Great. Good morning, everyone. It's my pleasure to introduce the Summit Therapeutics team. With us, we have Bob Duggan, co-CEO, with Meki Zangane, co-CEO, Manmeet Soni, CFO, Alan Yang, CRDSO, and Dave Gangars, CBSO. To start here, a big picture question. Ivo's the leading PD1 or L1, VEGF asset in development and China-based Phase 3 frontline lung cancer survival data was just recognized by the plenary at ASCO. Walk us through your overall strategy here, including across the various tumor types and combination approaches as you look to maintain your position and expand upon global development.
Yeah, we're trying to keep that a little bit close to our chest because every time we announce something our competitors announce the same thing and say we're going to do it as well. But, you know, when we think about PD-1, VEGF, first of all, I think that PD-1 versus PD-L1 does make a difference. I don't know if it changes too much your strategy, but it might change your overall baseline efficacy. But with that said, you know, three years ago when we were looking at this asset, we did the boil the ocean exercise. We looked at all the PD-1 indications, all the VEGF-approved indications. There was a lot of sort of history around those two targets, that they're validated targets. And we looked at where we could go and where we can contribute. So part of that is you look at PD-1, you look at BGF, you look at where those agents are approved. The overlap, like lung cancer, seems like a great target, and we're going after lung cancer. And what's interesting about the class is that when you look at the data that, you know, a KESO has generated, there are some targets that are very interesting, right? So it was very surprising to me that there was so much activity in CRC. We knew that there was an Avastin effect, but I think it's beyond that. So CRC is something that we've disclosed. We have an interest in head and neck cancer, right? So that study has been announced as well. And so, you know, we have that ongoing collaboration with Illumina, the Illumina study with Gore-Tex. So we're going after head and neck cancer. I think people weren't understanding that until they saw this recent data at ASCO showing the activity. So any PD-1 VEGF we're very interested in. Lung is our core, right? That is the biggest indication in PD-1s, and so we think owning that space is very important. That's why we have the Harmony 3 study, the Harmony 7 study, the Harmony study. The only indication that can rival that in unmet need is probably CRC, microsatellite-stable CRC, and that's why we have the GI-3 indication going. I think the Gore-Tex study ahead and neck is also very important, not as large an indication. But if you look at all the other indications, we are actively looking at them. A lot of times it becomes a business decision. How much better than Pembroke do you think we're going to be? And that's always our competition, it seems like, in most indications. And if you're expecting me to name those indications that we're planning in the next year, I'm sorry, I can't give those to you today.
As a standalone company without a multinational partner, do you think that your balance sheet and strategic perspectives alone are intact? And I guess really how do you think about it as you look to address the $90 billion-plus checkpoint oncology market?
Yeah, we've always said there will be dilution here. It could be 5 percent. It could be 10 percent on an annualized basis. You should invest with that. We'll do our best to better that as we can. This is a business that either go it alone, you can partner with someone that can assist you with sales and marketing, or you can merge. All three of those opportunities we will factor in. We're here for patients first. We also are here to make sure that wealth is created not only for patients but for all participants. So we think we're doing a good job of that. We think there's plenty of opportunity there. And we think we are the causative source as to any one of the three choices. And right now we enjoy the position we're in. Clearly on the big pharma side, OS is a major factor. But we have on the drug two OS readouts, one nominal. So we have three OSs. No one else has touched that. No one else has touched Pembro. We're at 36% less chance, 34% less chance of death. with a Pembroke equivalent, we think we're actually in a very profound and positive position moving forward. So we have an ATM. We have access to capital. We're in touch with those on the street that can provide that. I've participated in each of the fundraisers and would look forward
to continuing to do so. So I hope that gives you some color. And just to frame the discussion we're going to have here, what are the key events and milestones that we should be focusing on over
the next 12 months? Yeah, so certainly we have, over the course of 2026, we have our final PFS readout for Harmony 3 Squamous. Shortly thereafter, in the first half, rather, of 2027, we have the non-squamous readout for PFS as well. So in terms of short term, we have immediately two market opportunities reading out in the second half of this year, first half of next year, and then we also have our BLA in the post-TKI EGFR mutant with PDUFA date of November of
And Salvin, if I may say as well, the trials, they are going, I mean, we are really enrolling the patients very fast. Some of the trials really six to nine months is ahead of schedule on the non-squamous. But the Harmony 7 is moving very fast, and CRC as well. That has to be in consideration of what Dave is talking on the, you know, the readout very soon, hopefully.
