Thank you for standing by. My name is Kate, and I will be your conference operator today. At this time, I would like to welcome everyone to the Summit Therapeutics Q3 2025 Earnings and ESMO Data Update Call. [Operator Instructions] I would now like to turn the call over to Dave Gancarz. Please go ahead.

Good day, and thank you for joining us. We issued a press release on Friday morning regarding the expansion of our Phase III clinical development programs, unveiling the global Phase III study in first-line colorectal cancer. Yesterday, we issued a press release relating to the Phase III HARMONi-6 data featuring ivonescimab presented as a part of the Presidential Symposium at the European Society for Medical Oncology's 2025 Congress, otherwise known as ESMO 2025. The HARMONi-6 study was conducted in China, sponsored by our partners at Akeso. All relevant data was exclusively generated, managed and analyzed by Akeso. And finally, this morning, we announced our intention to submit a BLA this quarter for ivonescimab based on the results of the HARMONi study as well as expand our Phase III study plan with additional color to be provided in the first quarter. Additionally, on today's call, we will provide an update on our third quarter financial results and operational progress. Press releases are available on our website, www.smmttx.com. Our Form 8-K and Form 10-Q were also filed today and are available on our website and via the SEC's website. Today's call is being simultaneously webcast, and an archived replay will be made available later today on our website. Joining me on the call today is Bob Duggan, our Chairman of the Board and Co-Chief Executive Officer; Dr. Maky Zanganeh, our Co-Chief Executive Officer and President; Manmeet Soni, our Chief Operating Officer and Chief Financial Officer; Dr. Urte Gayko, our Chief Regulatory, Quality and Safety Officer; Dr. Allen Yang, our Head of R&D Strategy; Dr. Jack West, our VP of Clinical Development; and Dr. Fong Clow, our Chief Biometrics 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 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. One item of note, this presentation is being webcast with slides, so we'll be referring to information on these slides being displayed in the webcast link. I'd encourage you to use the webcast link to see these slides being presented this morning that will accompany our comments, and these slides are also available on our website. Following comments from our team, we will take questions. With that, I would like to hand it over to Jack to walk through the beginning of the presentation.

Thank you, Dave. Yesterday, as you're aware, ivonescimab data was featured in the presentation at ESMO 2025 as part of the Presidential Symposium. The presentation titled Phase III study of ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy as first-line treatment for advanced squamous non-small cell lung cancer, HARMONi-6 was given by Dr. Shun Lu, MD, PhD, Chief of Shanghai Lung Cancer Center at Shanghai Chest Hospital, Professor of Medicine at Shanghai Jiaotong University, and associate editor for the Journal of Thoracic Oncology. Revisiting the schema for the HARMONi-6 trial, this study evaluated ivonescimab in combination with platinum-based chemotherapy compared with tislelizumab, a PD-1 inhibitor in combination with platinum-based chemotherapy in patients with locally advanced or metastatic squamous non-small cell lung cancer irrespective of PD-L1 expression. HARMONi-6 is a single region, multi-center Phase III study conducted in China sponsored by Akeso, with all relevant data exclusively generated, managed and analyzed by Akeso. Key eligibility criteria are shown here. Patients were randomized 1:1 stratified by stage of cancer and PD-L1 tumor expression at baseline. Patients received either ivonescimab at 20 milligrams per kilogram plus carboplatin paclitaxel or tislelizumab-plus carboplatin paclitaxel for up to 4 cycles and then received either ivonescimab or tislelizumab as maintenance therapy for up to 24 months. Treatment was to be discontinued for intolerability, progressive disease or initiation of new antitumor therapy. The study's single primary endpoint was progression-free survival by independent Radiologic Review Committee. Secondary endpoints included response rate, duration of response, safety and overall survival. The trial included a total of 532 patients. Baseline characteristics show that this was a predominantly male population nearly all with Stage IV disease, and it's important to underscore that these patients with advanced squamous non-small cell lung cancer, included those with characteristics that we have traditionally considered as potentially associated with…

