Welcome to the Kairos Pharma Key Opinion Leaders Webcast Event. Today, all participants will be in a listen-only mode. Please note that today's event is being recorded. I would now like to turn the conference over to Jules Abraham from CORE IR, the company's investor relations firm. Please go ahead. Thank you, Chris. Good afternoon, and thank you all for participating in today's conference call. Earlier today, the company released a press release detailing the interim efficacy analysis for the phase II trial of ENV105, also known as carotuximab, in combination with standard of care hormone therapy, apalutamide, for the treatment of advanced prostate cancer. A copy of that press release can be found on the company's website at investors.kairospharma.com under the News and Events tab. Joining me today on the call from Kairos Pharma's management team are Dr. John Yu, Chief Executive Officer, and Dr. Neil Bhowmick, President and Chief Scientific Officer. During this call, the management, alongside their partners and colleagues, will be making forward-looking statements, including statements that address Kairos Pharma's expectations for future performance, including but not limited to its ability to complete the phase II clinical trials for ENV105 or otherwise obtain positive clinical results going forward. Forward-looking statements do involve risks and other factors that may cause actual results to differ materially from those statements. For more information about these risks, please refer to the risk factors described in Kairos Pharma's most recently filed annual report on Form 10-K and subsequent periodic reports filed with the SEC and Kairos Pharma's press release that accompanies this call, particularly the cautionary statements contained therein. The content of this call contains time-sensitive information that is accurate only as of today, September 18, 2025. Except as required by law, Kairos Pharma disclaims any obligation to publicly update or revise any information to reflect events or circumstances that occur after this call is completed. It's now my pleasure to turn the call over to Kairos Pharma's CEO, Dr. John Yu. John, please take it away. Thank you, Jules. It's my pleasure to begin our important discussion today around Kairos Pharma's interim safety and efficacy data that we've obtained on our phase II clinical trial of ENV105 in patients with metastatic castration-resistant prostate cancer. With 1 million men in the U.S. diagnosed with prostate cancer each year and millions more worldwide, the development of resistance to current hormone therapies is a growing unmet need, especially in light of an increasingly aging population. Castration-resistant prostate cancer refers to tumors that grow despite receiving hormone-blocking agents. For castration-resistant prostate cancer, treatment options remain limited after hormone therapies fail. Kairos Pharma seeks to provide a safe and effective alternative for these patients with ENV105, our lead candidate that is now in phase II clinical trial. The interim safety analysis of the same trial, announced in July of this year, demonstrated that ENV105 was well tolerated when combined with standard of care hormone therapy, apalutamide, from the first 10 enrolled patients. Thus far, there have been no dose-limiting toxicities or unexpected adverse events reported to date. In addition, the treatment-related side effects were manageable with standard supportive care. Notably, no serious adverse events or unexpected toxicities were observed. Today, we've shared a positive interim efficacy analysis of those same 10 patients, showcasing the potential that ENV105 shows in combination therapy for patients with advanced prostate cancer. Our therapeutics targeting cancer resistance continue to show the potential to revolutionize the way we treat cancer patients. With only interim data, we are excited to bring together the principal investigators and other industry experts for an important event this afternoon to lay out the primary benefits of our compound, as observed at the time of releasing the interim efficacy results, which we believe clearly demonstrates the clinical need that can potentially be filled by ENV105. This interim efficacy analysis is what brings us here today, along with myself and our Chief Scientific Officer, Dr. Neil Bhowmick, our key opinion leaders in the space of advanced prostate cancer, clinical trial management, and oncology. We're extremely excited to announce the panel we've convened to discuss diverse perspectives on the data and the path forward in the fight against cancer drug resistance. First, we have Dr. Edwin Posadas, who will give perspective on the data in relation to the present standard of care. Dr. Posadas is Director of the Experimental Therapeutics Program and the Medical Director of the Center for Urologic Oncology Research Excellence, Urologic Oncology Disease Research Group at the Samuel Oschin Comprehensive Cancer