Q2 2025 Compass Therapeutics Inc Earnings Call
Speaker #3: Greetings and welcome to Compass Therapeutics' second quarter 2025 earnings and business update call. At this time, all participants are in listen-only mode. A question-and-answer session will follow the formal presentation.
Speaker #3: If anyone requires operator assistance, please press *0 on your telephone keypad. As a reminder, this conference is being recorded. It is now my pleasure to introduce Anna Guilford, Chief of Staff.
Speaker #3: Thank you. You may begin.
Speaker #4: Good morning, and thank you for joining us. My name is Anna Guilford. I'm Chief of Staff at Compass Therapeutics. With me today is Dr. Thomas Schultz, CEO and Vice Chair of the Compass Board.
Speaker #4: Our CFO, Barry Shinn, will also join us for a short Q&A following Tom's comments. Earlier this morning, we released our financial results and the business update for the second quarter.
Speaker #4: The slide presentation accompanying this webcast and a copy of the press release are available on our site. Please note, we'll be making forward-looking statements during today's webcast.
Speaker #4: These forward-looking statements are described in our press release issued today and accompanied by SEC filings. With that, I'd like to turn the call over to Thomas Schultz.
Speaker #4: Tom?
Speaker #5: Thank you. We're incredibly excited today to be hosting this call with you this morning. As Anna just mentioned, earlier today, we released our quarterly financials for Q2 2025.
Speaker #5: In addition to the financials, we also provided very important updates for three of our development programs. These updates are summarized on the next slide, and I'll then provide additional details for each of these program updates.
Speaker #5: Most importantly today for our lead program, the DLL4 VegFA bi-specific antibody, in the ongoing randomized trial in patients with advanced biliary tract cancer, there are currently fewer total deaths in the study than we have projected.
Speaker #5: While this disclosure is a simple fact, it is very important to say this sentence differently. More patients are alive today than we have projected.
Speaker #5: I understand clearly that this is an investor call, but it's so important to reflect on what this could mean for the patients enrolled in this study.
Speaker #5: I'll update the timing of the survival analyses in one minute. Next, for CTX8371, our PD-1, PD-L1 bi-specific antibody, we have unexpectedly observed two deep partial responses in the early dose escalation cohorts of the ongoing Phase 1 study.
Speaker #5: One partial response is in a patient with non-small cell lung cancer, and one partial response is in a patient with triple-negative breast cancer.
Speaker #5: Later this year, we'll be initiating cohort expansions in patients with non-small cell lung cancer and triple-negative breast cancer. I will describe CT scans for each of these two patients in a few minutes.
Speaker #5: We hope to present these data at a scientific conference later this year. We're also disclosing results from preclinical head-to-head studies of CTX10726, our proprietary PD-1 VEGF bi-specific antibody, compared to the leading drug candidate in the class of an SMN.
Speaker #5: We will be presenting these data at a scientific conference later this year. So, let's begin with Tevesemig. This slide summarizes the design of the ongoing randomized study in the United States in patients with advanced biliary tract cancer.
Speaker #5: This study is a two-to-one randomization of Tevesemig plus paclitaxel versus paclitaxel alone. The primary endpoint of the study is overall response rate. We announced those results about four months ago.
Speaker #5: The secondary endpoints in this order are PFS, OS, and duration of response. We're using, of course, the hierarchical testing methodology to control for alpha spending in the study.
Speaker #5: The next slide summarizes the current status of the study that we call Companion 002. On the top right, as I mentioned, we achieved the primary endpoint, so the study is positive by definition.
Speaker #5: We had a 17.1% overall response rate, about tripling what was seen in the control arm, with a P-value of 0.031. On the top left box, I'll come back to this point in one minute.
Speaker #5: The trial was fully enrolled in August of 2024, enrolling 168 patients with advanced biliary tract cancer treated in the second-line setting. As of today, we're currently at greater than 17 months median follow-up in the study.
Speaker #5: So let's talk about the secondary endpoints of progression-free survival and overall survival. It's actually hard to say this, but the secondary endpoints are triggered by a total number of deaths in the study.
