Great. Welcome everyone to the Summit Therapeutics session. Yigal Nochomovitz, biotech analyst here at Citi. We launched coverage on Summit just before ASCO in 2024. 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. Welcome everyone. Bob Duggan is the Chairman and CEO, and Maky Zanganeh, also CEO, co-CEO, President. Dave Gancarz, who leads the business strategy and IR function. And Allen is the Chief Medical Officer. Welcome everyone. Thank you so much. And I think Manmeet is here, but he's in the audience. 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, you know, 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, you know, rise to the level of the one that, merited the investment?
First, it's wonderful to be here. 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 eight 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, but he did. We thank you for that. So our story goes back a while. We bought in. I bought into Summit when it was an antibiotic competitor to vancomycin. And it's a story for another day, but we did a good job there. We found out amazing impact that antibiotics have on the microbiome that had been underestimated and undiscovered.
We left that scene with a nice report that we're really proud of having done. At the end of that day, though, we'd assembled a very strong team and we were looking 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. As we scanned the area, I give a big shout out to Dave Gancarz in doing that business development. We looked at hundreds of companies.
Of course, all eyes would go, from my perspective, over to China. I have a key to the city of Shanghai, introduced robotics in China decades ago and have always had wonderful relationships, sharing respect for the people, for the hard work, for the insight, and for the brilliance that emanates. I noticed that at the FDA, up to 40% of new drugs being evolved were given credit to China, and 20 years earlier, it was like 2 or 3%. So they were definitely, you know, strong and powerful in the area of insight and innovation. We found several companies with products, but we ultimately came upon Akeso. Michelle Xia was running the company. She's Chinese, also U.S.A. passport, speaks perfect English. Baihua Li, the top scientist there, speaks perfect English, educated, spent good time in America.
So these were 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, good relationships. The challenge was 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 gonna be a multi-decade billion-dollar, you know, potential benefit to society. So how were they gonna 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 gonna be 100% on ivonescimab. And we were qualified, we were capable.
A previous drug we had managed got to $1 billion in revenues in year two. We took a market cap of $15 million and generated a value, 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 $500 million 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 at the time. And so we were able to do a transaction that others couldn't and wouldn't do. Big Pharma and in relationship to China was not a game that Big Pharma wanted to play at the time, just for geopolitical reasons.
We were there alone and put the package together. It turned out we raised money after that transaction up to $1 billion. The cost of those funds were less than $500,000. Unfortunately, you know, no Wall Street commissions were paid out on it. So we had contact with the investors that wanted to be in the game and played the game with us. Akeso owns 4% of our company. I own, full disclosure, 1.1% of Akeso. They're very happy with their ownership. I'm happy with mine. These are two teams of really great and fascinating people with a common denominator. How do we really make an impact on society in the world of healthcare and do so in a way that's new, novel, and sets a trend into the future that becomes very rewarding?
Of course, you do that and do that well, money's gonna fall off the trees. We don't focus on the money off the trees. We focus on making that huge difference. I'll turn this back over to my team now. I would just say this one last thing in passing. It was non-small cell lung cancer that we were really after. I, as I said, Michelle was a part of inventing the bispecific antibody that had done so well. 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. We wound up with a prize that was much bigger than any of us thought.
Our challenges are gonna 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.
Okay. Thanks, Bob. Great, great setup. So let's just level set. Maybe Dave or Allen, 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, you know, and then we can talk about some of the other attempts out there, some of the competitors and how you're different.
Yeah. Excuse me. Sorry, Yigal. So, thanks for the question. So, real quick, I'll just be upfront, say I won't say anything about any specific competitors because the gentleman to my right advises me against it. But, you know, first of all, you know, it's been a sea change in about a year. You know, 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. It's a drug in a lifetime, one of the drugs of a lifetime. So it has two 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?
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 microenvironment. And that's going to increase both efficacy and safety. Now, there's some other unique features. There's something called a Morrison format where you have two binding sites for PD-1 and two 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 two identical halves. And so a bevacizumab can bind each half of that molecule and that can bind to another VEGF and to another bevacizumab. And you get this daisy chaining 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 is dropped to about seven days. Bevacizumab's half-life is around 21 days. For Ivo, it's seven to nine 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 one of the VEGF receptors like VEGF receptor two. As far as we know, there's only one with a cooperativity, which we call allosteric cooperativity, which increases the affinity.
But you know, the people have not been forthright and you can't really tell from their patents, but those are the, at the high levels, the unique features of Ivo.
Okay. So you answered my question around why we're, 'cause 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 wanna expand on that point a little bit.
Yeah. You know, the key thing about the adverse events of both PD-1 and VEGF-associated adverse events, they're both on target, off organ events. So that's a key, right? So when you have binding of 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, myocarditis. 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 'cause 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.
