Senior Biotech Analyst here at RBC Capital Markets. Good afternoon. Really pleased to have our next presenting company at Corbus, represented by their CEO, Yuval Cohen. Yuval, thanks for being here again.
Thank you, Brian. Appreciate it.
Maybe just starting with, the most, I guess, timely, data event that we're gonna be looking towards, ASCO. Just a couple of weeks away. Can you maybe tee up for us what we should be expecting to see now from the more mature monotherapy data for seven zero one in terms of durability, PFS, some of the biomarker impacts, things like HPV positive or negative or some of the other subgroups that we might be looking at? Any sense as to the degree of follow-up data that we might see from your partner as well at the upcoming meeting and future near-term meetings?
Lots of very sensible questions.
I know there's a lot there.
There's a lot there, but it's pretty consistent. Let's start actually with this Thursday, the abstracts come out.
Yep.
A gentle reminder to everyone, our abstracts were obviously back in February. They are the ESMO data, it's a September data cut, so there's nothing new in the abstracts. Our data cut for ASCO is an April 2026 data cut, so it's last month. The abstract's gonna be a little bit boring, but ASCO hopefully will not be boring. The Friday of ASCO starts with our first data set, which will be an oral presentation of our cervical data. On Saturday we have a poster for our head and neck data, on the Monday morning, we have our KOL event, which will be very similar to the ESMO KOL event, which will be sort of a post-game analysis of the head and neck data. What to expect?
It is basically the ESMO data with a few more stragglers that came in for both cervical and head and neck. These are the only two tumor types we'll be showcasing at ASCO this year. They, at this stage, as I said, have been at it for quite a while, and it means a bunch of things. One, at ESMO we showcased both the confirmed and unconfirmed responses. By now everything's confirmed, so you're gonna see a cORR. That's gonna be the first question we address for both of those indications.
The second one at ESMO, we didn't have enough data for durability. At ASCO, you'll see for the first time ever both DOR and PFS. It's still growing, it's still evolving. For the first time you'll have numbers to put around those concepts. The last one, Brian, is something that is peculiar to head and neck. That, as you mentioned, is a stratification between HPV positive or negative, or if we use the anatomical definition, oropharyngeal head and neck or oropharyngeal squamous cell carcinoma versus the other forms of head and neck. At ESMO, for 60% of our patients, we did not know what their status was at the time.
Your assumption is we've since then gone back and double-checked every biopsy, historical biopsy we had, and know for the vast majority of patients whether they're HPV positive or negative, whether they're oropharyngeal or non-oropharyngeal. The reason that's important is several fold. One is it will tell us what the path forward is. Is the path forward in all comers similar to what Merus at the time and now Genmab had embarked upon? Is it more similar to what Bicara and Johnson & Johnson are doing in the front line, which is to focus on a subset? In their case, of course, since they're EGFR bispecifics, they're focusing on HPV negative.
That's where the EGFR bispecifics work very well. The other reason that's important is, there are some interesting little tidbits out there that people can hypothesize. One is head and neck is the third richest tumor type in Nectin-4, right? We like those, just like we like cervical. If you dig a little bit more into the literature, it's actually not really head and neck, it's oropharyngeal that is Nectin-4 enriched. There's an interesting analogy here, is we have another tumor type that's HPV driven that's also Nectin-4 enriched, and that's cervical.
That's an interesting sort of hypothesis that starts to emerge. The more concrete thing that we can wrap our heads around from the outside, at least until we showcase the data, is PADCEV. What did PADCEV do in head and neck? ESMO 2023 Seagen present PADCEV monotherapy second line, it's not very informative, neither the poster nor the subsequent paper. We know what the overall response rate was, which was 24%, but there's no breakdown between HPV positive or negative.
We just don't know. We can guess, but we just don't know.
Okay.
Last year at ESMO in Berlin, Pfizer, what felt like sort of a closing of a circle, present PADCEV plus pembrolizumab in front line head and neck. Now they did stratify it. This was a poster on a corner of a room type of thing. Very unloved, very unnoticed. The all-comer overall response rate was pretty unremarkable 39%.
