Great. Good morning, everyone. It's my pleasure to introduce the Summit Therapeutics team. With us, we have Bob Duggan, Co-CEO, with Maky Zanganeh, Co-CEO, Manmeet Soni, CFO, Allen Yang, CRDSO, and Dave Gancarz, CBSO. To start here, a big picture question. ivonescimab is the leading PD-1 or PDL-1 VEGF asset in development and China-based phase III 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-
Of course.
You look to maintain your position and expand upon global development.
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." When we think about PD-1 VEGF, first of all, I think that PD-1 versus PDL-1 does make a difference. I don't know if it changes too much your strategy, but it might change your overall baseline efficacy. With that said, 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 history around those two targets, that they're validated targets. We looked at where we could go and where we could contribute. Part of that is you look at PD-1, you look at VEGF.
You look at where those agents are approved, the overlap, like lung cancer seems like a great target. We're going after lung cancer. What's interesting about the class is that when you look at the data that Akeso has generated, there are some targets that are very interesting, right? That 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. CRC is something that we've disclosed. We have an interest in head neck cancer, right? That study has been announced as well. We have that ongoing collaboration with the ILLUMINATE study with GORTEC. 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. Any PD-1 VEGF, we're very interested in.
Lung is our core. That is the biggest indication in PD-1s. We think owning that space is very important. That's why we have the HARMONi-3 study, the HARMONi-7 study, the HARMONi study. The only indication that can rival that in unmet need is probably CRC, microsatellite stable CRC. That's why we have the HARMONi-GI3 indication going. I think the GORTEC study head and neck is also very important. Not as large an indication. 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 pembrolizumab do you think we're going to be? That's always our competition, it seems like, in most indications. 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. Yeah.
As a standalone company without a multinational partner, do you think that your balance sheet and strategic perspectives alone are intact? 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%, it could be 10%, 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 you either go it alone, or 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. We think we're doing a good job with that. We think there's plenty of opportunity there. We think we are the causative source as to any one of the three choices. Right now, we enjoy the position we're in. Clearly, on the big pharma side, OS is a major factor.
We have on the drug two OS readouts, one nominal, we have three OS's. No one else has touched that. No one else has touched pembrolizumab. We're at 34% less chance of death with a pembrolizumab equivalent. We think we're actually in a very profound and positive position moving forward. 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. Hope that gives you some color.
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. Certainly we have over the course of 2026, we have our final PFS readout for HARMONi-3 squamous. Shortly thereafter, in the first half rather of 2027, we have the non-squamous readout for PFS as well. 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. Then we also have our BLA in the post-TKI EGFR mutant, with PDUFA date of November of this year.
Salveen, 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. The HARMONi-7 is moving very fast and CRC as well. That has to be in consideration of what Dave is talking on the readout very soon, hopefully.
In the HARMONi-6 overall survival data that was presented at ASCO, ever demonstrated a 34% survival benefit over pembri 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. 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. That's really important because we replaced the PD-1 therapy in this setting. With that, there's now an overall survival benefit. When coming into ASCO, it was really important. One of the remaining questions was, hey, you've shown strong PFS benefits. HARMONi-A was statistically significant. HARMONi showed the nominal P value that implies significance.
In the frontline lung setting, this is really the cornerstone of where pembro and the other PD-1 inhibitors have really dug their heels in terms of entrenched. ivonescimab has gone head-to-head against the PD-1 regimen and shown a statistically significant overall survival benefit. 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? That certainly improves confidence with respect to what does this mean globally. I think there's also a really important concept here as well. People talk about, hey, there's a VEGF inhibitor is a part of, or VEGF inhibition is a part of the novel mechanism of ivonescimab. Historically, we've seen VEGF inhibition degrade from PFS to OS.
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 frontline 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? 0.6 in PFS or 0.66 in OS. What that really represents is statistically are numbers that are very close together and highly correlated. We're not seeing a big gap between PFS and OS. That's the key takeaway, right? As we talk about, 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 OS? What do you need to achieve?
