Thank you for standing by. Welcome to the Merck & Co., Rahway, 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.
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. We are 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 speaker's prepared remarks and has been posted to the investor relations section of Merck's website. 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 2024 10-K, which identifies certain risk factors in cautionary statements. I'd now like to introduce Dr. Dean Li, President of Merck Research Laboratories, who will open with a few remarks and outline our agenda and speaker lineup. Dean.
Thank you, Peter, and good evening, and welcome. We are 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 are two major goals. One is, first, to diversify across oncology using the power of KEYTRUDA. The second is to expand in additional therapeutic areas such as HIV, vaccines, immunology, cardiovascular, and ophthalmology. The focus today at ASCO will be on the substantial progress of oncology programs. KEYTRUDA has been a source of extraordinary impact for the world and for medicine and for Merck. It's been such an important medicine with a remarkable impact for patients and providers.
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 III oncology trials with statistically significant overall survival, 56 FDA-approved indications, and a significant impact to patients with more than 3.4 million treated globally. 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 2031, and in 2032. Here is 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 agnostics, two tumor agnostic indications. Essentially, KEYTRUDA has laid a roadmap across solid tumors and increasingly in the earlier stage and curative intent setting.
In the light green, you can see nine approvals in the earlier stage. As Marjorie and Eliav suggested, we hope to have that turn into 10. 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. We listed the four sort of major topics that we'll be talking about here. First, the progress made in curative intent setting, including more accessible options and new treatment paradigms. What do I mean by that?
In terms of more accessible options, it's a subcu administration has the 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 subcutaneous pembrolizumab in a non-infusion center such as a physician's office. Marjorie will touch on subcu pembrol. 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. We think that separation of those populations creates a platform for us to, for example, really think about how we can do more good for those who are non-responders.
In our collaboration with Moderna and developing INT and individualized neoantigen therapy, which essentially for the last 30 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 and in non-small cell lung cancer, and those that are PD-1 and oncology sensitive. The second is the combination of KEYTRUDA with chemotherapy that has absolutely been transformative. Often people throw out the words of being KEYNOTE-189 in the late stage of cancer and KEYNOTE-671, but it's actually true in many other cancers than just lung cancers. We now ask, how can KEYTRUDA amplify the impact of next-generation chemo? We have antibody-drug conjugates, and we're advancing next-generation chemo with a broad ADC program.
What we'll outline there 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. In that one, we have 14 studies that's publicly acknowledged. Of those 14, nine of them are in indications where we believe that we're clearly going to 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. We'll touch on this. We'll focus on doing this with MK-1084, our KRAS G12C, which is designed to be highly potent and highly combinable with potential benefit in both earlier and late stages of cancer.
Marjorie and Eliav will speak more about it momentarily. Finally, we also have learned where PD-1 or KEYTRUDA has not been as effective. 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 hemes. This has led us to go into other agents, including KRAS G12C, but also T-cell engagers, ADCs, and combinations amongst them. Today, we hope to just give you a flavor of our broad efforts across oncology, across early and late phase, across multiple mechanisms of actions, and across multiple modalities. By focusing on a subset of our robust registration of clinical trial portfolio, we hope to give you an insight into the strategic context and, importantly, the timing of these readouts.
First, Marjorie Green will provide recent notable data updates from ASCO, AACR, and the European Lung Cancer Congress. Dr. Eliav Barr will take a more expansive view of our oncology development strategy, providing compelling exemplars of our strategy in action, including how we are leveraging our foundational position in immuno-oncology and advancing combinations to improve standard of care. Finally, Chirfi Guindo 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&A. Now I'll turn the podium over to Marjorie.
Thank you, Dean, and hello, everybody. We're excited about the data that we presented early this year as well as at ASCO. We continue to make significant progress in our portfolio. One advance has been the development of a subcutaneous fixed dose combination of pembrolizumab with beta hyaluronidase alfa. We presented the results of D77 at ELCC, evaluating the combination of pembrolizumab and beta hyaluronidase 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 subcu formulation compared to IV and demonstrating non-inferiority. Important secondary efficacy endpoints, which were descriptive, showed 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 and D77, given 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 with the patient benefit of a median injection time of two minutes. Moving on to more KEYTRUDA news, Dean spoke to that 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, again, the curative or in the metastatic setting.
KEYNOTE- 689, 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 20 years. The data demonstrates that improvement in event-free survival was seen in ITT as well as in the populations whose tumors expressed PD-L1. 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 MK-1084, 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 KANDLELIT-001 study of MK-1084, one data set looking at non-small cell lung cancer, looking at it as monotherapy as well as in combination with pembrolizumab. That combination showed that for people who have PD-L1 positive non-small cell lung cancer, the overall response rate was 77%. 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. That's something that's really exciting about this.
In colorectal cancer, we also presented data looking at MK-1084 as monotherapy as well as combined with cetuximab. Finally, the triplet of MK-1084, cetuximab and FOLFOX also demonstrating very robust responses. Both of these showed manageable safety and tolerability and, again, promising anti-tumor activity. 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 MK-1084 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 MK-1084 combined with pembrolizumab shown in this study, a trial comparing the combination of MK-1084 with subcutaneous pembrolizumab compared to the KEYNOTE- 189 regimen of chemotherapy combined with KEYTRUDA.