In the Harmony 6 overall survival data that was presented at ASCO, Ivo demonstrated a 34% survival benefit over 10 Vibra at a hazard ratio of 0.66. Can you frame the results in the context of your global programs and speak to any KOL feedback post the plenary session.
Sure. So I want to pause for a second with what you just said. This is the first randomized Phase III study to ever go head-to-head with PD-1 plus chemo and show a statistically significant, clinically meaningful overall survival benefit. Full stop, right? There's never been a drug that has been able to replace PD-1 inhibitor therapy and show both a PFS and OS benefit in this case. And that's really important because we've replaced the PD-1 therapy in this setting. And so with that, there's now an overall survival benefit. So when coming into ASCO, it was really important. One of the remaining questions was, hey, you've shown strong PFS benefits. Harmony A was statistically significant. Harmony showed the nominal p-value that implied significance. But in the frontline lung setting, this is really the cornerstone of where, you know, Pembro and the other PD-1 inhibitors have really dug their heels in in terms of entrench. This has now gone, Ivanesimab has gone head-to-head against the PD-1 regimen and shown a statistically significant overall survival benefit. So I think that's really important to be clear on. I think with respect to what does this mean for the program globally, you certainly don't feel worse going into the rest of the program now knowing that, right? And so that certainly improves confidence with respect to what does this mean globally. I think there is also a really important concept here as well. People talk about, hey, there's a VEGF inhibitor as a part of, or VEGF inhibition as a part of the novel mechanism of ibanesimab, historically we've seen VEGF inhibition degrade from PFS to OS. And one of the things that you heard us talk about over the past six months is that's not something that we expect in the front-line setting. What we now have coming out of ASCO is a PFS benefit and an OS benefit that statistically are highly consistent and highly correlated, right? So a .60 in PFS, a .66 in OS, but what that really represents is statistically our numbers that are very close together and highly correlated, so we're not seeing a big gap between PFS and OS. That's the key takeaway, right? As we talk about, you know, I think I'm going to guess here, but one of the questions that we tend to get a lot from the street is, hey, what's a clinically meaningful benefit? What does this mean in the West? What do you need to achieve? And we've always been pretty clear that, you know, from a KOL perspective, community perspective, the academic and treating community at large, 0.8 hazard ratios and overall survival was kind of a gold standard benchmark. What we now show is a wide buffer with respect to what we see in the Harmony 6 trial from what that OS gold standard benchmark is. And we also see highly correlated PFS to OS. So as we take that forward, we now have more confidence with respect to the global applicability of Ivanesimab in terms of its ability to show an overall survival benefit based on a few of those points. So you asked, you know, more broadly, there's been some noise with respect to the forest plots of the Harmony 6 trial showed a benefit for all patients. No patients crossed the hazard ratio bound of one. And so, but hey, maybe there were, you know, somewhere within the 20 or so cohorts, we saw one that was a little bit, you know, a little bit more spread than others, and that was age. And so I want to hit that point head on as well, because I think that's something that people have spoken to. And so one, all patients received the benefit, period, right? There were no patients who had a hazard ratio that crossed one. Secondly, as we talked about at ESMO last year, when you do not stratify for every subgroup or every variable, you will have some imbalances across those. And specifically with those patients greater than 65 in the TISLI arm, the Tivember arm, and those patients greater than 65 in the Ivo arm, there was an imbalance, and there were prognostic factors or those components that maybe favor the outcome more so on the Tevembra side. So, for example, the median size of the lesion was larger in that subgroup in the Ivo arm. There were more distant metastases. There were more brain metastases at baseline in the Ivo arm. And so those sorts of things can happen in a randomized Phase III study. What we still saw, even with that, was a benefit for Ivo in all scenarios. Finally, this is the fourth phase three. So not only by starting do I talk about this is the first trial ever to go head-to-head against PD-1 plus chemo in solid tumors and show a statistically significant benefit. There was another study that went head-to-head against PEMBRO in the Harmony 2 study that was monotherapy Ivo, monotherapy PEMBRO, and showed the benefit in PFS. We just haven't reached the OS readout yet. That showed highly consistent results greater than and less than 65. I also have the Harmony and the Harmony A, the second and third phase threes to read out. Those also showed highly consistent benefit less than and greater than 65. So three other phase three studies all showing a consistent benefit less than and greater than 65. And so when we look across this, the question becomes, hey, is this something that worries you? No, it doesn't at this point in time because we have the totality of the evidence across all four phase three clinical trials is very strong.
