Great. Thank you, everyone, for joining us this afternoon. My name is Daniel Bronder. I'm a biotech associate here at Cantor, and it is our pleasure to welcome Thomas Schuetz, Co-Founder and CEO of Compass Therapeutics. For those in the audience who are less familiar with the Compass story, can you level set and highlight some recent key achievements and the milestones that we should be looking out for over the next six to 12 months?
Sure. Thanks, Daniel, and thanks to Cantor for inviting us here today. Really appreciate it. So, Compass, we're located in Boston. We're a monoclonal antibody discovery and development company in oncology. We currently have three drugs in the clinic, and we're driving toward a fourth IND submission later this calendar year. Our lead program is a drug called tovecimig, which is a DLL4xVEGF-A bispecific antibody. And earlier this year, we announced that that drug hit the primary endpoint in a randomized study in patients with advanced biliary tract cancer treated in the second-line setting. So, we recently provided a very important update to the status of that randomized trial, and we updated in our Q2 earnings release about a month ago that we're observing fewer deaths in that study than we had originally projected.
We're now driving toward the overall survival and progression-free survival endpoint readouts in Q1 of the coming year. That'll be an extremely important milestone for us coming up in the next approximately, call it, six months or so. We also announced recently that in a Phase 1 dose escalation study of our PD-1 / PD-L1 bispecific antibody that we call CTX-8371, we have deep responses in patients with non-small cell lung cancer and triple-negative breast cancer. The triple-negative breast cancer patient, in particular, was treated in the fourth-line setting, and that patient had over 90% decline in their linear tumor burden. The non-small cell lung cancer patient actually had 100% decline in their linear tumor burden. We have, I would say, really solid signals of efficacy already in our phase one dose escalation program.
The IND that we're driving toward at the end of this year is for a PD-1x VEGF-A bispecific antibody that we call CTX-10726, and we also announced some data recently that we will present at a scientific meeting later this year, suggesting that that drug is superior to drugs like ivonescimab in preclinical studies. Take that for what it is. These are preclinical studies, but when we embarked on head-to-head comparisons, you know, the hypothesis was that this drug would be better, and indeed it was, so we're looking forward to bringing that drug into the clinic and developing clinical data next year.
Very cool. Lots going on. Let's stick with tovecimig first, since this is the most advanced program. You already had mentioned that you met the primary endpoint of your COMPANION-002 trial. As we head into the Q1 2026 readout, what efficacy benchmarks on PFS or OS would you consider sufficient to meet potential regulatory approval?
Sure. So, one very important caveat here is FDA never articulated a benchmark for us. So, I just want to be super clear about that. So, you know, the benchmark that we're expecting, you know, is a mix of some market research results, KOL interviews. And I think it's also important to keep in mind that in the patient population that we're treating, which is patients with advanced biliary tract cancer treated in the second-line setting, there's literally no labeled therapy. So, there is no bar, really, to think about, because there are no approved drugs for this patient population. In a randomized trial, the three-drug combination of FOLFOX, 5-FU, leucovorin, and oxaliplatin, compared with best supportive care, had a 0.9-month improvement in median overall survival. So, those are the results of one randomized trial.
We, as part of preparing for commercial efforts at Compass, recently completed some third-party market research that was, you know, done by one of the, you know, well-recognized leading firms, and I must tell you, I was quite pleasantly surprised by, you know, KOL comments in that, you know, even a very modest improvement in progression-free survival would be considered very meaningful for these docs, because they have nothing, so you know, in answer to your question, you know, I think the study is powered for a hazard ratio of 0.6. It's about 80% power to detect a hazard ratio of 0.6, which, I mean, a hazard ratio of 0.6 would be a staggering treatment effect, so if we see that, you know, we would feel incredibly good.
Okay, so mostly focusing on the hazard ratio and what we'll see.
