Right. Good morning, everybody. Thanks so much for joining us. I'm Seamus Fernandez, one of the biopharma analysts here at Guggenheim Securities. This is day two of our inaugural Healthcare Innovations Conference, and I'm really pleased to be joined by Corbus Pharmaceuticals. CEO Yuval Cohen is here with us today and really thrilled to have the opportunity to have Yuval introduce the Corbus story here at our conference for the first time. So, Yuval, maybe you can just kick us off with a brief overview of Corbus. And I know the company's had a lot of iterations, but you're hitting on a number of products in your overall life cycle now, which is really interesting. Good morning, everyone. Seamus, thank you for having us. It has not been a boring year for us, that's for sure, or a boring couple of years, so Corbus is really a relaunch of a company with a completely new pipeline, and this year has been really gratifying and, in many ways, very humbling to see interest around our new pipeline. Our pipeline, on the surface of it, doesn't actually make a lot of sense. We have two oncology products and one obesity product, but a little bit deeper into the surface, there is sort of a weave that fits within them. The one thing is these were three assets that we thought were interesting, that we could afford, that we felt had a good chance of success. But the other thing about them that unites them all is, in our first-ever pipeline that we had, we had not only a first-in-class and only-in-class drug, and that's exhilarating from a scientific perspective, but it's kind of terrifying from other perspectives. You just don't know if it's going to happen. There's no one ahead of you. There's no one to learn any mistakes from, lessons from. What unites our three assets now is each one of them, in a sense, is a fast follower to somebody who's ahead of us, typically a much larger company. And yet, at the same time, each one of our assets is, we think, better than the asset that's in front of us. And so, as they move forward and step on landmines, which is normal, we get to learn important lessons. We also get to see and sort of test in what ways is our asset differentiated from the one in front of us, and so, yes, it has been really wonderful to see both of our assets be of interest, our lead asset be of interest in this. Great. And then, just in terms of the, I guess, if there are synergies in R&D at all, what might they be, just kind of tackling those diverse indicators? I think there are some synergies, right? These are assets that we like that are just before the clinic and then moving them into the clinic. None of our assets is an asset where we, as a company with 29 people, can reasonably sit here and say, we will commercialize. I mean, you just never know, but it does seem unlikely. And we think that the right thing for patients and shareholders, et cetera, is for our assets to eventually end up with partners that have the ability and expertise to do late-stage and marketing studies. But the synergy there is, I think, again, the ability to juxtapose with who's ahead of us and the ability to learn lessons from who's ahead of us. And that's something that we've really internalized, and I think we respond very quickly to. OK. So more of a profile of pursuing best-in-class potential medications over necessary and perhaps even best-in-class clinical development in the early phases that could reveal those assets. I think, for example, we're seeing this acting out right in front of us. For obesity, Novo with monlunabant and we with CRB-913 were both CB1 inverse agonists. The main difference is the degree of exclusion from the brain. We are 15 times more excluded from the brain than monlunabant. Now, monlunabant is ahead of us. Objectively, it's obviously ahead of us. They are starting, I guess, a Phase 2a or Phase 2b. But what's interesting, Seamus, is in 2026, they should be coming up for air in their latest dose response study. And that's exactly when we will be coming up for air with our first, potentially only, dose response study. Just because, again, we can see the mistakes that they've inherited. And so we can incorporate that into a single study, rather than the case with Novo, where they really have to do over three studies where they learn mistakes from one study into another. And so that's an example where we think we have a potential best-in-class. But in 2026, we may not be a follower anymore. We should actually line up right next to them. And after that, it's an open lane. One of the things that Novo kind of points out about the monlunabant data in particular is just that, as they press the dose higher, they saw an outsized number or dose response on adverse events, neuropsychiatric adverse events specifically, versus the dose response on actual weight. What is that sort of threshold or magnitude that's achievable from a weight perspective that you have to achieve from a weight perspective in your view? And is there a sort of safe zone, a comfortable safe zone, that you believe exists between the two? These are great questions, so Novo's press release is not easy to understand, let's put it that way. It's not exactly a paragon of clarity, and I think, actually, we've seen a number of press releases from a variety of big pharma and obesity recently that are just not very clear, so what do we think we know from the Novo press release? They have this phrase there where they say they're not disclosing the higher doses, but they say limited additional benefit. They seem to be slightly backpedaling on that in the earnings, but they don't actually give us the data, which is a little bit curious. Now, every