Summit Therapeutics Inc. Q4 FY2024 Earnings Call

Good morning and welcome to Summit Therapeutics Fourth Quarter and Year End 2024 Earnings and Update Call. All participants will be in listen-only mode until the question-and-answer portion of this call. Please refer to the company's website for updates. Please note that today's call is being recorded. Thank you. At this time, I would like to turn the call over to Dave Gancarz, Summit Therapeutics' Chief Business and Strategy Officer. You may proceed.

Good morning 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.smmttx.com. Joining me on the call today is Bob Duggan, our Chairman of the Board and Chief Executive Officer; Dr. Maky Zanganeh, our Chief Executive Officer and President; Manmeet Soni, our Chief Operating Officer and Chief Financial Officer; and Dr. Allen 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, Maky and Manmeet, we will take questions. With that, I will turn the call over to Bob.

Thank you, Dave. Good morning, everyone, and thank you for joining us today. I am very pleased with the recent accomplishments of Team Summit and the accelerating positive information and enthusiasm surrounding Ivonescimab, our lead investigational asset. In Q4 of last year and to date in 2025, we have reached several meaningful milestones around the development of Ivonescimab, importantly with our partners in China as well as here in the US 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 Ivonescimab 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 to 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 HARMONi, our global Phase III 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 Ivonescimab's first global registrational Phase III trial HARMONi is expected in mid-2025. Additionally, in October of last year, we announced a steady amendment to the HARMONi-3 protocol expanding the study to include patients with both squamous and non-squamous histologies. With this amendment, HARMONi-3 is a multi-regional registrational Phase III trial assessing Ivonescimab 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 of squamous histology and we have begun enrollment in patients in the United States with non-squamous tumors. HARMONi-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 Ivonescimab can potentially help. Towards the end of the year, we announced our third global Phase III trial, HARMONi-7 we would be initiating in early 2025. Initial trial sites have begun activating in the United States and HARMONi-7 continues to progress as planned. As a reminder, HARMONi-7 is evaluating Ivonescimab monotherapy against pembrolizumab monotherapy in first-line metastatic non-small cell lung cancer patients whose tumors have high PD-L1 expression without actionable genomic alterations. Maky 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 Ivonescimab in non-small cell lung cancer and very importantly, indications beyond lung cancer. We are a mission-driven organization with the 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 Ivonescimab to realize this goal. With that, I will turn the call over to Maky for additional context and recent highlights for consideration.