Center at Cedars-Sinai Medical Center. He has both clinical and research interests in the treatment of advanced prostate cancer and the biology of cancer metastasis. Dr. Posadas received an MD at Johns Hopkins University School of Medicine and completed his residency at the University of Michigan Medical School and a fellowship at the National Cancer Institute. Second on our distinguished panel is Dr. Umang Swamy, a site principal investigator at the University of Utah, who will give his perspective on the ramifications of the phase II prostate trial for ENV105. Dr. Swamy is an Associate Professor in the Division of Oncology, Department of Internal Medicine at Huntsman Cancer Center, University of Utah. He is a specialist in medical oncology with a focus on genitourinary cancers. He completed his medical school from Sawai Man Singh Medical College, India. Thereafter, he worked as a visiting scientist at Montefiore Einstein Cancer Center in New York and collaborated on phase I studies of novel drugs and regimens for patients with refractory or advanced solid tumors. He completed his residency training in internal medicine at St. Barnabas Hospital in New York, a hematology oncology fellowship at the University of Iowa, and obtained an MS in clinical investigations from the College of Public Health at the University of Utah. Lastly, we'll hear from Dr. Richard J. Lee of Massachusetts General Hospital, who will give his perspective on the standard of care of prostate cancer. Dr. Lee is the Clinical Co-Director at the Claire and John Bertucci Center for Genitourinary Cancers at Massachusetts General Hospital, Harvard Medical School. After completing a bachelor's and a master's degree at Harvard, Dr. Lee then completed his medical school degree and graduate school degree training at the Albert Einstein College of Medicine in the Bronx, New York. He came to Massachusetts General Hospital for internal medicine residency training and then completed medical oncology fellowship training through the Dana-Farber Cancer Institute MGH Joint Program. During that time, he performed basic science research at the Whitehead Institute at MIT. Now I'd like to turn the call over to Dr. Neil Bhowmick, our Chief Scientific Officer, who will speak in more detail about the trial and moderate our discussion. Dr. Bhowmick is also a Professor of the Department of Medicine at Cedars-Sinai Medical Center and completed a fellowship at Vanderbilt University Medical Center. He holds six patents for biomarker detection platforms and stromal targeted therapeutics, including ENV105 and ENV205, and has been NCI/NIH funded for over 15 years and has been cited in publications over 11,700 times. Take it away, Neil. Thanks very much, John. To get right into it, we're going to be talking today about a randomized phase II trial where we're set to enroll 100 patients total at Cedars-Sinai Medical Center, the Huntsman Cancer Center in Utah, and the City of Hope. This study is designed to evaluate the safety and tolerability and early signs of efficacy for ENV105. Before I really get into the data, I wanted to share with you, if you don't mind, a little bit of why we had this trial in the first place and the basis, the mechanism of action. I hope you can see this slide that I have up here. Just to explain what ENV105 is, this is a neutralizing antibody. It's a biologic. It's also known as carotuximab. This neutralizing antibody blocks a protein called CD105. The reason we wanted to block this is because when we gave androgen receptor signaling inhibitors like enzalutamide, apalutamide, darolutamide, when we give these kinds of drugs, what we find is that this protein, CD105, is elevated. It's expressed in the cancer cells and the cancer-associated fibroblasts. That last part is actually quite important. By blocking CD105, we find all of a sudden we sort of turn back the clock and have the hormone therapy work again. We're very excited with these preclinical studies. We found Dr. Edwin Posadas, who got excited about these preclinical studies as well. We initiated this trial that you see here. This is a combination with apalutamide. This is a Janssen product that we combine with ENV105. They asked us to do a safety arm, and that's what we're going to be reporting on today, the efficacy of the safety arm. We previously reported on the safety for this arm at the two-month mark for the 10 patients that were accrued. As John just mentioned, there weren't any serious adverse events. Now we're actually in the randomized portion where we're doing head-to-head apalutamide alone as a single agent. That's the green arm there, or the combination of apalutamide and ENV105. When and if these apalutamide-only patients have recurrence, they're allowed to cross over into the combination arm, and that's what I have indicated over there. The measure of recurrence is based on RECIST criteria and the Prostate Cancer Working Group 3 criteria. That is that we are going