will also be made available later today on our website, www.smmttx.com. Joining me on the call today is Bob Duggan, our Chairman and Chief Executive Officer, Dr. Maky Zanganeh, our Chief Executive Officer and President, Manmeet Soni, our Chief Operating Officer and Chief Financial Officer, Dr. Allen Yang, our Chief Medical Officer, and Dr. H. Jack West, our VP of Clinical Development. 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 our team, we will take questions. With that, I would like to turn the call over to Manmeet for some opening remarks. Thanks, Dave, and good morning, everyone. This morning, we announced that the company received and accepted an unsolicited offer from an institutional investor to purchase 200 million worth of common stock at $9 per share, a premium to the closing price on Friday, for aggregate gross and net proceeds to the company of approximately $200 million. This offer was accepted by the executives and approved by the board. In addition, we also announced an extension of our license territories for ivonescimab, via an amendment to our existing collaboration and license agreement with Akeso. Under the terms of this expanded agreement, now we will have Latin America, including Mexico and all countries in Central America and South America, in addition to Middle East and Africa. This expansion adds to the territories licensed by Summit earlier, which included United States, Canada, Japan, and Europe. In exchange for these expanded territories, the total deal value is worth up to $70 million. Now, I will hand the call over to Dave. Thanks, Manmeet. Before I hand the call over to Allen and Jack, I would like to take a moment to remind everyone of the four Phase III clinical trials to which we have recently spoken. On slide three here, starting in the top right-hand corner of the slide and moving counterclockwise, HARMONi-A is a randomized, single-region, multicenter clinical trial that was presented by Dr. Li Zhang at ASCO last Friday. This is the clinical trial that was sponsored and conducted by our partners at Akeso that is the basis for the approval of ivonescimab plus chemotherapy in China. The study evaluated patients with advanced or metastatic non-small cell lung cancer, whose tumors were positive for an EGFR mutation, and enrolled patients whose tumors had progressed after previously receiving an EGFR TKI. The next trial to the left is our multi-regional phase III clinical trial, HARMONi, in a similar setting. Our HARMONi trial is for patients who previously received a third-generation EGFR TKI. It also have evaluated ivonescimab plus chemotherapy as compared to placebo plus chemotherapy. The analysis for HARMONi intends to include all patients from the HARMONi-A trial who previously received a third-generation TKI, in addition to patients enrolled from the US, Canada, and Europe. Planned total enrollment for our phase III multi-regional HARMONi trial is approximately 420 patients, for which Summit intends to complete enrollment during the second half of 2024. Moving down, HARMONi-2, the HARMONi-2 clinical trial is a frontline non-small cell lung cancer trial, is a randomized clinical trial evaluating monotherapy ivonescimab as compared to monotherapy pembrolizumab in patients whose tumors had positive PD-L1 expression or a PD-L1 TPS score of 1% or greater. This is a single-region, multi-centered phase III clinical trial conducted and sponsored by Akeso, for which high-level clinical trial results were announced last Thursday. And finally, moving to the bottom right of the screen is HARMONi-3, our multi-regional randomized phase III clinical trial, evaluating ivonescimab plus chemotherapy versus pembrolizumab plus chemotherapy in frontline metastatic squamous non-small cell lung cancer. So with that, I would like to hand the call over to Jack to speak quickly to the HARMONi-A trial results that were discussed at ASCO last Friday. Thank you, Dave. On slide four, we have the schema for the HARMONi-A trial. HARMONi-A is a phase III trial of chemotherapy with either ivonescimab or placebo in Chinese patients with EGFR mutation-positive non-small cell lung cancer that has progressed on prior EGFR tyrosine kinase inhibitor or TKI therapy. Key eligibility criteria are shown here. Patients were randomized 1:1 and stratified by prior exposure to a third-generation EGFR TKI and presence of brain metastases at baseline. Patients received either ivonescimab at 20 milligrams per kilogram plus pemetrexed carboplatin, or placebo plus the same chemotherapy backbone, then received either ivonescimab or placebo in combination with pemetrexed as maintenance for up to 24 months. Treatment was to be discontinued for intolerability, no clinical benefit, or initiation of new antitumor therapy. The primary endpoint was progression-free survival by independent radiologic review committee. Secondary endpoints were overall survival, response rate, duration of response, and safety. Next slide. Here is the primary endpoint of progression-free survival by independent review, demonstrating a significant improvement for ivonescimab with a hazard ratio of 0.46, corresponding to a 54% improvement over the control arm and a median PFS of 7.1 versus 4.8 months, favoring ivonescimab. Next. PFS benefit was observed in both patients with baseline brain metastases, shown on the right, and those without brain metastases on the left. CNS metastases are unfortunately not uncommon for patients with EGFR mutant non-small cell lung cancer, and they comprised about 22%-23% of this study cohort. At the request of the Chinese Regulatory Authority, an early overall survival analysis was conducted approximately two months after the initial data cutoff, and with 30% data maturity, show an early separation of the curves. Next slide. That is maintained on a subsequent regulatory request with data maturity of 52%. Next slide. As would be expected, there were more Grade 3 or higher and serious adverse events on the