Yeah, and I think regulators, in general, focus on the hazard ratio rather than any absolute delta in median overall survival. Just for your reference, the power assumptions for PFS were 3.0 months in the control arm and 5.3 months in the combination arm. So, you know, that gets you to a hazard ratio of about 0.6, which would be incredibly meaningful if we were to demonstrate that.
Okay, cool. So, what's your plan for the approval path forward? Will you try to seek accelerated approval based on the ORR, or are you going to wait it out until you have survival data, the HR, and if you hit that?
Yeah, yeah. So, importantly, the PFS and OS data will come at the same time. So, the trigger for both of those time-to-event analyses is 80% OS events. So, we will have the PFS and OS results at the same time, which we are currently projecting to occur in Q1 of the coming year. So, we've never had a conversation with FDA about accelerated approval. It has always been our plan to file for full approval, to seek full approval.
Okay. That makes a lot of sense, given that you will have the totality of data available.
Exactly. ORR, PFS, plus OS, we would seek full approval.
Speaking of the OS event trigger that has been pushed out moderately to the first quarter next year, where do you think the OS is lagging behind? Do you think it's on both arms, or is it focused on one arm? Can you give us some clarity?
Yeah, so super important here, so we get pooled mortality data, so we cannot know, you know, which arm these patients are in, so that's very, very important, so we are following pooled mortality, and that's the information that we get, so and I think it's also important to just articulate very clearly what is meant by pushed out. Pushed out means that more patients are alive, period. That's what it means, so that is an incredibly good thing, so you know, and just based on what we saw in the ORR analysis, where we saw 42.1% progression in the control arm at week 8 compared to 16.2% in the combination arm, you know, there's no, we have no suggestion from the response rate data that paclitaxel is behaving in any way differently from FOLFOX, so and the median overall survival for FOLFOX is 6.2 months.
This coming weekend, we will hit 18 months of median follow-up in the study. 18 months of median follow-up, and we're not approaching 80% mortality. What we're seeing is clearly different from what has been seen before in this disease.
Okay, okay. And we're assuming that the projection that you're using now to determine that the data will come in Q1, or that it will trigger the event in Q1. How confident are you that you will be able to show us these data in Q1, and how quickly after you reveal the data, you flip the data card, will you be able to submit a BLA?
So, when we made a projection previously, we based it on the mortality that we were seeing in the study. And what happened over the past approximately six months is that the mortality that we were seeing substantially decreased month to month. And it's as if we are seeing the formation of a tail on the Kaplan-Meier curves in real time. So, what we have done is we have projected based on the mortality that we have seen over the past approximately five months or so. And so, that's the best we can do. So, you know, we believe that we'll drive toward this result in Q1. And I'll say the same thing that I said at banking conferences in June.
If the data are later than Q1, that means the treatment effect is overwhelmingly positive, you know, because by that time, we'll have two years of median follow-up, which would just be staggering. So, you know, right now, you know, we're confident in that. I think to answer the first part of your question, you know, I think we would get those data, you know, have an interaction with the FDA as quickly as possible, which could put us in a position to submit a licensing application in the middle of next year.
Okay. Exciting times ahead. You've alluded to the absence of labeled drugs in second-line BTC before. Are you at all concerned, or rather, how confident are you in the agency accepting paclitaxel as a, you know, adequate control arm in your randomized trial?
Sure. I've been asked this question many, many times, you know, and many times people ask me the question in this way, right? Why did you select paclitaxel as the control arm? Okay? The answer to that question is incredibly simple. FDA told us we had to do that. So, FDA is the one who picked paclitaxel as the control arm. So, we asked FDA if we needed to have a FOLFOX control arm, and they specifically said no, because they don't consider FOLFOX to be standard of care, because there is no standard of care.
Okay. So, you're feeling fairly confident that it shouldn't be a problem?
Yes.
