Summit Therapeutics Inc. (SMMT) Earnings Call Transcript & Summary

All right. Good afternoon, everyone. My name is Cory Kasimov, one of the senior biotech analysts here at Evercore. It's my pleasure to host this next discussion with Summit Therapeutics. So we have Dave and Allen on stage now. We might have Bob and Maky jumping in here in the midst of this. And so in case that happens, don't be surprised. We fortunately have a little bit more time for this discussion. I'm sure you guys are excited about that. It's obviously been a very, very busy year for the company. So I mean, Dave, maybe I'll turn it over to you to kick things off by reviewing kind of the company's accomplishments thus far in 2025 and kind of act as a level set for our conversation.

Sure. Thanks, Cory, and I appreciate you hosting us and appreciate the invitation to the event. So we have accomplished quite a bit in 2025, and I think I would level set with speaking a little bit on the background of ivonescimab. So importantly, there are 14 Phase III clinical trials that have been launched either by our partners at Akeso or by Summit on the global stage. So 4 global Phase IIIs in addition to 10 that are being currently run in China. That results in about 3,000 patients who -- over 3,000 patients who have been administered ivonescimab in a clinical setting. And I believe our partners at Akeso have also noted that over 40,000 patients have been administered ivonescimab when you consider the commercial market in China. And so a lot has been accomplished over the course of the last 2 years and in particular, over the last year. And so as we came into 2025, there were some critical points that we were looking to prove over the course of the year based on the expected readouts. And that started with HARMONi-2 had a tremendous result in monotherapy in 2024. And now the question as we got into 2025 would result in with the backbone standard of care for solid tumors largely being PD-1 plus chemotherapy, would the addition of chemotherapy to both arms effectively water down that benefit? Or would the benefit hold? And we saw a pretty definitive answer in the HARMONi-6 study at ESMO about 6 weeks ago where there was a very strong PFS signal in HARMONi-6. And so congratulations to our partners at Akeso on the tremendous results there. And that really showed that the benefit of ivonescimab really goes beyond niche settings and is really applicable in a broad stage. We looked at as well the difference between PFS and OS, and we looked at would the benefit we're seeing in PFS look to be translated and ultimately result in OS benefits. We saw with longer follow-up. The HARMONi-A study conducted by our partners in China was statistically significant and was the first study that was opened with ivonescimab and also achieved a statistically significant benefit. In addition there, too, we saw the HARMONi study where with longer-term follow-up, a nominal p-value that showed the benefit of ivonescimab in an overall survival setting there as well. And finally, earlier this year, we saw the HARMONi-2 study, the ad hoc administrative request for the NMPA to look at overall survival prior to approval of HARMONi-2 and that showed a clinically meaningful early ad hoc look with a hazard ratio of 0.777. So under that clinically meaningful threshold, if you will, that's generally accepted of around 0.8. And so that's the second point. Third point then becomes, as we look at the translation of that data from China studies that were conducted by Akeso into a more global broader population, we saw the HARMONi data readout at the World Lung in September. And that showed remarkable consistency regionally across both PFS and OS. From overlaying the curves from a PFS perspective, we saw remarkable consistency. Overall survival, the gold standard in oncology, especially on the global setting, showed high consistency across the regions. We saw medians that were nearly identical between the East, the West and the ITT population. And what we also saw, when you look at the same follow-up time, HARMONi sequential enrollment first in Asia, then globally. But when you look at the same follow-up time, remarkable consistency even from a hazard ratio. And that really extended beyond what we see in other PD-1 trials, other frontline lung cancer studies in terms of that consistency. You see the shapes of the curves as well with maturing data from the West really being very consistent with what we saw from an Asia-only population. So we came in looking to show PFS to OS, East translating to West and monotherapy into a chemo combination. And throughout 2025, that was really accomplished, accomplished, accomplished. In addition there, too, beyond the studies that have been run in non-small cell lung cancer, our partners at Akeso have opened up several studies outside of lung cancer. And now in a global setting, we have opened up a frontline and are now enrolling in the frontline colorectal cancer study as well. So that is now showing as we look beyond just the lung cancer setting into more of the solid tumors landscape as a whole, we're also pursuing those settings as well.