Thanks, Jack. I would like to echo Jack's comments around our gratitude for the patients who enrolled on HARMONi-6 family members, trial site personnel, investigators and, of course, the Akeso team. We are slightly encouraged by the readout of this study to our other ongoing Phase III study in frontline non-small cell lung cancer, HARMONi-3, HARMONi-7, PD-1 therapy with or without chemotherapy depending on the PD-L1 status is the more overwhelming standard of care in frontline driver mutation negative lung cancer. Ivonescimab both as monotherapy and in combination with chemotherapy compares favorably to the result of the PD-1 monoclonal antibody previous studies. While additional overall survival data will be important to see in the future, consistent, clinically meaningful, statistically significant resource in progression-free survival in HARMONi-6 and progression-free survival and interim overall survival data of HARMONi-2 announced previously are very encouraging when we look to global studies HARMONi-3, HARMONi-7 and beyond. Yesterday's HARMONi-6 results presented at ESMO and subsequently published in the Lancet are highly encouraging in showing the consistent performance of ivonescimab and its ability to break into a setting where existing anti-VEGF therapy is not an option due to historically observed tolerability concerns from early phase clinical trials. HARMONi-6 continues to validate the opportunity presented by ivonescimab to make a significant difference across a vast number of patients facing solid tumor diagnosis. I would also like to highlight several important updates to our Phase III clinical development program that we have announced over the past few days. As we announced Friday, our clinical development plan has expanded beyond lung with the addition of our global Phase III HARMONi-GI3 trial, a brand new study evaluating ivonescimab as first line therapy in first-line unresectable colorectal cancer, including studies sponsored by our partner, Akeso. This brings a number of planned or…

Thank you, Maky, and good morning, everyone. Today, in addition to providing with you an update on our cash position and operating expenses, I will also provide color on our clinical operations. Let me start with an update on the clinical operations product. The HARMONi-3 study is enrolling ahead of our goals. And as Maky mentioned, we have enrolled over 80% of the newly planned 600 squamous patients cohort, and now expect to complete enrollment for the squamous cohort of HARMONi-3 during the first quarter of 2026. To remind you, the non-squamous cohort in HARMONi-3 was initiated during first quarter of 2025, and that too is enrolling ahead of the plan. And now we expect to complete enrollment for 1,000 patients during the second half of 2026. Our HARMONi-7 study was initiated during the first quarter of 2025 and we have activated over 50% of the selected sites globally. And for our newly announced Phase III, the HARMONi-GI3 study, we have already started planning and sites are planned to begin activating in the United States prior to the end of the year 2025. On the financial front, let me start with our cash position. We ended the third quarter of 2025 with a cash position of approximately $238.6 million. Turning to operating expenses. I'll provide details on 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. As a reminder, our non-GAAP expenses exclude stock-based compensation expenses. Our total GAAP operating expenses for the third quarter of 2025 was $234.2 million, compared to $568.4 million for the second quarter of 2025. The decrease in GAAP operating expenses was primarily due to the higher stock-based compensation expense of approximately $348.2 million as a result of the modification of unvested stock options recorded during the previous quarter. Overall, our non-GAAP operating expenses during the third quarter of 2025 were $103.4 million, compared to $89.6 million for the previous quarter. The increase in non-GAAP operating expenses was primarily related to an increase in R&D expenses related to HARMONi-3 and HARMONi-7 trials. And with that, I will hand it back over to Dave. Dave?

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

[Operator Instructions] Your first question comes from the line of Yigal Nochomovitz with Citi.

So the first one I had is, when could we expect to see the first OS cut from HARMONi-6? Would it be before the second half 2026 PFS readout for HARMONi-3 and squamous? And then the other question is given HARMONi-6 was powered 86.3% for a hazard ratio of 0.7 but you hit on a lower hazard ratio of 0.6. I'm curious what that may imply about OS powering for the study given that was powered at 80% for a hazard ratio of 0.73, the implication potentially that you may have more OS power than originally designed?

