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

Great. So welcome, everyone, to the Summit Therapeutics session. Yigal Nochomovitz, biotech analyst here at Citi. We launched coverage on Summit just before ASCO in 2024. So obviously, a lot has happened, a lot of interesting things to talk about. They've set some records. They're setting a record now with the most chairs on the stage for a panel. So welcome, everyone. Bob Duggan, is the Chairman and CEO; and Maky Zanganeh, also CEO, Co-CEO and President; Dave Gancarz who leads the business strategy and IR function. And Allen is the Chief Medical Officer. So welcome, everyone. Thank you so much. And I think Manmeet is here, but he's in the audience. So the other -- just a quick housekeeping thing. If you have questions, you can type them into your laptop and I'll see them on the tablet, and I can ask the questions.

So with that, Bob, maybe we could just start with the sort of easy big picture question, which is tell us how you came to identify ivonescimab in your very comprehensive asset search several years ago, what was -- what were the factors that you were looking for? And why did this asset rise to the level of the one that merited the investment?

First, it's wonderful to be here. I thank each of you for attending. I'll give a shout out to Yigal. We leveraged some of his internal skills. I call him the man with 8 eyes. He sees everything that is going on in a room from whatever perspective. And it was not easy to pick us as a significant winner at the time that he didn't, we thank you for that. So our story goes back to a while. We bought -- I bought into a Summit when it was an antibiotic competitors to vancomycin. And it's a story for another day. But we did a good job there. We found out the amazing impact that antibiotics have in the microbiome that have been underestimated and undiscovered. And we left that scene with a nice report that we're really proud of having done. At the end of that day, though, we've assembled a very strong team, and we looked at the field of oncology. We knew we wanted to make a significant investment into the field. We made a decision that I think most VCs would not make. Let's get the very, very top people even before we have a product because those people will guide us in the direction of what product we want to bring in. So we brought together just, I think, a treasure trove of top oncologists. And as we scan the area and I give a big shout out to Dave Gancarz, and doing that business development, we looked at hundreds of companies. And of course, all eyes would go from my perspective, over to China, the key to the city of Shanghai introduced robotics in China decades ago and have always had wonderful relationships here in respect for the people for the hard work, for the insight and for the brilliance that emanates. And I noticed that at the FDA, up to 40% of the new drugs being evolved and we'll give them credit to China. And 20 years earlier, it was like 2% or 3%. So they were definitely strong and powerful in the area of insight and innovation. And we found several companies with products, ultimately, we came upon Summit. Michelle Shao was running the company. She's the Chinese, also USA Passport, speaks perfect English, [indiscernible] young, the top scientists there speaks perfect English, educated, spent a good time in America. So these are Americans that were in terms of training and Chinese in terms of citizenship, culture and birthright. And we thought that mix was awesome. And we got together with them created good relationships. The challenge is we were just a team of like 30 people, and they were looking to bring a world class drug in, which we all know ultimately is going to be a multi-deca billion dollar potential benefit to society. So how are they going to do business with a little company like us? They already had a partnership with Merck. And it took a bit of communication. In fact, a lot of communication to convince them that the team we assembled was going to be 100% on ivonescimab and we were qualified, we were capable. The previous drug we had managed was -- got to $1 billion in revenues in year 2. We took a market cap of $15 million and generated a drug value of $42 billion. And so we were small in numbers, but we were large in terms of impact. So that won the day with them, and we put the partnership together. She wanted $0.5 billion upfront. Our company had a market cap of $200 million at the time, but I had that money in my back pocket, fortunately. Not that I always had that, but I did it the time. And so we were able to do a transaction that others couldn't and wouldn't do. Big pharma and relationship to China was -- that was not a game that big pharma wanted to play at the time just for geopolitical reasons. So we were there alone put the package together. And we turned out, we raised money after that transaction up to $1 billion. The cost of those funds were less than $0.5 million. We had -- unfortunately, we had no Wall Street commissions were paid out on it. So we had contact with the investors that wanted to be in the game and play the game with us. Akeso owns 4% of our company. I own full disclosure of 1.1% of Akeso, and they're very happy with our ownership. I'm happy with mine. These are 2 teams of really great and fascinating people with a common denominator. How do we really make an impact on society in the world of health care and do so in a way that's new, novel and sets a trend into the future that becomes very rewarding. And of course, if you do that and do that well, the money is going to fall off the trees. We don't focus on the money off the tree. We focus on making that huge difference. So I'll turn this back over to my team now. We've -- I would just say this one last thing in passing. It was non-small cell lung cancer that we were really after and as I said, Michelle was a part of inventing the BCK particle that have done so well. So we got together, we worked hard on it and much to our great surprise. We think there's a market outside of NSCLC that's as big as, if not bigger, than inside NSCLC. So we wound up with a price that was much bigger than any of us thought and our challenges are going to be moving quickly, moving fast and doing appropriate trials so that we can get through the FDA and regulatory approvals. But Yigal, I'll turn that back over to you now.

