Hi everyone. My name is Maury Raycroft, and one of the biotech analysts at Jefferies. I'd like to welcome Yuval Cohen, the CEO of Corbus. Thanks so much for joining us today, Yuval.
Thank you, Maury. Thanks for having us over.
Maybe to start off, if you want to give a one-minute intro to Corbus for those who may be new to the story.
Sure. Morning, everyone. Thanks for coming here this morning. Corbus is, we're based just south of Boston. We have been around since 2014. This is our second pipeline. We had a pipeline from 2014 to 2020, and that did not work out as we had expected. So we learned some very important lessons. And then earlier this year, we sort of launched our new pipeline. The pipeline has three assets. The two that I think are most relevant for our discussion today is we have a CRB-701, which is a Nectin-4 ADC armed with MMAE for solid tumors expressing Nectin-4. And that's partnered from China from CSPC. That's well in the clinic. And then our second asset hails back to our days where we were focusing on the GPCRs of the endocannabinoid system.
And so this is an asset we brought in a number of years ago, which is a highly peripherally restricted small molecule CB1 inverse agonist for obesity. That one is starting its journey in the clinic early in Q1.
Got it. Yeah, that's a great intro. And with, you mentioned the Nectin-4 ADC from CSPC, you're going to have an update first quarter of next year from your phase one, which includes U.S. and E.U. patients. Maybe talk about that and what expectations should be and how to compare and contrast versus the data CSPC has already shown.
Sure. So this year in 2024, we got to showcase the first clinical data, the first and second data cuts out of China. So that was a dose escalation study in China that was showcased at ASCO GU this year, and then more patients and longer at ASCO. What we will be showcasing in Q1 is data from our Western, mainly U.S., some U.K. site bridging study. And so the idea behind the bridging study is the following. The patients are similar. It's the top four doses of the dose escalation in China. We didn't have to do the lower doses. So it's the top four therapeutic doses. It is four cohorts. It's a three plus three BOIN design. So at least three patients per cohort. But the BOIN allows the investigators to recruit more and backfill.
The idea behind the bridging study is to showcase first and foremost, to contextualize data from China into the West, into primarily the U.S. So we want to see what does the PK look like outside of China in a mixed Western population. We want to see what the safety looks like outside of China in a mixed Western population. We want to see that the ADC is not clinically inert outside of China. That's likely to happen, but nevertheless, we want to see what its efficacy is, efficacy signals. There are a couple of interesting differences, Maury, for the audiences. The two that come to mind are the following. China is allowed to exclude low expressors of Nectin-4 even in dose escalation. You can't do that in the West. In the West, you have to include everyone and then show if there is actually a difference.
So you'll see a wider range of Nectin-4. You should see a wider range of Nectin-4 on our patients. So that'll be really interesting. A reminder, for example, when it comes to Padcev and bladder cancer, it actually pretty much doesn't matter. That's why we don't have a commercial CDx for Nectin-4. There was no point developing one. The other difference, which we're excited about, is in China, our partner CSPC started to enrich for bladder and for cervical very early on in the dose escalation. And if you look at the data on our, whether it's on those posters or on our deck, what you see is as we go into, as they went to those higher doses, it really is down to just bladder and cervical. They're very effective at excluding other tumor types.
Our Western bridging study is an opportunity for us to sort of open our arms a little bit wider and bring in other types of tumors that are known to be Nectin-4 expressors. For some, that may work. For some, it may not, but it will be interesting to see and to share what does this ADC look like in those other non-bladder cancers other than cervical.
Got it. And for cervical and for bladder too, will you have enough patients in your update to be able to compare to the CSPC data? And how are you setting expectations there based on the Nectin-4 expression differences that you mentioned?
Oh, sure. So you'll have to wait and see. Bladder is easier to find in the West than cervical. Remember, for us, cervical is interesting because it is a rare malignancy. For CSPC, it's interesting because it's not a rare malignancy in China. So that'll be interesting to see. For bladder, it's interesting as well. In the dose escalation study in China, they did not have patients who are pretreated with Padcev. Padcev has yet to be approved in China. In the U.S., that's not the case. In the U.K., that is the case. So it'll be interesting to see if we do have a mixture of pretreated with Padcev versus Padcev naive. And then, as I said, what do we have in terms of those other swim lanes? That'll be interesting to see.
Got it. Anything more you're saying about the other tumor types, the other swim lanes?