ivonescimab-containing arm, though the difference in discontinuation rates was only approximately 3% between the two arms, and there were no treatment-related deaths. Grade three or higher immune-related adverse events were slightly higher in the ivonescimab arm, as expected, though there were no differences, no clear differences in VEGF-related Grade 3 adverse events between the two arms. Next. Specifically, the most common adverse events were hematologic, with rates of non-hematologic Grade three or higher adverse events, all 3% or less. Next. Immune-related events were as expected for an immune checkpoint inhibitor targeting PD-1. Interstitial lung disease was very uncommon, with rates comparable between the two arms. Next. While low-grade proteinuria and hypertension were more common in patients assigned to ivonescimab, as consistent with targeting VEGF, there was no increase in Grade three or higher bleeding or thromboembolic complications. Next. Thank you very much, Jack, and I think the next slide now shows the pipeline for ivonescimab, which includes trials run by both Summit, as well as those that have been previously or currently sponsored by our partners at Akeso. You see, in addition to the phase III clinical trials that are currently being conducted, there are several phase II clinical trials also in progress, being currently conducted by our partners at Akeso in China. This gives us substantial opportunity in terms of our ability to move forward with our next phase II and phase III clinical trials that we'll choose to move forward with, and we're very excited to move forward in the short term. And finally, on the, on the next slide, we see the headline, with respect to the first trial, that I earlier mentioned, the HARMONi-2 study, which we are very excited to provide more details at a major medical conference upcoming, likely in September. And with that, we'll now like to see if there are any questions, that our team can help answer. And so I would turn to the operator to see if there are any, open questions on the line. Thank you. We will now begin the question-and-answer session. If you would like to ask a question, please press star one on your telephone keypad to raise your hand and join the queue. If you would like to withdraw your ques tion, simply press star one again. Your first question comes from the line of Yigal Nochomovitz from Citigroup. Your line is open. Hi, Summit team. Congratulations on the, on the flurry of excellent data over the last several days. I think for those less familiar with this story, it would be great if you could frame and help people understand ivonescimab's mechanism action and why it's more than just the sum of the parts of a PD-1 and a VEGF, discussing how it was rationally designed. And in addition, the, the data on HARMONi-2 and HARMONi-3, how that potentially could translate to OS when, say, a study in IMpower150, there was, bevacizumab Tecentriq, worked on PFS, but obviously didn't translate into OS. Thank you. Hey, Yigal. Thanks for the question. So the first question is about the mechanism of action of ivonescimab, and I think the data, clinical data is continuing to support the hypothesis that this is differentiated in terms of PD-1. As people know that ivonescimab targets both PD-1 and VEGF, but the secret or the sort of the strength of the molecule is really that there's cooperativity between the binding ligands of PD-1 and VEGF, such that VEGF binding increases the binding of PD-1 by greater than 18-fold, and the binding of PD-1 increases the binding of VEGF by greater than four-fold. In addition, what's known because of the Morrison format and the fact that there are two VEGF binding sites, VEGF is a dimer, and then VEGF can cross-link different ivonescimab molecules. So you can have sort of daisy chaining of ivonescimab and VEGF, leading to multiple, the presentation of multiple high-affinity PD-1 sites. In addition, there are some other properties that we think are important. The molecule has been engineered to be Fc null, which we believe helps with immune-related adverse events, and it has a shorter half-life, which we believe helps with the VEGF-associated adverse events. The second question around HARMONi-2 and HARMONi-3, remember, HARMONi-2 is a China-only study, and I think, we want to be clear that it, it was never anticipated that we would be able to file on the HARMONi-2 data. However, given the strength of the data, we're going to sort of make every way possible to make this therapy available to patients as soon as possible. In addition, the question around PFS translating to OS, I would say that, you know, for HARMONi-2 and HARMONi-3, in other words, the earlier you make a therapy available for patients, the more likely that you'll have a translation for PFS to OS. There's always the risk that PFS won't translate to OS, but again, given the strength of the data and the trends that we're observing, it gives us very good confidence that we'll hit those endpoints. And go ahead, Jack. Jack, I would also just note that with some of these trials in the first line setting, there can be sometimes differential crossover. And this is a setting where in our trials, the patients say the HARMONi-2, they're everyone has been exposed to a respected, a good immunotherapy checkpoint inhibitor. And so they're after Keytruda really would not be any expected big change from a crossover to any. Subsequently, really you have things like docetaxel that would be available to both arms at equal rates. So I don't think that there would be any reason to anticipate much movement from crossover effects. Okay, thanks. And then obviously, with the very positive top line interim on HARMONi-2, could you just broadly talk about some of those thoughts in terms of how you might develop ivonescimab in the non-squamous population in the United States? What sort of trials might you envision that would leverage that, given, as you point out, and we appreciate that