Summit Therapeutics Inc. ($SMMT)

Great. Good morning, everyone. It's my pleasure to introduce the Summit Therapeutics team. With us, we have Bob Duggan, Co-CEO with Macky Zanganeh, Co-CEO; Manmeet Soni, CFO; Allen Yang, our DSO and Dave Gancarz, CBSO.

To start here, a big picture question. IGO's the leading PD-1 or L1 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 as you look to maintain your position and expand upon global development?

Yes. We're trying to keep that a little bit close to our chest because every time we announce something, our competitors announced the same thing and said, we're going to do it as well. But 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, 3 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 2 targets that's their 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 VEGF, you look at where those agents are approved, the overlap like lung cancer, seems like a great target, and we are going after lung cancer. And 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? So 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. 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 we have that ongoing collaboration with the LUMINA study with Cortex. So we're going after head next 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 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, and that's why we have the GI 3 indication going I think the Gortex study head 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 pembro 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 flattening in the next year I'm sorry, I can't give those to you today.

Yes. As a stand-alone 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.

Yes. 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 either go alone, you can partner with someone that can assist you with sales and marketing or you can merge all 3 of those opportunities we will factor in. We're here for patients first. We're 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 with that. We think there's plenty of opportunity there. And we think we are the causative source as to what any 1 of the 3 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, 2 OS readouts on nominal so we have through OS as no one else has touched that. No one else has touched pembro. We're at 36% less chance, 34% less chance of depth with a pembro 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 participated in each of the fundraisers and we 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?

Yes. So 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 nonsquamous readout for PFS as well. So in terms of short term, we have immediately to 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 this year.

And Salveen, if I may say as well the trials that are going -- I mean, we are really enrolling the patients very fast. Some of the trials really 6 to 9 months is ahead of schedule on a 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, Ivo demonstrated a 34% survival benefit over temvibraat 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 replaced the PD-1 therapy in this setting. And so with that, there's now an overall survival benefit. So when coming into ASCO 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 implied significance. But in the front-line lung setting, this is really the cornerstone of where pembro and the other PD-1 inhibitors have really dug their heels in, in terms of entrenched. This has now gone -- ivonescimab 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 to the program globally, you certainly don't feel worse going into the rest of the program 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 talked about, hey, there's a VEGF inhibitor as a part of -- or VEGF inhibition in the part of the novel mechanism of ivonescimab. 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 6 months is that's not something that we expect in the frontline setting. What we now have coming out of ASCO is benefit and an OS benefit that statistically are highly consistent and highly correlated, right? So 0.60 in PFS, 0.66 and in OS. But what that really represents is statistically or 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 -- 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 from a KOL perspective, community perspective, the academic and trading 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. So 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. So 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 1. And so -- but hey, maybe there were somewhere within the 20 or so cohorts, we saw one that was a little bit 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 cross 1. Secondly, as we talked about at ESMO last year, there was -- 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 Tisley arm, the [indiscernible] arm, in 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 [indiscernible] side. So for example, the median size of the lesion was larger in that subgroup in the ivo arm. They were more distant metastases. -- there were more brain metastases at baseline in the IV. 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 IO in all scenarios. Finally, this is the fourth Phase III. So not only by starting to, 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 [indiscernible]. I also have the HARMONi and the HARMONi-A, the second and third Phase IIIs to read out. Those also showed highly consistent benefit in greater than 65. So 3 other Phase III 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 for us all 4 Phase III clinical trials is very strong.

Yes. And 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 discussions in our presentations. But 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 ivinesimab. And I think that presentation sort of sets IV as the leading molecule in a new class of agents, and that was the importance of that presentation, right, that she sort of told me miss. 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 is going to be. And 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? And I'm saying this in the context of the translation from the HARMONi-6 trial to yours where the U.S. patient...

China?

Yes. So the HARMONi-3 and HARMONi-6 study are very similar in the sense, 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 1. There was no detriment, right? So traditionally, what you do in the study is you balance or criteria that you think may impact the outcome. -- the location of metastases, the region as well as 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, the discuss it 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 and 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. 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 to goes above 1. Everything is still under 1. So we still expect there to be a benefit broadly across patient groups.