Very good question. Dave?

Thanks, Yigal. This is Dave. So one thing that I want to make sure is clear, as we mentioned, this is a study that was designed and conducted by our partner, Akeso. And so one thing that we don't do is get in front of Akeso with respect to disclosing additional details beyond what they have currently disclosed. And so I think if we look overall, obviously, the protocol is included within publication. And I want to congratulate again our partner, Akeso, for both the presentation and the Lancet publication that became available yesterday. But in terms of differentiating details between the planned and adjusted power and whatnot, I leave that to our partners at Akeso. But I think one thing that you can see from, in general, the plan for testing is that there's likely something that can be reviewed in 2026. But it's important to remember that from a time to event perspective and a prespecified number of events in an analysis, we hope patients do well, and we hope patients continue to exceed expectations into knowing exactly the order of events becomes a little bit difficult. But this is events driven. So at some point next year is probably a fair estimate, but more specific to that is a little bit beyond where we would like to disclose at this point and defer to our partners there.

And then just the other follow-up. Obviously, Maky, you talked a lot about new studies, CRC, and then you mentioned additional set of Phase IIIs where you might get more details in 1Q '26. So all of that points to questions around funding. I'm just curious if you could speak at least to some extent as to what options are being evaluated to extend the runway, what the priorities are in terms of how you may raise additional capital?

Maky prefers that I answer the questions.

[indiscernible].

She doesn't have [indiscernible]. Yes, we have an ATM out there with give or take $350 million. I have already had some inbound interest in additional capital. I'm interested. I've invested a few weeks ago additional capital. So yes, we'll move straightforward on that. And I'm happy to have the opportunity and I think others are too. So you'll see that as it plays out. I won't predict the amount right yet, but I'm aware of all the numbers and aware of the plans going forward. We have empirical evidence that this is a product that is crying out for significant investment. It is to demonstrate its capacity to enter into a business that the leading player is generating roughly $34 million in revenue over the next 3 years, $17 million, $18 million, [ $3 billion ] in free cash flow. So this is a significant opportunity, and we do not want to miss it. We have -- we also feel that the key to making that happen is for this team to have control to be able to start, stop and change a number of variables leading to our ultimate success, and we're happy with the position that we have. So I hope that gives you some addressment to the issues of finance.

And as soon as we have more information regarding other clinical trials, for sure, we are going to communicate as time allows.

Your next question comes from the line of Tyler Van Buren with TD Cowen.

Congratulations on the unprecedented HARMONi-6 results. I guess I want to ask about the BLA submission. Given the confirmation of the ivonescimab BLA by year-end based upon the HARMONi data, can you provide any color as to how your interactions with the FDA have gone? And how the present approvals with amivantamab or Dato might support approval of ivonescimab?

Thanks for the question. So yes, we announced today [indiscernible] that we are planning to file in the fourth quarter of this year. We are actively finalizing and putting the match together. We have continued interaction with the FDA. And obviously, after we have made the submission, we are looking forward to getting specific feedback and giving some color earlier next year after the submission. We have indeed reviewed the most recent doctor's approval backwards, as you mentioned, [indiscernible], the approval of [indiscernible] previously treated EGFR patients that [indiscernible] actual approval in also previously EGFR patients. And as you are aware, and obviously we are fully aware that neither of those other people included a significant OS benefit. We have also disclosed previously, but I'm just repeating that FDA has told us that they are looking to inspecting OS in our setting. But we do think that the totality of our data from a combination of efficacy and safety is a strong package and should be moved forward to becoming available for these patients. So therefore, we are moving forward with the submission as we have announced.

That's great. And just as a quick follow-up, did you discuss the latest overall survival data that surpassed the statistical threshold at World Lung with the FDA?

Yes, we are not going to go into the details of exact discussions with the FDA, but I can confirm that we are in close contact with them and will be sharing information whenever appropriate with them.

Your next question comes from the line of Brad Canino with Guggenheim Securities.