Thanks, Bob. Great setup. So let's just level set maybe Dave or Alan, you could just give us the quick pitch on ivonescimab's mechanism of action. Obviously, it's doing something very interesting, no doubt, given what we've seen over the summer. So tell us about the design, why it's special, what are the properties? And then we can talk about some of the other attempts out there, some of the competitors and how you're different?

So thanks for the question. So real quick, I'll just be upfront and say I won't say anything about any specific competitors because the gentleman to my right advises me against it. But first of all, it's been a sea change in about a year. People really didn't understand ivonescimab. And I think now there's a clear understanding that ivonescimab is really unique. There's something special there. That's a drug in a lifetime, one of the drugs of a lifetime. So it has 2 validated targets. And I think that's what people were turned off of. PD-1 and VEGF are well-known targets in oncology. They're validated why would you need to put them together in a single molecule. And I think what people don't realize is by putting them together in a single molecule and engineering it in a very unique way, it creates properties that go beyond each individual target. So the key is cooperativity. So the binding of one ligand increases the binding of the other ligand. For instance, when VEGF binds the binding of PD-1 increases by greater than tenfold. And that tight binding and the need for both of them to be present for that means that the drug will target areas where both PD-1 and VEGF are most highly expressed, which we believe to be the tumor micro environment. That's going to increase both efficacy and safety. Now there are some other unique features, there's something called the Morrison format, where you have 2 binding sites for PD-1 and 2 binding sites for VEGF. And that leads to a unique property as well. It's well known in the bevacizumab literature that VEGF is a dimer. So 2 identical halves. And so bevacizumab combined each half of that molecule and that combined to another VEGF into another bevacizumab and you get this daisy trading effect. The same thing can occur with ivonescimab, and that will lead to daisy chaining of ivonescimab with VEGF to these large immune complexes, which will then present multiple high affinity PD-1 sites and this increases the avidity of the molecule. So you now have multiple hands grabbing onto the T lymphocytes stimulating the immune system. And the final feature of that Morrison format is the half-life changes. So the half-life has dropped to about 7 days. Bevacizumab's half-life is around 21 days, for IVO it's 7 to 9 days, depending on the dosing. And so that sort of respite leads to an identical peak level of VEGF inhibition but a trough allows some VEGF recovery, and we believe that, that helps with the VEGF associated toxicities. So those are just some of the high-level points about ivonescimab that make it unique, but we believe that all of those features are important. Now the validation of those hypotheses and the bioengineering that Akeso did would be all the competitors. We now know there's about 21 competitors for the PD-1 VEGF. Some of them target PD-1, some of them target PD-L1, some of them target VEGF, the ligand. Some of them target what are the VEGF receptors like VEGF receptor 2. As far as we know, there's only one with a cooperativity which we call Allosteric cooperativity which increases the affinity. But the people have not been forthright and you can't really tell from their patents. But those are the high levels, the unique features of IVO.

So you answered my question around why we're -- because I get this question a lot around why we aren't seeing the typical bleeding risk that you see with the anti-VEGF. So I think you've answered that unless you want to expand on that point a little bit?