No, you know, on our deck, we have a little graphic with a type of tumor types that are well known to be Nectin-4 positive or enriched, and a reminder to the audience, that's really the idea behind us as a standalone company in terms of our vision of seeking a label. We are not interested as a standalone company to go out there and pursue bladder as a commercial opportunity. We are tiny. Pfizer are enormous. We will always have bladder patients because it's within bladder that we can juxtapose our data set to Padcev, but we're not about to duke it out with Pfizer. That to us makes no sense as a company of our size.
What we're very, very keen on is how quickly can we pursue labels in those swim lanes outside of bladder, especially since those swim lanes to us appear in our assessment to be clear. Padcev is not ahead of us, and we don't even think it will be ahead of us in some of those swim lanes. So that's where we can actually have an advantage.
Got it, and I know this is pestering a little bit, but you mentioned that patients who had already had Padcev experience, how many do you think you could have in your study that fit that profile? And what are the expectations there? Is there rationale for responses to occur in patients who already have Padcev, have already had Padcev?
It'll be really nice if it does, doesn't it? And I mean, look, the rationale is it really boils down to, is the Nectin-4 still there, right? I think that's probably quite sensible. And the bigger thing is, has the pretreatment with Padcev rendered these patients so damaged by, for example, peripheral neuropathy that you don't want to introduce a second MMAE ADC? But yeah, if you could see something there, that would be really interesting.
Got it. Okay, and maybe talk about safety. It's one of the key areas that investors are focused on. Maybe highlight some of the safety measures that are important and what your expectations are there.
Sure. So remember, Padcev is a really good drug. The problem isn't its efficacy. It's the accumulation almost invariably of peripheral neuropathy and then skin. And so we know so much about that within bladder. We know when they show up within bladder, right? The skin shows up typically within the first cycle. Peripheral neuropathy starts to show up at around two and a half months for any grade and around four months for the grade threes. And if we look at the duration of response for Padcev, which is about five months, it's usually not because patients stop responding. It's just they're broken. They can't tolerate it anymore. And so one of the most interesting concepts around our ADC is by holding onto that MMAE for tighter, for longer, can we deliver a drug that doesn't have that sort of collateral damage from free MMAE?
Does that translate into a drug that you can dose for lengthier periods of time before the wheels fall off and at higher doses? If you could do that, that should be a more efficacious drug. The one thing that has come as a surprise to us, a pleasant surprise, is if you think about it conceptually, our ADC on a piece of paper is like a, it's Padcev but tweaked, right? It's Padcev as you would develop it today. It has site-specific conjugation versus the randomized conjugation. It has a stable, cleavable linker that wasn't available at the time. It has very precise DAR and a lower DAR, which is for MMAE, lower DAR seemed to be better and better tolerated. We are really surprised by how different it's behaving than Padcev. We would not have anticipated that. So, and there's a variety of reasons.
It's all of those things. The MAB is proprietary. A gentle reminder, the MAB itself has twice the rate of internalization of enfortumab . What was impossible to model is when you put all that together, what actually comes out the other side in the clinic. We're really looking forward to sharing that.
Got it. And one of the measures that was in focus too was ocular toxicity with the CSPC data. With your study, you're doing a few things differently there. Maybe talk about that and what expectations should be there.
Sure. So another big difference in China and the West, the FDA, for example, for all ADC, pretty much mandates that you have a pretty aggressive ocular prophylaxis program. We've seen over and over and over again with these new stable ADCs that they accumulate in the eye and you get typically surface of the eye, dry eye AEs. We see that over and over again. So in the dose escalation in China, except for the very highest dose, they did not use prophylaxis. So we actually got to see, and you got to see what does the safety look like when you don't use prophylaxis. The other thing about China is base level. They have a lot more dry eye issues. Half of them are smokers. There's a lot of pollution.
So 50% of the patients who walked into the study in China already had dry eye and related conditions. What you'll see in our dose escalation is what does it look like, not only in the West where the air tends to be cleaner and people smoke less, but with a lot more aggressive prophylaxis. What is also interesting is later next year, we should see the dose expansion data out of China. And that's where we will see what does Chinese data look like before prophylaxis and after prophylaxis, because now they're using it.
Got it. Okay. That's helpful. And can you bookend the number of patients that you'll have in the update? You've got the four dose cohorts.
Three plus three, but it's a BOIN design. So 12 plus. Let's see what we do. The first patient was dosed April 2nd. We announced two weeks ago, I think, that the third patient of the highest dose cleared their DLT. There is definitely a plus after that 12.
Got it. And how much on durability should we expect?
First patient walked in April 2nd. So just keep that in perspective. What's nice about it, as I said, is certainly for bladder, we just know so well when the problems arise for skin and peripheral neuropathy with Padcev, so we can pretty much benchmark against that.