to look at imaging on these patients, as well as the detection of PSA or prostate-specific antigen in the blood. As you would expect, these patients that were accrued that I just showed, they had taken hormone therapy prior to joining this trial. That was actually the criteria for enrollment, that they would have had to have failed at least one, if not two, hormone therapy regimens in the past. As you can see in this slide, a couple of the patients even had targeted radioligand therapy as well and had elevated PSA, as well as, apart from two of the patients, had stable disease at the 16-week mark. I just want to put into context why we use the 16-week marker for four months. That was because at the time when this trial was put together, we were aware of this trial, the CARD trial, where they had switched hormone therapies. They found that 3.7 months was the PFS, or the progression-free survival, meaning that the patients didn't get progression when they switched the hormone therapy just alone. The comparator was cabazitaxel, which is the next-generation taxane chemotherapy. They found in that trial that eight months was the PFS, the median PFS achieved. That was actually the initiation of the use of cabazitaxel in combination with hormone therapy earlier on in the spectrum. More recently, a trial was published. This is Pluvicto, as people know it as. It's a lutetium. It's a PSMA-targeted lutetium. In this study, they did a very similar thing. They switched hormone therapies. In this case, they found 5.6 months of PFS. They found the lutetium, the targeted lutetium, achieved 11.6 months of progression-free survival. That means they didn't have recurrence for about 11.6 months. In our trial, we found no unexpected toxicities. Putting what you just learned in context of past trials, we found that the PFS, the median PFS for ENV105 plus apalutamide, we had a median PFS of 13.7 months. That's about 59 weeks. If you can read this, what's called a swimmer's plot, each of these bars that are running across the screen, these are individual patients. Two of the 10 patients withdrew for unrelated reasons. The blue vertical line, as you can see there, that's at the four-month mark. That's how we had originally initiated when we initiated the trial. As you can see here, the red line is a vertical line, and that's at the one-year mark. We had five patients that have already crossed the one-year mark. The red triangles indicate that these patients are still on trial. We had a decrease in PSA, but it's very important to understand this is very, very early days. These PSA numbers, even though they decreased, it is more than likely, almost definitely due to apalutamide, the hormone therapy that we gave in combination. Importantly, we found preclinically that hormone therapy works better only when we give ENV105. We were excited with these initial studies. I'll end my presentation right here so I can pass it on and ask a few questions of our KOL members. John, are you going to pass it on, or is it going to open up to? I think you'll ask the questions. OK. To Dr. Posadas first. All right. Dr. Posadas, I'll go ahead and ask you the first question. Given that five of the 10 in the safety arm are still on trial and 86 or so more patients will still be accrued, this is very early days, we're just receiving this rather heady data. Could you bring us back down to the ground and, having prescribed carotuximab to many of those accrued on this trial thus far, would you help us understand from the perspective of the patient and the treating physician how should carotuximab or ENV105 be perceived if this data holds true a year from now? I would say that I think, while this is very early on, and any clinician will tell you in a small sample set, you need to be careful about the conclusions that you draw. Even in our preliminary experience, we're seeing a level of activity, which is unusual. I think the firmest thing we can say right now is in regard to safety. For those of you that are savvy to the prostate cancer world, Neil showed the toxicity table rather quickly. Nosebleeds are probably the most common thing that we've seen with this agent. In comparison to the other studies of this drug, while Neil did focus on our particular interest in the biology of CD105, it is a co-angiogenic signal. Its expression is increased in the setting of VEGF blockade, so things like hypertension and nosebleeds were actually expected. They're not commonly expected in the setting of hormonal therapy, but as Neil said, they have been manageable. It is a twist. The nice thing is, I will tell you, most medical oncologists dealing with CRPC are used to dealing with a number of other agents. For example, in the GU world, we deal with a lot of VEGF-targeted agents in kidney cancer, and these types of toxicities are just part and parcel of what it is that we do. I think it's fair to say that these are quite manageable. Only one patient had what we call