Afternoon, everyone, welcome back to Oppenheimer's 36th Annual Healthcare Conference. I'm Jeff Jones, one of the biotech analysts on the team here, I'm delighted to welcome Yuval Cohen, CEO of Corbus Pharmaceuticals. Well, I can talk. Good afternoon, Yuval. How are you? Hello, Jeff. How are you? Good. Thank you for joining us today. It's, you know, a great way to kick off an exciting 2026 for you guys. Mm-hmm. It's a catalyst-rich year, and we'll definitely dig into that. Maybe first, to set the stage, for those who are less familiar with the Corbus story, maybe just a quick introduction, for those who, you know, haven't followed it as closely. Sure. Corbus is based just south of Boston in Norwood, Massachusetts. There are 36 of us, so we are a small company. We like to keep it that way. We have a pretty unusual pipeline in the sense that we have an asset, or we have an interest in oncology, where the lead asset is CRB-701, which is a Nectin-4 ADC. Then, side by side with that, we have something that couldn't be more different. We have a small oral molecule in obesity, which is a peripherally restricted CB1 inverse agonist known as CRB-913. They're both in the clinic. They've both shown last year, late last year, sort of preliminary data in their respective indications. They both have a big year this year, because this summer, we'll have data that I think is not incremental, I think it's truly exponential for both CRB-701, our ADC, and our CB1 inverse agonist, CRB-913. All right. I guess CRB-701, it's a Nectin-4 targeting ADC. Nectin-4 is obviously well-validated, PADCEV approved, first, you know, and standard of care really in combination with the checkpoint inhibitor. Why don't we start out in talking about what differentiates CRB-701 versus PADCEV, and what's the data now that's getting you really excited, having shown some clinical data, both in with respect to efficacy and safety? Sure. 701 is, as you said, a Nectin-4 ADC armed with MMAE. Conceptually, that's the same approach as PADCEV, or enfortumab vedotin. There's some very big differences. Lynette, I'm going to, if I may, share a slide. It's really all about the structure of it, Jeff, and audience, and what derives from the structure. On the face of it, this is a classic ADC, right? There's an antibody, a linker, and a warhead. The antibody is a proprietary antibody. It is not enfortumab. What's interesting about it is it targets a different epitope, a Nectin-4, and it is also has twice the rate of internalization in vitro to enfortumab. When it does bind to Nectin-4, more of it gets internalized. You have your linker, and like most new generation ADCs, this, too, is a site-specific conjugated linker. A reminder that PADCEV is an older generation. PADCEV uses randomized or stochastic linking, one of the peculiarities about PADCEV is it doesn't actually have a precise DAR. The DAR is on average 3.8 because it's a build curve. The novel ADCs, this is one of them, have a very precise DAR because they're they use site-specific conjugation, so you always conjugate the same amount of warhead. This one uses click technology. There's a number of them that use click technology. The linker is proprietary. It is a very short, very stable linker. There are 2 of these, so the DAR is 2, and at the end of it, we go back to PADCEV, is MMAE, which is still probably the most commonly used warhead. Certainly, 1 of the most powerful, maybe the most powerful warhead out there. What you get out of this, Jeff and audience, is a hyper stable ADC. Whereas PADCEV, for example, has this built-in instability that causes the MMAE to fall off, so it has relatively high levels of free MMAE circulating. The problem with that is that triggers some of the challenges that PADCEV has, like peripheral neuropathy and skin. What we did with CRB-701 is we created, or our partners, I should say, created an ADC that holds onto that MMAE much, much, much better. Our levels of circulating MMAE are much lower than PADCEV's, even at much greater concentrations of the drug. More of the intact ADC reaches the tumor, and then again, that's where the mAb comes in. When it does reach the tumor, more of it gets internalized into it. From that, what you get is a drug that can be dosed less often, and that has a markedly better tolerability in terms of peripheral neuropathy and skin, while delivering a potent clinical effect. Having said all that, Jeff, as you know, and I think as the audience knows, we're still not going after PADCEV. We're not competing in bladder. There are 36 of us trying to compete with Pfizer head-to-head in an area where they have this dominance, strikes us as ambitious, even for us. The strategy for CRB-701 is go where PADCEV is not. Go after tumor types, where we generate clinical efficacy and signals of clinical efficacy, where PADCEV is not a competitor, where Nectin-4 is a very sensible target. We are especially interested in what we call empty swim lanes, in tumor types, where the competitive landscape is such that we have an advantage. Yeah, I think you really highlighted some of the key potential differentiators here. You know, as you noted, you recently provided some substantial clinical updates at ESMO in the fall. Since you flagged safety, why don't we start and talk about what you've shown to date for safety? Yep. Peripheral neuropathy being a key standout here, and rash potentially as well. Then we can talk about the efficacy and the. Sure sort of the key indications you're looking at. There is no such thing as a free lunch as we go. What do we win, and what do we have to give up on? We have by far the best-in-class peripheral neuropathy. We have our data