Great to see the data at ESMO and a large crowd yesterday. Maybe another follow-up on the BLA. I understand the logic of trying to get this drug to patients as quick as possible, given the data that you have, but from a business perspective, can you help me understand the strategic thinking of now wanting to submit the HARMONi study and undertaking that review issue of how to deal with the OS as the first time the FDA will review a BLA package for ivonescimab especially when you have HARMONi-3 potentially coming as soon as second half '26 for PFS and OS. I guess my thinking was that might be a better package to submit first and then have HARMONi come as a supplement or something like that. So just how you're thinking about that would be helpful to hear.

Sure. So we have had certainly many discussions just to confirm internally and there are many open scenario. But in principle, our thinking is that each indication will have its own submission. This particular package is ready now. We have mature data. We have shown consistency in the data with our long-term follow-up between the rest of patients and the Asian patients. And we think this is the right opportunity, and we are going forward. That doesn't mean in the future we will continue going to look at this as we might do other packages in the future. And depending on exactly what comment or feedback we ultimately also get from FDA, we will make those adjustments to support it in the future.

And then separately, just quickly on the colorectal Phase III. You mentioned there's some undisclosed in-house data. Can you talk qualitatively about what that is, the extent of it and what thesis were explored? And then when we expect to see those data presented to further support the Phase III?

Sure, Brad. This is Dave. And so I think one of the things that Maky spoke about was we had previously presented data with our partners at Akeso in 2024 at ESMO. And that was validating with respect to not just colorectal, but head and neck as well as triple negative breast cancer. What then has since happened, both Akeso as well as an expansion of that Phase II to include patients in the U.S. was conducted. And so with that, we've had multiple backbones of chemotherapy, which have been reviewed with ivonescimab as well as a novel-novel combination with ivonescimab in this setting. And so what that's done is it's given a bit of exposure to the drug as well as the ability to compare historical results with different chemo backbones in order to kind of validate what we're seeing and the consistency of that data. And so we ultimately chose based on the standard of care that exists in the strong preference for both patients and physicians to move forward with the FOLFOX regimen. But there's quite a bit of data that's been generated across a number of different backbones, which gives us quite a bit of confidence. And it is -- I'm sure you're aware but also to note our partners, Akeso, are running a Phase III study in this setting as well. And so it's another -- just another data point with respect to confidence that we have in terms of ivonescimab's opportunity in this setting.

Your next question comes from the line of Salveen Richter with Goldman Sachs.

With regard to HARMONi-6, the PD-LI by status was interesting, and we see -- PD-L1, sorry, negative outperformed PD-L1 positive. Could you just help us maybe understand what's playing out there and then the translational work that you're going to be doing to kind of help the oncologists with determining how to best position here?

In terms of HARMONi-6 and the PD-L1 expression, I would say that it's not -- I don't see it as necessarily that the negatives are outperforming the others, but rather that the differential effect is a little greater in the PD-L1 negative patients. To me, that's not that surprising. I would say that as a clinician talking with all of my other clinician colleagues, we've long recognized that although other regimens that are FDA approved here have some incremental benefit from the addition of the checkpoint inhibitor that benefit is tepid. It's rather minimal, and these are patients -- this whole group is one that has disappointing outcomes even with our current standard of care. And so there's really a lot of room to do better. In this case, I would say that it may be suggested that this is a setting where there are -- I'm sorry, this may be a setting where VEGF components may be especially relevant. And I will say that it's important to also recognize that these are subsets. We're going to have additional information to look at these, whether it's consistent trends between HARMONi-6 and HARMONi-3, but that it's important to note that in the patients, particularly with the high PD-L1, that group had a smaller -- that was about half of the size of the other groups. And so I wouldn't want to put too fine a point on any of these subset analyses. They're just suggested and all of them showed the same trend or the same overall conclusion of being superior with [indiscernible] just to varying degrees.

