Yeah, no, chairs are a little rough. All right. Good morning, everyone. I'm Stephen Willey, one of the senior analysts here at Stifel. Glad to have with us in the next session, Tom Schuetz, who's the CEO of Compass Therapeutics. We're going to have a casual discussion. If anyone has a question, feel free to raise your hand. Tom, thanks for coming as always.
Sure. Thank you for having us.
Any opening statements you'd like to make before we jump right into Q&A?
Sure. Again, thanks for having us here. Always happy to come. For those of you who don't know, Compass, we're located in Boston. We're a monoclonal antibody discovery and development company in oncology. We've got four drugs in the clinic, which we'll talk about today. Our lead program, tovecimig, a couple of weeks ago, we presented data from a randomized trial at ESMO, and we simultaneously published all that data in the Journal of Clinical Oncology on October 24th. We're in the middle of re-engaging with FDA right now in order to have a conversation about a path forward to get this drug approved for the treatment of patients with biliary tract cancer.
Okay. And congrats on the JCO publication. I know that kind of puts a good bow on COMPANION-002.
Yeah. Thank you.
Just curious, I know that there were kind of some incremental pieces of information that were disclosed and came out of both the presentation and the manuscript. Anything you want to highlight there?
Sure. I think, interestingly, so you are correct, getting a publication in JCO simultaneously with an ESMO presentation does require some aligning of the planets.
Yeah.
And, fascinatingly, during the review of the draft JCO manuscript, one of the reviewers specifically asked for the Two-Stage Estimation method to do the crossover correction on OS, and that, I think, the question about the ITT analysis versus the crossover analysis clearly showed that the hazard ratio is below one. Yeah, but I think as you and I have talked about before, the intent to treat analysis is sort of anything but that.
The patients initially randomized to the control arm were not intended to be treated with tovecimig. That analysis is kind of irrelevant. It is really irrelevant. So, I think what we showed, not only in the JCO paper but also in the ESMO presentation, the patients, if you got tovecimig at any time during this study, you lived longer. We need to just be clear about that and talk about that more clearly in our regulatory conversations.
Maybe this is a little bit too much of a statistically wonky question, but how does this second post-hoc analysis that was requested to look at the impact of patient crossover, how did that look, or how is that mechanistically or philosophically different from the rank-preserving model that you had pre-specified within the stats plan?
I am going to pounce on your use of the word wonky.
Okay
if you don't mind.
Feel free.
Because I'm not going to be fully able to go into that wonk.
But my understanding is for the RPSFT, when the ITT hazard ratio is above one, the mathematics of that can't work.
Yep.
Conceptually, the two methods are similar, which is in the Two-Stage Estimation method, the first stage is a modeling exercise to determine how patients did after crossing over to tovecimig, the control patients. Once you model that, then you use that model in the second stage, Two-Stage Estimation method, to calculate something called counterfactual survival, which simply adjusts patients' survival in the control arm to a point where the assumption is how they would have done if they had not crossed over. That is my conceptual understanding of that method. I certainly could not describe the math.
Okay. I thought it was interesting that the hazard ratio of that post hoc kind of perfectly aligned with what Astra tried to do in that TROPION-Breast trial-
Sure. Yep.
where they did that post hoc-
Yep
On survival, which was a co-primary with no crossover. I know we've talked about this, but that post hoc was also 0.85, and it was part of the regulatory submission.
Yep. Yeah, so we, by the way, you didn't ask this, but that was not included in our regulatory submission in the summertime.
Okay.
That's something that we're sort of doing right now. We're right in the middle today.
Okay
Of re-engaging with FDA.
Okay.
We need to present that data very clearly to FDA.
Okay. Maybe before we get into that re-engagement, I thought in the presentation and the manuscript, we also learned a little bit more about these crossover patients with respect to their patient baselines.
Yep
The subsequent therapy that they received, the response that they achieved once they crossed over. I guess I am still really surprised by the fact that these patients did as well as they did from a survival perspective. Are you still trying to do some of the work, some of the biological work to understand if this hypothetical priming effect is real?
You bet. We have done a fair amount of work over the past several months, continuing to analyze the data that we have, both serum and biopsy specimens, to try to help us get at this answer. By the way, I thought the discussant of the ESMO presentation, he was spot on because he specifically highlighted this.
Correct.
He said, "Hey, there are some patients here who did staggeringly well." It is incumbent upon us to do everything we can to try to figure that out. I think maybe early next year, hopefully, at a scientific meeting, we're hoping to present some of that work. But it's a big hypothesis.
Yeah.
