Summit Therapeutics Inc.

And thank you for joining us. Two press releases were issued earlier this morning and are available on the homepage of our website. Our Form 10-K was also filed earlier this morning and is available on our website. Today's call is being simultaneously webcast and an archived replay will also be made available later today on our website, www.smmtx.com. Joining me on the call today is Bob Duggan, our Chairman of the Board and Chief Executive Officer, Dr. Mekshbi Zangade, our Chief Executive Officer and President, Manmeet Soni, our Chief Operating Officer and Chief Financial Officer, and Dr. Alan Yang, our Chief Medical Officer. Before we get started with the rest of the call, I would like to note that some statements made by our management team and some responses to questions that we may make today may be considered forward-looking statements based on our current expectations. Summit cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Please refer to our SEC filings for information about these risks and uncertainties. Summit undertakes no obligation to update these forward-looking statements except as required by law. Following comments from Bob, Maki, and Manmeet, we will take questions. With that, I will turn the call over to Bob.

Thank you, Jay. Good morning, everyone, and thank you for joining us today. I am very pleased with recent accomplishments of Team Summit and the accelerating positive information and enthusiasm surrounding Ivanisumab, our lead investigational asset. In Q4 of last year and to date in 2025, we have reached several meaningful milestones around the development of Ivanisumab, importantly, with our partners in China, as well as here in the U.S. and Western markets. We continue to progress towards our mission of building an organization, making a significant positive difference in serious unmet medical needs. Specifically, earlier today, we announced a clinical trial collaboration with Pfizer, which will evaluate ibanizumab in combination with multiple Pfizer antibody drug conjugates, or ADCs, in unique solid tumor settings, rapidly developing novel mechanisms that go beyond what is currently available to patients and physicians is what we believe will make the most significant impact for those facing the greatest challenges from cancer today. We believe this collaboration with Pfizer will accelerate the advancement of potentially landscape-changing therapeutic combinations, which intend to improve the standards of care for patients facing serious unmet needs. Clinical trials associated with this collaboration are expected to start by the middle of this year. In October of last year, we completed enrollment in and received fast-track designation for Harmony, our global phase 3 trial in patients with EGFR-mutated advanced non-small cell lung cancer who have progressed after treatment with a third-generation EGFR tyrosine kinase inhibitor, or TKI. Top-line data from Ivanizumab's first global registrational phase 3 trial Harmony is expected in mid-2025. Additionally, in October of last year, we announced a study amendment to the HARMONY-3 protocol, expanding the study to include patients with both squamous and non-squamous histologies. With this amendment, HARMONY-3 is a multiregional, registrational Phase III trial assessing ivenizumab as first-line treatment for patients with metastatic non-small cell lung cancer with both squamous and non-squamous histologies. Enrollment is ongoing globally for patients with tumors with squamous histology, and we have begun enrollment in patients in the United States with non-squamous tumors. Harmony 3 now addresses a patient population two to three times larger than prior to the amendment significantly expanding the numbers of patients with cancer that Ibenizumab can potentially help. Towards the end of the year, we announced our third global phase 3 trial, Harmony 7, would be initiated in early 2025. Initial trial sites have begun activating in the United States, and Harmony 7 continues to progress as planned. As a reminder, Harmony 7 is evaluating ibenizumab monotherapy against pembrolizumab monotherapy in first-line metastatic non-small cell lung cancer patients whose tumors have high PD-1 LPD-L1 expression without actionable genomic alterations. McKee will further discuss these accomplishments, including additional strides taken to drive our continued belief in what could be accomplished by Team Summit, as well as our conviction in the potential of avanisimab in non-small cell lung cancer, and very importantly, indications beyond lung cancer. We are a mission-driven organization with an overriding patient goal to improve quality of life increase potential duration of life, and resolve serious medical needs. We are the right team, and we believe we have the molecule in Ibonizumab to realize this goal. With that, I will turn the call over to Mackie for additional context and recent highlights for consideration. Mackie?