Not exactly a showstopper. The stratification was fascinating. PADCEV plus Keytruda in HPV negative, where the EGFRs work so well, that overall response rate, objective response rate was 23%. It kind of felt basically like Keytruda doing its thing on its own. PADCEV plus pembro in HPV positive, where Bicara really struggle, where peto really struggles, PADCEV plus Keytruda in HPV positive was a confirmed response rate of 82%. It was nine out of 11 confirmed responses.
We know that's not due to any better prognosis in those patients?
It doesn't seem to be, because if we juxtapose what the EGFR bispecifics do there, Bicara actually last week published their phase I data, and for the first time we saw what they did in HPV positive. In their setting, Keytruda plus the Bicara EGFR bispecific, HPV positive was just 27%.
Peto plus pembrolizumab in frontline, last time we saw it was four out of eight responses. There are some indications coming out of the study, coming out of Genmab, that are a little bit worrisome. Genmab have now added 200 patients to their frontline study from 500 to 700. As of yesterday, they now have added 100 patients to their second line, 500 to 600. I think the most likely hypothesis is that they need to compensate for a drag from their HPV positive.
It's not what PADCEV plus pembrolizumab saw wasn't because of what pembrolizumab does in HPV positive. There really seems to be a specific contribution coming from that Nectin-4 MMAE. I think it will be highly informative at ASCO with our data set to see, to test that hypothesis as a monotherapy in second line with the ability to look separately at HPV positive versus negative, or again, at oropharyngeal versus non-oropharyngeal. From a regulatory perspective, the anatomical definition is better. From a clinical perspective, the anatomical definition is better.
Got it. As we sort of think about the go forward plan, I know a lot is going to depend on the data that we see. Looking forward to that, you did recently lay out a path forward for CRB-701 in head and neck cancer, a single randomized study of the drug versus physician's choice.
In 2nd line patients, an ORR accelerated approval endpoint. I know very much kind of in, all in line with what your goals had been. What were the FDA discussions like around that? What sort of data do you think would be required for approval and use, and when will we learn more about the exact design and population you plan to go forward with?
I think ASCO will be highly informative to those questions. ASCO will tell you as the audience, what is the target population. That, in return, will tell you what the physician's choice is. A reminder, MacroGenics in second-line monotherapy, the physician's choice was methotrexate, taxane, and cetuximab.
Hypothetically, if you are looking at an oropharyngeal or HPV positive, it'll be very similar, but cetuximab is probably not an option for that. It's not used in that population. It will also guide you in terms of us providing guidance on the size of the study, et cetera. We've already publicly stated that the study is starting this summer, I think we have a pretty high degree of clarity around what we wanna do and a high degree of confidence that we wanna do it. Cervical, Brian is even easier because there really isn't a lot of mystery. 99% of cervical cancer is HPV driven.
Yep.
The standard of care for physician's choice is going to be either Tivdak or chemo. Chemo is there because the majority of women do not use Tivdak, do not go forward to use Tivdak. It is just such a difficult drug to tolerate, and its efficacy is modest. That one we will start the registrational study next year. The last piece of the puzzle will be early next year when we start to get the first data, efficacy data in the frontline setting for head and neck of CRB-701 plus pembro.
Plus pembrolizumab.
That will be especially intriguing whether or not do we look PADCEV-ish or not in that setting.
I wanna touch on that, but first I wanna go back to cervical. How do you see 701 potentially differentiating in cervical cancer? You mentioned a lot of women don't end up going on Tivdak. I assume that's because of the tolerability issues. I guess, what type of ORR as well as safety profile do you think would make 701 most competitive in that indication?
Let me start with the safety, 'cause I think that picture's already emerged even at ESMO. Like TIVDAK, like ELAHERE, like BLENREP, although BLENREP is a really extreme version of this, all of us have the surface of the eye transient ocular tox of dry eye and keratitis. Where we were at ESMO is we were slightly worse than TIVDAK and slightly better than ELAHERE, and all three of us are about a log better than BLENREP.