That is going to be something that is going to be potentially a chemotherapy-free, IV-free regimen for patients with non-small cell lung cancer. We are also initiating—we have initiated, excuse me—the KANDLELIT-012 study in colorectal cancer, and first patient enrollment is imminent. We are really excited about the host suite of studies that we have, and we are 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, we presented data from MK-2140, otherwise known as zilovertamab vedotin, 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 MK-2140, in the frontline setting, combining 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 II/III 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 R-GemOx showed a response rate of the mid-50% range, and historical control data shows that that response rate is estimated at 35%-40%. We are excited about the combination data.
We have a 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-010. We also have a phase two study that is looking at ZV versus polatuzumab vedotin in the GCB subtype in waveLINE-11. I'd like to touch on additional data from our ADC portfolio, looking at data that our partners at Kelun-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 Kelun-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 OptiTROP-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 sac-TMT is very manageable, and we believe that it is a differentiated ADC in the TROP2 space. This is the first TROP2 ADC approved for lung cancer in China, and two global phase III 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 phase II OptiTROP-Breast05, 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 70%, and consistent results were observed across PD-L1 expression level. The median duration of response is approximately 12 months, showing the promise of this asset in triple receptor negative breast cancer. As with the data that Kelun has generated in China in lung cancer, the data they've generated has helped engage as initiating studies globally in triple receptor negative breast cancer.
The data continues to demonstrate a manageable safety profile, and the phase III studies we have underway include TroFuse-011, 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-12 in the setting of residual disease for patients who do not have a pathologic complete response with the KEYNOTE-522 regimen, and very recently we have started TroFuse-32.
This is a neoadjuvant study of sac-TMT as a replacement for anthracycline-based therapy as part of the KEYNOTE 522 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 Eliav. I'm going to hand it over to Eliav now.
Thank you, Marjorie. Again, thanks to all of you for making it at the end here at the end of ASCO. As you've heard, we have a broad and deep pipeline, and it's divided into three groups.
Our immuno-oncology medicines are designed to stimulate anti-cancer immune responses, and they include the subcutaneous pembrolizumab with hyaluronidase alfa, 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 MK-1084 that Marjorie just pointed to. We anticipate important readouts for belzutifan, epivastat, and nemtabrutinib over the next year or so. Finally, our ADCs and T-cell engagers are designed to target chemotherapy and immune cell activation to tumors while mitigating the effects in normal tissue. You've heard about sac-TMT and zilovertamab vedotin from Marjorie, and we're also excited about our other DXd assets. I want to particularly point to our highly active rising star, again, from Kelun-Biotech, MK-3120, a Nectin-4 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 want to touch on 3120. 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—it 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. We're also working hard on biomarker selection, and I'll talk a little bit more about that. Where feasible, we think that that's going to 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. 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 III studies read out. Now, our investment in treating early-stage cancers and new medicine like INT, or now it's called intismeran autogene, is based on our goal of effectively treating cancer in the curative intent setting before it metastasizes. KEYTRUDA continues to provide important data, and of course, KEYNOTE- 689, which you just heard about, is one of those things.
I would also 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 MK-3120. We're also going to have some readouts of KEYNOTE- 756 in HR-positive breast cancer, and I think that's going to 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 want to show you how the combination of industry-leading foundation of KEYTRUDA and the rich pipeline can enable us to provide unique opportunities to advance cancer care. I show you four examples here, and we'll go through—I will 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. We'll start with the first one. KEYTRUDA and KEYNOTE- 671 have demonstrated that perioperative treatment with pembrolizumab improved outcomes in patients, in 671's case with non-small cell lung cancer. There is a whole series of studies, as Marjorie pointed out and Dean, where we've shown that perioperative therapy with KEYTRUDA can really improve outcomes, and especially OS. Patients with detectable viable tumor at the time of surgery remain at high risk for recurrence. As an example, the percentage of patients in KEYNOTE- 671 who do not achieve pathologic complete response is 80%. There are 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. We are keen on adding to the platforms that things like KEYNOTE- 522 in triple negative breast cancer or KEYNOTE- 671 in non-small cell lung cancer are using, those platforms to improve outcomes for patients in particular populations that are at high risk. 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. KEYNOTE- B96 provides us with a pole position to create combinations with R-DXd, which is highly active in this setting. Finally, as a last example, or within the third example, I should say, KEYNOTE -189 set a very high standard for benefits in patients with newly diagnosed locally advanced metastatic non-small cell lung cancer.