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, Ivonescimab. Before providing some additional detail and reviewing the current pipeline, I would like to touch on the clinical work that has been conducted with Ivonescimab and some of the interest and recognition received last year. Since first entering the clinic with our partner Akeso back in 2019, more than 2,300 patients have been treated in clinical trials with Ivonescimab. In 2024 alone, Ivonescimab was featured in 14 publications across seven tumor types and selected for five oral presentations at major medical conferences. Currently, between our partners at Akeso 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 HARMONi 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 Akeso-sponsored trials studying Ivonescimab in head and neck, biliary tract, triple-negative breast cancers. Akeso 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, HARMONi completed enrollment in the fourth quarter with top-line data expected in mid-2025. This data is expected to contain data for both primary endpoints, progression-free survival and overall survival. HARMONi-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 HARMONi-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 Ivonescimab, 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 ISTs to date, which will either enhance our sponsored clinical development activities or can show signals in settings where Akeso has not yet had the opportunity to explore. In 2024, we started our collaboration with MD Anderson, 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 Ivonescimab, 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 Ivonescimab in combination with several of Pfizer's vedotin-based ADCs in multiple tumor types. As we seek to accelerate the development of Ivonescimab across non-small cell lung cancer and other solid tumor settings, this collaboration will allow us to quickly advance beyond our promising late-stage development plan to evaluate Ivonescimab 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 Ivonescimab and additional support for the overseas study. As a reminder for those new to the Summit story, Ivonescimab has significant lead in the clinical development of this novel class of compounds. Ivonescimab 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 HARMONi 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 III clinical trial readout for Ivonescimab, 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-small cell lung cancer in 2025 and 2026 in addition to continuing engagement with a rapidly increasing number of investigators seeking to conduct investigator-sponsored trials at various institutions across a large number of different tumor types. And you will see continual activation of additional ISTs in a variety of solid tumor settings. This is in addition to Akeso continuing its execution of its Phase III studies, including completing the enrollment of HARMONi-6 in frontline squamous non-small cell lung cancer with Ivonescimab combined with chemotherapy as well as continuing the enrollment of its Phase III biliary tract cancer, triple-negative breast cancer, and head and neck cancer studies. Over the course of this year, we will continue to see clinical trial data readouts from Akeso in a variety of tumor types. And finally, we expect to see more Phase III initiations from Akeso in non-small cell lung cancer and beyond, likely in indications in which Phase II data has been generated, which we touched on earlier. We are excited for the catalyst switch path ahead of us; our conviction and belief in the potential for Ivonescimab to improve patient lives for the better remains strong and consistent. Now, I would like to take a moment to review the study design for our two ongoing global Phase III trials, HARMONi-2 and HARMONi-7. Here we have the study design for HARMONi-3. HARMONi-3 is a randomized, double-blind global Phase III clinical trial, evaluating Ivonescimab in combination with chemotherapy against pembrolizumab in combination with chemotherapy as 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 HARMONi-3 include progression-free survival and overall survival and results will be stratified by squamous and non-squamous histology. Next, we have the study design for HARMONi-7. HARMONi-7 is a randomized double-blind global Phase III clinical trial evaluating Ivonescimab monotherapy against pembrolizumab monotherapy as first-line treatment for the metastatic non-small cell lung cancer patients with tumors with high PD-L1 expression. Dual primary endpoints for HARMONi-7 include progression-free survival, overall survival, and results will be stratified by squamous and non-squamous histologies. As a reminder, our HARMONi-7 study shares similarities with Akeso sponsored HARMONi-2 Phase III trials, which reported data last year, but specifically targeted PD-L1 high expressing tumors consistent with the standard-of-care for monotherapy immunotherapy in the US and Europe. Turning to the market opportunity for Ivonescimab, the value proposition here is clear. Ivonescimab 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 III studies conducted by either Akeso or Summit. Non-small cell lung cancer alone has an addressable market that could ultimately approach $20 billion for checkpoint inhibitors according to research from the likes of TD CON and others. But this is just the start. There are more than 50 indications where PD-1, PD-L1 or VEGF therapies have been approved. Ivonescimab will continue to be rapidly tested and developed beyond non-small cell lung cancer. Across all checkpoint inhibitors indications, the addressable market approached $90 billion globally in the next couple of years according to IQVIA research. However, this still excludes the full impact that Ivonescimab could have where it has shown promising data in multiple tumor types where checkpoint inhibitors have not been effective, including microsatellite stable colorectal cancer, PD-L1 low 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 Ivonescimab has a market potential much larger than non-small cell lung cancer and our current ongoing global Phase III clinical studies that we are sponsoring at Summit. There are multiple Phase II trials that have been conducted providing encouraging data to continue to explore Ivonescimab and its opportunity to become a standard of care across several solid tumor settings, which we intend to continue to explore with a 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 Xia, and the entire Akeso team, as we continue to pave the way for rapid development of Ivonescimab 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 unmet cancer needs. It's 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 Manmeet to provide details on our financial position and operations update.

Thank you, Maky, and good morning, everyone. This morning, we issued our earnings release for the fourth quarter and year ended 2024. Today, in addition to providing you with an update on our cash position and operating expenses, I will also be providing an update on our progress on clinical trial enrollment on HARMONi-3, HARMONi-7 and update on tech transfer for manufacturing in our licensed territories. On the financial front, let me start with our cash position. We ended 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 expense. 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 reflects the expansion of our clinical trials related to Ivonescimab. 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 Akeso for the licensing agreement. The $50 million expense in the year 2024 is related to the amendment of the licensing agreement with Akeso to include Latin-America, Middle-East, and Africa regions into our licensed 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 Ivonescimab. To remind you that last quarter we announced that we plan to expand the HARMONi-3 study to include non-squamous patients in addition to the squamous patients. I'm very pleased that our Summit team was able to activate the non-squamous arm in 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 squamous patients in all the territories. Additionally, during last quarter, we had given guidance that we will initiate our newly announced global trial, HARMONi-7 in frontline non-small cell lung cancer for PD-1 high patients in early 2025. Ahead of our schedule, Team Summit has already begun to activate sites in the United States. We expect to initiate activating sites in the other regions during the second quarter of 2025. Turning to tech transfer for manufacturing, we continue to make progress in transferring 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.

Thank you, Bob, Maky, and Manmeet. 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.

Your first question comes from the line of Yigal Nochomovitz with Citigroup. Please go ahead.

Hi, great. Thank you so much for taking the questions. Obviously, we're getting a lot of inbounds on HARMONi-2 and Akeso 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 HARMONi-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 or is there any expectation that we could see a glimpse of some early OS data in that China label? Thank you.

