Conference Transcript - CMPX 2026-06-04

Maury Raycroft, Analyst — Jefferies

My name is Maury Raycroft, and I'm one of the biotech analysts at Jefferies. It's with great pleasure that I'd like to welcome Tom Schutz, the CEO of Compass Therapeutics. We're going to do fireside chat format, so I'll pass it over to Tom to provide an intro to the company and programs, and then we'll switch over to a fireside. And so, Tom, I'll let you start out.

Thomas Schuetz, MD, PhD, CEO

Thanks, Maury, and thanks for inviting us to present at the conference. I really appreciate it. I'll go through a few slides, and then, as Maury mentioned, we'll have some Q&A following a brief presentation. Just one quick reminder, I will be making forward-looking statements today, and I will refer you to our regulatory filings for descriptions of those. Compass is located in Boston. We're a monoclonal antibody discovery and development company in oncology. We currently have four drugs in the clinic. Our most advanced asset is Tevesimig, a DLL-4 VEGFA bispecific antibody. We recently read out the results of secondary endpoints for that study. The study hit the primary endpoint of overall response rate and hit the key secondary endpoint of progression-free survival. Next steps there will be a meeting with FDA in advance of preparation for the submission of a biologics license application. Later this year, we're going to initiate a Phase II study for our second program, a next-gen CD137 agonist in patients with NCAM-positive tumors. And we also have a PD-1, PD-L1 bispecific antibody, potentially a first-in-class asset. We presented data at ASCO this past weekend, in which we showed that we have confirmed responses in patients with triple-negative breast cancer and Hodgkin's lymphoma, as as well as non-small cell lung cancer in a Phase I post-PD-1 study. We also have a PD-1 VEGFA bispecific that has recently entered Phase I testing. So let's talk about Tevesimig, and we'll talk more about this, of course, in the Q&A. So we recently completed a randomized study of Tevesimig plus Paclitaxel versus Paclitaxel alone in patients with advanced biliary tract cancer who had received one prior line of therapy. This was a two-to-one randomization. 111 patients randomized to the combination arm, 57 patients randomized to the control arm. Crossover from the control arm was allowed following centrally confirmed progression, and a very large number of patients crossed over to the active arm, 54% of patients. So 142 or 85% of patients in the study received Tevesimig at one point in the study, either at randomization or upon crossover from the paclitaxel control arm. As I mentioned, we hit the primary endpoint in the study of overall response rate. Importantly, all responses in this study were assessed by blinded independent central review. The overall response rate in the Paxotexel arm was 5.3 percent, very consistent with what you see with three-drug chemotherapy regimens in the second-line setting. Folfox, for example, in a randomized study, had a response rate of 4.9 percent. We more than tripled the response rate by adding Tevesimig, and that was statistically significant. In the bottom of this slide, we also had a significant improvement in disease control rate, 61.3% in the combination arm, 36.8% in the pack-only arm with a p-value of 0.0027. That disease control rate translated into a significant improvement in progression-free survival. Here are the PFS curves for the study. There was a very significant improvement in PFS with a hazard ratio of 0.44, with a p-value less than 0.0001. So a very important improvement here. I would argue that this is a clinical endpoint, because in this disease, where patients are where complications of biliary tract obstruction, any extension or prevention of progression in this study is very clinically meaningful. Recall, I mentioned to you that more than half the patients in the control arm crossed over to receive tevesimig. So in the intent-to-treat analysis, there was no difference in overall survival. But remember, this is sort of a confounded analysis because the patients who crossed over to receive tevesimig are allocated to the control arm here. And more than half the patients in the control arm are actually not, quote-unquote, control. One of the prospective secondary endpoints in the study was something we called PFS-2. This also indicates that tevesimig has significant treatment effect in the study. PFS-2 is an analysis of the patients who crossed over, comparing their progression-free survival on paclitaxel alone to their subsequent progression-free survival on tevesimig plus paclitaxel. So the patients who crossed over, their paclitaxel median PFS was 1.9 months. When adding tevesimig, that improved to 3.5 months. So a very significant difference simply with the addition of tevesimig plus paclitaxel. When we saw PFS2, that led us to do a subset analysis where we looked at the patients in the control arm specifically. So this slide