The Citizens Life Sciences Conference 2026

Mar 11, 2026

All right. We'll go ahead and get started. Good afternoon, everyone. Thanks for being with us to the second day of the Citizens Life Sciences Conference here in Miami. It's my pleasure to welcome Summit Therapeutics joining us here. Joining us is Dave Gancarz, CBO and Strategy Officer, as well as Allen Yang, Chief Medical Officer. Thank you guys both for being here. I never know exactly who's in the audience, who knows the Summit story, who may not. I don't know who's listening in on the webcast as well. I always like to start these discussions off with maybe a 2-5-minute overview of Summit as a whole. Sure. And really appreciate, Ren. Thank you for the invitation and happy to be here. Summit Therapeutics focuses primarily on our main pipeline asset, which is ivonescimab. We entered into a strategic partnership with Akeso Inc. in December 2022. That deal went effective in January 2023 for ivonescimab. Summit Therapeutics has the rights to ivonescimab in North America, South America, Europe, Africa, the Middle East, and Japan. Major markets, you know, effectively outside of China and Korea. As we look through the strategic process, what that involved was getting going in late-stage clinical studies as soon as possible. Part of the impetus behind that deal was really a significant amount of data that was highly encouraging in phase two in order to allow for that immediate progression into the pivotal studies. Immediately upon in licensing ivonescimab, we began by expanding the HARMONi-A study into the global HARMONi study, and that was performed over the course of 2023 and 2024. We've read that data out, and that was positive with results displayed at World Lung last year. That was statistically significant in progression-free survival, although not statistically significant in overall survival in the primary analysis, and part of that due to the follow-up period with respect to Western patients based on you know kind of expanding that study from a China-specific study into a global study that became with additional follow-up time of Western patients showing a nominal P value of less than 0.04. As we look through the strategic steps for ivonescimab frontline solid tumors was the core of the priority. We went shortly after initiating the HARMONi study. We launched HARMONi-3 in frontline non-small cell lung cancer in combination with chemotherapy. While that started as a squamous specific study, that ultimately became squamous and non-squamous. We had mature phase 2 data in frontline squamous non-small cell lung cancer in the AK112-201 study. That prompted us to go immediately into the squamous cohort once we saw the data from the phase 3 HARMONi-2 study in China, as well as maturing data from the 201, that same phase 2 study in the non-squamous cohort that went into both histologies. That brings us to a full frontline chemo combination study. We also have the HARMONi-7 study, the monotherapy non-small cell lung cancer study in PDL1 high expressing populations. Recently we initiated the HARMONi-GI3 study, which is a global study in microsatellite stable colorectal cancer. Four phase 3 studies are sponsored by Summit at this point, 3 in non-small cell lung cancer, and one in MSS colorectal cancer. Where do we sit then today based on some of the work that we've done as well as our partners at Akeso? Between the two companies, 4 phase 3 clinical studies have read out. At this point, 4 phase 3s have read out with positive data, it's been a good start from that perspective. All 4 are positive with respect to progression-free survival. In addition, HARMONi-A was statistically significant in overall survival in China, post TKI EGFR mutant lung cancer. 3 of the 4 have had some level of readout in overall survival. All three of those have had a hazard ratio less than 0.8, if you will, that generally accepted clinically meaningful threshold for overall survival when we speak to physicians, you know, KOLs, investigators, and so on and so forth. As we look forward, you know, we have quite a bit coming now in 2026. That includes the squamous cohort of the HARMONi-3 study has now completed enrollment. We'll look to an interim PFS analysis in the second quarter and then a final PFS and an interim OS analysis in the second half of 2026. The non-squamous cohort completes enrollment in the second half of this year, and then final PFS interim OS or final PFS in the first half of 2027, and then there is an interim OS planned. We haven't, you know, definitively guided in terms of when that is. That puts us in a pretty Good position with respect to upcoming events. We have the PDUFA for the BLA with respect to the HARMONi study in November of 2026 as well, so several catalyst events in 2026. I think finally the larger point, if you look at the totality of ivonescimab, 10 phase 3s currently being run by our partners at Akeso. We have the 4, there's a fifth that's ours, a head and neck frontline study that's multi-regional. That is being performed by a cooperative group in Korea called the ILLUMINATE study. Fifteen phase 3s throughout. Over 4,000 patients have now been dosed in clinical studies sponsored by either Summit or Akeso. Akeso has achieved approval in China for ivonescimab in two settings, and that has led to over 60,000 patients who have now been treated in a commercial setting in China. Good uptake there. I think the final point I would highlight is the enthusiasm, you know, across solid tumors from investigators. Over 140 clinical trials are registered on ClinicalTrials.gov. You know, a little over 40 of those are sponsored by either Summit or Akeso. That means there's a significant amount of interest globally, both in our regions as well as in China with respect to investigators initiating investigator-initiated trials in order to evaluate ivonescimab in several settings beyond those of which we have discussed. I think, thank you very much, right, for that overview. We'll dig in a little bit more on maybe some specific HARMONi studies. 