Okay. Like I said, it's been a busy year.

It's been a busy year.

So there's a lot to dig into clearly. I want to start, though, bigger picture. And we've all seen the competitive intensity really get ratcheted up this year in the PD-1 VEGF bispecific space. How much does it ultimately matter being first to market in some of these larger indications like lung cancer?

I mean I think we've seen historical data would tell you that it's incredibly important, right? I think when we look back at the PD-1 race in particular, pembro not necessarily was the first mover in the PD-1 space as a whole, but became really the first mover in terms of non-small cell lung cancer, and that proved to be pivotal in terms of the trajectory of pembro from both acceptance perspective amongst physicians as well as commercial uptake. And so I think -- and there are many other analogies as we go into other drugs. But by and large, there is a significant advantage for first mover because then at that point, you get experience and comfort with actually using the drug, and that really then puts the onus on second and third movers to then become better or differentiated in some ways. So it's incredibly important. We believe we have both first-in-class and best-in-class with ivonescimab, which is also the other critical difference, which effectively prevents that second and third mover from having differentiated or better profiles because we really believe 4 Phase III clinical trials have read out, 4 Phase IIIs have been successful, right? And that's a pretty high bar to set when you think about drug development. There aren't a lot of drugs that have produced 4 Phase III studies that have all read out positively that aren't pretty successful ultimately at the end of the day. And it speaks to the broad -- the breadth of the potential program, but also the potential of the compound as a whole. And so the way we look at the competition now, there's really 2 approaches, one of which is to be as close to ivonescimab as you can to try to replicate those results, at which point, second and third movers don't have the ability to differentiate if they're intending to be the same or you have to make a meaningful change with the intent to modify the molecule, if you will. At this point, again, being 4 for 4 in Phase III studies, when you look to modify, you also run the risk of not necessarily being able to show those same results. And so it becomes more of a risk at this point than it does a benefit to make those modifications given the proof that has been shown across 4 Phase III studies with ivonescimab.

Right. Okay. So then speaking to the breadth component of this, we've noticed a large number of investigator trials popping up in various indications. You also mentioned the work being done by your partner Akeso across indications. How much do those go together to kind of maintain this competitive advantage as well?

Yes, great question. And so if you think about the breadth of the program, part of why we complement so much our partners at Akeso is the breadth, speed and depth at which they've studied the program, including the 10 Phase IIIs, but that's backed up by a substantial data set in Phase II. In addition there, too, there are also a number of settings where those tumors aren't as prevalent in China. And so as you mentioned, the IST program, we also have clinical trial collaboration set up at MD Anderson. And in addition there, too, we have the clinical trial collaboration that we plan to begin in terms of dosing patients shortly in 2026 with Revolution Medicines. We have -- we take all of that and are able to compile a substantial amount of data, which provides that comfort and data-driven decisions, if you will, in terms of the ways we can expand that pipeline. And so as we looked at colorectal cancer, for example, we had extremely encouraging data that was published in 2024 at ESMO. In addition there, too, we opened that study, that Phase II study in the U.S. and expanded it as well in China and ultimately looked at 3 different chemotherapy backbones to really understand ivonescimab's performance across a number of historical comparators in bevacizumab plus different chemotherapy combinations. And that data set really allowed us to make an informed decision in terms of moving forward with the FOLFOX combination, and now that's open and enrolling. So there -- some of the competitors need to run the Phase II/III in order to catch up from an Optimus perspective on that. And so that data that's being generated both in China as well as by the IST programs, the clinical trial collaborations are incredibly important.

Okay. So taking this notion of combination treatments a step further, obviously, combinations are sort of are crucial to developing oncology drugs. What kind of novel combinations do you believe are best suited for ivonescimab? And can you discuss kind of your plans to accelerate these efforts?