shows the overall survival analysis of patients who crossed over to receive Tevesimig versus those who did not. And you can see from this slide, the patients who crossed over to receive Tevesimig did extraordinarily well in this study with a median overall survival of 12.8 months, which is actually what you see in the frontline setting. These crossover patients, of course, were treated in the second-line setting with Paclitaxel, and then Tevesimig Paclitaxel in the third-line setting, and their median overall survival was similar to what you see in the frontline setting. The patients who received paclitaxel only had a median overall survival of 6.1 months. If you got to Vesimig at any point in the study, either at randomization or at crossover, the median overall survival of those patients was 9.9 months compared to 6.1 with paclitaxel Obviously, with an analysis like that, like this, you can question whether or not these patients would have done better anyways, but they did not. Keep an eye on the red versus blue line on this slide. When you look at PFS, it actually reverses. The patients who crossed over actually did worse with Paclitaxel than patients who didn't cross over. Interestingly, these patients also had their performance status deteriorate while on paclitaxel. So on the last slide, what we're seeing here is a clear effect of Tevesimeg following crossover. On the safety side, most common AEs that we saw on mechanism for VEGF blockade were hypertension. Obviously, the bone marrow suppression here is related to paclitaxel. Here's a summary of the Companion 002 study. Met the primary endpoint with a significant improvement in overall response rate. We had a very significant improvement in progression-free survival with a hazard ratio of 0.44 with an extremely low p-value, representing a 56% reduction in the risk of progression associated with Tevesimig. The OS ITT analysis was confounded by crossover, and we know those crossover patients drove the control arm ITT analysis because those patients lived a median of 12.8 months, again, clearly indicating that Tevesimig has had an effect on overall survival. Next steps here are to meet with FDA and discuss these data in advance of a biologics license application. And clearly, when you compare what we saw with tevesimig-paclitaxel to regimens that are used in this disease, we clearly are seeing something different. In the bottom of this slide, full FOX, full FURY, two 2.8-month median PFS. We saw 4.7 months, 6.2-month median overall survival. Again, spot on from what we saw with paclitaxel. And when you got to Vesemig in this study, your median OS was 9.9 months. In the last minute or so, I'll just talk briefly about 8371. 8371 is a novel PD-1, PD-L1 bispecific antibody that emerged from a screen we did for synergy with PD-1 blockade using a technology we developed at Compass called StitchMabs. We recently completed a dose escalation phase one study. This was a three-plus-three design at five different dose levels. We had no dose-limiting toxicities in the study, and we presented at ASCO this past weekend. We have two at the top dose, two dose levels. Out of six patients treated, we have two very important responses. These are PET scans from a patient with Hodgkin's lymphoma. You can see the PET-positive tumors circled in blue here that nearly completely disappear. This patient on the bottom was post-transplant and post-nevo. This patient continues on study more than 10 months out. Perhaps the most important patient in the study is this patient. This is a patient with metastatic triple-negative breast cancer who relapsed while receiving adjuvant ketruta. The patient then received Tredelvi followed by two additional chemotherapy regimens. This patient had about 9 centimeters of linear tumor burden at baseline, 2 centimeter lung metastasis on the top that disappeared, on the bottom a 5.2 centimeter pericardial metastasis that has completely disappeared. This patient we presented at ASCO was in a durable PR at week 48. I can tell you today that this patient actually is now out more than 13 months with a durable PR and continues on therapy. So in summary, four drugs in the clinic, lots of upcoming milestones this year, FDA meeting for Tevesimig. We're also going to start some additional Phase II studies with Tevesimig, probably combining that with Paclitaxel because we believe we might have discovered something interesting with the combination of tevesimig and paclitaxel. NCAM-positive biomarker study for 471. For our PD-1, PD-L1 bispecific, we've initiated cohort expansions in the Phase I study in patients with non-small cell lung cancer, triple negative breast cancer, and Hodgkin's lymphoma. That study's enrolling extremely well, and we expect to report cohort expansion data in the second half of this year. And finally, our PD-1 VEGFA bispecific antibody has initiated phase one testing, and we should be in a position to have some preliminary data from that study later this year.