Speaker #5: So that's how these time-to-event analyses are commonly done. We need 80% OS events to trigger the analyses of progression-free survival and overall survival. Today, we have fewer total deaths in the study than we originally projected when we forecasted that we would be presenting analyses of these endpoints in Q4.
Speaker #5: We made that projection in April of this year. Since that time, the number of deaths in the study has continued to decline. Clearly, the 80% OS event threshold has not been met.
Speaker #5: So, the analyses of PFS and OS are now projected to occur in Q1 of 2026. I think the bottom of this slide is very important.
Speaker #5: Recall the study that was titled ABC06. That study was published in 2021 in Lancet Oncology by Lamarca et al. It was a randomized study of the three-drug combination FOLFOX: 5-FU, leucovorin, and oxaliplatin.
Speaker #5: In patients with biliary tract cancer treated in the second-line setting, so the exact same population that we're treating in Companion 002, if you look at the Kaplan-Meier curves for that study, at 18 months, the overall survival was less than 10% in that study.
Speaker #5: With a median overall survival in the FOLFOX arm of 6.2 months. Where we are today, and again, it's important to point out, this is a pooled survival number.
Speaker #5: We're greater than 20% overall survival, with greater than 17 months median follow-up. Although it is difficult to predict, we probably will not reach 80% mortality until we have something like greater than 20 months median follow-up.
Speaker #5: So very interesting data today. Obviously, this is extremely important. As we mentioned in our press release, we don't know this for certain, but it appears that Tevesemig could be affecting overall survival in this patient population.
Speaker #5: Okay. Let's now move to CTX8371, our PD-1, PD-L1 bi-specific antibody. Just a reminder of the differentiated mechanism of action here. Recall that this drug emerged from a screen using a proprietary technique at Compass.
Speaker #5: In which we can screen bi-specific drug candidates for synergy. That screen identified PDL1 as a synergistic partner for PD1 blockade. As I've discussed many times before, that was a rather unexpected scientific discovery.
Speaker #5: And because of that, we spent a long time investigating the mechanism of action. We published all that data; the PubMed ID for that paper is at the bottom of this slide.
Speaker #5: We have always envisioned 8371 to be on the leading edge of defining next-generation checkpoint inhibition. This mechanism of action, on the right-hand side of this slide, with the bi-specific being unequivocally a cell engager, and quite fascinatingly, the bi-specific actually converts PD-1 positive T cells into PD-1 negative T cells by removing PD-1 from the surface of those cells.
Speaker #5: So, it is a very differentiated mechanism of action. And again, we believe that this drug could be on the cutting edge of defining next-generation checkpoint inhibition.
Speaker #5: We're currently running a Phase 1 study. This study is a standard three plus three dose escalation study. Importantly, we, of course, as all Phase 1 studies do, started with a minimal dose of 0.1 milligrams per kilogram.
Speaker #5: And we have finished enrolling the first four dosing cohorts: 0.1, 0.3, 1, and 3 milligrams per kilogram. We have not seen any dose-limiting toxicities in those 12 patients.
Speaker #5: So again, a three plus three design: three patients times four dose levels, totaling 12 patients. We're currently enrolling the fifth dose level, which will be the 10 milligram per kilogram dose level.
Speaker #5: The patient population in this study, importantly, is all post-checkpoint inhibitor. So, patients with melanoma, non-small cell lung cancer, head and neck cancer, Hodgkin lymphoma, and triple negative breast cancer are being enrolled in this study.
Speaker #5: As I mentioned earlier, we now have two deep partial responses in the first patients enrolled in this study. And again, I will emphasize to you that the first dosing cohort was really a de minimis dose.
Speaker #5: These are CT scans on slide 10. From a patient in the study with non-small cell lung cancer. For reference, these scan images across the top show the patient lying on their back.
Speaker #5: Dark color is air, so that's the lungs. Lighter color is tissue, and the bright white color is bone. Inside of the blue circle at baseline, you can see a 45-millimeter metastatic tumor in this patient.
Speaker #5: Which over time completely disappears. In fact, this patient had 59 millimeters (5.9 centimeters, more than 2 inches total) of metastatic tumor, which actually all disappeared. Really interestingly, in this patient.
Speaker #5: This patient actually had initial pseudo-progression at a lymph node, which has been described with checkpoint inhibitors like Keytruda and Opdivo. It's interesting to speculate on what that might mean.