Absolutely. That's a meaty question. And so short term, we have a clinical trial collaboration with Revolution Medicines that will look to start early in 2026, right? And so that takes multiple RAS inhibitors, pan-RAS inhibitor and a couple of specific inhibitors, RAS inhibitors and look to explore multiple tumor settings. So that becomes critically important. If you think about opportunity there, you take a subset of patients, but on target mutation, targeted therapy has shown extension of both progression-free and ultimately, the hope for overall survival. When we look at adding the benefits of ivonescimab on top of that, that's extremely exciting. So that's one place that we're very excited about. It also opens up opportunities that aren't necessarily as applicable to PD-1 and VEGF like pancreatic cancer, right? And so there's a significant amount of opportunities that we've talked about, and I think we released in our initial press release some of the details behind that. In addition there, too, ADCs become really important within the landscape of where the puck is going, if you will. Novel, novel combinations will become very important. And there are places where we have the opportunity. So part of where we believe we have a strategic advantage really becomes the ability to make data-driven decisions here, right? And so there are a number of different ADCs. We see in EV, the Nectin-4 ADC in bladder cancer that's standard of care and just read out very positively. In the earlier stage setting, we see a couple of TROP2 ADCs showing very promising data ultimately looking for approval in triple-negative breast cancer. We're seeing multiple lung cancer ADCs going. But a lot of those are -- even the TROP2 ADCs from the Nectin-4 are different platforms, right? And so what we don't believe is that there is a single platform that will overtake, become essentially backbone therapy across solid tumors. So what the competitive advantage we have is we can look at each of these, look where the puck is going, if you will, the future standards of care and look to combine with multiple of those across multiple different ADC platforms, right? And that's one of our goals in 2026 is really to expand the novel, novel combinations that are able to be done, but without looking to optimize our own pipeline and really looking to optimize ivonescimab, follow the data and make the biggest difference that we can for patients. So it's a very broad opportunity, but it's something -- because we are -- to your earlier question with respect to the lead, those companies are coming to us and looking to combine with us as well. So that gives a strategic advantage as well there in terms of the ability to move quickly.

Yes. Those are some good points. All right. So let's dig into some of those specific studies, and I'll apologize in advance, do you want to...

Yes, Cory, I was going to add something just to go commercial and get into trouble. So this ADC question in combinations is terrific, right? But to be honest with you, from a scientific perspective, the way I look at it, it's these companies that have huge investments in ADCs justifying those investments. There's this whole adage of being prepared to fight the last war, right? And so the strategy was pembro was unbeatable. Let's buy something to add on to pembro, right? I think what people don't appreciate is ivonescimab is something new, it's not just a better PD-1. If you look at the largest opportunity for PD-1s, it's non-small cell lung cancer. That's the largest unmet need. That's the largest commercial opportunity. The one thing that ivo is doing that can exceed that is colorectal cancer. That's something that doesn't -- wasn't on the radar, right? That's a huge opportunity. It's the one indication, one unmet need that could potentially be larger than non-small cell lung cancer. We saw that very early with the Phase II data. We were the first ones in that space, right? That doesn't need anything else. That doesn't need an ADC, doesn't need a RAS inhibitor. That's just ivo. There's a lot of those opportunities that are very large that these other guys don't realize yet. And with Akeso's Phase II data, with our own internal data, those, I think, are the unmet opportunities, not the sort of let's combine with the drug I just paid several billion dollars for, right? So I just wanted to add that out.

No, that's a good point. I'm glad you did. All right. So as we get into these, as I was about to apologize in advance before, I know some of these questions get annoying. I still have to ask them. Deflect where you need to deflect. But we'll start with.

That's a great lead-in, by the way.

All right. We'll start with HARMONi-2 given the pending interim update on overall survival. Is there anything more you can say on the anticipated timing of this disclosure? And I think more importantly, at the end of the day, how much does it really matter as an underpowered secondary endpoint as if it's stat, if it's 0.77 or 0.79 or whatever?

