent improvements of PFS either in the randomized data sets or in the single arm compared to historical control across a multitude of indications, confirming that the the biology about how VEGF and PD one, an anti VEGF combined with an anti PD-one can really be effective in the immune system. The question has been, the lingering one, is about the overall survival.

So I think that there were actually analyst reports that had predicted the original OS in the 0.7 to 0.8 range, and that’s where it’s hitting. So these are still clinically meaningful overall survivals. The open question is, what do the curves look like? And so right now, we are still very intrigued by the data that’s been generated to date because you’re seeing, again, consistency of data with multiple assets and meaningful improvements of progression free survival is still immature, and so we are continuing to progress our portfolio, and looking at DIMK ’20 ’10.

Dean Lee, President, Merck Research Laboratories, Merck: Yeah. I I I agree with you, with Marjorie. I mean, I think one of the one of the points to make is that a lot of the the data is in EGFR mutant non small cell lung cancer where the PD-one component of the bispecific hasn’t been particularly as effective as one would see in non small cell lung cancer without EGFR mutation. So one has to keep that in mind. We’re encouraged by the fact that Summit seems to have added non Chinese patients in this, the effect size seems to be relatively similar.

We’re just waiting for, to make sure that the OS benefits translate and that there’s more robust delineation of the data. That’s not withstanding, we have tremendous opportunities with a drug like this. And the reason why we’re doing the studies in China is because simply we’ve got an enormous infrastructure there that enables us to work together along with our wonderful partners at Kulin Biotech who can help us move things along faster in terms of combination strategies with some of their assets. Ultimately, we will come to The US, we have to do dose optimization and so on, but suffice it to say, we’re anticipating when the time comes having a rather large program similar to what we’ve seen with some of our other assets that I just mentioned. I think there was a So so the head and neck, I was gonna ask Marjorie to make a comment and then actually have Joe speak in terms of The US market in relationship to keynote June.

Marjorie Green, Doctor, Merck: I think when you look at the June data the control arm or people who went straight to surgery, there is no difference in the rates of surgery between treatment arms. And so patients did not lose the opportunity to have surgery when they received preoperative Keytruda. And I think that if you think back to triple receptor negative breast cancer, that people did not routinely give neoadjuvant therapy until there was a labeled indication. And so I think that getting that data out there, showing again that it was safe, that there wasn’t a risk of patients not being able to undergo surgery, the amount of chemo radiation given in the KEYTRUDA arm is actually less. The patients still receive radiation.

But the overall benefit is observed by that perioperative approach. And so I think it is something that as clinicians and particularly the surgeons see the data and understand it, that it will hopefully alleviate their concerns. Joe?

Operator: Yeah. And I can just add something. I I think what’s unique about the head and neck perioperative indication is that it’s two doses upfront. It’s not like lung cancer where it’s more doses. So you can give a dose and then three weeks later another dose.

And usually, there’s a three to a week delay for scheduling surgery anyway. So I’m not sure it’s gonna meaningfully delay. I’m not sure everyone knows, you know, that it’s a different regimen than what we see in other early cancers.

Peter Dannenbaum, Senior Vice President, Investor Relations, Merck: Thanks, Vamil. Next question, Steve Scala. Steve Scala from TD Cowen. Despite a history of leading in maybe five or six different therapeutic categories over the last thirty five years, Merck seems much more dug in and less willing to pivot this time, of course, away from oncology into something else. I realize there’s a lot of sufferers of cancer, but there are other diseases as well.

Do you agree with that? Or is that incorrect, and you’re perfectly willing to move on even quickly to a completely different therapeutic category? So that’s question number one. Question number two is, what are Merck’s plans to push back on CMS’s view that subcu versions of injectable drugs should be treated the same under IRA? And would you like us to be optimistic on your ability to prevail or you have no ability to call that?

Dean Lee, President, Merck Research Laboratories, Merck: Thank you. So I’ll take the first question and then I’ll think who best to talk about the second question. We talked about diversifying in oncology and we’ve provided how fast we’ve moved. But I would sit there and say, when I talk about expanding into other therapeutic areas, immediate reaction is you’re gonna expand in vaccines and you’ve seen that. We’re gonna expand in infectious disease and HIV and so we’re moving a new class of NR TTI as an anchor medicine for Q day to drug regimen and then to Q week and then potentially to Q month.