You and I have talked about this before. How does two months of paclitaxel alter angiogenesis in the tumor microenvironment that makes tovecimig work better? My God, that's a complicated hypothesis.
Yeah.
But I think we have to do everything we can to figure it out.
I think in the presentation, maybe just kind of last question related to this, but we also saw granular safety data for the first time.
Yep.
I know it's always really challenging to interpret safety data in these second-line biliary cancer patients. They're incredibly complex.
Yep.
Just how do you think about the safety tolerability data just in the context of the broader risk-benefit that you think
Sure
Exists here?
Yeah, I think it's a good question. I think the real difference between tovecimig and other VEGF-targeted drugs, I think, is hypertension.
I think that's the real difference. We talked to a lot of docs about that at ESMO. We probably met with , like, 30 docs, or something like that, at ESMO, just thinking about developing hypertension management guidelines and how we think about that compared with other sorts of VEGF-targeted agents. I think that's what we're going to need to do.
Okay. Maybe just on the re-engagement side, right? You've talked previously about wanting to meet with them again to discuss accelerated approval prospects. Where are you in that process right now?
Right.
And when should that next meeting occur?
Unfortunately, in the summertime, we were not afforded a meeting. All of the communications with FDA were via email.
Okay.
Yeah, I think so. I know this. I apologize, Stephen. I'm not trying to sound trite here.
But our first goal for the meeting is to have a meeting.
Okay.
Yeah, we want to have a live conversation about the data and put it in context and put it in context of the very important meta-analysis that was published at the end of 2025 by Castet et al, which showed that that's a 10,000-patient meta-analysis that showed that PFS hazard ratio of less than 0.61 was predictive of an OS benefit. That's an extremely important paper that we have to sit down with FDA and have a conversation about. We've got a hazard ratio of 0.44 on PFS, following the publication of a meta-analysis with 10,000 patients. We have to sit down and put those data in context. I think that, look, as you know, once a, quote unquote, "surrogate endpoint" is validated, it is no longer a surrogate, right? I think probably the best example of that ever is probably serum cholesterol, right?
When cholesterol-lowering drugs were first being developed, everybody said, "Blah, blah, blah. Serum cholesterol is a surrogate." Well, not anymore, right?
Because it was validated. I would just like to be able to have that conversation with FDA about PFS as a validated surrogate in this disease. If FDA says, "All right, let's talk about accelerated approval," I'll be like, "Okay, let's talk about a confirmatory study and what that might look like.
What might that confirmatory study look like?
I think there are maybe three possibilities. I think probably the simplest and most straightforward design would be tovecimig plus paclitaxel versus FOLFOX. In the second-line setting, we had some conversations with folks in the E.U. when we were in Madrid a couple weeks ago, at ESMO, about that study. There are folks in the E.U. who are very interested in conducting that study. That would be the regulatory significance of that study would maybe be twofold. That would get us E.U. approval and would be a confirmatory study for accelerated approval in the U.S. Obviously, that's a straight-up one-to-one randomization with OS as the primary endpoint, and obviously no crossover. Another potential study design would be a frontline study.
We've got an IST ongoing at MD Anderson where we're adding tovecimig to the TOPAZ-1 regimen of gemcitabine, so there'd be a very straightforward design that would come out of that. That's probably a bigger, longer, more expensive study, but I think that's something on the table. We could also potentially do tovecimig paclitaxel versus paclitaxel, the similar design to COMPANION-002 with OS as the endpoint. There's probably not a lot of enthusiasm for that study. We've already demonstrated a treatment effect in COMPANION-002, but I just want to be complete.
Right
with the question that you asked.
Okay. You are going to go to this next, or I guess first, meeting now with FDA, hopefully, with this confirmatory trial design in hand, or I guess some options in hand. Is the expectation here still that we should expect a BLA submission sometime in the first half of next year, kind of regardless of whatever happens from an FDA feedback perspective?
I would generally say yes, but to be fair to the way you asked the question, if we have a sit-down meeting with the FDA and they say, "No way, no how, no chance," right? I mean, gosh, we would have to listen to that, I think.
Okay.
Especially if they said, "If you send this in, we are going to send it back to you," right? I think absent that, we would move forward with a BLA submission in the first half of the coming year.
Okay. You mentioned the frontline setting as a potential place in which to run a confirmatory trial, and you referenced the MD Anderson-sponsored trial that is ongoing. Should we expect to see any data from that?
I met with the PI from that study, also at ESMO, a couple weeks ago. We are clearly seeing efficacy in that study, coming clearly. We are now going to expand to some additional sites in the MD Anderson network. I would like to get that study fully enrolled in the coming year, and then the primary efficacy endpoint of that study is a six-month PFS landmark. I would love to be close to that by the end of the coming year. That would be the goal.
