Corbus Pharmaceuticals Holdings, Inc. (CRBP) Earnings Call Transcript & Summary

Good morning, everyone. Welcome. We're excited to be continuing our 44th Annual JPMorgan Healthcare Conference. My name is Roland Ye. I'm associate on the health care investment banking team. And today, it's my pleasure to introduce Corbus Pharmaceuticals and CEO, Yuval Cohen. We'll have time for Q&A at the end. And with that, we'll hand it over to Yuval.

Good morning, everyone. Roland, thank you so much for that introduction. It's a delight to be here. We're very grateful to the JPMorgan team for hosting us again. I'm going to focus this morning on 2 of our assets. I'll start with important milestones coming up this year for our ADC. And then I'll talk a bit more about a refresher of our recent obesity data and the milestone there. I'm assuming everyone in this room and probably everyone listening knows the background of Corbus, understands our pipeline. So let's dive straight into it. The key questions, I think, for CRB-701 in 2026 are the following, and I'll divide it into the 3 possible indications of this study -- of this drug. The first one revolves around our second-line monotherapy in head and neck. We presented updated data on that at ESMO. We have more and more patients. The duration is getting longer and longer, but it's still an earlier data set that we presented from this September data cut. Later this year at a large oncology conference, our aim is to present the maturing data, where the key question revolves around the duration of response for these patients. I think we've established that CRB-701 is active in second-line head and neck. And now the question is how durable is that activity? How durable is that response. Coinciding with that is on schedule this quarter, we're having discussions with FDA around what does the registrational pathway look like for this second-line monotherapy in head and neck for CRB-701. We don't anticipate that being a particularly dramatic discussion. There is a very clear and sensible precedent from [ PETO ] around second-line head and neck, and we will provide that update later this quarter. And so between that update and the durability data, that would give us the informative data set that will enable us to move forward. At the same time, the second key combination of both registrational pathway and data revolves around our cervical data. And so here, again, at ESMO, we presented a young emerging data set in second-line cervical cancer. Again, clear signs of clinical efficacy. In cervical, it's a little bit easier to triangulate because our partners in China, CSBC already shared some of their cervical data. And in fact, for that matter, their competitors in China, Mabwell, with a different construct of Nectin-4 MMAE ADC also shared data and all 3 data sets look remarkably similar. The question here, again, is durability. How durable is the response that we're seeing in these women in the second-line setting in cervical cancer. And in an analogous fashion to what we just described for second-line head and neck, what is the registrational pathway. So also this quarter, parallel discussions with FDA around what does that look like. Here, the precedent is not helpful to us. The precedent would be TIVDAK in second-line head and neck -- second-line cervical apologies. TIVDAK harks back to a time where FDA was probably a lot more open to single-arm accelerated approval stand-alone studies. Our assumption is that this FDA is less welcoming of that. And frankly, we wouldn't be particularly interested in that if that were a pathway. And so the discussion with FDA around second-line cervical is around a controlled study versus physician's choice. The discussion will revolve around what is that physician's choice. TIVDAK is certainly one of those choices, but not the most common choice for physicians. And so we'll have that clarity from FDA. And again, in an analogous fashion to second-line head and neck, we will share that clarity. We will share the maturing data set, the durability data set this year. And those 2 would allow us to really chart the path forward. The last milestone this year is around the data set that we don't actually have yet, but is increasingly being brought up in conversations we're having. And that is the -- our most recent study with CRB-701, which is frontline in combination with KEYTRUDA in head and neck. That study started relatively recently. It's a very young data set. It should start to mature towards the end of the year. And that is a very, very different type of pathway unlike the second-line monotherapy head and neck, which is a pretty quiet swim lane for us. Frontline is seeing a lot of interest, a lot of competition, but with a very different mechanism of action. The emerging frontline landscape in first-line head and neck is EGFR-dominated combinations that are either entirely biased or partially biased towards HPV-negative patients. And so that leaves us with an interesting possibility of positioning ourselves in combination with a checkpoint inhibitor, in our case, KEYTRUDA in that frontline setting. We don't know what that data would look like. We look forward to that data maturing and to sharing it with you later in the year. What we do know is that Nectin-4 -- there is an example of a Nectin-4 MMAE working very, very well together with KEYTRUDA, and that is, of course, PADCEV plus KEYTRUDA in frontline bladder. It will be fascinating to see if we replicate some of that additivity in the frontline setting of head and neck. And so just to summarize on our ADC front, 3 cards that are sort of flipping this year as it were, second-line head and neck durability and regulatory clarity, second-line cervical durability and regulatory clarity. And the last one, the most intriguing one perhaps, but a very unpredictable one is the emergence of the frontline head and neck in combination with KEYTRUDA. So not a lot of drama, a pretty understandable, a pretty clear set of actions that are required from our perspective on CRB-701. And with that, to a field that could not be more different, which is obesity, of