Please note this conference is being recorded. At this time, I'll now turn the conference over to Dr. Thomas Schuetz. Doctor, you may now begin your presentation. Thanks so much. Good morning, everyone, thanks for joining us today. We're gonna 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 gonna 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. We'll have a Q&A session afterwards. Here is our disclaimer. I will be making forward-looking statements today during this presentation. Just a brief review of CTX-009. CTX-009 is a bispecific antibody that targets DLL4 and VEGF-A. DLL4, Delta-like ligand 4, is the cell surface ligand for Notch1. 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. CTX-009 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 mgs per kg, that CTX-009 can deliver approximately the same VEGF capturing capacity as bevacizumab. To our knowledge, CTX-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 I-B study, in combination with paclitaxel, CTX-009 was observed to have deep and durable responses in two patients with cholangiocarcinoma out of four patients treated. That simple observation led to the design of an adaptive Simon's two-stage. This slide shows the design of that study, including the statistical assumptions. All of these patients have advanced biliary tract cancers, and patients have received 1 or 2 prior regimens. CTX-009 is given at 10 milligrams per kilogram bi-weekly, and paclitaxel is given at 80 milligrams per meter squared of body surface area three weeks out of every four. Statistically, if there were three or more partial responses confirmed in the first 21 patients evaluable, that would trigger a decision to move to stage 2 of the Simon Two-Stage. I will also comment on that decision in 1 minute. 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 four major medical centers in Seoul, South Korea. The next few slides, I'm going to go through the data that were presented at ASCO GI on Friday. 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. 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, 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 two prior lines of therapy. This is a mixed second and third-line patient population. Almost all the patients had prior gemcitabine plus 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. This is a non non-genetic selected population. Ultimately, we'll be targeting the entire second-line BTC population with our studies. This slide presents the overall response rate. There were nine 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. Couple 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 four anatomic subtypes. I think also, just to state the obvious here. Every patient that was evaluable has some measurable decline in their linear tumor burden. There are no patients above the line. 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, and 1 at month 6. You can see we have several quote-unquote long swimmers, in this study, you know, patients on drug, for well over a year, which is something we also observed in the phase I-B study. We had more or less disclosed the previous two slides previously. The last two slides have slight updates from the data that we presented last May. The next couple of slides are new data. The data cut off for the presentation at ASCO GI was November 9th. We had a median follow-up of slightly more than one year in the study. We now have maturing progression-free survival and overall survival data. 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, and durvalumab in patients treated in the front line setting. We believe that that is a real signal. The duration of response, quite nice at 6.9 months median. In the smaller box on the top right, you can see a subset analysis where we're looking at patients who received either one prior line of therapy or two. You can see that if you take the 11 patients who were treated in the second line, seven of the nine PRs occurred in patients treated in the second-line setting for a 63.6% overall response rate confirmed in 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. These are all treatment-emergent adverse events, which is important. This is every AE. Previously, we reported adverse events as treatment related, and there are some small differences to what we previously presented. 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. You can see 5%-18% Grade 3 hypertension seen in the various studies of bevacizumab. In the box on the left, we had six 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. You know, 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. The incidence of TAEs was 95%, with 52% Grade 3 or above AEs. That's just the baseline TAE incidence in a patient population with biliary tract cancer, which obviously has a tremendous amount of comorbid disease. 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. 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, P FS 4.0 months, median OS 6.2 months compares with 9.4 and 12.5, 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. Shared all that, you know, 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 Two-Stage, and they encouraged us to move forward with a randomized trial. 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. This is a randomized study in patients who have received one prior line of therapy only. This is a second-line study. It's a 2-to-1 randomization of CTX-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 CTX-009 plus paclitaxel at about 64%. We cut that in half to about 33%. 