It's also a great lead-in. So yes, I would say in terms of timing, just to take that off the top, I think we defer to our partners at Akeso in terms of the specific timing. Part of that because it's an underpowered study, that's a secondary endpoint. I just want to -- as I think we talked about early, but haven't as much lately. When we entered into the transaction with Akeso and that went effective in January 2023, Akeso was running the study, right? And with the attempt of a stand-alone company in China that was looking to achieve approval in China with a PFS endpoint, we do the deal a couple of months later past they complete enrollment. And then everybody wants to go, well, let's talk about overall survival in a study that was never designed for that and its purpose. And so I think more specifically, when we looked at the interim -- or not even interim, actually, the ad hoc data cut that read out in the spring of this year, what we saw was a 0.777 hazard ratio. This is -- I just want to like take a step back and just make sure we're all acknowledging what we're talking about here. There are approximately zero drugs that have gone head-to-head, not on top of, but replacing pembrolizumab and have shown benefits here. There are 2 studies that have now done that. It's HARMONi-2 and it's HARMONi-6, right? And so monotherapy and chemo combination. Then at an early look because, again, this is underpowered and it's immature at this point, we're now seeing a clinically meaningful hazard ratio in overall survival. That's incredible. Like I just want to make sure like we're taking a step back and thinking about what the implications of that are. Now one of the potential criticisms that came off of that was, well, hey, there's a VEGF component. This will degrade over time. The OS will raise up. Well, that was also -- as we looked at more follow-up time in HARMONi-A, we saw an improving hazard ratio in terms of overall survival and ultimately, a statistically significant benefit. What we're not seeing in these studies are high discontinuation rates. What we're not seeing are high death rates due to adverse events. What we're not seeing are these complications that are coming up that are requiring large interruptions in therapy. Ultimately, what we saw in some of these earlier studies of PD-1 plus VEGF, VEGFR-TKI, where a lot of those showed PFS benefits, but the interruptions that were being seen in treatment was causing ultimately the lack of benefit because the patients weren't receiving the drug, right? And so what we're seeing is the ability to continuously administer ivonescimab. And that's a differentiated approach as well within this -- it's a novel mechanism, but within this combination itself is novel, right? And so when we look at HARMONi-A, we're seeing improving overall survival hazard ratios over time. And so for us, HARMONi-2 showed exactly the scientific point of what we were looking for, obviously, very successful for Akeso with respect to commercialization opportunities in China. We've designed HARMONi-7 powered now for overall survival in addition to PFS. But we're continuing to see very positive momentum here that we're less focused on studies for -- that are not powered for OS, that are not designed for U.S. approval, we're now focused on the HARMONi-3 study looking to complete enrollment shortly, which will then have readouts in 2026, right? Like that's much more where the opportunity ultimately lies for us. We've seen the good news come from HARMONi-2 already. And HARMONi-A, really with the OS benefit, alleviates any of those concerns with respect to VEGF toxicities and OS.

So then let me maybe ask this OS question from HARMONi-2 in another way. When you get that readout, does it impact your powering assumptions for either HARMONi-3 and/or HARMONi-7? Like maybe asked another way, are there patient expansion levers that are built in? Or do you already have the answer you need for those trials?

Of course, we're going to look at the data when it comes in. But what we've powered for HARMONi-3 and HARMONi-7, we're pretty confident and comfortable with where we're at.

And to be clear, is the pending HARMONi-2 OS update, is that still -- is that an interim look? Or is that the final look?

I mean I think the protocol was -- there's some reactions, but it was published at the Lancet at the time. So that's still -- the interim has not taken place.

Right. Okay. Okay. All right. So moving on, let's talk about HARMONi, which is exploring ivo in EGFR-mutant patients. So the final overall survival results from Akeso's HARMONi-A study in China demonstrated the emergence of this tail, right, for the ivo arm. Have you been able to or has Akeso been able to look into that data? I can offer my seat if I need to, to identify trends within -- with these responders to give that encouraging tail that you're seeing?

Yes. There are not that many patients in the tail yet. I mean it will take some time. I'm trying to remember like which data I saw and where I saw it. So there's a treasure trove of data that Akeso has created across multiple randomized studies. So we are developing an understanding of which patients we think that benefits, not necessarily just coming from the EGFR study, if that's fair.

Okay. And then given the smaller sample size and the unique tumor type here, how much can you read from the data you're seeing in HARMONi over to the much bigger and broader frontline non-small cell lung cancer indication?