Got it. Okay. And just with kind of logically thinking about which tumor types you could pursue, it seems like cervical would make a lot of sense. What does a regulatory approval path look like there? And is there potential for an accelerated approval path?
It's certainly a rare condition, right? It's 15,000 women per annum in the U.S., similar number in the E.U. Interestingly enough, the numbers are not coming down due to vaccination. Not because the vaccine doesn't work. It works really nicely. It's immigration. We have a steady stream of adult women moving into the West where it's too late to vaccinate them. So that 15,000 is very steady. 4,000 fatalities, tragically. These are women in a childbearing age. So these are young women or youngish women. So it's a really tragic condition. Tivdac, which is the other, actually Genmab to Seagen to Pfizer now, is another MMAE-armed ADC. It's got a label for second-line monotherapy. It is in cervical. It is a standard of care, not the standard of care. Difficult drug to tolerate. Response rates are about low 20s%. And that was approved at the time based on accelerated approval.
Single arm, 101 women, of whom 16 were in the U.S. and the rest were in Europe, and ultimately, like all of these things, it's going to depend on what does the data look like and talking to the regulatory agencies.
Got it. And do you think you'd have to run some sort of a study versus another agent out there or show superiority versus Tivdac?
I think it depends on. It's unlikely it'll be against Tivdac. Again, the data will determine that, and it depends. Are we looking at second-line monotherapy? Are we looking at first-line, perhaps combination? It's all data-driven, but it's really nice that you have these options that you can explore, and depending on what the data looks like, we will then decide which path to go through. The reason the bridge is so important is if the bridge is tight, we can leverage China. The degree to which we can leverage China is a discussion we need to have with the regulatory agencies. Is China, for example, sufficient just for safety? That in and of itself is not too bad because they have a lot of patients.
But if we can leverage the efficacy out of China as well, again, not exclusively, but as well, you can imagine that's a meaningful shortcut for us.
Got it. And maybe, yeah, talk about with CSPC, can you say how many patients they have in their study at this point and how often you're meeting with them?
Oh, we meet very regularly. It's a really nice tight relationship. Your assumption is that CSPC, like all other Chinese pharmas, certainly in oncology, are recruiting very, very, very well. Even this year, we saw the patient numbers double between January and March. And China is a very, very good place to run oncology studies. So they're recruiting, they're exceeding our expectations, and they'll probably exceed your expectations too, my guess would be.
Got it. And maybe last question for Nectin-4, just you mentioned potential niche opportunities in the bladder cancer space. You don't want to go head-to-head versus Padcev. What could those niche opportunities look like?
So I think the way I would think about bladder, more in the audience, is don't think of it as Corbus, right? For us, we are not interested in pursuing a label for bladder. But if you're a strategic, especially a strategic with your in-house checkpoint inhibitor, bladder is supposed to be a $6 billion market. The calculus is very, very, very different. In the hands of a strategic, a Nectin-4 ADC armed with MMAE that could appear to be superior to Padcev is a very different calculus, right? Which is why we will, one of the reasons we will continue to have bladder patients is we want to continue generating data for a variety of audiences, and one of them is strategics. And yes, for the niche population, it sure would be interesting to look at before treatment with Padcev and then after treatment with Padcev.
All these things for a strategic are really interesting opportunities.
Got it. And let's shift gears, talk about 913, the CB1. Novo Nordisk had an update a couple of weeks ago with a press release top line of their Monlunabant program. Maybe talk about your latest interpretation of the press release and what that data update means for you.
Thank you. It has not been boring. We've obviously gotten a lot of questions about that press release. So there was a press release and more recently now, I think last week there was their earnings call where they had some verbiage around it. So what do we know? The press release is very cryptic, right? It's not the most, it's not exactly a study in transparency. And that seems to actually be a pattern, to be fair, not just from Novo, from a bunch of big pharma. What we know is we know how much they lost on the lowest dose and we know they're moving forward. That's it. Those are the two data points we have. It's very encouraging that they're moving forward. They're moving into what they've disclosed to be a 600 patients dose response study.
And to be fair to them, they inherited a study that was designed by Inversago, and they've always kind of grumbled about it. It was Canada only. It was not under IND. So now they get to do the study they really wanted to do, which is lots of different doses. We just don't know how long it is. The other thing that we now know, but we really sort of folks had to pry it out of them was that the most important endpoint in the study was the primary safety endpoint, which was C-SSRS, which is suicidality, and that was negative. It's puzzling that they did not include that in their press release, but it is what it is. It looks like there was no depression either, which is remarkable.
