All right, good afternoon. Thanks, everybody, for joining Jefferies Healthcare Conference in London. My name is Clara Dunn. I'm one of the biotech analysts here at Jefferies. So sitting next to me, we have Chief Business and Strategy Officer Dave Gancarz and Manmeet Soni, Chief Operating Officer and Chief Financial Officer of Summit Therapeutics. Welcome. Thank you for having us. Summit is definitely a very well-recognized name in the industry. But just to set the stage for our discussion and for our audience here, can you share a little, a brief overview of the company? You know, what's your mission? What's the current development of your bispecific ivonescimab and your just broader strategic vision? Sure, happy to. Summit Therapeutics is a mission-driven organization. Our mission is simply put to make a significant difference for patients who are suffering from cancer. Our co-CEOs, Bob Duggan and Maky Zanganeh, have a storied history with their experience in not only biotechnology, but the healthcare sector as a whole. In our current state, we are focused, as I mentioned, on cancer. The way in which we are seeking to execute on that mission is through the development of ivonescimab, our PD-1 VEGF bispecific antibody. ivonescimab is a specifically engineered bispecific antibody, and its intent is really to improve upon the previously established efficacy and safety standards of those two targets. That intent is what we look to carry out our mission on. Very importantly, this is not a concept anymore at this point. And so there are over 3,000 patients who have been dosed in a clinical setting with Ivanacimab. And when you expand that into and incorporate the commercial setting in China, where the drug is approved, that number expands to over 40,000 patients who have received Ivanacimab. Currently, there are 14 phase III clinical trials. There are four global studies that Summit's sponsoring, in addition to 10 additional trials that are being sponsored by our partners at Kesso in China. So you can see the vast breadth and depth of the program from that point. And so with that, that becomes our mission, the execution path for our mission. Great. And you did have a lot of data events this year, and we will definitely touch on all of that. But maybe before we talk about the efficacy of Ivanacimab in broad indications, I also just want to take a step back and talk about the safety profile of Ivanacimab. As you mentioned, a lot of patients have been treated. And how's the patient experience, especially on the safety so far, compared to single-agent anti-VEGF and PD-1? No, thank you for that question, Clara. I think it's a really important point because as we speak about, you know, I talked about the molecule was designed by our partners at Akeso to improve upon both the safety and the efficacy standards that were established in those two targets, and specifically with respect to safety. Nothing illustrates the tolerability of ivonescimab better than the recently disclosed HARMONi-6 data by our partners at Akeso. So this is a single-region phase three study conducted in China that met its primary endpoint in progression-free survival. Importantly, it is in a space where anti-VEGF monoclonal antibodies really haven't been able to be developed. If we go all the way back to 2004 and the JCO paper that spoke to the difficulties of bevacizumab and the history of hemorrhage, and significant hemorrhage, you know, fatal hemorrhage events that took place for squamous non-small cell lung cancer patients, what we've been able to show through our partners at Kesso is the tolerability of IvanaciMab in squamous patients. And so that was very important. That was also demonstrated as a part of the Harmony 2 study as well in the monotherapy setting that included both non-squamous and squamous patients. And then when we take that forward in the Harmony study, the global study that Summit sponsored, we saw very consistent results with the safety profile that was demonstrated in the Harmony A study in China in the same setting in that second line EGFR mutant population. And so we saw consistency of that data between the East and the West. And then we saw two particular phase three trials whereby historically anti-VEGF has not been tolerated. And this is a place where we think there's a clear distinguishment when we talk about, hey, is it the VEGF contributing more? Is it the PD-1 contributing more? This is really where we speak to the novel mechanism of Ivanacmab that's really different than the two administered individually. Yeah, and I would add, right, this is distinguished, right, because we had engineered, right, our partner, Akeso, had engineered it so smartly, right, so that because of the cooperative binding, we see this impact, right? And another thing to note is the half-life, right? Half-life for IVO is approximately seven days, seven to eight days, which is much less than other comparable drugs and whether it's VEGF or PD-1 alone. And that cooperative binding and the half-life makes it, right, much heavier, having much better