Yes. The key thing about the adverse events of both PD-1 and VEGF associated adverse they're both on-target off-organ events. So that's a key, right? So when you have binding a PD-1 or VEGF in the circulation, you're going to get things like T lymphocytes that are activated that go to the thyroid or the heart to cause thyroiditis, myicarditis. When you suppress VEGF in the circulation or in the endothelial cells, you'll get poor blood vessel, wound healing, you can get thromboembolic events, bleeding events because you're not regenerating endothelial cells. So those are the toxicities. But if you can accumulate the drug in the tumor microenvironment, you can really avoid that. And that's the key, and I think the clinical data, and I think that's the most important thing about ivonescimab is that it's been proven clinically to be better than pembrolizumab and all the other ones have yet to do that.

So let's move over to clinical trials, starting with the one that's the most topical HARMONi-2 , which I'll give you a chance to just -- first of all, just Allen, just to kind of review the design and so everyone understands what the trial showed in the PFS result and then we can ask from there.

Yes, Yigal. So thanks for the question. So there's been 2 randomized studies that show that ivenesumab is very effective, both placebo-controlled blinded studies. So the first one was HARMONi-A which was IO chemo versus chemo in the EGFR second-line population. The one Yigal is referring to is HARMONi-2, which we believed always to be a very important experiment because it was monotherapy ivonescimab versus monotherapy pembrolizumab, a very clean experiment in frontline non-small cell lung cancer. And what it showed was a very significant improvement in PFS, which was the primary endpoint. So for ivonescimab, it was well over 11 months. And then for pembrolizumab, it was under 6 months. So a significant improvement. What was more exciting about that was the AE profile. So remember, ivonescimab targets both PD-1 and VEGF, and pembro targets just PD-1. So in terms of immune-related adverse events, they were about the same in that study. Actually, it was numerically lower in ivonescimab for these immune-related adverse events. Overall, the number of adverse events was higher in ivonescimab. But if you look at those adverse events, they were mostly related to VEGF, particularly hypertension and proteinuria, which are very manageable from a clinical perspective. And if you look at the things that were important adverse events from VEGF bleeding and thromboembolism, they were about the same between the 2 groups. Thromboembolism is the same. I think there was numerically 1 or 2 more bleeding events in ivonescimab compared to pembrolizumab. If you look at the treatment discontinuation rate due to adverse events. Remember, this is a blinded study it was actually numerically higher in pembrolizumab. And that's also why we're so excited. We think the efficacy is clearly improving, but the safety profile looks better as well.

Great. So now let me just go through 2 of the most common questions that I get from my desk in New York on HARMONi-2 and give you a chance to respond and explain how you see things. Obviously, the first one is related just to the geography where the trial was conducted in China and the fact that it was at a limited number of sites. So that's one. And then the second question, of course, is on a bigger question of overall survival, and how some people are making parallels, perhaps inappropriate perils from what's seen in the second-line setting to what may happen in the frontline setting. So we could just tackle those 2 important questions. That would be great.

So for the number of sites, it wasn't a limited number of sites actually. There were 60 sites that screen patients in 55 sites that enrolled patients. So it is a single region study. It was conducted in China. It was designed to be a China registration study. This anecdote of -- is Chinese sites different or anything like that. That's not true. If you look at most non-small cell lung cancer studies today, a majority of the enrollment comes from China or Asia in general. In terms of PFS leading to OS, it's always hard to sort of pin down like which study they're talking about. Is it a subset study? Is it a post-hoc analysis? I mean if you look at the history of studies with a very strong PFS, well below 0.7, 0.6. Now you're talking into the 0.5 ranges, it's unlikely that OS is going to miss, right?

