Crofton, and one of the biotech analysts at Jefferies. It's with great pleasure I'd like to welcome Thomas Schue tz, the CEO of Compass Therapeutics. Thanks so much for joining us today, Tom.
Thanks, Maury. Thanks for inviting us. Appreciate it.
We're going to do fireside chat format, so maybe for those who are new to this story, if you can give a one-minute intro to Compass.
Sure, thanks. Compass, we're based in Boston, Massachusetts. We're a monoclonal antibody discovery and development company in oncology. All of our drug candidates are either monoclonal antibodies or bispecific antibodies. We currently have three drugs in the clinic, which hopefully we'll go over today. Our most advanced program is a DLL4-VEGFA bispecific antibody. We just got our first ever USAN name, which is very exciting for us. So that drug is called Tevesemig. Our second most advanced program is a next-gen CD137 agonist antibody. We call that Drug 471. We also have a PD1-PDL1 novel bispecific antibody in the clinic. That's in the middle of phase one dose escalation. We should be able to report some data on that later this year.
Finally, obviously the intersection of our work on angiogenesis and checkpoint inhibition over the past several years led us to explore the potential of PD1-axis VEGF-axis blockers. After a couple of years of working on that, we now have a VEGF PD1 bispecific antibody in development. That drug is called CTX-10726, and that'll go into the clinic later this year, which will be our fourth drug in the clinic.
Got it. Yeah, good overview, and we'll definitely talk about the individual programs. Maybe to start off for Tevesemig, you reported data in early April. Maybe just recap what you showed there and talk about key aspects that investors need to know about the data.
Sure, thanks. We're currently executing in the United States a randomized trial in patients with advanced biliary tract cancer who have received one prior line of therapy. This is a pure second-line study. It's a randomized trial of Tevesemig plus paclitaxel versus paclitaxel alone. The design of that study was informed by some of our earlier stage studies, and that's a two-to-one randomization of Tevesemig plus paclitaxel versus paclitaxel. The primary endpoint of the study is overall response rate. The key secondary endpoints in this order are progression-free survival, overall survival, and duration of response. The reason I say in this order is because we're using the hierarchical testing method to control alpha spending in the study. Earlier this year, we announced the results on the primary endpoint.
The overall response rate in the combination arm was 17.1%, including a complete response with a disease control rate above 60%. In the paclitaxel control arm, the response rate was 5.3%, with a disease control rate less than 40%. A very, very meaningful difference between the two arms. The difference in response rate, of course, was statistically significant with p- equals 0.031.
Got it. Yeah, I think nice update with the response rate delta there, showing 3X improvement versus the control arm. One of the questions we had is just with the initial data where you showed a much higher response rate, which I think we've got some explanations for why you're seeing that difference, but I guess what are your thoughts on just how to reconcile the 64% response rate?
Sure. Yeah, I think importantly, one very big difference was in the single-arm phase two study. All of those responses were investigator assessed. That is a very big difference. In the randomized trial, of course, all of the responses were assessed by blinded independent central review, so-called BICR, B-I-C-R. All of these responses are centrally reviewed. That is really the biggest difference. In the frontline setting, chemotherapy with Gemcitabine plus a checkpoint inhibitor, which the checkpoint inhibitor includes one of maybe the best drugs ever developed in medical oncology, Keytruda, the response rates to Gemcitabine/Keytruda are in the mid-20s. At 17% in the post-checkpoint inhibitor patient population, we feel very good about that signal.
Got it. Okay, and part of the plan is to report the PFS and OS results in the fourth quarter of this year. You previously guided that approximately 80% of OS events would occur by September. Wondering if this timeline is still intact or could it be earlier or later?
It's definitely not going to be earlier. That's for sure. One of the things that we've discussed publicly is that our modeling on overall survival, the total number of deaths in the study, is occurring later than we had originally modeled. In the second-line setting in advanced biliary tract cancer, one regimen that is used is the three-drug combination FOLFOX, 5-FU, leucovorin, oxaliplatin. In that study called ABC-06, that study, FOLFOX had a 6.2-month median overall survival. If you look at the Kaplan-Meier curves, which I would encourage you all to do, at 12 months, the pooled survival in ABC-06 was only 18%. So 82% mortality at month 12. We used that data in order to model what could occur in our study, and it turns out we were way off.
Today we have 15-month median follow-up from the study, and we're not projecting to hit the mortality level until we have at least 19 months of median follow-up. This is not my opinion. This is just simple math. We already have median overall survival in the study that is way longer than was seen in ABC-06.
Got it. That's really helpful. In your top-line cut, approximately 42% of the control arm patients had progressive disease as their best response. Based on this, what's your expectations for control arm PFS?