course, and our oral once-a-day small molecule CB1! inverse agonist. Those of you who have been following the Corbus story know that we have a deep passion and expertise in this field and really have been championing the reemergence of these peripherally restricted CB1 inverse agonism. This is a mechanism that, as a reminder, was of great interest exactly 20 years ago. This year is the 20th anniversary of rimonabant being approved in Europe and then had a really very significant setback to say the least, and that has come back. And it's come back with 2 parallel efforts. The one these days resides in Novo Nordisk, and that was or is Monlunabant. And the other one is CRB-913. A reminder, they are related. They're cousins, not very close cousins, but cousins. We both share the same ancestor. Novo Nordisk, of course, reported their data in November of '24. That was a pretty memorable day. It wasn't a very pleasant day for us, and it was an extremely unpleasant day for them. And they recently published that data. That has not been picked up by many people. That was in the September issue of the Lancet diabetes. CRB-913 finally got into patients, although we did it in a record time, but finally got into patients with a SAD/MAD data that we announced in December and is now in the dose range response data, the Phase Ib. A reminder that there is something fundamentally different about our 2 drugs. They are cousins. But while the Novo Nordisk, while Monlunabant is peripherally restricted, there is less of it in the brain than rimonabant, we are more than order of magnitude more restricted than they are. Our drug is very, very, very, very, very low levels in the brain. And of course, there is a mirror slide to this slide, which could ask how much is in the brain and then how much is in the periphery. That's a bit more tricky for us to do because we don't know the exact levels of Monlunabant in obese individuals. But nevertheless, we can do some fancy modeling, and we reckon we are about 30% to 40% higher levels in circulation and obese fed individuals than Monlunabant. So the differences are there's markedly less of us in the brain compared to Monlunabant and markedly more of us in circulation compared to Monlunabant at the same dose. This was the design of our SAD/MAD study. It's a pretty unremarkable design. We don't want to be particularly creative in the field of obesity. And so we have a ladder of SAD and a ladder of MAD. All the blue cohorts are cohorts that were not selected for any BMI requirement and the 2 green cohorts are cohorts that were exclusively selected for high BMI. So these are individuals with obesity. And a reminder that the doses we gave in SAD/MAD, as is normal, are doses that are much, much higher than you would normally end up giving in the clinic. So our 150-milligram a day dose is about 15x more than the clinical dose of Monlunabant, and we have every reason to believe that we are equally potent to Monlunabant. So what did we see? We'll start with safety. This is a Phase Ia. And in the case of CB1 inverse agonism, it really is all about the safety. CB1 inverse agonism is very, very likely to work in patients. Every CB1 inverse agonist ever tested in the clinic has led to weight loss. I don't think there's a lot of controversy around that. The question is, have we solved the issues of safety surrounding that first generation. The first safety event, which was of interest to us and which frankly surprised us was GI toxicity or GI tolerability. CB1 inverse agonism does not tend to affect gastric motility. If we go back to rimonabant's data, they have GI adverse events, but they tend to be pretty mild and at about 10%. It's not at all the same degree of GI tox that we would get with either an incretin analog or an incretin agonist. One of the surprising data points in that Lancet diabetes paper on Monlunabant was the degree and magnitude of GI tox with Monlunabant. That is highly atypical of a CB1 inverse agonist. It is so atypical that we think that, that might be an off-target effect. Monlunabant in some ways can be thought of as being almost a prodrug. It has a remarkably high degree of an accompanying metabolite. And CB1 inverse agonism has never shown these levels of GI tox. This looks a lot like an incretin analog. What was very reassuring was to see in our data set on the right-hand side, a very, very mild profile of GI adverse events. It is in line, if not better, than the first generation, and that is typically what you would expect from a CB1 inverse agonist. The difference is remarkable. GI adverse events were the second most common reason for discontinuations with Monlunabant. These were not an inconvenience. These were a serious problem for these participants. So that is a case where the 2 safety profiles look markedly different. But of course, if we think about that first-generation CB1 inverse agonism, we always think about the neuropsychiatric adverse events. After all, that was the issue around that first generation. We have a very, very granular view into the Monlunabant adverse events from their 4-month study, just like we had with GI adverse events. And what we see, there are a number of things. The one is very typical. Neuropsychiatric adverse events regardless of the mechanism of action, for that matter, regardless of indication, tend to appear very early on. They tend to not be adverse events that occur much later in the study. And that is exactly what we see with monlunabant. It is dose responsive, which is also very reassuring in that sense. The problem is there are a lot of them -- so in 180 participants, they had 111 events of neuropsychiatric adverse events. Now while the vast majority were mild, that's not great. That is problematic. And they were the member on cause of dropouts in the study. Again, that is a problem, especially in a study that is actually quite short, 4 months of dosing. And so despite monlunabant being at about 50% of the brain penetration or the brain levels of rimonabant, there's clearly a problem. There's clearly a problem there. It was especially gratifying, especially as a scientist at heart, it