We've always been pretty clear that 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 HARMONi-6 trial from what that OS gold standard benchmark is, and we also see highly correlated PFS to OS. As we take that forward, we now have more confidence with respect to the global applicability of ivonescimab in terms of its ability to show an overall survival benefit based on a few of those points. You asked more broadly, there's been some noise with respect to the forest plots of the HARMONi-6 trial showed a benefit for all patients. No patients crossed the hazard ratio bound of one.
Hey, maybe there were somewhere within the 20 or so cohorts, we saw one that was a little bit more spread than others, and that was age. I want to hit that point head on as well, because I think that's something that people have spoken to. 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 tislelizumab arm, the TEVIMBRA 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 TEVIMBRA side.
For example, the median size of the lesion was larger in that subgroup in the Ivo arm. There were more distant metastases, and there were more brain metastases at baseline in the Ivo arm. 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 III. 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 HARMONi-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, less than 65.
The HARMONi and the HARMONi-A, the second and third phase IIIs to read out, those also showed highly consistent benefits less than and greater than 65. Three other phase III studies all showing a consistent benefit less than and greater than 65. 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 III clinical trials is very strong.
Yeah. I would just add, Salveen, when I was talking to physicians after the meeting, they're very excited about Ivo, right? I think Summit has a tradition of drawing very tough sort of discussants in our presentations. 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 ivonescimab. 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, 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? That's the more important question.
To follow up here, in your HARMONi-3 study, the global lung cancer trial, how are you accounting for imbalances on baseline characteristics? I'm saying this in the context of the translation from the HARMONi-6 trial to yours, where the U.S. patient China.
Yeah. The HARMONi-3 and HARMONi-6 study are very similar in a sense. In tradition, in China, they do cap enrollment at 75. That's not an unusual thing. That is common and same 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, that the hazard ratio was still under one. There was no detriment, right. The location of metastases, the region, as well as the PDL-1 expression. Those things are accounted for as in stratification factors for randomization.
To date, we have not seen age as an important factor. The other thing too, 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 that age, the hazard ratio was 0.88 for the age greater than 65, but they had accounted for that by imbalances in terms of other criteria, brain metastases, size of the lesions, and so forth. 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. We still expect there to be a benefit broadly across patient groups.
Go ahead.
Yeah. The only other thing I would add to that, Salveen, right, 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, then you look at the balance across that subgroup. Across our HARMONi-3 study, just like in HARMONi-6, in totality across the Ivo arm in total and the tisli arm in total in their study and our study across the Ivo arm and the Pembro arm, those criteria are balanced.
For the HARMONi-3 study, you recently disclosed in the squamous population interim PFS analysis, it did not achieve statistical significance despite read-through from HARMONi-6. Can you speak to what drove the divergence here? Was it event maturity, the higher statistical bar, or other factors such as control on performance or regional differences?
Yeah. It's a good question. We really haven't given details with respect to the statistical plan, 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. That was, we already have a substantial lead within the class. 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, roughly six months or so, in order to have a conversation earlier with the health authorities. 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 is a little bit different with respect to HARMONi-6 within our study and whatnot. 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. That's also an important point. It's not the same bar, looking again and hoping to change things. This is a meaningfully higher bar in the interim than what we'll see in the final. 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. If you take what we saw in HARMONi-6, then you take also HARMONi and HARMONi-A, HARMONi-2, all of the data is pointing to and trending to in the same direction. We have over 4,000 patients who have been treated in clinical studies with ivonescimab to date between Summit and Akeso. The totality of that information, we're able to look at and really understand across pathology, across tumor types, early stage, late stage clinical trials, so on and so forth. The totality of that evidence really points us into where our confidence is on the trial as a whole. I think if we look at individual points per threshold, I think it's obviously important to set up statistically significant and clinically meaningful trials that show a statistically significant and clinically meaningful bar.
That really becomes our threshold for both PFS and OS.
How are you thinking about the interim OS read at the same time?
That's a great question. The second half of this year is the final PFS. 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. It'll 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. There are other in-class trials that are being run in the phase III setting. Bristol Myers and BioNTech are running their study in frontline non-small cell lung cancer as well.