efficacy and reducing toxicity. So that helps us a lot. Since you already mentioned the ESMO data, HARMONi-6, perhaps we start talking about that first. You reported a higher ratio of PFS 0.6. Perhaps just help us contextualize that number. What does that really mean to patients? Squamous non-small cell lung cancer, I think, you know, historically has been really difficult to treat by just anti-VEGF single agent because of the hemorrhage risk you just mentioned. Can data from HARMONi-6 change people's perception on that? I think the best way to change perception is through data and through a randomized clinical trial, right? So when we step back, contextualizing the results as a whole, you know, a 0.60 hazard ratio effectively is intended to represent a 40% improvement over existing standard of care. When we started this journey, the first trials that read out were HARMONi-A, which was in the second line EGFR, ivonescimab plus chemo versus chemo alone. That was a place where the PD-1 antibodies had historically been unsuccessful, both from a PFS and an OS perspective. So the next question became, good, you were successful in a place where PD-1s weren't, how about going head to head? HARMONi-2, monotherapy ivonescimab versus pembrolizumab and head to head against a PD-1, that was successful. And the next question became, but the standard of care is largely dominated by chemo combinations. And some of these questions might have been asked by a lady to my left. And the, well, can you carry that forward? That's really what will be the dominant standard of care in frontline lung cancer. And can you show a result there? And so this 0.60 hazard ratio in Harmony 6 answers the third question of frontline, you know, the overwhelming standard of care across many solid tumors is immunotherapy plus chemotherapy. And so this was really the groundbreaking piece of rising tides raise all ships was the concern. And this was a clear difference, the curve separate and continue to separate really through the median follow-up time for Harmony 6. And so we see a median PFS difference of 11.1 versus 6.8 months. So there's about a four-month difference there in terms of just the median difference. And then the hazard ratio represents about a 40% difference in the single region study that was conducted by our partners at Kesso. And so that then reads into the global study that we're conducting with Harmony 3, which looks at both squamous and non-squamous patients. And that'll be the most direct answer to your question, Clara, with respect to changing care. But the feedback has been extremely positive from physicians, both KOLs and in the community with respect to the data at this point. Yeah. So Clara, one thing to add, right? If you remember 18 months ago, right, there were in early 2024, right, there were a lot of questions whether this China data will translate into, you know, Western patients, whether the PFS will translate to OS and the early OS will be sustained. And now we have answered all those three questions through these four positive trials, right? And that's how it is. It's a combination of the data and the safety, as Dave mentioned earlier, right, that we have now the safety pool of that over 3,000 patients. We don't update it on a monthly basis, but it is much higher now. And it's increasing as we are enrolling. And we already mentioned, right, Harmony 3 study, which is the squamous study, is now over 80% enrolled, right? So those tell you, right, that the safety efficacy is all there. And it's the combination of the data sets altogether. Great. And then you just mentioned Harmony 3 trial, the global trial. So I mean, recently you also shared an update of the patient number for the trial. And then you said you will conduct separate analysis for squamous and non-squamous populations. So maybe just walk us through the rationale here. Yeah. So I think on Harmony 3, right, we wanted to make sure that we have enough probability of success on both arms, right? Squamous and non-squamous, they are two distinct populations. And you know, there is different even the treatment, right, over their durations over there. And non-squamous is twice as bigger as squamous. And it's growing. So it was very important for us to make sure we have enough that we didn't want it that in future when we read out the data that one data set is more stronger than others. So now we have powered them individually in the same protocol. And that will allow us to have the squamous results much sooner. As I said earlier a few minutes ago, that squamous study, even with 600 patients, we are saying it's over 80% enrolled, right? So the data set, we said we expect to complete the enrollment in the first half of 2026. I can say that we are enrolling pretty good on that metric. And on non-squamous, it is expected to complete enrollment by second half of 2026. So you will see the data sets for squamous, right? The results should come out in second half of 2026. And in first half of 2027, you will see non-squamous. So we are accelerating the timeline because the enrollment