As Marjorie notes, we can now define segments of the populations with the potential for even better outcomes using MK-1084, which has really quite exceptional duration of response and objective response rates. The last example is gocatamig and I-DXd. These are two agents that are being developed in partnership with Daiichi Sankyo, and these have orthogonal mechanisms of action in high activity in small cell lung cancer. In all of these settings, in each one of these settings, we're very excited about the potential for MK-2010, which is our PD-1 VEGF bispecific, to enhance the foundation that pembrolizumab gives us. As promised, I'm going to take each of these four examples and give you a little bit more of a deep dive. As you can see, these are a suite 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. There are more than 30,000 patients in over 30 active phase III 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. Again, you can look at KEYNOTE- 671 as an example. We have mentioned already a couple of times the importance of KEYNOTE-671 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.
In these patients, we're evaluating both INT, and you can see in that second line intismeran autogene, as well as sac-TMT. Now, these are drugs with very different profiles, and we don't think that they're going to be overlapping. These are 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 already have studies planned to add settings where readouts with pembrolizumab in the perioperative setting are imminent. 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. Now, we and Daiichi Sankyo have shown the outstanding activity of raludotatug deruxtecan, or R-DXd, in later lines of therapy in ovarian cancer. Further exciting data are going to be released in the upcoming months. It's really a great drug. We'll now combine pembro and R-DXd with the potential to further improve outcomes in these cancers, as well as in earlier lines of therapy within ovarian cancer. 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 MK-2010 with R-DXd in the future. We've talked a lot about MK-1084, but I want to 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 that co-administration of MK-1084 with pembrolizumab is generally well tolerated and results in a very high rate of extremely durable responses up to 24 months and counting. The reason why it's just 24 months is because that's pretty much where we started the study. It's a really quite remarkable drug. I'm particularly excited about the imminent start of KANDLELIT-007. This study is a phase III study.
We'll compare MK-1084 plus subcutaneous pembrolizumab with barohialuronidase alfa and the KEYNOTE- 189 pembro chemo regimen in patients with newly diagnosed locally advanced or metastatic KRAS G12C positive non-small cell lung cancer. On the one side, we'll have subcu pembro and an oral tablet administered once a day, and on the other side, we'll have KEYNOTE- 189. You can imagine how that combination of a pill and a subcutaneous injection that can be given over one to two minutes is going to be really a revolution for patients if you can see that the efficacy is as we expect. 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 I've chosen small cell lung cancer because this is not an area where pembrolizumab has been a foundational drug. In the U.S., there are about 34,000 patients per year that are diagnosed with small cell lung cancer, and that represents about 15% of all lung cancers. You all know that the prognosis is quite dismal. gocatamig, MK-6070, and I-DXd, we call it MK-2400, have orthogonal mechanisms of action, and each has shown high activity in small cell. 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 I 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. 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 in targets, bispecifics, and new payloads, as well as other opportunities to improve outcomes for patients and create unique combinations. You can see all of the different ADCs here, some with our colleagues at Kelun-Biotech and some with our colleagues at Daiichi Sankyo, which really is a group that really has done an enormous amount of benefit in advancing the field of ADCs. sac-TMT is our most advanced ADC.
Kelun-Biotech studies in China have provided us with confidence in this asset, as well as important data to aid in the designs of our sac-TMT studies. Now, we recognize that there are other TROP2-directed ADCs with different antibodies, linkers, and payloads, but our foundation with KEYTRUDA and the strength of this particular asset and our execution teams has led us to a multifaceted and unique program that's 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. Of course, there'll be other studies that will present it in due course. How does this huge pipeline and our overarching strategy translate into phase III 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 analyses 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 MK-3475A, with the potential to meaningfully lower the barriers to access for patients and providers. The studies will also enable combination strategies. I am excited about the WELIREG studies that are finally getting close to being ready for readouts, as they have the great potential to advance therapy in RCC where there's significant unmet need. Here are our new pipeline programs. You can see in the bright green the sac-TMT program, which is really a huge effort on our part. We also have studies of MK-1084.
We have studies of bevacizumab, our CYP11A [audio distortion] inhibitor for prostate cancer, bomedemstat, our LSD1 inhibitor for essential thrombocythemia, and nemtabrutinib, 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 are advancing MK-2010 in China, where we have highly efficient operational capability. This PD-1 VEGF bispecific has potential across many tumor types. As you see from our presentations, we have unique assets and a highly experienced operations engine that in aggregate will enable rapid evaluation of MK-2010 alone or with other agents in a large number of patients. Our unique pipeline provides us with important insights as well as opportunities to develop this drug for patients across the spectrum of cancer.
In closing, I hope I've shown you that we've moved with urgency to execute a tremendous strategic pivot beyond KEYTRUDA to a more diversified, multifaceted pipeline of innovative candidates, not just with signal generation phase I studies, which is mostly what you saw with the exception of sac-TMT in this ASCO, but with a tremendous cascade of phase III studies that over the next few years will readout, and I think will make a tremendous impact on cancer care going forward. We really think that this pipeline will help us write the next chapter in the book of cancer therapeutics for Merck. With that, I'll turn it over to Chirfi.
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 today over 3.4 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 U.S., 44 in the EU , and 41 in Japan. Of those, KEYTRUDA is approved in an unparalleled 41 indications in the U.S., 31 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. We've got a lot more opportunities ahead. As you've heard from my colleagues, we're driving impact in early-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- 689 study. This is the first positive trial in 20 years for patients with resectable locally advanced head and neck cancer.