Brad, if I may just touch back on your question on EGFR. We were really pleased that the FDA approved or taking that trial on. There were a number of major issues to hand on that trial. One of them was China versus U.S.A. data translatability. That was -- we put a real feather in the cap that there is some significant translatability. That's obviously a very dynamic issue. There was also the issue of bleeders in EGFR and we certainly put that one to rest. There was also the issue of brain mets, something very serious, that's members of my own family. We put that issue to rest. Then there was the bispecific, very novel, and we put that issue to rest. So that would not have happened had the FDA not allowed us to move forward. Now in a continuation, our trials will always have China patients. It won't be 2/3 to 1/3, it will be more like to 1/3 to 2/3, and we're very pleased about that. But on the record ivonescimab performed incredibly well. We had a progression-free survival hazard ratio of 0.52. We did better than any other drug in that marketplace. On the p value. We had [ 0.57 ]. [indiscernible] It's important to note that when you receive feedback from the FDA, it's a game you got to play and we played it. We needed 150 at least patients from outside of China, and we were able to get to 175. What really wasn't told was we underestimated the degree of difficulty to get the to doctor to take this trial on. There was an inertia there. And that inertia caused us to get off to a very slow start. So we think as all that becomes incredibly available to others, they will look at it as a very successful human patient trial and we certainly appreciate the fact that the FDA allowed us to move forward on that. So that gives you a little background on why we'll submit. We feel -- we are a patient-based company, and we feel patients can benefit and did benefit, and we would like to see more of that, and the FDA will make the final decision. There probably isn't a U.S.A. agency today that has more respect around the world than the FDA, and we totally support that. So I hope that gives you a little bit of color as to we've made the investment, and we'll make a further investment. And if it goes well and we get into patients' hands, everybody will have a win on it. If it doesn't, we certainly will try to make [indiscernible].

Your next question comes from the line of Cory Kasimov with Evercore.

Curious, was there something in the HARMONi-6 data that prompted the protocol amendments to HARMONi-3 beyond this kind of the staggered enrollment run rate? And what impact will these changes have on the powering of the HARMONi-3 subset?

Cory, this is Dave. So thanks for your question. So I mean, I think there are multiple reasons in terms of updating the design of HARMONi-3. So one, it accelerates our frontline lung cancer opportunity as a whole. Since we began enrolling the squamous cohort first, we believe that we'll be able to complete enrollment in the first half of next year, and this will allow for a data readout in the second half. And because we're rapidly enrolling the squamous cohort as well, we can complete that enrollment in the second half of next year. But two, it reduces regulatory risks by separating the 2 histologies to individual ITT analyses, we do not risk the overall population being statistically significant, but one subgroup looking a little better than the other mainly through sample variability, and this could lead to risks regarding approval for one histology and the other. And so -- and additionally, we've seen advisory committees from the FDA earlier this year that there's an increased importance on the results of U.S. patients, which becomes a subset of the 2 histologies. So without the change, U.S. patients are effectively a subset of a subset at that point. And now we have individually powered squamous and separately powered non-squamous histologies for both primary endpoints of PFS and OS. And so they're individually powered at the histology level now, and so 2 ITTs. So separately powering the individual histologies is effectively a cleaner assessment of the data. And three, it allows us to keep pace in non-squamous as well because given the PD-1 plus chemo therapy performs a little bit more favorably in non-squamous patients, i.e., typically, it has a longer overall survival than squamous patients. The progress in additional targeted therapies that we see in non-squamous mutation, variability, some…

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

Congrats on all the progress. One repeated question we get from experts is that when you compare a VEGF PD-1 to PD-1, or previous PD-1 VEGF combo, it is very clear that the VEGF component is better than the VEGF component that was tested before, but it's not clear that if PD-1 component is better. Now where do you stand on that? And if that is the case, isn't that an issue for OS benefit here because it does seem like PD-1s are the ones which are causing the -- using the long tail in those trials. So I think that's the biggest issue right now. If you could help us understand the confidence around OS here.