Thank you, Bob, and good morning, everyone. As Bob said, I remain incredibly enthusiastic about the future of Summit and the possibilities of what can be accomplished with our lead candidate, Ibonizumab. Before providing some additional detail and reviewing the current pipeline, I would like to touch on the clinical work that has been conducted with Ivonecimab and some of the interest and recognition received last year. Since first entering the clinic with our partner Ecesobac in 2019, more than 2,300 patients have been treated in clinical trials with Ivonecimab. In 2024 alone, IVANISIMA was featured in 14 publications across seven tumor types and selected for five oral presentations at major medical conferences. Currently, between our partners at ECESO and our team at SUMMIT, four Phase III trials have been completed enrollment, two of which are awaiting top-line data readout, including the SUMMIT-sponsored HARMONY trial. Five phase III trials are currently ongoing. Two of these are summit-sponsored trials in first-line non-small cell lung cancer, and three are ECASO-sponsored trials studying abonissimab in head and neck, biliary tract, triple negative breast cancers. ECASO has also announced its intention to start a clinical study in pancreatic cancer later this year. A significant amount of additional data is being generated in additional indications, including colorectal cancer, ovarian cancer, gastric cancer, and hepatocellular carcinoma, in addition to more data to support the lung cancer program. Turning specifically to the summit-sponsored pipeline, as Bob mentioned last quarter, Harmony completed enrollment in the fourth quarter with top-line data expected in mid-2025. This data is expected to contain data for both primary endpoint progression-free survival and overall survival. Harmony 3 was amended by significantly expanding the addressable patient population to include all frontline metastatic non-small cell lung cancer patients without driver mutations by including patients with non-squamous tumors in addition to squamous tumors. Squamous tumors represent approximately 25% to 30% of non-small cell lung cancer in the United States, with non-squamous tumors representing a large proportion of the rest. As a reminder, this trial includes patients with tumors that are PD-L1 negative, PD-L1 low-expressing, and PD-L1 high-expressing. We announced our intention to initiate Harmony 7 in early 2025, for which we have begun to activate clinical trial sites in the United States. Later this year, we expect to announce additional details around expanding our clinical development plan around ibanesimab, specifically beyond lung cancer. After receiving interest for more than 75 investigator-sponsored trials in the most recent open window, we have approved over 30 IDCs to date, which will either enhance our sponsored clinical development activities or can show signals in settings where a case has not yet had the opportunity to explore. In 2024, we started our collaboration with MDN, which now has studies that are activated and open for enrollment in Houston. We have committed $15 million to this collaboration to quickly discover additional opportunities for Ibonizumab, including several tumor settings outside of its current development plan, as well as the possibility of identifying biomarkers through additional research activities. Finally, as we announced this morning, our clinical trial collaboration with Pfizer will look at ibanesimab in combination with several Pfizer vedotin-based ADCs in multiple tumor types. As we seek to accelerate the development of ibanesimab across non-small cell lung cancer and other solid tumor setting, this collaboration will allow us to quickly advance beyond our promising late-stage development plan to evaluate ibanesimab in combination with some of the most innovative ADCs from Pfizer. Clinical trials as part of this collaboration are expected to start mid-2025. Pfizer will be responsible for the operations and costs associated with these trials. We will provide abonissimab and jointly oversee the study. As a reminder for those new to the summit story, abonissimab has significant lead in the clinical development of this novel class of compound. Abonissimab brings two highly validated targets together into one novel bispecific antibody that targets both PD-1 and VEGF. Next, I would like to review upcoming catalysts for this year and beyond. As we touched on a moment ago, we are expecting Harmony top-line data in mid-2025, which we expect will include both primary endpoints of progression-free survival and overall survival. This will be the first global phase three clinical trial readout for Ivonecimab, which provides a potential path to applying for marketing authorization in our territories, including potentially the United States. Secondly, we intend to expand our sponsored clinical development plan to go beyond non-sponsored lung cancer in 2025 and 2026. In addition to continuing engagement with a rapidly increasing number of investigators, beginning to conduct investigator-sponsored trials at various institutions across a large number of different tumor types. And you will see continual activating of additional ICDs in a variety of solid tumor settings. This is in addition to ECHESO continuing its execution of its Phase III studies, including completing the involvement of Harmony6 in frontline squamous non-small cell lung cancer with ibanesimab combined from E-Queso in non-small cell lung cancer and beyond. Luckily, we have seen indications in which phase 2 data has been generated, which we touched on earlier. We are excited for the catalyst switch path ahead of us. Our conviction and believe in the potential for Ibanezumab to improve patient lives for the better, remain strong, and consistent. Now, I would like to take a moment to review study design for our two ongoing global phase three trials, Harmony T and Harmony Sub. Here we have the study design for Harmony Harmony 3 is a randomized, double-blind, global phase 3 clinical trial evaluating Ivanizumab in combination with chemotherapy against PEMBRO in combination with chemotherapy as a first-line treatment for patients with metastatic non-small cell lung cancer. This trial includes patients with squamous or non-squamous histologies with no activating genomic alterations regardless of PD-L1 expression, including high, low, and negative PD-L1-expressing tumors. Dual primary endpoints for harmonic metastatic non-small cell lung cancer patients with tumors with high PD-L1 expression. Dual primary endpoints for harmonic metastatic include progression-free survival, overall survival, and result would be stratified by squamous and non-squamous histologies. As a reminder, our Harmony 7 study shares similarity with AKSO-sponsored Harmony 2 Phase 3 trials, which reported data last year. but specifically targeted at the PDR1 high-expressing tumors consistent with the standard of care for monotherapy, immunotherapy in the U.S. and Europe. Turning to the market opportunity for Ivonisimab, the value proposition here is clear. Ivonisimab has the potential to be a platform blockbuster drug and is well-positioned to make a significant impact across the treatment landscape of non-small cell lung cancer and beyond. Specifically in non-small cell lung cancer, there are a combined six announced or ongoing phase three studies conducted by either ACASO or Summit. Non-small cell lung cancer alone has an addressable market that could ultimately approach 20 billion for checkpoint inhibitors, according to the third-party research from the likes of TD Khan and others. But this is just the start. There are more than 50 indications where PT1, PTL1, or VEGAS therapies have been approved. Ivonizumab will continue to be rapidly tested and developed beyond non-sponsored lung cancer. Across all checkpoint inhibitors indications, the addressable market approach $90 billion globally in the next couple of years, according to IQIO research. However, this still excludes the full impact that Ivonizumab could have where it has shown promising data in multiple tumor types where checkpoint inhibitor have not been effective, including microsatellite stable colorectal cancer, PDR1 low, negative triple negative breast cancer, and EGFR mutant non-small cell lung cancer after targeted therapy. We are excited to continue to progress our development in non-small cell lung cancer in 2025. Additionally, Data shared in 2024 showed that Ibanissima has a market potential much larger than non-small cell lung cancer and our current ongoing global phase 3 clinical studies that we are sponsoring at Summit. There are multiple phase 2 trials that have been conducted providing encouraging data to continue to explore Ibanissima and its opportunity to become a standard of care. across several solid tumor settings, which we intend to continue to explore with the goal to improve the lives of as many patients as possible facing high unmet medical needs. I would also like to take the opportunity to thank, most importantly, the patients in our clinical studies, as well as our investigators, hospitals, including our collaborators at MD Anderson, and our partner in China, Dr. Michelle Shaw, and the entire AKSO team, as we continue to pave the way for rapid development of Avonissima globally. And of course, the Summit team. As Bob and I look back on all of the many achievements over just the past two years, Team Summit has done a tremendous job across every department in making our goals a reality and appropriately condensing time when and where possible. We continue to look at opportunities to accelerate our timeline in bringing additional therapeutic options to patients with high cancer needs. It is an honor and privilege to work with each member of Team Summit, and I would like to express my heartfelt thanks to every one of our team members. With that update, I will now ask many to provide details