Yeah, and I would just add, Helene, when I was talking to physicians after the meeting, you know, they're very excited about IVO, right? I think Summit has a tradition of drawing very tough sort of discussants in our presentations, but, you know, I think she sort of missed the point of that presentation, right? We've now proven an OS benefit. The PFS can transition to OS benefit. It works as a monotherapy. It works well in combination with chemotherapy. That doesn't mask the benefit of IVAN-SMF. And I think that presentation sort of sets Ivo as the leading molecule in a new class of agents, and that was the importance of that presentation, right, that she sort of totally missed. It's not just about lung cancer. It's about all the PD-1 VEGF indications that are addressable. It's not a question of does this drug work. It clearly validates the class. It's just how big is this class going to be, and that's the more important question.
To follow up here in your Harmony 3 study, the global lung cancer trial, how are you accounting for imbalances on baseline characteristics? And I'm saying this in the context of the translation from, you know, the Harmony 6 trial to yours where the U.S. patient population.
Yes. So the Harmony 3 and Harmony 6 study are very similar in a sense. You know, in tradition, in China, they do cap enrollment at 75. That's not an unusual thing. That is a common thing for Chinese studies. In the U.S., we tend to be more sort of liberal in terms of the age. First of all, I want to say that that was the only study that showed a difference in the hazard ratio of age. The other thing I wanted to point out, it still showed a slight benefit. The hazard ratio was still under one. There was no detriment, right? So, you know, traditionally what you do in a study is you balance for criteria that you think may impact the outcome. You know, the location of metastases, you know, the region, as well as, you know, the PD-L1 expression. So those things are accounted for as in stratification factors for randomization. To date, we have not seen age as an important factor. And the other thing, too, you know, the discussant made a big point of bringing this out, but had she looked back at the ESMO presentation in 2025 where they presented the PFS, they saw this age. The hazard ratio was 0.88 for the age greater than 65, but they had counted for that by imbalances in terms of other criteria, brain metastases, size of the lesions, and so forth. So, again, I think there's always going to be the statistical noise, but if you look at that forest plot, there's nothing that crosses over to the right side or goes above one. Everything is still under one. So we still expect there to be a benefit broadly across patient groups.
yeah the only other thing I would add to that it's really important to remember that overall across the study across the two arms those are balanced those pieces are balanced it's when you get into a subgroup and then you look at the balance across that subgroup so across our Harmony 3 study just like in Harmony 6 in totality across the Ivo arm in total in the Tisley arm in total in their study and our study across the Ivo arm in the Pembro arm So those criteria are balanced.
For the Harmony 3 study, you recently disclosed in the squamous population interim PFS analysis, and it did not achieve statistical significance despite read-through from Harmony 6. Can you speak to what drove the divergence here? Was it event maturity, the higher statistical bar, or other factors such as control and performance or regional differences?
Yeah, and it's a good question. and I think we really haven't given details with respect to the statistical plan, but I'll make two points, one of which is we had one specific purpose when we were looking to include this, and this was a late addition to the study with respect to the interim analysis, and that was we already have a substantial lead within the class. And so this was an opportunity really to take the readout in the second half of this year that's already planned and look to accelerate that by even more time, you know, roughly six months or so, in order to have a conversation earlier with the health authorities. So anytime you have an opportunity to speak with the health authorities with a statistically significant primary endpoint, that was a calculated risk that was taken. Obviously, follow-up time was a little bit different with respect to Harmony 6 within our study and whatnot. But I think the calculated risk was for that very specific purpose. I think overall, as we look at the final analysis at the end of 2026, there is a meaningfully different bar in terms of the thresholds to achieve there. And so that's also an important point. It's not the same bar, you know, looking again and hoping to change things. This is a meaningfully, you know, higher bar in the interim than what we'll see in the final. And obviously now that you have the information with respect to ASCO, the high correlation between the PFS and OS is also very
relevant as well. What do you view as the bar for the final PFS analysis in the second half, and how should we calibrate the probability of success here? Yeah, I think we've seen overall
the data. So if you take what we saw in Harmony 6, and then you take also Harmony and Harmony A, Harmony 2, all of the data is pointing to and trending to in the same direction. So we have over 4,000 patients who have been treated in clinical studies with Ivanesimab today between And so the totality of that information we're able to look at and really understand, you know, cross-histology, cross-tumor types, early-stage, late-stage clinical trials, so on and so forth. And the totality of that evidence really points us into where our confidence sits on the trial as a whole. I think if we look at individual points for thresholds, I think it's obviously important to set up statistically significant and clinically meaningful trials that show a statistically significant and clinically meaningful bar. And so that really becomes our threshold for both PFS and OS.