Yes. I mean I think there's a couple of critical components, right? We talk about a very tolerable and manageable safety profile that's clearly differentiated from historical combinations of PD-1 and VEGF, VEGF-A, VEGFR-TKIs, any combination of VEGF inhibition. And so when we look at that, a lot -- one of the major components that people had was, hey, we're seeing very good safety in China, will that translate into a global setting? I think kind of irrespective of setting, the randomized Phase III that includes a very representative portion of Western patients and seeing very comparable safety between the 2 is extremely important, right? And so this is something that I think for us is not -- it was not something that we were particularly concerned about given the diligence and the work that we had done and the data that we had seen. But I think this was reassuring for external folks, physicians, investors and any -- depending on wherever you take that in the sense of from a safety perspective, what was seen in the single-region studies was replicated in the global studies. I think we can -- that's one. I think, two, in general, that you take away the translatability from East to West was very consistent. And so when you look at these additional studies like HARMONi-6 and how does that translate into HARMONi-3, you feel very confident that both from the efficacy and the safety perspective, the HARMONi-6, which is ivo plus chemo versus PD-1 plus chemo in frontline squamous non-small cell lung cancer as compared to HARMONi-3, the squamous arm, which is ivo plus chemo, PD-1 plus chemo, frontline squamous lung. There's no better representation of a proof of concept than running a randomized Phase III study with your drug in the right -- in that setting to then show the translation there. So by seeing the safety and the efficacy translate directly, seeing the overall survival in HARMONi-A, the nominal p-value that showed the survival in HARMONi, I mean, those are very important in terms of the applicability across studies.

Got it. Got it. So I want to go back on this translatability question and go back to the HARMONi update you provided at World Lung this year, this fall. A question or if people wanted to take issue with and we kind of got pushed back on was this how the European patients did in that study relative to patients in North America. Do you see the European patients underperforming this? Is it small numbers, timing of coming on the study? Is there anything to it?

Let me give you an analogy for that one, right? So one of the strongest drugs currently in lung cancer today is actually in the frontline setting of EGFR mutant, which is TAGRISSO, right? It's an exceptionally strong drug. It's wonderful for patients. It's very well positioned both in the FLAURA study and the FLAURA-2 study. So FLURA frontline, osimertinib monotherapy. FLURA2, TAGRISSO plus chemotherapy. Both of those had subgroups regionally that showed a hazard ratio of 1.00. I don't think anybody should read into that. I think that's a subgroup that is not intended to be looked at statistically. It shows nothing meaningful in terms of what that means for the ability of the drug. And so now we're looking at a much tighter look in terms of Western patients versus Eastern patients, which is much more in line with the ITT overall. So our hazard ratios in overall survival, in particular, are a couple of basis points off of each other. I think trying to look at subs and subs, I mean, at one point, you can just keep going down and down and down. I don't think in any way that there's anything more than trials that aren't powered to look at that level of detail. All patients -- I think we're very clear on this, all patients had a -- in the long-term follow-up analysis, we -- you had the forest plot there, all showed a benefit. I think overanalyzing those levels of details is not really what the trial is powered for or designed for.

Okay. That's a very good point. All right. So I have a couple of questions for you on the plans to file for approval for this EGFR-mutant indication. And I guess one question that comes up is, why even pursue the indication given the IRA implications here of getting that clock started like 18-plus months earlier? I guess this goes back to one of the first things we talked about, like how strategically important is it to get onto the market ASAP. Is that the reason you do this?

Yes. I'd say 2 things there. One, I don't know that it's 18-plus months before, right? We talked about reading out frontline squamous in the second half of 2026, right? So that readout can come before a BLA decision. And so I don't know that I would put quite as long of an arc on that. I would also say you're now talking 11, 12 years out that the entire U.S. health care landscape doesn't change in that period of time. Maybe, maybe not. And so I don't know that a decision to look quite that far out on ivonescimab makes a lot of sense in terms of assuming nothing will change with the IRA over the course of multiple administrations, multiple congresses coming through. I think the other thing that's really important, too, is when we in-licensed ivonescimab, one of the -- we had a couple of things. One, we saw the frontline squamous data. It was clearly differentiated. It was -- we needed to go very quickly into that space. But the other piece was we saw an unmet need in relapsed EGFR-mutant patients. And part of the reason we looked, one, there was an ability to get on to market more expeditiously and provide a broader set of physicians with the opportunity to use the drug. But I don't want to lose sight of the fact that what we also did was we saw an unmet need where patients needed improved therapies. And so we ran a clinical trial. We asked patients to trust us and to trust their physicians and the physicians to trust us with a drug that has now shown clinically meaningful benefits, right? And now to say we're going to not put that, we're not going to make that drug available to patients who need it. And we still believe there's a real unmet need in that space. We can go into that in more detail. But we have a very tolerable regimen that showed clear benefits from an efficacy perspective. The idea of withholding that for maybe in 12 years, the way in which we approach economics with drugs doesn't change, I don't think that's ethically the right thing to do. We have something that can benefit patients. We should take that opportunity to provide that benefit to those patients, should the agency agree.