Yes. The only other thing I would add to that, Salveen, right, it's really important to remember that overall across the study, across the 2 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 HARMONi-3 study, just like in HARMONi-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, those criteria are balanced.

S For the HARMONi-3 study, you recently disclosed in the squamous population, interim PFS analysis, and it did not achieve statistical significance despite read-through from HARMONi-3, 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? .

Yes. And it's a good question. And I think -- so we really haven't given details with respect to the statistical plan, but I'll make 2 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, roughly 3 months or so. in order to have a conversation earlier with the health authorities. So any time 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 HARMONi-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 threshold to achieve there. And so -- 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. And obviously, now 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?

Yes. I think we've seen, overall, the data -- so 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 the same direction. So we have over 4,000 patients who have been treated in clinical studies with ivonescimab to date between Summit and Akeso. And so the totality of that information we're able to look at and really understand crosssology across 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 is 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 at the same time?

Yes. 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 maker 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, but I don't want that to be misconstrued as any lack of confidence in that end point. 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 in 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 so -- and we see that validated through the results of HARMONi-6 as well. So we have no hesitation whatsoever with respect to where we are looking with respect to ivonescimab in the future.

Great. And one last question here on HARMONi-3. So for the non-squamous cohort, we'll see final PFS analysis in the first half -- what gives you confidence in the readout and maybe speak to the mechanistic or structural differences between the squamous and non-squamous population.

Yes. So when I started oncology, which was like a long time ago, they were actually treated as 1 group. So a couple of things. I think let's talk about the differences and why we're confident -- so the chemo backbone is a little bit different for non-squamous, they use pemetrexate instead of a taxane. The methotrexate stays on is maintenance, right? So traditionally, adeno 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, ivinesimab 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, we believe that it will work. There are some adjustments you have to make because nonsquamous 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 nonsquamous 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.

Yes. 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? And so when we initially entered into the deal with accesso, there was strong squamous Phase II data in frontline lung cancer in combination with chemotherapy. Because of the enrollment pattern, they had -- they -- our partners at Cash enrolled the squamous cohort first and then the nonsquamous cohort. -- was enrolled afterwards. And so the data took a little bit more time to mature. So 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 was very 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. And so -- 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 Allen 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 IGO is not just first-in-class but also best-in-class and what data would prove this differentiation? And was -- in that context, interesting, you see the CRC data at ASCO versus competitors?

Jump and I'll follow up.

Okay. I mean, it's for sure, 1 CEO have a drug that is going to perform. It's very obvious that left and right, you're going to have other pharma biotech. They are going to start to develop other molecules. The interesting part was when we started with a VEGF PD-1, nobody was there. Nobody believed in us. And it was lucky 2.5 years ago. And that was really difficult even at this moment of time to enroll 1 patient -- now you are everywhere. Everybody is talking about VEGF FPD-1, which is great for us because that shows that we were right at this moment of time, and we continue to keep our position and being a leading this process. I always say, you know what, we will see at the end, how everything will go. Every single patient deserve any drug that is work -- but at this moment of time, especially, I can say the data of Pfizer versus us, you see the overall response rate. For sure, there's a lot of different things behind this trial that I know that Allen can talk more in details. But that shows as well that even in this regard, aim 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 or drug or clinical trials. And as I mentioned multiple times, and I'm very proud to say that you cannot right now find any rig PD-1 inhibitors or dbispecific that is in multiple clinical trials. I mean we have 47 sponsored trials, 15 Phase III, 155, including all of the collaborations -- if it's with other ADC is a KRAS inhibitors, is ISP program. So that is really I mean, it's interesting right now, we are enrolling but in 2, 3 years from now, even 1 year from now, you will see 1 data after the other will hit the market, and that is the beauty of this strategic work that the team did during this past 2 years. And as well, I can say is from even from financial part, you will see it very cost effectively, we are doing all of our trials. I mean AKSleads with a Phase II. We catch it on the Phase III 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 as some things that, over time, you will see how we did our deal of collaboration. So all of them, I can say I'm proud the way that the team work and I'm sure this 1 would never stay behind the cloud will come very soon up.