Okay. Any thoughts on the Akeso phase III?
Oh, yeah.
Biliary data that we saw, and it looks like that data would suggest that we're going to see this agent become standard of care at some point within the major pharma markets. How do you think about having VEGF targeting in the frontline, and then what the implications, if any, of that might be for tovecimig as a second-line agent?
Sure. I was at that presentation two and a half weeks ago, so I was super happy with that result for two main reasons. One, it showed that VEGF targeting in this disease is a valid mechanism to target, which has never been shown before. So I was super happy about that. Secondly, we have our own PD-1 x VEGF-A bispecific, and this is just more data to suggest that this is a real class of drug. The second half of your question, honestly, I don't really worry about too much because I think how many diseases are there with VEGF after VEGF after VEGF is part of standard
Yeah
standard treatment, right? Colorectal cancer. Frontline, second line, third line, fourth line therapy consecutively all have VEGF targeting. Chemo Bev, chemo Bev, chemo Bev, followed by VEGF TKIs. Renal cell. How many VEGF-targeted TKIs are there in renal cell that are simply used consecutively?
VEGF after VEGF, that's just not something I worry about.
Yeah. No, that's a good point. I remember you showed that in your tovecimig later line colorectal data, right?
Yep.
Most of the patients had seen two plus prior lines of Bev.
Correct
Still able to confer responses in some patients in stable disease.
Similarly, in our phase I study with gastric, right?
Yeah.
Patients had ramucirumab, a VEGF receptor-targeted agent, followed by tovecimig, and they still respond. It's not just something I really worry about.
Gastric, I know that you had highlighted gastric and ovarian as maybe some other tumor types in which you would like to do some more development work with tovecimig. Are those plans still in place?
Where we are today is, I think we've had so much investigator interest in tovecimig. We're starting and have started and are continuing to start investigator-sponsored studies. I think we're probably going to use those ISTs as our, quote unquote, "signal finding.
Okay.
Right? We've got a second line gastric study on the table, which is quite fascinating. We're going to do paclitaxel tovecimig with CTX-8371, our PD-1/PD-L1 bispecific. We've also got a glioblastoma study ongoing, and as you and I have talked about this before, I am not afraid for one second to use the word glioblastoma in a sentence. It's just another bad disease, right? That study's ongoing at WashU in St. Louis, combining tovecimig with CTX-471. Met with the PI of that study also in Madrid two and a half weeks ago, and we're sort of clearly seeing signals in that study already. We're also going to do a second line colorectal cancer study combining tovecimig with FOLFIRI, which is also something very, very interesting to think about. And those two, the gastric and the colorectal, are going to get started very soon.
Okay. In both ISTs?
Both ISTs, correct.
Okay. You mentioned the PD-1 x VEGF-A that you have. This is CTX-10726.
Yep.
I know you just presented some of the preclinical data for this at SITC. I think in my naive interpretation of it, certainly appears to support a case for mechanistic differentiation. How do you view this to be different than some of the other molecules in this class? More importantly, why do you think that differentiation will matter clinically?
Sure. Don't be so hard on yourself.
No.
You're not naive. Come on. You are correct. We clearly have mechanistic differentiation. I think one of the things that maybe we have not made clear enough in the past is the PD-1 binding end of our PD-1/PD-L1 and our PD-1 x VEGF-A bispecifics are the same. With both of those drugs, we've now identified PD-1 stripping as part of the mechanism of action. I think we can now say that PD-1 stripping is a characteristic of our PD-1 binding antibody, and I think that's very important. We have done some comparison studies. Not every PD-1 binding antibody does this. It's something characteristic of that drug. Yes, we believe that we are mechanistically differentiated. Gosh, look, I have to be fair here, right? Ipilimumab, I don't know how many patients have been treated in clinical trials with ipilimumab. Thousands and thousands, right?
In order to convert our scientific mechanistic differentiation into clinical differentiation is going to take some time. But, I think it's a good place to start.
Okay. I know you have the phase I dose escalation that's ongoing. I guess it's interesting, your dose escalation schema, you're topping out at 10 mgs per kg.
Which we know is like two to three times lower than where the other sponsors seem to be pushing their PD-1 x VEGF-As in terms of dose. Just any thoughts around why you're at such a lower top dose relative to what we've seen from the class?
Yeah. So, very, very complicated question for sure. One of the things that has very, very much perplexed me in this class of drugs is the doses that are used. I mean, these are just staggeringly high doses. I mean, think about this, like 20 to 30 mg per kg. If you're an 80 kilogram patient, right, we're talking about 2 to 3 grams of antibody for the dose. I mean, that's like, it's crazy.