'Cause I always get the nomenclature a little bit mixed up, two, three, A, right? All this stuff. Absolutely. I think, you know, we unanimously hear that this could be one of the game-changing molecules in in IO, right? There was Keytruda, Opdivo, right, Yervoy, and people have always been trying to improve upon that, right? Those are phenomenal molecules, and I don't want to say was. They are phenomenal molecules. Mm-hmm. We've been trying to improve on it forever, whether it's other checkpoints, right, combinations and the like. It seems like ivonescimab has really, you know, potentially cracked the nut. Can you just tell us the uniqueness of this molecule? I know everyone knows it's a bispecific, but the uniqueness of the molecule and, you know, if you had to pick, like, out of the many studies you highlighted, had to pick one study to showcase the ORR, the PFS, and the OS, what would it be? Okay, I'll take that. In terms of the molecule itself, it has two validated targets, PD-1 and VEGF. I think what was underappreciated at the time when that molecule came out is like, well, why can't you just give pembro and bevacizumab together? You know, there were studies with atezolizumab that went around and showed maybe some activity, no clear better activity than pembro alone. I think what people underappreciated was that the way the molecule was designed, it wasn't just targeting the molecules, it's the way that it targeted it. We talk about cooperativity, and when we talk about cooperativity, there's two types of cooperativity. One we call sort of allosteric cooperativity, where the PD-1 binding increases the binding of VEGF, and the VEGF binding increases the binding of PD-1. You get the tightest binding where you have both ligands present, which is the tumor microenvironment. The other thing that's underappreciated is that it's a tetramer, so it has two VEGF binding sites, two PD-1 binding sites. VEGF-A is actually a dimer, and what's been well shown is you can actually cross-link one Ivo to VEGF to another Ivo to another VEGF to another Ivo. This is what we call associative cooperativity. This cross-linking does two things. It presents these high affinity PD-1 binding sites. You can imagine multiple PD-1 binding sites binding to a T cell. We now have evidence that it actually causes clustering of the PD-1 receptor on the cell membrane, and that leads to actually internalization and degradation of the PD-1 receptor. We believe that's gonna be important as well. I think the take home message is that unlike the PD-1, PD-L1 story from the previous checkpoint inhibitor era, where there's about a dozen approved and they seem to be interchangeable, the format is gonna be very important. We think ivonescimab is not only the first in class, but probably the best in class. However, there's not enough data for the other molecules to sort of compare it to. I think as more data evolves and more data is compared, you'll see that the format matters. The one study that I think sort of demonstrates this the best is the HARMONi-2 study run by Akeso. That was a pure experiment. We always knew that that was gonna be important. That study was ongoing at the time of the deal, where Summit licensed this from Akeso. Monotherapy pembrolizumab versus monotherapy ivonescimab. You know, clear in non-small cell lung cancer, sort of a showdown between the two drugs. What we were very interested is looking at the data, not only would it win, we assumed that we would have an advantage in those patients that had low PD-L1 expression because of the VEGF. But what was interesting was that ivo beat pembro not only in the low PD-L1 expressing, but also the high PD-L1 expressing. We know that ivo is making the PD-1 aspect of the molecule better. You know, now there's good evidence that it's not only the sort of mechanical cooperativity, but there's probably some biological cooperativity because VEGF probably plays a role in, you know, immune sort of exhaustion and so forth. We're very excited about the molecule. The molecule has performed very well and, you know, several studies have been positive now. Can you just remind us of kind of the delta? Like, that's a great example, right? Sure. Head-to-head. Everyone asks in the IO space, like, "Do you have monotherapy activity? Yeah. This like concretely showed it, right? Yes. Now when you're going into chemo combinations or ADC combinations, no one can sit back and debate, "Oh, does it have monotherapy activity? Yeah. Can you just, you know, remind us of that benefit that you saw over Keytruda? Yeah. The you