Maury Raycroft, Analyst — Jefferies

Great. That was a good highlight and summary of the company. Maybe starting off with Tovesimig, which you talked a lot about there. You're definitely seeing a signal in the second-line BTC study. There's been debate around the crossover subgroup where the crossover patients appear to do better than those initially randomized to active, and so the 12.8 months versus 8.9 months. As you're doing additional work on the data, I guess, what are some observations or nuances about that finding? Is it related to baseline imbalances, timing of crossover, subsequent therapies?

Thomas Schuetz, MD, PhD, CEO

So thanks again, Maury. So, yeah, I agree with the way you framed the question. You know, we unequivocally, you know, have evidence here that the drug is working. I mean, we have tripling of overall response rate and just an unequivocal and very important improvement in progression-free survival. Yes, the patients who crossed over from the control arm to receive Tevesimig plus Paclitaxel, those patients did extraordinarily well. And you're correct. They did better than the patients, slightly better than the patients who were initially randomized to the combination. So we don't know yet what the explanation for that is, but we do know what it isn't. You know, there's no, you know, clear imbalance in prognostic factors. It is definitely not post-study therapy. You know, one of the things is very topical, obviously, but, you know, when I first saw that, I wondered, you know, if those patients all went on to receive RAS inhibitors, right? So that is absolutely not the case. There are slightly, there are more patients with intrahepatic cholangio that crossed over. But again, given the fact that those patients did worse with paclitaxel, I'm not sure what to make of that. So we're left with sort of two explanations, right? One rather unsatisfying, which is small n, right? It's 31 patients. Or something much more important, you know, which is, you know, does paclitaxel prime the tumor microenvironment to make tevesimig more effective? That's a very provocative question, and we've started some preclinical work to begin to try to address that question, because it's an important question, because it would influence our plans for studying tevesimig in multiple other indications.

Maury Raycroft, Analyst — Jefferies

Yeah, that's an interesting one, definitely worth looking into. do. And for next steps with FDA, I'm not sure if you have any more granularity on the slide up there, but just walk through the next steps for the timing for FDA interactions, what type of meeting you want to have, and the key topics you expect to address.

Thomas Schuetz, MD, PhD, CEO

Sure. So the meeting will be in approximately the first half of August. So backing out from From that, approximately July 4th-ish, you know, we would submit the full briefing package to FDA. And then going forward from early to mid-August, approximately Labor Day, we would expect to have minutes from that meeting that we would then, of course, discuss publicly. I mean, the real goal of that meeting is to align on a pathway for submission of a biologics license application for tvesimine. And if we align on that, we could begin the BLA submission process later this year. You know, we would look to do a rolling submission and initiate that this year, you know, finish that in the first quarter of next year, which should, you know, put our PDUFA date for Tevesimig in the second half of next year because we have a fast-track designation. and in this indication that has no labeled therapies for patients without an actionable mutation, we would certainly, I'd be shocked if we didn't get a priority review. Yeah.

Maury Raycroft, Analyst — Jefferies

Okay. Yeah, it makes sense. And given you hit STAT-SIG on ORR and PFS, do you think that can be sufficient from FDA standpoint, even if the ITTOS signal is confounded by the crossword?

Thomas Schuetz, MD, PhD, CEO

Sure. I mean, you just described something like 80% of oncology drug approvals in the United States over the past 15 years or so. So we're squarely in the middle of the fairway, as it were, hitting ORR, hitting PFS. And again, I think this is a very important point. Unlike many other diseases where you can wonder about the clinical significance of altering progression, you know, in biliary tract cancer, you know, these patients have anatomic complications in the biliary tree. You know, so when these patients get obstruction of their biliary tree, that, frankly, that is fatal. So halting progression in this disease and potentially delaying the time to bilayer obstruction is, I would argue strongly, is a clinical endpoint. So we believe that, you know, this could support full approval. And I think, importantly, at the end of last year, there was a large meta-analysis published which showed that But the best predictor of OS in studies of patients with biliary tract cancer is actually PFS.

Maury Raycroft, Analyst — Jefferies

Got it. Okay.

Thomas Schuetz, MD, PhD, CEO

And that's a very, very important paper.

Maury Raycroft, Analyst — Jefferies

That's helpful. And so going into the FDA interaction, what scenarios are you planning around? Do you think FDA could require a confirmatory study, and if so, what would your views be Would you do front line or second line?

Thomas Schuetz, MD, PhD, CEO

Sure. So, you know, you're asking, you know, whether or not the data support full approval or accelerated approval. You know, both of those are approval. So, you know, I think with accelerated approval, I think if we had to do a confirmatory study, one potential study design that you alluded to would be a frontline study. So adding Tevesimig to GEMSIS-DERV, which is a single arm study that's ongoing now at MD Anderson. And we're seeing some very interesting things from that study that make us, you know, very confident that we could add Tevesimig to that regimen. Obviously, that's a large randomized study that, you know, would be expensive and take a long time, but it would lead to a frontline label. You know, another study we could do conceivably if asked for a confirmatory study would be Tevesimig-Paclitaxel versus investigator's choice of chemotherapy. You know, that's probably a study we do in Europe so that, you know, we would not have the control arm be confounded by crossover to commercial to Vesimic pack.

Maury Raycroft, Analyst — Jefferies

Got it. Going back to the biliary tract obstruction, is that, how many of those events did you see in your study? Is that something you think?

Thomas Schuetz, MD, PhD, CEO

We have not disclosed that, but that's something we're looking at closely.

