All set?
I can give you the truth.
I'd love for you to give it. No, I insist you do.
Okay. All right. Thank you all for coming. I'm Spencer Kent. I'm from the TD Cowen Healthcare Investment Banking team in San Francisco. Pleased to welcome the Corbus team to present today, and I'll leave it to you to lead.
Thank you, Spencer. Thank you for those who are in the room and listening to us online, I guess. I'm Yuval Cohen. I'm the CEO of the company. I'll walk you at a brisk pace through really sort of the latest updates, and I'll just reflect the questions we're getting from buy-side, etc. I'll make it very quickly. A reminder, this is our pipeline, and I'm going to focus on CRB-701, which is our Nectin-4 ADC, and also an update on CRB-913, our CB1 asset, just because that question keeps coming up, and so it's certainly of interest. By now, I suspect everyone listening knows the construct that we have. It's a next-generation classic ADC with a site-specific conjugation and a cleavable linker targeting Nectin-4 and armed with MMAE at a DAR of precisely two.
One of the advantages of this construct, which is a stable construct, is that we can dose it at a meaningfully less frequent regimen than Padcev. We dose once every 21 days. On this slide, it's the first of several slides where we are going to juxtapose the data out of China that came out at ASCO last year, their dose escalation data, compared to our dose escalation data presented at ASCO GU in February of this year. In terms of trial design, the trials were nearly identical. In terms of patient baseline characteristics, not particularly different if you just account for the fact that obviously the Chinese study involves patients who are all ethnically Chinese. We have sites in the U.S. and a handful of sites in the U.K. in this data cut. Overall, very similar patients. The one big difference are the tumor types.
China focused primarily on cervical and on bladder. We also had a meaningful number of additional tumor types that we looked at. In terms of treatment-emergent adverse events, no drama. Very similar, in fact, even lower levels of TAEs compared to China. That's not surprising. Chinese clinical practitioners tend to report grade I and II more frequently than Western practitioners, but overall, very similar TAE profile between the East and the West, unsurprisingly. TAEs of interest for us, of course, based on Padcev's clinical data, are skin rash and peripheral neuropathy. If we look at skin rash, narrow definitions, which lines up with a Chinese study, nearly identical, and peripheral neuropathy narrow definition is nearly identical. That's very reassuring.
Patient numbers were the same: 37 patients in the database at the time of ASCO from China, 38 at the time of this data cut for us at ASCO GU. We also included the broader definition of these two just to be able to give full transparency. Very few, very rare, very reassuring, and markedly different than what we would see with Padcev. Discontinuations, interruptions, dose modifications, we see more in the West than in China, and that reflects clinical practice. Chinese clinical practice in oncology clinical studies tends to really emphasize maintaining the dose, even at the expense of patient quality of life, etc. In the West, we have the opposite. We emphasize quality of life, and so Western practitioners tend to lower doses in order to maintain patients in the study.
Overall, for Project Optimus, compared to the Chinese dataset, again, very, very similar, and both of us are markedly different, whether it's China or the West, than Padcev. We only had one drug-related discontinuation out of 38 patients. Ocular tox is probably unsurprising that it's different. In the West, we're mandated to very aggressively manage, in real time, as it were, ocular toxicity, whereas Chinese dose escalation studies do not mandate that. Unsurprisingly, we have fewer ocular tox. China has now switched for their dose expansion study to ocular tox management, so we expect that dataset to reflect a reduction as well. This pattern has been seen in many, many studies now, East versus West for ADCs. That's reassuring.
If we look in general at the safety and tolerability of our construct versus our peers, so by peers, what we focus on is who's targeting Nectin-4 armed with MMAE. So it's Pfizer, of course, with Padcev, Bicycle, and then Mabwell in China. And what we see as we combine our data to have higher patient numbers is we are differentiated. In fact, what's interesting is that all of us are differentiated from each other. Our constructs are actually very different from each other in a variety of ways. Our PK unsurprisingly looks very similar to Chinese PK. Moving on to efficacy, again, we juxtaposed China data with Western or U.S. and U.K. data. You'll see a lot more colors in our waterfall. We had many more tumor types that were not explored in the Chinese dose escalation study.
Overall, the pattern is quite similar, but where it becomes really more interesting is when we focus on specific tumor types of interest to us. Our swim lanes are similar to China. The median duration at the time of this data cut, which was a December data cut, was 88 days. That is more than enough for skin toxicity. Skin toxicity with Padcev appears in the first cycle. For peripheral neuropathy, they tend to show up at around the two and a half month mark for any grade. For the more severe ones, at around the four-month mark. Let us look now at the three tumor types that we highlight in this deck. Again, China on the left if there is Chinese data versus West on the right. The first one is bladder or metastatic urothelial cancer.