was especially gratifying to see what our data looked like in terms of neuropsych. Remember, it's -- the whole premise here was keeping this drug as much as possible from the brain would lead to a differentiated neuropsychiatric adverse event profile. It's wonderful on paper, but it's especially satisfying in our industry to actually see that happen in real human beings. And so to our delight, we had absolutely no clinical events of neuropsychiatric. So CSSRS, PHQ-9, GAD-7 were negative for all patients at all time points, time points were daily. And at all doses, remember, these individuals or some of these individuals are getting doses that are 15x higher than the Monlunabant doses. And so that was really, really wonderful. We had, of course, no cases of suicidality, depression or dysphoria, which is delightful. Not even in the case of insomnia, which is remarkable given that this is a Phase I unit. These participants are not in their house or not in their home. So that was really, really nice to see. We had the sum total of 3 cases of mild anxiety. This anxiety did not breach CAD-7 or PHQ-9. In other words, this is everyday human experience anxiety. One of which was situational. In other words, something happened to that participant that triggered them feeling anxious. And the other two happened outside of the dosing window, one of which corresponded with gaining back weight once the drug was clearing out. So that's really encouraging. Now of course, this is a short amount of time, and we need to see more and for longer, but it is already so remarkably different than what we saw with Monlunabant, for that matter, with the first generation that we really are very, very excited about this. The second question was, does it actually work? So in most of our SAD/MAD cohorts, we were not selecting for BMI, as I've mentioned. So we have a collection of people who are thin and overweight and obese. But we did have one cohort in the MAD that was exclusively high BMI. 12 individuals in total, they spend a week being dosed and then another week observed in the clinic. So it's 2 weeks of them living effectively in a fish tank. And that allows us to have a very controlled environment in terms of what they're eating and what they're experiencing and what they're exposed to. And so we, at the end of the study, look back and asked the question, did anyone lose weight? We were not expecting this degree of weight loss this quickly. And so what we saw were every single participant who was dosed with Monlunabant lost weight that in and of itself is unusual and delightful. And the weight loss was significant. These are not small fluctuations in weight in such a short period of time. On average, it was nearly 3% weight loss after 1 week of dosing measured at the 2-week mark. To put that in context, if we look at sort of -- there's an interesting league of weight loss as it were in different mechanisms of action. And if we look at that league and the speed of weight loss and the depth of weight loss, we are in the top 4 mechanisms that have ever shown such a weight loss that quickly. The other 3 are all incretin analogs. That were remarkable in their weight loss, but associated with a very high level of gastrointestinal adverse events. A reminder that you can lose a lot of weight if you have -- that's accompanied by a lot of vomiting and gastrointestinal intolerability. We had no GI adverse events. We had one mild case of possibly related diarrhea. That's it. And so CRB-913 acted in a very robust manner to reduce weight. The other question we had was this graph shows that it is clearly not just driven by a single patient, but we wanted to know the temporal cadence of this. Did this all happen on the last day? Or was this gradual? And that's very easy data for us to pull out of the study as well. And so what you see in red are the placebo participants and nothing much happens to them, as you would expect. And in blue is the cohort that are high BMI. And you can see that weight loss starts early, and it just keeps deepening as the study continues. A reminder that we dosed them only for the 7 first 7 days. The momentum of this compound is really, really satisfying to see. All CB1 inverse agonists have long half-lives measured in several days. That's not atypical. So that momentum makes sense. Still, it was really quite remarkable to see this type of -- in this depth of weight loss. So we're really delighted with that. We have -- we did not have dose response cohorts that were exclusively high BMI, but we did have a dose response -- 3 dose response cohorts or dose escalation cohorts in the non-BMI selective cohorts. And maybe it's a factor of just where the Phase I unit was in the United States, but our average participant in these 3 cohorts was already overweight to a certain extent and some of them were obese. And so what we see is a clear signal of weight loss even in the lower doses. The other thing you'll notice is that our 75 milligram a day dose and our 150 milligram a day dose in these 2 cohorts look really similar. That's encouraging. We think the 150 dose is beyond the linear S curve. And so it means that 75, we would expect initially to be quite as efficacious as the 150 -- in other words, it means that we can afford to dose lower and still get the same efficacy. Next 2 slides are cross-trial comparisons, which are comparisons that are very popular in the world of obesity with all the caveats, of course, that come with them. The first one is very easy to generate. We have so much data around rimonabant. So it's very easy to generate a 16-week rimonabant weight loss curve that's placebo adjusted. And then the 3 curves that come out of the Phase IIa from Monlunabant. There is also the small curve that comes from the Phase Ib for Monlunabant. And then lastly, the very short green line is our high BMI 2-week dosing for CRB-913. And so what you're seeing are a couple of things that I think are worth thinking about. Both Monlunabant and CRB-913 are clearly more potent than rimonabant. This is a very, very important observation. One of the concerns with the emergence of this