Compass Therapeutics, Inc.

Greetings and welcome to Compass Therapeutics second quarter 2025 earnings and business update call. At this time, all participants are in a listen-only mode. A question and answer session will follow the formal presentation. If anyone should require operator assistance, please press star zero on your telephone keypad. As a reminder, this conference is being recorded. It's now my pleasure to introduce Anna Guilford, Chief of Staff. Thank you. You may begin.

Good morning and thank you for joining us. My name is Anna Gifford. I'm chief of staff at Compass Therapeutics. With me today is Dr. Thomas Ritz, the CEO and vice chair of the Compass Board. Our CFO, Barry Shin, will also join us for a short Q&A following Tom's comments. Earlier this morning, we released our financial results and a business update for the second quarter. The slide presentation accompanying this webcast and a copy of the press release are available on our website. Please note, we'll be making forward-looking statements on today's webcast. These forward-looking statements are described in our press release issued today in the company's SEC filing. With that, I'd like to turn this call over to Tom.

Thank you. We're incredibly excited today to be hosting this call with you this morning. As Anna just mentioned, earlier today we released our quarterly financials for Q2 2025. In addition to the financials, we also provided very important updates for three of our development programs. These updates are summarized on the next slide, and I'll then provide additional details for each of these program updates. Most importantly today, for our lead program, Tevesimig, the DLL4 VEGFA bispecific antibody in the ongoing randomized trial in patients with advanced biliary tract cancer, There are currently fewer total deaths in the study than we have projected. While this disclosure is a simple fact, it is very important to say this sentence differently. More patients are alive today than we have projected. I understand clearly that this is an investor call, but it's so important to reflect on what this could mean for the patients enrolled in this study. I'll update the timing of the survival analyses in one minute. Next, for CTX8371, our PD-1, PD-L1 bispecific antibody, very unexpectedly, we have two deep partial responses in the early dose escalation cohorts in the ongoing phase one study. One partial response is in a patient with non-small cell lung cancer, and one partial response is in a patient with triple negative breast cancer. Later this year, we'll be initiating cohort expansions in patients with non-small cell lung cancer and triple negative breast cancer. I will describe CT scans for each of these two patients in a few minutes. We hope to present these data at a scientific conference later this year. We're also disclosing results from preclinical head-to-head studies of CTX10726, our proprietary PD-1 VEGF bispecific antibody, compared to the leading drug candidate in the class of Inesimab. We will be presenting these data at a scientific conference later this year. So let's begin with Tevesimab. This slide summarizes the design of the ongoing randomized study in the United States in patients with advanced biliary tract cancer. This study is a two-to-one randomization of tevesimib plus paclitaxel versus paclitaxel alone. The primary endpoint of the study is overall response rate. We announced those results about four months ago. The secondary endpoints in this order are PFS, OS, and duration of response. We're using, of course, the hierarchical testing methodology to control for alpha statistical spending in the study. The next slide summarizes the current status of the study that we call Companion 002. On the top right, as I mentioned, we achieved the primary endpoint, so the study's positive by definition. We had a 17.1% overall response rate. about tripling what was seen in the control arm with a p-value of 0.031. On the top left box, I'll come back to this point in one minute, the trial was fully enrolled in August of 2024, enrolled 168 patients with advanced biliary tract cancer treated in the second-line setting. As of today, we're currently at greater than 17 months median follow-up in the study. Let's talk about the secondary endpoints of progression-free survival and overall survival. It's hard to say this, but the secondary endpoints are triggered by a total number of deaths in the study. That's how these time-to-event analyses are commonly done. We need 80% OS events to trigger the analyses of progression-free survival and overall survival. And today we have fewer total deaths in the study than we had originally projected when we projected that we would be presenting analyses of these endpoints in Q4. We made that projection in April of this year. And since that time, the number of deaths in the study has continued to decline. Clearly, the 80% OS event threshold has not been met, so the analyses of PFS and OS are now projected to occur in Q1 of 2026. I think the bottom of this slide is very important. Recall the study that was titled ABC06, That study was published in 2021 in Lancet Oncology by LaMarca et al. That was a randomized