So that’s within our wheelhouse of HIV, but I’m not, and then I would sit there at cardiovascular metabolic. We have a history of it. So I’m sure there will be news about enlistatide in the coming year, in this coming year or coming weeks, coming months and winravir. But I don’t know that people suggest thought that we would move heavily into therapeutic areas that we had not been historically or recently in, and that’s in immunology, which we’re moving with enormous speed in relationship to T01A and other agents. And I think it caught many people surprised that we would drive into ophthalmology with totally new novel mechanisms.

So, you know, I can respond to the comments, but I think the most important thing for Merck and for Merck Research Labs to execute and demonstrate not just that we can say that we pivot, not just say that we’re doing the studies, but that we bring it home. So that’s what we want to focus on. In relationship to the CMS, I do think that the FDA has a very clear structure of two active agents. And I think a broader concept of going away from that, not just in relationship to their hyaluronidase or any hyaluronidase, but just as that structure, that FDA structure is really important. And I don’t believe that this would be a good precedent to set.

In this specific case of their hyaluronidase and pembrolizumab, we look at it as we don’t think this is a good precedent to make, but we also recognize that people have questions about beryllaronidase, pembro and our pembro launch. Everything we have with the FDA is that launch is going on and we have committed to making sure that that pembrolizumab subcu we think is so important, not just for the past approvals we have, but as a baseline as Elliot has said, how much we’re building on that foundation, that we really want that to be available. And so we’re really looking for access as an important standpoint. And we do recognize in The US, is gonna have biosimilar competition in ’28 and ’29. And our concept of advancing sub key pembrolizumab with very high lilanidase takes that into account.

But most importantly, it takes into account of how important we think it’s a foundation for what else we’re building as well.

Peter Dannenbaum, Senior Vice President, Investor Relations, Merck: Murphy or Joe have anything to add on on settled wealth hedge. Okay. Great. Evan?

Evan Segerman, BMO Capital Markets: Evan Segerman from BMO Capital Markets. Can you walk me through some of the evidence that you have to support the statement that you believe 30 to 40% peak adoption, eighteen to twenty four months post the launch of subcu Keytruda? How do you get there? You know, there’s a lot of questions with the launch approval of the Opdivo version. And what headwinds may you not be anticipating?

Chirfi Gwindow, Merck: So I’ll give a broader kind of a high level answer and then maybe Joe can chime in more specifically for The US. She’s in charge of the pre launch preparation. She’s working on exactly that. So first of all, we have market research and deep insights from customers and patients suggesting that this adoption will happen. Now I do wanna caution, as I mentioned in my prepared comments, that we do anticipate some slower uptake initially until we get the permanent J code issued by CMS.

That’s kind of the caution there. But we do have confidence based on the insights and the differentiated profile. I mean, you’re marrying really the reference now in IO treatment with the convenience of, you know, one minute to two minute push, which really will be very beneficial. So maybe, Joe, you can provide more insights.

Operator: Yeah. Thank you for the question. We have done number of quantitative adoption studies across the market looking and asking about adoption, sharing the profile and understanding where they’re gonna use, where providers will use sub q. We, and all of them have validated the thirty to forty percent. One of them was slightly higher than that, but we’ve landed on the thirty to forty percent as sort of the average across all the studies that we’ve done.

I think we expect to see greater uptake in monotherapy indications, early stage indications and oral combo, and lower uptake in the metastatic chemo combo, whether hanging a bag already and they already have a port. And so it’s not that much time saving to hang two bags. So, but when you blend it all together, it’s a thirty, forty percent. And as, Chirky mentioned, it will be slow in the first six months, because when you normally, providers will take a chance with a temporary j code if it’s a product that doesn’t have good alternatives. But when they have Keytruda IV that is a good alternative that has very reliable reimbursement, they’re not as willing to take the chance to make the transition until the permanent J code is in place, which essentially guarantees them they’re gonna get reimbursement within thirty days.

So we expect the first six months to be slow, and then we expect acceleration following that. There’s also some operational things that practices need to do to sort of work it into the EHR and and and all of those things, which we expect to happen over the course of the first six months. So by six months, we would expect the adoption to accelerate to the 30 to 40% of peak, which will be about eighteen to twenty four months post approval.

