Okay, good morning, everyone, and welcome to our next session. I'll be your moderator, Sara Nik, Equity Research VP at H.C. Wainwright, and it's my pleasure to introduce our next presenter, Thomas Schuetz, CEO of Compass Therapeutics, a clinical-stage oncology-focused biopharmaceutical company focused on the development of antibody-based therapeutics for cancer treatment. With that, the floor is yours.
Thank you so much, and thank you to H.C. Wainwright for inviting us to present today. Just importantly, I will be making forward-looking statements today, and I'll refer you to our and I'll refer you to our regulatory filings for risks associated with those. So, as Sara mentioned, Compass, we're located in Boston. We're a monoclonal antibody discovery and development company in oncology. We currently have three drugs in the clinic, and we're about a quarter away from our fourth drug entering the clinic. Our lead program is called Tovecimig, a DLL4 VEGF-A bispecific antibody. Earlier this year, we announced that we hit the primary endpoint in a randomized study in patients with advanced biliary tract cancer. I'll talk more about that, of course, in a minute.
This patient population, believe it or not, has no labeled therapy in the United States, so we believe that this is a very significant commercial opportunity, well north of $1 billion annually in the United States, and I'll talk a little bit about that in a couple of minutes. Last month, we announced some clinical data from two of our programs that was followed by a financing. That financing has given us $230 million in pro forma cash at the end of Q2, which is cash runway well into 2028 and allows us to execute on everything that you see on this slide. These are our three clinical programs, the program about to enter the clinic, so our lead program, again, Tovecimig, a DLL4 delta-like ligand-4 VEGF-A bispecific antibody.
Currently, in a randomized study in patients with advanced biliary tract cancer, and we're going to start a basket study early next year in patients with DLL4-positive tumors. I'll talk more about that in a minute. Our next most advanced program is called 471. That's a next-generation CD137 agonist antibody. I'll talk more about that in a minute as well. I'll spend more time today on a drug we call 8371. 8371 is a novel PD-1/PD-L1 bispecific antibody, and last month, we announced unequivocal signals of efficacy in the dose escalation phase portion of a phase I trial, and I'll show some CT scans from patients in that study. And finally, obviously, the intersection of what we do scientifically here with angiogenesis disruption and checkpoint inhibition led us to a PD-1 VEGF-A bispecific antibody, and we'll file the IND for that drug in the fourth quarter of this year.
Some folks in the room with me here today and others at Compass, so let's talk about Tovecimig. Again, a DLL4 VEGFA bispecific antibody. VEGF-A, of course, the well-known soluble ligand for the VEGF receptor family. The flagship drug in this class, of course, is Avastin. DLL4 is the cell surface ligand for NOTCH1. These two signaling pathways have different phenotypic effects on angiogenesis in the tumor microenvironment, and dual blockade has been shown to be synergistic. I think, importantly, this bullet point here, second from the bottom, could turn out to be quite meaningful as we think about how we develop this drug clinically. So we believe that DLL4 is upregulated in the tumor microenvironment, and that mediates resistance to VEGF-targeted therapies such as Avastin.
In a phase I study, we had confirmed responses on the far right in patients with gastric cancer and colorectal cancer, something you don't commonly see with VEGF-targeted therapies as monotherapies, so clearly blocking DLL4 is associated with clinical activity. In a phase IB study where we combined Tovecimig with chemotherapy, we had additional confirmed responses on the right. The two bars on the far right in orange are two patients with advanced biliary tract cancer that were treated in our phase I study. Those two patients had deep and durable responses, and in this study, we combined Tovecimig with either paclitaxel or irinotecan. Serendipitously, perhaps, those two patients on the far right happened to get Tovecimig in combination with paclitaxel. That singular observation was followed by cohort expansions where we confirmed clinical activity in patients with advanced biliary tract cancer.
We shared those data with FDA, and those discussions led to the design of a randomized trial that we are currently executing. So this is a randomized trial in the United States that combines CTX-009 with paclitaxel versus paclitaxel alone. It's a two-to-one randomization in patients with advanced biliary tract cancer who've had one prior line of therapy. So this is a pure second-line study. The goal of this study is to provide data to establish this regimen as second-line standard of care in this disease. Last month, we made a very important announcement, which is there are fewer deaths in this study than we had initially projected. So, said a different way, people in this study are living longer than we had initially anticipated. More people are alive for a longer period of time.
Currently, we have greater than 18 months of median follow-up in this study, and believe it or not, one chemotherapy regimen, FOLFOX, three chemotherapy drugs, 5-FU, leucovorin, and oxaliplatin, at 18 months has less than 10%, think about that number, less than 10% overall survival. We need to get to 80% OS events in order to trigger the analyses of the secondary endpoints of progression-free survival and overall survival, and we're now projecting that analysis to occur in Q1 of 2026. Earlier this year, we announced the results for the primary endpoint analysis. The primary endpoint was overall response rate. All of this is blinded independent central review. The overall response rate was 17.1% in the combination arm, more than triple what we saw in the control arm at 5.3%, statistically significant. We also had a centrally confirmed complete response, something that's extremely unusual in this disease.