is going so strong on both sides and making sure the probability is increased. And then how should we think about the timeline for pivotal readout? And are you going to conduct both PFS and OS analysis? That's correct. Yep, that's right. So for the squamous population, we've been clear that we plan to the data that Manmeet just spoke to in terms of second half of 2026, the intent there is that that would be a primary PFS readout. And then there would be an interim look at overall survival at that point in time. Great. And then also very recently, as CIDIC, your partner at Kesso also reported an updated data for Harmony A with an updated health ratio for overall survival at 0.74. So maybe just tell us a little bit more about the data. Like what's the key takeaway from that updated data, especially in the context of long-term overall survival benefit? Yeah, great question. And so part of what Manmeet just spoke to in terms of when we look at PFS translating into OS, and then there's also been a notion where anti-VEGF has been combined to monoclonal antibodies or a monoclonal antibody and a TKI. But there's been a lot of combinations of PD-1 and VEGF. And there's been good data with respect to progression-free survival. But does that always translate into overall survival? Anti-VEGF tends to compound adverse events over time. And so the longer you administer anti-VEGF, the more the toxicities tend to arise has been the notion. And that ultimately leads to either discontinuation of therapy, which is harmful in terms of achieving your OS standard, or frankly, those adverse events can become life-threatening at times. And so what this showed was that that notion that the anti-VEGF portion of the antibody is going to be a PFS driver and not an OS driver, it basically kind of broke that notion. It was direct evidence against the idea that this compound is going to be mainly PFS without OS. The first study that was conducted that was a randomized phase three is a randomized phase three that showed an overall survival benefit over standard of care. And so what we didn't see were discontinuation rates that were high. What we didn't see were compounding toxicities. What we saw was a tolerable regimen that over time showed an overall survival benefit that was statistically significant. And that's the single region study conducted in China. But it's the first phase three study that was run with Ivanacimab. And it's very important that that now has a statistically significant overall survival benefit as well. And then as you mentioned in the beginning, the novel mechanism. So do you think this sustained overall survival benefit actually offers any new insights into the contribution of PD-1 and VEGF benefit components? And we're seeing what appears to be a long tail effect with IVO and a point that, you know, many physicians we've spoken with have frequently discussed and agreed upon. So do you agree with that as well? Yeah, I mean, I think the IO tail or that long tail is generally, you know, associated with immunotherapy, right? And so the Harmony A data, as well as, you know, I would say the Harmony A overall survival curve and the Harmony overall survival curves were generally a consistent shape. The hazard ratios were generally consistent as well. The long-term follow-up analysis was a 0.78 with Harmony and a 0.74 on Harmony A. And so you can see that very consistent result, consistent shape of the curves. And so with that, you see what appears to be the IO tail there. And that further, you know, speaks to two things. One, PD-1 monoclonal antibodies themselves weren't successful in showing PFS or OS benefits. This showed both a PFS and an OS benefit. It appears to have that IO tail. And there's been a lot of discussion with respect to anti-angiogenic therapy for EGFR mutant patients. And so the contribution of both targets is clear. I think the one thing I would go further though is I often want to break apart from the idea of how much was PD-1 and how much was VEGF. I think what Manmeet spoke about in terms of this is a novel mechanism. This is different. It is, you know, through its cooperative binding capabilities, a new approach to treating cancer. And I think that's something that was demonstrated. Even when we look historically at PD-1 plus VEGF in monoclonal antibodies in EGFR mutant, we have not seen an overall survival benefit. But I think another thing to note is the sustained OS benefit, right? And Harmony A has already demonstrated, right? When we did the earlier maturity data cuts, right? At 50% maturity, right? It was around 0.79, 0.80. It was ranging at different times. Now it's 0.74 when it has matured. Same thing we have demonstrated on the Western patients' data in Harmony, right? Even after waiting like with the September data cut, which we did, it was coming into, you know, a significant number. So it is showing that as you sustain, right? Because you have to wait for the maturity of the data. And that has been pretty encouraging. And then before we move to Harmony trial, I also want to ask, you