Speaker #5: Subsequently, all of these patients' target lesions disappeared. We also have two patients with non-small cell lung cancer among the five patients treated so far, with prolonged stable disease, resulting in a clinical benefit rate of approximately 60%.
Speaker #5: So, on the next slide, I'm going to spend a little bit more time on this slide because this slide is incredibly important. So, this is a patient with metastatic triple-negative breast cancer.
Speaker #5: Who had three metastatic target lesions at baseline. I'm showing two of these three lesions on this slide. The third lesion was a lymph node.
Speaker #5: Across the top, same thing as the previous slide, patient lying on her back. Black color is air. So inside the blue circle, you can see a metastatic tumor in the lung which completely disappears.
Speaker #5: By eight weeks, on the bottom, this is a sagittal view. So this is a reconstruction where you're looking at the patient from the side.
Speaker #5: Inside the blue circle, on the bottom left, is a metastasis to the pericardium—the lining of the heart. That metastasis is 52 millimeters in size.
Speaker #5: 5.2 centimeters, more than two inches. Both of these tumors completely disappeared. The other target lesion went from 15 millimeters to 7 millimeters. So, the total tumor decline in this patient from 87 millimeters to 7 millimeters is greater than a 90% reduction in this patient treated in the fourth-line setting, who had previously received pembrolizumab.
Speaker #5: This patient is one of three patients treated in the study with triple-negative breast cancer. So, moving to CTX10726, our proprietary PD1-VEGF bi-specific antibody.
Speaker #5: So this is a drug candidate that we worked on internally at Compass for about 18 months. We nominated it as a development candidate. Earlier this year, we disclosed previously that we have more potent PD-1 blockade in vitro than has been reported for other drugs in the class.
Speaker #5: Over the past six months or so, since we disclosed this as a development candidate, we've locked down our CMC process. I think one of the things that we have not talked much about at Compass is that we've developed a fair amount of proprietary know-how around bispecific manufacturing.
Speaker #5: And our manufacturing process has commercial-level yields for this drug already. Before we're in Phase 1, we're on track to file our IND in the U.S. in Q4 of this year.
Speaker #5: Today, we're announcing some really interesting preclinical head-to-head comparisons of CTX10726 with Ivanesemab. These next three slides are, of course, complicated preclinical experiments, and I'm going to go through these in some detail.
Speaker #5: In this study, we're using a transgenic mouse model that expresses PD-1 and PD-L1 as in humans. So the extracellular domains of PD-1 and PD-L1 are not in humans.
Speaker #5: So you can directly test human-targeted checkpoint inhibitors in this experiment. Importantly, though, there's no human VEGF in this experiment. I'll come back to that point in a minute.
Speaker #5: Here, we're directly comparing the PD-1 blocking arms of 10726 with Ivanesemab. You can see that, in terms of tumor control in this mouse model, in a head-to-head study, 10726 is superior to Ivanesemab.
Speaker #5: For those of you who are looking at these graphs very carefully, you can see that the control and Ivanesemab arms end at week 28.
Speaker #5: Because those animals had to be sacrificed due to uncontrolled tumor growth. On the next slide, in the same model, we compare 10,726 directly with pembrolizumab.
Speaker #5: So again, this experiment is simply testing the PD-1 blocking arm of 10726 and comparing that head-to-head with pembrolizumab. And 10726 is equivalent to pembrolizumab in this study.
Speaker #5: The next slide is a little bit more complicated experiment. So this is a xenograft experiment in which a human tumor, a non-small cell lung cancer model called HCC822, is injected into mice.
Speaker #5: That tumor secretes human VEGFA. So this experiment tests both PD-1 blockade and VEGFA targeting. These experiments, of course, are done in immunocompromised mice. So a human immune system is added back to the mice.
Speaker #5: PDMC is peripheral blood mononuclear cells. So, on the bottom left, you can see the control in black. Bevacizumab and Ivanesemab are about the same in this experiment.
Speaker #5: And the best drug in this head-to-head experiment is CTX10726. As I mentioned earlier, we will be presenting these data at a scientific meeting later this year.
