Compass Therapeutics, Inc. (CMPX) Earnings Call Transcript & Summary

Greetings. Welcome to Compass Therapeutics' CTX-009 Phase II results in BTC presented at ASCO GI. [Operator Instructions] Please note, this conference is being recorded. At this time, I'll now turn the conference over to Dr. Tom Schuetz. Doctor, you may now begin your presentation.

Thanks so much. Good morning, everyone, and thanks for joining us today. We're going to review our data for CTX-009 that was presented at ASCO GI on Friday in a Phase II study in patients with biliary tract cancers. We're super excited about the data and excited to talk to you all today about it. We're also going to be joined later today -- we're joined today by Dr. Richard Goldberg, who's Professor and Director Emeritus at the West Virginia University Cancer Institute, who is truly one of the world's experts in GI malignancies and was instrumental in the development of the FOLFOX regimen. I'll be moving through slides, and then we'll have a Q&A session afterwards. So here is our disclaimer. I will be making forward-looking statements today during this presentation. So just a brief review of CTX-009. 009 is a bispecific antibody that targets DLL4 and VEGF-A. DLL4, Delta-like ligand 4, is the cell surface ligand for Notch-1. VEGF-A, of course, is the well-known soluble ligand for the VEGF family of receptors. VEGF-A, of course, is the target of bevacizumab. 009 is -- does not induce ADCC. The Fc fragment is inactive, which we think is ultimately going to be important for the therapeutic window for these drugs. At 10 mg per kg, CTX-009 can deliver approximately the same VEGF capturing capacity as bevacizumab. And to our knowledge, 009 is the only bispecific that has demonstrated monotherapy activity in patients with colorectal cancer and gastric cancer. I'll come back to that point in a minute. In a Phase Ib study, in combination with paclitaxel, 009 was observed to have deep and durable responses in 2 patients with cholangiocarcinoma out of 4 patients treated. That simple observation led to the design of an adaptive Simon 2-stage. This slide shows the design of that study, including the statistical assumptions. So all of these patients have advanced biliary tract cancers, and patients have received 1 or 2 prior regimens. 009 is given at 10 milligrams per kilogram biweekly, and paclitaxel is given at 80 milligrams per meter square of body surface area 3 weeks out of every 4. Statistically, if there were 3 or more partial responses confirmed in the first 21 patients evaluable, that would trigger a decision to move to Stage 2 of the Simon 2 Stage. I will also comment on that decision in 1 minute. So on Friday at ASCO GI, the PI for the study, Dr. Do-Youn Oh presented updated data. You may recall, last May, we disclosed interim data from the study. The study has been run at 4 major medical centers in Seoul, South Korea. So the next few slides, I'm going to go through the data that were presented at ASCO GI on Friday. So this slide presents the patient demographics. 24 patients were enrolled in Stage 1 of the study. The protocol had a provision to enroll 10% additional patients, so instead of 21 patients, 24 patients were enrolled in Stage 1. On the left-hand side of this slide, you can see standard demographic data for a patient population with advanced biliary tract cancer, age, median age in the 60s, men, women, a mix of performance status about 50%-50%, 0 and 1. On the right-hand side of this slide, about half the patients had one prior line of therapy and about half the patients, slightly more, had 2 prior lines of therapy. So this is a mixed second- and third-line patient population. Almost all the patients had prior gemcitabine/cisplatin. On the bottom right, I think importantly, patients with all anatomic subtypes of biliary tract cancer were enrolled, both intra- and extrahepatic cholangiocarcinomas, gallbladder cancer and ampullary cancer. So this is a nongenetic selected population. Ultimately, we'll be targeting the entire second-line BTC population with our studies. So this slide presents the overall response rate. So there were 9 confirmed PRs out of 24 patients enrolled for an overall response rate of 37.5%. I'll put that data into context in 1 minute. A couple of important points about this slide from my point of view. First of all, on the right, inside the PR box, you can see that there are confirmed PRs in at least one patient with each of the 4 anatomic subtypes. And I think also just to state the obvious here, every patient that was evaluable has some measurable decline in their linear tumor burden, so there are no patients above the line. So this is an extremely unusual-looking waterfall plot, of course. The updated Swimmer Plot is on the next slide, where you can see the onset of partial responses. Scans were done every couple of months in this study, partial responses appearing at month 2, month 4, 1 at month 6. You can see we have several "long swimmers" in this study, patients on drug for well over a year, which is something we also observed in the Phase Ib study. So we had more or less disclosed the previous 2 slides previously. The last 2 slides have slight updates from the data that we presented last May. The next couple of slides are new data. So the data cutoff for the presentation at ASCO GI was November 9. So we had a median follow-up of slightly more than 1 year in the study, so we now have maturing progression free survival and overall survival data. So in the table on the left, you can see each of the various endpoints, the overall response rate in the full population, 37.5%. 54.2% had their best overall response as stable disease, of course, leading to a clinical benefit rate of over 90% in this study. The median progression free survival for the entire population was 9.4 months. The median overall survival, 12.5 months. That number compares quite favorably to what you see with gemcitabine/cisplatin/durvalumab in patients treated in the frontline setting. So we believe that, that is a real signal. The duration of response, quite nice at 6.9 months median. And in the smaller box on the top right, you can see a subset analysis where we're looking at patients who received either 1 prior line of therapy or 2. So you can see that if you take the 11 patients who were treated in the second-line, 7 of the 9 PRs occurred in patients treated in the second-line setting for a 63.6% overall response rate confirmed in the patients treated in the second-line. The next slide shows the Kaplan-Meier curves for both progression free survival and overall survival, also fractionated by whether or not patients received therapy in the second- or third-line setting. Median PFS in the whole population, 9.4 months; median OS 12.5 months; median PFS in patients treated in the second-line setting, 10.0 months; the median OS in the second- and third-line setting about the same. On the next slide, we summarize the safety data from this study. So these are all treatment-emergent adverse events, which is important. So this is every AE. Previously, we reported adverse events as treatment-related, and