know, this is a second line EGFR mutation. So do you think this long-term overall survival benefit has any reason to frontline trial as well? Yeah, I mean, it's certainly a fair question. I would say it's difficult to make that assertion without the data. That's why we're running the studies. What I would point to though is the consistency of the results of the phase II and III data. And we saw that again, even with Harmony 6, the phase II data showed 11.1 months of median PFS. The phase III data showed 11.1 months of median BFS, right? So we saw that consistency in translating through. I think when we look at the frontline data, you know, some of that, there was longer-term follow-up in some of the phase II data that we saw there. This was presented at ELCC in 2024 with about 22 months of median follow-up time. And we're seeing that tail that you talked about. You know, it's a single arm study. It's a phase II, but you see that tail. You're seeing the consistent results when Akeso ran the phase three study. And so I think when you take the totality of all of this data, that's really what encourages most. Again, four phase III have read out, four positive phase IIIs. Different settings within lung cancer and now the 10 phase three trials that Akeso is running that are now well beyond just non-small cell lung cancer. We have that trial that's now up in microsatellite stable colorectal cancer. And so when we look at all of the, it's really the totality as opposed to kind of saying this one piece is this directly read through. It's really the totality of the evidence across all of the studies. And then for Harmony trial in second line EGFR mutated non-small cell lung cancer, maybe tell us what's the significance of this trial and what are the key takeaways from the data and especially in the context of, you know, BIOA submission as well? Yeah. So I mean, I think this is the first global study, right? And so this was, you know, a place where people were looking at the comparability of what was seen in the readouts from China and how that translates in. I think when we look at, you know, the gold standard of overall survival, we saw extraordinarily consistent results both looking at hazard ratios and medians. And so when we look at medians, basically 16.8 to 14 months, 17 months to 14 months when we compare the east and the west, when we look at hazard ratios at the same follow-up time. So Manmeet spoke about as we continue to follow the drug. And again, contrary to what people have assumed that you'll continue to get worse, we saw an improvement in overall survival with longer follow-up time. And so when we look at now consistent follow-up time, as we know, Harmony was enrolled sequentially. And so the follow-up times between the east and the west were different. But when we look at that, about 50% data maturity, if you will, number of events over total patients enrolled, we saw in China about a 0.8 - 0.82 at that point in time. We see in the west a 0.84. So remarkably consistent results at the same follow-up time, which is incredibly important when we look to, you know, as we continue to expand our development plan, looking at the results that are coming from our partners at Akeso, looking around at the standards of care, this becomes really important to show that. So I mean, that's first and foremost an incredibly important data point. And then secondly, this is an area of high unmet medical need, right? There's one fully approved regimen in this space in post-TKI EGFR mutant patients. And so this is a place where, you know, we believe Ivanacimab plus chemotherapy has a significant place to make a difference for patients. And hence, that's the reason for, you know, when we see the results moving forward with an application. There is no regimen in this space that has demonstrated an overall survival benefit that's been approved by the FDA. And so that's an important, you know, point as we think about the risk-benefit profile, which we, you know, in our review of the data is there in this space. And I guess based on your interactions with the FDA, like how should we think about the balance of importance of the primary overall survival analysis as well as the long-term follow-up data? Because obviously the changes in long-term data will likely be driven by ex-China patients. Yeah, I think I understand where you're going with that question. So as we said, we announced we intended to submit our BLA in this quarter. And part of that was really taking into account all of those factors, right? The consistency of the data the east to west, the long-term follow-up analysis that was performed. Understanding to your point, the FDA had asked for a statistically significant overall survival benefit. And so, you know, when we take all of those factors together, that's really where we come to the conclusion that we believe that, you know, this is meaningful in this space for patients and it's in the best interest of patients to move forward and this is our perspective. And you've also noted, right? None of the approved therapies have