the grade 3 anemia epistaxis because he required a transfusion. He's an older patient with a more exhausted marrow, likely due not only to age, but also due to previous exposure to a PSMA-targeted lutetium radiopharmaceutical. I think it is quite interesting to see that the biology of the laboratory is being mimicked in the clinic, where we've been able to induce a certain degree of ARE sensitization. The way that the patients have been consented and informed about this trial is that it is an alternative to chemotherapy. One of the requirements for the trial is that the patients decline chemotherapy. This was important because of the benchmark established by the CARD study that Neil showed. The data that he showed you next to that from PSMA4, which is the PSMA radioligand trial, came out after we opened the study. It is important to point out that in PSMA4, there is no overall survival benefit. There was a progression-free survival benefit noted. The control arm in that trial is the same as the control arm in the CARD study, and that is close to our benchmark of relative early progression. Even in our first 10 patients, you can see that we're seeing a longer than expected progression-free survival. Plus, our PSA responses do seem to point towards some degree of sensitization towards an AR-inhibiting agent like apalutamide. That drug was chosen for this trial because, comparatively speaking, the use of apalutamide compared to enzalutamide, darolutamide, and abiraterone is low. In order to keep the control arm as clean as possible, that agent was, in fact, selected. I wanted to make that statement because this may not be limited only to abiraterone. In fact, we had a previous study that used this drug after abiraterone and enzalutamide. This appears to be more of a class effect of resensitization. I think that we're seeing an experience in this population, which looks very promising. Thank you for that. Thank you for actually broadening the application of it's not just apalutamide. It could be other androgen receptor inhibitors and maybe even androgen ligand inhibitors. We're yet to see. Thank you for that again. Dr. Swamy, you've also had the opportunity to start accruing to this trial now at the Huntsman Cancer Center. How does therapy toxicity play into the calculus? Dr. Posadas brought this up. I purposefully did not discuss that when we talk about the CARD trial with cabazitaxel, as well as now with the lutetium, the targeted lutetium drugs. When you prescribe ENV105 to your castrate-resistant prostate cancer patients, what's the calculus? How do you have toxicity play into your thinking? When we look at this patient population of hormone-refractory prostate cancers, many of them have received androgen blockade, leuprolide, and other ARPIs for many months to many years. They are now very much concerned about anything impacting their quality of life. When we talk about the treatment options in this setting, the options are switching androgen receptor pathway inhibitor, like if they have received ABI, ENZA, or maybe an option or vice versa. Frankly, me and many other clinical investigators have shown that this is the most commonly used treatment in hormone-refractory prostate cancer. The other option is using a taxane chemotherapy, and the most commonly used therapy in this setting is docetaxel. The side effects of this are low blood counts, neuropathy, and fatigue. Patients are reluctant to use chemotherapy in this setting just to preserve their quality of life. That's why alternate ARPI is the most commonly used treatment. Now we have a new treatment, which is PSMA-directed radiopharmaceutical, Pluvicto, and its use is being picked. There are certain other challenges with it, which include PSMA scans and prior authorization for it. If eligible, we need to have some coordination with nuclear medicine and receiving Pluvicto. There are some side effects which may be unexpected, including bone marrow toxicity as well as loss of taste sensation with these agents. In this context, patients are looking for something where the side effects are manageable, potentially reversible withholding the treatment. In this scenario, when we discuss agents like carotuximab, which has a good toxicity profile based on prior studies, with epistaxis being one of the common side effects, maybe some headaches, fatigue, and nausea, I think patients like these types of therapies. From my perspective, we are still in the early phases of enrollment, and we would like to continue building our experience in this regard. Thank you so much, Dr. Swamy. That was great. To carry this forward, Dr. Lee, in the same line with the CARD study, you found with the cabazitaxel chemotherapy, we had a PFS of 8 months. With the targeted lutetium, we had a PFS of 11.6 months, both of which have been just explained to us right now with sizable toxicity associated with this. Now with ENV105 coming right along with PFS in that realm, very early days, I