Thanks, Yigal. And this is Dave. So I appreciate the question and I know there's a bit of commentary with respect to HARMONi-2. As our partners at Akeso have 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 continuing partnership with Akeso. But at this point, there's been nothing new on that front with respect to any additional information. But I appreciate the question.

Okay. No worries. And then on the second-line EGFR, the HARMONi trial, I think Maky mentioned you will have the OS data in the topline readout. What is your understanding as to whether you need that to be only a trend or actually hit on the statistical significance to be in a good position for approval in the US? Thank you.

Yes, Yigal, this is Allen Yang. Thanks for the question. So I think there's two things. I think we would of course 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 to be adequate.

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

Yes. Hey, Yigal. This is Manmeet. You heard it correct, right. We have just initiated our sites in the US and we have started enrolling for the US 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 HARMONi-6, you're also correct, right, that trial has been completed enrollment, which was fully in China in the squamous arm. And what I believe as per the guidance from Akeso that should read out sometime in the middle to end of this year. We don't have visibility into any more details further than that.

And then last quick one, I would be remiss if I didn't ask you about the news this morning on the Pfizer collaboration. Anything you could say there in terms of additional details, which of the vedotin ADCs, what tumor types? How big would these OE studies be and things of that nature? Thank you so much.

Yes. Thanks, Yigal. This is Dave. Really appreciate the interest there. I think so what we've said this morning, multiple ADCs from Pfizer. We plan to go into multiple solid tumor settings and expand that beyond just non-small cell lung cancer, obviously. We haven't given specifics in terms of which ones just yet, but they are likely to be Phase 1b/2 level trials at this point. We need these are the first combinations that we'll do with Ivonescimab in these specific ADCs. So in normal course of 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, this is one of the strategic advantages that we feel we have in terms of the opportunity to combine Ivonescimab with a number of different products from a number of different 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.

Thanks, Yigal.

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

Hi. Good morning. Thanks for the questions. 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 Ivonescimab outside of lung with a better probability of success?

Hi, Brad. Thanks for the question. Both, but probably the latter more. So clearly ADCs are going to be important across solid 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.

And maybe just a quick follow-up on that. In lung specifically, as I look at the Pfizer pipeline of ADCs, can I check your confidence level in Integrin beta-6 for an ADC target over TROP-2 where obviously competitors have frontline Phase IIIs reading out this year?

Yes. So I appreciate the question, Brad. And I think we'll be in a better position to give a little bit more detail as we get closer to launching the Phase 1b/2 clinical trials. But at this point, we're not really getting into the specifics just yet in terms of the design as we want to allow for these trials to get up in the activation portion and then ultimately get up and running.

Brad, 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 from me. With the HARMONi 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 Akeso's China patients? Thank you.

Thanks, Brad. Yes, I mean, I think that is going to be a key component. I think we and especially Allen have been talking about this for over the course of the past year or so. One of the key components will be showing 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 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 data can be interpreted.

Thanks again.

Thanks, Brad.

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

Congrats on the progress. Thank you for taking my questions. Maybe a couple of questions, HARMONi trial, global trial design. So regarding the prior 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?

Yes. Kelly, this is Allen 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.

Okay. Thank you. Okay. Thanks. And you guided mid-year for data disclosure. Just want to confirm, this is referring to June, July or actually could it be like the entire Q2, Q3 timeframe?

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

Okay, terrific. And one more on Pfizer's collaboration. So regarding EV in bladder cancer, just curious, is there like a possibility to add some combo arm to the ongoing or the initiating Phase III trials running by Pfizer or should we expect more like early phase trials?

Yes. I don't think we've disclosed anything. We're exploring every opportunity to move as quickly as possible. We haven't said anything about EV specifically, but we believe that EV is important in bladder cancer. And, yes, more to come.

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

Okay, great. Thank you for the color.

Thanks, Kelly.

Your next question comes from the line of Mohit Bansal with Wells Fargo. Please go ahead.

Hi. This is Sadia Rahman on for Mohit. Thanks for taking the questions and congrats on all the progress over the year. So I wanted to ask on the Pfizer collaboration. Curious how you're thinking about the overlapping toxicities with VEGF inhibition and vedotin-based ADCs and how this could differ from combinations with ADCs using topoisomerase payloads?