there are some small differences to what we previously presented. So the most common AE was neutropenia. These are Grade 3 AEs, of course, that is expected with paclitaxel. Anemia, thrombocytopenia, again, a common AE associated with paclitaxel. The most common Grade 3 AE seen that is likely related to 009 is hypertension. Hypertension is a well-described adverse event seen with agents that target the VEGF pathway. On the right-hand side of this slide, I simply present data from the labels for bevacizumab and paclitaxel. And you can see 5% to 18% Grade 3 hypertension seen in the various studies of bevacizumab. In the box on the left, we had 6 patients who discontinued the study because of adverse events and those are all listed there. Two of those events, of course, creatinine and BUN. Those, of course, are in the same patient population. I think one of the things that's very important to keep in mind, in a patient population with biliary tract cancer treated in the second-line setting, one of the things that I would encourage you all to do is take a look at the incidence of AEs in the control arm for the FOLFOX study. In the control arm of the FOLFOX randomized study, patients got only supportive care. That's all they got. And the incidence of TAEs was 95% with 52% Grade 3 or above AEs. So that's just the baseline TAE incidents in a patient population with biliary tract cancer, which obviously has a tremendous amount of comorbid disease. So the next slide is just a summary of where we are with the Phase II study, and then I'll talk about how we use that information to plan our Phase III program. So on the box on the left, 37.5% overall response rate in the full population, 64% in patients treated in the second-line setting, Median PFS, 9.4 months, Median OS of 12.5 months, no new safety signals in the Phase II compared with what we saw in the Phase I. On the right-hand side here, I'm trying to put some of these data into context by comparing what you see with FOLFOX in the second-line setting. 5% overall response rate would be comparable to 64%, PFS 4.0 months, Median OS 6.2 months, compares with 9.4 months and 12.5 months, of course. I think very encouraging for us is the data that we're seeing are equivalent to what you see in TOPAZ-1 gem/cis/durvalumab in patients treated in the first-line setting. So shared all that -- almost all of this information, of course, with FDA. Had conversations with FDA last year, and they encouraged us not to move forward with Stage 2 of the Simon 2 Stage and they encouraged us to move forward with a randomized trial. And after discussions, we have landed on this design. This study is now open in the United States. We're initiating sites. This month, we've initiated almost 10 sites so far, patients now beginning the process of being screened for this study. So this is a randomized study in patients who have received 1 prior line of therapy only. So this is a second-line study. It's a 2:1 randomization of 009 plus paclitaxel versus paclitaxel alone. There's no crossover in this study. The primary endpoint of this study is overall response rate. The power calculations for this study, we were quite conservative, I think. We took the overall response rate of FOLFOX at 5%. We simply doubled that to 10% and we took the observed response rate in 009 plus paclitaxel at about 64%. We cut that in half to about 33%. And with those assumptions, this study has a greater than 90% power to detect those differences. BTC, of course, is a very common malignancy that's really increasing in incidence. Some estimates over the next decade or so are projecting a very significant increase in the incidence of biliary tract cancer. The 2023 data have just been released from SEER, 18,400 cases projected in the U.S. As I'm sure you all know, AstraZeneca presents a higher number. We're sticking with our analysis here of the SEER data, but U.S., EU5 and Japan easily north of 50,000 patients annually. And really, despite how common this malignancy is, there's no consensus second-line standard of care in this patient population. So we believe this is a tremendous opportunity for 009. Just in my last 2 slides, I'll just highlight another study with 009 that we have ongoing and just remind you that in our Phase I monotherapy dose escalation study, we treated 6 patients with colorectal cancer in cohort expansions and saw 2 confirmed PRs out of 6 patients treated. And the median time to progression in those 6 patients was 6.7 months. I'll talk more about that in 1 minute. So we now have an adaptive Simon 2 Stage ongoing in the United States where we have treated our first patients in that study. That patient -- that study, we believe, is going to enroll quite rapidly. That's a Simon 2 Stage design also. Patients could have received 2 or 3 prior lines of therapy. So this is a mixed third- and fourth-line study. In the first 37 patients, if we have 10 -- if we have 3 responses, that triggers the decision to move to Stage 2. Let's just talk briefly about that data and how we're thinking about 009 monotherapy in patients with colorectal cancer. Obviously, as you all know full well, colorectal cancer is a much more common disease. Again, I have, for the United States here, 153,020. That's the new 2023 number. Third-line, regorafenib, a 1% overall response rate. LONSURF in the third-line setting has a 1.6% overall response rate in the SUNLIGHT study that was presented 2 days ago at ASCO GI. LONSURF itself had a 0.9% overall response rate in that study. Bevacizumab, of course, when added to LONSURF improved overall survival in the SUNLIGHT study. So we believe there's a real opportunity here for 009 as a monotherapy in patients with advanced colorectal cancer. So here we are today. Our Phase II study in patients with third- and fourth-line colorectal cancer has been initiated and we've treated several patients on that study already. Our Phase II/III randomized study has been initiated in patients with biliary tract cancer in the United States. Patients now beginning the screening process for that study, and we're continuing to open up sites as we get to approximately 30 total sites in the United States. And then finally, considering a third indication that we would begin in the second half of this year, there's clearly scientific data to support the use of this drug in patients with ovarian cancer. We ourselves have monotherapy responses in patients with gastric cancer, and we're going through the process right now of reviewing what our third indication will be. Okay. I'm now going to turn it over to Richard, who's going to do 1 more slide. Richard, as I mentioned, Professor and Director Emeritus at the West Virginia University Cancer Institute. Again, one of the world's leading GI oncologists, and Richard himself was instrumental in the development of the FOLFOX regimen for the treatment of patients with advanced colorectal cancer. On this slide, Richard is going to review some of the safety information for several different regimens in patients with advanced biliary tract cancer. And I'll turn it over to Richard, and then we'll go to Q&A.