Yes. This is Jack West. I think it's difficult to impute too much into the value of one side of a molecule or another. We don't -- we haven't historically done that with other molecules that target met and EGFR and say, well, that -- you don't dismiss or minimize that because, oh, this is just working on the met side. I would say that the most important thing is, we should see what the data show at the subsequent final ongoing reading. So if the efficacy is there, and the tolerability is favorable, you look at the totality of the data, and you decide whether that is enough to change from whatever you're competing current standards. And I don't think that we have or should have a separate set of criteria for a presumption that this is working through a VEGF action or immunotherapy action. I think we just make inferences. And I think different clinicians or others make inferences based on their own suppositions or biases. So I would say that -- yes, I'm not sure it really matters. I think that the reality is you look at the efficacy, you look at the tolerability and you weigh all of that against what the current prevailing options and standards are. And if it bubbles up is better, we have lots and lots of therapies that have a benefit that is not sustained over many, many, many years, and that's still valuable. So there are many different kinds of efficacy benefits that have varying degrees of appreciated utility to clinicians and patients. So I think I would focus more on what the actual clinical outcomes are than a supposition of which side of a molecule is more important in one setting or another.

Yes. William, I'll add. This is Allen Yang. I'll add that we've always been under the hypothesis, and I think the data are showing that the 2 put together are cooperating and better than the sum of the parts. Akeso smartly designed this molecule such that the PD-1 and VEGF work together. So the HARMONi-6 data reading out positive doesn't indicate that it's just the VEGF. And it's not just an indication. But again, I think VEGF is important in a lot of different diseases, and this puts them together a smart way. If you look back to the HARMONi-2 data, remember, there was an improvement, not only in the low PD-L1 expressing, that was probably indicative of the VEGF, but also the high PD-L1 expression. This is the sweet spot for PD-1. So the VEGF clearly makes it better. I think [ John Heymach ] also alluded to in the discussion of that, that not only were they cooperating, that the VEGF may play a role in immunotherapy as well, and there's growing data to support that as well. So the answer to your question is, we think, again, both sides are important and how they're engineered and put together indicates that the MOA is important. I also want to add that the safety that we've seen across 4 randomized double-blind placebo sites suggest that this is not [ VEGF ].

Your next question comes from the line of Clara Dong with Jefferies.

Congrats on the impressive HARMONi-6 data. So I think there's a lot of great questions on HARMONi-6 already. So I want to actually talk about your plan for colorectal cancer. So for the Phase III study, are there any plans to stratify or analyze outcomes based on the presence of liver versus non-liver mets given some prevalent evidence of their impact on treatment responses in MSS CRC? And then you mentioned the global components of the Phase II FOLFOX combination study. So what's the expected time line for the next update on whether we should expect some U.S. data from this trial in the next update as well?

Thanks, Clara. I think all good questions. And I think we do -- we certainly do have stratification factors within our current trial. I don't think at this point quite this early we're looking to make public all of those individual factors just yet. Your points are well taken in terms of the specific patient characteristics that you mentioned. And I would say with respect to the publishing of additional data, including those data that were based on U.S. patients, we're determining the appropriate time if and when that -- if and when we do that. And part of that is we continue to have Phase III readouts that becomes important to prioritize that. Publishing data across multiple different chemotherapy lines for us or chemotherapy options important for us to make decisions. It is not necessarily something that we need to individually go through. And so I think there's a piece where the Phase III will become very important to publish. And obviously, our partners at Akeso are running a Phase III as well, which will provide significant additional context when that study concludes.

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

Also my congrats on all the progress and the great data presented yesterday. To start off on HARMONi, the takeaway from World Lung was that your OS benefit would become more pronounced with the appropriate level of follow-up. So the HARMONi filing with the FDA, do you need to take a new data cut or are you filing what you have right now? And then I have a follow-up.

Yes. Thanks for the question, Asthika and appreciate the words at the beginning. I think we haven't publicly spoken to the specific details with respect to how we'll work with the agency. As Urte mentioned earlier, we maintain communication with the agency. It's important to work through the submission process. And so as she mentioned, currently working on the application at this point. So I think that is clearly just given where we are today, only 1.5 months later from the data cut based on what we saw at World Lung. And I think in terms of next steps with that, I think part of that will involve discussions with the agency.