Maury Raycroft, Analyst — Jefferies

Got it. And for a confirmatory study, if there is some sort of priming with Paclitaxel, is that something you could try to incorporate into the study?

Thomas Schuetz, MD, PhD, CEO

You know, that's a very interesting question. I think we would need more scientific data in order to do that.

Maury Raycroft, Analyst — Jefferies

Yeah, makes sense. And so going back to the data, so if we focus only on the patients who did not cross over, OS looks at like approximately 8.9 months versus 6.1 months. you view the 2.8 months Delta is potentially supportive enough for FDA to take a positive view.

Thomas Schuetz, MD, PhD, CEO

Yeah. Yeah, for sure. You know, I think full Fox compared to best supportive care had a 0.9 month improvement in median overall survival, and that was thought to be good. So, so that is a, you know, a very, very important, you know, that's a, what is that 40, 40% improvement in overall survival. So, yeah, I think that would be very, very meaningful. Got it.

Maury Raycroft, Analyst — Jefferies

And you mentioned just in oncology, you see a lot of approvals based on just ORR and PFS, 80%. What's the closest analog or example for your guys' situation?

Thomas Schuetz, MD, PhD, CEO

Oh, there are so many. FDA just published, actually FDA just published an analysis of, help me, the selperketamab, one of the targeted therapies in non-small cell lung. They published that in JCO in April, and that's a very important paper. You know, ORR, PFS, clearly, with a crossover and a hazard ratio of 1.26, right? You know, and FDA published a full analysis of that. But FDA also published a couple years ago, the first author in that paper is Marino. Rick Pazder is actually a co-author on that paper. You know, there's like five or six different approvals in that paper where the hazard ratio is above one, you know, due to crossover. Actually, Copictra actually didn't have a crossover and straight-up lost to one of the CD20 antibodies, alfatumumab, and that drug still got approved.

Maury Raycroft, Analyst — Jefferies

Interesting. Okay. And on the safety front, you reported approximately 52% grade 3 hypertension. Were there any grade 4 hypertension events, and what's the standard mitigation strategy?

Thomas Schuetz, MD, PhD, CEO

I think there was maybe one, I think, but I'm not certain on that. You know, hypertension is an on-mechanism AE associated with VEGF blockade. Right. Whether it's a monoclonal antibody targeting the ligand, the receptor, VEGF kinase inhibitors, hypertension is sort of the most common on mechanism AE. So there are now published algorithms for managing the hypertension associated with VEGF blockade.

Maury Raycroft, Analyst — Jefferies

Okay. Yeah, so there's nothing surprising in the study on that front.

Thomas Schuetz, MD, PhD, CEO

No, no. And we use those algorithms in the study. Got it.

Maury Raycroft, Analyst — Jefferies

Okay. Are you planning any biomarker analyses to compare crossover patients versus those initially randomized to active? And if so, like what biomarkers are most relevant?

Thomas Schuetz, MD, PhD, CEO

We don't have enough time to talk about that question. So the short answer to your question is for sure, yes. So we conducted a whole series, we collected a whole series of specimens to assess for biomarkers. And we're going to full court press that. So we had a very nice investigator meeting at ASCO this past weekend. And one of our lead PIs is going to take the lead, you know, on, you know, helping us with those biomarker analyses. And we're going to do everything that everybody can possibly think of. Because, again, trying to figure out why those patients did so amazingly well, I think, is a very important question.

Maury Raycroft, Analyst — Jefferies

Are there any hunches? Do you think it could be target expression related, maybe ctDNA?

Thomas Schuetz, MD, PhD, CEO

All of those would be on the table. Yeah, makes sense. And we collected ctDNA, so we'll take a look at all that.

Maury Raycroft, Analyst — Jefferies

And so as you continue to analyze the data, are there, I guess, what are going to be the key crossover adjustment approaches that you think could build a strong case for FDA?

Thomas Schuetz, MD, PhD, CEO

So you alluded to statistical methodologies, and there are numerous statistical methodologies that are available, you know, as sensitivity analyses to look at crossover. We used, in the prospective design, we used the RPSFT, which stands for the Rank Preserving Structural Failure Time. Unfortunately, the statistical assumptions for that methodology were not met, so we couldn't use that. But there are multiple others that are actually, those analyses are ongoing right now. I want those analyses to be available for our FDA meeting package. You know, just, again, you know, to try to help, you know, understand the effect of crossover. You know, there's the inverse probability of censoring weights, IPCW, which is one that's commonly used. All of those analyses are ongoing right now.

Maury Raycroft, Analyst — Jefferies

Got it. And you'd want to have those done by the July 4th time frame. You wouldn't share those with the public beforehand. Really wouldn't be a better.