Thank you, Tom. All right. So this slide is busy, and I'm going to spend a minute going through the logistics sub. So at the top, you see the different regimens. So CTX is on the left. FOLFOX, which is a standard of care and many think the standard of care for second-line treatment biliary tract cancer. And then the 2 right-hand columns describe the TOPAZ trial with and without durvalumab. So one is just with chemotherapy gem/cis in the third column over, and then gem/cis/durvalumab. And so we're looking at 2 second-line studies and also including third-line patients for CTX and FOLFOX and 2 arms of a first-line study for gem/cis and gem/cis plus durva. And if you look at the overall response rate on the left-hand side, you remember, Tom has said 37.5% overall for a combination of second- and third-line patients but an exceedingly high response rate of 64%, albeit in a small number of patients who are treated in second line. And this compares to a 5% response rate in a very similar population in the Lamarca trial of FOLFOX, ABC-06. That also compares favorably to the first-line responses in both arms of the TOPAZ study, where 26% response rates were seen in first-line therapy. So a 64% response rate in second-line therapy is notable. With respect to overall survival, the 12.5 months of CTX-009 result compares favorably to the first-line study of the new standard of care gem/cis plus durva at 12.9 months and is more than double what it was observed with FOLFOX. Also at this GI ASCO, there was a real-world experience looking at a large database in the United States that actually gave about a 4- to 5-month median overall survival regardless of lines of therapy in patients with BTC. If you look at the progression-free survival, it is also dramatic at 9.4 months as compared to 4 months for FOLFOX and exceeds the progression-free survival observed in first-line therapy with the current standards of care. And speaking about adverse events in biliary tract cancer patients, this is a sick patient subgroup. Individuals who have biliary tract cancer generally will have some degree of obstruction of their biliary tracts, which predisposes them to infection and other potential side effects. And as Tom had mentioned, in the supportive care arm of the FOLFOX study, there was about a 50% rate of grade 3 and higher events in patients who are getting no treatment. So the baseline of this disease is quite different than colorectal cancer, for example, where the patients tend not to be as sick or as symptomatic. If you look at the Grade 3, 4 adverse events, the rate is relatively high at 92%. But this, again, is a sick group of patients, and I'll remind you that many of these patients were being treated in the third line. The toxicity of new drugs is often something that we learn to manage better as we have more experience in delivering these drugs. And that would be my expectation with this drug. Also because there will be a single-line study with only CTX-009 in colorectal cancer, we'll be able to isolate the toxicity related specifically to that drug and not attributable to paclitaxel in that patient population group as we gain more experience. Deaths on study are always a tragedy, and we take that risk anytime we're treating patients with advanced cancer. The 4% death rate on the CTX-009 is actually less than what was observed on the FOLFOX study or in the first-line studies. So again, often, as you learn to use the drug, you can learn to avert severe toxicity through experience. And again, the adverse events leading to discontinuation were relatively high in this. But if you look at what those toxicities were, some of them may have been attributable to disease rather than to treatment in this setting. So we'll have to watch that. I would remind you that 24 patients is not a big sample size. And therefore, the confidence intervals for these events are relatively large. And we need a bigger experience in order to both optimize our use of the agents and to get a real sense of their potential as well as their potential toxicities. So I'll stop there and turn it back over to Tom.