Got it. And then just on the amendments to the HARMONi-3 study. So the original HARMONi-3 study, which was in -- originally was restricted to just squamous patients, that had about a trial recruitment of about 400 or 450 patients or so. The HARMONi-6 data came out showing a really great benefit in similar kind of patient population. But now you're expanding the recruitment for the HARMONi-3 squamous cohort to 600 patients. I know that's also in line with what KEYNOTE-407 recruited. But I just want to get your guys' thoughts on the rationale for increasing the target size?

This is Urte. [indiscernible] We are basically splitting the cohorts into 2 parts. There will be separate analysis and it's very important that we are powering for both endpoints for PFS and OS. And this is a very good sample size. We have obviously high confidence in the readout of the squamous cohort, but this is appropriate to cover those endpoints.

Your next question comes from the line of David Dai. with UBS.

I also want to add my congrats on the great data here. So a couple of questions. One, just a clarifying question on HARMONi-3 Phase III trial update. So Dave, you mentioned that the trial update derisk regulatory aspects. I just want to clarify that, does that mean that you're able to file each histology separately? I'd say if one histology failed while the other succeeds, then you can file for the successful one irrespective of the failed histology?

In short, yes, they're independent ITTs. So they're independent analysis.

Got it. [indiscernible].

It's just the nature of what has happened. So they will not need on executives [indiscernible].

Got it. Okay. Great. And then secondly, just on the combo strategies for non-small cell. I know a lot of other companies are thinking about doing ADCs and chemo combos. What are your thoughts around like combination strategies with ivonescimab in different solid tumors?

Yes. And David, I think you talked about novel-novel combinations, if I understood that right. And so yes, I think we've talked about this a little bit in the past, but we're very excited in terms of our clinical trial collaboration with [ RevMed ] in terms of evaluating multiple RAS inhibitors in combination with ivonescimab. And so I think we'll be able to, in collaboration with [ RevMed ] dosing patients earlier, early in 2026. But in addition, there too, I think we're planning on multiple additional combinations, and those would likely be with ADCs to where I think you were heading with that, David. And so part of what we believe is a strategic advantage for Summit as a whole, ivonescimab, in the global development of ivonescimab is because we don't have specific ADCs that are part of our portfolio as well. It allows us to follow the data. And so we're working with multiple other companies in terms of collaborating in order to test ivonescimab in combination with multiple ADCs that are multiple targets with multiple different payloads, different structures. And that will allow us ultimately to follow the data. I think you've heard us speak to in the past in reality. What we don't believe -- and similar to -- if you look at solid tumor therapy today, there is not a single chemotherapy or chemotherapy regimen that is applicable across solid tumors, right? There are different regimens that are applicable even in non-small cell lung cancer. Pemetrexed is used very frequently in non-squamous tumors and it is not used in squamous tumors and paclitaxel as the backbone. And so as we think about -- just within non-small cell lung cancer, key difference is in terms of the chemo regimens. That implies, as you keep going…

Your next question comes from the line of Ren Benjamin with Citizens.

Congratulations on the very impressive data yesterday. I guess the first question is the HARMONi-6 safety profile, I mean, really reaffirms to us like ivonescimab's tolerability especially given it's largely comparable control arm. Were there any specific like -- squamous specific related events that's different from the non-squamous cohort in HARMONi? And related to that, I think there's just an apparent kind of underdepreciation for the safety profile, specifically bleeding. I think discussion brought that up. I'm kind of curious as to how you guys are addressing that especially with KOLs?