And I think another question that you had in there, Yigal, was with respect to HARMONi-A, that had a very good PFS benefit, about 0.46 hazard ratio that translated into roughly a 0.72, 0.8 overall survival ratio. And so I think as we look at HARMONi-2, there's a couple of real key differences that exist between those 2 studies, right? One of which is the HARMONi-A was a second-line study in an actionable genomic alteration. So that was post 2-plus years of targeted therapy prior to. So those are much more heavily, pretreated patients who have multiple years post diagnosis. With respect to HARMONi-2, this is now a frontline setting. Also, it's important to keep in mind because of those differentiators, the PFS benefit that we saw that Allen just mentioned, over 11 months of PFS from a median PFS perspective in HARMONi-2 versus about 5.5 months in the pembrolizumab arm. So that's a greater than 5 month difference that we see there. So that significant increase from a PFS perspective, just on a gross magnitude perspective that is very different than what we saw in second line. Second line is going to be because they're more pretreated, that was a 7.1% versus 4.8 or about a 2-month, 3-month difference. So when you carry in HARMONi-A, that study carried the PFS benefit into overall survival. But this becomes math in some ways, the denominator is a little bit different. It was a 14-month overall survival in -- from the baseline from chemotherapy and then 2.5-month benefit in HARMONi-A for ivonescimab plus chemo. What that translated into was a lower hazard ratio from a survival benefit. In the frontline setting, though, it's a little bit different in the sense of that 5-month difference is basically on a similar 17 to 20-month benefit for pembrolizumab based on those historical studies. So if we look back at KEYNOTE-042, for example, which is a reasonably replicable or referenceable study for this particular setting, 17 to 20 months of survival. If that 5-month benefit stays or slightly increases as was seen with HARMONi-A, that would be a very different result from a hazard ratio perspective, when we get into stat and clinically meaningful differences. So I wouldn't draw parallels between a second-line actionable genomic alteration based study. into a frontline monotherapy study because I think those are very different in terms of both settings, just the basic math behind that, et cetera. And so hopefully, that gives a little bit of color there.

Yes. And the other piece, if I could add quickly because we spoke with an expert in lung cancer at UCSF yesterday, Victoria Wang. And she made the point that, look, in the second-line EGFR KEYTRUDA, it didn't work, right? I mean, keynote. What was it?

789.

Yes, right. So just it's not a very good parallel to begin to consider.

I believe Yigal, you're making a very important point because -- that is where we are differentiating as well in all of the immunotherapy with our bispecific. It could be a lot of places that eventually cater all of the immunotherapy that they were and they show result. They didn't show results, we can't show results just is by specific aspect of the drug, and that is allow us to be in a different market, not just the market of KEYTRUDA or pembro and everything or avastin or anything that any other drug didn't really respond. And that is really the beauty of this molecule at this point.

Thank you. And the other common question I get, there was a third one, which is -- everyone is asking me, can you provide some window or visibility into when we might get a look at the overall survival for HARMONi-2? And I know that's going to be more of an Akeso question than a Summit question, but still a Summit question.

Yes. So I appreciate the question, Yigal. But as you alluded to, so first and foremost, this is a study conducted in sponsored by Akeso, right? So it's important that we keep in mind, we don't want to supersede our partners with respect to disclosing information about their studies. And I think as we've mentioned in the past, I think we mentioned this on the earnings call as well as I think our partners at Akeso have been clear about as well. This was a PFS primary endpoint. And so with that, that is the registrational endpoint in China that was completely appropriate in terms of design and whatnot. And so -- but with that comes a smaller sample size based on a single primary endpoint. I think the -- so there's 2 kind of aspects of that question, one of which is when will we see an OS readout. The other is what do you do with the information once you see it, right, which is, if you think about it from a summit perspective, the you see positive results in the study and that then gives you the confidence to go into the next step with respect to the clinical development plan. i.e., launch a global Phase III study, right? And so from our perspective, we've made that go decision. We are -- we have announced HARMONi-7. HARMONi-7 is in the PD-L1 high monotherapy setting, ivonescimab monotherapy, pembrolizumab monotherapy, frontline non-small cell lung cancer, right? And so we're taking the direct results from HARMONi-2, and we've made that actionable go decision. -- you'll note in HARMONY 7, just from a design perspective, and you can see this on our website, there -- it's a dual primary end point with PFS and OS, and I think that reflects the way in which we reviewed the studies in our licensed territories, particularly in the U.S. and Europe. With that comes a larger sample size to account for those 2 primary endpoints and in particular, the OS endpoint, right? And so because of the smaller sample size in China, as well as when that endpoint hit that PFS hit on the first interim analysis in order to show survival that -- which is part of the preplanned statistical analysis plan. And I think Akeso's been clear on that. That's going to take a little bit more time because of the small number of events in order to avoid statistical noise, you simply need a higher number of events to show in order to be able to work through the statistics and avoid any statistical noise. So the preplanned analysis comes a little bit later than would be expected. So we haven't given out specifics on time line, but it's not something that we think is in the immediate term because of the design of the trial, but we've made that go decision. So from our confidence perspective, if you will, like when we look at the data and what we want to do, we've made that go decision, and we will be enrolling patients in HARMONi-7 in early 2025. And so all of that work is already being done to open that study now.

