One, I'm Amin Makarem, one of the biotech analysts here at Jefferies. I'm happy to introduce and welcome Yuval Cohen, CEO of Corbus. This is a fireside chat format, and with that, thank you for joining us today, Yuval. Thank you for having me, Amin. Just to start, can you give us a brief overview of the company and the two lead drug candidates you have currently in development? With pleasure. Corbus is based just south of Boston in the town of Norwood. There are just under 40 people at Corbus. We are a drug development company, and we have a pipeline that has two assets that are very different from each other. The one is a Nectin-4 ADC that we licensed from CSPC in China in 2023, and the other one is a small oral daily drug targeting the CB1 receptor in obesity. Both of them are in the clinic. We just read out data on the one. We'll have data on the other later in the summer, then it goes back to data on the ADC. We have a cadence of clinical readouts at the moment between these two assets. All right. With that, let's dive into CRB-701. Your Nectin-4 ADC asset. You recently presented some interesting data at ASCO. Since it's pretty fresh, can you give us a quick recap on the key takeaways from that data? With pleasure. This was the maturing data from phase I we had previously shown at ESMO. The data matures and continues to also crystallize. It is around two solid tumor types. The one is head and neck, the other one is cervical, that was at ESMO as well. At ESMO, we still had both confirmed and unconfirmed responses. The data set was too young for durability, around head and neck, there was a real question, or not a real question, there was a question that kept being asked around, does the drug have a preference for one of the two forms of head and neck, the HPV positive or the HPV negative? The other way to think about it is the oropharyngeal version of head and neck, which is HPV positive, versus the non-oropharyngeal, which is HPV negative. ASCO provided answers to those questions. What we saw was. I'll start with cervical because that's even easier. In cervical, we saw the data continue to mature. Our confirmed overall response rate, Amin, now is in the mid-30s. That's about twice the response rate we see with Tivdak, which is the only ADC approved in second-line cervical. Our durability coming out of for the first time is looking very promising, very attractive. We have a DOR that's already at eight months and growing, PFS that's at four months and something and growing. We have still a very meaningful number of patients who are on the drug. That's a good problem to have. That all needs to mature. On cervical, we have an alignment with FDA around a single registrational study, which will be based on physician's choice as a control arm with accelerated approval based on interim RR and a final approval based on OS. That's pretty straightforward. Head and neck is more exciting in some ways, there's some more novelty there versus our ESMO data. We have now confirmed responses. We have the durability is growing for the first time we can see it. The biggest reveal for us was when we started getting the HPV data in terms of stratifying the patients that were responding or not. What we saw was that the drug had a very strong bias in favor of HPV positive. The other way to think about it is the anatomical version of the head and neck, which is driven by the virus, which is known as oropharyngeal, or colloquially, that's throat cancer. It's interesting that the other solid tumor that we work well in is cervical, which is almost entirely driven by HPV. We have two solid tumors where HPV is the main driver of efficacy. The other interesting thing, if you start to dive into our oropharyngeal data, is that the bias we are seeing with our Nectin-4 MMAE for the oropharyngeal was actually previously noted with PADCEV, which of course is the poster child for Nectin-4 MMAE ADCs. It's a very successful drug in bladder. Last year at ESMO, Pfizer presented their phase I data in head and neck. For them, the focus was on frontline patients, first-line patients with combination with pembrolizumab, and they showed an equally dramatic bias towards the HPV positive or the oropharyngeal. Like us, they had barely any responses in HPV negative patients, and like us, they had a dramatic response in the HPV positive. That's reassuring. Pfizer have already announced publicly that they will not be pursuing head and neck with PADCEV. We speculate, but I think we're right, that their obstacle there are their high rates of peripheral neuropathy. It's incompatible, especially with oropharyngeal and especially with frontline patient clinical practice. It just would be a price that will be very difficult to pay for patients or to bear for patients. Where we're going from here, Amin, is now we know which patients respond best. We have alignment there as well with FDA around a single registrational study, accelerated approval based on interim RR, final approval based on OS, control arm is physician's choice. That study will start this summer, and we think it will enroll relatively quickly. We are the only study that will be enrolling oropharyngeal patients. The three experimental EGFR bispecifics, Johnson & Johnson, and BioAtla, and what was Merus and is now Genmab, two of those exclude oropharyngeal entirely. The third one, which is petosemtamab from Genmab, limits the number of oropharyngeal patients in their study and is unlikely to be including those anymore. It looks as though we will be enrolling in the context of a tumor type that now represents half the patients in the West at those second-line