And how are you thinking about the interim OS read at the same time?
Yeah, and that's a great question, right? And so the second half of this year is the final PFS. So historically within trials we look at OS as well to ensure that you don't have any sort of detriment to survival. We are not looking at the interim overall survival in the second half of this year as a be-all, end-all, make-or-break for that endpoint because we have additional looks set up in the future. And so it will be important to show that there's no detriment there. However, what I don't want that to be misconstrued as is any lack of confidence in that endpoint. So there are other in-class trials that are being run in the Phase III setting. So Bristol-Myers and BioNTech are running their study in frontline non-small cell lung cancer as well. They have taken out overall survival as a primary endpoint, and they have a PFS sole primary endpoint. We have not. We have a PFS OS primary endpoint. The reason why we will maintain overall survival as a primary endpoint is because we strongly believe in that endpoint for this drug in this setting in this trial. And we see that validated through the results of Harmony 6 as well. So we have no hesitation whatsoever with respect to, you know, where we are looking with respect to IVANES and MAP in the future.
Great. And one last question here on Harmony 3. So for the non-squamous cohort, we'll see final PFS analysis in the first half of 27. What gives you confidence in the readout and maybe speak to the mechanistic or structural differences between the squamous and non-squamous population? Adam?
Yeah, so, you know, when I started oncology, which was, like, a long time ago, they were actually treated as one group. So, you know, a couple things. I think let's talk about the differences and why we're confident. So, you know, the chemo backbone is a little bit different. You know, for a non-squamous, they use pemetrexate instead of a taxane. The pemetrexate stays on as maintenance, right? So traditionally, you know, adenos or non-squamous tend to do better in terms of OS and PFS with treatment. With that said, we're confident, because if you look back at the Phase II data, there was a benefit, right? If you look at the Harmony II data, which was monotherapy, ivanesimab versus monotherapy, pembrolizumab, it showed a very clear benefit both in the squamous group and the non-squamous group, and that benefit was about the same, right? So finally, when you look at the study, you know, we believe that it will work. there are some adjustments you have to make because non-squamous patients do better overall. They get a little bit more chemotherapy, so the treatment effect may be a little bit harder to detect, but that's why the non-squamous cohort is larger in size, right? And it may not be that you need more power. You just want to bring those events in soon enough that you can see it in a reasonable amount of time. Now, finally, the leap from squamous to non-squamous histology is actually not that big. I get the concern, but think about the jump from squamous non-small cell lung cancer to microsatellite stable colorectal adenocarcinoma, another adenocarcinoma. We see good activity there. Again, I think the biology is such that this molecule is going to be broadly applicable, and I want to say that we have the superior molecule as well. Yeah, the one thing I would
add to that as well is when we look at the phase two data that was generated in both settings, right? And so when we initially entered into the deal with Acheso, there was strong squamous phase two data, frontline lung cancer in combination with chemotherapy. Because of the enrollment pattern, our partners at Acheso had enrolled the squamous cohort first, and then the non-squamous cohort was enrolled afterwards, and so the data took a little bit more time to mature. So in addition to what Alan said with respect to Harmony 2, the other thing that's really important is the Phase 2 data in both squamous and non-squamous was very important in Phase 3. Our partners at Aqueso effectively replicated what they saw in Phase 2. That was the AK-112-201 study, where there was an 11.1-month PFS benefit in the Phase 2 and an 11.1-month PFS benefit in the Phase 3 Harmony 6 study. And then we saw overall survival at ASCO. And so when we look at the non-squamous cohort, we also see highly encouraging data in that setting as well. And so part of that is also it's everything that Alan spoke to in addition to some Phase II data underneath that to support them.