you may not be able to directly use the HARMONi-2 for U.S. registration? Yeah, Yigal, thanks for the question. We're not going to give details on that today. However, I will say that PD-1 and VEGF have been well-described targets. You can sort of look at the precedent molecules and see where they have indication. And so we're looking at that. And again, what's very helpful is that Akeso has been very prolific in their clinical trial program, so we have a lot of upcoming phase II data that we're reviewing to help inform those decisions. Yeah. Got it. Thank you. Your next question comes from a line of Bradley Canino from Stifel. Your line is open. Hey, good morning, and I will echo my congratulations to the team on a successful ASCO. A few questions from me. First, I was wondering if you could just walk through the process of how HARMONi-A data becomes incorporated into your registrational HARMONi-1 study, and when would it be reasonable for investors to expect the first BLA filing to the FDA? Hey, Brad, thanks for the question. I think, you know, for those following along, I think the easiest way, in some ways, is to walk through that is also from the press release that we issued last Friday, in terms of how that data gets incorporated. But I'd be happy to walk through that right now. So, excuse me, the HARMONi-A trial incorporated 320 patients, or a little over 320 patients who received the previous EGFR TKI. What we did when we established the deal was create a multi-regional Phase III study, the HARMONi study, and that will take all patients who previously received a third-generation EGFR TKI from the HARMONi-A study. And that was about 85% of the patients. The vast majority of the patients who were enrolled in the HARMONi-A trial will then become the Asia region for the HARMONi trial. So the HARMONi trial is a multi-regional trial, incorporating patients from China, from North America, and from Europe. And so about 85% or 276 patients from the HARMONi-A trial will be incorporated in the HARMONi study. And then we will, from there, enroll an additional 150 patients in the HARMONi trial to enroll a total of about 420 patients in total there. So we'll have multi-regional input from Asia, North America, and Europe. And that will be what is analyzed as part of our total study. I think, Brad, for the second question that you have in terms of when can we expect BLA filing? What we have said at this point is, for the patients from North America and Europe that we plan to, that we're adding to enrollment, we plan to complete that enrollment in the second half of this year. And so based on some of the data that, that Jack walked through, while we haven't specifically said when that BLA filing will be, you can, you can sort of back into when we would get to a data readout at that point. And hopefully, that's at some point in 2025, and then the, the BLA filing process that comes thereafter. Right. And then separately for HARMONi-2, how important was the consistent benefit for patients with PD-L1 high as you think about the potential for ivonescimab's development? Yeah, thanks. Thanks, Brad. I think... What I heard from you there, sorry, was how important was the PD-L1 high expressers in terms of our overall evaluation? So I mean, I think that's very important considering our mechanism of action. So I'm going to hand the answer over to Allen to really elaborate there. Question? ... In HARMONi-2 or HARMONi? Yeah, 2. Yeah, so I don't think we've actually disclosed that data, Brad. So, you know, HARMONi-2 has always been an interesting experiment, and as we've discussed in the past, it would inform a lot of our development strategy. It included patients that had a TPS score of 1% or greater, which is not currently the standard of care in the U.S. Now, ivonescimab targets both PD-1 and VEGF, and so the question we had always had scientifically is whether the benefit is predominantly seen in the patients that have lower PD-1 expression, suggesting that the targeting of VEGF is the true benefit, or is the cooperativity helping both patients with the low PD-1 expression, as well as, or as well as those with high PD-L1 expression? What I will say is that I will refer you to our press release, and we look forward to seeing you in September at that major medical meeting. If I can add anything, this is Jack. For me, I think it was extremely important that the press release specifies that the PFS improvement was observed broadly across the different subgroups. That included the low and the high, as well as adeno and squamous, and we'd seen extremely promising results in Squamous. And this really showed us it is not, it is not limited to any one group kind of pulling anybody else across the goal line, but rather that this is really seen everywhere. I'd also note that, of course, pembrolizumab was the first of these agents that was approved in first-line non-small cell lung cancer back in 2016. It changed everything, and it has been the pace setter with great results in high PD-L1. That was back in 2016, the first of them. That's been a high bar, and showing that you can beat pembrolizumab in a setting where it has achieved very well is a very strong statement. So it's not just winning in the setting where there might be some relative weakness, but winning across the board and even in an area where pembrolizumab has been known to be an extremely strong treatment, and you can hope to do better than that is a real statement, I would say. Okay, and then finally, last for me. Given that this weekend has served as a good introduction to ivonescimab, could you just give us highlights from your meetings with the clinical investigator community as you discussed the drug? And should we expect investigator-sponsored trials to emerge in the near future? Thank you. Yes, is the short answer. I fortunately have a history of decades as an academic or a treating oncologist, and I've been a close part of this tight community. So I have