Good morning, everyone, and thank you for joining the H.C. Wainwright 26th Annual Global Investment Conference. I'm Dr. Jade Montgomery, an associate biotech research analyst at the firm, and I'd like you to please join me in welcoming Dr. Thomas Schuetz, CEO of Compass Therapeutics, a biopharmaceutical company developing antibody-based oncology therapeutics. Thomas?
Thanks, Jade, and thanks to H.C. Wainwright for inviting us here today. Really appreciate it. As Jade mentioned, I'm Tom Schutz. I'm the CEO and scientific founder of Compass Therapeutics. This is our disclaimer. Importantly, I will be making forward-looking statements throughout the presentation today, and I refer you to our regulatory filings for details associated with that. As Jade mentioned, we're a biopharmaceutical company located in Boston, Mass.
We currently have three drugs in the clinic. Our lead asset that I'll spend most of the time on today, we call 009 . That's a DLL4 VEGF-A bispecific antibody. We also have a next generation CD137 agonist antibody called CTX-471. And finally, our novel next generation checkpoint blocker, a PD-1, PD-L1 bispecific antibody, has entered phase I testing earlier this year.
Here's a summary of our current pipeline, again, largely focused on 009 . Currently, we are coming to the end of a randomized study in patients with advanced biliary tract cancer. This study, called COMPANION-002, is a randomized study of CTX-009 plus paclitaxel versus paclitaxel alone in patients with advanced biliary tract cancer who have received one prior line of therapy. We announced earlier this summer that this study is fully enrolled, and we're on track for a top-line readout from that study toward the end of Q1 of the coming year.
We also announced about a month ago some top-line data from a phase II study in patients with advanced colorectal cancer, and I'll give a high-level summary of those data today. And we're now planning for a second line study in patients with advanced colorectal cancer. For CTX-471, we've completed our phase I testing, and we're beginning planning for a biomarker-driven phase II study.
We're gonna present data at a medical meeting later this fall, looking at the identification of a potential biomarker of activity of 471, and we're really excited about that presentation, and as I mentioned, 8371 has just begun phase I testing, so here are some structures of our three drugs that we have in the clinic. From left to right, 009 , N-terminal Fabs that scavenge VEGF-A, C-terminal scFvs that bind to DLL4 at a two-by-two valency.
471 is a standalone monoclonal antibody agonist. It's an IgG4 of CD137, also known as 4-1BB, and finally, 8371 is also a two-by-two bispecific. Both ends are Fab fragments that is enabled by our Common Light Chain technology that we developed at Compass. We've been expanding the management team recently, summarized here. So let's talk more about the data that we have.
So 009 , again, a DLL4 VEGF-A bispecific antibody. DLL4, delta-like ligand 4, is the cell surface ligand for Notch1. VEGF-A, of course, is the well-known soluble ligand for the VEGF family of receptors. Blockade of these signaling pathways has different phenotypic effects on angiogenesis in the tumor microenvironment, and I think a couple of important observations from preclinical studies.
Dual blockade has been shown to be synergistic. And what I think ultimately could turn out to be most important is that upregulation of DLL4 in the tumor microenvironment has been shown to mediate resistance to VEGF-targeted therapies such as Avastin. So we've completed our phase I program. I've got three slides summarizing those data, as some of these data have been presented publicly already.
This is the waterfall plot from our phase I monotherapy study. So this was a standard multiple ascending dose escalation study. Nine doses were tested in patients with a set of very advanced malignancies. Fascinatingly, we had monotherapy responses that were confirmed by RECIST in this study. Why do I say fascinatingly? As many of you may know, VEGF-targeted agents as monotherapies don't commonly have single-agent response, readouts.
The real therapeutic potential of VEGF targeting was only uncovered once these drugs were combined with chemotherapy. But we had confirmed responses in patients with both gastric cancer and colorectal cancer. Perhaps even more importantly on this slide, there's an unequivocal dose response. So all confirmed responses were seen at doses of 10 mg per kg or above, which is given every other week.
So because of the well-known synergy between VEGF blockade and chemotherapy, we moved quickly to a phase Ib study, where we combined 009 with either paclitaxel or irinotecan. Why those two drugs? So because on the last slide, we had responses in patients with gastric cancer and colorectal cancer, we chose paclitaxel and irinotecan. Paclitaxel plus ramucirumab, the VEGF receptor-blocking antibody, is second-line standard of care in patients with gastric cancer.
And of course, irinotecan is part of the well-known backbone of FOLFIRI that is used to treat patients with colorectal cancer in the second-line setting. In this study, we had additional confirmed responses, including something quite surprising. In the orange bars here, are patients with cholangiocarcinoma treated in the third-line setting. We had two deep and very durable responses in these patients.