I appreciate the question. To provide some context, we aim to combine Ivonescimab with the most effective treatments on a tumor-by-tumor basis. Part of our strategy includes conducting safety run-ins for any combination involving Ivonescimab, and this approach will apply here as well. Currently, we are not in a position to offer specific comments on the various types of antibody-drug conjugates, whether they are MMAE-based or topoisomerase-based. Historically, we have observed data related to combinations with immunotherapy such as pembrolizumab in some of these ADCs, including both MMAE-based and topoisomerase-based. At this moment, we are excited about the profile demonstrated by Ivonescimab so far and are mindful of the profiles for the advancing ADCs. We plan to pursue rational combinations step by step and will advance as we gather more data.

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

Got it. Thank you. Regarding the upcoming readout this year in EGFR mutant lung cancer, I believe you mentioned that most of the patients are from the China HARMONi study and that most of these patients received either a first or second-generation TKI before receiving a third-generation TKI. Will all the patients in the HARMONi study receive only a third-generation TKI in the first-line setting? Also, could you discuss any differences in those populations we might anticipate in terms of time from diagnosis or survival after the third-generation TKI and whether that might lead to any variations in efficacy when considering the next line of treatment?

Yes, just to be clear, the majority of patients in HARMONi-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 and 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 then maybe one more on the HARMONi-2 trial and your global trial. So the time to separation on the PFS curve in HARMONi-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 and how that could affect timing of when you hit on PFS relative to when HARMONi-2 hit on PFS?

Yes. I think we've put out a decent amount of data with respect to AK112-201, which was the Phase II trial that looked at Ivonescimab plus chemotherapy in multiple settings, including both squamous and non-squamous in the frontline setting. That's probably the earliest or best rather in terms of an early thought process with respect to what we would see from data with Ivonescimab plus chemo and comparing that against the historical benchmarks that you would see from trials such as KEYNOTE-189, KEYNOTE-407, etc. 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 HARMONi-6 from our partners at Akeso in the squamous frontline setting, those will be additional inputs that we'll provide more color.

Great. Thanks so much.

Thank you.

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

Hi, everyone. Thanks for taking the questions and congrats on this deal. Just could we just talk about kind of when you were searching for a BD transaction like this, can you just talk about 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 preclude those for a while? And could you just talk about if you expect future business development to be in the pursuit of combinations similarly like this? And if importantly if there are any particular BD opportunities that you're not considering?

Yes. Thanks for the question, Mitchell. I think you know, if I again take a step back here, I think one of the things that we've talked about is the strategic advantage for Summit and Ivonescimab is that we don't have that pipeline internally that we're kind of 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 Ivonescimab plus one of those whether antibodies or small molecules make sense then that will be an opportunity where Ivonescimab can combine there. So I would say as a whole we don't believe that there is 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 they be topoisomerase-based, whether they be MMAE-based, whether it's switching out the linkers of the antibodies in different settings. Obviously, there's a number of, for example, TROP-2 ADC with different antibodies. So what we can do is really explore different combinations of Ivonescimab plus X, Y, or Z ADC, antibody small molecule. So we're not really giving guidance in terms of we plan to do additional collaborations like this or what not. But in general what we certainly feel well-positioned for is that we will take Ivonescimab and look to combine it with the best possible alternative, if you will, out there from a standard of care perspective to bring the most potential value to Ivonescimab and ultimately help patients in any way that we can there.

Yes, Mitch, and this is Allen Yang. I would just add that we just want to pursue the best science to help patients, right? And so I think there was a lot of interest in combining with pembrolizumab in terms of combination therapies with different immunotherapies in different other agents. And based on the HARMONi-2 data as we had suspected that now companies are interested in sort of pairing with Ivonescimab, 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 specific things we're not open to. I think it's more about what is possible with Ivonescimab.

Yes. 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.

Okay. Great.

And Mitch. This is 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 from doing any other regional or 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 about the HARMONi-3 enrollment? I know you briefly touched upon that, but does HARMONi-7 site activation compete for patients for the PD-L1 high enrollment for HARMONi-3 at all?

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

Great. Thank you all very much for taking the questions and congrats again on this collaboration.

Thanks, Mitchell.

Your next question comes from the line of Asthika Goonewardene with Truist Securities. Please go ahead.

Hey, guys. Thanks for taking my questions and congrats on all the progress as well. I want to dig into HARMONi-3 a little bit please. Will this primary statistical analysis for that study, are you doing the primary analysis on the combined non-squamous plus squamous population or will you do it more in a step-wise manner kind of looking at the squamous and non-squamous subgroups individually first and then look at the overall population? I ask this because I believe the BioNTech study is structured more like the latter. And I'm curious to know if you're taking a different approach and if so why you prefer your method?