Speaker #5: And filing our IND, which is on track for Q4. So, on my last slide, we have some updated milestones here. I think over the next six quarters, we have an incredibly rich milestone list.
Speaker #5: So let's start with Tevesemig. In Q1 of the coming year, we'll read out our important progression-free survival and overall survival data from our randomized study.
Speaker #5: I would imagine that that readout would be followed by a very robust interaction with the FDA, which would put us into a position to potentially file a license application in the middle of 2026.
Speaker #5: Of course, we have fast track status—fast track designation—so I would anticipate that we would get a priority review. We will be initiating our planned basket study for Tevesemig following that analysis in patients with DLL4-positive tumors.
Speaker #5: Including potentially gastric cancer, ovarian cancer, hepatocellular cancer, et cetera. Still working on that design, but that study should be ready to go in the coming months.
Speaker #5: For CTX471, we're planning to initiate our NCAM-positive basket study later this year. That biomarker was discovered in the Phase 1 study of CTX471, and we presented scientific data for that drug twice last year.
Speaker #5: And then finally for 8371, very important update on that program today. The next step is initiating the cohort expansions in patients with non-small cell lung cancer and triple-negative breast cancer.
Speaker #5: Those cohort expansions will begin later this year. With clinical data from that those cohort expansions next year. Hopefully, presenting the dose escalation data at a scientific meeting later this year.
Speaker #5: Finally, for 10,726, the preclinical update that we've provided today. We're going to present that data at a scientific conference later this year. IND filing in Q4.
Speaker #5: Which should put us in a position to read out clinical data next year. Lastly, as part of our disclosure today, we ended Q2 with $101 million in cash.
Speaker #5: Which is cash runway here at Compass into 2027. Executing on all these programs and delivering the milestones that you see here. So with that, I'll thank you again for joining the call today.
Speaker #5: I'm happy to take questions.
Speaker #3: Thank you. If you would like to ask a question, please press star one on your telephone keypad. A confirmation tone will indicate your line is in the question queue.
Speaker #3: You may press star two if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset.
Speaker #3: Before pressing the star keys, one moment while we pull for questions. Our first question is from Andrew Barrons with Learning Partners. Please proceed.
Speaker #5: Okay, so two questions for me. You're allowing crossover on the PAC arm to Tevesemig, so is there any chance that a decreased S you're seeing reflects performance of Tevesemig from, you know, the drug crossover?
Speaker #5: Can you give us any idea how many patients are crossing over on progression from the control arm? And then you mentioned interacting with the FDA.
Speaker #5: Any comments on potential breakthrough designation? And then I have one on the DLL4 biomarker testing after that.
Speaker #4: Okay. Two important questions, thanks, Andrew. So, on your first question, I just went back to the study schema. Yes, we allow progression in the control arm, and we allow crossover in the control arm.
Speaker #4: Following centrally confirmed progression, I'm going to answer your second question next. Ballpark, about half the patients crossed over in the control arm. So, the statistical methodology that we're using is called the rank preserving structural failure time.
Speaker #4: Was the same methodology used in the IDH1 inhibitor analysis in biliary tract cancer? That statistical analysis adjusts the overall survival analysis for crossover. That is the defined primary method of analysis of the overall survival endpoint.
Speaker #4: In terms of the general first question, you know, I think potentially the answer to your question is yes. You know, that potentially even in patients treated in the third-line setting, you know, Tevesemig could be extending overall survival, and would not that be fantastic?
Speaker #4: Because if you look at the presentation of the clarity data, the rank-preserving structural failure time analysis was a little bit better than the intent-to-treat analysis, which indicates that the drug was active even after crossover.
Speaker #4: Now, in our presentation of the overall response data, and that data is currently in our corporate deck on our website, the rate of progressive disease at week eight was substantially different in the control arm than in the combination arm.
Speaker #4: 42.1% progression at week eight versus 16.2% progression. So it doesn't seem like paclitaxel alone is particularly effective. So I'm happy to take your additional question, Andrew.
Speaker #5: Yes. And then just on BTD, is there any thoughts about doing that or would it not be if you're if you're waiting for the OS analysis, would there not be any real benefit to applying for that at this point?
Speaker #4: Probably not.