Yes. I think that's a very fair point. So in terms of the agency agreeing, how much risk do you see to the filing given the dialog you've had with the FDA in the past about needing a statistically significant improvement in overall survival?

Yes, you want me to take that?

Sure.

So I think we've been pretty transparent that we've had discussions with them. They said we need OS. But if you look at it from a physician's point of view, this is an important therapy for patients. And I think Dave touched on that. I don't think Bob and Maky would allow us for a business reason to deny patients this drug, right? If you look at the clinical data and you look at the efficacy, it seems comparable to amivantamab, right, with a much better AE profile, any way you look at it, number of AEs, number of discontinuations or dose reductions, right? So we're comparable to that. And that's the one of the 2 drugs that is approved in that space.

The only fully approved drug.

Fully approved drug. The other approved drug was approved on overall response rate and duration of response in a pooled data set, right? And that was conditional approval. We're a lot closer to the other drug and probably a little bit better from a tox profile. The physicians say they want this drug. And this is the drug that they would want to give to their patients, right? In addition, if you look at it, amivantamab with lazertinib in combination is now approved in the first line setting, right, with an OS benefit over a third-generation TKI, right? So many patients will move on to that therapy. And what do those patients have available to them second-line, right? So here's another unmet opportunity. So given all that, sort of a arbitrary agreement based on OS, which no other drug has hit, doesn't seem fair to us or the patients, right? And so let the FDA say that. Let them look at the data and see what we see and then make their decision.

Right. Okay. All right. So moving on to HARMONi-6, where we saw the really strong PFS data at ESMO. I guess similar to HARMONi-2, when could we expect to get an overall survival update from that study? And again, much like HARMONi-2, how do you think about this in the context of it again being a relatively underpowered secondary endpoint?

Sure. Yes. So again, that study was run by our partner, Akeso. So I won't -- I'll defer in terms of specific timing. I think we saw the protocol again in the -- Lancet publications are strong. And so we have multiple of them now. So in the Lancet publication, we saw the protocol. We can kind of surmise that it's -- there's an interim somewhere in '26, somewhere, but that's up to -- in terms of more specifics, I won't shed light there. But I think when we look at what does that mean, right? And so this is -- the other thing to consider is we'll see HARMONi-3 data in 2026 as well, right? So we said we'll complete enrollment in the squamous patient population in the first half of 2026 with a data readout in the second half of 2026, right? And so depending on timing, which comes first will have an impact there. But I think we saw incredibly encouraging signs from the HARMONi-6 data. If you look at the curves, the curves continue to separate beyond chemotherapy induction, and those curves grow over time basically through the median follow-up time. You have a higher numerical overall response rate, duration of response is longer. And those curves again stay separated until the median follow-up time. And so it's important to consider how long patients have been on therapy when looking at those curves. We see an AE profile that's pristine. We see low and comparable discontinuations and death. So with all that, if you look at what's a prognostic factor in terms of looking at what are ways in which you ultimately shed light early on what potential survival can look like, it's a pretty good start. And so part of this is time in terms of the actual analysis. I think that's important. It's important to remember that the HARMONi-6 study hit on an interim PFS look, right? And so typically, you have interim overall survival linked more to the final PFS look, which would have been much later, but the interim PFS hit, which is where it's just simply too immature for OS at that point.

So then to piggyback on that, the global Phase III equivalent of HARMONi-6 is HARMONi-3. And this is where you've now -- and it's great to see if you did is split it up into the squam and non-squam -- and we'll get that first update from HARMONi-3 in the squamous population in the second half of next year is what's anticipated. Big difference here versus HARMONi-6 is that PFS and OS are co-primary endpoints. So should we expect an overall survival look when you get to that data readout in the second half of next year, assuming that's the time it hits on?