For context, in the U.S., there were 58,000 new cases of head and neck cancers diagnosed last year, and sadly, 12,000 deaths from the disease, which speaks to the large unmet medical need in this space. Approximately 60% of these cases are diagnosed at the locally advanced stage, and a portion of those would be addressable by KEYNOTE- 689. We look forward to bringing this treatment option to appropriate patients. If approved, KEYNOTE- 689 would mark the 10th earliest stage approval for KEYTRUDA, unprecedented. Our commitment to innovation and addressing the unique needs of patients and healthcare providers and systems extends to the development of subcutaneous pembrolizumab in combination with barohyaluronidase alfa. We hope to bring this innovation to patients in the U.S. later this year. subcutaneous pembro pairs well with 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 Q3 week injection, two minutes for the Q6 week injection, and the lowest volume injected. We're seeking all adults or the tumor indications where KEYTRUDA is currently approved. subcu 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 healthcare systems as well. By optimizing healthcare 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 30%-40% within 18- 24 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 adoption, in the adoption of this formulation. Outside of the United States, we also anticipate strong adoption of subcutaneous pembro with 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 billion 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-1 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 Eliav's presentation a moment ago. We have a multitude of ADC candidates that are really, really exciting. In the next slide, I'll give you an example of market opportunity specifically focusing on sac-TMT or TROP2 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. 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, P-DXd, R-DXd, and I-DXd, 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 WINREVAIR and CAPVAXIVE, which are still in the launch phase in many countries over the next number of years. 20 new launches over the next number of years. 13 out of those are in the oncology space. 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.
Thank you, Chirfi. What I hope to do in this effort today is to just give a framework in how we're seeking to diversify in oncology. We have more than 60 phase III trials across 16 candidates. We didn't cover 60 phase III trials or 16 candidates. 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. Hopefully, today's presentation gives some context of our strategy and how we prosecute clinical trials. I can promise you, you will see more trials posted by the end of the year. We're in an advantage position to improve patient outcomes, and we look forward to further improving efficacy, treating patients optimally, and treating them earlier.
I'll turn it over to Peter for Q&A.
Thank you, Dean. We look forward to taking your questions. As you are all aware, Joanne Monahan, who leads our U.S. oncology commercial business, is with us and can answer questions pertaining to her areas of expertise. We will start here in the room. 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?
Absolutely. Ladies and gentlemen, if you wish to ask a question, please press star one on your telephone keypad. You may withdraw your question at any time by pressing star two. If you are using a speakerphone, please pick up the handset before pressing the numbers. Once again, if you have a question, you may press star one. One moment, please, for our first audio question.
Denise, we're going to hold off on the questions. I just want to make sure they are aware of how to enter the queue. We're going to start here in the room. Dominique 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. We'll start with questions. Vamil.
Thank you. Vamil Divan. I'm Guggenheim, so maybe a couple of questions. One on 2010. There's obviously a lot of focus on the sort of market evolution with PD-1, PD-L1, and [audio distortion] bispecific. 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? You mentioned you have the ongoing trial, phase I/ II trial in China. I'm just curious what your latest thoughts are on when you'd be starting any sort of development work in the U.S.. My second question was just on 689. You mentioned sort of the number of patients that are diagnosed with head and neck cancer every year. Some of the cables we've spoken to have mentioned that patients locally advanced may not want to wait for surgery.
I'm just curious if you could maybe sort of quantify a little more just your thought on the market opportunity there. Going down further from that 60%, they're diagnosed early. What percentage do you think would be interested in?
Why don't we have Marjorie just talk a little bit about the PD-1 VEGF space and relationship to the molecules and Summit's data and ours, and then Eliav can give a broader sort of view as to how we think about advancing MK-2010 and also what we believe is our advantage position.
Thanks for the question. I think that we all are watching the emerging data with interest, and 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 biology about how VEGF and PD-1, an anti-VEGF combined with an anti-PD-1, can really be effective in the immune system. The question has been, the lingering one is about the overall survival.
I think that there were actually analyst reports that had predicted the original sort of OS in the 0.7-0.8 range, and that's where it's hitting. These are still clinically meaningful overall survivals. The open question is, what do the curves look like? 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. It's still immature, and we are continuing to progress our portfolio and looking at MK-2010.
Yeah, I agree with Marjorie. I mean, I think one of the points to make is that a lot of the data has been in EGFR mutant non-small cell lung cancer where the PD-1 component of the bispecific hasn't been particularly as effective as one would see in non-small cell lung cancer without EGFR mutation. You have to keep that in mind. We're encouraged by the fact that Summit seems to have added non-Chinese patients, and the effect size seems to be relatively similar. We're just waiting to make sure that the OS benefits translate and that there's more robust delineation of the data. That notwithstanding, we have tremendous opportunities with a drug like this.
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 Kelun-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 U.S. We have to do dose optimization and so on. 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 follow-up.