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. Really, despite how common this malignancy is, there's no consensus second-line standard of care in this patient population. We believe this is a tremendous opportunity for CTX-009. Just in my last, two slides, I'll just highlight another study with CTX-009 that we have ongoing and just remind you that in our phase I monotherapy dose escalation study, we treated six patients with colorectal cancer in cohort expansions and saw two confirmed PRs out of six patients treated. The median time to progression in those six patients was 6.7 months. I'll talk more about that in 1 minute. We now have an adaptive Simon's two-stage ongoing in the United States, where we have treated our first patients in that study. That study, we believe, is gonna enroll quite rapidly. That's a Simon T wo-Stage design also. Patients could have received two or three prior lines of therapy. This is a mixed third and fourth line study. In the first 37 patients, if we have thee 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 two days ago at ASCO GI, lonsurf itself had a 0.9% overall response rate in that study. Now the bevacizumab, of course, when added to lonsurf, improved overall survival in the SUNLIGHT study. We believe there's a real opportunity here for CTX-009 as a monotherapy in patients with advanced colorectal cancer. Here we are today. Our phase II study in patients with 3rd and 4th 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. Finally, considering a 3rd 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 gonna turn it over to Richard, who's gonna do one 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. 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. I'll turn it over to Richard, then we'll go to Q&A. Thank you, Tom. All right. This slide is busy, and I'm gonna spend 1 minute going through the logistics of it. At the top you see the different regimens. CTX is on the left, FOLFOX, which is a standard of care, and many think the standard of care for 2nd-line treatment, biliary tract cancer. Then the two right hand columns describe the TOPAZ trial with and without durvalumab. One is just with chemotherapy Gem/Cis in the 3rd column over, and then Gem/Cis durvalumab. We're looking at two 2nd-line studies and also including 3rd-line patients for CTX and FOLFOX, and two arms of a 1st-line study for Gem/Cis and Gem/Cis + Durv. 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 were treated in second line. 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 of both arms, of the TOPAZ study, where 26% response rates were seen in first line therapy. A 64% response rate in second line therapy is notable. With respect to overall survival, the 12.5 month CTX-009 result compares favorably to the first line study of the new standard of care Gem/Cis + D urv, at 12.9 months and is more than double what it was observed with FOLFOX. Also, at this ASCO GI, there was a real world experience looking at a large database in the United States that actually gave about a four to five 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 four months for FOLFOX, and exceeds the progression-free survivals observed in first line therapy with the current standards of care. In speaking about adverse events in our 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. 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 were getting no treatment. 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%. 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. That would be my expectation with this drug. 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 any time we're treating patients with advanced cancer. The 4% death rate on this CTX-009 is actually less than what was observed on the FOLFOX study or in the first line studies. Again, often as you learn to use a drug, you can learn to avert a 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. 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. I'll stop there and turn it back over to Tom. Great. Thank you, Richard. I'll turn it back over to the moderators here, and we're happy to take Q&A. Thank you. If you'd like to ask a question at this time, please press star one from your telephone keypad, and a confirmation tone will indicate your line is in the question queue. You may press star two if you'd like to remove your question from the queue. For participants who are using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. One moment please while we poll for questions. Thank you. Thank you. Our first question is from the line of Andrew Berens with SVB Securities. Please proceed with your question. Hi. Thanks for doing this call, Tom, and congrats on all the progress. A couple for me. I think everyone agrees this is an extremely active drug, at least in the trials we've seen so far. I think much of the investor concern 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 tops, which I think from the doctor's slide was the highest of any of those regimens. Just wondering how you think of this commercially with BTC, and then more importantly, how should we think about this drug combined with the various drugs used in colorectal cancer like FOLFIRI and FOLFOX? In ovarian cancer, how well do you think this drug might play with the PARP inhibitor in the first line? One more on why the CTX-009 activity had such a steep step-up going from the third line to the second line in this trial. Is that something that you would expect to see in this trial, in this setting? Okay. Several questions there. Thanks, Andrew. Let me go to the first one. First, you know, I think, you know, for me, the... And I mentioned it specifically on the call, I haven't, you know, we haven't necessarily, like, talked publicly about it before. 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. The control arm, which again got nothing, just supportive care in this patient population, has a 95% incidence of AEs and 52% Grade 3. That's the baseline patient population. I think all investigators that see patients with biliary tract cancers, you know, understand that this is, you know, one of the highest incidences of comorbidities, as Richard described, you know, just based on anatomic obstruction of the biliary tree. Adding paclitaxel on top of that, you know, I think what we see in this study is what you would expect, you know. On a patient population that has a baseline of 52% Grade 3 toxicity, you know, we're adding paclitaxel and a potent angiogenesis inhibitor to that, you know, and I think this is a real regimen. I think that the efficacy data that we're seeing, you know, always it's gonna be a risk-benefit calculation commercially, you know. The efficacy that we're seeing