Yes. And so -- and I think that's where, again, I'd differentiate HARMONi-3 and 6, which is we won't have an interim PFS look. We'll have a single PFS look. And so with that coming in the second half of 2026, we would also expect in the second half of '26, an interim OS look as well.

Okay. Do you plan to disclose the powering assumptions for HARMONi-3, HARMONi-7? Any journals we should be looking into?

We likely will not publish the results of the study before we disclose them. I think there's no imminent plan in terms of powering. I would just say a similar comment we've made before, it's powered for a clinically meaningful benefit. We're very much -- we feel very confident in terms of where we sit today, and that's where the study is designed to show that success.

Okay. I did want to spend some time talking about opportunities beyond lung cancer and just kind of the strategy around ivonescimab overall. As you alluded to upfront, you committed -- you've started now the Phase III in colorectal. You talked about how large of an opportunity that could be, and we totally concur with that. I guess one question is, when do you expect to be in a position to announce additional indications? And then the follow-on specifically of colorectal, will we see additional data there that kind of helped inform the move into that Phase III trial?

Yes. So I think -- the second one first, which is the more data to help inform that. Probably. In terms of timing, not yet in terms of where and when. I think importantly, though, if you look at the data that was used in -- or presented rather at ESMO 2024, you saw a FOLFOXIRI, ivo combination that showed about an 82% overall response rate. And so that obviously is significantly encouraging to us, if you will, in terms of what that looks like compared to historical results of bev plus FOLFOXIRI. So we ran, again, those multiple chemo settings in addition there, too, and ultimately landed based on physician preference, standard of care in the Western markets with FOLFOX. That data -- we have that Phase II data. So we will likely make that more available in the future. In terms of additional indications, there are obviously a number, whether you look at the Phase IIIs that Akeso has opted to run outside of lung cancer in addition to some of the Phase II data that's been generated. Even if it hasn't been published, you can see where some of that data is being generated in terms of the Phase IIs in addition to what's being done with clinical trials at MD Anderson, other IST programs and so forth. So we said at ESMO, we plan to run additional Phase III studies. We -- because of -- we have multiple companies out there with PD-1 VEGFs, we have no intention of taking the treasure trove of data that we have access to and kind of giving any more insight in terms of where we plan to go and where we think we should go next because we can make those informed decisions. If you look at -- we announced CRC mid- to late October and are now in the beginning of December here enrolling patients. And so we have no need to foreshadow multiple places to allow others to be at the same track.

No, that makes a lot of sense. All right. So this is where I want to bring the discussion full circle and bring it back to strategy. And Bob, I'm thrilled you're sitting up here with us. Do you believe you need a large pharma partner to maximize the potential of ivonescimab? And maybe another way of asking this is, how big can you feasibly go without a partner?