In the red box here, highlighted are differences in the rates of progressive disease in the combination arm, 16.2% at week eight, in the control arm, 42.1% at week eight. So we believe these data suggest that the progression-free survival analysis could be meaningfully positive. Here are the waterfall plots from the two arms in the study. So each bar on this plot is an individual patient. Control arm on the top, you can see that the majority of patients have increases in their linear tumor burden. Here is zero. Anything above the line is tumor getting bigger. Below the line is tumor getting smaller. In the combination arm, you can see the vast majority of patients have significant decreases in their tumor burden. You don't really need any statistical analysis to see that these two plots are clearly different.
As I mentioned, there's relatively little available for these patients, despite the fact that it's an incredibly common cancer. Frontline therapy is two chemotherapy drugs, gemcitabine and cisplatin, plus a checkpoint inhibitor. Response rates in the frontline setting to those regimens are in the mid-20% range. Median progression-free survival, six, seven months. Median overall survival, approximately one year. Again, one chemotherapy regimen that is used in the second-line setting, but importantly, is not labeled, FOLFOX has a 5% response rate with a 6.2-month median overall survival. We're currently at 17.1%, again, tripling what is seen with a three-drug chemotherapy regimen, and now with greater than 18-month median follow-up, we're not at 80% mortality in the study. So an extremely important observation.
We are now preparing to commercialize this drug ourselves in the United States, and we recently commissioned some third-party market research, which has confirmed how common this disease is, about 25,000 patients annually in the United States. As I mentioned, there is no labeled second-line therapy if you do not have an actionable mutation. The only drugs in this patient population are targeted therapies: FGFR2, IDH1, or HER2. The total of that patient population is only about 15%-20% of the population. The remaining 80%-85% of patients have no labeled therapy. We're now positioning the combination of Tovecimig with paclitaxel to become second-line standard of care. How many patients would make it to second-line therapy?
The market research we did suggests that about 15,000 patients annually would make it to second-line therapy, and at any standard current assumption of oncology drug pricing, this is well north of a $1 billion market in second-line biliary tract cancer in the United States alone, but there are other indications that are potentially treatable with Tovecimig. There are many DLL4 positive malignancies, mostly intra-abdominal malignancies, because DLL4 notch signaling is involved in embryology of the GI tract in humans, so we're going to start a basket study in Q1 of the coming year looking at treating DLL4 patients with DLL4 positive malignancies, so here's where we are today with Tovecimig. Our randomized trial, by definition, is positive. The progression-free survival and overall survival data will come in Q1. That will be followed by a meaningful FDA interaction, followed by a potential U.S.
License application in the middle of the coming year. We have fast-track designation, so I would assume we would get a priority review. Interestingly, we also have a frontline study going on at MD Anderson. This is an investigator-sponsored study. MD Anderson was the second largest enroller in our second-line study that's ongoing, and MD Anderson approached us early last year with a proposal to add Tovecimig to the frontline regimen of gemcitabine, cisplatin, and durvalumab, and that study is underway at MD Anderson. Hopefully, we'll get some data from that study later this year or next year. Moving on to CTX-471, again, a CD137 agonist antibody. I'll spend less time on this today, but because we presented scientific data from this study twice last year, we presented clinical data at ASCO, and we presented biomarker data at SITC last year.
And briefly, we clearly have responses in the post-PD-1 patient population. An analysis of biopsies of these patients revealed NCAM as a biomarker of activity. I think this is a really novel discovery that we've made. We had five responses in patients who were treated in the post-checkpoint inhibitor setting, including a complete response confirmed by PET in a patient with metastatic small cell lung cancer. And this patient's tumor was highly positive for neural cell adhesion molecule, also known as CD56. That made us look at other patients' biopsies, and what we discovered was patients who were CD56 negative all had progressive disease. So we believe we've potentially discovered a biomarker of activity for this drug, and we believe this makes mechanistic sense. I think it's possible that we might have discovered a novel immunophenotype in the tumor microenvironment.
Up here in the top right, tumors that are NCAM negative cannot attract NK cells to the tumor microenvironment. So this is important because CD56 is its own ligand and receptor. So NCAM positive tumors, on the other hand, can attract NK cells to the tumor microenvironment where they can be activated by 471 providing CD137 activation. So this we're going to test in a so-called basket study phase two study where we're going to look at patients with NCAM positive tumors, and there are a substantial number of those patients because many common solid tumors, colorectal cancer, non-small cell lung, prostate cancer, have small fractions of patients that have NCAM positive tumors. This study is slated to begin later this year. Okay, let's spend a little bit more time on CTX-8371.