level. Secondly, that is not being pursued by the EGFR bispecifics. All right. That's very helpful. Just digging deep into the data, you had around 43% ORR for HPV positive. The efficacy in HPV negative was very modest. Mechanistically, what did drive that difference in the efficacy between these two cohorts? It's the same phenomena that was seen for PADCEV frontline. PADCEV frontline in HPV negative has an ORR that is equivalent to pembrolizumab on its own. PADCEV plus pembrolizumab in HPV positive had an astonishing response rate of 82% confirmed ORR. A really dramatic bias, the same bias we're seeing. What's driving it, Amin, is Nectin-4. That's our target. There's no magic here. There are a number of publications out there that highlighted, well before we started down this path, that within head and neck, it is the oropharyngeal head and neck patients who are the most enriched in Nectin-4. I go back again to, I think, an interesting observation that oropharyngeal, in a sense, is the male equivalent of cervical cancer. These are two solid tumors, oropharyngeal is overwhelming in male, cervical cancer is exclusively female, that are driven by the HPV virus. I think the more we focus on it, the more work gets done within head and neck, the more we will see a bifurcation into what's known as HPV-negative or non-oropharyngeal, where it's the EGFRs bispecifics that do so well, and the oropharyngeal, where it's the Nectin-4 ADCs that do very well, and there is almost no overlap between them. To put it in context, the amount or the frequency of HPV-positive non-oropharyngeal patients in head and neck is something like 4%. If you're oropharyngeal, you're almost certainly HPV-positive. If you're non-oropharyngeal, you're almost certainly HPV-negative. I see. How does the durability you're seeing compare to the current second-line options? I know there is not much of an option right now. Yeah. So- Yeah, it's pretty tragic at the moment. Second-line options for oropharyngeal patients, because remember, these are patients that are unlikely to be getting cetuximab. The virus suppresses EGFR, we've known for many years now that they don't respond well to cetuximab. You're really down to either taxanes, assuming you haven't had them in your front-line, or things like occasionally methotrexate or 5-FU. All of these are very modest in efficacy. An interesting benchmark to think about is petosemtamab in their HPV negative, in other words, petosemtamab in the population that they do well in. We're already seeing our durability match and perhaps even exceed that. That's a very good start. We still have patients on study, that needs to fully mature. We've certainly exceeded the six months by now. Is there a bar for your pivotal study that you think you need to hit that PFS bar to be largely adopted in real world? If we look at the current available options for that second-line, we've exceeded that already. Those bars are typically 2-3 months. It's so tragic that we've done third-party commissioned third-party market research and a lot of KOL and looked at publications. We estimate that there are 14,000 patients per annum in the U.S. who are eligible for second-line oropharyngeal. The key here is eligible, because of those, only about 5,000 actually elect to have a second-line therapy. The remainder are patients who failed the front-line, and having consulted with their oncologist of what the available options are post-failure in the front-line, elect to do nothing. That's how tragic the current situation in second-line oropharyngeal is. Okay. That's helpful. From the data you currently have, when should we expect to see the OS data from these patients? Are you talking about the registrational study or about the current running phase II? The current running phase II. We don't know. It needs to mature. It's certainly encouraging that the durability is looking good. That tends to be a good predictor of OS. Stay tuned. We'd like to talk through scientific conferences, and so we'll see when we have the data, then we'll need to see where we could submit the data for a conference, et cetera. As of now, do you think it's going to get to the maturity soon, or it will take some time? We don't know. We certainly are not there yet, which is probably a good sign. We'll see how it matures. Okay. Sounds good. You've chosen to focus on. Oropharyngeal cancer, rather than requiring the HPV testing. Yep. Where do you see the biggest upside in this strategy? Versus the? Versus doing the HPV testing. Oh, goodness. I'll start by saying that what we're doing follows other examples. We are the second ADC company that has gone ahead to FDA and agreed on an anatomical definition and not an HPV definition. Also, if you look at the EGFR bispecifics, if we look at the exclusion criteria of BioAtla and Johnson & Johnson. If we think about it, we think of BioAtla and Johnson & Johnson as targeting the HPV negative. The exclusion criteria, Amin, is actually more interesting. What they exclude for are oropharyngeal patients who are only allowed to be in their study if they are oropharyngeal and can prove that they're HPV negative, something that is effectively impossible to do. They themselves are using the anatomical. Now, for them, the anatomical is the exclusion. For us, the anatomical is the inclusion. The reason you don't want to include or exclude based on a p16 test are the following. A. Whenever possible, you want to avoid a CDx. They're expensive. They cause delays in dosing of patients, and they cause, obviously, an enrollment of patients as well. There is no validated target for p16. p16 is tested locally. Lastly, p16 