Fireside chat with Thomas Schuetz, CEO of Compass Therapeutics. Just from a disclosure standpoint, we cover Compass Therapeutics with a Buyer Rating. Thank you, Tom, for joining and participating in our conference. Before we get into your key assets, maybe to first orient our audience, could you provide a high-level overview of your core technology and StitchMabs , and your general approach to developing antibody-based therapeutics for cancer treatment?
Great. Thanks, Sarah. Thanks for inviting us here today. I'll give my forward-looking disclosure. I will be making forward-looking statements today. Thanks again for having us here today. Compass is located in Boston. We're a monoclonal antibody discovery and development company in oncology. As you mentioned, we also developed a screening tool that we call StitchMabs . StitchMabs is a tool that allows us to screen for synergy in bispecific antibody drug candidates. Today, we have three drugs in the clinic and a fourth drug about two quarters or so away from the clinic. Our lead program is a DLL4 VEGF-A bispecific antibody called Tovecimig. Our second program is a monoclonal antibody agonist of CD137. We call that drug 471. Our third program, a drug that we call 8371, is a really unique molecule.
It's a PD-1 x PD-L1 bispecific antibody that came out of our StitchMabs platform during a screen for synergy with PD-1 blockade. Finally, and obviously quite topical today, we also have a PD-1 x VEGF-A bispecific antibody that is about two quarters away from IND filing. We recently announced that we had a successful pre-IND interaction with the FDA earlier this year.
Yeah. Let's start with your lead asset, as you mentioned, Tovecimig. We certainly have a lot to talk about, particularly with the recent biliary tract cancer data you reported. Can you start off just briefly describing the design of the asset and maybe why you believe a two-pronged approach for anti-angiogenesis could be differentiated from a mechanism of action perspective?
Sure. As you correctly point out, Tovecimig is a next-generation angiogenesis disruptor. Tovecimig targets two different angiogenesis pathways. Obviously, the well-known VEGF-A pathway. VEGF-A is the soluble ligand for the VEGF family of receptors. There are now multiple drugs that target either the ligand, the receptor, the kinase on the receptor, et cetera. It is now a well-validated approach in medical oncology. DLL4 is delta-like ligand 4. That is the cell surface ligand for Notch 1. Those two signaling pathways have different phenotypic effects on angiogenesis in the tumor microenvironment. I think a couple of very important things. First of all, dual blockade has been shown to be synergistic in preclinical models. We truly believe that this will be a next-generation angiogenesis disrupting agent that ultimately we believe could replace Avastin in all of those indications.
Now, another very important thing is that unlike some other VEGF or angiogenesis targeted drugs, we actually have monotherapy activity, suggesting or indicating, I think quite clearly, that blockade of the DLL4 pathway is also very important. We believe that the way this drug works is because DLL4 is a cell surface ligand that anchors Tovecimig in the tumor microenvironment where it can provide high local capture of VEGF-A. Finally, you know, I think what ultimately could turn out to be very interesting is DLL4 upregulation in the tumor microenvironment has been shown to mediate resistance to VEGF targeted therapies such as Avastin. I think ultimately, you know, that could prove to be a very important observation.
Currently moving forward with that now into the clinic, your lead indication for Tovecimig is second-line biliary tract cancer. You recently reported positive top-line data from your pivotal phase II/III study. Maybe you can take the time to give a bit of a summary of the data amassed to date and how you see the results reported reinforcing the potential of the drug to fill the current unmet need in biliary tract cancer and maybe what we could look forward to next.
Sure. I would just like to maybe highlight one very important thing that you said, you know, which is second-line biliary tract cancer and the unmet medical need. Believe it or not, you know, in such a common cancer, in the second-line setting in the U.S., there is literally no labeled therapy. It is an extreme unmet need. The only labeled therapies in the second-line setting are targeted therapies for patients with actionable mutations. That is only, unfortunately, about 15% of the patient population. The other 85% of the patient population does not have any standard of care. We are currently running a randomized trial in patients who have had one prior line of therapy. It is a pure second-line study. It is a randomized trial of Tovecimig plus paclitaxel versus paclitaxel alone. It is a two-to-one randomization. The study has enrolled 168 patients.
We recently announced the analysis of the primary endpoint of the study, which was overall response rate. The overall response rate in the Tovecimig plus paclitaxel arm was 17.1%. The overall response rate in the paclitaxel-only arm was 5.3%. We more than tripled the response rate with Tovecimig. That difference was statistically significant with a p-value of 0.031. We also had a complete response in the combination arm, which is extremely unusual in this disease. The waterfall plots clearly show that there are differences, and we clearly have an active drug. The other piece of data that we have reported is something quite important. All of these responses were assessed by Blinded Independent Central R eview, so-called BICR. The assessment of best overall response can occur at any time in the study. The study was fully enrolled in August of 2024.