on our financial position. We entered the year 2024 with a strong cash position of approximately $412 million. Let me remind you that we have paid off our debt in entirety and now we are debt free. With a strong cash position and zero debt, we are well positioned to continue to execute on our clinical trials. Turning to operating expenses, I will be providing details to both GAAP and non-GAAP numbers. You can refer to our press release issued this morning for a reconciliation of GAAP to non-GAAP financial measures. Just to remind you, non-GAAP expenses exclude stock-based compensation expenses. Our GAAP R&D expenses during the full year 2024 were $150.8 million compared to $59.4 million for the previous year. And non-GAAP R&D expenses were $134.8 million during the full year 2024 compared to $55 million for the previous year. The increase in the R&D expenses reflect the expansion of our clinical trials related to Avonisumab. Our acquired in-process R&D expenses during the year 2024 were $15 million compared to $520.9 million for the previous year. To remind, acquired in-process R&D expenses for the year 2023 which were $520.9 million were related to the upfront payments made to ACASO for the licensing agreement. And $50 million expense in the year 2024 is related to the amendment of the licensing agreement to the ACASO to include Latin America, Middle East, and Africa regions into our license territory. Our GAAP G&A expenses during the full year 2024 were $60.5 million compared to $30.3 million for the previous year, and non-GAAP G&A expenses were $25.5 million during the full year 2024 compared to $20.6 million for the prior year. Our GAAP G&A expenses primarily increased due to an increase in the stock-based compensation charges related to achievement of certain market conditions on performance milestones which vested during 2024. Overall, Our non-GAAP operating expenses during the full year 2024 were $175.3 million, compared to $596.5 million for the previous year. The decrease in non-GAAP operating expenses was primarily related to the decrease in acquired in-process R&D expenses, as mentioned earlier, which were offset by the increase in R&D expenses due to the expansion of clinical studies and development costs related to the 1S map. To remind that last quarter we announced that we plan to expand how many E3 study to include non-squamous patients in addition to the squamous patients. I'm very pleased that our summit team was able to activate non-squamous in a record time and we recently started enrolling patients for non-squamous in the United States. We expect to start activating sites to enroll non-squamous patients in other regions during the second quarter of 2025. We continue to enroll SCMIS patients in all the territories. Additionally, in the last quarter, we have given guidance that we will initiate a new level of strength relevant know-how to third parties to establish additional supply sources in our licensed territory. And with that, I will hand it back over to Dave. Dave? Thank you, Bob, McKee, and Mahmoud.