study of the three drug combination, Folfax, 5-FU, Leucovorn, and oxaliplatin in patients with biliary tract cancer treated in the second line setting. So the exact same population that we're treating in companion 002. If you look at the Kaplan-Meier curves for that study, At 18 months, the overall survival was less than 10% in that study, with a median overall survival in the full FOX arm of 6.2 months. Where we are today, and again, it's important to point out, this is a pooled survival number. We're greater than 20% overall survival, with greater than 17-month median follow-up. And we probably, although it's hard to predict, of course, we probably will not be at 80% mortality until we have something like greater than 20-month median follow-up. So very interesting data today, obviously extremely important. And as we mentioned in our press release, Obviously, we don't know this, but it appears that tevesimib could be affecting overall survival in this patient population. Okay. Let's now move to CTX8371, our PD-1, PD-L1 bispecific antibody. Just a reminder of the differentiated mechanism of action here. Recall that this drug emerged from a screen using a proprietary technique at Compass in which we can screen bispecific drug candidates for synergy. That screen identified PD-L1 as a synergistic partner for PD-1 blockade. As I've discussed many times before, that was a rather unexpected scientific discovery, and because of that, we spent a long time investigating the mechanism of action. We published all that data. The PubMed ID for that paper is at the bottom of this slide. We have always envisioned 8371 to be on the leading edge of defining next generation checkpoint inhibition. This mechanism of action on the right-hand side of this slide with the bispecific being unequivocally a cell engager. And quite fascinatingly, the bispecific actually converts PD-1 positive T cells into PD-1 negative T cells by removing PD-1 from the surface of those cells. So it is a very differentiated mechanism of action. And again, we believe that this drug could be on the cutting edge of defining next generation checkpoint inhibition. We're currently running a phase one study. This study is a standard three plus three dose escalation study. Importantly, we, of course, as all phase one studies do, we started with a minimal dose of 0.1 milligrams per kilogram, and we have finished enrolling the first four dosing cohorts, 0.1, 0.3, 1, and 3 milligrams per kilogram. We have not seen any dose-limiting toxicities in those 12 patients. So again, a three plus three design, three patients times four dose levels, 12 patients. We're currently enrolling the fifth dose level, which will be the 10 milligram per kilogram dose level. The patient population in this study, importantly, is all post checkpoint inhibitor. So patients with melanoma, non-small cell lung cancer, head and neck cancer, Hodgkin lymphoma, and triple negative breast cancer are being enrolled in this study. As I mentioned earlier, we now have two deep partial responses in the first patients enrolled in this study. And again, I will emphasize to you that the first dosing cohort was really a de minimis dose. These are CT scans on slide 10 from a patient in the study with non-small cell lung cancer. For reference, these scan images across the top, the patient is lying on their back. Dark color is air, so that's the lungs. Lighter color is tissue. and the bright white color is bone. Inside of the blue circle at baseline, you can see a 45 millimeter metastatic tumor in this patient, which over time completely disappears. In fact, this patient had 59 millimeters, 5.9 centimeters, more than two inches total of metastatic tumor, which actually all disappeared. Really interestingly in this patient, this patient actually had initial pseudoprogression at a lymph node, which has been described with checkpoint inhibitors like Keytruda and Opdivo. And it's interesting to speculate on what that might mean. Subsequently, all of these patients' target lesions disappeared. We also have two patients with non-small cell lung cancer among five patients treated so far with prolonged stable disease for a clinical benefit rate of approximately 60%. So on the next slide, I'm going to spend a little bit more time on this slide because this slide is incredibly important. So this is a patient with metastatic triple negative breast cancer. who had three metastatic target lesions at baseline. I'm showing two of these three lesions on this slide. The third lesion was a lymph node. Across the top, same thing as the previous slide, patient lying on her back. Black color is air. So inside the blue circle, you can see a metastatic tumor in the lung, which completely disappears. by eight weeks. On the bottom, this is a sagittal view. So this is a reconstruction where you're looking at the patient from the side. Inside the blue circle on the bottom left is a metastasis to the pericardium, the lining of the heart. That metastasis is 52 millimeters in size, 5.2 centimeters. more than two inches. Both of these tumors completely disappeared. The other target lesion went from 15 millimeters to seven millimeters. So the total tumor