Evan Segerman, BMO Capital Markets: Quick follow-up there. You know, are these oncology centers ready for the potential impact to kind of their economic model with chairs and buy and bill and that whole kind of infrastructure that they’ve set up? And are you going to help walk them through that change?

Operator: Yes. So we are when we consider the price of sub q, we’re considering not only the the price of IV, but also the admin fees and other things that they get for IV relative to sub q. We also have targeted accounts based upon who has infusion share time challenges, where those are gonna be our early adopter accounts. So we’ve mapped the market based upon, where there are infusion challenges. Those are gonna be the places that we’ll adopt first is our expectation.

Peter Dannenbaum, Senior Vice President, Investor Relations, Merck: Great. Thanks, Evan. Chris Schott.

Evan Segerman, BMO Capital Markets: Great. Thanks very much. Just two for me. First, can you just elaborate on the differentiation you see with your TROP-two versus peers. Maybe it’s a 10, so you’re thinking about approaching some other assets in the more competitive categories.

Is this more about the molecule or the asset itself? Or is it Merck can take a different development approach and can leverage its portfolio to differentiate the clinical data available? I’m trying make some sense of like, is it Merck can take a less differentiated asset and turn it into something different? Or is the molecule really critical part of that? And the second one, just wanted to follow-up on the subcu TruDA comment.

I know you disagree with the idea of moving away from the kinda dual agent and if this were included in negotiations. But just given the availability of a biosimilar, has it really changed the outlook? Or or was the biosimilar gonna be kind of the key component of how you think about the longer term price for sub q? Pricing strategy, you mean? Pricing wise.

Dean Lee, President, Merck Research Laboratories, Merck: Okay. So why don’t we take the pricing wise first and Sure. Fee and Yeah. However you wanna handle that,

Chirfi Gwindow, Merck: and then we’ll take the other question. So I think we’ve, said it, already. I just wanna repeat it, you know, so that we’re clear. You know, we will price to access. We will price to, value and market share.

We’re going to be competitive looking at all those three dimensions. That’s all we can say about at this point.

Dean Lee, President, Merck Research Laboratories, Merck: Then in relationship to trope two, is it the molecule? Is it the clinical development team? I won’t say both, but I’ll let Marjorie and Alyette say both.

Marjorie Green, Doctor, Merck: I was thinking that I was right. I just wrote down differentiation schedule, toxicity, and development plan were the notes that I that I put down. And I I think, you know, that Coon has has generated a really remarkable ADC. Described it publicly before as Goldilocks and the Three Bears. This is just right.

Because there are day one, day eight schedules. There are Q3 week schedule. This is a Q2 schedule. And so it’s a little bit more frequent than the Q3 schedule. But you also have this efficacy, tolerability.

That therapeutic index is really critical for patients. And so I think it is just right in what you see with the manageable side effects that have been reported to date. And so the Phase III data sets will hopefully help confirm that. And I do think that we do have a differentiated development plan and taking advantage of the efficacy as well as the publicly disclosed tolerability aspects of the drug. We are doing maintenance approaches.

We’re not adding platinum chemotherapy on top of it, which is very difficult to do, and you get dose modifications and reductions, which can affect your efficacy. And so we really have developed a plan that is very robust. So I think it is both.

Dean Lee, President, Merck Research Laboratories, Merck: Right, I think that it’s the plan and it’s the molecule. First of all, the dose that we chose, think is gonna be very useful for a workhorse ADC. An ADC that’s going to be developed in multiple settings, in multiple stages of disease and where a lot of the therapy is gonna be in maintenance. It’s gonna be important to look as you all see our data and as you compare how limited it is to do cross study comparisons but if you, when you do to look at duration of therapy, time on treatment and how important that is in helping patients get to the right outcome. And of course that also has some commercial implications as well, but I think that the overall picture is a workhorse ADC that is just right.

And in new indications, the biomarker and or combination selections that I think will be differentiating. So of course the proof is in the pudding of the phase three program, but we really believe in this and there’s good reason why we put quite a bit of muscle behind this. And we’re really excited to be able to share all those data as they roll out and they’ll be rolling out in spades starting in as you look at the PCD dates 2027 and on. So I was gonna just add, it’s molecule, it’s development, and we said both, but I would just emphasize as a third issue. We have a great partner.