Okay. 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 kind of review the design and so everyone understands what the trial showed in the PFS result. And then we can ask from there.
Yeah, Yigal. So, thanks for the question. So there's been two randomized studies that show that ivonescimab is very effective, both placebo controlled blinded studies. So the first one was HARMONi-A, which was ivonescimab 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 six 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 two groups. Thromboembolism was the same. I think there was numerically one or two 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.
Okay, great. So now let me just go through two 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, you know, 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 the bigger question of overall survival and, you know, how some people are making parallels, perhaps inappropriate parallels from what's seen in the second line setting to what may happen in the frontline setting. So we could just tackle those two important questions. That'd be great.
Yeah, sure.
Oh, go ahead.
Go ahead [crosstalk].
I've been talking a lot. You wanna go?
Oh, okay, so for the number of sites, it wasn't a limited number of sites actually.
Okay.
There were 60 sites that screened patients and 55 patients, 55 sites that enrolled patients. So, you know, it is a single-region study. It was conducted in China. It was designed to be a China registration study. You know, this anecdote of, you know, 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, you know, PFS leading to OS, you know, 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, you know, it's unlikely that OS is going to miss, right?
And I think, you know, another question that you had in there, Yigal, was with respect to HARMONi-A that had a very good PFS benefit about a 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 two studies, right? One of which is the HARMONi-A was a second line study in an actionable genomic alteration. So that was post, you know, two plus years of targeted therapy prior to. So those are much more heavily treated, 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, you know, over 11 months of PFS, you know, from a median PFS perspective in HARMONi-2 versus, you know, about 5.5 and a half months, in the pembrolizumab arm. So that's a greater than five 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 gonna be because they're more pretreated, that was a 7.1 versus 4.8 or about a two month, 2.3 month difference. So when you carry in HARMONi-A , you, we, 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, you know, from the baseline from chemotherapy and then, you know, 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 five-month difference is basically on a similar 17- to 20-month benefit for pembrolizumab based on those historical studies.
If we look back at KEYNOTE-042, for example, which is a reasonably replicable or, you know, referenceable study for this particular setting, 17-20 months of survival, if that five-month benefit, you know, 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 sig and clinically meaningful differences. It 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. Hopefully that, you know, gives a little bit of color there.
Yeah. And the other, the other piece of, I could add quickly, 'cause we spoke with an expert in lung cancer at UCSF yesterday, Victoria Wang, and you know, she made the point that, look, in the second line EGFR, Keytruda, it didn't work, right? I mean.
Very short.
KEYNOTE, what was it? KEYNOTE [crosstalk].
789.
Yeah. Right. So it just, it's not a, it's not a very good parallel to begin to consider.
I believe, Yigal, you are making a very important point because that is where we are differentiating as well in all of the immunotherapy, you know, with our bispecific, you know, is could be a lot of places that eventually Keytruda or all of the immunotherapy that they were and they show result, they, they didn't show results. We can show results, you know, just this bispecific aspect of the drug. And that is allow us to be in the different market, not just the market of Keytruda or Pembro and everything or Avastin or anything that any other drug didn't really respond at. 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, for HARMONi-2? And I know that's maybe more of an Akeso question than a Summit question, but still a Summit question.
Yeah. So appreciate the question, Yigal. But as you alluded to, so first and foremost, this was a study conducted and sponsored by Akeso, right? So it's important that, you know, we keep in mind we don't want to supersede our partners with respect to disclosing information about their studies. And I think it is, we've mentioned in the past, I think we mentioned this on the earnings call as well as I think, you know, our partners at Akeso have been clear about as well. This was a PFS primary endpoint, right? And so with that, that is the registrational endpoint in China that was completely appropriate in terms of, you know, design and whatnot. And so, but with that comes a smaller sample size, based on a single primary endpoint.
I think so there's two 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, you know, if you think about it from a Summit perspective, you know, you see positive results in a 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, you know, we've announced HARMONi-7. HARMONi-7 is in the PD-L1 high monotherapy setting, ivonescimab monotherapy, pembrolizumab monotherapy, in 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 HARMONi-7 , just from a design perspective, and you can see this on our website, there it's a dual primary endpoint with PFS and OS. And I think that reflects, you know, the way in which we reviewed the studies in our licensed territories, particularly in the U.S. and Europe. And with that comes a larger sample size to account for those two 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.
I think 'Carz has been clear on that. That's gonna 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, you know, 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 timeline, but it's not something that we think is in the, you know, 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, you know, enrolling patients in HARMONi-7 in early 2025.
And so all of that work is already being done to open that study now.
Okay, so just make sure everyone understands HARMONi-7 is monotherapy versus monotherapy.