new peripherally restricted CB1 inverse agonist was that they would take a hit on efficacy. It seems to be exactly the opposite. The fact that they are so much more in the periphery than rimonabant was has translated into even better efficacy. And remember, these are equi doses, especially around monlunabant, the doses are not dissimilar to rimonabant. And so what we're seeing here is a new class of CB1 inverse agonist that is markedly more potent than the first class that is unexpected and very, very welcome. It opens the door to speculating what could this class show as monotherapy. A reminder that Novo Nordisk were guiding back in September of 2024, before September of 2024 to mid-teens to high teens eventual efficacy of Monlunabant, presumably at the 1-year mark. They did generate open-label extension data that has yet to be published. But if we look at the Monlunabant curves from their RCT, it is not very hard to imagine that those do end up at the 1-year mark in the high -- in the mid- to high teens. It will be fascinating to see if they publish that. It makes us increasingly more and more confident that we may actually have a markedly more potent compound than we anticipated. The other slide we can do is compare -- cross trial compare to a completely different compound, and that's Orforglipron. If Monlunabant is not a relevant competitor anymore, then what is a relevant at least benchmark. And that would be the easiest one is orfoglipron. Luckily, there is an Orforglipron publication, which is a very appropriate comparator, of course, with all the caveats. And what you see there in green is CRB-913. What you see in the other colors are orfoglipron. And a couple of observations, CRB-913 does not look like orforglipron. It looks markedly more potent in at least a short period of time that this SAD/MAD provides, both for us and orfoglipron. A gentle reminder that orforglipron at a year is effectively sub-10%. Monlunabant at 4 months was at 8% already. And so we really are talking about something that could be not just similar to orfoglipron, but potentially really surprise us on the upside. The other very big difference is this little table on this slide. Orforglipron is after an incretin agonist. And the gastrointestinal adverse events are as to be expected for the class. And again, a reminder of juxtaposing what was seen with orforglipron in a 4-week period versus what was seen with CRB-913 in a 2-week period, and they really are markedly, markedly different. So what could you do with this compound? And then we'll talk maybe about upcoming milestone this year. In Slide 49, what we endeavor to do, and some of this is sort of back of the envelope, but I think it's pretty accurate. It's pretty robust, is we take the data set of approved incretin analogs, and we divide it into 3 slices. And the first one are responders and about 60% of patients are responding and do well and can tolerate them to various degrees. For that slice of the pie, what would be intriguing to do with CRB-913 conceptually would be an induction maintenance usage. We have very, very, very good ways of losing weight for these 60% of patients with the injectable incretin analogs. What is more challenging perhaps is lifelong weight maintenance and doing so with an injectable incretin analog is could be perhaps improved upon. And so conceptually, the idea would be you lose weight with an incretin injectable incretin analog and then you replace that with a daily oral pill that does absolutely nothing. You don't lose further weight. That's not the point of the exercise. What it does is it prevents you from regaining the weight. It keeps your weight stable. And the key there will be tolerability, especially GI tolerability. The other slice of the pie are the intolerant patients. So these are individuals who start incretin analogs and presumably the same thing will happen with incretin agonists and they just can't take it. The GI adverse events are just too much. There, an orthogonal mechanism of action is desirable. The chances of being intolerant to both seems to strike us as being unlikely. And so there, the idea would be to offer them a replacement, especially if that replacement alternative could be equipotent at least to an incretin agonist. That could be really, really disruptive. The last ones are the nonresponders. So these are the individuals who can tolerate incretin analogs or agonists presumably, but it just doesn't do much or doesn't do anything. And so there, what we know is patients who are non-responsive for one of the incretin analogs tend to also be non-responsive for the other incretin analogs. There, an orthogonal mechanism is, again, intriguing, potentially either as a combination to try and kickstart the system perhaps or again, as a stand-alone with an orthogonal mechanism. So what are we doing now? And what is the important milestone here this year for Corbus, apart from the ones we talked about for oncology, and that's CANYON-1. That is our version of effectively what Novo Nordisk did with Monlunabant. There are some interesting tweaks. CANYON-1 is U.S. only. It's pretty similar doses. It's a pretty similar period of time. It's an identical number of patients. The one thing that is different is we are the first CB1 inverse agonist to ever implement titration, effectively because we can. Everybody else does it. Titration is a very sensible thing when looking at anti-obesity medications, and we think it makes a ton of sense to do so also with CB1 inverse agonism. And so we will be titrating into the highest dose. And at the end of the study, figure late summer of this coming -- of this year of 2026, we'll have that data and that critical mass of data. This will be a highly informative data set. It is more than enough patients for us to have a very granular idea of the safety, especially neuropsychiatric adverse events. And in addition to that, a very granular idea around dose response and being able to model what the weight loss is up to a year. So we very much look forward to that. And I think with that, Roland, I'm pretty much ready for any questions you might have.