Sure. That's an extremely important question. When we reported our data, we reported best overall response from the study. Best overall response is either complete response, again, which we had in the combination arm, partial response, stable disease, or progressive disease. Because it's best overall response, the assessments of response can occur any time during the study, except if it's progressive disease. If your best overall response is progressive disease, that means that occurred at the first scan time point, which is week eight. We already know at week eight, we have 42% progression in the control arm. Our median progression-free survival in the control arm is probably going to be something like two months. In the combination arm with Tevesemig, the progression at week eight was only 16.2%.
We already have substantial separation of the progression-free survival curves, and hopefully that will continue throughout the study and will translate into a very meaningful PFS curve.
Got it. Yeah, it's helpful and a good segue to the next question. The study is powered for a hazard ratio of 0.6 for both OS and PFS. What level of separation between arms would you consider both statistically significant and clinically meaningful, particularly with the context of FDA expectations?
Sure. A hazard ratio less than 0.6 is, I would say, by any definition, massively clinically meaningful. The hazard ratio, just for reference, in the Gemcitabine/Keytruda study for overall survival, the hazard ratio was 0.83. A hazard ratio less than 0.6 will be sort of no-brainer, clinically meaningful. The statistical meaningfulness of that, of course, will be determined by the p-values.
Got it. Okay, that's helpful. On the regulatory front, when do you plan on meeting with FDA next? Are you planning to wait until after the PFS/OS data disclosure in the fourth quarter, or could you meet with them beforehand?
A little bit of a work in progress today as I'm talking to you today. I don't have any update on that today. I think we have always assumed that the PFS and OS analyses would be required for a license application because we have always asked FDA about full approval. We never asked about accelerated approval. It's our intention that this study, with the totality of the data, will support full approval.
Got it. Okay, and it's actually another question we had. With this study, this should be sufficient for confirmatory approval. You don't think they could ask for potentially another?
If we have a hazard ratio less than 0.6 on PFS and OS, it will not be possible to do a second study in this indicator. You would not be able to do such a thing. It is our intention to seek full approval based on this study.
Got it. Okay, and you've mentioned that upcoming frontline data from the MD Anderson IST study could be available by the end of this year. How might those results influence your regulatory discussions or future development plans, particularly if they show stronger efficacy in the earlier lines of therapy?
Sure, that would be great if we saw that, for sure. Yeah, I think just how that study came to be, I think, is interesting in and of itself. The randomized second-line study that we're doing is being conducted at 33 sites in the United States. MD Anderson was the second largest enroller in that study. After they had enrolled, I don't know, six, seven, eight patients or something, they sent us a proposal for an investigator-sponsored study to add Tevesemig to the frontline regimen of gemcitabine, cisplatin, and durvalumab. That study is now ongoing at MD Anderson. I think later this year, we could get some preliminary readout from that study. Ultimately, purely commercially, we'd love to advance Tevesemig to the frontline setting in BTC. I think that study could help inform another study design.
Only because of the way you asked the question, if the efficacy data from that study are blowout, maybe that's enough. I don't know, to sort of inform migration to the frontline setting. I don't know. We'll see.
Got it. Interesting. Assuming that the data later this year on OS and PFS are positive, what are the gating factors for a BLA submission, and what are you seeing about timeline for submission?
Sure. I think so let's fast forward here. Q4 data readout from the study, followed by some sort of pre-BLA interaction with the FDA, would put BLA application inside of the first half of next year. We have fast-track designation already. In an indication where there's literally no labeled second-line therapy, we would certainly get a priority review. That would put our PDUFA date inside of 2026 for a potential launch in the second half of 2026.
Got it. For the program, when you did the update in April, you mentioned safety was as expected and consistent. Wondering if you're providing any additional details on safety profile.
I know only that, again, the study was monitored by an independent data monitoring committee that has met four times during the study and comprehensively evaluated the adverse event data between the two arms and did not see anything that would require any kind of modification to the study.
Got it. Okay, when you do the update later this year, are you going to maybe talk about just the logistics of that and what you're going to have in the top line?
Yeah, I think we'd certainly have the PFS and OS data. We'd have a full set of demographic data. I think we'd have some top-line safety data as well to share at that time.
Got it. Okay, and wondering if you have conducted or plan to conduct any retrospective biomarker analyses, such as looking at DLL4 expression levels or any other genomic markers.
Sure. We are collecting that data from the study. Including, we have collected the diagnostic genotyping data from all of the patients. Obviously, we have not looked at that yet, but we will definitely do a comprehensive evaluation of that after the PFS and OS readouts.
Got it. Would that inform patient selection or, I guess, how could you leverage biomarkers?
I think that analysis, I think, will be more relevant for future studies in other indications. One of the things that we're planning on doing is a more traditional phase two basket study, looking at DLL4 positive indications. We'd love to get that study going in the second half of this year. Ideally, we would get some data out of that in 2026 that could help inform the design of post-approval label expansion studies after the approval of Tevesemig in the second half of 2026.