CB1 inverse agonist ever tested in the clinic and preclinically has had a dose response curve. We don't know what that is for monlunabant because, when NIH published that data, NIH is not in the business of doing dose response curves. And for monlunabant, we just don't know it because Novo hasn't disclosed what those higher doses are. Certainly, we recently, last week at Obesity Week, showcased a very wide range of dose response preclinically. And we think it is very, very, very likely that CRB-913 will behave like any other CB1 inverse agonist, so we'll see a dose response in the clinic. To the second part of your question is, you're right. They have this unusual phrase there about the secondary neuropsych. So it's not the really scary ones. It's not suicidal ideation as measured by C-SSRS. We now know they've clarified that that was negative. It's not even depression, which is measured by PHQ-9. They clarified that that was negative. But it's this murmur, this sort of intangible murmur of anxiety, irritability, insomnia. And because we don't have the numbers, we really don't know what that is. What we know is it's not bad enough for them to stop. But is it within what you would normally see with weight loss agents? Because we always see, at the beginning of studies, that sort of background murmur of this, or is it more than that? What is, I think, for us, a very simplistic way of looking at it maybe is they have engineered out the really bad stuff. By peripherally restricting the drug, they've engineered out the things that would have been showstoppers: suicidality, depression. And we anticipate that will continue to be the case. And now, let's say that they continue to have a sort of squeaky wheel somewhere, these secondary neuropsych that are sort of hard to fathom, and they'll get more and more data about them. What we think is advantageous for us is, with either both Cmax and AUC, in our case, being 15 times less in the brain than theirs, we think it is entirely reasonable to hypothesize that that squeaky wheel will go away. Ultimately, data will showcase everything. But one thing, for example, Novo did not include in their press release, and I certainly wish they had, is, within the context, for example, of what they see in semaglutide for these imbalances, what do these imbalances look like? And we just don't know. The only thing we know is they're moving forward. Very good. So maybe let's talk a little bit more about your program specifically. So CRB-913, we now know that it's sort of 15 times less in the brain. Can you talk a little bit about, is there a necessity for some CNS activation, in your opinion? And do you have data to sort of support that argument? We believe that, at the core of, frankly, all weight loss drugs, is central activity around appetite suppression. I'm unable to think of an exception to that, and so if we look at the first generation of CB1 drugs and now at the second generation, while we have reduced the level of exposure in the brain markedly, and in our case, very markedly, we're over a log less than monlunabant, there is still engagement in the brain. We'll never know what the human equivalent of that is because you just can't run the experiment, but there are a couple of interesting telltale data that help us. The one is the CB1 animal, a mouse knockout, is a pretty remarkable animal. It's completely impervious to obesity, unless you force-feed it. It's otherwise perfectly normal. What Josephine Egan and George Kunos did at NIH is they have a series of beautiful, beautiful papers where they knock out CB1 selectively in different organs of the periphery, in muscles and liver, et cetera. Always weird and wonderful things happen, but it's never quite as good as the whole animal knockout. The other sort of piece of data that we have is, more recently, I think last month, data from a paper from South Korea where occasionally academic groups come up and say, hey, we have a peripherally excluded drug, truly peripherally brain-excluded drug. They have one, and it actually looks kind of convincing. It has no effect on weight loss and DIO, none whatsoever. If you look at the liver of those animals, you actually see a profound effect on liver fat. The last thing I'll leave you with is we have probably, certainly north of 1,000 APIs now that we've made. We must have stumbled on a brain-excluded one. By just sheer luck, we must have stumbled on one. And it's worth noting that it's not one that we're moving forward. Again, it's not that they don't work. It's that, at the core of this weight loss is central activity. What we have demonstrated, and Novo as well, but I think we're just a more extreme demonstration, is it's remarkable how much you can withdraw from the brain and still have similar effects. You just need to compensate for it in the periphery. Rimonabant may have been a perfectly fine drug. It was just focused on the wrong organs and the wrong ratios. Way too much of it went into the brain. Frankly, probably not enough of it went into the periphery. Just in terms of the selectivity of the molecule itself and its actual direct activity as an inverse agonist to the CB1 receptor, how does it compare to the other agents? We can talk about peripheral exclusion, but you also have to bring that in the context of the selectivity of the molecule. Yeah. So monlunabant and 913 share the same backbone. We are all the grandchildren of ibipinabant, which was the BMS one. Both of us decided very purposely not to use a rimonabant backbone. Honestly, more of a narrative issue than anything else. We are both selected for CB1 in the single-digit nanomolar. The next thing we bind