Good afternoon, everybody. I'm Seamus Fernandez, one of the senior biopharma analysts here at Guggenheim Securities. This is our SMID Cap Biotech Conference, which we host every February. I am really pleased to have Corbus Pharmaceuticals CEO Yuval Cohen here with us. You know, Yuval, maybe just to start us off, big picture, you know, give us an overview of the Corbus story, and, you know, maybe talk a little bit about the pipeline, both across oncology, which is near term, and obesity as well. Thank you, Seamus, and thank you for having us here. We are based in Norwood, Massachusetts, and we have an unusual pipeline, although maybe not quite as unusual these days. We have two assets in oncology and an asset in obesity. The assets have no similarity between them whatsoever. The only thing that they have in common is all of them are bets, as it were, Seamus, where somebody else is ahead of us. The idea is to have a de-risked asset that is differentiated from the asset that is ahead of us. We have our lead program in terms of development is a Nectin-4 ADC that we licensed in from China, like so many other ADCs. There is a, hopefully, a meaningful milestone coming up next Friday at ASCO GU, so we look forward to that. We also have a CB1 inverse agonist. That's an area that we've been interested in since 2018. There, the compound in front of us is monlunabant from Novo. There was some more data on that this morning, or some more news around that this morning. Last but not least, we have a mAb t hat we brought in from UCSF two years ago, which is a latent TGF-beta play. It is a neutralizing antibody against the integrin alpha-v beta-8. All three, as of a few weeks from now, will be in the clinic. Great. Maybe we can start with your most advanced asset. We'll talk about the Nectin-4 targeting ADC. Just describe the status of the program first, and, you know, and then the, hopefully the data that we'll see at, or at least data that we've seen so far. Sure. Maybe not the data that we will see, but the data we've seen so far, at in ASCO 2024, with the China dose escalation study. You bet. The ADC comes from CSPC in China. It is yet another next generation ADC, site-specific conjugation, stable but cleavable linker, precise DAR. The first data came out of China last year in a dose escalation study looking at bladder and then cervical. That was the first time a Nectin-4 ADC was tested in cervical. The data was certainly encouraging and, in terms of efficacy, and differentiated in terms of safety. That was nice to see. What we will be sharing next Friday at ASCO GU is our first ever data from our Western study, mostly US, with a handful of U.K. sites. It really is about contextualizing the China data. It's no different than what I suspect all other companies that have been bringing in assets from China are doing. To what extent is Chinese clinical data a reflection of what we get in the West? At a minimum, what we'd like this to be is a sort of a bridge, as it were. It would be encouraging if the PK were similar. It would be encouraging if the safety profile were similar. It will be encouraging if we see signals in bladder and cervical patients. The tighter the bridge, the more predictive Chinese data can be thought of. Later this year, when we anticipate to see Chinese dose expansion data, hopefully with a tight bridge, you'll be able to look at that data and it will be somewhat predictive of what we will have in the West. There are the four top doses that were tested in China. These are all four therapeutic doses. It is the same drug, the same dosing regimen. There are two questions that we are exploring that were not explored in China. That's beyond the bridge. What else could we be seeing? The first question is around the importance of patient enrichment, individual patient enrichment. Chinese clinical studies are allowed to enrich for patients using a biomarker even as early as dose escalation. This is something that in the West is not available to us. In the West, our regulatory agencies will ask us, how do you know that your threshold is indeed clinically valid or not? What we will be showcasing in our Western dataset is what happens when you do not enrich. The interesting thing about Nectin-4 is there is sort of contradictory data. For example, Padcev in bladder does not require enrichment. Even low Nectin-4 expressing patients respond well enough to merit treatment. Some of our peers, for example, looking at other tumor types, identical tumor types, claim that you need enrichment versus you don't need enrichment. We strongly believe that it's actually a function of the construct. It will be very intriguing and I think informative to see what does our construct look like outside of bladder in the absence of a priori, patient level enrichment. The second question that we want to explore is the Chinese dataset in a sort of a very pragmatic, highly efficient manner, really looked at bladder and then at cervical. That meant that there is a large family or largish family of Nectin enriched tumor types that were just never explored in China at the dose escalation. We use this Western study as an opportunity to explore some of those. We can't explore all of them, but to explore some of those. It will be interesting to see whether or not, in addition to cervical, which is our first non-bladder tumor of interest, are there