know the number. Yeah. Go ahead. Yeah. Hazard ratio in the monotherapy study, PFS was at 0.51, so about a 49% improvement over monotherapy, pembrolizumab. I think, you know, equally as important, following on to what Allan said was then that was tested, in the chemo combination setting as well, right? The HARMONi-6 study read out in frontline chemo combination, non-small cell lung cancer head-to-head at PD-1, plus chemotherapy. That also showed a significant improvement that was clinically meaningful, hazard ratio 0.60. Now we're seeing, you know, activity clearly in monotherapy head-to-head to Allan's point with respect to that monotherapy activity. Now in the, you know, what is the overwhelming backbone therapy in solid tumors? PD-1 plus chemo. You know, a clear separation of those curves within the HARMONi-6 study, performed by our partners, Akeso, in China that showed clear benefit, in that chemo combination study as well. Everyone, you know, kind of asks us about the HARMONi study, right? This is what you've just filed on. You have a BLA in November, or sorry, PDUFA date in November. It was a very anticipated, you know, data set, right? It was bittersweet. Like you hit in PFS, but the first look at OS didn't meet, but then as you mentioned, the second look, you know, did meet. Normally, you know, one would require some encouragement from the FDA, from investigators, something to kind of, you know, give you the gumption to go ahead and still file, right? you did. Can you just give us maybe a little bit of the background or, you know, why did you decide to just go ahead and file for this indication? Yeah. A couple key points, right, in terms of the setting. This is the post TKI setting for EGFR mutated non-small cell lung cancer. Osimertinib either as a monotherapy through the FLAURA trial or in combination with chemotherapy through the FLAURA2 study. That's an EGFR TKI, is standard of care, as well as the MARIPOSA regimen of amivantamab and osimertinib. That's your kind of frontline standard of care. Second, or post the TKI, you know, regimens are really a dearth of opportunity for those patients, right? That's amivantamab plus chemotherapy, is the only post TKI fully approved regimen at this point. Part of what becomes important, one is taking a look at what's out there from a landscape perspective or from, you know, what patients and physicians have the opportunity to in one regimen. I think there's, you know, general understanding in terms of some of the tolerability concerns within that regimen. When we look at the results of the HARMONi study, we see, you know, very, you know, reasonably consistent, if you will, results from an efficacy perspective, statistically significant PFS, and then, not statistically significant, but a good trend in OS both with hazard ratios and the 0.7s in that. But neither statistically significant from the, you know, the statistical analysis perspective. Very comparable on efficacy, and then we look at the tolerability and we do see a difference in terms of, you know, a tolerability profile for the ivonescimab chemotherapy arm that's, you know, when we get feedback from physicians that there's a high level of tolerability there. Anecdotally, we hear feedback with respect to, you know, treating physicians on the HARMONi studies. You know, it was ivo plus chemo compared to placebo plus chemo. Oftentimes, those physicians wouldn't know which of the two arms the patients were on initially because they weren't seeing tolerability concerns that would traditionally come from add-on therapy. A good, you know, kind of read through in terms of that. When we looked, you know, at the opportunity, we saw a lot of enthusiasm from physicians. We saw the package that we were able to have in totality, and we thought that was, you know, highly relevant to patients and physicians, and that drove the decision. Okay. I, you know, I don't wanna speculate on the regulatory interactions and what might be an ODAC panel or not an ODAC panel. We'll leave it at that. That's going to come, you know, one way or another in November. We do hear from clinicians and KOLs, especially when they're on scientific boards of other companies, when they're giving advice, they're already thinking about ivo, you know, being there and being, you know, one of the frontline molecules. It's that's already, you know, a good stamp of approval, I think, for it. Let's talk about HARMONi-3 just in the eight minutes or so we have left. You know, some people kind of challenge us, right? They're like, "Well, in HARMONi, they should have just waited longer with OS. They shouldn't have unblinded it together." You know, how do we know that something like that isn't gonna happen in HARMONi-3? HARMONi-3 now is the global study you guys have run, right? Following HARMONi, right, which had both patients from China as well as global. Yep. This is all you. How are you feeling about the statistical analysis? You just, I think at the most recent earnings call, said that we're gonna have an interim analysis in the second quarter. It was a surprise to me, maybe not to other people. Kinda just take us through how confident you feel about the stat plan and your pacing of, you know, the unveiling of data. Yeah. Importantly, you know, the HARMONi study was sequential enrollment, China