Well, thank you, Yuval, for that overview. Yes, we can open it up for questions, and I can start with the first question on my mind. So I think it's really interesting to see how CRB-701 is moving into first-line treatment for head and neck. And you mentioned an interesting kind of comparison with PADCEV. Can you talk about the similarities or differences between CRB-701 and PADCEV?

Certainly. And again, apologies for those who are less familiar with the story. So CRB-701 is a classic next-generation ADC. And like all of those, we're looking at a structure that looks like this for those of you watching here or -- there we go. Site-specific conjugation, so a precise DAR, that's pretty standard. It's using CLIQ technology. There's a bunch of those out there. A very, very, very, very stable linker, and this one is also very short. Again, it's a proprietary linker, but the approach has now become standard. So it's a DAR of exactly 2 for MMAE and a very, very stable ADC. The mab here is not enfortumab. It's a proprietary mab for a different epitope of Nectin-4, and it has twice the rate of internalization as enfortumab. What does that all boil down to? It boils down to in humans to a markedly lower level of circulating MMAEs. That's really the big takeaway here, Roland. The ability to have less free MMAE means the ability to have fewer adverse events, especially when it comes to peripheral neuropathy and skin. The other important differentiator is the ability to have a very stable ADC means that we can dose less frequently than PADCEV. But otherwise, conceptually, it's Nectin-4, highly validated with Nectin-4 MMAE, which is highly validated in bladder. And we've seen a bunch of Nectin-4 MMAEs now coming out primarily out of China, showing confirmatory data in bladder, which is not a focus for us; in cervical, which is a focus for us and in a bunch of other tumor types that are not the focus for us, at least not yet.