other tumors of interest that have come up. Other more minor things, but nevertheless intriguing. In the West, we are mandated to very aggressively manage ocular tox in ADCs, something that in China is not necessarily the case yet. This will be an interesting juxtaposition between Western data with active management of ocular tox prophylactically versus Chinese dose escalation data where there was no management. Are we going to see difference, between the two? Other ADCs have shown an improvement, so it'll be interesting to see what we see. Last but not least, bladder is not of interest to us as a standalone company. We will have bladder patients, continue to have bladder patients, because that's our positive control. That's also, Seamus, where we can juxtapose with Padcev. One interesting thing about our bladder patients in certainly the U.S. is they're typically Padcev pretreated. In China, they're all Padcev naive, and in the U.K., they're Padcev naive. That's another interesting subtlety, that we will look at. Okay. You know, maybe just talk about, you know, it sounds like there are opportunities for differentiation. You know, you've got Q3 week dosing. You know, what are the opportunities for differentiation outside of choosing and pursuing different tumor types? If we think of us compared to Padcev, which again, it's a tiny bit of a misnomer since we're not interested in bladder, but others may be interested in this asset for bladder. The Padcev, the average patient can stay on Padcev for about five months, and it's usually driven by AEs, peripheral neuropathy especially, and then skin. The hypothesis here is that by having a more stable linker that can be dosed less frequently, you could have patients stay on the therapy for longer because it's more tolerable while still delivering efficacy, and that should translate into a superior product. Outside of bladder, it becomes intriguing because their Padcev is not a competitor. And there the idea is, what do we look like targeting Nectin-4, sometimes for the first time in these Nectin-4 enriched tumors compared to whatever else that tumor happens to be treated with? For example, in cervical, Padcev is not an issue, probably never will be because of their ownership of Tivdak as well. Tivdak is a competitor, right? It's a second line monotherapy as a standard of care. Tivdak has relatively modest efficacy and challenging safety and tolerability profile. The question is, within that context, what do we look like targeting a different biomarker than Tivdak, but with the same warhead? Yeah. When you think about the opportunity in the different tumor types, what are you most excited about? Is there one or two tumor types that you would say, okay, this is where we think investors should be laser focused, or should we just kind of treat this dataset as exploratory and then look forward to the expansion dataset in China? It's kind of all of the above. It is an exploratory dataset, right? It's our first peek into dose escalation. It's four cohorts. It's a three plus three BOIN design. So it's 12 plus. When we showcased the Chinese data last year at ASCO GU, it was, I think, 17 or 18 patients. The first patient walked in in April. The last patient walked in in October. So we're looking at a handful of patients, correct? It's, it's, having said that, I think it will be a very informative dataset. And as we have now shifted to Project Optimus, for each tumor type, we allocate a cohort in Project Optimus. So it's very sensible that we will have a bladder cohort for two reasons. It's our positive control and for strategics. It's very reasonable that we have a cervical cohort within there. It remains to be seen whether next Friday there'll be data that will guide towards additional cohort or cohorts, within Project Optimus. It ultimately is all a question of what does the data look like? Are the tumors interesting? What is the competitive landscape, the unmet medical need, et cetera? How would you characterize your willingness and interest to advance this ADC on your own, you know, or is it a sort of a strategic outlicensing opportunity from your perspective? I think that in oncology, drugs are better served ultimately in the hands of big pharma than in the hands of very small companies. We enjoy being small. We enjoy discovering and developing drugs. I think commercialization and late stage studies are better for patients and other stakeholders, or often better for patients and other stakeholders when they are conducted by large pharma. Part of that is because of the cost of development itself, but also combinations adding to cost of development, things like that. All of it and the ability to move programs, late stage programs very quickly, the ability to market them successfully, et cetera. It's sensible. Okay. Let's talk about your thoughts on CB1. Sure. just CB1 mechanism. Yep. As a starting point, and some of the datasets that we've seen over the last year, you know, from monlunabant and, there was some, admittedly, I'm mildly embarrassed that I missed it, but I had something else going on today, that we were tackling at the same time. Maybe we could talk a little bit about the, some of the monlunabant story. It's not been a boring year for, last year was definitely not boring, and this year is starting to be not boring either. It's us and monlunabant, right? We are the