as a test is notoriously inaccurate. It has error rates of 10% to 20%. For example, oddly enough, eight of our nine patients were p16 positive. Our best responder is p16 negative. That doesn't actually mean that, A. They're not HPV positive. They might be. They could have been infected and cleared the infection decades ago. The damage was done. What we will do, Amin, is we will enroll based on the anatomy, as is the precedent, and then stratify based on p16, which is done locally then, without the need for a CDx. Okay. That's helpful. Moving to your phase III TEMPO-1 study. Can you highlight the key element of the design? You also have an adaptive feature in that. If you can highlight that as well. It's wonderfully boring. The design we have is effectively identical, for example, for the Merus design in their second line, including the adaptive design, which is becoming more and more common. It really boils down, Amin, to the inclusion criteria. The Merus design has an all-comers inclusion with the HPV positive being limited to 30%. Otherwise, we are exactly the same, except our inclusion criteria is oropharyngeal. In that sense, like I said, we're a lot more similar to Johnson & Johnson and BioAtla on the front line, where literally our inclusion is their exclusion criteria and vice versa. Are you saying anything on powering of the study, the expectations for the control and the active arm? Yeah. It's 125 patients in each arm. We can afford to have a smaller study than Merus had in second line, precisely because we don't need to compensate for a population of patients where we work less well, which they did. I think that, and you heard this in the KOL event we had at ASCO, it really boils down to how the taxanes will do. We know the literature data on taxane, but since then, the anecdotal evidence out there is taxane have grown more effective in the era of pembro pretreatment. Still, the consensus is you're looking at something like an ORR in the mid to high teens. We certainly power for that. The adaptive design is exactly for that. It's to make sure that at a certain point through the study, we test that, and if that turns out to be underpowered, that we have the mechanism to add patients, which is what Merus, for example, are doing as we speak. All right. I also think we have enough time to also talk about the frontline plus KEYTRUDA. Of course. Where does that study stand today? When should we expect to see the data? How should we set our expectations for that data? We should have about two dozen patients or so in time for early next year to look at objective response rate. I think that what we would be very keen to see is, do we get the same type of efficacy that PADCEV saw in their, again, oropharyngeal/HPV positive patients? If we do, that's wonderful. That's highly actionable. We are not burdened by their very high levels of peripheral neuropathy, so that's a meaningful advantage. If the data looks promising, then we would be interested in engaging FDA around the design of a frontline study in combination with pembro. It's not particularly difficult to figure out what that would look like. Again, it would look very similar to the EGFR bispecifics frontline studies, except it's the opposite patients. They go for the 50% of the patients who are HPV who are non-oropharyngeal in their definition. We will go for the 50% of patients who are oropharyngeal. Okay. Just to go back on the second line. This is one of the questions we get a lot on the opportunity there, the market size there. Since you are going after oropharyngeal specifically, how should we think about the market sizing? It's the number one question we got in the last week, and it's slide 14, I think, in our deck, for those of you watching later. Eligibility annual, so U.S. members annual eligibility. Second-line, 14,000 patients. Front-line, 18,000 patients. That translates roughly into about one in two head and neck patients in total in those settings. What's been interesting was just educating buy-side and continuing to do so, and I think there's two reasons that are important to educate them. The one is we've had, for very sensible reasons, the EGFR bispecifics, whose narrative has been, look, these non-HPV-negative. The HPV-positive, these oropharyngeal throat cancer patients, they're only about 20% of the market. That's not accurate, and it's certainly not accurate in the West and especially the United States. The dynamic in head and neck are very interesting. The average HPV negative patient is a man in his mid-70s who smoked three packs of cigarettes a day or drank too much. That demographic, tragically, is literally dying off, and so what we see in the West is that the HPV negative population is shrinking. Your HPV positive or oropharyngeal, remember, that's the manifestation of HPV positive. Your HPV positive oropharyngeal patient is, on average, 12 years younger. They can be as young as in their 30s now. They have no history of excessive smoking, no history of excessive drinking. What they did is they contracted HPV, which is the most common STD in the Western world and is typically completely asymptomatic. That population is actually increasing. Data out there indicates that your oropharyngeal patients or your HPV positive patients are already the majority in the U.S., and that dynamic is only going to increase more and more. It's been fascinating to talk to KOLs who are in large academic urban centers in the United States. Some of them are reporting that 80% of their patients walking in to the late settings of the disease are oropharyngeal patients. Okay. Certainly interesting. Just moving