Great. Thank you, Richard. And I'll turn it back over to the moderators here, and we're happy to take Q&A.

[Operator Instructions] Our first question is from the line of Andrew Berens with SVB Securities.

Congrats on all the progress. A couple for me. I think everyone agrees that this is an extremely active drug, at least in the trials we've seen so far. I think much of the investor concerns has been the safety profile. I know much of the toxicity was related to paclitaxel. But when you add a strong VEGF agent, you see almost 100% Grade 3 tox, which I think from the doctor's slide, it was the highest of any of those regimens. Just wondering how you think of this commercially or BTC and then more importantly, how should we think about this drug combined with the various drugs using colorectal cancer like FOLFIRI and FOLFOX. And then in ovarian cancer, how well do you think this drug might play with the PARP inhibitor on the first line? And then one more on why the 009 activity had such a steep step-up going from the third line to the second line in its trial. Is that something that you would expect to see in this trial -- in this setting?

Okay. Several questions there. Thanks, Andrew. So let me go to the first one first. I think for me, the -- and I mentioned it specifically on the call, I haven't -- we haven't necessarily like talked publicly about it before. But when you think about this patient population, and I would encourage, again, everyone to review the safety data in the control arm of the FOLFOX randomized study. So the control arm, which again got nothing, just supportive care in this patient population has a 95% incidence of AEs and 52% Grade 3. So that's the baseline patient population. And I think all investigators that see patients with biliary tract cancers understand that this is one of the -- probably one of the most sort of -- one of them -- has one of the highest incidences of comorbidities, as Richard described, just based on anatomic obstruction of the biliary tree. So adding paclitaxel on top of that, I think what we see in this study is what you would expect. On a patient population that has a baseline of 52% Grade 3 toxicity, we're adding paclitaxel and a potent angiogenesis inhibitor to that. And I think this is a real regimen. And I think that the efficacy data that we're seeing always, it's going to be a risk-benefit calculation commercially. And the efficacy that we're seeing is, I think, unprecedented really. 63.6% overall response rate in the second-line setting has never been observed before to my knowledge. So I think it will be a risk-benefit calculation, getting to your question commercially. You asked about ovarian cancer. Could this agent be combined frontline with a PARP inhibitor? For sure. I think that's a great question. And I think for each of these indications, biliary tract cancer, colorectal cancer, gastric cancer, ovarian cancer, just a reminder that we had a confirmed PR in our Phase Ib study, in a patient with pancreas cancer, in combination with paclitaxel. So how do we think about ultimately moving this drug to the frontline setting in all of those indications? This weekend at ASCO GI, I had 2 conversations with investigators about, just thinking about how to move this drug forward into the first-line setting in patients with biliary tract cancer. So I think we're also going to be doing some preclinical work in the lab here trying to characterize the activity of 009. And I think with a PARP inhibitor, it might be nice to do that. So I think I addressed all your questions, I think.