The staff plan dictated that the primary endpoint analysis was to occur seven months after the last patient was enrolled. August of 2024 gets you to March of 2025. Patients began to be enrolled in that study in mid-2023. When the primary analysis was done, patients had anywhere between seven months and about 20 months of follow-up. Anytime during that period of time, your best overall response could be assessed. However, if your best overall response is progressive disease, that means by definition that occurred at the first scan point, which is week eight. If you had stable disease or a partial response at week eight, you would be in that category. If your best overall response is progressive disease, that means we know that that occurred at week eight.
We disclosed that there is a very large difference in progressive disease as best overall response between the two treatment arms. In the paclitaxel-only arm, again, at week eight, the progressive disease rate is 42.1% at least. It could be higher than that, you know, depending on the assessment of progression-free survival. In the combination arm, it is only 16.2%. We already know today that there is very significant separation of the progression-free survival curves. We also announced when we disclosed this data, I think we announced something quite important that, you know, maybe has not been fully appreciated, which is that the overall survival analysis is going to occur later than we initially modeled. Why is that important? I am just trying to just distill this down.
It's sort of hard to say this, but it means there are fewer patients who have died than we initially thought there would be. Why is that? Okay. Maybe the control arm is performing better than we thought it would. We do not believe that's the case because we already have 42% progression at week eight. I think it's quite unlikely that that's the case. Of course, we could conceivably be missing data, but I also know that that's not the case. That leaves the third possibility, which is we're seeing a treatment effect and as being manifested by fewer deaths in the study.
The time-to-event analyses, progression-free survival, and overall survival will not—those points will not read out until late Q3, early Q4, which will be when we have 20 months of median follow-up, which, you know, if you assume a 6.2-month median overall survival in the control arm, you know, hitting 80% mortality until 20 months median follow-up, that's really quite unexpected. We are, you know, we are quite enthusiastic about both the PFS and the OS readouts later this year.
Definitely a large opportunity there. We'll be looking forward to those readouts. You're also moving forward with Tovecimig with a recently announced basket study in DLL4 positive cancers across a range of solid tumor indications. Could you maybe discuss the rationale of this study and kind of where it stands now?
Sure. DLL4 Notch signaling is involved in the development of the human GI tract. Of course, when you, you know, develop a malignancy, that is commonly, you know, de-differentiation, right? You know, some of these early markers will commonly appear on tumors. There are many intra-abdominal malignancies that are enriched for DLL4 expression, including gastric cancer, liver, colorectal, ovarian, renal. There is an enormous opportunity here for Tovecimig. Because we have demonstrable monotherapy activity, we saw responses in patients with colorectal cancer and gastric cancer in our phase one population, which was in, you know, a typical heavily pretreated phase one population. Because we had monotherapy activity, we are now going to pursue a phase two basket study in patients with malignancies that are known to be DLL4 positive. How will we use the results of that study?
Fast forward to a data readout later this year, pre-BLA meeting with the FDA, potential license application in the first half of 2026. Tovecimig could be approved in the second half of 2026 if we get a priority review because we have fast-track status. Once Tovecimig is approved, thinking about phase four studies and label expansion. We would use this basket study to inform label expansion studies following the approval of Tovecimig.
Great. Let's do a quick shift over now to CTX-471. Looking at the rest of your pipeline now, this targets CD137. Could you talk briefly about that target and the clinical program, which actually recently showed compelling biomarker correlations and your plans to expand the studies as well?
Sure. 471, again, is a monoclonal antibody agonist, so an activator of CD137, also known as 4-1BB. We tested that in a phase I study where we enrolled patients who had previously received checkpoint inhibition. This is, as everybody knows, one of the most challenging patient populations today in medical oncology, the post-checkpoint inhibitor patient population. In that patient population, and in 2024, we presented data twice. We presented clinical data at ASCO last year. Then we presented some analysis of some biomarker data at SITSI. At ASCO, we showed that in the post-PD-1 patient population, we had five responses. We did a cohort expansion coming out of our dose escalation phase I, where we took all comers who were post-PD-1 blockade. We had patients enrolled with 17 different tumor types.
It was not so easy to analyze the data, but we had three patients out of 11 with melanoma who had responses, so a 28% response rate, again, in the post-PD-1 patient population. We had a response in a patient with mesothelioma, and we also had a complete response in a patient with metastatic small cell lung cancer. This is a patient who was on drug more than three years, who was treated in the third-line setting. You know, a very, very robust clinical observation. We also then obtained biopsies from patients in the study, both at baseline and on treatment. When we looked at those biopsies, we discovered something quite interesting, which is the patients who responded, so either complete response, partial response, or stable disease, so any patient who had disease control, all of those patients had tumors that were NCAM positive.