Our team -- the top 10 people have worked together for over 10 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. 4 years ago and American presses, like allergic to it. It's not the case now. There's not 1 big pharma company. It 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 tendership -- it's not because some of them weren't educated in America because they're hard working 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 stood for new what it meant. Akeso is the source of the bispecific typtavea. Pembro is a monospecific bivalent and there is no comparison between the 2. If you need an enemy going after cancer, you're going to pick the bispecific every single time. So we made 2 immediately great calls there. paid $0.5 billion raised $500 million overnight with our commissions launched into the partnership with Akeso, 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, I hope we pay. We pay those monies and we're not sitting here at an $11 billion market cap. Five years ago, SpaceX had a $0.25 billion market cap and is sitting there probably within the next few days at $1.7 trillion. I will tell you that bispecific heptavalent we'll dose over 1 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 GLPs are at $100 billion and prices are coming down. We're also at that $90 billion, $100 billion market cap and some of his going to get value to pay for it. pembro will generate over $60 billion in the next 3 years, the tail end of what it produced, Meanwhile, we're trading at $11 billion, and we have the lead -- there was an added by Merck at ASCO saying 20 years of pembro success. -- now is the time for a little change in the approach and they went dot, and it's a subcu therapy. And I put after dots -- 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 in a very challenging business. and we've come up space, and we're going to do the same thing on this one. And those that own it. Congratulations and 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 Bob said that we're first-in-class, best-in-class, right? We're first in class because Bob and Key had the foresight to sort of see this asset years ahead of everybody else. They went to China, found this [indiscernible] we're 2 to 3 years ahead of everybody, right? So 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. and our closest competitor is probably going to have their first Phase III 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 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. Now they all say they have cooperative binding, right? We say that 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 call 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 an important role, but it's a numbers game when you took 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 that what we can dose and the clinical efficacy, although only in Phase II so far, doesn't seem to be comparable to us as well. And 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-1 right? That was a commodity. Here, the technology that Akeso has built is, I think, superior and best-in-class.

Salveen, I love Allen passion. As soon as you sort you can never stop -- and to answer Bob's question, I believe Ionis faster in a market as you see me in the mood. I mean, you cannot put me in this box to send it to space ship. So -- got a lot

Allen came in and interview just I really had no idea given how to pronounce as being. And that we had a great interview, I said, why did you come to us. She's all equipment at the company, I said, "Why did you quit?" I disagreed with the Chief Executive Officer. -- said who was right. He said, "I was a said, you're hired. This guy is 1 sharp guy. -- anchors. Salveen is one sharp lady. McKeesport billionaire and that met is really, really brilliant. So you've got brilliant people doing the right thing to think in the same way you do. I don't take a salary. I make or break it just the way you make a rat's either going up when I win, where is it 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 I think if we're here next year, this place will be packed.

Maybe 1 quick last question for Manmeet here. Given the planned Phase II expansions we just talked about in the commercial build-out, how should we think about cash runway?

So we have been pretty efficient in our capital allocation, right, running 4 phase trees 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 we will keep doing. We did -- and every year for the last 3 years, we have raised $0.5 billion approximately every year, which is sufficient for us to keep it. We don't want to keep like billions of dollars on the balance sheet because we believe in the drug, and there are so many more milestones which are coming in the next 12 to 18 months, which will give us ample opportunity to raise money. For commercialization going there yes, we are preparing. We have hired our commercial leadership team and market exist 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 apparent, but there is no concern. We -- in this company, I think we make budgets for the sake of merger. But if there is a value add for avunizumab, we just cleared it, right, over here. There's nothing like a budget which stops for people for -- to doing something, whether it's collaborations or whether it's anything.

Okay. With that, thank you so much. Really appreciate the time today.