to three logs more would be CB2. And that's pretty much it. After that, it's a desert. It helps that, in the animal kingdom, we only have one CB1. It's a pretty unusual GPCR. It never replicated. So it's highly, highly, highly selective. Both of us have this biased agonism when it comes to beta-arrestin. I know that, in the NIH paper, and for that matter, Inversago themselves really emphasized that as a hypothesis for neuropsych differentiation. I'm not entirely sure I subscribe to that hypothesis, but I'm fine with it because we do the same thing. So if you were to design a Phase I, how would you structure it? I mean, I know the ideal scenario, in my mind, to sort of disabuse investors and the scientific community of the view that CB1 does have increased neuropsych impact, to me, would be to run a parallel arm, if you're allowed, of just sort of head-to-head versus semaglutide. Now, again, sema, unfortunately, you would also have to start with a higher dose at the same time, to some degree, maybe to achieve that 5% weight loss. Or 5% or better weight loss at, let's say, 16 weeks. But what would the Phase I trial design, the ideal trial design, to really be the killer experiment to say, OK, this is our fill or kill experiment that we have to run? Or is that only doable with a Phase II? So our view in obesity is boring is good. Boring allows you to compare to others. And so under an IND, in the U.S., we are going to start early next year, SAD followed by MAD, as vanilla as you can. And you want it. In my personal view, you don't want to be creative in SAD and MAD. Following that, what we would want to do is a dose response curve as monotherapy in the U.S. in overweight patients. And what you want to achieve there, Seamus, is a couple of things. Sure, safety is important. C-SSRS is always going to be our primary safety endpoint. PHQ-9 is always going to be our secondary endpoint. GI for CB1s is known to be milder than for the incretin pathway, so that one's easy. But what you want to see in the dose response is you want to see that there is a dose response. And this is where that back and forth with Novo's data is so important to us. And this is where we have the ability to potentially overtake them because both of us will have that answer in 2026. In terms of the secondary neuropsychs, because we're no longer worried about the primary, but in terms of the secondary neuropsychs, I think the idea of running it with a parallel arm for semaglutide is intriguing. But frankly, there's just a lot of data out there already. And I think, for us, in the dose response, we want to see the imbalances to begin with versus placebo and then understand, is this something real or not? Are we seeing a pattern or not? But I think there's a critical mass of data out there that can be benchmarked. The next study is the one you're talking about, not just for safety, but also, fundamentally, what do you want to do with this drug if it's an either/or? Are you thinking of it as monotherapy? So monotherapy for patients who cannot or do not want to or are not allowed to go on an incretin analog or agonist? Are you looking at this as an additive drug on top or in combination with an incretin analog or an incretin agonist? And/or are you looking at it as induction maintenance? And with the Obesity Week data last week, we've now completed that trifecta. We have, pre-clinically in DIO, shown every one of these scenarios. Each one of these scenarios is a different Phase II study because they ask a very different question. And so we'll see. The data has to guide us. But the first thing is line up next to Novo where they are and then juxtapose it. Even if we think of the Novo press release, the way we would have reported that data, assuming that our interpretation of the data is accurate, would have been quite different from theirs. There are things that we would have emphasized, like the primary safety endpoint, that they decided not to mention. We would not do the same thing. Yeah. OK. So maybe we'll shift gears to your oncology program. Sure. Let's talk about Nectin-4 and CRB-701. First off, just remind folks about the target itself and then the differentiation of your antibody-drug conjugate technology. Yeah. Nectin-4, as targeted by an ADC armed with MMAE, Padcev, is a highly clinically validated mechanism of action in urothelial cancer. Padcev is a very, very successful drug, initially as monotherapy, second line, and now as frontline therapy combined with Keytruda. And so it's another one of those, like 913, where you're not so much wondering, is it going to work? But what are the differentiating between our drug and whoever is in front of us? And there's a variety of things. So this is a very typical next-gen ADC, which means it's site-specific conjugation versus the stochastic or randomized conjugation of Padcev and the older generation. It has a stable, cleavable linker. It has a very precise DAR. Padcev is a DAR of an average 3.8 that can range from 0-8. Ours is 99 point something DAR of exactly 2. Very similar to the Ambrx construct, for example. It's just the conjugation technology is different, and the linker is different. So we've gotten very comfortable with these types of constructs. The idea is, hold on to your MMAE for longer. It really boils down to that. What I think is surprising is how the benefits that you get from holding on to your MMAE for longer, coupled with, I think, an acceptance now that, for MMAE, a lower DAR is better than a higher DAR. MMAE, remember, is incredibly potent, anyway. And so what we have seen coming out of China and what we will showcase coming out of our U.S. and a little bit of