Yes. Two very good questions. Let me interject another one. Should we have had one already? And I can assure everybody in the audience here that had we had a big partner, we would not be where we are today. If we had a partner, we would have done maybe half the revenue or we could have sold the company. We looked and examined the partners, and we would not have gone into the IST program we've gone into. We have over 50 IST programs, and they're flourishing. We would not have gone outside of NSCLC. We've gone outside of CLC, and we do have plans of at least 3 more, and those look really, really appetizing. And we've not refiled for the -- we would never have done the EFRG (sic) [ EGFR ] study. EFRG study for patients was a nominal p-value success. And it took courage to do it, but there was an opportunity to do it, page back. This is our second-generation team, by the way, was a wonderful drug in their hands. The Pharmacyclics team was the first generation. And some people followed me even over from robotics, which is the early beginning where the outsiders said that's not going to happen. And we'd love to hear that because if we win, we win big. So the EGFR, there's a need there. And we have a solution to the need. And so let's go ahead and do it. And we did it. What we misestimated was the angst and the concern about the transfer of China data to the U.S.A. data. I have a key to the city of Shanghai. I'm proud of that. I love the Chinese. I love their innovation. I was there in 1987, and I saw things then that I've now seen and I don't look back with amazement, I look back with admiration for what they've really accomplished, the best and the brightest that are out there. So we took that trial on, and we're glad that we did. But in the first 4 months, we enrolled 2 patients. The American doctors were, you want me to go guinea pig for Chinese data. It's not going to happen. Bispecifics is a new word to me. I don't really know it. And what are the class of doctors do? They do what they read that others have done that have worked. There's nothing to read to show that it worked. So by the way, there's bleeders in the study, and we're going to show them. And then if nothing that, there will be complication of brain mets, none of which have occurred, the translatability there, the brain mets didn't occur, bleeders didn't occur. The bispecifics are out. There's 40 of them and everybody is in them, except there's not one that looks like we look like. If they're exactly like us, then with the lowest royalties. So we're an aggressive courageous company that goes for what we see is true, not what we can go to others and say, it looks true to us, does it look true to you? And if we get 10 out of 10, then we go ahead and do it. And oftentimes, they're wrong. If it's good for us, it's good. But we've got these 2 on the table like this, how many of you would not hire them immediately if we let them go tomorrow to be on your research team. There's no 2 people better than this. And the third one is better sitting in the front row, which is the [indiscernible]. We got a pack of winners here. Yes, the brilliant -- I was telling Dave Rick, you took a weight loss drug and you made it cure everything, and now you've got a $1 trillion company. Congratulations because he deserves -- he really did a hell of a job there. That's a big drug. Then you've got pembro, another big drug and add OPDIVO to it, another big drug. We go beyond. We could have the biggest of those 3 sitting right here in this room today at a $12 billion market cap. And that's why I got $1 billion. I listen to these guys chat back and forth every day of the week, 7 days a week because we're on phone or working with them one way or another and just get validation for the courage that I had to put the money in here and to do business when others were doing it. So this is a victory for patients first, for having the courage to go with what you see is true, not what other people see is true, and this is a follower in the industry. So I don't mean that, that doesn't work. It does. There's a lot of me-toos and a lot of followers, but this is not what this company is about. It's an aggressive company and a partner with Akeso. There is not a company that I've seen or found in my 25 years in this business that has more new products doing better than Akeso. There isn't one. They don't have 5 losers and 2 winners. They don't have 25 losers and 3 winners. They're all f******* winners. I mean they are unbelievable people that are working their a** off and they're incredibly bright. And by the way, the leaders have American citizenship. And by the way, we borrowed -- we took that technology from China and brought it to America and the rest of the world and are going to generate a lot of revenues of it. Thank you very much, boys and girls in China. So -- and we're going to get paid for it. And that's why we haven't partnered yet. Now to your 2 questions, when is the right time? Well, when it's recognized, when there's enough written data to show you that you can follow the written data. So when you follow the written data and if it doesn't work, you don't get fired because say, look, that's what they freaking told me that that's going to come as we're sitting here. And it's in the next 12 months that's coming. And then we'll see what the enthusiasm is and what the price is. If we do anything, it won't be partner because in a partner, you've got to give up control, control equals income, you've all made money, you know that. You turn control over and you may go to Las Vegas to be the effect of somebody else's rolling the dice. So that's not going to happen. So if you don't give up control, then they need to control. But we can still own it and control if we pick the right partner and we get equity and not cash. So that's what, in my opinion, you should expect. So we're -- first place, we're in wealth -- the health business, health. You're born, you die because nobody gets through without needing HEAL, healing to cure the disease. We all need that. And aside from that, we're in the wealth business. And we're going to create wealth doing that, and that's what makes the world go around. So if you like that kind of a game and you own it, hold on. If you don't like it, buy it. If you're short, you should go. At the end of the day, nothing beats big pharma when you've got the machine. But you've got to load the gas tank and it's got to have the right bullets in it. And we're a loaded gas tank. We've got the right bullets. And we just, rest assured, we will pick the group that can really take this to market and shares our enthusiasm for patient-first therapy. And I'll be a shareholder.

I love it. I was going to ask for a sneak peek into '26. I think we all know what's coming in '26. That's too good not to end right there. Bob and the rest of the team, thank you guys very much.

I mean who doesn't love Evercore. If you followed Evercore and not made money, go and do another business.

Thank you very much. I appreciate it. Thank you, guys, and good luck.

Thank you, Cory.