only CB1 inverse agonist out there. Novo may have inadvertently created an interesting moat around us. We're within the moat whether we want to or not, and that's probably not a bad thing. The thing about this mechanism is a gentle reminder. These are all small molecules that you take once a day. You can literally make metric tons of them if you wanted to. Certainly rimonabant, we're making metric tons. The question isn't whether they work or not. It is a highly, highly, highly clinically validated mechanism of weight loss. After the incretin pathway, it's probably the second most highly validated. Every single CB1 inverse agonist ever taken to the clinic has worked. The issue is sort of the ghosts of the past of that first generation of drugs where rimonabant, which was the only one that went to FDA review after approval in Europe, encountered, frankly, a very hostile reception, rightly or wrongly, where there was the specter of the risk of suicidality, which is a horrible neuropsychiatric adverse event, goes without saying. A second generation has come about of peripherally restricted drugs, and it's us and monlunabant, CB1 inverse agonists. The idea is quite simple. Keep them as much as you can out of the brain, and you should avoid those issues. monlunabant is first to the clinic. There was a press release from Novo late September, which had a pretty not great impact on them and on us. It was not exactly a study in clarity, I have to say. That press release probably raised more questions than it answered. The bottom line is that they're moving forward with weight loss and obesity. This morning, and please don't feel badly for missing it. This morning, they announced in the earnings call, or referenced the second of the Inversago exploratory studies that were done in diabetic kidney disease. The study did not meet its primary endpoint. I have to say, Seamus, that one's not a shocker at all. That was based on some pretty flimsy animal data. What was interesting was a reference to seeing weight loss in those patients. These are big patients, right? They're type two diabetics. Seeing weight loss, which was encouraging, again, not exactly a shocker since this mechanism always leads to weight loss. There was some sort of a reference to seeing milder neuropsych adverse events than were seen before, and then reiterating that they're interested in moving forward in obesity, et cetera, that they think they can, I'm paraphrasing, can find the right dose for it. We think it's, you know, they very much seem to be very much committed to it. We'll be starting our SAD later this quarter, followed by MAD. Honestly, those are not going to be particularly informative. I hope they're not informative. Nothing should be happening in a SAD and a MAD, any type of drug. Yeah. And then late summer, late summer, early fall, we'll start our dose range finding study. And that comes up for air in 2026. We reckon about the same time that Novo will come up for air with their dose exploration study that they have to repeat. It is a very large study from them, curiously so. Maybe they're combining it with semaglutide. Otherwise, it's hard to imagine why they need 600 patients otherwise. And I think in 2026, we both have our doses. We both have our data. And at that stage, we'll know who has the better drug. And so I think the only wild card is, do they publish the data on monlunabant or not this year? Yeah. I'd love to see it. It's entirely their choice, of course. In terms of the preclinical data and the validation of 913 in terms of achieving that peripheral restriction, can you just remind us what you've seen with your own molecule? Sure. We've made monlunabant, and we ran it in a mouse model and looked at PK. It's pretty straightforward. We have similar peripheral exposure, so that's good. Both of us are much more peripherally exposed or prevalent than rimonabant. rimonabant, the brain for rimonabant was a big sinkhole in terms of PK. It's really the differences in brain penetration versus rimonabant and us versus monlunabant. We are 15 times less in the brain than monlunabant. I think we're one- fiftieth compared to rimonabant. We are markedly, markedly more brain excluded than monlunabant. Yet in the DIO mouse model, which is the standard preclinical model for obesity, we're equipotent to rimonabant and they're equipotent to rimonabant. We do not seem to be taking a hit on the fact that there is so much less of us in the brain compared to them. Ultimately those are mice, and we will need to see what the dose range finding data looks like. Expect a 90-day study. Ninety days should give us two things. Certainly a PD signal, you should lose weight in 90 days. CB1 inverse agonism is more than capable of making you lose weight in 90 days quite nicely. Ninety days should also be enough for neuropsych. Neuropsych is one of these odd things, Seamus, that happens at the beginning or tends to not happen. A one-week MAD is not going to tell you that, but a 90-day dose range finding should tell you that. Got it. In terms of the sort of milder neuropsychiatric events and how you're evaluating, neuropsych events, or you will evaluate in that 90-day study, you know, how will that sort of compare and contrast to, you know, the, the approach that Novo is taking? Do we really know what Novo's approach is? We do, because all of us have to do the same