and then, expanding into the US and Europe, right? This is a global study, you know, from the start with HARMONi-3. That involves, you know, multiple regions around the world, Asia, and you know, the Americas, Europe, but it's a traditional global study from that perspective. When we look at the, you know, the recent announcement as you referenced with respect to the interim PFS, important to note that there are two phase 3 studies that have replaced PD-1 and have been successful, right? Those are the HARMONi-2 and the HARMONi-6 studies. The only replacing of PD-1 to be successful is an ivonescimab-based regimen or based study, right? Both of those were successful in PFS at the interim PFS analysis. When we talk about learning from the data, you know, we've said this a lot in terms of the importance of learning from the data being generated by our partners at Akeso, in learning from data that we're generating here, always applying that information. This is an example. We read out the HARMONi-6 study at ESMO last fall in taking a look, seeing another study hit at the interim PFS that became important in terms of leveraging that information with respect to our design. The other piece in terms of, "Well, why do that?" is the easiest way to have a conversation with, you know, the health authorities, in particular the FDA, is to go with a statistically significant primary endpoint. Mm. Right? What that effectively does is pulls in that conversation with the health authorities in terms of a statistically significant, you know, primary endpoint should that come true within the interim analysis, and then that allows for accelerating that conversation and what does it look like in terms of bringing this opportunity forward to patients as well. We learned from the data that that has been generated previously, not once but twice, head-to-head against PD-1, and then said, "How do we, you know, make this regimen available to patients as soon as possible? Have you provided any more detail in terms of, you know, what the alpha spending is for this interim? If it hits, obviously everyone knows what happens there. If it doesn't hit, does it preclude you from other further analyses? Like, how should we be thinking about that? Yeah. No. This is an interim analysis. We haven't given details with respect to statistics other than to say the interim analysis is a higher bar, if you will. Mm than the final analysis, right? No, there's nothing that would preclude you know moving forward with the pre-planned final analysis that we had talked about previously in the second half of this year. Nothing changes that. It's a higher bar at the interim, certainly nothing that would say not you know meeting the interim then leads to the inability to hit the final analysis. One thing we've also said is in effect, we did not move the bar very much at all in the final analysis, so kinda maintain where we were to not really change you know probability of success throughout 2026, but bring in an opportunity at a higher bar based on what we've seen head-to-head with Ivo against PD-1s historically. that gave us the confidence to add in that step, if you will. There's, you know, in effect, if you think about it, there's no better read-through to a randomized phase 3 study than a randomized phase 3 study using your own compound in a very similar regimen, you know. Yep. In with a, you know, extremely similar control arm. We saw HARMONi-6, and that was, you know, highly positive and that gives us the confidence to, you know, pull in an interim PFS analysis and then, you know, take that opportunity to go forward in order to accelerate. I think some will say, "Hey, are you hedging?" Not at all. You know, in reality, we're not moving anything with respect to the final in terms of, you know, the bigger picture. What we are doing is bringing in an opportunity a little bit sooner. I think it's important for investors to also realize that enrollment for these large studies, this is a fairly large study, right? Yeah. There's 600 patients in this cohort. Enrollment went pretty rapidly, right? You've been able to maintain these. Normally, we see companies that are pushing out, you know, for one enrollment issue or another. You guys went very quickly. You're bringing in this interim, you know, into the second quarter. Now just help me understand or just correct me if I'm wrong. Interim in the second quarter, final in the second half. Yep. Interim OS in the second half. Yep. Final OS in the first half of next year, possibly? Haven't talked about final OS. Okay. Yeah. We're always very clear when we guide, we wanna be, you know, reasonably certain about something, and so that we're not, you know, constantly moving things around, to your point, in terms of changing timing. We haven't given timing with respect to final OS, but there would be an interim OS look in the second half of this year, as well as the final PFS if necessary in the second half of this year. What we've said is in the non-squamous portion also, that completes enrollment in the second half of this year to be able to look at final PFS and then, you know, around that period, an interim OS. Both squamous and non-squamous. Yeah Right? Yep. Coming out, which is great. Like, everyone's gonna be, you know, looking out at that. We only have about. I