That's correct.
In the high PD-L1 squams and. [crosstalk]
Squamous and non-squamous. So it's, it's both histologies.
Right.
And then PD-L1 high expressors.
Okay. 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? 'Cause originally HARMONi-3 was, you know, you had the data when I first met you in ASCO 2023, you had the phase II data and the squamous and that looked great. And then you went into HARMONi-3 with squamous 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.
No, exactly, Yigal.
So maybe I can go a little bit to the background there. That will help explain. 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 in the low, 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 the IVO could make the PD-1 better. And we found that the PD-L1 high population, ivonescimab also significantly beat Pembrolizumab. So that meant that it was active.
Finally, it was active across both the squamous and non-squamous population. That gave us the scientific confidence to amend HARMONi-3 to include not only the squamous, but also the non-squamous. 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. We can combine those two indications into a single study and execute and bring this therapy to patients faster. With the HARMONi-3 and the HARMONi-7 study, those two 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 is, in speaking to the same expert yesterday, you know, she was saying the United States, you know, even if you're above TPS 50%, 60%, 70%, and we talked about this, you know, you're probably gonna 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, do you, I mean, you could get away with HARMONi-3 and then let people decide what to do, right?
Yeah. Sorry. So the TPS high or the PD-L1 high expressors, 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 that, but there are a significant number of patients who still receive monotherapy. So it is important to really show that benefit both from a 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, you know, across the PD-L1 scores. Of course, there'll be patients who are, you know, slightly under 50% who may not be able to tolerate chemotherapy.
You really wanna make sure that you have the clear evidence that this is, you know, a very viable, you know, option for those patients.
Okay. And now just similar timeline 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?
Yeah, absolutely. So, we won't give away yet the timelines with respect to HARMONi-3. And part of that is really we announced the amendment, you know, just basically five or six weeks ago, right? And so we're still going through, you know, finalizing all of those details, initiating additional sites. So we wanna 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 in that it's a chemo combination and 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 setting.
But, you know, 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, Akeso, our partners haven't given specific timelines, it is safe to say that that study will complete enrollment and read out, you know, more quickly than our HARMONi-3 study will with that, because it's a frontline study that, you know, effectively covers half of, still half of the HARMONi-3 population, right? So, and it's against, as you mentioned, PD-1 plus chemo. So it's, they're using BeiGene's PD-1 in that instance, tislelizumab. There are some obvious read-throughs that will be able to be seen from that.
So we have very good phase II data, in single arm, you know, ivonescimab plus chemo, but this'll 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, that were run, you know, those, those showed very comparable results, you know, big picture to what pembrolizumab plus chemotherapy looked like as well. So it's a good proxy.
A couple other things cause we've got a lot to cover in the next five minutes and 57 seconds. So with the chemo backbone for HARMONi-3 , you know, a lot of people ask me, you know, all the, the rising tide, you know, rises all boats, right? So you're gonna have chemo in both arms. Now that could blunt, maybe blunt PFS a little bit 'cause of chemo, but, but are you still gonna be able to extract the OS delta that you've potentially, you know, got from the HARMONi-2 , assuming that, as, as Dave was saying, assuming the PFS, you know, plows, plows on to OS. So if you could just comment on terms of how you think about the odds of success, given that you're, you know, it's, it's a different, it's a different now that you have chemo on both sides.
Yeah. So Yigal, I think what you're asking is once you combine ivonescimab with chemotherapy, do you blunt the benefit of ivonescimab?
Yeah. Yeah.
The answer is, you know, you need the data, but no, because if you look at the history, right? So pembrolizumab 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, you know, adding chemotherapy to ivonescimab will blunt its benefit over pembrolizumab. In fact, you know, the data that we do have clinically is from the 201 study, which was, you know, a frontline study of ivonescimab in combination in the squamous and non-squamous population. They used 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.
Okay. Let's move very quickly. We had another interesting conversation yesterday with the breast cancer expert from Dana-Farber, who was 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 if Manmeet's here, but, you know, how are you thinking about the investment in the other tumors, assuming things continue to look good in lung cancer? What, are you gonna wait till you get an OS result before you kind of pull the trigger on going, you know, further in the other settings or?
Yeah. No, no, fair point. So five additional phase II trials have had data provided between ASCO, where it was frontline BTC and biliary tract cancer. And then at ESMO, we had triple-negative breast cancer, colorectal cancer, and head and neck cancer. And then also, a lung was earlier stage or the perioperative setting for non-small cell lung cancer, right? So five 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 wanna do is kind of lay the full roadmap out right now. And part of that is strategic. Part of that's, you know, it is we've seen more PD-1 VEGF or PD-L1 VEGF compounds come out. You know, we wanna make sure we're, you know, working through all of the.