When we first were thinking about developing a drug like 8371, we asked ourselves a very fundamental question: Can we define next-generation checkpoint inhibitors? Post-checkpoint inhibition, frankly, in my view, is one of the most unmet medical needs in medical oncology today, and there really have been no meaningful therapies for patients who have progressed on checkpoint inhibitors. We set out to try to define a new class of drugs. In order to do that, of course, we had to develop a novel technology. We call that technology StitchMabs. That technology allows us to screen for synergy in bispecific antibodies. It also allows us to do something quite unusual, which is we can actually do screens of biologics.
So we did a screen in which we were looking for PD-1 synergy, and we made, I think, a fundamental discovery here that the best partner for PD-1 blockade is actually PD-L1 blockade. Dual ligand receptor blockade in a bispecific antibody is between 100 and 1,000-fold more potent than either antibody alone. So this is really a fundamental discovery. We published all these data last year. And interestingly, this drug has an extremely novel mechanism of action. First of all, it is unequivocally a cell engager. It also leads to the cleavage of PD-1 off the surface of effector T cells. So this drug actually converts PD-1 positive T cells into PD-1 negative T cells. This truly is a first-in-class molecule.
It is superior to known checkpoint inhibitors in preclinical mouse studies, and we took that into a phase 1 study last year, five dose escalation cohorts in a 3 plus 3 design, patients with five different malignancies: melanoma, non-small cell lung cancer, head and neck cancer, Hodgkin's lymphoma, and triple-negative breast cancer, all of whom are post-checkpoint inhibitor. Three patients in the 3 plus 3 design, so we only have data so far on 12 patients. We're in the fifth and final dosing cohort, and we announced last month that we really have, frankly, some stunning efficacy data in this dose escalation study. This is a patient with metastatic non-small cell lung cancer. This patient was treated in the fourth-line setting. Six cm of total tumor burden that has completely disappeared. You can see the CT scan here, baseline, week eight, week 16, completely disappeared.
More importantly, potentially, is this patient. So this is a patient with triple-negative breast cancer, progressed while receiving KEYTRUDA, then got TRODELVY, again treated in the fourth-line setting with nearly nine cm of linear tumor burden. Okay, so this is something like 4 in. CT scans at baseline here. If you could look at this blue circle on the lower left, this is a 5.2 cm metastatic tumor to the patient's pericardium, the lining of the heart. It has completely disappeared, 87 mm to 7 mm. This is something truly unprecedented. We're now planning for cohort expansions in this study in patients with non-small cell lung cancer and triple-negative breast cancer. Those cohort expansions will begin later this year and will present data next year. We hope to present the dose escalation data at a scientific meeting later this year.
Finally, in the last minute or so, I'll talk about our fourth drug, which is called 10726. This is a PD-1 VEGF-A bispecific antibody. I'm sure it's a class of drugs that you all are well familiar with. The leading drug in this class is called Ivonescimab. We spent probably a year investigating and developing these drugs, and we landed at a 2 by 2 bispecific antibody that is comprised of components of the drugs that we have in the clinic already: VEGF blocking arms, PD-1 blocking arms, leading to a 2 by 2 bispecific. Interestingly, in vitro, this drug is more potent at blocking PD-1 signaling than other drugs in the class. That led to a very specific hypothesis and led us to do head-to-head preclinical mouse studies.
This is a head-to-head study comparing 726 to Ivonescimab, the leading drug in the class, in a human colorectal model, and this mouse expresses human PD-1 and PD-L1. In this model, 726 is superior to Ivonescimab at controlling these colorectal cancer tumors in mice, and 726 is equivalent to KEYTRUDA in this mouse model. Now, importantly, the last two slides I showed do not include human VEGF-A. So this is a pure test of the PD-1 end of this drug. When you add VEGF-A to the experiment with a human non-small cell lung cancer tumor that makes human VEGF-A, 726 is the best drug in this molecule, superior to Ivonescimab, which is about the same as bevacizumab, Avastin. So here's where we are today: positive randomized study in patients with biliary tract cancer, progression-free survival and overall survival readout from this study in Q1, potential U.S.
license application next year, DLL4 positive basket study for 471, an NCAM basket study for 8371, our PD-1, PD-L1 bispecific antibody. Phase I dose escalation will be complete in about a month. We'll move to cohort expansions in patients with triple-negative breast cancer and non-small cell lung cancer. We'll present those data, hopefully, at a scientific meeting later this year, data next year, 726 IND filing, preclinical data presentation at a scientific meeting, clinical data next year. And as I mentioned earlier, we're now well funded to execute on all of these milestones over the coming several years. So thank you very much for your attention, and again, thank you to H.C. Wainwright for inviting us here today.