Yes, Asthika, thanks for the question. This is Allen. Our plan is to conduct a primary analysis of the combined population, which we believe is the best way to bring this product to patients as quickly as possible from an operational perspective. There is always ongoing data being released, and the HARMONi-6 study will provide useful information as well, but our current approach is to perform a combined analysis.

Got it. Thanks, Allen. Have you discussed with the FDA any way to accelerate the filing with HARMONi-3? I'm curious if you're seeing a strong PFS signal. Have you talked to the FDA about possibly pursuing an accelerated filing 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 Ivonescimab could better leverage the immunogenic cell death versus PD-1 or is there rationale behind this deal mainly about layering on a classical antiangiogenic pressure in addition to PD-1 with ADC?

Yes, Asthika, that's a great question. We could discuss this in depth. However, part of it is based on empirical data. We know that many of these drugs are effective in various tumor types, and we want to consider their combined efficacies. Whether there will be some synergistic effect through the immune system will differ from the additive or synergistic effects seen with pembrolizumab. We believe all of these scenarios are possible, and we are excited about exploring these combinations. It's definitely intriguing.

Great. Thanks for taking my questions guys.

Thanks very much.

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

Thank you for taking my questions and congratulations on the progress. With HARMONi-3 and 7 underway, could we discuss the next solid tumor indications you plan to focus on? We had some ongoing study data reported last year. Can you share when we might see updated results from those studies? Additionally, do you strategically follow Akeso based on their solid tumor data and conduct global studies based on their findings, or do you pursue indications they may not be addressing?

Sure, Reni. Thanks very much for the question. In reality, everything that you mentioned resonates, right? And so if you think about the last part of your question, which is, do you follow Akeso or do you look to branch out? As Maky talked about, part of our MD Anderson collaboration 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 Akeso, which were released over the course of last year, whether it be BTC, colorectal cancer, head and neck cancer and triple-negative breast cancer, there are some promising signals that we see in that Phase II data. There are also additional indications that have been explored in Phase II where data hasn't yet been fully disclosed from that perspective, which give us opportunities. And then obviously, we can run additional signal-seeking or Phase II studies as well, whether on our own or through things like the collaboration, the clinical trial collaboration with Pfizer here, which we'll look to do that as well. So as a whole, I think, as Maky 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 lung cancer as well and that's part of our '25, '26 development plan.

Got it. Sorry, go ahead.

No, Reni, I was just going to add. So we haven't disclosed it. We're in the midst of multiple regulatory discussions around that. I would just say that we have been thinking about this for a long time. So we did this exercise even before the HARMONi-2 data readout shortly after the deal was done, looking at all the prior checkpoint inhibitor approvals, looking at all the antiangiogenic 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 II data coming out from Akeso 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 concluded and it really it's about the Phase III studies that are up and running?

Yes, you will continue to receive updates as we move forward with the studies for which we provided some initial top-line data last year. I would also like to highlight our excitement regarding colorectal cancer, especially since we have recently partnered with Akeso for the Phase II study that we are starting to activate on our side. You can expect to hear more details about this in the upcoming 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 HARMONi-7. Can you talk a little bit about how many sites globally you expect to have onboard by call it by the end of 2025 and for both HARMONi-3 and HARMONi-7?

Hi, Ren. This is Manmeet again. I think we don't give the specific number, but on the sites we activate, because we go into multiple regions. This is a global multi-regional study. But I would expect by the end of 2025, most of the sites should be activated close to 100%.

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

Thanks very much.

Thank you.

I will now turn the call back to Dave Gancarz for closing remarks.

Yes. I want to discuss business development. It involves multiple components. One aspect is optimizing IVO to ensure it is the best product, both as a monotherapy and in combination therapy, which we aim to achieve with our partner Akeso. We continuously assess this, and there is still ample opportunity for improvement, as evidenced by the trials we are commencing. The second aspect focuses on timing and strategies for capturing additional market opportunities and market share. This is also a critical component of business development. We are actively engaged in both areas. The first focus is with Pfizer, looking at how we can enhance the product. We are also pursuing other initiatives. It's important to clarify that Pfizer is not the sole focus of business development at Summit, even though it may appear that way to many of you. Now, I’ll hand it back to Dave.

Really appreciate it, Bob. Thanks very much. And I want to thank everyone for attending today's earnings call. An archived version of the webcast will be available later today on our website www.smmttx.com. Thank you very much for your participation, and we hope you enjoy the rest of your day. Thank you.

Bye-bye.