Bob and McKee, with multiple PD-1 VEGF drugs in development here, how do you support the view that Ivo is not just first-in-class but also best-in-class, and what data would prove this differentiation? And it was, you know, in that context, interesting to see the CRC data at ASCO versus competitors.
Jump and I'll follow.
Okay. I mean, it's for sure, you know, once you have a drug that is going to perform, you know, it's very obvious that left and right you are going to have other pharma, biotech. They are going to start to develop other molecules. The interesting part was when we started with the VGF PD-1, nobody was there. Nobody believed in us. And it was like a two and a half years ago. And that was really difficult even at this moment of time to enroll one patient. Now you are everywhere. Everybody is talking about VGF PD-1, which is great for us because that shows that we were right at this moment of time and we continue to keep our positions and being leading this process, I always say, you know what, we'll see at the end how everything will go. Every single patient deserves any drug that these work into, but at this moment of time, especially I can say the data of Pfizer versus us, you see the overall response rate, for sure it's a lot of different things behind this trial that I know that Alan can talk more in details, but that shows as well that even in this regard, at minimum in this therapeutic area, we are leading even on the safety and efficacy process. So, yes, other drug existing, we continue to execute. We focus our attention to where we are, our drug, our clinical trials, And, as I mentioned multiple times, and I'm very proud to say that you cannot right now find any VGF PD-1 inhibitors or this by specific that is in a multiple clinical trial. I mean, we have 47 sponsored trials, 15 phase 3, 155 including all of the collaborations. If it's with other ADC, if it's the KRAS inhibitors, if it's ISD program. So that is really interesting right now. We are enrolling, but in two, three years from now, even one year from now, you will see one data after the other will hit the market, and that is the beauty of the strategic work that the team did during the past two years. And as well, I can say, even from financial part, you will see it's very cost-effectively we are doing all of our trials. I mean, AKSO leads with a phase two, we catch it on the phase three. The IC program is really giving us a lot of information while we are moving along the way. The collaboration with the big farmer right now is as well something that over time you will see how we did our deal of collaboration. So all of them, I can say, I'm proud of the way that the team works, And I'm sure, you know, the sun will never stay behind the clouds. It will come very soon.
Our team, the top ten people have worked together for over ten years, and we've had extraordinary success where others wouldn't go. We didn't succeed by following. We succeeded by leading. We went to China when only Chinese went to China four years ago, and the American press was, like, allergic to it. That's not the case now. There's not one big pharma company that won't straight out admit that China is the leading developer of novel therapies. And it's not because some of them don't have American citizenship. It's not because some of them weren't educated in America, because they're hardworking, smart human beings benefiting the rest of us. And it's not that others won't catch up. We saw the bispecific type of valent. I think very few people knew what it stood for, knew what it meant. And the KESA is the source of the bispecific tetravalent. PEMBRO is a monospecific bivalent, and there is no comparison between the two. If you need an enemy going after cancer, you're going to pick the bispecific every single time. So we made two immediately great calls there. We paid half a billion dollars, raised $500 million overnight without commissions, launched into the partnership with the KESA. So 70% of what we, 80% of what we remain to owe them is on revenue payout at the $10 billion, $20 billion, $30 billion. These are monies that I really, as I sit here, hope we pay. We pay those monies, and we're not sitting here at an $11 billion market cap. You know, five years ago, SpaceX had a quarter of a billion market cap, and it's sitting there probably within the next few days at $1.7 trillion. I will tell you that Bi-Pacific Tetravalent will dose over a million people before anyone will colonize Mars. But pick what you want here, but this is a business that is every bit as big as the GOP. The GOPs are at $100 billion, and prices are coming down. We're also at that $9,800 billion market cap, and someone's going to get value and pay for it. Pembro will generate over $60 billion in the next three years to tail into what it produced. Meanwhile, we're trading at $11 billion, and we have D-Lead. There was an ad by Merck at ASCO saying, you know, 20 years of Pembro success. Now's the time for a little change in the approach. And they went dot, dot, dot, and it's a sub-Q therapy. And I put after dot, dot, dot, it's abenicumab. So we'll see how this turns out. But this team that is in front of you today and those behind us have an unbelievably impeccable track record and a very challenging business, and we've come up spades, spades, and spades, and we're going to do the same thing on this one. And those that own it, congratulations. Those that don't, you should probably look at doing it. That's my advice.