is, I think, unprecedented really. A 63.6% overall response rate in the second line setting has never been observed before, to my knowledge. You know, I think it'll be a risk-benefit calculation, getting to your question, commercially. You asked about ovarian cancer. You know, could this, you know, could this agent be combined frontline with a PARP inhibitor? For sure. You know, I think it's a great question. You know, I think for each of these indications, you know, biliary tract cancer, colorectal cancer, gastric cancer, ovarian cancer. Just a reminder that we had a confirmed PR in our phase I-B study in a patient with pancreatic cancer, in combination with paclitaxel. How do we think about ultimately moving this drug to the frontline setting in all of those indications? you know, this weekend at ASCO GI, I had, you know, two conversations with investigators about, you know, just thinking about how to move this drug forward into the first line setting in patients with biliary tract cancer. you know, I think, you know, we're also gonna be doing some preclinical work in the lab here, you know, trying to characterize, you know, the activity of CTX-009, you know, and I think with a PARP inhibitor it might be nice to do that. I think I addressed all your questions, I think. Yeah. 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 didn't seem like that's the one that was on there. Maybe if the doctor could comment on the commercial implications of using pacli 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. You know, I think in my conversations with U.S. investigators, I think folks are not excited about FOLFOX. You know, 5% ORR, you know, 0.9 month improvement in overall survival compared with supportive care. Docs are just not excited about that. You know, also, you know, we asked regulatory authorities specifically, you know, if FOLFOX would be required as a control arm, in this study, you know, they said no to that. You know, I was encouraged this weekend, you know, even though the SWOG S1815 study was overall negative, quote-unquote, and gemcitabine paclitaxel is not gonna become the frontline standard of care. I think there were some hints in that data, you know, that taxanes have some activity in this disease. I think I asked numerous investigators specifically, and I think the uniform, the consensus answer that I got was, you know, SWOG S1815 really helps our study in terms of thinking about paclitaxel as a control arm. 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 CTX-009 with was based on preclinical studies that showed some synergy between CTX-009 and paclitaxel as well as CTX-009 and irinotecan. When additional research was done, it was clear that paclitaxel beat irinotecan in terms of a partner for the drug. You know, 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. CTX-009 is distinctive, I think, because of its bi-functionality as a VEGF inhibitor and having a single agent activity. In terms of pairing it with paclitaxel, you know, 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 granulocytopenia, which may be more of an issue in patients with a compromised biliary tract system. I do believe that having two experiments in terms of the clinical trials, one with single agent and 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, Richard. Thanks for answering. Thanks for answering all the questions, and congrats again, guys. Thank you. Next question is from the line of Joseph Pantginis with H.C. Wainwright. Please proceed with your question. Hi, everybody. Thanks for taking the question and all the details. I wanna take some of Dr. Goldberg's questions and go down two avenues. 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.? Secondly, you know, what is the, you know, 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 said it's a continued evolution. Thanks, Joe. Yeah, I'll maybe take that and if, you know, if Richard has anything to add, please chime in, Richard. In terms of the first half of your question, yeah, I think there's really no difference in terms of the management of, you know, chemotherapy, toxicity, you know, between South Korea and the U.S. I would also highlight, right? Especially, you know, investigators and treating physicians have decades and decades of experience with managing the cytopenias of chemotherapy. We now have, you know, GCSF was first began testing about 40 years ago. We're seeing, you know, we're seeing what you would expect from chemotherapy and a VEGF blocker. You know, we now have 20+ years of experience with bevacizumab and, you know, the hypertension that you see with bevacizumab, you know, there are now published algorithms, you know, for managing that hypertension and mostly anchored around the use of calcium channel blockers. I'll also highlight for you something I think fascinating from the Avastin label. You know, if you see hypertension in the label, you know, you're specifically encouraged not to stop Avastin, but treat the hypertension. You know, so we have hypertension and cytopenias. You know, this is not, you know, not gonna be a challenging management issue for treating physicians. To your second question, Joe, you know, all of this safety information, you know, we review with investigators at our site initiation meetings. You know, there are specific, very specific procedures for, you know, managing, you know, various AEs in the clinical protocols themselves. Richard, do you have anything to add to that? Well, I would add two 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? 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. That's one answer. The other thing is that, you know, 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. 