They have taken out an 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. We see that validated through the results of HARMONi-3 as well. We have no hesitation whatsoever with respect to where we are looking with respect to ivonescimab in the future.
Great. One last question here on HARMONi-3. For the non-squamous cohort, we'll see final PFS analysis in the first half of 2027. What gives you confidence in the readout? Maybe speak to the mechanistic or structural differences between the squamous and non-squamous populations.
Allen?
You want to start it?
Yeah. When I started oncology, which was a long time ago, they were actually treated as one group. A couple things. I think let's talk about the differences and why we're confident. The chemo backbone is a little bit different. For a non-squamous, they use pemetrexed instead of a taxane. The pemetrexed stays on as maintenance, right? Traditionally, 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 HARMONi-2 data, which was monotherapy ivonescimab 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? Finally, when you look at the study, we believe that it will work.
There's some adjustments you have to make because non-squamous patients do better overall. They get a little bit more chemotherapy, the treatment effect may be a little bit harder to detect, but that's why the non-squamous cohort is larger in size, right? 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. 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. 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 II data that was generated in both settings, right? When we initially entered into the deal with Akeso, there was strong squamous phase II data in frontline lung cancer in combination with chemotherapy. Because of the enrollment pattern, our partners at Akeso had enrolled the squamous cohort first, then the non-squamous cohort was enrolled afterwards, the data took a little bit more time to mature. In addition to what Allen said with respect to HARMONi-2, the other thing that's really important is the phase II data in both squamous and non-squamous went forward with the phase III. Our partners at Akeso effectively replicated what they saw in phase II.
That was the AK112-201 study, where there was an 11.1-month PFS benefit in the phase II and an 11.1-month PFS benefit in the phase III HARMONi-6 study. We saw overall survival at ASCO. When we look at the non-squamous cohort, we also see highly encouraging data in that setting as well. Part of that is also it's everything that Allen spoke to, in addition to some phase II data underneath that to support them.
Bob and Maky, 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? What data would prove this differentiation? Would, in that context, interesting to see the CRC data at ASCO versus competitors?
Jump and I'll follow.
Oh, okay. I mean, it's for sure, once you have a drug that is going to perform, 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 VEGF PD-1, nobody was there, nobody believe in us. It was like it's 1.5 years ago. That was really difficult even at this moment of time to enroll one patient.
Now you are everywhere. Everybody's talking about the VEGF PD-1, which is great for us because that shows that we were right at this moment of time. We continue to keep our positions and being leading in this process. I always say, you know what? We will see at the end how everything will go. Every single patient deserves any drug that they work in. At this moment of time, especially, I can say the data of Pfizer versus us. If you see the overall response rate, for sure, it's a lot of different things behind these trials that I know that Allen can talk more in details. 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. Yes, other drugs existing, we continue to execute.
We focus our attention to where we are, our drug, our clinical trials. As I mentioned multiple times, I'm very proud to say that you cannot right now find any VEGF PD-1 inhibitors or this bispecific that is in a multiple clinical trial. We have 47 sponsored trials, 15 phase III, 155, including all of the collaborations, if it's with other ADC, if it's the KRAS inhibitors, if it's IIT program. 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. That is the beauty of this strategic work that the team did during these past two years.
As well, I can say is from even from financial part, you will see it's very cost effective if you are doing all of our trials. Akeso leads with the phase II, we catch it on the phase III. The IC program is really giving us a lot of informations while we are moving along the way. The collaboration with the Big Pharma right now is as well, something that over time you will see how we did our deals of collaboration. All of them, I can say, I'm proud the way that the team work. I'm sure the sun will never stay behind the clouds, will come very soon.
Our team, the top 10 people, have worked together for over 10 years. 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. The American press was allergic to it. That is 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. 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. It's not that others won't catch up. We saw the bispecific tetravalent. I think very few people knew what it stood for, knew what it meant. Akeso is the source of the bispecific tetravalent.