thing. All of us is all obese, anti-obesity companies. The FDA guidelines, the old guidelines and the new guidelines are very clear. Every anti-obesity drug must measure for the following. It must measure for suicidality using the C-SSRS score prospectively. It needs to measure for depression using PHQ-9. It's regardless of the mechanism of action, all of us have to test the same. Yeah. Those, interesting enough, were negative for monlunabant. It's one of the sort of hidden gems, I guess, in their press release, which was not in the press release itself. It was discussed later on that in 120 days, they had a negative C-SSRS and a negative PHQ-9. That's really unusual. That's very encouraging to us. Okay. The signals, again, those minor neuropsychiatric signals were sort of low-level, you know, presumably low-level anxiety and, and maybe other low-level. Yeah, it was, it was anxiety, insomnia, and irritability. The last two are a bit of head scratchers. They're not that much of a showstopper, unless the numbers are really imbalanced. If that were the case, it'd be surprising if they'd move forward. Those three, anxiety, irritability, and fatigue, and, and insomnia are also the hallmarks of weight loss. Yeah. You see them pretty much across the board in all weight loss regimens. They're not unusual. In the absence of actual numbers, we just don't know what they saw and why they're mentioning it. Yeah. Talk a little bit about the, you know, that selectivity and peripheral exclusion argument, of 50 to 1 versus rimonabant, and I think you said, 10 to 1 or 20. One fifteenth. One fifteenth. Okay. I was bracketing it, I guess. Very nicely. Mentally. Yep. When you sort of look at that dynamic, I think we've also talked about why not complete peripheral restriction. What data do you guys have on that? Did you ever have a molecule that was completely peripherally restricted? You know, what did you learn from it? We strongly believe that you need some minimal brain engagement. We have over a thousand compounds. It would be very odd if we did not, even by sheer accident, stumble upon a purely brain impenetrable one. Clearly we are not moving it forward. There was a really interesting paper out of South Korea in November or December. I cannot remember. It is an academic group. They have a purely brain impenetrable CB1 inverse agonist. There are a bunch of those floating around in academia, but this one I think is really credible. It is really interesting, Seamus. They ran it in a DIO mouse study. It barely does anything. They look at the liver of those mice and they have a really nice reduction in fat. If you think about weight loss drugs, every weight loss drug that I'm aware of, at its core, has an appetite suppressant factor to it. That's your brain. There's no other organ that does that. How it does it is a different story and, you know, gut-brain axis, et cetera. We know even from the incretin analogs that there is very meaningful brain engagement. I think the secret is rimonabant was a very effective drug, probably underdosed in the sense of efficacy, but just flooded the brain completely unnecessarily. What we've shown, what Novo showed, but what we've shown, I think in a more extreme version of it, preclinically at least, is you can afford to markedly withdraw from the brain, logarithmically withdraw from the brain and not affect the efficacy. We are not fans of, for CB inverse agonism, we are not fans of peripheral exclusion. Okay. You know, one of the things that was a little odd was, and again, limited data, not super long for Novo, was the sort of absence of a robust dose response. What is sort of the dose response characteristics and what do you think are the potential limitations in that regard? Again, that press release was just so mysterious. The phrase they use is that there was a limited additional benefit. I honestly don't know what that means. It's three words, but I just don't know what they mean from a, I have no feel for the numbers. It's odd. It's odd for a variety of reasons. Every CB1 inverse agonist ever tested had a dose response preclinically and in the clinic. Even for monlunabant, we only have two data points. We have the data point that disclosed for 10 mg a day at 120 days, and then the data point that Inversago disclosed at 25 mg a day for 28 days, right? They're nowhere near on top of each other. The 25 mg a day looks a lot more potent than the 10. Now, maybe something happens in the ensuing three months, although that's a little bit hard to imagine. The publication of that data would be immensely helpful because we just don't know what they saw. They're not helping us by not telling us what they saw. Yeah. Maybe just to wrap up, your, you know, sort of hope for profile, in the, in your own 90-day data, obviously SAD, MAD will, will learn PK characteristics, things like that in humans. But, you know, just to wrap up, your hope for profile at 90 days. I want a, no imbalances in neuropsych. That's what we want to see. Yeah. The weight loss will be there. I mean, again, anything can happen. Odd things have happened, but it is very likely that the weight loss will be there just because the mechanism is so validated. Got it. It's really the neuropsych. Great. All right. Unfortunately we have to wrap up. It was a lot to cover, but, Yuval, thank you so much for the time here. Looking forward to actually.