Speaker #5: Yeah. You know, I think that's, you know, sort of a work in progress. You know, but it's obviously something we would, you know, obviously we're thinking very, very, very seriously about.
Speaker #5: Okay. And then, just wondering, did the DLL4 biomarker testing change from that which was employed in some of the Korean trials?
Speaker #4: It's the same. We kept transferred that analysis into the US and we're using we use that. And we're continuing to use that in the evaluation of biopsy specimens from some of the studies that we've done.
Speaker #5: Okay. Thank ou.
Speaker #4: Thanks.
Speaker #3: Our next question is from Mori Raycroft with Jefferies. Please proceed.
Speaker #6: Hi. This is Amin An for Mori. Thank you for taking our questions. A couple of questions from us. You mentioned the PFSOS analysis happening in Q1.
Speaker #6: Can you clarify whether enough events might come in during Q4 to allow for analysis in early Q1? Or are you expecting that 80% of the event threshold will actually be reached in Q1 itself?
Speaker #6: And I have a follow-up.
Speaker #4: Sure, thanks for the question. That's a very hard question. You know, what we had originally projected is that we would hit the 80% event threshold by the end of Q3.
Speaker #4: What we know today is that it's not going to happen. So beyond that, it's almost impossible to project accurately. And what we have simply said is we believe that the analysis will read out in Q1.
Speaker #6: All right. Sounds good. And when it comes to the readout, should we be thinking about a full data set release, or will some of the data be held back for medical meeting presentation?
Speaker #4: Yeah. I think we're planning to present a priority data set at that time, which would be PFS, OS, demographic data, and top-line safety data.
Speaker #4: With the rest of the data to be presented at an ICal meeting.
Speaker #6: Okay. Very helpful. anks.
Speaker #3: Our next question is from Michael Schmidt with Guggenheim. Please proceed.
Speaker #7: Hey, good morning. Thanks for taking my questions. I had just a logistical question. So, if the companion OO2 study, in fact, succeeds on PFS and OS, I guess what else needs to be done to support a possible BLA submission around, you know, CMC, for example?
Speaker #7: How far along are you with some of the other sections that are required for BLA submission? And then I had a...
Speaker #4: Sure.
Speaker #7: separate question on 8371.
Speaker #4: Okay, thanks, Michael. Yeah, great question. Our so-called PPQ batches, or Process Performance Qualification, the batches that are required for a BLA submission, are all underway.
Speaker #4: So, our CMC process should be very much locked down. So, that should not be limiting.
Speaker #7: Okay, great. And then, yeah, on 8371—interesting. New data here today. Could you just provide some additional commentary on the dose level where these responses were seen?
Speaker #7: And yeah, have you seen any other patients with tumor size reduction? Or in fact, I think you mentioned two other patients with lung cancer with stable disease.
Speaker #7: Did you see tumor shrinkage in those as well?
Speaker #4: So a couple of questions there. The non-small cell lung cancer response was at the 0.3 milligram per kilogram dose level. And the triple negative breast cancer response at the 3.0 milligram per kilogram dose level.
Speaker #4: We're not releasing any other clinical data at this time. You know, again, hoping to present all of that data at a scientific meeting later this year.
Speaker #4: Including the patients from the 10MIG per kid cohort.
Speaker #7: Okay. Anything else you can share on the treatment history of the two case studies? Obviously, they did have a PD1 inhibitor before, but anything else you could share there?
Speaker #4: Yeah. Most of these patients, you know, sort of a typical, you ow, phase one population, you know, many many lines of therapy. You know, this you know, this patient with triple negative breast cancer had three lines of therapy in the metastatic setting.
Speaker #4: You know, including previously some neoadjuvant and adjuvant therapy. So, you know, typical phase one population heavily pretreated. All the patients in the study having received prior therapy with a checkpoint inhibitor.
Speaker #7: Great. Thank you.
Speaker #3: Our next question is from Byron Amin with Piper Sandler. Please proceed.
Speaker #8: Hey. Yeah. Hi, guys. Thanks for taking my questions. Maybe just to start on Tevesemig. Your projections for the OS analysis and timelines for Q1; is that based on the current event rate that you're seeing?