We will now see if there are any questions that our team can help answer. Kate, if you could please open up the line for questions.

At this time, I would like to remind everyone, in order to ask a question, press star then the number one on your telephone keypad. We will pause for just a moment to compile the Q&A roster. Your first question comes from the line of . Please go ahead.

Hi, great. Thank you so much for taking the question. Obviously, we're getting a lot of inbounds on Harmony 2, and has provided some comments on the timing of the OS. If you could help us understand what you believe to be the timing for the Harmony 2 OS, and given the fact that It may be approved in China as early as the third quarter of this year for the second indication for frontline. What is the potential? Is there any expectation that we could see a glimpse of some early OS data in that China label? Thank you.

Thanks, Egal. And this is Dave. So I appreciate the question, and I know there's a bit of commentary with respect to Harmony 2. As our partners mentioned, they expect to reach the number of events required for their interim analysis by the end of the year 2025. We ultimately don't have more information on that front other than you know, continuing partnership with the CASO. But at this point, you know, there's been nothing new on that front with respect to any additional information, but appreciate the question.

Okay, no worries. And then on the second line EGFR, the Harmony trial, I think Naki mentioned you will have the OS data in the top line readout. What is your understanding as to whether you need that to be only a trend or actually hit on that SIG in order to be in a good position for approval in the US? Thank you.

Yeah, this is Alan Yang. Thanks for the question. So I think there's two things. I think we would, of course, would want to hit OS and be statistically significant. However, if you look at the precedents of previous approvals in this space, they have not required OS for PFS has been adequate.