set, we have China's data set. Combined, it's several hundred patients, and the peripheral neuropathy levels are extremely low. I rarely use, you know, these terms, but they really are exceptionally low. In terms of skin, again, very low levels of skin. What do we have to give up for that? We pay the price that many of these stable or hyper-stable ADCs, especially those with MMAE pay, which is ocular tox, so this is the surface of the eye. Nobody quite knows why. There's some very good theories, nobody quite knows exactly why stable ADCs accumulate in the eye or the surface of the eye. Whether it's us, whether it's Tivdak or Eli here, or Genmab, Blenrep, which is really a sort of an extreme example of this, but we all have the same issues of dry eye and keratitis. Again, it's the surface of the eye, it's not the back of the eye. PADCEV itself actually had that. It's just that it wasn't particularly exciting. It was mostly grade one and two. Compared to their peripheral neuropathy, it really wasn't particularly noteworthy. All of us in this world now of these stable ADCs, deal with it in the same way, eye drops. We use eye drops before as a prophylactic. If we do see these events rise, we use it as the event flares up. All of us dial down the dose if the event is flaring. It is now so common, Jeff and audience, that the FDA mandates an ocular vigilance protocol for all ADCs. They just have seen this now so many times. It's predictable, it's manageable. They tend to resolve, again, not just with us, with other of these stable ADCs that are MMAE-enabled, and they're a known entity. That's where we are on safety. We'll have, again, an ever more mature data set coming up in the middle of the year. Don't expect any drama on the safety side. Okay. It's pretty much a good grasp of the safety. You mentioned the China data set, obviously from CSPC, your partner on this program, who we haven't really mentioned. We haven't had an update from them in quite a while. Correct. As you mentioned, they've enrolled several hundred patients. They're looking at urothelial… Cervical, yep. Do you think that's something we might see this year as well as another major update on the 701 program? They have bladder and cervical. For them, cervical is a relatively common gynecological tumor type. I think it's kind of hard because I have to respond as though I'm on the outside. From the outside, Jeff, I think what we see with Chinese, big pharma especially, is they like to have critical masses of data. They like big oncology conferences. They like to go for oral, late breaking presentations, too. We'll see what they do this year. Intuitively, it feels right or ripe, but of course, again, we can't speak for them. Okay. We're pretty excited. We get to see visibility on their data, so we're excited about that. There's some read-through. Okay. In, let's talk about efficacy now. Yes. What we showed at ESMO are signs of efficacy in both second-line head and neck, and second-line cervical. I think what's interesting coming up in the middle of the year would be the following. Let's start with cervical, just because it's easier conceptually. Cervical maturing data set, we'll see what the data, what the efficacy looks like. Key question is durability. It's nice to triangulate because we have our data, we have CSPC's data, we even have data from Mabro in China on a different mechanism for MMAE construct, and it pretty much all triangulates. All 3 of us look markedly more efficacious than Tivdak, which is the only other ADC in second line that's approved, and we're certainly much better tolerated than Tivdak. Tivdak has ironically, ocular toxic similar, but it has other issues that none of us have: bleeding, peripheral neuropathy, skin, et cetera. I think the question in cervical is, right, what does this maturing data look like? What does the registrational pathway look like? I don't think there's a lot of mystery there. It's really about the size of the study and when we can wrap it up. Cervical is a really interesting one. Second-line cervical is a rare population in the US or the West. Only one in five women who are eligible for Tivdak actually gets Tivdak, and that's because of its tolerability, right? These are tolerability, efficacy ratio is just very not attractive. What surprises audiences when we talk about this is Tivdak still made $300 million last year. The annual WAC for Tivdak is absolutely astonishing. It is $462,000. It's actually one of the most expensive oncology drugs out there. Jeff, that is exactly the face everybody makes when we mention that number, because it is an astonishing number. Tivdak $ million by effectively targeting very few patients. There is clearly room to replace Tivdak with a better agent, albeit in a niche second line, a relatively rare tumor type. With Tivdak, you know, what does the bar for success look like in terms of objective responses? As you said, the bar is relatively low, and curious about the durability of response, how long those patients are staying on therapy to drive those $300 million in revenue. That's not too hard well, actually, that's simple math. That's 600 patients. Yeah. The confirmatory study, Tivdak did, which was a controlled study versus chemo second line. Chemo's response rate was about 9.5% ORR. Tivdak was 17%. The durability, if I remember, is several months. It's not super long. Yeah. It's very hard to stay on it because the adverse events are so challenging. Got it. It's a very, very challenging drug to be on. That is not a seemingly a difficult bar to beat. Yeah. Um. Now- Head and neck. Yeah, shifting over to head and neck- Sure. Larger indication. A lot larger. Lot more