Speaker #8: You know, you mentioned that the event rate had slowed since your projection earlier this year. Or is the projection based on a lower event rate from what you know one would anticipate?
Speaker #8: I guess I'm trying assess confidence on the Q1 analysis.
Speaker #4: Yeah. Great question. So, I think the short answer to your question, Byron, is yes. Our projection is based on the current mortality rate that we're seeing.
Speaker #4: And you know, I ink over the last approximately four or five months, you know, we've clearly seen a decrease so we're basing the Q1 projection on the current rate.
Speaker #8: Got it. Okay. And then as far as the phase one ISP, any update on that in terms of when we can expect first data from the quadruplet combination?
Speaker #4: No. I don't have an update on that. The study at that time at this time that study is, you know, enrolling patients at MD Anderson, but I don't have an update today.
Speaker #8: Okay. And then I do have several questions on 8371. Congrats on the data in the dose escalation. Cohort. So I just wanted to maybe ask for the non-small cell lung cancer patient, the patient had zero centimeters tumor why is that patient not considered a complete response?
Speaker #4: Yeah. That is a great question. And actually, that question applies to the triple negative breast cancer patient as well. Because so with this patient, this patient had some non-target lesions that did not qualify the patient as a CR.
Speaker #4: For the triple negative breast cancer patient, the target lesion three is actually a lymph node. And a lymph node less than 10 millimeters in the short axis.
Speaker #4: And this is seven. By resist 1.1 is not pathological. So this patient's target lesion response was actually read as a CR. This patient also had non-target lesions that did not disappear.
Speaker #4: So, because of that, this patient is a resist PR.
Speaker #8: Got it. And then maybe just a few more on 8371. You mentioned that the triple negative patient had prior pembro. What about the non-small cell lung cancer patient?
Speaker #8: Did they have prior PD1 and what was the therapy? And then I guess and then also can you talk about what their PDL1 status was when they received 8371?
Speaker #4: Oh, what a great question. So the answer to that question is, I don't know. We did not read biopsy patients. Before the Phase One study, I do know that the non-small cell lung cancer patient at their diagnosis.
Speaker #4: So take that for what it's worth. Had a very low PDL1 expression, but we did not read biopsy patients for the Phase One study.
Speaker #8: Great. Thank ou.
Speaker #3: Our next question is from Steven Willy with STIFO. Please proceed.
Speaker #9: Hey. Good morning, guys. This is Tulia on for STIFO. Congrats on the progress. I just have two questions: one on Tevesemig and one on CTX10726.
Speaker #9: Just to start with the Tevesemig, Tom, like I know that you will present patient demographics later when you know both PFS and OS analysis are ready.
Speaker #9: But like the fact that you haven't accrued you ow like enough you ow like any death events how confident are you that these patients are actually reflective of like historical clinical trials and just the rest of you know like a real world data?
Speaker #9: So that's the first question. And the second question on the CTX10726 by the way, very nice impressive preclinical data in terms of tumor shrinkage.
Speaker #9: What can you what can you say about the safety data and are you guys planning to present any preclinical data like prior to or soon after you ow IND submission?
Speaker #9: Thank you.
Speaker #4: Thanks, Tulia. Complex first question about demographics in this study. I'll simply say you know it's hard to know without the final data set you know and you ow cross trial comparisons to demographics.
Speaker #4: I think I probably can't really answer that. You know, I think I'll simply say that the randomization in this study was stratified.
Speaker #4: By three important prognostic variables: performance status, zero versus one; metastatic disease outside the liver, yes or no. The vast majority of these patients had metastatic disease outside the liver—something like 80%.
Speaker #4: And it was finally it was stratified by anatomic subtype intrahepatic olangiocarcinoma or other. So because the randomization is stratified, I think the demographics in the two treatment arms will be very well balanced.
Speaker #4: So you know I think that's very important. Yeah. Thanks for your comment on 10726 yes. We will be presenting scientific data for 10726 at a scientific conference later this year.
Speaker #3: Our next question is from Aiden Hosinov with Ladenburg-Salmon. Please proceed.
Speaker #7: Hi. Good morning. Congrats on the progress this quarter. A couple of questions from us. So first on Tevesemig, the question is about the duration of response.