What was publicly revealed as to when we partnered with Keelin, we had partnered with them for some period of time. And their ability to give us clear signals and great interactions allows them to navigate within China in a way that’s extremely useful for Merck as the global presence to really learn.

Peter Dannenbaum, Senior Vice President, Investor Relations, Merck: Thank you, Chris. Next question, Courtney.

Courtney Breen, Bernstein: Everyone, Courtney Breen from Bernstein. A couple of questions. One is just a clarification. When it comes to MFN, I know everyone’s dealing with the potential and kind of probably developing 10 or 50 scenarios to think about what that might look like. Can you talk a little bit about kind of either changes to global launch strategy or kind of flexibility that you’re building into development plans as to to kind of how you’re dealing with that future uncertainty?

And then the second was just on m k sixty eight thirty seven that I noticed on the

Operator: on the

Courtney Breen, Bernstein: ADC slide. Is that a a Merck internally developed asset, or can you give us any more context on that one?

Dean Lee, President, Merck Research Laboratories, Merck: Can we take the m $3.60? Yeah. That’s internally developed.

Courtney Breen, Bernstein: Through capabilities that you gained from one of your partners? Or can you talk a little bit about

Dean Lee, President, Merck Research Laboratories, Merck: It’s our own. Okay. Homegrown. It’s our own. And and, you know, what’s not listed here is there’s and and Elliot alluded to the direction that we’re going and also that we have an equally robust internal pipeline that will go into phase one and then it’ll become visible, but that’s the tip of the iceberg.

In relationship with MFN, you know, I’ve I’ve been in meetings with you and with Rob and with Caroline and and, you know, the the way that I would just sort of emphasize is US is is the heartbeat of medical innovation. This is the market that drives market innovation. There is a concern by this administration as to whether that concept is recognized by all countries and all biopharma. One thing I can say is as a US based company, we will always launch our home country, which is the base of the whole industry, where that base of that whole industry actually values innovation. You know, I don’t wanna say what we will do in the future or this, but we have that concept that we will all always launch in The US, and we’re gonna have to be thoughtful as to how we launch in other countries and all of this, especially as these policies become not just things that is said, but become sort of ironed out and and actually put into practice.

So we watch the MFN space. I think Rob has talked about how MFN is really an important thing for us to keep track of, and we’re keeping track of it. Next question. Trung?

Vamil Devan, Guggenheim: Trung Wind from UBS. One on U1 and then one on radiotherapy. So it looks like MK twenty ten is a tetravalent into your slides there. It’s similar to ibonesumab. Looks like the main difference to me is nanobody part where it binds two p d ones.

Just wondering how you think that structure affects how effectively it works in the tumor microenvironment. Does having a nanobody here just reduce the allosteric steric hindrance that you get, bringing immune cells and tumor cells to some thoughts about that. And then pipeline has a lot of breadth with ADCs.

Dean Lee, President, Merck Research Laboratories, Merck: You have bispecifics.

Vamil Devan, Guggenheim: One area that you’re, noticeably

Dean Lee, President, Merck Research Laboratories, Merck: less versus your peers is is radiotherapy. So just thoughts there. So this is the DME question. It is. Yes.

Is. Was like Finally. Together. I’m like, finally, someone gives me a question. So one of the things I would just emphasize is I I think what is interesting to us is what Marjorie and Ellie have alluded to.

Initially, if you look at the different constructs, you can think of cooperativity and tissue targeting and all of this and you would sit there and you go, the Kiso compound and our compound, you could get that feeling that if there’s cooperative, if there’s some tissue targeting, sort of aspect that we would act similarly. The only problem with the answering that question is everything’s fun and games until you put it in a human. And what you recognize is you wouldn’t necessarily in the hypothesis that you have to do VEGF, immediately when you go to PD L1 VEGF, you’re like, okay, that hypothesis is no longer true. And if you look at BioNTech data, which is related to someone making an action right now, we’ll have to see whether it’s distinguished or it’s the same. And then other people have looked at molecules where the binding to the PD-one and the VEGF is like right on top of each other.

And so I’d love to tell you what I thought, whether the antibody was important or the construct was important in this. I believe in the general construct of what would you would say a casso and us, but the only way that I could say with certainty that I was right is if the data starts separating clinically to the different readouts for those different types of constructs. So we’re confident in our construct. We’re actually a little bit surprised at the clinical results from some of the other constructs. Radioligand.