OK. And then I know, and Manmeet just mentioned that you're starting to add the patients for non-squam in the second quarter for Harmony 3. Is there any possibility you could provide even a rough guideline as to the timing for the top line readout for Harmony 3? And if you can't do that, anything you can say around Harmony 6, given that's possibly, you know, helpful in terms of a read-through to Harmony 3? Thank you.

Yeah. Hey, Gal. This is Manmeet. You heard it correct, right? We have just initiated our sites in U.S. and we have started enrolling for U.S. in the non-squamous arm. It's too early to give clarity on the completion of the enrollment until we complete all the sites in other territories, which is obviously in Europe and other regions, which we plan to initiate. We would be able to provide once all those sites are activated and we have a quarter or two of the run rate, then we will have clarity in our timelines over there. Related to Harmony 6, you're also correct, right? That trial has been completed enrollment, which was fully in China in this famous arm. And what I believe that's for the guidance from a case, so that should read out sometime in the middle to end of this year. We don't have visibility into any more details on that.

And then the last quick one, I would be remiss if I didn't ask you about the news this morning on the Pfizer-CoVab.

Anything you could say there in terms of additional details, which of the vedodin ADCs, what tumor types, how big would be the vasomab in these specific ADCs?

So, you know, normal course operations there. But we'll give additional details as we get closer. But we are very excited to get moving here. And I think, as we've mentioned before, you know, this is one of the strategic advantages that we feel we have in terms of the opportunity to combine ibanesimab with, you know, a number of different products from a number of different, you know, organizations, pharmas and biotechs. And so this is one of the first steps in terms of moving forward from that perspective, but we will be giving additional details as we continue to get closer to the beginnings of these trials, which are expected in the middle of this year, so short term from that perspective.

All right. Thank you very, very much.

Your next question comes from the line of Brad Canino with CFO. Please go ahead.

Good morning. Thanks for the question. In the Pfizer-ADC collaboration, do you think about this more from the perspective of providing further therapeutic enhancement beyond the Keynote 189 benchmark, or more from the perspective of bringing Ivanesimab outside of lung with a better probability of success? Hi, Brad. Thanks for the question.

Both, but probably the latter more. So, you know, clearly, you know, ADCs are going to be important across all the tumor oncology. I think the data in lung cancer is interesting, but the data outside of lung cancer has been stronger. And I think the fact that there's multiple ADCs involved in this is important.

At this point, we're not really getting into the specifics just yet in terms of the design that we want to, you know, allow for these trials to, you know, get up and, you know, the activation portion and ultimately get up and running.

For what it's worth, it's an important question. Love to answer it, but we can't do it yet.

All right, maybe last for me. With the Harmony EGFR data coming mid-year, how do you plan to show the data to investors to demonstrate that there is comparable efficacy and safety and its effect in Western patients relative to KESA's China patients? Thank you.

Thanks, Brad. Yeah, I mean, I think that is going to be a key component. I think, you know, we and especially Alan have been talking about this for over the course of the past year or so. You know, one of the key components we'll be showing you know, the comparability of the data, to your point, both efficacy and safety in the eastern and western population. So, while we haven't explicitly described, you know, the ways in which we will show this, we'll obviously have presentations at major medical conferences, and the granularity will be there so that that data can be interpreted. Thanks again. Thanks, Brett.

Your next question comes from the line of Kelly Xu with Jefferies. Please go ahead.

Congrats on the progress. Thank you for taking my question. Maybe a couple of questions. How many trial, global trial design? So regarding the assumptions on both PFS and OS, should we assume it is a design based on a total of 420 patients, but not a subgroup of ex-China patients?

Yeah, Kelly, this is Alan Yang. Yes, it is a primary analysis of the total study population. Of course, as Brad alluded to, that there will be looks at the regional differences. We've had discussions on this from a regulatory standpoint about how the data should be analyzed and presented. But then, of course, during the analysis and then during the review process, they could always ask for additional studies as well.

Thank you. Okay, thanks.

And you've got an amazing year for data disclosure. I just wanted to, like, confirm, this is referring to, like, June, July, or actually could it be, like, the entire Q2, Q3 timeframe?