Speaker #7: In the Tevesemig arm of the trial, could you provide any comments on the duration of response, and are these patients who initially responded still on the trial?
Speaker #4: Thanks, Aiden. So, I went back to the study schema here. We don't have any analysis of duration of response at this time, because in the statistical methodology, the first two secondary endpoints to be analyzed are PFS and then OS.
Speaker #4: So duration will be the last secondary endpoint analyzed. So I 't have any information on that. I don't you know I don't most of the patients are in survival follow-up.
Speaker #4: I don't I don't have a number today. On how many patients are still on the study. I'm sorry. Sorry about that, Aiden.
Speaker #8: Okay, that's okay. Another question is on the GFPD1 bi-specific. So, just trying to understand how the future is going to look for this asset.
Speaker #8: So, in the future, how do you see the regulatory path for your GFPD1? And is it going to be as a singular path, or like a head-to-head to pembro, nivo?
Speaker #8: Just to just curious about the your thoughts on this.
Speaker #4: Sure. You know I think great question, obviously. You know So I think the way we've been thinking about this is I you know think the regulatory path you ow depends on you ow very you know very thoughtful indication selection.
Speaker #4: And you know where our thinking is with this drug is where we want to explore indications where both VEGF targeting and PD-1 targeting as monotherapies have been demonstrated to be effective.
Speaker #4: So what are some of those? So renal cell you know nivolumab and VEGF kinase inhibitors. Gastric cancer where the VEGF receptor blocking antibody Simrasa is approved.
Speaker #4: As well as PD-1 targeted agents, obviously in hepatocellular cancer, where Bevacizumab and Atezolizumab are frontline standard of care. You know, and maybe you know something like endometrial cancer.
Speaker #4: You know where VEGF kinase inhibitors have also been shown to be effective. And I think for some of these indications, you know say you know the post PD1 VEGF patient with renal cell cancer.
Speaker #4: You know I think I think you know those could be singular pathways to approval. You know I ink the non-small cell lung cancer indication you know is going to be obviously as you know incredibly competitive and we would probably not go there first.
Speaker #8: Okay. Thank you. Very helpful.
Speaker #3: Our next question is from Robert Driscoll with Whitbush Securities. Please proceed.
Speaker #10: Thanks. Morning, Tom. Thanks for taking the question. Maybe just a follow-up on Byron's question. For the 83-71 expansion cohorts, do you expect to select patients based on PD-L1 expression at this stage?
Speaker #4: So we don't. We expect to leave the selection criteria the same as for the dose escalation portion of the study.
Speaker #8: Okay. And then anything you can say with regards to immune-related adverse events here, kind of you acknowledging we're still in dose escalation?
Speaker #4: Sure. Yeah. You know, it's interesting. We believe that the way this drug might work, although we have some data to support this preclinically, ultimately we're going to need a lot more data to support what I'm about to say.
Speaker #4: So just that caution. You know we believe this drug could be anchored in the tumor microenvironment by PD-L1, where it can provide very high concentration PD-1 blockade in the tumor microenvironment.
Speaker #4: So, you know, I'll simply say that in the first four dosing cohorts, we've not seen any dose-limiting toxicities. And look, as a next-generation checkpoint inhibitor, there's no reason to believe that the safety profile might not be better.
Speaker #8: Got it. Looking forward to the update here. Thanks, Tom.
Speaker #4: Thanks, Robert.
Speaker #3: Our next question is from Sean McClutchins with Raymond James. Please proceed.
Speaker #11: Hey, guys. Thanks the question. Just a couple for me. How are you thinking the necessary magnitude of benefit over paclitaxel on PFS? Given that paclitaxel not a commonly used chemo and second line biliary tract cancer and you know what gives you confidence that you've cleared the, say, the PFS bar?
Speaker #11: For clinical adoption over FOLFOX. And then, separately, could you give some context on how you're thinking about overall survival (OS) and how the FDA may be approaching OS?
Speaker #11: You know what you need to see as a trend on an ITP basis versus a crossover desert basis? Thanks.
Speaker #4: Thanks, Sean. So for the first question, I have sort of a two-part answer perhaps. So the first part, I'll simply summarize what the statistical power calculations are for the PFS analysis.