always been able to reach and share plans and develop plans with my colleagues who are thoracic oncologists. But I'll tell you, as you might imagine, that the news that had been anticipated at ASCO, compounded by the press release about HARMONi-2, has only increased everyone's interest. And so that is the first question that I get in my meetings that have been up and down all throughout ASCO of, "How can I work on this, whether it is as an institutional IST or a cooperative group, et cetera?" But we'll have many potential platforms and many eager partners for this. So for us, it is, our big challenge will be to prioritize what should come first for us. But we have a lot of different people to work with and cooperative groups who will be eager to be partners with us. Yeah, and Brad, if I could just take a moment to thank our investigators and the patients involved in our studies. You know, when we told our story, there were a handful of investigators that really sort of understood and took the time to understand the beauty of this molecule, and we wanted to thank them. You can only imagine now they feel sort of validated in that belief. There have been now new people approaching us. We had a very active IST program before in terms of, you know, patients approaching us, given, given the unique mechanism action and the known or familiarity with the targets, but that has only accelerated at this meeting. Great. Congratulations again. Thank you. Thanks, Brad. You're welcome. Again, if you'd like to ask a question, press star one on your telephone keypad. Your next question comes from the line of Carter Gould from Barclays. Your line is open. Good morning. Congrats on all the progress, and thanks for taking the question. I guess one for Allen and Dr. West. I guess particularly after sort of, you know, in ESMO last year, in which there was a lot of discussion in terms of sequencing of EGFR agents and, you know, the various approaches there. Can you just speak as you think about now, sort of ivonescimab positioning, you know, even as a second line versus, you know, some of the questions around, you know, how you position amivantamab and sort of how you see that playing out? And then maybe just a more pointed question to Dave and the team around sort of the next steps for clinical development there. You talked about some of the, you know, working with the Akeso, and they clearly have a broad set of studies going on. But sort of the timeframe for really kind of like teasing out that broader clinical development plan, is that something we should expect by the time we get to World Lung? Thank you. ... Okay, this is Jack. I'm happy to field things. I've had lots of conversations with my colleagues about their how they perceive the HARMONi-A data and how that may change the landscape. Obviously, at this time, it's not going to be commercially available to physicians and patients in the US. We have the ongoing HARMONi global trial. But I've also talked to them about the range of options. There's FLAURA2 and the potential integration of chemotherapy into the first-line setting, and there's amivantamab and potentially lazertinib. But, many, many of my colleagues, if not the majority, have a lot of patients who have been doing well on osimertinib for years, some for more than five years, and they are not eager to necessarily bring in chemotherapy and IV treatment in general into a setting where so many patients can do well on oral therapy for years at a time. In fact, one I spoke with yesterday shared that she has brought it up with several patients who have essentially categorically refused to consider it. So FLAURA2, and that concept of chemo and osimertinib is going to be a component for selected patients, but I don't think it is going to become the prevailing approach broadly. So I would say a lot of patients will have progression on osimertinib and still be chemotherapy naive or will not have received it for a long period of time and would be an appropriate candidate for the HARMONi or HARMONi-A approach. Of course, there is amivantamab, and we did see data from a few days ago that there's a subcutaneous administration that shortens the treatment time. But that has its own challenges that are largely related to toxicities not abrogated by the administration route, and specifically, the dermatologic ones that are a real challenge. I would say that it is somewhat in flux, but just showing that you have a therapy that can be such a critical component to significantly improving outcomes is an important message, especially when that is not saddled with accompanying toxicity challenges like some of the other competing options. What's the second part of the question again? The development program. Oh, okay. Yeah, so, I remember the question, and it was it more based around EGFR or lung cancer? I'll try to answer both, right? So a couple things. In the EGFR post space, it's pretty well-defined what we need to do to add on, given the changing landscape of different therapies, the FLAURA2 and MARIPOSA, and so we'll have a strategy around that. In terms of a broader development program, you know, we're very excited that HARMONi-2 answers the questions we need to be answered, but we've only had the data for a couple of days, and so we're not going to sort of tell you all of our plans at this time. There are no further questions at this time. I will now turn the call back over to Dave Gancarz for some final closing remarks. I really want to thank everyone for taking the time to attend our call this morning, and thank you very much for your continued and accelerated interest in Summit Therapeutics. An archived version of the webcast today will be available on our website, www.smmttx.com, and I really hope you appreciate the time we've taken this morning. Thank you for your time, and we hope you enjoy the rest of your day. Thank you. This concludes today's conference call. Thank you for your participation. You may now disconnect.