So just to make sure everyone understands HARMONi-7 is monotherapy versus monotherapy?

That's correct.

In the high PD-L1 squams and

Squams and non-squams. So it's both histologies and then PD-L1 high expressors.

And now explain HARMONi-3 and you made a modification to broaden it so that capture basically the whole spectrum. So can we just go through the logic? Because originally, HARMONi-3 was -- you had the data when I first met you in ASCO 2023. You had the Phase II data in the squams and that looked great and then you went into HARMONi-3 with squams and then you saw HARMONi-2 and it changed the thinking perhaps and now you're broadening it. So let's kind of go through that.

No, exactly Yigal. So maybe I can go a little bit through the background there, that will help explain so. So HARMONi-3 was initially, as Yigal mentioned, based on the study called 201, which are Phase II data, it had very good squamous data in combination, so ivonescimab in combination with chemotherapy. At the time, we didn't have the HARMONi-2 data, right? So we thought that the squamous population was an unmet need and low-hanging fruit for ivonescimab because ivonescimab targeted both PD-1 and VEGF, we thought it could be developed in squamous more easily. The reason being is that VEGF or Avastin or bevacizumab was never developed in squamous due to a concern around bleeding. So what happened was we started that study as sort of a low-hanging fruit sort of study after our fast-to-market strategy, which is the EGFR HARMONi study, then the HARMONi-2 data came out. We've always said that, that was a gating event for us. Like that scientifically was very important. And what it showed was that ivonescimab beat pembro not only in the low expressing PD-L1 population, but as well as the high-expressing PD-L1 population. We knew the likelihood of beating pembro in the low PD-L1 expression was high because we added the VEGF. But we always thought that maybe Ivo could make the PD-1 better. And we found that the PD-1 high population, ivonescimab also significantly beat pembrolizumab. So that meant that it was active. And finally, it was active across both the squamous and non-squamous population. So that gave us the scientific confidence to amend HARMONi-3 to include not only the squamous, but also the non-squamous. And the rationale really for doing that was efficiency and execution. This will save about a year's time in terms of setting up and planning a new study analogous to something called the KEYNOTE-189 study. So we can combine those 2 indications into a single study and execute and bring this therapy to patients faster. So with the HARMONi-3 and the HARMONi-7 study, those 2 studies will wrap up and secure ivonescimab for the metastatic non-small cell lung cancer area.

And then the other interesting question that I just thought of was, in speaking to the same expert yesterday. She was saying the United States, even if you're above GPS 50%, 60%-70%, and we talked about this you're probably going to give them chemo anyway. And so that makes me wonder, like, I know it's kind of checking all the boxes with HARMONi-7, but do you really need HARMONi-7? Or do you I mean you could get away with HARMONi-3 and then let people decide what to do, right?