Yeah, I appreciate the question, Kelly. I think We're probably a little bit broader on that, more in the Q2, Q3 timeline, but as we get closer to that, we'll be letting people know.

Okay, terrific. And one more side of this collaboration. So regarding ED in bladder cancer, just curious, is there like a possibility to add some combo to the ongoing?

Bladder cancer and yeah, more to come.

Yeah, we're excited to give you a little bit more details in the upcoming couple of months.

Okay, great. Thank you for the callers.

Thanks, Kelly.

Your next question comes from the line of Mohit Bansal with Wells Fargo. Please go ahead. Hi, this is Sadia Rahman. I'm from Mohit. Thank you for taking the questions and congrats on all the progress over the year. So I wanted to ask on the Pfizer collaboration, I'm curious how you would thinking about the overlapping toxicities with GADGF inhibition and the dosing-based ADCs and how this could differ from combinations of ADCs using topo or isomerase payloads.

Yeah, I appreciate the question there. I think, you know, part of – so if I take a step back, one of the things that, you know, we've expressed more broadly is that we want to be able to take ivenesumab and combine it with the best available treatments on a tumor-by-tumor level, right? And so part of what we will be doing is ADCs, whether it be, again, MMAE-based, But at this point, we're excited about, you know, the profile that's been shown to date for Ibanezumab. You know, we're very aware of the profile to date for, you know, many of the progressing ADCs, and I think that's where we're going to take the opportunity to do, you know, rational step-by-step combinations, and then we'll take that to the next step as we see the data.

Yeah, and I would just add that there's emerging data in combination with pembrolizumab that, you know, that these types of ADC combinations are feasible. And, you know, we have good safety data comparing ibuprofen to pembrolizumab, so we don't expect any additions or surprises in the combinations.

Got it. Thank you. And then on the upcoming readout this year in EGFR mutant lung cancer, I think you said the majority of those patients are coming from the China Harmony study and the majority of those patients received a first or second gen TKI before getting a third gen TKI. Would all of the patients recruited into the Harmony study receive only a third gen TKI in that first line setting? And can you talk about how about any differences in those populations that we could expect in terms of time from diagnosis or survival after that third-gen TKI and whether that could result in any differences in efficacy when looking at the next line of treatment.

Yeah, Batik, just to be clear, the majority of patients in Harmony A did receive a third-generation TKI as part of the standard of care, and those patients will be included. whether they received a first or second generation before receiving a third generation, they would still be eligible. And in terms of differences in responses in those that got first or second versus third generation and where they got them, that's outlined in the Lancet publication by Zhang et al., and we don't expect any differences.

Okay. Thank you. And maybe one more on the Harmony 2 trial. and your global trials, the time to separation on the TFS curve in Harmony 2 happened very early on. Can you talk about what you would expect for the global study since it adds on chemo combination, just trying to understand how much the curves could shift how that could affect timing of when you hit on PFS relative to when Harmony 2 hit on PFS.

Yeah, I think, you know, we've put out a decent amount of data with respect to AK1 plus chemo and comparing that against the historical benchmarks that you would see from trials such as Kino 180. Keynote 407, et cetera. So I think those are probably the landmarks that I would look at from an early read in terms of what's publicly available. And then obviously as we get continuing data, including Harmony 6 from our partners at Acaso in the Squamous Frontline setting, those will be additional inputs that will provide more color.

Great. Thank you so much. Thank you.

Your next question comes from the line of Mitchell Kapoor with HSC Wainwright. Please go ahead.

Hey, everyone. Thanks for taking the questions and congrats on this field. Can we just talk about kind of, you know, when you were searching for a B2B transcript like this, You just talked about, you know, what you were looking for before you came to this arrangement with Pfizer.