Oh, the Radioligand therapy? I think we follow the Radioligand therapy very closely. There is some really important movement in prostate. We note that some companies are, for example, looking at ADCs and essentially using the same tissue targeting sort of thing and putting a radioligand. Our view is that an antibody drug conjugate in the right setting and in the right combination, if it can have meaningful impact and meaningful impact first, it may be hard for radioligand therapy to displace that given the complexity with it.

But there are clearly places with radioligands where ADCs may not work. And so we’ll have to figure that out as we develop our pipeline and other people. And then we’ll have to see where our unique places that radioligand therapy can attack. But you’re right. Right now we’re focused on tissue targeting with T cell engagers and with ADCs.

Peter Dannenbaum, Senior Vice President, Investor Relations, Merck: Great. Thank you, Trung. Next question, Mohit.

Mohit Bansal, Wells Fargo: Thank you. Mohit Bansal from Wells Fargo. One follow-up question, a clarification question, another question here. So, Jeffrey, we have heard that for Opdivo Sub Q, it is still in infusion centers, not not as certain in clinics. So what what what could you do to make it happen in clinics?

Because that that’s a that’s an issue for for a lot of for the uptake. The other one for Dean. I know it is a little bit early, and you have that column blank in terms of 02/00/2010 develop development. Most of the early players are all going after lung cancer, which is where KEYTRUDA is the strongest. So how do you think think about the development plan?

I mean, go after the the most difficult indication for a for a new player or go after somewhere where p d one has activity, but but it is easier to actually surpass that.

Dean Lee, President, Merck Research Laboratories, Merck: So why don’t I give Turfi that? And then I’m gonna actually see if Marjorie and Elliot wanna talk about potential.

Chirfi Gwindow, Merck: Yeah, I’ll pass on to Joe in a moment,

Mohit Bansal, Wells Fargo: but just as a general,

Chirfi Gwindow, Merck: I just wanna remind everyone that, we believe based on insights once again, that physicians will choose brand. So I just wanna provide that context because we don’t really look at Opdivo as necessarily a benchmark for pembro sub q. So just to put that out for context. Maybe, Jo, you can address the other question.

Operator: Every all the research we’ve done, providers say they’re gonna pick based on the clinical profile first and then go for the convenience Got second. I think what you might be seeing is that, as I mentioned, when in those first six months, there’s a couple things that have Right? One is the reimbursement picture needs to solidify with the temp permanent J code. Second is the operational factors.

So they have a very clear workflow of how they deal with immunotherapy today with IO and infusion chairs. They have to think through now how am I gonna do sub q? And so there’s operational decisions they’re gonna have to make for how they work it into their workflow. So you might be seeing I I can’t speak to Opdivo’s utilization, but I will say you might be seeing it in infusion centers because they haven’t figured that out yet. But over time, as they as they work it through, they put it in their EHR, they figure out where they’re gonna give it, then it I think you’ll start to see it, broaden beyond infusion centers.

That’s my guess. But that might be what’s going on. But we do know that that is something they have they’ve told us that we’ve got to figure out how how we fit it in.

Dean Lee, President, Merck Research Laboratories, Merck: So I’ll just give a broad statement and I’ll let Marjorie and Elliot sort of give more me. But essentially, as we’re moving very fast with MK twenty ten, there will be inflection point that we have to make as to how broad the program you wanna go and where do you go first. And we will go to Intruder playbook, look at what we’ve done. We will look at the LEAP playbook when people talk about PD-one and VEGF and what the past history is, oftentimes they’re talking about that playbook. And then we will also look at the playbook of every one of the compounds that you’ve seen right here and ask, did we alter that playbook?

But with that, I’ll bring it to Marjorie and Elliot to give you more detail.

Marjorie Green, Doctor, Merck: Yeah. I I think, you know, you agree with Dean is that you’re you want granularity that I I think that we’re not quite ready to to tell you our secret sauce yet. But part of what we’re doing is we do have an extensive database with Keytruda and have learned a great deal about what we can do. But what I really love about this from a development standpoint is the ability to combine with all of our internal assets that are things that that we have. And we already are have robust programs with multiple assets that we anticipate will be changing standard of care, And therefore, are going be very well positioned.