Thomas Schuetz, MD, PhD, CEO

Probably not. But it would probably be part of our disclosure around the outcome of the FTA meeting. Got it.

Maury Raycroft, Analyst — Jefferies

But there are options. I think that's kind of the key. Okay. And for MD Anderson frontline study, just a status update on there. How's that going?

Thomas Schuetz, MD, PhD, CEO

I met with the investigator last Saturday at ASCO. So that, you know, in rolling well, we've, there was a, because we're adding Tevesemig to a new regimen, you know, there was a safety run-in as part of that study. That's now completed, and we're now going to expand that study outside of MD Anderson proper into the MD Anderson network in the coming months, you know, looking to, you know, just enroll more patients and get more data from that study. But we're really, really confident and excited about what we're seeing there.

Maury Raycroft, Analyst — Jefferies

Got it. Could that be an update later this year, potentially?

Thomas Schuetz, MD, PhD, CEO

Maybe.

Maury Raycroft, Analyst — Jefferies

Yeah, maybe.

Thomas Schuetz, MD, PhD, CEO

Yes.

Maury Raycroft, Analyst — Jefferies

And so for next steps for TevesaMig, so you get the meeting request in, meet with FDA, do some sort of disclosure, probably, just make sure I got it right, first half of August?

Thomas Schuetz, MD, PhD, CEO

No, the disclosure would probably be around Labor Day. After you get the minutes.

Maury Raycroft, Analyst — Jefferies

Yeah, around Labor Day, right. So those are the kind of key events there. Anything else that would happen in between as it relates to the program?

Thomas Schuetz, MD, PhD, CEO

Probably not. You know, that's what we're really focused on that, you know, and then that will, you know, help us, you know, sort of guide our next step.

Maury Raycroft, Analyst — Jefferies

Are you going to publish the data or have that at, like, a medical conference later this year?

Thomas Schuetz, MD, PhD, CEO

We're hoping to present the data at a medical conference later this year.

Maury Raycroft, Analyst — Jefferies

And so I wanted to talk about 80 through 71 briefly, too. You mentioned the poster at ASCO. What are next steps for the program, and when should we expect the full expansion core data?

Thomas Schuetz, MD, PhD, CEO

Sure. So, you know, we're really excited about, you know, what we saw in the dose escalation portion of the study, right? You know, this is a next-generation checkpoint inhibitor. In 15 patients treated, you know, six patients at the two highest dose levels, we've got three responses in the study, two out of six at the highest dose level. So, you know, patients with non-small cell lung cancer, Hodgkin's lymphoma, and triple negative breast cancer, you know, all had, you know, very, very important and meaningful responses. You know, again, all post-checkpoint inhibitor. You know, I think, obviously, as you know, I'm biased. But I mean, I think, to my knowledge, we have the best phase one checkpoint inhibitor data ever, I think. And so we've moved to cohort expansions. So we're doing cohort expansions in those three indications. top two dose levels, 3 and 10 mg per kg. We're doing 14 patients in each dose level, so 28 total, with triple negative breast and non-small cell lung, so that's 56. And then at the top two dose levels for Hodgkin's lymphoma, 6 and 6, so another 12. So we're adding 68 patients to the 15 patients enrolled in the dose escalation portion of the study. And the dose expansion, is enrolling extremely well. And that just got opened in Q1. You know, we're already, you know, north of 10 patients in that study. So I would expect that we could be able to, you know, present an important data update from the cohort expansions later this year.

Maury Raycroft, Analyst — Jefferies

So that could be a big update later this year. And you've also guided to having the 10-726 data second half of this year too. How are we setting expectations for that? Could we see early durability?

Thomas Schuetz, MD, PhD, CEO

Sure. So I think, so 10-7-26, our own, you know, PD-1-VEGF bispecific, we presented preclinical data at CITSI about 18 months ago, you know, demonstrating that that drug was better than, you know, other PD-1-VEGF bispecific antibodies in preclinical studies. We're now in phase one. We selected indications based on indications where either checkpoint, where checkpoint inhibition and VEGF blockade are effective. So the phase one indications are hepatocellular, renal, gastric, and endometrial. First cohort fully enrolled, should get to the second dosing cohort in the coming month or so, which would put us in a position, I think, if it continues at this rate later this year, we can present some early data from that study. Would love to have some efficacy signals, just like with 8371. Probably not durability, but just probably initial efficacy data from that study.

Maury Raycroft, Analyst — Jefferies

Got it. Makes sense. Look forward to the updates. Thanks so much for joining us. Great.

Thomas Schuetz, MD, PhD, CEO

Thanks, Maury.