The head and neck, I was going to ask Marjorie to make a comment and then actually have Jo speak in terms of the US market in relationship to KEYNOTE-689.
I think when you look at the 689 data, the control arm were people who went straight to surgery. There is no difference in the rates of surgery between treatment arms. Patients did not lose the opportunity to have surgery when they received preoperative KEYTRUDA. I think that if you think back to triple receptor negative breast cancer, people did not routinely give neoadjuvant therapy until there was a labeled indication. I think that getting that data out there, showing again that it was safe, that there was not a risk of patients not being able to undergo surgery, the amount of chemoradiation given in the KEYTRUDA arm was actually less. The patients still received radiation, but the overall benefit is observed by that perioperative approach.
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.
Jo?
Yeah, and I can just add something. I think what's unique about the head and neck perioperative indication is that it's two doses up front. It's not like lung cancer where it's more doses. You can give a dose and then three weeks later another dose, and usually there's a three to plus week delay for scheduling surgery anyway. I'm not sure it's going to meaningfully delay. I'm not sure everyone knows that it's a different regimen than what we see in other early cancers.
Thanks, [audio distortion]. Next question, Steve Scala.
Thank you, Steve Scala from TD Cowen. Despite a history of leading in maybe five or six different therapeutic categories over the last 35 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 of other diseases as well. Do you agree with that, or is that incorrect in your perfectly willing to move on even quickly to a completely different therapeutic category? That is 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? Would you like us to be optimistic on your ability to prevail, or do you have no ability to call that?
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. I would sit there and say when I talk about expanding into other therapeutic areas, the immediate reaction is you're going to expand in vaccines, and you've seen that. We're going to expand in infectious disease and HIV, and so we're moving a new class of NRTTI as an anchor medicine for Q day to Q drug regimen, and then to Q week, and then potentially to Q month. That's within our wheelhouse of HIV. 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 imbecitide in the coming year, in this coming year, coming weeks, coming months, and when we're there. I don't know that people suggested 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 CO1A and other agents. I think it caught many people surprised that we would drive into ophthalmology with totally new novel mechanisms. I can respond to the comments, but I think the most important thing for Merck and for Merck Research Labs is 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. 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 barahyaluronidase or any hyaluronidase, but just as that structure, that FDA structure is really important. I don't believe that this would be a good precedent to set. In the specific case of barahyaluronidase 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 barahyaluronidase.
Pembrol and our pembrol launch, everything we have with the FDA is that 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 Eliav has said, how much we're building on that foundation. We really want that to be available, and we are really looking for access as an important standpoint. We do recognize in the U.S. it is going to have biosimilar competition in 2028 and 2029, and our concept of advancing subcu pembrolizumab with barahyaluronidase takes that into account. Most importantly, it takes into account how important we think it's a foundation for what else we're building as well.
Thank you for your Joanne. Anything to add on?
No, well said.
Okay. Great. Evan?
Thank you. Evan Sugerman from BMO Capital Markets. Can you walk me through some of the evidence that you have to support the statement that you believe 30%-40% peak adoption, 18-24 months post the launch of subcu KEYTRUDA? How do you get there? There's a lot of questions with the launch and approval of the OPDIVO version, and are you going to what headwinds may you not be anticipating?
I'll give a broader kind of a high-level answer, and then maybe Jo can chime in more specifically for the U.S. She's in charge of the pre-launch preparation. She's working on exactly that. First of all, we have market research and deep insights from customers and patients suggesting that this adoption will happen. I do want to 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. 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 one minute to two-minute push, which really will be very beneficial. Maybe Jo, you can provide more insights.
Yeah, thank you for the question. We have done a number of quantitative adoption studies across the market looking and asking about adoption, sharing the profile, and understanding where they're going to use, where providers will use subcu. All of them have validated the 30%-40%. One of them was slightly higher than that, but we've landed on the 30%-40% 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, where they're hanging a bag already and they already have a port. It's not that much time saving to hang two bags. When you blend it all together, it's a 30%-40%.
As Chirfi mentioned, it will be slow in the first six months because normally providers will take a chance with a temporary J code if it's a product that doesn't have good alternatives. If 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 going to get reimbursed within 30 days. We expect the first six months to be slow, and then we expect acceleration following that. There are also some operational things that practices need to do to sort of work it into the EHR and all of those things, which we expect to happen over the course of the first six months.
By six months, we would expect the adoption to accelerate to the 30%-40% of peak, which will be about 18-24 months post-approval.
Quick follow-up there. 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? Are you going to help walk them through that change?
Yeah, so when we consider the price of subcu, we're considering not only the price of IV, but also the admin fees and other things that they get for IV relative to subcu. We also have targeted accounts based upon who has infusion chair time challenges, where those are going to be our early adopter accounts. We have mapped the market based upon where there are infusion challenges. Those are going to be the places that we'll adopt first is our expectation.
Great. Thanks, Evan. Chris Schott.