And most of these are where KEYTRUDA already exists, and we have KEYTRUDA combinations. So then being able to build on this, so as Elliot talked about, for example, with RDXD, we now have the B96 data in ovarian cancer. You can imagine, bevacizumab is used in ovarian cancer, the potential then with RDXD to do something really innovative.

Dean Lee, President, Merck Research Laboratories, Merck: Yeah, I think that’s right. You know, if you look at the one of the things I would suggest that you look at is all of the waterfall plot of studies or the sequence of studies and ask yourself, are these just Sac TMT studies or ten eighty four studies? Or are these studies that serve as the intermediate step in the final place where we’re going. So I would encourage you to look as the pipeline progresses understand that it’s not about just saying everything that pembro was there and this was as you put 2010. You know, that would be okay.

What would be even super more okay is this both combinations that we’re putting together. And I’ll leave it at that. Yep. Alright. Dana.

Peter Dannenbaum, Senior Vice President, Investor Relations, Merck0: Two questions for me. Hopefully, one fast, one longer. So you talked about using digital pathology and AI and that we’re going to learn more soon. Should we expect you’re already employing that prospectively in any of your Phase III ADC trials? And then my second question is actually about ZV and lymphoma.

So we recently heard from FDA in their ODAC for STAR GLOW hypothesis that arGemox is not an appropriate preferred SOC comparator arm for U. S. Studies. And I wonder what you think about that and how that could impact your development of ZV for lymphoma.

Dean Lee, President, Merck Research Laboratories, Merck: So who wants to take digital? Who wants to take I’ll be very quick on digital path and tell you that we really don’t wanna share at present what we’re doing because, well, we’d rather share the information first in a in a academic setting.

Marjorie Green, Doctor, Merck: Yeah. And then for ZV, I I think, you know, the two studies I talked about are really first line studies, and I think what we really see as the biggest benefit is going there.

Peter Dannenbaum, Senior Vice President, Investor Relations, Merck: Great. Next question, Akash.

Dean Lee, President, Merck Research Laboratories, Merck: Thanks so much. Okay. So just a few. Medicare Part D D and D draft guidance, there were two changes. Right?

One, it made it seem like sub q and IV were considered the same drug. But I feel like the other part was you had meaningful changes to the term bona fide marketing, where they basically said, if you can have a biosimilar launch, even if it takes de minimis share, as long as there were no agreements to prevent uptake, you are considered bona fide marketing, and then you have the biosimilar exclusion apply. In the past, Mirka has talked about both IRA negotiation and biosimilar entry in 2028. Can you maintain that position given the new draft guidance? And then number two, with you know, you have 14 trope two studies that are written out here, this is like a question I asked by OnTech.

You have, like, to your point, version one point o and then two point o trials where it’s novel novel combos. Are you alluding that you can take p d one VEGF combinations and apply them to the current phase three trope two studies you’ve already announced? And and why not delay some of those studies because you really want two novel agents? Why spend, you know, the money for 14 phase three when that might not be where you’re ultimately headed? I’ll try the last one and two ones with the first one.

K. So I’ll I’ll I’ll take the rephrase the first one. Okay. Let’s put it this maybe bluntly. What would stop Merck from settling with one biosimilar in 2028?

You have IP out to 2032 or beyond. You are now excluded from the IRA, and SUBQT TRUDA is no longer negotiated. This is very similar to what EYLEA and high dose EYLEA is right now.

Operator: Yeah. So I can address that one. So we actually did did the math on that, and it was giving up near term value pre LOE that did not justify uncertain value post LOE. I think that’s the bottom line. We did we we actually did evaluate that, and and the, the financials did not make sense.

Dean Lee, President, Merck Research Laboratories, Merck: I’m sorry?

Operator: Yes. Yes.

Dean Lee, President, Merck Research Laboratories, Merck: Yeah. In relationship to we are going to have FROP-two, but we’re gonna have a lot of ADCs and a lot of agents coming through. So I just wanna put that context and we intend to develop them appropriately if they’re a signal. So the question that you’re having is this first tranche that you see, should we delay that as the field is trying to figure out PD-one VEGF? Should we do that now?