And then maybe just a follow-up. Just about the rationale for using paclitaxel in the second line as a chemo partner. From the slide about standard of care, it's doesn't seem like that's the one that was on there. And maybe if the doctor could comment on the commercial implications of using pac as a chemo partner and a control in this trial.

Sure. Maybe I'll take the first part of your question and then let Richard address the second part. So I think in my conversations with U.S. investigators, I think folks are not excited about FOLFOX. 5% ORR, 0.9 month improvement in overall survival compared with supportive care. So docs are just not excited about that. Also, we asked regulatory authorities specifically if FOLFOX would be required as a control arm. And in this study, they said no to that. I was encouraged, this weekend, even though the SWOG 1815 study was "overall negative" and gem/cis/nab-paclitaxel is not going to become the frontline standard of care, I think there were some hints in that data that taxanes have some activity in this disease. And I think I asked numerous investigators specifically, and I think the uniform -- the consensus answer that I got was SWOG 1815 really helps our study in terms of thinking about paclitaxel as the control arm. And Richard, if you -- Andrew had asked you to comment on paclitaxel in patients treated in the second-line setting.

Right. Well, as I remember, the reason that paclitaxel became a candidate to pair 009 with was based on preclinical studies that showed some synergy between 009 and paclitaxel as well as 009 and irinotecan. And when additional research was done, it was clear that paclitaxel beat irinotecan in terms of a partner for the drug. In general, we're used to giving cytotoxic drugs with VEGF inhibitors because bevacizumab by itself has virtually no activity in any of the diseases that it's indicated for at the present time. And 009 is distinctive, I think, because of its bifunctionality as a VEGF inhibitor in having single-agent activity. In terms of pairing it with paclitaxel, paclitaxel is not a [ freebie ] in terms of toxicity, particularly with respect to bone marrow suppression. Fortunately, if that becomes a major issue, we can always use colony-stimulating factors to try and moderate the granular cytopenia, which may be more of an issue in patients with compromised biliary tract system. So I do believe that having 2 experiments in terms of the clinical trials, one was single-agent in colorectal cancer and one with a cytotoxic agent in biliary tract cancer will help us understand both the toxicity and the best ways to deliver this drug so that toxicity issues will recede in their importance with more experience.

Thanks for answering all the questions. And congrats again, guys.

Thank you.

Next question is from the line of Joe Pantginis with H.C. Wainwright.

So I want to take some of Dr. Goldberg's questions and go down 2 avenues. So first, I guess, is there anything to point to or the company can comment on this as well with regard to the geographical differences between South Korea and what the U.S. is doing now with regard to the management of these AEs as the study moves to the U.S.? And then secondly, what is the company especially going to be doing proactively, as Dr. Goldberg mentioned, to address these AEs with physician learning and how they're doing it as he says it's a continued evolution?

Thanks, Joe. So yes, I'll maybe take that, and if Richard has anything to add, please chime in, Richard. So in terms of the first half of your question, I think there's really no difference in terms of the management of chemotherapy toxicity between South Korea and the U.S. And I would also highlight, right, especially investigators and treating physicians have decades and decades of experience with managing the cytopenias of chemotherapy. We now have -- G-CSF was first began testing about 40 years ago. So what we're seeing, we're seeing what you would expect from chemotherapy and a VEGF blocker. And we now have 20-plus years of experience with bevacizumab. And the hypertension that you see with bevacizumab, there are now published algorithms for managing that hypertension and mostly anchored around the use of calcium channel blockers. And I'll also highlight for you something, I think, fascinating from the Avastin label. If you see hypertension in the label, you're specifically encouraged not to stop Avastin but treat the hypertension. So we have hypertension and cytopenias. This is not going to be a challenging management issue for treating physicians. To your second question, Joe, we just -- all of this safety information, we review with investigators at our site initiation meetings. There are specific, very specific procedures for managing various AEs in the clinical protocols themselves. Richard, do you have anything to add to that?

Well, I would add 2 things. Often I'm asked, when I talk to investors, is biliary tract cancer in Asia or in South Korea different than biliary tract cancer in the United States? And there actually was a supplemental analysis of the TOPAZ trial presented that showed that there were no differences by population in terms of management and outcomes in that almost 800-patient trial. So that's one answer. And then the other thing is that it's daunting running a Phase II study at the other side of the world because it's not as easy to go and observe how patients are being managed and to meet with investigators to be sure that we're listening to what they're telling us in terms of toxicities and management. And so I think having these studies in the U.S. will give Compass a much better opportunity to look at the drug and its toxicities more closely.

Got it. I really appreciate the feedback, and congrats on showing a survival benefit compared to the prior line.