Thank you, Yuval. Any questions in the audience? Yes, please.

Trying to understand the mechanism of your weight loss.

Sure.

Have you studied whether these patients are eating less or drinking less because when you lose that much weight that quickly, we know for the GLP-1s, the concept is that they tend to eat less. So it takes some time for that to kick in and then it happens. You're seeing immediate weight loss starting day 1. How do you explain it?

Appetite suppression. So the patients are -- the participants are reporting a reduction in food craving, a reduction in food noise as it were, very positive. So it's -- we're not seeing something which is anhedonic. The case studies are interesting. The case report forms are -- I'm paraphrasing, but it's pretty accurate. I'm no longer thinking about eating. I'm no longer obsessing about eating. What is intriguing, and I think I wonder if that's where you're going for was for 20 years, we've wondered what would happen if you took the site of activity of CB1 inverse agonism from the brain into the periphery, would you still get that because that was very typical of that first generation. What is wonderful to see because we see the weight loss in mice very quickly, right? But it's very hard to interview a mouse about its eating habits. You can see the food consumption go down in mice almost instantaneously. But what's been really delightful from a scientific point of view is being able to actually interview and interact with humans. How does it do it from the periphery into the brain is super intriguing. I don't think anyone has a very clear answer, but we know a bunch of things about CB1. And a gentle reminder, CB1 inverse agonism, there are over 9,000 papers on that with metabolism. It's 30 years' worth of research. It's one of the most studied mechanisms or mechanisms of action in metabolism. So what do we know? We know a bunch of things. CB1 is heavily, heavily found in the organs of metabolism, not so much the digestive organs, but the organs of metabolism. When you knock out CB1 in the whole animal, you get an animal that is obesity resistant. But Egan et al. at NIH did a series of marvelous selective organ knockouts in these mice. So they, for example, have a mouse that CB1 is knocked out only in muscles, right? And what you see is absolutely an effect on metabolism, on food consumption, et cetera. And there is a slight analog here to -- or analogy to the incretin analogs at least, especially the really big one, where at least theoretically, it shouldn't be crossing into the brain or at least primarily crossing into the brain, and yet we have a very, very clear effect from the periphery into the brain that is not necessarily just GI toxicity mediated. We have plenty of patients who have very mild to no GI adverse events, and they're reporting food noise reduction or craving reductions. So there's a lot more to explore there, but it is absolutely fascinating how that actually worked out.

So as you said, there are many ADC Nectin-4 in China. I had worked with some, right? So I don't know if your study were done in Asian population. If it was in just Caucasian, I want you to share a little bit the safety profile because what we have seen was a lot of SAEs around joint and also skin rash, very, very severe, very painful where the patient decided to discontinue on the study. So I would like you to share a little bit about that.

Wonderful question. So one of the advantages of where we find ourselves is we have a Chinese partner, that's CSPC. They run a completely independent program in China on ethnic Chinese everything I just showed today was our U.S. European clinical study. And if we compare the 2, and we had that poster in 2020 -- at ASCO GU 2025, they're actually remarkably similar. A little bit more ocular tox in China, and I think that's maybe an environmental aspect as well. But otherwise, remarkably similar, low, low levels of peripheral neuropathy. We have what seems to be the best-in-class peripheral neuropathy, low levels of skin and overall, a very tolerable safety profile that is echoed in the Chinese population. But you're so right, they're not always the same, and it's really important to compare.

We have time for maybe one more question, about 2 more minutes, if there's any questions from the audience.

Actually, before I forget Roland, I apologize, I'm looking at my CFO, who reminds me gently telepathically cash position. That's kind of important in our industry. So we had $172 million in the bank, and that gives us runway with both of these, both oncology and obesity into 2028.

Awesome. All right.

Thank you so much, everyone. Really appreciate it. Thank you, Roland.