understand you have to be cautious. How do you think carotuximab may fit into the clinic, into the very fast-evolving prostate cancer landscape right now, as you see it, Dr. Lee? Oh, yeah. Thank you. I'll just say, as someone who is not involved in this particular trial, it's very eye-opening to actually see these data and understand from my colleagues about how the patients are doing. Really remarkable, especially, I mean, this audience knows prostate cancer remains the number two cancer cause of death in the U.S. It is a very large population of patients for whom additional therapies continue to be an important need, and I will call it an unmet need for continued improvements in treatments. As we think about these treatments, I'll step back a little bit and just say that when I'm sitting with a patient and talking about the potential options that he may have, I usually tell them that over the course of the years that we're going to be managing this disease together, you're probably going to see most of these treatments that are on this list. Now we have to just figure out what is the right treatment for you for right now. To have a treatment that you're describing here that early days, though it may be, includes progression-free survival that's greater than a year, PSA responses in patients, six of whom, as I was counting, had already received enzalutamide, so same class as apalutamide. It does seem like you are resensitizing some of these patients to the antiandrogen or the ARPI. I think it's very exciting. What we have failed to do with this in the prostate cancer space is resensitize cancers to the androgen receptor pathway inhibitors. As we've seen many, many different failed attempts at trying to use immunotherapy with this disease, we have to think about new directions. I think this is a very fascinating one for us to take. Thank you for that. Now I've forgotten, Neil, your original question. I think you addressed it very well because we talked about the safety. We talked about the efficacy. I would like to add that preclinically, we did find a reversal of lineage plasticity. This is thought the stemness or when cancers get really angry. The ENV105 actually reversed that. That's what we saw preclinically. It's very gratifying to see it in the clinic and to have you say it not being related to this study. In our field, we talk a lot about how aggressive these cancers become after we've given all the available treatments. There's a lot of talk about neuroendocrine or small cell or aggressive variants, and very challenging to treat those sorts of cancers. If you can reverse lineage plasticity, if you can revert these cancer cells to become more sensitive to things like AR antagonists, ARPIs, that could be a very big win. Very exciting. Thank you. Thank you again, Dr. Lee. I'd like to turn the call over to the operator at this stage and allow the analysts on the line to have an opportunity to have the benefit of our KOL today. Thank you, Neil. Our first question will come from Dr. Joe Pantginis. Dr. Pantginis is Managing Director and Senior Health Care Analyst at H.C. Wainwright. Prior to joining H.C. Wainwright, Dr. Pantginis worked as a Senior Research Analyst and the Head of Biotechnology Research at Roth Capital Partners. Dr. Pantginis also worked at Regeneron Pharmaceuticals, where he founded the Retroviral Core Facility. Dr. Pantginis' educational background includes both a PhD in MS and Molecular Genetics from the Albert Einstein College of Medicine, as well as an MBA from Pace University. The floor is yours, Joe. Thank you, John, for that. I appreciate it. It's nice to see also so many Einstein alumni here on this call. Thank you for all the details. If you don't mind, I have two questions, one sort of higher level, diving down into carotuximab as well, and one specifically about the data. Dr. Lee and anyone else that would like to chime in, you mentioned about a patient's treatment continuum really depends on the patient specific to that time. I guess it would come down to, is there any particular sort of cookbook that fits into an NCCN guidelines type of parameter where you could see carotuximab come in? Because you're seeing all the AR degraders, bispecific antibodies, Pluvicto. Is it going to be fitting into different areas, or will there be a particular cookbook? What's the variability you might see? It's a great question that's very challenging because there is no average prostate cancer patient. Every patient is unique. For each patient, we have, I mean, I can't tell you that we have a playbook or a cookbook of exactly what we're going to give in what sequence. It very much depends on what the patient looks like at the time and when we need to make a change. It is how much the cancer is impacting his quality of life at that very moment. I do think that for the data that you've shown, if it's borne out by the larger studies, if we are able to reverse lineage plasticity, we'd