So I think what they've shown is that you can engineer the bad things of the first generation by being peripherally restricted. And that's certainly the narrative. And that's a very powerful narrative. A couple of things that are in the press release or between the lines, we know what their weight loss is for the lowest dose, for the 10 mg dose. Now think of 10 mg dose as half a pill of Rimonabant, right? Rimonabant was 20 milligrams a day. We have the data and they lost about placebo adjusted 6% in four months. What's interesting about that, what's not in a press release, you would only know this if you're obsessed about Rimonabant as we are, is that's a lot more potent than Rimonabant.
In fact, that's the second time that this compound has shown efficacy that's superior to Rimonabant. The Inversago 28-day study was also superior to what you'd get with Rimonabant. It's interesting because preclinically they look like Rimonabant, as do we, but we're wondering now if this backbone really is actually more powerful. The second thing is they do have this verbiage around these secondary neuropsychiatric adverse events, right? Anxiety, insomnia, irritability. These are not the most obvious events to usually mention in a press release. We also have no numbers. We don't have a feel other than they're mild to moderate and they're not stopping. What we don't have is an idea of to what extent are they different than what you'd see with any weight loss agent. All weight loss agents, especially early in studies, have exactly those type of neuropsychiatric imbalances.
We speculate that whatever they saw couldn't possibly have been scary enough for them to stop, and they are known to have a high threshold. If what they saw, for example, was in line with what you'd see with semaglutide, then that's perfectly fine. What they mentioned in their earnings, which was interesting, is they seem to be rephrasing the notion of their higher doses not being more potent, and that seems to be now being recast as they may have been more potent. We were very surprised that they were saying that they were not seeing higher doses being more potent simply because the 25 mg dose from Inversago to us seems to be clearly more potent than the 10 milligram dose, so all that will be revealed when they finally show us the data.
Yeah. And Novo has mentioned 16%-19% per annum for weight loss. And we don't know if that estimate has changed at this point, but what are your views on that? Do you think that that is what you want to show for a monotherapy? Do you need that much weight loss?
It depends what you want to do with a monotherapy, so they also didn't disclose the OLE. They have an OLE up to a year and that was not disclosed. That'll be really interesting. They have mentioned previously that that number was based on blinded data, so OLE is by definition that. I think it depends. If you want to go monotherapy in order to compete with Orforglipron, then you want something in the mid-teens at least. If you're thinking of monotherapy as going after patients who are incretin insensitive, right? That's 10%. Or are incretin responsive but can't tolerate them. Or are at risk of sarcopenia since CB1 inverse agonism is not sarcopenic. If you have all that, then you could do with less than 10%, less than mid-teens. I think the other thing to think about is we've shown preclinically that they're additive to the incretin pathway, right?
Because they're orthogonal, so that's really interesting. You could take an Orforglipron, add an inverse agonist, and have Orforglipron excel, and then recently, as two weeks ago, at Obesity Week, what we showed preclinically is an induction maintenance model. The future of obesity, in our humble opinion, isn't so much the weight loss. We know how to make you lose weight very, very quickly. It's what do you do afterwards? How do you stay on something for the rest of your life that's easy to tolerate and that you can manufacture for a mass market, and that's when oral daily pill that is milder than an incretin pathway could be very attractive.
Got it. Makes sense, and you're planning to start your study in the first quarter of next year.
Yep.
When should we expect to see early safety and efficacy data from this study? How much follow-up is needed to get a clear picture on what you have?
Yeah, SAD-MAD, SAD followed by MAD should be done by summer. And after that, we do a dose response. So what's interesting is at the moment, Novo are way ahead of us, right? By 2026, we actually both line up because we will have our dose response data and they will finally have their dose response data. And so that's unusual. We don't see that a lot in pharma. But yeah, we will update everyone. Our interests are to be hyper transparent. Novo's interests are the opposite. And that's fine. They're a big pharma. That's normal.
Anything else you're going to do strategically different versus what Novo's doing?
In obesity, you want to be as least imaginative as possible.
Got it. And I think we're pretty much out of time, but maybe in closing, if you want to talk about 601, what the latest status is there and key catalysts ahead that investors should be focused on.
Sure. So 601 is a TGF-beta story, which is coming back now with Bicara and other things. It is very, very, very similar to a Pfizer program that's in phase two and that has yet to read. It is a monoclonal antibody against the integrin alpha V beta 8. That's going to start dosing very, very shortly. Big catalyst on 701 will be Q1 for our data and then mid-year for China expansion. And then for 913, IND clearing, SAD, MAD, dose response.
Got it. Yuval, thanks so much for joining us today.