decline in this patient from 87 millimeters to seven millimeters is greater than a 90% reduction in this patient treated in the fourth line setting who had previously received pembrolizumab This patient is one out of three patients treated in the study with triple negative breast cancer. So moving to CTX10726, our proprietary PD-1 VEGF bispecific antibody. So this is a drug candidate that we worked on internally at Compass for about 18 months. We nominated it as a development candidate earlier this year. We have disclosed previously that we have more potent PD-1 blockade in vitro than has been reported for other drugs in the class. Over the past six months or so since we disclosed this as a development candidate, we've locked down our CMC process I think one of the things that we have not talked much about at Compass is we've developed a fair amount of proprietary know-how around bispecific manufacturing and our manufacturing process has commercial level yields for this drug already before we're in phase one. We're on track to file our IND in the US in Q4 of this year. Today, we're announcing some really interesting preclinical head-to-head comparisons of CTX10726 with Ivanesimab. These next three slides are, of course, complicated preclinical experiments, and I'm going to go through these in some detail. In this study, we're using a transgenic mouse model that expresses PD-1 and PD-L1 as humans. So the extracellular domains of PD-1 and PD-L1 are not in as human, so you can directly test human-targeted checkpoint inhibitors in this experiment. Importantly, though, there's no human VEGF in this experiment. I'll come back to that point in a minute. Here we're directly comparing the PD-1 blocking arms of 10726 with Ivanethamab, and you can see that in terms of tumor control in this mouse model in a head-to-head study, 10.726 is superior to ibanesimab. For those of you who are looking at these graphs very carefully, you can see that the control and ibanesimab arms end at week 28 because those animals had to be sacrificed due to uncontrolled tumor growth. On the next slide, in the same model, we compare 10-726 directly with pembrolizumab. So again, this experiment is simply testing the PD-1 blocking arm of 10-726 and comparing that head-to-head with pembrolizumab, and 10-726 is equivalent to pembrolizumab in this study. The next slide is a little bit more complicated experiment. So this is a xenograft experiment in which a human tumor, a non-small cell lung cancer model called HCC822, is injected into mice. That tumor secretes human VEGFA. So this experiment tests both PD-1 blockade and VEGF-A targeting. These experiments, of course, are done in immunocompromised mice. So a human immune system is added back to the mice. PBMC is peripheral blood mononuclear cell. So on the bottom left, you can see the control in black. Bevacizumab and Ivanesumab are about the same in this experiment. And the best drug in this head-to-head experiment is CTX 10726. As I mentioned earlier, we will be presenting these data at a scientific meeting later this year and filing our INB, which is on track for Q4. So on my last slide, we have some updated milestones here. And I think over the next six quarters, We have an incredibly rich milestone list here. So let's start with Tovesimig. In Q1 of the coming year, we'll read out our important progression-free survival and overall survival from our randomized study. I would imagine that that readout would be followed by a very robust interaction with the FDA, which would put us into a position to potentially file a license application in the middle of 2026. Of course, we have fast track status, fast track designation, so I would anticipate that we would get a priority review. We will be initiating our planned basket study for tevesimig following that analysis in patients with DLL4 positive tumors, including potentially gastric cancer, ovarian cancer, hepatocellular cancer, et cetera. Still working on that design, but that study should be ready to go in the coming months. For CTX471, we're planning to initiate our NCAM positive basket study later this year. That biomarker was discovered in the phase one study of CTX471, and we presented scientific data after that drug twice last year. And then finally, for 8371, very important update on that program today. Next step is initiating the cohort expansions in patients with non-small cell lung cancer and triple negative breast cancer. Those cohort expansions will begin later this year with clinical data from those cohort expansions next year, hopefully presenting the dose escalation data at a scientific meeting later this year. Finally, for 10-7-26, the preclinical update that we've provided today, we're going to present that data at a scientific conference later this year, INB filing in Q4, which should put us in a position to read out clinical data next year. And lastly, we also, as part of our disclosure today, we ended Q2 with $101 million in cash, which is cash runway here at Compass into 2027, executing on all these programs and delivering the milestones that you see here. So with that, I'll thank you again for joining the call today. I'm happy to take questions.