seen any OS, which got recently got approval, right? So yes, we understand the bar is high, but I think if you look at the combination of all the data, including Harmony, which has shown OS significant, Harmony A, right? There. So all those things will be combined and now we have much more data sets which will be coming in the next six to nine months. Great. And also you recently opened a new trial in colorectal cancer. So maybe talk about your opportunity there and your development path. Absolutely. So we've been clear from the beginning of this year that there's a significant opportunity in non-small cell lung cancer for Ivanacimab, but this is not a lung cancer drug. It happened to be the place where we started. And that's evidenced as well by the pipeline demonstrated by our partners at Akeso with so many trials outside of lung cancer. But obviously at ESMO 2024, there was data that was provided with FOLFOXIRI chemotherapy backbone that was highly encouraging. And we continued to run that phase two study with multiple chemotherapy backbones. We also enrolled patients in the United States in that setting. And so when we looked at the totality, we were able to compare several data points, different chemotherapy backbones, different follow-up times. We had multiple endpoints that we were able to assess, both safety and efficacy. And so that gave us the confidence with which to move forward in this space. And it was another example of a place where PD-1s have not been historically as active. There has been a VEGF component, but we think that the novel mechanism that exists here is explaining that increase that we're seeing in the efficacy profile to Manmeet's point with the half-life maintaining that tolerable safety regimen profile as well in the regimen. And can you also talk about your collaboration with Revolution Medicine about the RAS on inhibitors combination? Absolutely. We're extremely excited about this and we're looking to begin dosing patients early next year. And so what that really does is the next step becomes as we move forward as an industry in oncology, novel novel combinations are exceptionally important. And this is really the first step for Ivanacimab from that perspective. And so in walking through the tolerability of Ivanacimab, that gives us confidence with which to combine with several different targets. So the multi-RAS and the targeted KRAS inhibitors from RevMed are extremely exciting and are something that we watch closely. And it became very much a clear pathway by which we could look to combine and do what's best for patients. That is step one for us also in terms of, you know, potential combinations. We've been very clear that, you know, we believe we have a strategic advantage by not looking to combine with those, you know, molecules in our pipeline, but to follow the data to collaborate in a clinical trial collaboration setting, you know, with multiple other targets that exist. We can follow the data and then we can find where the data points to. I think we've talked about this historically, but we don't believe there's a single platform of ADCs that will become the standard of care across all solid tumors. And we've seen this with chemotherapy as well. There's not a single chemotherapy backbone that is, you know, the standard of care for all solid tumors. And so it's very important for us to, instead of, you know, looking to synergize within our own pipeline, really to follow the data to do what's best for patients. Great. And lastly, what are the key milestones in the next 6 - 12 months that investors should watch for? A lot of them, right? I already mentioned about obviously BLA filing this quarter, right? Which we plan to submit for Harmony for EGFR 2nd line, completing enrollment for squamous arm for Harmony 3 in 1st half of 2026, completing enrollment for non-squamous arm in 2nd half of 2026, and then finally pivotal data for squamous arm in 2nd half of 2026. So those are a lot of milestones in near term. And that's why that was the reason, right? We, you know, made sure our balance sheet is strong enough, right, to carry on for next, you know, 12 - 18 months. And now we are, we can say that we had $750,000,000 in the bank, right, after doing this latest $500 million financing. And that allows us to look to expand the lead that we currently have in this space. Yeah. And our success has been, right? The mantra for our success has been, right, focus, retention, and massive action. And by putting focus, we think we can achieve much faster than what anybody can do. And that is pretty much visible that we have already a lead in lung for over two years, right, based on other people who are following in lung and similar in CRC, right? Other companies are going to start their phase II, III. We are starting phase III. So that would be a distinguished, you know, we are ahead in the game. Great. Very much looking forward to all those milestones. And thank you so much, Dave and Manmeet, for this session. Thank you for all the audience here joining us. Thank you, Jack Clark. Enjoy the rest.