Pembro is a monospecific bivalent. 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. We made two immediately great calls there. Paid a $500 million , raised $500 million overnight without commissions, launched into the partnership with Akeso. 80% of what we remain to owe them is on revenue payout. That's $10 billion, $20 billion, $30 billion. These are monies that I really, as I sit here, hope we pay. If we pay those monies and we're not sitting there at an $11 billion market cap. Five years ago, SpaceX had a quarter of a billion market cap and is sitting there probably within the next few days at $1.7 trillion. I will tell you that bispecific tetravalent will dose over 1 million people before anyone will colonize Mars.
Pick what you want here, but this is a business that is every bit as big as the GLP-1. The GLP-1s are at $100 billion. Prices are coming down. We're also at that $9,800 billion market cap. Someone's going to get value paid for it. Pembro will generate over $60 billion in the next three years. The tail end of what it produced. Meanwhile, we're trading at $11 billion. We have the lead. There was an ad by Merck at ASCO saying, "20 years of Pembro success. Now's the time for a little change in the approach." They went. It's a sub-Q therapy. I put after, it's ivonescimab. We'll see how this turns out.
This team that is in front of you today and those behind us have an unbelievably impeccable track record in a very challenging business. We've come up spades, and spades. We're going to do the same thing on this one. 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. Bob has said that we're first in class, best in class, right? We're first in class because Bob and Maky had the foresight to sort of see this asset years ahead of everybody else. They went to China, found this asset from Akeso. We're two to three years ahead of everybody, right? We have a BLA under review. We have our second phase III readout that's going to read out by the end of the year, approximately at the end of the year. Our closest competitor is probably going to have their first phase III readout in 2028. We're way ahead in terms of being the first in class.
We are clearly, I think, also the best in class. I'll little geek out here, but I'm kind of cautious because every time we say we have cooperative binding, they say, "Oh, I don't believe in cooperative binding." They all say they have cooperative binding, right? We say that there's internalization, they say there's internalization, right? Some food for thought here. PD-1 and PDL-1 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 PDL-1 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? Then you lose the drug, and you lose the effect. The other thing is that PD-L1 is expressed broadly across different tumor types. PD-L1 expression levels are going to make important role, but it's a numbers game when you look at 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 at what we can dose. The clinical efficacy, although only in phase II so far, doesn't seem to be comparable to us as well. Therefore, 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 Akeso has built is, I think, superior and best in class.
Salveen, I love Allen's passion. As soon as you start, you can never stop. To answer Bob's question, I believe ivonescimab is about to come faster in the market as you see me in the mood. I mean, you cannot put me in this box to send me to spaceship. God help a lot, Bob.
Allen came in and interviewed us. I really had no idea even how to pronounce his name. We had a great interview. I said, "Why'd you come to us?" He said, "Well, I quit another company." I said, "Why'd 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's one sharp guy. Dave Gancarz is one sharp guy. Salveen is one sharp lady. Manmeet, fortune billionaire, and Manmeet is really brilliant. You've got brilliant people doing the right thing and 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. This is either going up and I win, or it's going and I lose. We're not going to lose.
We have plenty of ways to make this go right. Thanks for your attention. Thanks for your past support. I think if we're here next year, this place will be packed.
One quick last question for Manmeet here. Given the planned phase III expansions we just talked about and the commercial build-out, how should we think about cash runway?
We have been pretty efficient in our capital allocation, right? Running four phase III's by ourselves. Our run rate for last quarter was $120 million. We ended last quarter with over $600 million in cash. As Bob said, there is no scarcity of cash, and it's our choice at what time we want to raise, and we will keep doing. We did in every year from the last three years, we have raised $500 million approximately every year, which is sufficient for us to keep it. We don't want to keep 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- 18 months, which will give us ample opportunity to raise money. For commercialization going there, we are preparing.
We have hired our commercial leadership team. 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 see map 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 ivonescimab, we just clear it, right, over here. There is nothing like a budget that stops for people for to doing something, whether it's collaborations or whether it's anything.
Great. With that, thank you so much. Really appreciate the time today.