going on. Second line head and neck in the U.S. is probably 24,000 patients. First line is about 50,000-60,000. Completely different animals. What did we show? We showed that we had this preliminary signal in efficacy. I don't think anyone wonders if the drug is clinically effective. The key questions are the following: What is the durability of that effect? An even bigger questions from which everything else emanates, Jeff, and the audience is: What distinguishes us, what differentiates us from what is now Genmab's peto in second line, right? A secondary question is: If we are differentiated from peto in second-line monotherapy, what does that mean for frontline mono combination therapy with KEYTRUDA? Coming up in this summer at a hopefully conference, we will have this mature data from second-line monotherapy that should be able to answer a couple of important questions. Questions around confirmed response rates, questions around the evolving durability. There's some really important questions around stratifications, Jeff. For example, Peto, petosemtamab, works well in HPV-negative patients. It has very modest efficacy in HPV-positive patients, right? That's a stratification that's very sensible to us. Peto, for example, is very unlikely to work following in a patient that previously had an EGFR bispecific or therapy, right? In fact, there's an argument to be made that peto, in and of itself, long-term, is probably unlikely to be a second-line therapy, simply because they'll try and capture as many patients in frontline, and any patient that they don't capture, especially if it's an HPV-negative patient, if it's not captured by peto, it's going to be captured by Baiquara or Johnson & Johnson, right? That stratification is also important. Where do we stand there? How do we thrive in alongside peto is an important question, let alone after peto. In other words, when peto is no longer there as a second line. Then beyond that, as I said, that we think that this data, we'll be able to answer, I think, quite conclusively, actually. Then beyond that is that line of sight to frontline. We will have frontline data in combination with KEYTRUDA at the end of the year. The frontline, again, is essentially the same question. The frontline question is: in a situation where that frontline, especially if you're HPV negative, is dominated by either Genmab or by Kite Pharma or Johnson & Johnson, where is there space to grow? Where is the space to shine and thrive as a therapy, right? There you don't worry about the preceding therapy because there is no preceding therapy. It's a question of if you're a patient and you're diagnosed with metastatic head and neck, why would you end up on our drug versus one of the EGFR bispecifics? All of us, in combination with KEYTRUDA, that bit stays the same. We'll have the data for that at the end of the year, but I think we'll have the line of sight to that data in from the second-line monotherapy data in the summer. Okay. On the safety, as I said, there's no drama on the safety. At this stage, we have a very good idea of what the safety looks like. You've talked about going to the FDA to sort of talk about planning around what a phase 3 then looks like. Correct. For 701 and these two indications in particular. Just any updates on that timeline and planning- Yep ... around phase 3? We said it's a Q1 event, both for head and neck second line and cervical second line, we should have an update later this quarter. A couple of thoughts for you. Let's start with cervical. Cervical is different. We cannot do what Tivdak did. At least we don't think we can. We have Fast Track, but we still don't think we can. Tivdak dates back to a time where they were given a path of a single-arm study for Accelerated Approval, and then a separate sequential study, which was a controlled study against physician's choice for the final approval. Our assumption is that this FDA doesn't do single-arm studies. I think it's a safe assumption and probably a sensible thing. In cervical, I think what is sensible would be a controlled, single-controlled study against physician's choice. The physician's choice will be either chemo or Tivdak. Most patients will not be getting Tivdak. You do an Accelerated Approval based on your overall response rate. What you're left with is just discussing with the FDA if it's overall survival PFS for the final approval. That's, I think, pretty drama-free. On the head and neck, we do have a precedent. The precedent we have is Taranabant second line, even Bialda second line. Bialda is HPV positive only, or oropharyngeal, they have to be the same thing. What both of them have done is a single-controlled study against physician's choice of 1 of 3 things. It's either chemotherapy, taxanes, or cetuximab, or methotrexate. It's very sensible, makes a lot of sense. It's one of those things where you probably don't want to be particularly creative with FDA. We should have the outcome of those conversations in time for the end of the quarter. We're waiting for one to sort of announce both, but we're not expecting any particular surprises on that. All right. That's helpful. I think we've covered the oncology story pretty well, and now wanna flip over to the little bitty indication of obesity. Little bitty indication, yep. And CRB nine one three. Correct. Your CB1R inverse agonist. Mm-hmm. Let's talk a little bit about mechanism of action. What has you excited about, you know, the 913 program, you know, validating data, rimonabant, monlunabant, and, you know, go from there. Sure. Sad but data came out December. Let's talk about the mechanism first. What's interesting about CB1 inverse agonist