could talk to you guys for a long time about this. I, you know, we're really fascinated by the molecule. We love the data that we see. Seems like it's gonna be a game changer. I guess I'd love to, you know, maybe take a step back and think about strategy a little bit. We know from Merck, you know, how they were able to get Keytruda to be the best-selling checkpoint inhibitor, right? By a significant amount, right? It's not like there weren't fast followers, right? But clearly there was a game plan there. As you think about ivonescimab, is it, you know, this BLA that's coming up? Is it the squamous, non-squamous data from HARMONi-3? What is it that kind of triggers you to, you know, really kinda go out and get the broadest footprint possible for ivo? Is that even like, you know, part of the plan, or do you wanna, you know, kinda slowly grow this and just have maybe a partner come in and take over? Give us an idea as to how you're thinking about this. Yeah. I'll name a couple bullet points. I wanna make sure Alan has a chance as well. A couple of important things. Cornerstone indications for the PD-1 VEGF class are, you know, non-small cell lung cancer as it was for the PD-1 class. A place where PD-1s were not successful in microsatellite stable colorectal. First two tumor settings that we took a look at is others, you know, if you will, in class are looking at, you know, starting phase 3 clinical studies in first line non-small cell lung cancer. We're now talking about readouts in that path forward. That's a pretty significant difference with respect to placement there. Obviously, we are enrolling now in the colorectal setting as well. What differentiates here? 4 phase threes have read out for ivonescimab. There are 4 that have read out for the class, right? Only ivonescimab has had a readout, 4 for 4. Alan made a really important point. These are not monoclonal antibodies interchangeable. If you make a difference to the molecule construct that, you know, when you're 4 for 4 in ivonescimab and you're gonna make a change to that, there's more room to go down than there is to go up. That's one. Two, the 10 phase threes being run by Akeso right now. That speaks to the broad applicability of ivonescimab because there's obviously data supporting moving ahead there. That, that's another differentiator. We do plan to go much more broadly, but what we are gonna do is kind of give you that information as we're ready to enroll as opposed to showing everybody else where to go and where to start planning, right? That becomes important. Anything else that Yeah. No. I would just say that we're going after all of those, right? Like I think Dave mentioned that non-small cell lung cancer is our anchor or cornerstone indication, right? With the studies we have on hand, you know, we will probably, you know, sort of corner the market on metastatic non-small cell lung cancer, right? That's probably about 80% of the market. The one indication that could actually be bigger than non-small cell lung cancer is microsatellite stable colorectal cancer. We have a phase 3, and we're ahead on that as well. You know, I think those are the important cornerstone or anchor indications, right? If you look at how Merck beat atezolizumab and Nivo in the old days, it was because they won in lung cancer, right? Even though all three of them started about the same time. Now we're looking across all the indications, right? With our Akeso partners, you know, we're running 4 global phase 3s. They have over 10, so there's like 15 phase 3s running. You should probably ask yourself like, "Why aren't we doing certain indications?" Like Akeso's doing TNBC. They're doing small cell lung cancer, right? They're doing pancreatic cancer. It's not that we're not able to join those studies. We think that the standard of care in those diseases are going to change, and so maybe we're waiting for something to happen there. And then the other indications you'll hear more. I think Maky, our CEO, sort of alluded to that you'll hear more phase 3s out there. The idea is to go after all of these things in parallel. I think it's important for investors to also know that you guys are disciplined, you know, with the utilization of your cash. You've set up some collaborations with Revolution Medicines and GSK so that you're not necessarily growing this R&D engine to come up with new ADCs or new combination metrics. There are potential partners there to work with. That's an important point also because what we're not gonna try to do is force the optimization of our own pipeline, right? So we're gonna follow the science. We're gonna go out. We're gonna combine with several different ADCs. We've seen there isn't a single ADC platform that is optimized across solid tumors. So we can combine with platform A in this setting, platform B in this setting, and that, to your earlier point, what led Keytruda to be as explosive as it ultimately ended up being. Merck was able to go after each of those different combination agents or different settings based on following the data as opposed to trying to optimize within its own pipeline that may not be the optimal combination in each setting. Terrific. Dave, Allen, thank you very much for coming. I apologize for going over time. All good. Really appreciate it. Thank you. Thank you.