U.K. study in Q1 is the emergence of a clinical profile that seems to be markedly better tolerated than Padcev, where what we're focusing on are the peripheral neuropathy and skin. Coupled with that, a construct that is clinically potent. That's what we want to see. The idea, ultimately, would be twofold. One, the patients will be able to stay on the drug for longer than with a Padcev-like construct and potentially dose higher than a Padcev-like construct. The second part of it, Seamus, is, what do we want to do with this? There are 29 of us, and we love being just 29 people. So again, we are not going to sit here and pretend that we're going to commercialize an oncology drug. That's going to be immensely challenging and, frankly, not the right thing to do. What we want to do with this is, as a standalone company, focus on non-bladder cancer indications, where we have open swim lanes. We will continue to have bladder cancer data, both from us and from China. But that's for two different audiences. It's for strategics and, honestly, for regulatory agencies, because it's there within bladder that we can juxtapose with Padcev. But as a label, as long as we're standalone, it's outside of bladder that we're interested. OK. And in terms of the programs that you're looking to follow and compete with, who are the competitors? And what are the challenges in urothelial? I'm going to add one more question to this, which is, you mentioned sort of nascent swim lanes. What would those be separately? Sure. So the way we look at competition is very narrow. We have to. So what we look at is who out there is focusing, with an ADC or some sort of a similar construct, on Nectin-4 armed with MMAE. So that's Pfizer, Bicycle Therapeutics, us, and Mabwell. And so Bicycle Therapeutics and Pfizer, quite rightly, are deeply, deeply focused and committed to bladder. That makes perfect sense. Mabwell, on the other hand, is not yet in the U.S. or China only. And from our perspective, what we like in these nascent swim lanes are ones where our competitors are not. That's actually quite straightforward. Padcev, we think, may not even be eligible for cervical, not because it wouldn't work, Seamus. It's because they also own Tivdek. And it would mean cannibalizing Tivdek, and that might be quite tricky for them. So we like those swim lanes a lot. The way we go about it is, first, we have the data, and then we tell you about it. So the first swim lane out of China was cervical. But I will point out that, in our U.S. or Western data, we have opened our arms to more types of Nectin-4 cancers than were open in China, China enriched for bladder and cervical very early on in dose escalation. We have a more open approach. And so it will be interesting to see, do we capture additional tumor types or not? OK. Very good. So when are we likely to see data from your ongoing program? You will see data in Q1. OK, great. And what are we looking for at that point? What are the sort of comparisons, the data comparisons? What are you most focused on, particularly as it relates to response rate in different tumor types? This is a bridging study from China. That's the first most important thing. The idea is to juxtapose the China-only data in the context of primarily U.S. and some European sites. What do we want to see? We want to see that the PK looks the same. We want to juxtapose our safety to theirs. The tighter it is, the better. We want to see that it's not inert in Western patients. Beyond that, as I said, what we're adding are tumor types that were not explored at the time in China. We will juxtapose our dose escalation experience to this. Bridge comes from somewhere, and that's from the Chinese dose escalation experience. We look forward to sharing that. Beyond that is Project Optimus for us. For each tumor type, we will do a Project Optimus cohort. Some will be monotherapy. Some will be combo therapy. And at the same time, remember that China continues to move forward. They'll always be ahead of us. They will always have more patients than we do. And so if the bridge is tight, Seamus, we can leverage Chinese data with a variety of audiences. Again, certainly strategics, people sitting in this audience, the buy side. But also, if it's a tight bridge, there is the ability to have a dialogue with FDA around what is the value of that China data. But it starts with the tightness of the bridge. OK, great. Maybe we can just, as you just sort of look forward to the opportunity, the catalysts in 2025, maybe just sort of how those catalysts are likely to sort of sequence out. I think we've got early 2025 as the Nectin-4 data. And then, following on to that, we'll have the IND and the advancement. But how do you see sort of the cadence of catalysts in 2025? So for Nectin-4, it will be the bridge study in Q1. I think it is reasonable to expect a mid-year update from our partners in China on their dose escalation study. So that's not an incremental patient number. That's quite a large amount of patients. And then, on the obesity side, yes, it's our journey through SAD, MAD, and then into the dose response curve that we will generate. In the meantime, it will be interesting to see if we do see an update next year from Novo, if they will publish the data or not. I think that will be immensely helpful. And then, coming out of that, my guess is, in the first half of 2026, we will have the dose response for both of our companies. Great. Fantastic. Not going to be boring. Yeah. Well, thank you so much for joining us. Thank you, Corbus, and thanks, everybody in the audience, for joining us here today. Hope you enjoy the conference and look forward to seeing y'all.