And now that this deal is on the table, do you foresee additional BD opportunities, or does this kind of reclude those for a while? And could you just talk about if you expect future... We don't have that pipeline internally that we're kind of, you know, almost... committed to combining with and will almost force through combinations as much as possible to try to keep internal synergies. And so in general, our approach will be to look out and say what are the best therapies, what are the standards of care across each of the different solid tumor settings. And to the extent that I have an SMAB plus, you know, one of those, whether antibodies or small molecules make sense, you know, then that'll be an opportunity where I have an SMAB can combine there. So, I would say as a whole, we don't believe that there's a single ADC platform that individually is the only way to move forward. But we do believe that multiple companies have multiple different types of ADCs, whether it be topoisomerase-based, whether it be MMAE-based, whether it's switching out the linkers of the antibodies in different settings. Obviously, there's a number of, you know, for example, TROP2 ADCs with different antibodies. So, what we can do is really explore different combinations of ibanesemab plus X, Y, or Z, you know, ADC antibody small molecule. So, we're not really giving, you know, guidance in terms of we plan to do X additional, you know, collaborations like this or whatnot. But in general, what we certainly, you know, feel well positioned for is that we will take ibanesimab and look to combine it with, you know, the best, you know, best possible alternative, if you will, out there from a standard of care perspective to bring the, you know, the most potential value to ibanesimab and ultimately help patients in any way that we can there.

Yeah, Mitch, and this is Alan Yang. I would just add that, you know, we just want to pursue the best science to help patients, right? And so, You know, I think there was a lot of interest in combining with PEMBRO in terms of combination therapies with different immunotherapies and different other agents. And based on the Harmony 2 data, as we had suspected that, you know, now companies are interested in sort of pairing with Ivanessimab, and that's where the puck is going.

Okay, great. And just to clarify the last point, are there anything, any particular BD opportunities that you're not open to at this juncture?

no i wouldn't say that there's you know specific things we're not open to but i think it's more about what is possible with i have an sms yeah and i would just add if there was some clear safety issue or something like that but we have not seen that signal yet so we're pretty excited that we have a lot of opportunity

Sorry, Manmeet. Sorry, Mitch. This is Manmeet. And I would just clarify, yes, to answer your question very specifically, this transaction with Pfizer doesn't preclude us to do any other, you know, regional or, you know, any partnerships or any other activities.

Very helpful. And the last one for me, just on the first-line trials, Can you talk about a little bit more?

A segment of patients, right, PD-1 high patients, which will be covered in our Harmony 3 also, right? So there is some sort of that, but as you know, we are much ahead in our schedule on Harmony 3 activations, and there will be not a full overlap of the sites, right, as compared to Harmony 7. We have just taken Harmony 7 initiation in the last few weeks, and Harmony 3 is already enrolling patients. Obviously, there is an overlap, but we don't expect there's a competition because of the new sites which we are planning to add in Harmony 7.

Great. Thank you all very much for taking the questions incorrectly. Congrats again on this collaboration.

Thanks, Mitchell. Your next question comes from the line of Asika Goon-Warden.

Squamous population or we do it more in a stepwise manner, kind of looking at the squamous and non-squamous subgroups individually first and then look at the overall population? I asked if the Biontech study is structured more like the latter. I'm curious to know if you would take a different approach, and if so, why do you prefer your method?

Yes. Thanks for the question. This is Alan. Yes. So it is a – our plan is to do a primary analysis of the combined population And we believe that that was the best way to bring this product to patients as fast as possible from an operational perspective. Of course, there is always data and ongoing data coming out. The Harmony 6 will be informative based on that. Of course, we want to bring this to patients as fast as possible. We've had several discussions with them on this study, but I can't disclose our discussions at this time.

Got it. Okay. And then on the Pfizer collaboration, do you feel IV and SMA could better leverage the immunogenic cell debt versus PD-1, or is the rationale behind this deal mainly about layering on a classical anti-antigenic pressure in addition to PD-1 with ADC?

Yeah, Steka, great question. We could talk a lot about that. But with that said, part of it is empiric. We know that both of these drugs or a lot of these drugs are active in different tumor types, and then, you know, you clearly want to add those efficacies. Whether there will be some synergistic effect through the immune system for the profile, would it be different from PEMBRO's sort of additive or synergistic effect? We think all of those are actually possible, and we're looking forward to these combinations. But yeah, it's very interesting.