Patients were both on drug north of a year, with duration of responses in the 10-11-month range. Just outside of the PR cutoff of 30%, there's a third patient with cholangiocarcinoma with a near PR. Empirically, we also saw those three patients happened to receive 009 in combination with paclitaxel. The fourth patient, second from the far left, with progressive disease, that patient received 009 in combination with irinotecan.
So it was a purely empirical observation that we looked to confirm in a phase II study, which I'll come to in one minute. Brief summary of our phase I program: 20%-25% response rate. Safety profile: drug generally well-tolerated, with hypertension being the most common drug-related adverse event, which is very common with VEGF-targeted agents. We see almost exactly the same level of hypertension that you see with Avastin.
So, as I mentioned, we wanted to confirm the observation from the phase Ib study in a larger phase II study. So this is the study that we did. This was Simon's two-stage design, but stage II was never initiated, and I'll talk more about that in one minute. These are all patients with advanced biliary tract cancers who'd received either one or two prior lines of therapy. So this is a mixed second- and third-line study. 009 was given at 10 mg per kg biweekly with paclitaxel.
And here's the waterfall plot from that study. So we had nine confirmed responses. A 10th response was unconfirmed, out of 24 total patients treated, for an overall response rate of 37.5%. The three-drug combination FOLFOX, 5-FU, leucovorin, and oxaliplatin, in the second-line setting, has a 5% overall response rate. So this was a real signal.
Couple of interesting things, I think, from this slide. We had at least one confirmed PR in each of the four anatomic subtypes of biliary tract cancer: intrahepatic cholangiocarcinomas, gallbladder cancer, and ampullary cancer. And just to state the obvious, nobody is above the line. So this is an incredibly unusual-looking waterfall.
When we shared these data with FDA, FDA suggested to us that we did not need to do Stage II of the Simon's two-stage, and they encouraged us to get to a randomized study as quickly as possible, which we have done. PFS and OS curves from the study, I'll put these in context, a couple of slides from now. In general, patients treated in the second line doing a little bit better than patients treated in the third line. Median PFS, 9.4 months. Median OS, 12.5 months.
Compares quite favorably to what you see with gemcitabine plus durvalumab in the front-line setting. So a very important signal here. Here's a summary of the phase II data. Again, 37.5% overall response rate. Really solid median duration of response here at 6.9 months. In the upper right-hand side of this slide, this is a subset analysis. It's important just to be careful about that. It's a subset analysis of a small study.
But when we looked at the nine confirmed responding patients, seven of those nine patients were treated in the second-line setting. So in the second-line setting, our overall response rate was 64%, and that piece of data informed the design of our current randomized study, which I'll come to in a minute. Again, hypertension, the most common on-mechanism adverse event.
Of course, when combined with chemotherapy, you pull in the bone marrow suppression, as seen with neutropenia, thrombocytopenia, and anemia. Right-hand side of this slide are data from the Avastin and paclitaxel labels, just showing we have very, very similar incidence of these AEs. So just to put these data in some context. So ABC-06, the column just to the right of the blue box, was a randomized trial of FOLFOX.
Again, that's 5-FU, leucovorin, and oxaliplatin, versus best supportive care in patients with biliary tract cancer treated in the second-line setting. 5% response rate, small improvement in median overall survival of 0.9 months, small improvement in PFS, very similar level of AEs. So the 5% response rate compares to our 64%, and the 6.2-month median OS compares to our 12.5 months.
Again, the data that we saw in the second and third-line setting, very similar to what you see with front-line regimens such as gemcitabine plus durvalumab or gemcitabine plus pembrolizumab. So based on that, we embarked on a randomized study. This is a two-to-one randomization of 009 plus paclitaxel versus paclitaxel alone in patients who have received one prior line of therapy.
The primary endpoint of this study is overall response rate. 100 patients is 90% powered to detect a difference in overall response rate of 33% in the combination arm versus 10% in the treatment arm. As I mentioned, this study is fully enrolled, and we should get the response rate readout from this study toward the end of Q1 of the coming year, about six months or so away from today.
Biliary tract cancer is a very common cancer, about almost 23,000 cases annually in the United States. AstraZeneca has said publicly that that number is 23,000. The data I quote here are from a presentation given at the Cholangiocarcinoma Foundation meeting. We believe that something like two-thirds of patients approximately would move to second-line therapy, so that means about 15,000 patients annually in the United States alone.
At any very conservative assumption of drug pricing, this is well north of a $1 billion market potential, fully penetrated in the U.S. alone. EU and Japan, of course, this becomes an extremely common cancer and is actually projected to become the third leading cause of death in the United States in about the coming decade.