Got it. Interesting. That is kind of a question I have later on too, just for that basket study. We can jump to that. Maybe for the basket study, how are you thinking about those different tumor types that would be enrolled?
Sure. Just thinking about DLL4 positive indications, that is a very significant patient population. Including renal cell, hepatocellular cancer, ovarian cancer, gastric, colorectal, BTC, of course. I'm not afraid to say the word glioblastoma either. It's just another type of disease. When you look at those seven or eight different tumor types, that's a very substantial commercial market. I think we'd like to use the basket study to help guide our phase IV program to begin in 2027.
We just had ASCO recently, wondering if you're getting feedback from investigators just on Tevesemig and also if you've gotten any feedback from FDA on this basket approach and how to move forward.
We have not submitted the basket study to FDA to answer that question specifically. Yeah, we had a whole series of conversations with investigators and KOLs at ASCO and others. I think those conversations went extremely well.
Got it. Okay, and going back to BTC, once you get to the point where you get the study results, you're going to file the BLA. What steps do you have to take to just figure out CMC and manufacturing and get you ready for commercial?
Sure. Our BLA enabling CMC batches are all underway. We're using a U.S.-based contract manufacturer. It has commercial experience. The CMC will all be ready to go.
Got it. Okay, and back to just the readout, will you announce that the database is locked and then a required period, or?
I think that's an interesting question. I think we'll probably go into a quiet period once the pre-specified number of events has hit, I think. Once that happens, I think we should probably be in a quiet period.
Got it. Okay, helpful. What are your thoughts on ex-U.S., and would you file potentially in Europe and Japan?
Sure, that's TBD, I think. We have some experience in Asia, of course. To be fair, I just want to be fair to your question. We have not approached regulators in Europe.
Got it. Okay, and want to shift gears and talk about the PD1 VEGF bispecific.
Do we have enough time?
No. Definitely been a lot of activity in the space. It would be great to hear your perspective on that and maybe just talk about how what you're doing is differentiated versus some of the other players.
Sure. When we started thinking about this concept of bispecifics, it's not so straightforward because there are two signaling pathways involved here. All four members of those signaling pathways have approved monoclonal antibody-based therapeutics: PD1, PDL1, VEGF-A, and the VEGF receptor. When you think about that, how do you think about bispecifics? We spent an enormous amount of time thinking about this and developed a lot of preclinical data. We ended up in a position where we are similar to some other drugs with a two-by-two valency bispecific that targets PD1 and VEGF-A. In our hands, so take this for what it is, preclinical, PD1 blockade is better than PDL1 blockade in our hands. I think maybe not such a surprising outcome given the fact that I think clinically, I think everybody would agree that PD1 blockers are superior to PDL1 blockers.
Not super surprising. The two components of our bispecific are different from others in development. We have said publicly that we have more potent PD1 blockade than other drugs in development in this field. I think ultimately, having more efficient PD1 blockade is going to turn out to be a very big part of the picture for these bispecifics. We now, and we'll probably disclose some of these data. We'll certainly discuss these data at a scientific meeting, hopefully later this year. I think we'll disclose some of these data before that time. We clearly have data to suggest that our bispecific is superior to other VEGF PD1 bispecifics in this field. I think we have superiority in preclinical anti-tumor models that I think probably reflects the superiority of PD1 blockade that we see in vitro.
I think in the not-so-distant future, I think we're going to start to talk about some of those data.
Got it. Kind of getting into the weeds a little bit, if the PD-1 is more potent than others, presumably you've got a unique epitope going after there.
Yes, we clearly have a unique epitope.
Maybe just talk about how that came about with that discovery. For the VEGF, is that similar to bevacizumab or?
Sure. In terms of the first part, the PD1 blocking epitope that came out of a screen, an antibody screen for PD1 blockade that we did ourselves. That is a homegrown antibody from our discovery group. It is interesting the way you asked the question, I think. I am not sure that drugs in this class are really going to be able to be too well differentiated on the VEGF end. I think most of these drugs are going to have low single-digit nanomolar KDs for blocking VEGF-A. We are obviously very, very similar to that. I think something that is a bit underappreciated in this space is the concentration of VEGF in the body is extraordinarily low. We will have the same kind of VEGF scavenging that Avastin has, for sure.
Got it. It is helpful. You are planning for IND year-end. Are you also planning to maybe talk about just what else you have to do for the IND?
Sure. Of the very big things in the IND preparation, let's start with CMC. We've got CMC all locked down. We have a tremendously productive cell line that our cell line productivity is commercially viable already preclinically. Very happy about that. We've got some GLP tox to do, followed by IND filing in Q4.
Got it. Okay, and with this asset in particular, based on some of the activity that we've seen in the space, can you comment at all just on inbound interest and conversations you're having related to it?