Okay. Cool. And, you know, so far, in terms of efficacy, you know, we've discussed a little bit the benchmarks. Let's switch to the safety profile. You haven't said very much, but just to give us a sense, can you tell us a little bit about potential discontinuation rates, potential AE events? How safe is the drug combination?
Sure. So, I don't know the discontinuation rate. So, to answer that question specifically, what we have said publicly is that the study, the randomized study, has an independent data safety monitoring committee, and that committee has met four times during the conduct of the study and did not identify any new safety signals. So, you know, that's an independent committee of experts that reviewed the arm-specific safety information throughout the study. From our Phase 1 and Phase 2 data, the adverse event profile we see is quite similar to what you see with Avastin. So, hypertension is the most common adverse event we see, whether or not tovecimig is used as a monotherapy or in combination with chemotherapy. And there are now published algorithms for managing the hypertension associated with Avastin. So, that's the most common AE that we see that's drug-related.
Okay. Cool. So, I think we've, you know, covered efficacy and safety. Let's switch gears a little and, you know, take a look at the future and talk about commercialization. Tell us a little bit about the commercial opportunity in second-line BTC. You've mentioned before that the opportunity might be a little bit larger than appreciated, and what kind of market research have you done to support your conviction in this?
Sure. So, earlier this year, you know, again, as we're preparing, you know, for potential commercialization, you know, we conducted a comprehensive, you know, third-party market research analysis of the patient population, the treatment landscape. We also interviewed payers, you know, as part of that effort as well. So, you know, I think as opposed to many other diseases, epidemiology in oncology is not particularly complicated, right? Because, you know, the SEER database, S-E-E-R, you know, the Surveillance, Epidemiology, and End Results Database of the National Cancer Institute, just has all the data. So, you know, you can interrogate that data. If you look at the epidemiology data, there are 23,000 patients annually in the United States. There are now claims aggregators, such as Komodo Health, for example, you know, that can look at U.S. claims data.
We used Komodo, and Komodo comes up with something like 25,000 new patients annually in the United States. So, it is a very substantial commercial opportunity. Based on the work that we did, we estimate that about two-thirds of those patients would get to second-line therapy. So, that would be about 15,000 new patients annually, call it ballpark triple of the platinum-resistant ovarian cancer market. So, whatever, you know, in our Phase 2 study, patients were on drug, you know, something like six months. The Jazz-Zymeworks drug, Ziihera, recently publicly disclosed their pricing at about the HER2 bispecific, which was labeled in biliary tract cancer. That drug is $35,000 a month. So, in terms of a fully penetrated market, the math here is pretty straightforward. You know, six times $35,000 times 15,000 patients, if you just put that into a calculator, that number is greater than $3 billion annually.
That's the fully penetrated market opportunity, and that is second-line BTC in the United States alone. You know, I think our ultimate commercial vision for this drug is it really defines the concept of next-generation angiogenesis disruption, and our ultimate goal would be to replace Avastin in all of the Avastin indications, which would make the commercial opportunity for this drug globally a 10-figure, 10 to 11-figure number.
How are you planning to capture that market? Are you planning to build out your own sales force, or are you planning to look for a partner?
Sure. You know, I think, as Barry, our CFO, likes to say, we're going to do what's in the best interest of shareholders. You know, we're currently preparing to commercialize this drug ourselves in BTC in the United States. You know, if a partnership makes sense outside of the United States, we would certainly look very carefully and closely at that. But we're currently preparing to commercialize this drug ourselves in the United States. I think one of the things about biliary tract cancer, as opposed to maybe some other malignancies, is biliary tract patients with biliary tract cancer, unfortunately, have some complex, you know, anatomic adverse events. So, many of these patients have obstruction of their biliary tract, and that requires, you know, endoscopic, you know, ERCP, retrograde cholangiopancreatography envisioning. So, you know, that's not something that's done in the community.
So, many of these patients are seen at tertiary referral centers. So, we believe we could cover that patient population with a sales and marketing force of around 50 people, you know, with very, very targeted sales and marketing force. So, we're preparing to commercialize this drug ourselves.