Remember, for our partners in China, that is a very attractive commercial opportunity for us as a standalone company. That is a commercial opportunity that has to be pursued with a strategic partner. Nevertheless, some interesting data emerging. We did not have a lot of patients at this point. We'll have more for Project Optimus, of course. Of the four patients that were included in this data cut, three of those patients were Padcev pretreated. Remember, in China, Padcev at the time was not approved, so all the Chinese patients were Padcev naive. For us in the U.S., most of the patients are now Padcev pretreated. For patients who are Padcev pretreated, our drug does not look particularly exciting. The one patient who was not Padcev pretreated had a very fast and sharp and very satisfactory response.
This further emphasizes for us the reason that as a standalone company, we're not pursuing bladder as a commercial opportunity. Cervical. Cervical is a rare tumor type in the West. It is a much more common one in the East. Nevertheless, on the left is the signal that was achieved in China, certainly very encouraging. On the right, only two cervical patients were captured in the data cut in December. Both of them showed a very meaningful reduction in tumor type, including our first-ever complete response. We have the other patient, unfortunately, developed a new tumor elsewhere, and so she's marked as a PD. She's still in the study, and so we'll monitor how she does. In Project Optimus, we will have a dedicated cohort, or we already have a dedicated cohort for cervical patients. Cervical patients in the US tend to not be in phase I units.
They are more geographically located in medical centers that deal with a population of women that tend to have cervical cancers. That is what we're focusing on for Project Optimus. The surprise that we had is a tumor type that at the time was not explored in China. This is head and neck, so we were the first to explore that in a Western setting before it was explored in China. These, I'll remind you, all of these tumor types were not enriched for Nectin-4 in terms of patients. The tumor types are known to be Nectin-4 rich, but on a patient-by-patient, there was no enrichment of Nectin-4. These are seven—there is an additional patient not on the waterfall plot here—these are seven randomized head and neck patients, mostly from the U.S., a few from the U.K.
They are not enriched for Nectin-4, and they are not enriched for HPV status. We have both HPV positive and negative. We were very reassured to see a preliminary response that was really robust and very encouraging. It's not entirely surprising. Padcev has shown efficacy in head and neck, just not particularly exciting efficacy, but nevertheless has shown that head and neck would respond to a Nectin-4 ADC armed with MMAE. We just seem to have a more robust response than they do. We also include here the competitive landscape for head and neck, which is not dominated by any Nectin-4 targets, or for that matter, MMAE constructs. This is something that we're excited about. Project Optimus will give us more patients and the ability to have a higher degree of confidence in this dataset. This was an interesting patient.
Normally, we would not show case studies, but this is really a remarkable case study, and we were quite keen to show it. This is a head and neck patient that was in quite a serious condition, ECOG of two, oxygen supplementation, very limited mobility because of that, and within six weeks of treatment has had a pretty remarkable reversal in not only in their tumor but also in their clinical status. We are delighted for this patient. This slide is a thought experiment. What we do in this slide is on a single waterfall plot, plot both the China and the Western data. Of course, remember, these are different studies.
Nevertheless, the hypothesis here is that if the data is indeed bridged nicely, and we think it has bridged in a very satisfactory manner, we can start to think about what could this look like on a single waterfall plot. We also show here the tumor types of interest to us, which are bladder, head and neck, and cervical. It is really a lovely waterfall plot. I guess that is the only way I can describe it, especially if you look at the three patients on the left-hand side, the three green patients. Those are the three patients in bladder that did not respond. One of them comes from China, had no discernible Nectin-4, so that is probably not particularly shocking. The other two are ours that were pretreated with Padcev. Again, perhaps not that surprising. In the entirety of the rest of the patients, we saw promising responses.
As we develop more data and as we can start thinking about potentially combining data between East and West, this is an interesting exercise to have. We have started Project Optimus for a number of months now. Project Optimus will have a cohort for each indication. We have head and neck, cervical, and urothelial cancer. With each cohort are two doses. Back of the envelope for Project Optimus are 15-20 patients, so you can start doing the math in terms of the number of patients that we're building. Sequentially to this, we are also interested in exploring not just monotherapy, but also a combination with a checkpoint inhibitor. Again, two doses per cohort, about 15-20 patients in each. We think we'll be in a position to share this Project Optimus data in the second part of this year.