Speaker #4: So the PFS analysis is 80% powered for a hazard ratio of approximately 0.6. So a hazard ratio of 0.6 or lower would, I think, obviously be spectacular.
Speaker #4: You know, I take your point about paclitaxel. I think our overall response rate data showed that we had 42.1% radiographic progression in the paclitaxel arm at week eight.
Speaker #4: Suggests that the median PFS in the paclitaxel arm is going to be in the two to 2.5 month range, about the same as has been seen with FOLFOX, for example, in the FOLFOX versus FOLFIRI randomized trial.
Speaker #4: You know we recently completed some market research that was done by sort of a very well-known leading market research firm and I think we were very pleasantly surprised at the KOL feedback on PFS from that market research.
Speaker #4: Which frankly suggests that a hazard ratio of 0.6 would be off the charts. So, you know KOLs you know would be happier just given what they know about FOLFOX.
Speaker #4: You know with you know even less benefit. But a hazard ratio of 0.6 would be incredible. The second question I don't have any information on your second question.
Speaker #4: Never got any specific feedback from the FDA about the difference between the ITP analysis and the RPSST analysis of overall survival.
Speaker #8: Understood. Thanks.
Speaker #3: As a inder, to star one on your telephone keypad if you would like ask a question. Our next question is from Joe Pankines with HC Wainwright.
Speaker #3: Please proceed.
Speaker #7: Hey, Tom. Good morning. Thanks for all the details today. So first, on Tevesemig, first the logistical question. Can you just remind us of the level of meetings that you've already had with the FDA and what is planned, and what role you know the potential for accelerated approval based on response rates has had in those discussions?
Speaker #7: Number one. And then number two, obviously there's a lot of talk here about the control arm. There's a lot of variables that are in this study.
Speaker #7: You've obviously talked about you ow it doesn't seem like paclitaxel in the control arm is contributing to anything. You know with regard to the data you're seeing.
Speaker #7: So with that, I want to ask about what are your thoughts on the perceived risk of any better than expected impact from the control arm specifically from the fact that obviously these patients are receiving you know excellent clinical care.
Speaker #7: I am, it sounds like a rhetorical question, but I just wanted to get your views on the perceived risk.
Speaker #4: Yeah. Sure. Thanks. Thanks, Joe. Maybe I'll e the second one first. So you know again, in terms of the control arm, I'm again I'm going to go back to the the rate of progressive disease in the control arm at week eight.
Speaker #4: 42.1% radiographic progression at week eight. So we already have substantial progressive disease at week eight. And PFS, of course, is defined in the standard way.
Yes. Uh, so what we are, uh, currently planning, um, you know, in patients with triple negative breast cancer and non non small cell, lung cancer, um, uh, uh, randomized study to 2 doses. Um, you know, a small randomized study, something like 50 patients ballpark, um, you know, in order, you know, to start to explore a couple of doses have not picked the doses yet, um, because we want to get all the data from the 10 mg per kick, a dose level, um, we should have
Most of that data, um, by the end of this quarter, um, which would put us in a position, uh, to initiate those cohort expansions in Q4.
Got it. Thank you, Tom.
Thanks Joe.
There are no further questions at this time. I would like to turn the floor back over to Tom for closing remarks.
Great. Uh, thank you so much and I'm just going to go uh, to the last slide here again. Uh, thank you everyone uh, for joining today and just highlight, um, you know what the next
12 to 18 months could look like for us.
Read out from our randomized trial and patients with biliary tract cancer, followed by a robust interaction with the FDA and then potentially a license application, which would obviously be incredibly exciting.
A couple more clinical trials, uh, with Tessa Megan 471, and I think really exciting today, our cohort expansion for 8371. Is that us? As I mentioned earlier, we have always positioned 8371 to be on the cutting edge of defining next-generation checkpoint inhibition, and the data that we've reported today really puts us on track to achieving that goal. And then, lastly, our P1 VEGFA by-specific.
Antibody 10726. We have preclinical differentiation uh from Ivan. Me really looking forward to getting that drug in the patients in 2026 and Reporting uh Phase 1 clinical data.
Thanks again, everybody.
Thank you. This will conclude today's conference. You may disconnect your lines at this time, and thank you for your participation.