Great. Thanks for taking my question, guys.

Thanks very much.

Your next question comes from the line of Fran Benjamin with Citizens JMP. Please go ahead.

Hey, guys. Thanks for taking the questions, and congratulations on all the progress. With Harmony 3 and 7 kind of off to the races, can we talk a little bit about the next solid tumor indications you plan to invest in. And, you know, we've got some, we had some ongoing study data reported last year. Can you talk a little bit about when we might see some updated results from those studies? And I guess just as a sticking with this theme, you know, I guess broadly, do you kind of strategically follow a KISO based on, you know, their data, their solid tumor data and kind of you know, do global studies based on what they've reported, or do you kind of broaden exposure and go after indications that maybe they're not addressing?

Sure, Ren. Thanks very much for the question. In reality, you know, everything that you mentioned resonates, right? So if you think about, you know, the last part of your question, which is, do you follow ACESSO or do you look to branch out? You know, as McKee talked about, part of our MD Anderson collaboration, you know, looks to accomplish parts of that, as well as our IST program. If you look at some of the Phase II data generated by our partners at ACESSO, which were released over the course of last year, whether it be BTC, colorectal cancer, head and neck cancer, and triple negative breast cancer. You know, there are some promising signals that we see in that phase two data. There are also additional indications that have been explored in phase two where data hasn't yet been, you know, fully disclosed from that perspective, which give us opportunities. And obviously, we can run additional, you know, signal-seeking phase two studies as well, whether on our own or through things like the collaboration, the clinical trial collaboration with Pfizer here, which, you know, we'll look to do that as well. So, as a whole, I think, you know, As McKee mentioned in her comments earlier, we're very keen to, in addition to the significant work being done in non-small cell lung cancer, look beyond looking at all the anti-angiogenic approvals, looking at what we think the population size would be, what the comparator arm would be,

And then you layer on top of that the phase two data coming out from a test. So that all goes into the calculus of how we make those decisions. And hopefully we'll be able to disclose some exciting opportunities soon.

Outside of the opportunities, could we expect updated results from any of those studies? Or do you feel like they're largely... you know, largely concluded, and really it's about the phase three studies that are up and running.

Yeah. Hi, Ren. This is Manmeet. Yes, you will continue to hear more updates as we progress on all those studies which we had given the initial top-line data earlier in the last year. But I would also mention that, right, colorectal cancer, right, where we are pretty excited and we have just recently partnered with Acaso also on the phase two study which we are beginning to activate over here on our side and that would be the first one which you would hear more details in next coming quarters.

Excellent. Okay, thank you for that. And just one last one for us. I think ct.gov said that there are three active sites for Harmony 7. Can you talk a little bit about how many sites globally you expect to have on board by the end of 2025 and for both Harmony 3 and Harmony 7?

Hi, this is Manmeet again. I think we don't give the specific number, but on the sites which we activate, because we go into multiple regions, this is a global multi-regional. study, but I would expect by end of 2025, almost, you know, most of the sites, or like 100%, near to 100% of the sites should be activated.

Great. Thanks for taking the questions, guys, and congrats.

Thanks very much.

Thank you. I will now turn the call back to Dave Ganquers for closing remarks.

Thanks very much, and I'd like to hand it over to Bob Duggan just for a couple of remarks before we close.

Yeah, I just want to weigh in on the question of biz development. Biz development has a couple of arms. One is optimize Ivo and make it the best product monotherapy, combination therapy that the world can get from us and our partner, Keso. And we're daily looking at that and evaluating that. There's plenty of room to go, as you see with the trials that we're entering into. The second aspect of business development is what's the timing of gaining markets, additional market space, additional the market opportunity, and then how much share can you get and how do you go about doing that. And that's also a major part of business development. So we're very active on two footprints. Pfizer is footprint one.

How do we optimize? An archived version of the webcast will be available later today on our website, www.smmtx.com. Thank you very much for your participation, and we hope you enjoy the rest.