Patients who were NCAM negative, all of those patients had progressive disease. A very clear signal. What is NCAM? Neural cell adhesion molecule, also known as CD56. CD56 is a marker on activated NK cells. We believe we may have identified a novel immunophenotype in the tumor microenvironment because tumors that are NCAM negative cannot attract NK cells, whereas tumors that are NCAM positive can attract NK cells because CD56 interacts with itself. When the NK cells interact with NCAM, they're in the tumor microenvironment where they can be activated by 471. We're going to do an NCAM positive basket study looking at neuroendocrine tumors, of which, you know, the patient population there is very substantial, you know, well above 60,000 patients annually in the United States. That study will get started in the second 1/2 of the year.
Okay. Great. We'll be on the lookout for that. You're also developing CTX-8371, the PD-1, PD-L1 bispecific that actually recently entered phase one studies. Could you maybe highlight the features that you believe define this as a next-generation checkpoint inhibitor and anything maybe you want to tease us with regarding when we can expect a first look at data out of this program?
Sure. I love the label you attached to this, right? Next-generation checkpoint inhibitor, because, you know, the field, you know, has been looking for next-generation checkpoint inhibitors for a very long time. You know, we asked an incredibly simple question, you know, what is the best combination partner for PD-1 blockade in a bispecific antibody? We used our Stitch Maps screening platform, and much to our surprise, in that screen, we identified PD-L1 as the best combination partner for PD-1 blockade. You know, when we first got this result, it was really hard to understand, honestly, you know, like why would dual ligand receptor blockade be better? We studied the mechanism of action for quite some time, something like 18 months or so, and we discovered that that drug has very unique properties. It's a cell engager unequivocally.
It leads to the cleavage of PD-1 off of effector T cells. This drug converts PD-1 positive T cells into PD-1 negative T cells. It's an incredibly unique mechanism of action. We went into phase I. We're in the middle of dose escalation. Actually, we're now in the fourth dosing cohort. We believe, based on our modeling, you know, that the third, fourth dosing cohort, we're when we would begin to see clinical activity. We'll look to present clinical data for that drug in the second 1/2 of this year. Stay tuned.
All right. We will. And rounding out your pipeline, you're developing a novel PD-1 VEGF-A bispecific, which I think is maybe an interesting asset to round off our discussion with, given, as I'm sure people in the room have seen this morning, Pfizer did a licensing deal with the PD-1 VEGF bispecific with, I believe, 3SBio. So you're developing your CTX-10726. Maybe you could frame the opportunity there as you move towards the clinic.
Sure. It was not just any licensing deal. Pfizer paid $1.2 billion upfront for this molecule, which had, I understand, early phase II data in China. You know, we've been working on this for probably two years now. Obviously, the intersection of our scientific expertise is angiogenesis disruption and checkpoint inhibition. We spent some time in the lab, you know, thinking about the best construction of these molecules, because if you think about the two pathways, PD-1, PD-L1, VEGF-A, VEGF receptor, all four components of these two pathways have approved monoclonal antibody drugs targeting them. It is not so straightforward. We ended up in a very similar place to, you know, drugs like Ivonescimab, where we have a two-by-two bispecific targeting VEGF-A and PD-1. We have some differentiated features.
The PD-1 blockade in our drug is five times more potent than that reported by Ivenesimab. We believe we have a very good molecule. As I mentioned, we had a successful pre-IND meeting earlier this year with FDA. We are now in the middle of our manufacturing and IND enabling tox studies, and we will file our IND for that molecule in the fourth quarter of this year. Of course, you know, stating the obvious here, you know, this has now become, you know, an incredibly important space. You know, we would sort of be opportunistic and, you know, think about, you know, the best, best, do the best thing for shareholders as we sort of imagine the development of that drug.
Yeah, definitely, definitely interesting opportunity there. I guess for the sake of time, I think maybe as you wrap up, if you'd like to maybe summarize any key upcoming catalysts, just to reiterate or clarify anything that investors you believe should be aware of for Compass.
Sure. Sure. You know, I think a readout from our 8371 phase one, you know, probably next quarter, I would think. A readout from our progression-free survival and overall survival endpoints for the randomized Tovecimig study in patients with biliary tract cancer. Starting three more important clinical trials, our 471 basket study, the Tovecimig basket study in DLL4 positive malignancies, and our fourth phase I study for the drug that we call 10726, our PD-1 VEGF-A bispecific antibody.
Great. Thank you so much, for taking the time.
Thank you