Great. Thanks very much. Just two from me. First, can you just elaborate on the differentiation you see with your TROP2 versus peers? Maybe this extends how you're thinking about approaching some other assets in 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 just trying to get 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? The second one, I just wanted to follow up on the subcu KEYTRUDA comment.
I know you disagree with the idea of moving away from the kind of dual agent and if this were included in negotiations, but just given the availability of a biosimilar, does it really change the outlook, or was the biosimilar going to be kind of the key component of how you think about the longer-term price for subcu?
Pricing strategy, you mean? Pricing-wise?
Yes.
Okay. Why don't we take the pricing-wise first and fee and however you want to handle that, and then we'll take the other questions.
I think we've said it already. I just want to repeat it so that we're clear. 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 it at this point.
In relationship to TROP2, is it the molecule or is it the clinical development team? I won't say both, but I'll let Marjorie and Eliav say both.
I was thinking that I just wrote down differentiation, schedule, toxicity, and development plan were the notes that I put down. I think that Kelun has generated a really remarkable ADC. I 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 schedules. This is a Q2 schedule, and it is a little bit more frequent than the Q3 schedule. You also have this efficacy, tolerability. That therapeutic index is really critical for patients. I think it is just right in what you see with the manageable side effects that have been reported to date. The phase III data sets will hopefully help confirm that.
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. We really have developed a plan that is very robust. I think it is both.
Right. I think that it's the plan and it's the molecule. First of all, the dose that we chose, I think, is going to 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 going to be in maintenance. It's going to be important to look, as you all see our data and as you compare how limited it is to do cross-study comparisons, but when you do look at duration of therapy, time on treatment, and how important that is in helping patients get to the right outcome. Of course, that also has some commercial implications as well. I think that the overall picture is a workhorse ADC that is just right and in new indications with biomarker and/or combination selections that I think will be differentiating.
Of course, the proof is in the putting of the phase III program, but we really believe in this, and there's good reason why we put quite a bit of muscle behind this. 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 as you look at the PCD dates 2027 and on.
I was going to 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 Kelun-Biotech, we had partnered with them for some period of time. 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.
Thank you, Chris. Next question. Courtney.
Hi everyone. Courtney Brinch from Bernstein. A couple of questions. One's 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 kind of how you're dealing with that future uncertainty? The second was just on MK-6837 that I noticed on the ADC slide. Is that a Merck internally developed asset, or can you give us any more context on that one?
Can we take the [MK-6837]? Yeah, that's internally developed.
Through capabilities that you've gained from one of your partners, or can you talk a little bit about?
It's our own. Homegrown. It's our own. What's not listed here is, and Eliav alluded to the direction that we're going, and also that we have an equally robust internal pipeline that will go into phase I and then it'll become visible. That's the tip of the iceberg. In relationship with MFN, I've been in meetings with you and with Rob and with Caroline. The way that I would just sort of emphasize is the U.S. 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 biopharmas. One thing I can say is, as a U.S.-based company, we will always launch in our home country, which is the base of the whole industry, where that base of that whole industry actually values innovation.
I don't want to say what we will do in the future or this, but we have that concept that we will always launch in the U.S., and we're going to 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 are said, but become sort of ironed out and actually put into practice. 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?
Trung Huynh from UBS. One on [Q1] and then one on radiotherapy. It looks like MK-2010 is the tetravalent. Into your slides there. It's similar to [denosumab]. It looks like the main difference to me is the nanobody part where it binds two PD-1s. Just wondering how you think that structure affects how effectively it works in the tumor microenvironment. Just having a nanobody here just reduces the allosteric-steric hindrance that you get, bringing immune cells and tumor cells together. Some thoughts about that. The pipeline has a lot of breadth with ADCs. You have bispecifics. One area that you're noticeably less versus your peers is radiotherapy. Just thoughts there.
This is the Dean Li question.
It is.
Yes, it is.
I was like, finally.
It is rubbing its face together. I'm like, finally, someone gives me a question. One of the things I would just emphasize is I think what is interesting to us is what Marjorie and Eliav alluded to. Initially, if you look at the different constructs, you can think of cooperativity and tissue targeting and all of this. You would sit there and you go, the Kezo 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 me answering that question is everything's fun and games until you put it in a human. What you recognize is you wouldn't necessarily in the hypothesis that you have in the NIJF, immediately when you go to a PD-L1 VEGF, you're like, okay, that hypothesis is no longer true.
If you look at BioNTech's 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. Other people have looked at molecules where the binding to the PD-1 and the VEGF is like right on top of each other. I'd love to tell you what I thought, whether the nanobody was important or the construct was important or this. I believe in the general construct of what you would say a Kezo and us. 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. We're confident in our construct. We're actually a little bit surprised at the clinical results from some of the other constructs.
Radio ligands.
Oh, the radio ligand 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 a radioligand therapy to displace that given the complexity with it. There are clearly places with radioligands where ADCs may not work. We will have to figure that out as we develop our pipeline and other people. We will 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.
Great. Thank you, Trung. Next question. Mohit.