probably give this type of drug early in the castrate-resistant space to try to maintain sensitivity to the AR pathway inhibitors. That would be the way that I would be thinking about it. No, that's really helpful. Thank you. The fact that you all mentioned even the preclinical data about the ability to resensitize, could you also potentially see it later? Yeah. That is going to be a bit of an open question. The study that has been put forward will help to address some of those scientific issues. For the purpose of the trial, though, just to be clear, to get anything done, you have to have a clear question and a clear endpoint. We built this one to address a focal question. We will do our best to piggyback as much science as we can between the centers that will be collecting specimens, which will be ours, the University of Utah. We have made some inroads to discussing some science with the University of Wisconsin as well. Once those biospecimens are had, we will be able to further look at this because, as Dr. Lee was saying, one of the thoughts about how this fits into the cascade and array of options is its impact on plasticity and resistance, and modulation of resistance opens up or reopens up previously used and almost considered exhausted options for patients that we are already going to. Dr. Swamy already kind of pointed out that the ARPI or ARSI switch is a common practice despite existing large data sets that say it is not highly efficacious, but it is a preferred option by patients because of the toxicity profile, which is felt to be manageable. This is a fundamentally important scientific question to ask. It is interesting and exciting to see that we may be translating this into clinical practice and stuff to the patients. No, fantastic. I appreciate that. My data-specific question revolves around the prior therapies of these patients and the swimmer's plot as well. Just playing devil's advocate because it's early and it's nice to see these data, if you could put a little perspective on the swimmer's plots because they do look promising. I guess the devil's advocate question is, when you look at the prior therapies of many of these patients in the slide, the best RECIST that's seen has been stable disease. When you look at the swimmer's plot themselves, how much of the stable disease or the ability to hit these PFS numbers could be or not attributable to the prior therapy? I would tell you one lesson learned prior to the design of this study was that patients that have been overly exposed to the various options develop a degree of resistance, which is difficult to reverse. Specific to the study, it's an exclusion of more than two different androgen receptor pathway inhibitors and previous chemotherapy. In a sense, to address your previous question, in a very coarse fashion, the NCCN doesn't have a cookbook. It has four lousy boxes that say whether you've had an ARPI and whether you've had a taxane, and try to make sense out of that. This would fit into an "earlier pre-chemotherapy space." Scientifically, I hate that because that is a very lousy way to classify disease by treatment, but it is the standing tradition in prostate cancer. I do think that this is an earlier intervention. The patients that you're seeing have had comparatively few treatments, as opposed to, as Dr. Lee mentioned, the full seven-course meal of prostate cancer therapies that are available, that is continuing to expand. I would also tell you that if you're looking to make a difference, trying to tame this thing at the tail end of its dedifferentiation is likely a waste of time. Many of us who are trying to shift the paradigm are trying to shift the disease course early in its natural history when the disease may be "more pliable." Dr. Lee had suggested that as well, to do it earlier. Let's let Dr. Jason Colbert have a chance to ask a few questions. Dr. Colbert will not be here. We have a question from Jason McCarthy. Dr. McCarthy is the Senior Managing Director and Head of Biotechnology Research at Maxim Group. Dr. McCarthy joined the group in July of 2014. Prior to joining Maxim, he received his doctoral degree in biomedical sciences from the Albert Einstein College of Medicine. It's a reunion here. The floor is now yours, Jason. Yes. Like Joe said, a lot of Einstein alums here, which is great. I have a question. It kind of piggybacks on some of the prior question and discussion. When you look at the benchmark of 3.7 or 3.6 months for antiandrogen therapies, that was in 2019. We found some other studies today, some published papers that went up to close to six. When you think about that small n-value and you get over 13 months of PFS, you'd think maybe after 100 patients, maybe it comes in. Hopefully not. We thought this might be due to just improvements in how you manage patient care have evolved over that time. The long-winded way of asking, as this trial continues, what would you consider to be a meaningful improvement