We also have the potential optionality also just move right now where we are because it isn’t like we have a dearth of other opportunities to do that. And I think there’s gonna be a whole series of things that will come together. We’re advancing ten eighty four. We’re advancing lots of different agents. But one of the things that I would be a little bit careful about is to sort of the enemy of the good can be the perfect.

And I would be careful about that when we have such a great partner in Kalu who’s given us such clear signals to go now for me to sit there and delay for PD work. Is it this? Is it that? Is it this and this? So we will have that problem, but it may be further down the pipeline.

And at that moment, we will have to make a decision of shift as you’ve said. Right, I think it’s important to recognize that these studies are gonna not only read out important information about Sac TMT but also help us with some of the biomarker strategies that we’ve already launched. There’s also it’s important to recognize that PD one VEGF is not for free from an AE point of view. VEGF related AEs are just a fact, and so it’s important to understand these drugs in a little bit more detail before one would say, wait a minute, I’m gonna hold on and not do that. Not to mention the fact that the delta of time is sufficient that it doesn’t make sense from the patient outcomes point of view or the commercial point of view.

Peter Dannenbaum, Senior Vice President, Investor Relations, Merck: I think we still have hands in the room. John.

Evan Segerman, BMO Capital Markets: Thanks, Scott. John Miller from Evercore ISI. Two probably quick ones from me. Marjorie, you you said today and we’ve heard the team talk before about VEGF bispecific hazard ratio in point seven to point eight for OS being really compelling from a development perspective. But what if it’s more like point eight two to point eight five, like the like the lag threes in melanoma?

Is that a compelling enough signal to justify a real aggressive push into that market? And then secondly, maybe potentially broader than just oncology, what’s your current interest in acquiring assets ahead of a Phase III readout like you did with cetada?

Dean Lee, President, Merck Research Laboratories, Merck: Why don’t you take

Marjorie Green, Doctor, Merck: that first one, and and then, of course, I always appreciate, Elliot, your thoughts too. It you know, hazard ratios in the point eight to point eight five get a little bit more in the gray zone, and some of it has to do with the delta that you generate. So if you’ve got a frontline regimen where you’ve got a PFS that is twelve to fifteen months, then a point eight, point eight five still can be very clinically meaningful. Also, if you’re in a disease indication where you have multiple subsequent therapies, and OS is harder to differentiate or you’re able to treat in a second line setting, then the point eight to point eight five might still be reasonable. So I’m giving you a non answer because it depends.

It it really does.

Dean Lee, President, Merck Research Laboratories, Merck: In terms of appetite, I really like deals where where there’s a history of us understanding what we expect, and then we see data ahead of phase three that makes us go, wow. Our negative opinion of this needs to change pretty quickly. That’s Acceleron. That’s Prometheus. That’s iBile.

So we really like that because it creates value and a differentiated position for us. So we we we what you’ve outlined is what I really like.

Peter Dannenbaum, Senior Vice President, Investor Relations, Merck: Denise, are there any questions in the webcast?

Operator: I do have a question from James Shin with Deutsche Bank. Your line is open.

Peter Dannenbaum, Senior Vice President, Investor Relations, Merck1: Hey, guys. Thank you for the question. Got a few for Dean. I want to circle back on comments on being surprised by some of the PD-one VEGF data. Can you elaborate what surprised you?

Then given twenty ten’s data is relatively lagged from these existing PD-one VEGF players, does twenty ten have to demonstrate a superior efficacy safety profile to make up for the time gap? Finally, is Merck’s business strategy to focus on differentiated science and first in class assets, or is there now some appetite for a known target or derisk target? That’s it. Thank you.

Peter Dannenbaum, Senior Vice President, Investor Relations, Merck: May have had trouble hit hearing the third part of your question, James. Can you repeat it?

Peter Dannenbaum, Senior Vice President, Investor Relations, Merck1: Oh, yeah. The third question is for biz dev, is the focus still on differentiated science and first in class assets, or is there now some appetite for known targets or derisked assets?

Peter Dannenbaum, Senior Vice President, Investor Relations, Merck: I I would say, I mean, our business development strategy has not changed.

Dean Lee, President, Merck Research Laboratories, Merck: So So I should just be a little bit careful because the people in the room can see my hand gest gesticulations and you can’t. So when I look at p d one VEGF, I’m binding p d one and I’m binding VEGF and there’s a considerable distance there. Right? And p d one’s a receptor. Then all of a sudden, p d l one is on a different cell and that’s different.