Yes. So the TPS high or the PD-L1 high expresses, I think it goes a little bit institution to institution and depending on where within the country you are in the performance status of the patient. There's a lot of factors that go into them. But there are a significant number of patients who still receive monotherapy. So it is important to really show that benefit both from monotherapy perspective in the PD-L1 high where those patients receive the greatest value as well as the agnostic PD-L1-agnostic population to really show the benefit across the PD-L1 scores. And of course, there'll be patients who are slightly under 50% who may not be able to tolerate chemotherapy. And so you really want to make sure that you have the clear evidence that this is a very viable option for those patients.

And now just similar time line questions. Can you say anything at this point as far as the data disclosure plan for HARMONi-3? And then in answering that, there's another study which most people are not aware of, called HARMONi-6, which is an Akeso trial. It has certain parallels to HARMONi-3, except it's using the BeiGene PD-1. But that one, as I understand, it's a little bit ahead of HARMONi-3 perhaps, but tell us how much is it ahead? Could that be a read-through proxy for HARMONi-3? People that are watching in here?

Yes, absolutely. So I won't give away yet the time lines with respect to HARMONi-3. And part of that is really, we announced the amendment just basically 5 or 6 weeks ago. And so we're still going through finalizing all of those details, initiating additional sites. So we want to just kind of allow that to breathe for a minute before we give. But we will give additional context on that as we continue to move forward. But nonetheless, you bring up a good point with respect to the HARMONi-6. So basically, a couple of factors. So that is similar to HARMONi-3 and that it's a chemo combination in frontline it is exclusively squamous. So in China, they're not looking at both histologies the way we are now with the amended HARMONi-3 study. But a couple of factors, as you mentioned, they started a little bit earlier in HARMONi-6 and in China, just given the structure of the hospitals and health systems that exist in China, the enrollment just almost always takes place more quickly in China which -- so while they haven't given -- they, Akeso,our partners haven't given specific time lines, it is safe to say that, that study will complete enrollment and read out more quickly than our HARMONi-3 study will. With that, because it's a frontline study that effectively covers half of -- still half of the HARMONi-3 population, right? And it's against, as you mentioned, PD-1 plus chemo. So they're using BeiGene's PD-1 in that instance, tislelizumab. There are some obvious read-throughs that we'll be able to be seen from that. So we have very good Phase II data in single arm ivonescimab plus chemo, but this will be a randomized Phase III that will show head-to-head against a PD-1 plus chemo. And if you look back at the tislelizumab plus chemo studies, the rationale studies that were run, those show very comparable results, a big picture to what pembrolizumab plus chemotherapy looked like as well. So it's a good proxy.

A couple of other things because we've got a lot to cover in the next 5 minutes and 57 seconds. So with the chemo backbone for HARMONi-3, a lot of people ask me, the rising tide rises all boats, right? So you're going to have chemo in both arms. Now that could one, maybe blunt PFS a little bit because of chemo, but are you still going to be able to extract the OS delta that you've potentially got from the HARMONi-2 assuming that, as Dave was saying, assuming the PFS flows on to OS? So if you could just comment on terms of how you think about the odds of success given that you're -- it's different now that you have chemo on both sides.

Yes. So Yigal, I think what you're asking is once you combine ivonescimab with chemotherapy, do you blunt the benefit of ivonescimab ? The answer is no. You need the data, but no. Because if you look at the history, right, so pembro therapy was improved by the addition of chemotherapy. Avastin or bevacizumab therapy was improved by the addition of chemotherapy. We have no data to show that adding chemotherapy to ivonescimab will blunt its benefit over pembrolizumab. In fact, the data that we do have clinically is from the 201 study which was a frontline study of ivonescimab in combination in the squamous and non-squamous population. They use slightly different chemos, and using each of those chemos. And it showed a very clear, very strong improvement in PFS and OS, just not in a randomized fashion.

Let's move very quickly. We had another interesting conversation yesterday with the breast cancer expert from Dana Farber, who's quite impressed with the triple-negative data. But can we just go through quickly the other tumors. So you had some data at ESMO Phase II data in a variety of other settings. How are you thinking about the investment in that? And I don't know, Manmeet's here, but how are you thinking about the investment in the other tumors assuming things continue to look good in lung cancer? Are you going to wait until you get an OS result before you kind of pull the trigger on going further in the other settings or....