Thank you. Mohit Bansal from Wells Fargo. One follow-up question, clarification question, and another question here. Chirfi, we have heard that for OPDIVO subcu, it is still in infusion centers, not as in clinics. What could you do to make it happen in clinics? That is an issue for a lot of the uptake. The other one for Dean, I know it is a little bit early and you have that column blank in terms of 2010 development. Most of the early players are all going after lung cancer, which is where KEYTRUDA is the strongest. How do you think about a development plan? I mean, go after the most difficult indication for a new player or go after somewhere where PD-1 has activity, but it is easier to actually surpass that?
Why don't I give Chirfi that, and then I'm going to actually see if Marjorie and Eliav want to talk about potential.
Yeah, I'll pass on to Jo in a moment. I just want to remind everyone that we believe, based on insights once again, that physicians will choose a brand. I just want to provide that context because we do not really look at OPDIVO as necessarily a benchmark for pembro subcu. Just to put that out for context. Maybe Jo, you can address the other question.
All the research we've done, providers say they're going to pick based on the clinical profile first and then go for the convenience second. I think what you might be seeing is that, as I mentioned, in those first six months, there's a couple of things that have to happen. One is the reimbursement picture needs to solidify with the permanent J code. Second is the operational factors. 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 going to do subcu? There are operational decisions they're going to have to make for how they work it into their workflow. You might be seeing, 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.
Over time, as they work it through, they put it in their EHR, they figure out where they're going to give it, then I think you'll start to see it broaden beyond infusion centers. That's my guess. That might be what's going on. We do know that that is something they have told us that we're going to figure out how we fit it in.
I'll just give a broad statement, and I'll let Marjorie and Eliav sort of give you more meat. Essentially, as we're moving very fast with MK-2010, there will be inflection points that we have to make as to how broad the program you want to go and where do you go first. We will go to the KEYTRUDA playbook, look at what we've done. We will look at the LEAP playbook. When people talk about PD-1 and VEGF and what the past history is, oftentimes they're talking about that playbook. 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? With that, I'll bring it to Marjorie and Eliav to give you more detail.
Yeah, I think you agree with Dean is that you want granularity, but I think that we're not quite ready to tell you our secret sauce yet. 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. What I really love about this from the development standpoint is the ability to combine with all of our internal assets that are things that we have. We already have robust programs with multiple assets that we anticipate will be changing standard of care. Therefore, we are going to be very well positioned. Most of these are where KEYTRUDA already exists. We have KEYTRUDA combinations. Being able to build on this, as Eliav talked about, for example, with R-DXd, we now have the B96 data.
Ovarian cancer, you can imagine, and bevacizumab is used in ovarian cancer, the potential then with R-DXd to do something really innovative.
Yeah, I think that's right. 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 1084 studies? Or are these studies that serve as the intermediate step in the final place where we're going? I would encourage you to look as the pipeline progresses to understand that it's not about just saying everything that pembro was there and this will just put 2010. That would be okay. What would be even super more okay is bespoke combinations that we're putting together. I'll leave it at that. Yep.
Daina.
Two questions for me, hopefully one fast, one longer. 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? My second question is actually about ZV and lymphoma. We recently heard from FDA and their ODEC for StarGlow hypothesis that our GemOx is not an appropriate preferred SOC comparator arm for U.S. studies. I wonder what you think about that and how that could impact your development of ZV for lymphoma.
Who wants to take digital?
I'll be very quick on digital path and tell you that we really don't want to share at present what we're doing because, well, we'd rather share the information first in an academic setting.
Yeah. For ZV, I think the two studies I talked about are really first-line studies. I think what we really see is the biggest benefit is going there.
Great. Next question. Josh.
Thanks so much. Okay, so just a few. Medicare Part D, [audio distortion] draft guidance, there were two changes, right? One, it made it seem like subcu and IV were considered the same drug. I feel like the other part was you had meaningful changes to the term bonafide 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 were considered bonafide marketing, and then you have the biosimilar exclusion apply. In the past, Merck has talked about both IRA negotiation and biosimilar entry in 2028. Can you maintain that position given the new draft guidance? Number two, you have 14 TROP2 studies that are written out here. This is like a question I asked BioNTech.
You have, to your point, version 1.0 and then 2.0 trials where it's novel, novel combos. Are you alluding that you can take PD-1 VEGF combinations and apply them to the current phase III TROP2 studies you've already announced? Why not delay some of those studies because you really want two novel agents? Why spend the money for 14 phase III when that might not be where you're ultimately headed?
I'll try the last one. Who wants to take the first one? Okay, I'll take the rephrase the first one.
Okay. Let's put it this way, 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 subcu KEYTRUDA is no longer negotiated. This is very similar to what EYLEA and high-dose EYLEA is right now.
Yeah, I can address that one. We actually 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 actually did evaluate that, and the financials did not make sense. I'm sorry? Yes, yes.