The gynecologists are very, very, very familiar with that profile. The dynamics of it, even though we've not disclosed it, I think it's very safe to assume are similar in all of them, which is if you're gonna get it, you get it early, and it tends to be a single acute sort of wave function that you resolve at the end of it. The problem with TIVDAK isn't so much the ocular, it's the other bits of it. Because it is a Seagen platform, it has the peripheral neuropathy, it has the very severe skin adverse events, and then it has an on-target tox, which is bleeding, which is massively undesirable, especially in cervical cancer.
Yeah .
You put all that together and you combine it with an ORR of 17%. What comes out of it is less than optimal. Cervical, Brian, feels like one of those tumor types where the incumbent might actually become obsolete. If you look at our previous data, at CSPC's previous data, for that matter, even Mabwell's data, which is very China-centric, all of us were coming in markedly higher in terms of potency. In that case, it's very hard to imagine why anybody would go on TIVDAK.
Right.
That's the bar there. In head and neck second line, the bar is more intriguing because it depends a lot on what population we're going after. There is no specific therapy for second line to begin with. If we are looking at these oropharyngeal HPV positives, right, if we're behaving in a PADCEV-like manner, there's nothing specific for them other than they're not gonna get cetuximab. You're right, Brian, they're stronger, they're younger, they thankfully last longer. In second line, they're tired.
They've been through a lot already. It does mean they can actually stand your drug for longer, which from a commercial perspective is advantageous. The big question is peto even going to actually be a competitor or not? I said it is becoming increasingly less certain that that all comers label is within reach of Genmab for peto.
Okay.
At some stage, they may have to make a decision on whether or not they wanna dedicate their efforts to a label that is HPV negative.
Negative. Yep.
risk that by including their HPV positive.
Okay.
That's obviously their decision.
Got it.
We're speculating.
Then what data can we expect to see, I guess early next year from the combination of CRB-701 and pembro? How informative will that be? How much data we should we be looking for?
You know, our usual phase I cohorts are about two dozen patients or so. You'll get response rates. It's very unlikely you'll get durability, but you'll certainly get the flavor of it. That sounds a lot like what PADCEV plus pembrolizumab showcased in November.
Right. Is that the bar potentially?
I think so.
Okay. I wanna move on to, I guess anything that we didn't cover on CRB-701 before we move on?
No, those are very sensible questions I'd say ask, I think will be very informative.
Good. I'm looking forward to that. Maybe for 913 in obesity.
Yep.
Can you maybe talk about just the overall conduct so far of the phase I-B CANYON study? How the enrollment's going and, you know, what we should be looking for in the, in the obesity cohort later this year, maybe just the overall CB1 landscape. What else is going on with these other CB1 inverse agonists? And obviously CRB-913's been designed to be a little bit different.
Oh, yeah.
Maybe you can elaborate on that.
Enrollment's done, so that's easy.
Yep.
About 12 sites exclusively in U.S. Brian, you know me and my obsession about that. I only want U.S. sites in obesity. I have a strong bias against non-U.S. data in obesity, so it's U.S. sites. They're spread all over the place. You're not gonna see a concentration of sites, for example, only along the southern border, only in Florida or whatnot. Last patient first visit was April 10th.
We enrolled faster than we expected, and we expected to enroll fast, and we enrolled much faster than that. Surprising, especially since we don't offer GLP-1 as a control. That was really wonderful. The last patient last visit will be around about August 10th or so. Remember, it's 3 months of dosing and a month of follow-up. The month of follow-up is as important. I'd like them to regain weight, please. That'll be nice. We need to dust everything off, analyze it. Figure late summer we'll have data.
Okay.
We'll issue a top-line press release and then try and get it into the first conference we can possibly get into. First and foremost is safety. monlunabant in 180 patients who got it, had 111 neuropsych events. That is not good. There's no good way of spinning that data. That is just not good at all. That is what very bad looks like. We wanna see something a lot milder. We don't wanna see anything horrible happen.