Yeah.
I don't really understand the dosing. To be fair to your question, I think once we get through the dose escalation, we'll take a look at all the data, and maybe we'll go to 20. I don't know. We haven't really made that decision yet, but I'd like that decision to be data-driven, PK, PD, et cetera.
Okay. Is there any biomarker or translational data that you can evaluate in this phase I dose escalation trial that would somehow either inform or validate this PD-1 cleavage hypothesis?
We're looking at that right now, yes.
Okay. When might we expect to see the phase I dose escalation?
Yeah, we'll give a little status update on that before J.P. Morgan. We're moving into the third dosing cohort now. Haven't seen any dose-limiting toxicities. Hopefully we'll be in the fourth dosing cohort before the end of the year. We'll give an update on some potential efficacy signals that we're seeing as well.
Okay. How do you think about the next development steps?
Yeah
Obviously, single agent dose expansion, you kind of need to do some box checking there, but the field's moving towards combos.
Right
You've got a few assets in your pipeline that would seemingly be interesting.
Right. Yes, we will have some cohort expansions to do. I think that'll be very, very important to do that work. You also are, of course, correct. The entire field seems to be moving toward combinations with ADCs, and other combinations. I think we also have shown some data about the combination with our own CD137 agonist antibody CTX-471. I think that's something to think very hard about. And would there be a way to maybe do a collaboration, combining it with some ADCs or other targeted agents? We've had some inbound on this recently that we're evaluating for combining that drug with some targeted agents, and we're evaluating that right now.
Okay. There's obviously, this is, I don't want to say crowded, but there's a lot of different iterations of the PD-1 x VEGF-A mechanism in clinic.
Oh, it's crowded.
It's crowded, right. You said it. But there's obviously still a lot of strategics, big biotech, big pharma, who have very large oncology footprints who don't yet have one of these things. How would you characterize, and not necessarily from an inbound interest perspective, but how would you just kind of characterize the strategic interest that exists around this class? If you want to contextualize that
Sure
with respect to inbound interest, feel free.
Yeah. I think the way you summarized it was very, very good. I think the more data that are generated with ivonescimab, the better it is for everybody. At this conference earlier today, in one of our meetings with an investor, an investor said to me, "Oh, a year ago, I was talking to big pharma X executive who said they weren't sure if this was going to be a class of drugs. Last week, I talked to big pharma X executive who said, 'Oh, yeah, this is definitely a class of drugs.'" I think the fact that, we've got Merck, Pfizer, BMS, I'll put Summit in that
AbbVie
category as well, AbbVie. There are more not on the list than on the list.
It sort of reminds me in some ways of the early days of PD-1 targeting, right? In the early days of PD-1 targeting, which is only 10 years ago, people were like, "Oh, geez, we've got Pembro, we've got Nivo. What else do we need?" Today, gosh, there's like, I think, eight PD-1 pathway targeting drugs approved in this country, either PD-1 or PD-L1 targeted. I think there's plenty of room for differentiated and better drugs.
Okay. CTX-8371, you mentioned it. It's a little bit more advanced than-
A little bit more advanced, yes.
PD-1 x VEGF-A. You have it in dose expansion now. Just when should we see the next update, and what should that update look like in terms of what we're going to learn?
I think we'll give, again, a status update on that before the J.P. Morgan Conference for sure. Just where we are with enrollment. The study's been enrolling quite well. I think we've got mid-20s patients enrolled in the cohort expansion. Clearly, we're seeing additional signals of efficacy, which is great to see. We'll probably give an update on sort of where we might take that program, I think. Probably that study will probably be fully enrolled in the coming year, so a full data set is probably second half of next year. But I think in the coming months, we'll definitely give an update about where we are with that program.
Okay. Maybe last pipeline question. You did end up initiating that CTX-471
Yes
trial in NCAM-positive tumors.
Yes, that study's now open and recruiting patients.
Okay. Is that on the docket for maybe an update before the end of next year, or is that going to take-
I think before the end of next year, yes.
Next year?
Yes, next year, yes.
Okay.
Not this year.
All right. Balance sheet.
Yeah
Just kind of what that allows you to execute on.
Yeah. Financials, two days ago, $163 million cash well into 2028. So, executing on all these programs, getting us sort of multiple inflection points, I think, in the coming year.
Okay. Anything we didn't
No. Awesome.
talk about that you want to highlight? We're done?
No, this was great. Yeah.
All right. Thank you, Tom.
Thanks again.
Thank you, everyone.