Yes. No fair point. So 5 additional Phase II trials have had data provided between ASCO where its frontline BTC and biliary tract cancer. And then at ESMO, we had triple-negative breast, colorectal and head and neck. And then also at World Lung was earlier stage or the perioperative setting for non-small cell lung cancer. So 5 total settings from a Phase II perspective where there's been very encouraging data that's been shown for ivonescimab. So what we don't want to do is kind of lay the full road map out right now. And part of that is strategic, as part of that -- as we've seen more PD-1 VEGF or PD-L1 VEGF compounds come out. We want to make sure we're working through all of the steps internally from our perspective. But the data is very encouraging across a number of different places. So I think Bob alluded to this in the beginning, which is very important. When we invested in ivonescimab, this was very clear to us that we feel that there's a very obvious benefit to patients that can be seen in metastatic lung cancer. And I think now that's been borne out in multiple Phase III settings. What we certainly now believe is that this is what the upside opportunity was here. This is a pan solid tumor opportunity, which aligns with the targets that are associated with ivonescimab. So PD-1 and VEGF have 50-plus indications that are approved across the gamut of different opportunities there. So we very much intend with -- given the overall landscape in more PD-1, PD-L1 VEGF coming into play to move very quickly to continue to advance our development of ivonescimab. So that we're not waiting for -- we're not going to be having a conversation in 2027 here to talk about what's next after lung cancer by any stretch, right? And so we do plan to move quickly. What we haven't done and said, which tumors and what time. And part of that is we want to work through with the regulators as well to make sure we've firmed up our Phase III plans.

Let me just mention we take the global viewpoint to drug value is efficacy plus duration over toxicity squared. And you look at how we decisively went head-to-head with pembro and the results came out on that. And there are 4 different meaningful graphs that I can refer you to on our website that show you how those trends break out. And they break out immediately with the IVO performing much better, week 1, 2, 3, 4, 5 and 6, and then continuing to show its separation. I don't have an iota of data that says that that's going to change over time. That doesn't change over time. You have OS when that comes that's a question of the trials, and we push them through. Our viewpoint when you combine the 2 indications, non-small cell lung cancer and then you look at the other emerging, you've got about a $90 billion annualized business times 4. It's over 1/3 of $1 trillion market cap. That's why you're in the room. That's why people are chasing this. That's what people are looking at here. We look at it that way also but there's tremendous societal benefit to resolving these problems with leading therapeutics. And we think we've got the molecule that can do that and should do that. We'll be a little less transparent in terms of other than non-small cell, non-small cell. If we lose that, it's on us come back and point fingers, we don't think we're going to. That's a market that we lead by years, and we think we're going to carry away. The emerging market is up for grabs, but were KOLs now. We know what we're doing and people know us and we know them and they're watching every move we make. So we'll be as careful as we can to get that lead established and then take that all the way to the end. But it's a multi-decade opportunity. Our patents are good through 2039, if not extended. And we also have the rights to any second-gen molecule that our wonderful partner, Akeso comes up with. So we're company to look after to monitor, to measure for a number of reasons. I'm really proud of the people on stage here and the other 126 people that work for us. So we're very excited about the business. And proud to be covered by you.

Thank you very much. And I want to mention one other thing that we didn't talk about is, I know you can't tell us about time lines for HARMONi-2 and HARMONi-3, but you do have a trial called HARMONi with no letters or numbers at the end, which is reading out next year 2025.

So thank you, Ygal. It's a very important point. So we will have randomized Phase III data that includes Western patients, United States and Europe and Canada that will read out in mid-2025, which is a registrational intent study for ivonescimab . So that is our -- I think, as Allen mentioned, our fast-to-market strategy, but that is a short-term opportunity for us in mid-2025.

All right. Thank you so much. Enjoy the rest of the conference.

Appreciate it, Yigal. Thank you for your time. Thank you, everyone.