Yeah, in relationship to we are going to have TROP2, but we're going to have a lot of ADCs and a lot of agents coming through. I just want to put that context. We intend to develop them appropriately if they're a signal. The question that you're having is this first tranche that you receive, should we delay that as the field's trying to figure out PD-1 VEGF? Should we do that now? We also have the potential optionality to just move right now where we are because it isn't like we have a dearth of other opportunities to do that. I think there's going to be a whole series of things that will come together. We're advancing 1084, we're advancing lots of different agents.
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. I would be careful about that when we have such a great partner in Kelun who has given us such clear signals to go now. For me to sit there and delay for PD-1, is it this, is it that, is it this and this? We will have that problem, but it may be further down the pipeline. 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 going to not only read out important information about sac-TMT, but also help us with some of the biomarker strategies that we've already launched. It's also important to recognize that PD-1 VEGF is not for free from an AE point of view. VEGF-related AEs are just a fact. It's important to understand these drugs in a little bit more detail before one would say, "Well, I'm going to just 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.
I think we still have hands in the room, John.
Thanks, guys. John Miller from Evercore ISI. Two probably quick ones from me. Marjorie, you said today, and we've heard the team talk before about the VEGF bispecific hazard ratio in 0.7- 0.8 for OS being really compelling from a development perspective. What if it's more like 0.82-0.85, like the LAG-3s in melanoma? Is that a compelling enough signal to justify a real aggressive push into that market? 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 [audio distortion]?
Why don't you take that one?
Yeah, the first one. Of course, I always appreciate Elliott's thoughts too. Hazard ratios in the 0.8-0.85 get a little bit more in the gray zone. Some of it has to do with the delta that you generate. If you've got a frontline regimen where you've got a PFS that is 12-15 months, then a 0.8- 0.85 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 0.8-0.85 might still be reasonable. I'm giving you a non-answer because it depends. It really does.
In terms of appetite, I really like deals where there's a history of us understanding what we expect, and then we see data ahead of a phase III that makes us go, "Wow." Our negative opinion of this needs to change pretty quickly. That's Acceleron. That's Prometheus. That's iBio. I really like that because it creates value and a differentiated position for us. What you've outlined is what I really like.
Denise, are there any questions in the webcast?
I do have a question from James Shin with Deutsche Bank. Your line is open.
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-1 VEGF data. Can you elaborate what surprised you? Given 2010's data is relatively lagged from these existing PD-1 VEGF players, does 2010 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 de-risk target? That's it. Thank you.
You may have had trouble hearing the third part of your question, James. Can you repeat it?
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 de-risk assets?
I would say, I mean, our business development strategy has not changed. I mean.
I should just be a little bit careful because the people in the room can see my hand gesticulations, and you can't. When I look at PD-1 VEGF, I'm binding PD-1, and I'm binding VEGF, and there's a considerable distance there, right? PD-1's a receptor. All of a sudden, PD-L1 is on a different cell, and that's different, right? That's different. You guys got some people who are not PD-1 VEGF like this, with two hands being your PD-1 and my legs being VEGF. You have PD-1 VEGF right here and a PD-1 VEGF right here. If you would ask, if you were designing knowing certain hypotheses, 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.
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. 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. 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 10 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? As I alluded, especially move the market in the market that really, really values innovation, and that's the United States.
Right. We are over time. These have been really good questions. Are there any final one or two questions in the room? Mary Kate?
Hi, Mary Kate. I'm for Jeff's Citi. Just a quick one on MK-2010. Trial ongoing in China. Maybe, how are discussions going with regulators here? Could you comment on their expectations for the program? Maybe just broader, how has communication been in general with FDA and CMS?
I'll take the general question, which is we're a company that we tell you we've pivoted our pipeline, and we have a lot of launches. We've given numbers in relationship to that. Holding on to those PDUFA dates are especially important to us as we pivot. We have important ones in relation to plesrozemab. We have important ones in relationship to potentially WINREVAIR and labeling changes with the incredible data that we have with ZENITH. We have that with subcu Pembro. All of our interactions with the FDA for those most immediate ones have been constructive. In relationship to PD-1 VEGF, in relationship to regulatory interactions, I think we've kept that a little bit quiet, but I'll just ask Eliav if he had any questions that he wanted to.
Yeah, I mean, I think 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. Again, we're excited about this drug. We understand the value of the drug very well. We're also mindful about where we need to be careful with VEGF.
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 hopefully you found them very informative answers. Dean, any closing remarks you'd like to make?
Yeah, I just wanted to thank everyone and really appreciate your interest. I hope you got a little bit of sense of what Rob, Caroline, myself, and this leadership team has done since 2021, which is to diversify oncology and expand in other therapeutic areas. We have 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 III trials that are publicly known. I think 60 of them were in oncology, and we gave you a framework for it. We did not go through all of them. Twenty is within non-oncology. I have here that we have 25 distinct assets in those and 16 in oncology, 10 in non-oncology. We are very interested in moving the pipeline.
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. We have, I believe Rob has talked about 20 new growth drivers over the next coming years, including WINREVAIR and CAPVAXIVE. I hope you got a sense from that slide, and those are official PCD dates. As Eliav 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 the phase III 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 bring important medicines to patients. Thank you very much for your interest, and there's food back there.