You've mentioned before that you're already able to achieve commercial yields for your bispecific antibodies, including something that we'll talk about next year, PD-1xVEGF-A bispecific. Where are you in regards to prepare for a commercial supply and commercial readiness ahead of a potential BLA submission?
Yes. You know, I think this is something, you know, that has been somewhat underappreciated at Compass, you know, which is we've developed some really important know-how in terms of bispecific antibody manufacturing. And, you know, in the first generation of bispecific antibodies, I think we're really challenged by really low manufacturing yields. But through, you know, several years of really focused effort, we've been able to crack that code. And, you know, we now have, you know, we probably have something like five-fold higher production yields that you see with drugs like Humira. So, you know, one of the most successful commercial monoclonal antibodies ever, you know, our bispecifics manufacture with yields about five times greater. So, we have commercial-ready manufacturing processes with cost of goods that, frankly, would be in the small molecule range.
We are, you know, so we feel very, very good about where we are with our manufacturing yields. All of our manufacturing efforts to the second part of your question for tovecimig to prepare for a potential license application, all that work is underway.
Excellent. At this point, it might make a little more sense to switch over to your other programs.
Can I ask a question before we?
Yeah, of course.
Tom, remind me, you have crossover in the trial?
Yes.
So, are you worried now that we're entering this late stage of the trial and it seems to be taking longer than anticipated that this is going to be a problem when it comes to the analysis?
No. For those of you who didn't hear, I was asked a question from the audience about a concern about crossover affecting the overall survival analysis. We're using a statistical method that was pioneered in the ClarIDHy study. That's C-L-A-R-I-D-H-Y, ClarIDHy. That was a randomized study of the IDH1 inhibitor, ivosidenib, in biliary tract cancer. That study allowed a crossover, and they pioneered a statistical technique which corrects the survival analysis. It's called the Rank Preserving Structural Failure Time. That statistical method, we prospectively declared in both our protocol and statistical analysis plan. It's a statistical method that corrects survival analyses for crossover. We'll use that method. You know, the ClarIDHy study led to the approval of the IDH1 inhibitor in BTC. We have, I would say, perfect regulatory precedent for the use of that technique.
Cool. Well, thank you so much for the question from the audience. You know, on the PD-1xVEGF-A bispecific CTX-10726, there's obviously been a significant amount of interest given the data from Summit and Akeso on their drug in that space, ivonescimab. That said, there's now several players ahead of you in the space, and some feel that the space is getting crowded, and there might not be enough room for another entrant. What's your take on that thesis?
Sure, so you know, first of all, in terms of ivonescimab, the Summit-Akeso drug, you know, I think the most important aspect about that drug, from my point of view, is that I think that drug has established this set of bispecifics as a new class of drugs, okay? So, in a head-to-head study in patients with non-small cell lung cancer against Keytruda, of all things, that drug on PFS had a hazard ratio of 0.5. So, let's just stop there, right? You know, there's pretty much nothing that can say that they had a hazard ratio of 0.5 compared with Keytruda. So, that's great.
So, you know, I think part of my answer to your question is somewhat simple, which is when Keytruda and Opdivo were first approved, everybody said, "Oh, gosh, boy, the whole PD-1 field is so crowded," you know, but now we have eight, nine, 10 different PD-1 or PD-L1 inhibitors approved. You know, and I think the best example of the initial race with PD-1 and PD-L1 blockers, in my view, honestly, was Regeneron, right? Cemiplimab, right? What do they do? They define an indication, which is metastatic squamous cell of the skin, okay? When I was seeing patients at the Dana-Farber Cancer Institute in Boston, I never even heard of a patient with metastatic squamous cell of the skin.