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. Congrats on showing a survival benefit, compared to the prior line. Thanks a lot. Thank you. The next question is coming in the line of Dane Leone with Raymond James. Please proceed with your question. Hi, thank you for taking the questions. Yeah, there's just maybe a couple technical questions on my end that maybe could help people here. Do you any chance you guys know offhand what the systemic therapies were that the patients in this Korean study received? In the poster preso, it was about 45.8% had one prior systemic therapy, and then the remainder had two prior systemic therapies. We didn't see the actual disclosure of what they had received. you know, obviously the question goes to, is that comparable to what patients are going to receive in your study? Then I have a follow-up question. Okay. Thanks, Dane. I'm just going back to one slide. I have one piece of information for you is on this slide. 23 of the 24 patients, 96%, had received a gemcitabine cisplatin regimen frontline. You know, these patients got you know, Western world, if you will, frontline standard of care. You know, not every patient got only Gem/Cis. You know, many patients got Gem/Cis plus something else. Three of the patients, in fact, got Gem/Cis/Durvalumab. Fascinatingly, you know, two of those three patients had PRs, the 3rd patient had stable disease. You know, rolling out of Gem/Cis/Durvalumab, you know, I think we have very good data to support that. In the second-line setting, patients had a mix of many different things, 5-FU-based chemotherapies. Only a handful of patients, you know, had FOLFOX in the second line. Many patients also participated in second-line clinical trials. The second line set of therapies was diverse. Okay. It sounds fairly comparable. They were either. Yes. Got cis or were cis ineligible, got gemcitabine. Thank you. That's super helpful. In terms of the setup on the pivotal study, you know, we've seen more of these studies in later line indications where there's not really a standard of care, where when you have the combination, in this case, you know, 009 plus paclitaxel, you're using the combination agent as the control arm. What's your team's interpretation of how the FDA would tackle that from a regulatory point of view? You know, would they consider paclitaxel a true control where they could give you the survival metrics on the label, you know, in kind of like a normal controlled setting? Do you think the interpretation's gonna really be more on that ORR and mDOR basis? You know, not that that really matters from clinical interpretation. Sure. Just kind of curious from how the regulatory agency might handle it. Thank you. Sure. Sure. Thanks, Dane. I mean, the, the very short answer to the question is, you know, this will obviously be a quote unquote "review issue," you know, which is, you know, not surprising. We do know that, you know, FDA has signed off on the design of the study. To your point, you know, in terms of, you know, studies where there's really no consensus standard of care, you know, we're using the, you know, scientifically rational control arm here. To your specific question, you know, would that, you know, support, you know, survival, language, in a label? We have not had that conversation with FDA. I'm sorry, if I may, just one last quick one, for the doctor on the line here. You, you'd made the point that, the fair point around the confidence intervals of the study that we're discussing here today. Maybe you could put a nuance on that. You know, for our interpretation, we are looking at the lower bound of the confidence interval rather than the point estimate. Even the lower bounds on the survival metrics seem to convey, you know, better outcomes than what we've seen in the controlled studies or the comparable studies that we've been discussing. Is that a fair statement or do you have a different interpretation? Thank you. No, I absolutely believe that's a fair statement. The activity rates of this are unprecedented in this disease and relatively unprecedented for, you know, new agents given alone or in combination with chemotherapy in GI cancer in general. You know, as somebody who's taken care of a lot of these patients, I'm really excited about this, and that's part of the reason I'm interested in trying to help Compass get it objectively evaluated so that we can really understand its impact and potential impact. You know, based on these data, it would seem likely to me that a head-to-head comparison with the current first-line regimen wouldn't be out of bounds to consider in the future. Excellent. Thank you very much. Thanks, Richard. For those of you still with the slides up, I just went to in response to Dane's question, the lower bound of the confidence interval on the OS median is 10.9 months. Our next question is from the line of Robert Driscoll with Wedbush. Please proceed with your question. Great. Thanks, Tom. Just a couple of questions on the phase II/III randomized study. Are you stratifying patients at all? If there's an interim analysis built in? Yes, to the first question, we are stratifying patients. There are three stratification factors in the study. The first is metastatic disease, yes or no. Disease outside the liver or biliary tree is stratified versus disease confined to the liver or biliary tree. That's number one. Number two, we're stratifying based on anatomic subtype, and that stratification is intrahepatic cholangiocarcinoma versus other. There's some data to suggest that patients with intrahepatic cholangiocarcinoma do a little bit better. The third stratification factor is performance status 0 versus 1. Those are the three stratification factors for the randomization. Your second question, is there an interim efficacy analysis? The answer is no. Got it. Then for the small number of patients with targetable molecular alterations in the second line, are you assuming they're kind of excluded from the study or is there a way to capture those patients? Those patients are excluded from the study. Got it. Thanks very much. Thank you. At this time, we've reached the end of our question and answer session. I'll turn the call over to Dr. Schuetz for any closing remarks. Well, I just wanted to thank everyone, today for your time. You know, really appreciate the work that everyone is doing. Happy to answer any follow-up questions that anybody might have. I also wanna thank once again Richard Goldberg for participating in the call today. Thanks again, everyone. Have a great day.