This is Jack West. I would say there's differences between the squamous and the non-squamous largely based on the characteristics. Squamous tumors tend to be larger and more central than non-squamous tumors and then the fraction of proportion of brain metastases is present. There are some in HARMONi-6 and in other squamous cohorts. But it's far less common in patients with squamous than with adenocarcinoma and especially patients with EGFR mutation positive non-small cell where brain metastases are leading concern. But I would say, as I had alluded and the presentation yesterday as well, this is not just allowing patients with advanced squamous lung cancer, but this was bold and courageous in enrolling patients with several features that have historically been challenging, if not prohibitive with bevacizumab. And frankly, in China, they have years of experience, many of these investigators and growing comfort with that, that I would say that clinical oncologists outside of China or anywhere where they have less experience will need to not only look at these data, it's definitely going to be a point of education that we cannot be limited by and should not be limited by the historical precedence of a different drug with a very different safety profile. These are new times as the eligibility should be very different and liberalized. And yes, I think it will take both a combination of education and gradual experience for oncologists to get it, treat patients and reassure -- be reassured by their own favorable experiences with it over time.

Got it. And then just as a follow-up, do you think that the filing, has the FDA kind of indicated that this goes to ODAC. Will you be applying for accelerated or full approval? And your thoughts on European filings?

Yes. We think this is a good [ small ] package. We have statistically significant PFS. We have supportive OS data, which we think is very meaningful and will be evaluated in context. We have supportive efficacy data from OR and duration of response. So all seems to be a good [indiscernible] package for full approval. We cannot foresee what exactly the comments and the opinions of the FDA are. And as we said, as we're going through the review process and very specific information we get, then we will provide color on that. Other policy issues, I cannot comment on. We look all forward to FDA end up sharing with us what their plans are in terms of external feedback and those kind of things. So we will be watching that along with you.

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

Congrats on the data. Can you point to relevant regulatory precedents where a strong PFS benefit without a statistically significant OS benefit at the time of filing was still sufficient for FDA approval? And how do you think that -- can you just remind us how these situations were handled by the FDA? And then separately, can you just comment on the business development front on the change in the volume and the types of BD discussions you've been having lately?

I will take the first part. So in this exact setting in EGFR-positive previously treated patients, there were 2 relevant approvals, both of them occurred last year. The first one is for the [ Amuvatinib molecule ] based on the [indiscernible] study, which was approved on statistically significant [indiscernible], and was accompanied by a positive trend [indiscernible] OS. The other approval that happened as the accelerated approval is [indiscernible] molecule. Wording is slightly different, but it's previously treated patients with both chemo as well as [indiscernible] therapy, and that accelerated approval was based on ORR with the duration of response. And I can also note that the confirmatory study for that module in EGFR-positive in the frontline selling. So there isn't going to be any additional generation of statistically significant PFS, OS [indiscernible] was coming. Business development question?

Bob do you want to conclude with the business development.

This is Bob Duggan. We want to thank you for your attendance today. I only wish you could be at ESMO. There's at least 25,000 people here. We were really honored and Akeso was honored to be the first presenter at the presidential presentation with 9,000 people packed into a very large hub program. They gave resounding applause as they heard the data. This is a breakthrough. It's a break of magnitude. Undeniably, we have an excellent product. Lung cancer is the #1 killer. It's not going to be that way for long. We really are in the mitigation and hopefully, in some areas, we would move this forward even into [indiscernible]. Our team is very excited. We're very excited to have the product in our hands. The doctors, physicians those that support them are really excited. We've seen them in the hallways and in other meetings. We've been just packed with attendance and appreciation. You have to kind of be here to see. It's my first trip to Berlin, I must say it's a beautiful city, even for someone who lives in Miami. So yes, we're going straight ahead here, and we're enjoying ourselves. The future looks incredibly bright. Opportunities like this I haven't seen in my brief investment lifetime. I'm just really excited about helping patients here and making a significant difference [indiscernible]. I will say you see people from all cultures, all walks of life here. This health care business is one that brings the world together, not separates it. And we're just really happy to play a significant role, and we're thankful to our Akeso partners from China and to the FDA for giving us the platform which to really move forward. So thank you for being on the call. We look forward to talking to you soon. Have a great day.

Ladies and gentlemen, that concludes today's call. You can disconnect. Thank you, and have a great day.