back to frontline. I wonder in trying to understand what's the standard of care in frontline for HPV positive patients. What's the unmet need there that you think 701 can help? Pembrolizumab is approved for all patients in head and neck and frontline. It's not so much what the standard of care, I think is, but what will be the standard of care that's particularly fascinating to us. If you are an HPV-negative patient, in other words, you have anything but oropharyngeal, so you're that older smoker male patient, you are almost certainly going to get an EGFR bispecifics. There are three of them. They all seem to work really nicely, and you'll combine it with pembro. If you are an oropharyngeal patient, which almost certainly means you're HPV positive, those EGFR bispecifics, two of them will be excluded from the label already in any way. The third one, it's not exactly clear if they're going to end up with that label or not. If in any case, the data they've shown to date has shown a reduced efficacy compared to how they do in the HPV-negative. For that population, a Nectin-4 MMAE-armed ADC seems to be a much better solution combined with pembro, based on the example of PADCEV in front-line and then the example of us in second-line. PADCEV is not going to be a label issue, and so that leaves us as a potential in the future for those, again, half the patients out there who are oropharyngeal. Of course, the data has to fit that, but we think that's how the market's going to end up looking or potentially could end up looking. All right. Can probably talk more about the head and neck space. Or 30 minutes more. Let's switch to your obesity program, 913. What's the latest status of CANYON-1 study? Data are expected this summer. Can you narrow the timing for us, and clarify whether this will be a medical meeting or a company event? The last patient first visit was April 10th. He or she, typically it's a she, 70% of our patients are women, which is standard. He or she walks out of the study, Amin, four months later, so figure about August 10th or so. It's about a dozen sites. They're all in the U.S., so we figure sometime in September we should have the top-line data. There is an academic obesity conference that we really like that happens this year in November. We'll see if we can get in at last second or not. If not, it'll be probably something like ADA. In any case, we will not sit on the data. We will release top-line data with the expectation of releasing a fuller picture of the data at the closest possible academic center or clinical, sorry, not academic, clinical conference. All right. You showed some interesting weight loss signal. In your SAD/MAD cohort, how should we interpret that 3% placebo-adjusted weight loss at day 14 when thinking about that 16-week readout that you have in lower doses like 20, 40, and 60? You shouldn't. What I mean by that is it's a phase I, it's small numbers. It was a surprisingly strong signal. None of the placebo patients lost weight. Well, actually gained weight, which is normal in clinic. Every one of the volunteers on CRB-913 lost weight. Again, that's a little bit unusual. The weight loss was surprisingly deep and consistent. Still, it is small numbers. It is early days. What I will say is every CB1 inverse agonist ever tested in the clinic, there's no exceptions, has always led to weight loss. I'm going to hazard a guess and say I don't think anyone out there is wondering if we'll see weight loss. We may be wondering the degree of weight loss, and that's fair. Are we going to look more like that first generation, or are we going to look more like monlunabant that was markedly more potent than the first generation? We don't know. The main question, pretty much the only question is, are we going to look safer than monlunabant in terms of the neuropsychiatric AEs? Certainly, the SAD/MAD study looked very different than monlunabant. CANYON-1 is a much bigger study. It's meaningfully longer. We'll see what that looks like. It's going to be pretty binary, I think. Either we look like monlunabant in terms of safety, in which case, that's the end of that. If we look markedly safer than monlunabant, then not only are we the only CB1 inverse agonist standing, and we will be much farther ahead than any competition that could possibly appear. Beyond that, Amin, this is the only mechanism of action outside the incretins that actually is known to lead to monotherapy weight loss. How do you define the bar for neuropsych toxicity here? Nothing horrible has to happen. That's one. monlunabant in 180 patients who were dosed on the drug had 111 neuropsych events. That's not great. The last one, oh, couple more things. When does it show up? Does it last? The last thing is what is the weight loss? In other words, if you have a signal of neuropsych, is it worth the signal of neuropsych? The more weight loss you have, the more worth it is. Nothing horrible, that's for sure. We can't afford that, and we'll do what's responsible. That SAD/MAD did look very promising from that perspective. All right. We are at the end of our session. We are. In closing, maybe talk about the cash runway assumptions and highlight the key updates by the end of the year and the next year. Sure. We had $138 million in the bank. That gets us into Q1 of 2028. The next milestones are not even that far away. They are end summer, September-ish would be the CANYON-1 readout, the pendulum swings back to early next year, which will be the frontline data in 701 plus KEYTRUDA. All right. Should be interesting. Thank you very much. Amin, thank you so much. Thanks for our audience. Appreciate it.