If something truly horrible happened, we would know about it because there is a break-the-glass mechanism in terms of monitoring. We would never risk patients like that. We're delighted that that has not been the case. The second question is, how well would it work? It is very likely we'll see weight loss, and I say this because every single CB1 inverse agonist in the history of this world.
has always shown weight loss. What we don't know is what will we see. The two extremes are rimonabant, which is okay. Maybe not amazing, but approvable, and maybe good for combination. The other side of it is otenabant. It's not that we forget. The messaging around otenabant was so unhelpful. Otenabant was astonishingly potent.
Otenabant looks to be more potent than orforglipron. They lost 8% in 4 months. That is not too shabby by any stretch of the imagination for an all small synthetic drug. We have no idea where it's gonna fall. There's no preclinical way of feeling it. We had really nice weight loss in the MAD study, but those are small numbers in a short period of time.
That will be the second question. In terms of the landscape, there is no landscape that I know of, mon lunabant, while still alive on paper in the Novo quarterly reports, does not seem to be moving forward. We can't find any trace of it moving forward. They killed INV-347, which is sensible, had a very challenging PK.
Yeah.
We're not aware of any other CB1 inverse agonists out there that anyone's moving forward. Small molecule inverse agonist, there just isn't. I think our data read out is gonna be wonderfully binary. It's either gonna be a dud. Okay, fair enough. In that case, just throw in the towel. If this level of restriction doesn't work, then just throw the towel.
It's not a dud, in which case it is the only CB1 inverse agonist out there that can survive. Secondly, and maybe to put it in proportion or in perspective, it would be, I would submit to you, the only non-incretin oral drug that leads to weight loss, and that in and of itself is really intriguing. Either way, it's not gonna be boring.
Okay.
We'll see what we get.
As you sort of think about mapping the data you've seen so far to what to expect in weight loss, I know we don't know is it gonna be rimonabant is it gonna be otenabant, where is it gonna fall? I guess maybe talk us through the projected plasma concentrations at steady state for the phase I-B doses that you're looking at, 20, 40, and 60, and how do those compare to the 150 mg dose that you looked at after, at seven days where you saw, you saw some weight loss there? Is there, is there some line one can draw between from one to the other to try and project out what might be the expected degree of weight loss you'd see over this time period?
No.
Okay. I mean, I guess you chose your doses for a certain reason, right?
Right. I guess so.
I guess, what were you aiming?
Yes. Got it. We think that's the linear part of the weight loss.
Okay.
We think anything a lot higher than 75. The 150 we think is in the flat part of the S-curve.
Okay.
The 20 we reckon is towards the lower bottom of the S-curve. The 40 should be smack bang in the middle of the S-curve.
Okay.
That's about as much. You can do a lot of very fancy modeling, but honestly, you can just wait for a couple more months and get the data which will probably be a lot more informative.
Look, assuming this is not a dud, right?
It looks promising.
Yep.
Maybe just the last question in the last minute, I guess, how are you thinking about where this could fit, and what's your level of prioritization in terms of taking this forward on your own? At what point might you consider a partnership?
We have to talk to strategics because we have to understand what they want us to do with it. You could do monotherapy for incretin intolerant or incretin resistant patients. You could do combo therapy, for example, with orforglipron and generates an orforglipron XL, and take orforglipron from the 10% doldrums where it is to something more exciting.
You could do induction maintenance, right? You lose weight on an injectable incretin analog, which most people do, about 60% of people do very well. Then for the rest of your life, you will simply pop a pill every morning, just like you'll take a statin or a proton pump inhibitor, and you'll feel nothing. You're not gonna lose more weight. What it will do is it will simply maintain the weight loss you've achieved. All of those are viable. All of those we need to consult with strategics and understand what they do.
Okay. Good. Yuval. Not boring. Thank you again.
Thank you.
Look forward to ASCO. Thanks for coming.
Thank you so much, Brian. Thank you to the audience. I appreciate you being here today.