with a small molecule, it is highly predictable to lead to weight loss. That's not the issue. I don't think anyone's wondering if CRB-913 is gonna lead to weight loss. That's not the question here. The question is: What is the safety profile look like? Then the second question, which is the more intriguing one, is: How much weight loss? Len, I'm gonna share a slide for 1 second. I want to remind the audience of what's unusual about CRB-913. CRB-913 is the first truly peripherally restricted inverse agonist. We've never had an instrument like this to play with in humans. We've had the brain-penetrating ones, right? They worked, they have a lot of issues in terms of tolerability or risk of adverse events. Tolerability was actually fine. It was the risk of the adverse event. Mamenabant came along, it turns out Mamenabant is not particularly peripherally restricted. It's about half of the amount of that first generation, and there are a lot of challenges in Mamenabant, to say the least. There's us, we are something novel, I think we massively underestimated just how novel we are. When we went to the SAD/MAD, we saw a bunch of things that were really, really intriguing. The one thing we saw is, it leads to weight loss. That's not surprising. It would have been surprising if it didn't lead to weight loss. It's the extent of weight loss that we saw. Tiny numbers in a short period of time, but that makes it all the more odd. Every single patient that took CRB-913 lost weight. That's unusual compared to placebo. The degree of weight loss was highly unusual. We're almost at 3% at the 2-week mark, which is very unusual, and it wasn't a fluke because it actually started early, and it just kept. The question is going to be: what does that look like at the 3-month endpoint? Which is a study that we are doing, we're about to report at the end of the summer, and across multiple doses. I would submit to everybody that we may have, as I said, underestimated the potency of this mechanism. Monlunabant in and of itself, at a 4-month mark, led to an 8% placebo-adjusted weight loss. That's very, very impressive, right? That's orforglipron land. For an oral drug that's not GLP-1, that's very unusual. What we see is we can juxtapose it compared to the SAD/MAD data from orforglipron. It seems to head in the right direction. Again, we need to stretch that out and see what that looks like at the three-month data point, but I think we might actually be really surprised by what we see. Again, not that we see weight loss, it's the extent of weight loss. We are very optimistic on safety, right? Our GI safety is highly differentiated, and that actually fits nicely with what was seen with the old generation of CB1. It's the neuro site that's different. We were negative for all the validated marks. We had 3 cases in the entire study, 112 patients, 3 cases of subclinical anxiety, so that's anxiety that doesn't even rise to that level of PHQ-9 or GAD-7. Two of them happened after they were off the drug and back home, and then one of them was situation. That bodes very well. Compare that with monalizumab, that across 180 patients, had 111 instances of neuropsychiatric adverse events. That's not good. That's not good at all, and it's really very different, right? This exclusion from the brain seems to really be playing beautifully. We think the safety is gonna play nicely, but again, it's the efficacy. We did a very sort of interesting thought experiment, which is we looked at SAD/MAD data, right? Trying to compare apples to oranges, as much as we can make the orange look like an apple, and we looked at all the oral weight loss drugs that we could find. Again, the thing about MAD is it's short. These are all 2-week cuts, right? Later, it could change. In terms of the speed of decrease of weight, that's not too shabby. That's actually really encouraging. I think that we really need to see that data, but that's what I'm saying. I think that data is not gonna be incremental. I think that data could really be transformative. Let's see how much weight loss we see. On the safety, as I said, I think we're pretty optimistic. That's, that's the study, Jeff. This is it. Yeah. Right? What is the bar in your mind today? Because, you know, it does feel like we see new obesity headlines daily, almost. Yeah. Where is the bar, in your view, 3-month weight loss, where do you think you need to be to be competitive? I'm gonna start with this slide. This is a slide. We think we found everything. These are non-incretin pathway drugs. Some of these are incredibly exciting, right? They don't lead to weight loss, right? What they do is other things that are important or could be very important, but they're not weight loss drugs. CB1 really is unusual in that it's the only other GPCR that actually is known to lead to weight loss. I don't know what the bar is. I think trying to predict efficacy is a fool's errand, but what I will say is the bar at the one year, we will not have one-year data, right? The bar at the one year is, I think, orforglipron sets a mark, right? A reminder, orforglipron at one year is 10%. That's what we're talking about. orforglipron, I suspect, will be a very successful drug, for a couple of very obvious reasons. I think that we might be surprised. We'll see what we get. All right. In summary, really big year for you guys on both the oncology and on the obesity front. Yep. A lot to look forward to. Unfortunately, we are up on time. Yuval, always a pleasure. I hope you have some great meetings today. We will talk soon. Jeff, thank you so much, and thank you for the audience. Appreciate your attention. All right. Take care. Take care. Bye-bye.