if I could just add and sort of extend what they said. So, you know, Bob has said that we're first in class, best in class, right? We're first in class because Bob and McKee had the foresight to sort of see this asset years ahead of everybody else. They went to China, found this asset. So we're two to three years ahead of everybody, right? So we have a BLA under review. We have our second phase three readout that's going to read out by the end of the year, approximately at the end of the year. and, you know, our closest competitor is probably going to have their first Phase 3 readout in 2028, so we're way ahead in terms of being the first in class. We are clearly, I think, also the best in class, and I'll a little geek out here, but I'm kind of, you know, cautious because every time we say we have cooperative binding, they say, oh, I don't believe in cooperative binding. Now they all say they have cooperative binding, right? We say that if there's internalization. They say there's internalization, right? So some food for thought here. PD-1 and PD-L1 will make a difference in this class of agents, right? If you say that they're the same, they're not. If you believe internalization is a key component of the MOA, whether you target PD-1 versus PD-L1 is going to be important. PD-1 addresses the T lymphocytes, which my team calls serial killers. They keep killing and killing and killing. If you target PD-L1 and you get internalization, and that's important, then you get degradation of the drug. You're going to limit your internalization. You're only going to internalize in the tumor cell there directly, right? And then you lose the drug and you lose the effect. The other thing is that PD-L1 is expressed broadly across different tumor types. Now, PD-L1 expression levels are going to make important role, but it's a numbers game when you took a PD-1 versus PD-L1. If you look at the sort of third agent in the field, I think the clinical data is empirically showing that we're superior. They target PD-1, but it's very clear that they can't dose that what we can dose, and the clinical efficacy, although only in phase two so far, doesn't seem to be comparable to us as well, And therefore, you know, I think I've always said this, because of the bispecific, because of the tetravalent technology, the format and the targets will matter, unlike PD-1s, right? That was a commodity. Here, the technology that Aqueso has built is, I think, superior and best in class.
Salvin, I love Alan Passion. As soon as you start, he can never stop. And to answer Bob's question, I believe I'm going to come faster in the market as you see me in the moon. I mean, you cannot put me in this box to send me to spaceships.
So God help a lot, Bob. Alan came in and interviewed us. I really had no idea even how to pronounce his name. And we had a great interview. I said, well, why did you come to us? He said, well, I quit my other company. I said, why did you quit? He said, I disagreed with the chief executive officer. I said, who was right? He said, I was. I said, you're hired. this guy is one sharp guy he gave gang charges one sharp guy Selvin is one sharp lady McKee is a fortune billionaire and Mamita is really brilliant so you've got brilliant people doing the right thing but thinking the same way you do I don't take a salary I make or break it just the way you make or break it it's either going up and I win or it's going and I lose and we're not going to lose we've got plenty of ways to make this go right so thanks for your attention thanks for your past support and And I think if we're here next year, this place will be packed.
Maybe one quick last question for Munmeet here. Given the planned phase three expansions we just talked about and the commercial build-out, how should we think about cash runway?
So we have been pretty, you know, efficient in our capital allocation, right? Running four phase threes by ourselves, our run rate for last quarter was $120 million. We ended last quarter with over $600 million in cash. and as Bob said, there is no scarcity of cash and it's our choice at what time we want to raise and, you know, we will keep doing. We did, and every year from last three years we have raised half a billion dollar approximately every year which is sufficient for us to keep it. We don't want to keep like billions of dollars in the balance sheet because we believe in the drug and there are so many more milestones which are coming in next 12 to 18 months which will give us ample opportunity to raise money. For commercialization going there, yeah, we are preparing. We have hired our commercial leadership team and market access team is already in the field. We have started a lot of activities on that part, which is a long lead time. Otherwise, we will continue to allocate commercialization spend as we seem appropriate, but there is no concern. In this company, I think we make budgets for the sake of budget, but if there is a value add for Ivernosimab, we just clear it right over here. There is nothing like a budget which stops for people to doing something, whether it's collaborations or whether it's anything.
With that, thank you so much. Really appreciate the time today.
Thank you. Thank you.