Maybe. No, I think, yeah, obviously, I'm not trying to be glib here. It's an incredibly hot space, whatever that means. There are lots and lots of people interested in this class of drugs.
Got it. Okay, and let's talk about 8371. This is progressing through dose escalation. We haven't seen any DLTs so far in the first three cohorts. What are your initial thoughts on what you're seeing with safety and pharmacodynamic profile?
Sure. 8371 is a PD1, PDL1 bispecific antibody with a potential to be sort of first in class and best in class. We have said publicly that we have not seen any dose-limiting toxicities through the fourth dosing cohort. I feel very, very good about what we're seeing on the safety side. On the pharmacodynamic side, we clearly have appropriate cytokine responses to this drug. On the clinical activity side, again, I think would love to present something at a scientific meeting later this year, but could potentially start talking about some of those data earlier. Clearly in the second half of the year, I think we'll be ready to talk about some of the data from that study.
Got it. Makes sense. Is there more you could say about just what you would be able to share at that meeting?
Yeah, sure. I think we should be going to the fifth dosing cohort in the coming week or so. We would have full safety data from all five dose escalation cohorts, a review of the efficacy data, and the cytokine data.
Got it. Okay, and for your other asset, 471, you've mentioned focusing on NCAM expressing tumors with a phase two to start second half of this year. Just what's the latest status on that and your plans for this program?
Sure. A very timely question because we had sort of multiple investigator meetings at ASCO this past weekend. I think last year in 2024, we presented data from our clinical trials with 471 at two different scientific meetings. We presented clinical data at ASCO 2024, where we showed that we had responses in the post-checkpoint inhibitor patient population. As you know, the post-checkpoint inhibitor patient population is an extraordinarily difficult patient population to treat. We had responses in a basket study where we enrolled post-checkpoint inhibitor patients. We had patients with 17 different tumor types in that basket. Quite a large number of patients with different tumors. In melanoma, we had three out of 11 responses, a 28% response rate. We had one response out of four patients treated with mesothelioma.
Out of three patients with small cell lung cancer, we had one complete response, which is a very, very unusual finding. This is a patient treated in the third line setting after two different checkpoint inhibitor-containing regimens. We had a third line metastatic small cell lung cancer complete response. Quite an unusual thing to observe. We had collected biopsies as part of this study. When we looked at those biopsies, we discovered that the patient with small cell lung cancer, of whom we were able to obtain a biopsy, that patient's tumor was incredibly positive for NCAM, neural cell adhesion molecule. Not surprising, of course, because small cell lung cancer, unlike non-small cell, small cell lung cancer has neuroendocrine features. Not surprising that it's NCAM positive. NCAM is also known as CD56. CD56 is a marker on NK cells.
I think most interestingly, CD56 is its own ligand and receptor. CD56 interacts with itself. We believe that we may have uncovered a novel immunophenotype in the tumor microenvironment. CD56 positive tumors can attract NK cells, and CD56 negative tumors cannot. In a CD56 positive tumor with NK cells infiltrated, the NK cells there can be activated by 471 via CD137. We are activating the NK cells in situ in order to affect tumor cell killing. When we looked at other patients in the study work that was led by Chris Saxenmeier at the company, our Head of Translational Research, we discovered that patients who were NCAM positive were all in the bucket of clinical benefit, so CR, PR, and stable disease. Patients whose tumors were NCAM negative all had progressive disease. A really interesting observation that we are going to test clinically.
We're going to do an NCAM positive basket study, which includes neuroendocrine tumors, melanoma. About 30% of melanomas are NCAM positive. Small cell lung cancer, of course. Really excited about that. Of course, just to emphasize here, we had monotherapy responses in the post-checkpoint inhibitor patient population.
Got it. Interesting. And when that NK cell interacts with NCAM, does that suppress the NK? Is that why the tumor is expressing NCAM, or?
We don't know that yet. That's a very interesting question. From the preliminary work that we've done, I'm going to say no to your question. I think that interaction causes other things to be upregulated on the cell surface of NK cells. That is something we're working on. Stay tuned on that. A very, very interesting question.
Got it. We're pretty much out of time, but wondering for these three additional programs, how do you think about just potential for BD with these three programs? Maybe just comment on cash and key events investors should be focused on.
Sure. Of course, sort of any of these programs, all of these, any of these programs will obviously do what's best for shareholders. I think there's sort of BD potential in all of these. $113 million in cash at the end of Q1, which is runway into 2027. For the rest of 2025, I would say three very big milestones coming up. In the fourth quarter, the PFS/OS readout from our randomized trial of tevesemig in biliary tract cancer. The readout from the dose escalation study of our PD-1, PD-L1 bispecific in the second half of the year. Our Q4 IND filing for our PD-1 VEGF bispecific, which will be our fourth drug into the clinic.
Got it. Thanks so much for joining us today, Tom.
Great. Thanks, Maury.