A few hundred patients annually in the United States, but Regeneron said, "Hey, you know, let's find a niche indication where we can get this drug approved," and that's exactly what they did. You know, I think there are now, you know, several drugs in the clinic, as I mentioned, eight, nine different PD-1 or PD-L1 inhibitors approved, and I would just simply say, with one of the things that I think we learned from the PD-1 and PD-L1 development is, gosh, there's always room for better drugs. So, let's just make better drugs. That's what we're trying to do.
Okay. And your IND filing is expected in the fourth quarter of this year. You nominated this candidate quite a while ago. What were the gating steps that prevented you from moving a little bit faster in the past, and what gives you confidence that you will hit the ground running once you enter the clinic?
Sure. So, you know, we were very thoughtful, I think, about how we approached the development of a bispecific targeting these two pathways. Because if you think about it, you know, each of these two pathways, you know, VEGF-A and PD-1, both the ligand and the receptor in both pathways have approved monoclonal antibody therapeutics. So, VEGF-A, of course, Avastin, VEGF receptor, Cyramza, PD-L1 and PD-1 that we've already talked about. So, when you think about drugging both pathways at the same time, how do you think about that? Do you go after PD-L1 plus VEGF-A, which some people have done? So, we spent a long time investigating various permutations of this, and we, frankly, ended up at a very similar place to ivonescimab, which is a two-by-two valency bispecific targeting a PD-1 and VEGF-A.
And I think we're trying to look at indications, frankly, I'm just being honest with you, sort of inspired by how Regeneron, you know, developed cemiplimab. So, we're thinking about indications where both VEGF blockade and PD-1 access blockade are approved as monotherapies: renal cell, liver, gastric, endometrial cell. So, in renal cell, you know, PD-1 blockade with Opdivo plus VEGF kinase inhibition with Cabo, that has been frontline standard of care for quite some time. So, can we think about indications like that, you know, where we could perhaps establish a footing and potentially define a fairly rapid path to approval?
If you were to rank those four indications that you just mentioned based on the probability of success and the competitive landscape, as well as the commercial opportunity?
Sure. Nobody's asked me that before. You know, I would probably, at the top of the list, I would put hepatocellular cancer because frontline standard of care in hepatocellular now is bevacizumab plus atezolizumab, so straight-up PD-L1 blockade plus VEGF capture. So, I think the probability of success in hepatocellular would be very high. Obviously, that's a tremendously large commercial opportunity, probably ballpark something like 40,000 patients annually in the United States. So, you know, and sorafenib has moved to second-line standard of care once it was displaced by the combination of bev-atezo without any real data. So, could we define second-line standard of care in hepatocellular? So, I'd probably rank hepatocellular first. Renal cell is much more competitive than gastric and endometrial cell. So, I'd maybe put them in that order.
Excellent. Well, thank you so much for that. And then maybe to close out our fireside chat, give us an outlook on what would define success for Compass in 2026.
Sure. You know, I think in the first half of the year, you know, we're going to get our readout from our randomized trial of tovecimig. We'll get the PFS and OS data, and that will really define the regulatory path forward for us. So, you know, once we get those data, a successful FDA interaction followed by a license application, you know, that's a tremendous definition of success, I think. You know, we didn't get a chance to talk about our PD-1 x PD-L1 bispecific antibody today, CTX-8371, but we have, you know, really solid efficacy signals already in the middle of a dose escalation Phase 1 study. So, we're going to do cohort expansions in patients with triple-negative breast cancer and non-small cell lung cancer. So, developing those clinical data in 2026, potentially getting on a pathway to registration in triple-negative breast cancer, that would be unbelievable.
You know, and then finally, you know, our fourth drug in the clinic, you know, a next-generation novel PD-1x VEGF-A bispecific antibody that we discovered and developed ourselves. And we were able, based on our announcement at the beginning of August, to do a financing. We now have pro forma $230 million in cash at the end of Q2, which has run way well into 2028, which will allow us to execute and deliver these data on all of these programs.
Great. Thank you very much for joining us today.
Thanks, Daniel.