We hope that that will also coincide with the next update out of China of their dose expansion data that started last summer. Just to wrap up, this is some market analysis that we commissioned from a third party. You can see some interesting sort of very high-level points here. Cervical is a rare indication. It is about 14,000-15,000 women in the U.S., similar in Europe. It is a very steady number. Despite the wonderful effect of the vaccine, the West has a steady number of infected women because of immigration. We have a steady stream of adult women immigrating to the West for whom it is too late to vaccinate. It is certainly a rare indication that proposes or provides a potential faster path to a label, but of course, that is all data dependent. The opposite of that is head and neck.
Head and neck is a similar size to bladder cancer, but has some advantages. For one thing, it's not crowded with Nectin-4 agents. For another thing, it is a very serious indication with many more patients who are metastatic compared to bladder. I'm going to skip just to talk about CB1 and just to give you an idea of where we are. There we go. This will be my last slide. 2025 for CB1 or CRB-913, CB1 inverse agonist. Remember, it's us and it's monlunabant from Novo Nordisk. The difference between CRB-913 and monlunabant is degree of penetration in the brain. We are about one-fifteenth less brain penetrant than they are. Otherwise, preclinically, we look extremely similar to what they are, very, very similar indeed. We are about to start our SAD followed by our MAD studies.
Those should be wrapped up in the U.S. under an open IND sometime by the end of the summer, early fall. SAD and MAD should hopefully provide absolutely no drama. SAD is a single day, not even overweight population, and MAD is one week. We really do not want to see anything happen, especially nothing bad, and we do not expect that to happen either. There are the necessary steps in order to start what is the much more exciting clinical study, which is a dose range finding study. Unlike monlunabant, we will have more than three doses in our dose range finding. We are aiming for 90 days of dosing in the U.S. In 90 days, we should be able to establish two things. Ninety days is more than enough time for weight loss with a CB1 inverse agonist.
The other thing about 90 days is it should provide ample time for any neuropsychiatric adverse events to emerge. Neuropsychiatric adverse events tend to emerge early in a clinical study. There is sort of a hump around the two- to four-week, and that is where they come out. We should have a higher degree of confidence if we see a 90-day study without imbalances between placebo and the doses. We speculate that that may coincide with Novo Nordisk's next monlunabant dose range finding. They have to repeat one. It is a much larger study than the one we are envisioning. They have a 600-patient study. We do not know yet the design of that study. Given how many patients they have, it is not impossible that they are already including some combinations as well in that study, which will be lovely and very interesting to see.
We think that the only sort of wild card for 2025 in terms of this program would be whether Novo Nordisk publishes the monlunabant data or not. We obviously have no idea whether that will happen or not, but that, of course, would be very welcome. Just to conclude, on the financial side, we were very fortunate to have a very good year in 2024. We're well-financed. We've raised a goodly amount of capital, so we're delighted. Our earnings are next week, but our Q3 numbers where we ended Q3 with $160 million in the bank, and our runway is till Q3 of 2027. We do not expect to change that guidance in the upcoming earnings. We are well-capitalized, which we are immensely grateful for, and really look forward to a year of just providing more data. With that, thank you so much for being here.
On the off chance that anyone has any questions, happy to take them, and otherwise, happy to talk to people offline. Oh, please go ahead, sir.
I had a question, actually.
Yeah. Oh.
In between. I mean, I really just skipped over it. Where are you in the clinical trial?
Yeah. Thank you for asking. That's our sleeper program, as it were. So it's a program where, again, it's the same logic. We're following in the footsteps of a big pharma ahead of us. We'd like to be in that slipstream. In our case, Pfizer. Pfizer has a nearly identical mAb. That has started our study has started dosing in patients in the dose escalation study, both monotherapy and later on combination. We started dosing in December, in December. And so we expect to have data in the second half of the year. We have no idea what to expect.
Preclinically, this mechanism of action is really exciting. We've shown that. Pfizer has shown that. We just have no clinical data on this mechanism of action. Scholar Rock, AbbVie, and Roche have sort of the other side of the coin, which is targeting the latent TGF- beta directly. It was encouraging to see AbbVie launch a gargantuan study of 800 patients. That is encouraging. I think in the second half of this year, we'll see whether we have a program that's encouraging enough or not. Thank you for asking that question. Okay. Spencer, I think we're done for the day.
Thank you for being here. Thanks a lot.