Right? That’s different. And then you guys got some people who are not p d one VEGF like this with two hands being, you know, your p d one and the my legs being, VEGF. You have PD one VEGF right here and a PD one VEGF right here. If you would ask if you were designing knowing certain hypothesis, you wouldn’t necessarily design if you thought cooperativity or tissue targeting or something like that would have been important, a priori you wouldn’t necessarily design such different molecules.

But what I was trying to say is, it’s easy for me to say how smart I am, but the problem is that these clinical data are coming a little bit close to one another. And so I need to be a little bit careful that whatever the original question was, what do I think of the different designs? I have my preference. I made my preference, but I need to be a little bit thoughtful of saying I’m right because some of these other constructs actually gave me surprising results that I would not expect to work. Okay.

Anything further on the BD strategy, whether it’s changed or evolved in any ways? We are very interested in advancing business development in therapeutic areas that we’re well known for. And related to your question, we’re very interested in going to business development. I think surprise people where you don’t see us having a strong presence in the last ten years and we’re willing to go there. For us, the critical thing is does the pathway, does the technology, does the clinical design of how you would do this demonstrate unambiguous promotable advantage that we can meaningfully move the market and, as I alluded, especially move the market in the market that that really, really values innovation, and that’s The United States.

Peter Dannenbaum, Senior Vice President, Investor Relations, Merck: Right. So we are over time. These have been really good questions. Are there any final one or two questions in the room? Mary Kate?

Marjorie Green, Doctor, Merck: Hi. Mary Kate on for Jeff. Just a quick one on MK twenty ten. So trial ongoing in China. Maybe how are discussions going with regulators here?

Could you comment on their expectations for the program? And maybe just broader, how has communication been in general with FDA CMS?

Dean Lee, President, Merck Research Laboratories, Merck: I’ll take the general question, which is we’re a company that we tell you, you know, we pivoted our pipeline and we have a lot of launches. We’ve given numbers in relationship to that. So holding on to those PDUFA dates are especially important to us as we pivot. We have important ones in relation with clozroblimab. We have important ones in relationship to potentially winravir and labeling changes with the incredible data that we have with Xenith.

We have that with subcu pembro and all of interactions with the FDA for those most immediate ones have been constructive. In relationship to PD-one VEGF, in relationship to regulatory interactions, I think we’ve kept that a little bit quiet, but I’ll just ask Elliot if he had any questions that he wanted to. No, I mean, I think we’re the development strategy for 2010 is something that we’ll roll out and we’ll provide updates when we think it’s the right time. I I again, I’m we’re excited about this drug where we understand the value of the drug very well. We’re also mindful about where we need to be careful with VEGF.

Peter Dannenbaum, Senior Vice President, Investor Relations, Merck: Great. Thank you all very much for coming to our event. I’m sorry we went a little bit long, but they were really good questions. And, you found them very informative answers. Dean, any closing remarks you’d like to make?

Dean Lee, President, Merck Research Laboratories, Merck: Yeah, I just wanted to thank everyone and really appreciate your interest. I hope you gave, got a little bit of sense of what Rob, Caroline, myself and this leadership team has done since 2021, which is the diversify oncology and expand in other therapeutic areas. And we’ve just talked about a fraction of that oncology framework for you. And I thought that hopefully will be important Right now, I think we have around 80 phase three trials that’s publicly known. I think 60 of them were in oncology and so we gave you a framework for it.

We didn’t go through all of them. 20 is within non oncology. I have here that we have 25 distinct assets in those and 16 in oncology, ten in non oncology. So, we are very interested in moving the pipeline. But as we emphasize in oncology, we’ve learned a lot from oncology in relationship to KEYTRUDA, what it can teach us to do better and what it teaches us to do next.

And so we have, I believe Rob has talked about 20 new growth drivers over the next coming years, including weir and miricatvaxib. I hope you got a sense from that slide. And those are official PCD dates as Elliot said, there’s always possibility for interim analysis. This gives you a context of those comments that Rob and Caroline have made in relationship to using oncology and phase three trials as an exemplar of the type of framework as we move on to continue to do great work at Merck to move the needle and bringing important medicines to patients. Thank you very much for your interest, and there’s food back there.

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