So a tremendous unmet need with FOLFOX and a very low incidence of druggable mutations in this patient population. So we'll be going after a broad second-line label in this patient population. Switching now over to colorectal cancer. We did a phase II study. Treated forty-one patients were evaluable. Most of those were treated in the fourth line setting. We had two confirmed responses out of forty-one patients treated. We had two confirmed responses in our previous phase I study, median PFS of 3.9 months.
I think importantly, the disease control rate was 71%, and I think obviously, most importantly, the median overall survival in this study was 10.2 months. How does that compare with current third and fourth-line therapies?
Obviously, on the top of this slide, colorectal cancer is in a completely different epidemiologic category, one of the most common cancers globally. But you can see in the bottom right here, so regorafenib, labeled as Stivarga, in the same patient population, has a 1% overall response rate and a 1.9-month median progression-free survival. The most recent approval in this patient population fru quintinib, that Takeda licensed from Hutch Med. Again, 1.5% overall response rate, median PFS of 3.7 months.
Again, compares quite favorably to what we've seen in our study. And I think also, as I mentioned, our median overall survival of 10.2 months is equivalent to what you see with Lonsurf Avastin in the third-line setting, and we had two-thirds of our patients treated in the fourth-line setting.
Next steps with colorectal cancer here will be to evaluate a second-line study, so combining 009 with FOLFOX. So that's our current plan, and that's what we're currently working on designing now. In biliary tract cancer, I think interestingly, next steps for us will be the initiation of a frontline study at MD Anderson, which we announced in August.
MD Anderson was the second largest accruer to our second-line study, that is currently ongoing, and MD Anderson approached us to initiate a study at MD Anderson, combining 009 with gemcitabine in the frontline setting. So that's something we're super excited about, and then obviously, the top-line data from our second-line study coming at the beginning of next year. So in the last couple of minutes, I'll just go through our last two programs briefly.
471, we believe, has the potential to be a best-in-class CD137, 4-1BB agonist. In our monotherapy phase I study, we had five confirmed responses. We treated patients with 17 different tumor types in the post PD-1 setting, so obviously an incredibly difficult patient population. The biggest signal that we got out of that study is on this slide. This is a patient with metastatic small cell lung cancer. This patient had frontline chemotherapy, plus atezolizumab, followed by second-line nivolumab.
This patient started therapy in the third-line setting with 471 in October of 2020. This patient had a PR, which was confirmed, and this patient had a durable PR for over 3 years. At the end of last year, we got a PET scan. The patient is completely PET negative, so this is a PET-negative CR.
This is one of three patients that we treated. This patient actually came off study in January of this year and remains free of disease. This patient is probably cured now, almost four years out from initiating therapy with 471 . Just an incredibly important observation. We had three responses out of 11 patients treated with melanoma, and one patient out of four patients treated with mesothelioma also had a PR.
Analysis of biopsy specimens from the phase I study has indicated that we may have discovered a biomarker of response. So this is a marker related to NK cell biology. We're gonna present that data at a medical meeting this fall, and we're currently planning for a biomarker-selected phase II study using this biomarker that would begin at the beginning of next year. Finally, 8371 , a really unusual drug.
We did an empirical screen for synergy with PD-1 blockade in vitro. So we asked a very simple question: What is the best combination for PD-1 blockade in a bispecific antibody? We built some technology that allowed us to do a screen, and much to our surprise, the best combination partner for PD-1 blockade turned out to be PD-L1 blockade. The combination of dual receptor ligand blockade is between one hundred and one thousand fold more potent than either antibody alone or the combination of the two.
But it's not just dual ligand receptor blockade, and we published all of this data earlier this year. On the right-hand side of this slide, we discovered something fascinating, which is the bispecific exposes a metalloprotease cleavage site on PD-1 and induces cleavage of the extracellular domain of PD-1 off the surface of effector T cells.
So this drug converts PD-1 positive T cells into PD-1 negative T cells. I don't know if next generation checkpoint blockade, you know, where that's gonna go, but we believe we have some tremendous advantages. And as I mentioned, we're now in the middle of our dose escalation phase I. So this is the last slide. Upcoming milestones, most importantly, top-line data from our randomized biliary tract cancer second-line colorectal cancer study, and our biomarker-driven phase II study for 471 .
And we also have a set of VEGF-targeted bispecific antibodies that we're working on, and the combination of VEGF blockade and checkpoint inhibition, I think, is an incredibly novel pathway, and we have several new drug candidates that we'll be talking about in the coming year. Thanks very much for your time. Happy to take a couple questions if folks have questions.
Unfortunately, we-
I went too long.
... can't take any questions.
Sorry.
Yeah, I can tell that the room is very excited and desperate to ask you questions, though. So feel free to ask him questions, just not during the session. And if you are unable to fight your way to him during, afterwards, feel free to submit questions online. Yeah.
Thank you.
Thank you again.