in PFS? It seems like there's a little bit of a moving goalpost here. Would any of the KOL members like to chime in? We can have Dr. Lee. Can I ask you, do you have a pre-specified? He's asking. The trial? Yeah. He's asking, is the change in PFS because Dr. Posadas and Dr. Swamy are such good oncologists that they're treating them way better than the rest of the world? Right. We see them in different categories where you see one, there's a range, right? It seems that medical treatment has just improved over the last decade since these therapies have been introduced. At 13 months that you're seeing for the eight patients in that group, maybe that comes in a little bit. There seems to be a range. There's a moving goalpost in terms of what PFS could be, what would be clinically meaningful for ENV105 in the larger phase II study, the whole thing. Yeah. I think that PFS in this context doesn't have anything to do with what subsequent treatments they get, right? This is how long before they actually have progression. Unlike overall survival, which would then include subsequent therapies, which keeps on getting longer and longer, PFS in this setting, you're right. We've seen, I think, 3.5 months up to 5.5 months in the couple of lutetium studies. One was post-chemo, one was pre-chemo, as well as the CARD study where ARPI switch was in the control group. What would be clinically meaningful? I think that if I were just to put a number, I would say eight to 10 months for PFS because I think that's probably going to translate into a longer overall survival. I'd be curious about Dr. Swamy and Dr. Posadas and their thoughts. I want to just salute Dr. Lee's recommendation. When we design phase II trials, we kind of think about a go big or go home signal. Moving up your PFS from somewhere between three to five months to eight to 10, that's a doubling of PFS. That's a pretty high bar that Dr. Lee would put forward. I respect it. The good news about a high bar is it keeps your n small. You try to look for a 10% shift in PFS, you're going to take hundreds and hundreds of patients and still leave yourself kind of scratching your head saying, is a four-week shift in PFS meaningful? Remember that these are the kinds of things that we did in pancreas cancer. We got an approval for Gemzar, gemcitabine, based on a four-week shift in time to symptom evolution. Mitoxantrone did the same thing back then. The bar is much, much higher now. Given the fact that this is tolerable, we've set a 45% increase, a 45% improvement in PFS as the bar for a phase II signal, which is still, I think, by most standards, a non-trivial bar. We're still at least preliminarily looking pretty good over that. I think the more important thing to address, even your earlier question, is because of concerns about shifting patterns of care and patient identification. This is a problem we hit early on in an earlier iteration of this. We did a single-arm phase II trial. People were telling us it's more difficult to interpret. This trial very specifically is built with a randomization to monotherapy versus combination to give us, within this exact population, amongst these investigators, so we've kind of normalized out a lot of variables, what the PFS on apalutamide alone will be. We will make that comparison at the conclusion of the trial. We should be able to very definitively say whether or not the carotuximab does, in fact, add to the effect of the apalutamide. By all current data, it looks to be that way. We did need to address that head-on, hence the trial design. Just one mechanistic focus question. To your knowledge, I know you get this increased CD105 expression. Is there any redundancy within these cancer cells? Are there other proteins that are expressed that could be similar, where ultimately you might see you're going to see progression at some point that pops up that you know of? I'm not sure. This is Bhowmick. Preclinically, we are currently, we received a $3.2 million grant from the NIH where we're identifying biomarkers that would help predict the efficacy of this trial. They're being validated in this trial currently. In those, are they similar to CD105 in angiogenic or other similar things? We haven't identified such a thing. We have found biomarkers, of course, but not along the lines of what I think you're asking. No. Yeah, got it. Thank you for taking the questions, guys. Thank you. Our next question will come from Sara Nik. Dr. Nik is the Vice President of Equity Research and Biotech at H.C. Wainwright, specializing in biotech sector analysis and investment research. Dr. Nik completed a PhD at the Albert Einstein College of Medicine. Over to you, Sara. All right. Thanks. Just two questions from me. First, I was curious about how we should think about that PSA variability at baseline, maybe for the KOLs. Is that something that could potentially inform the outcomes in second-line therapies and beyond? Or maybe for purposes of this study, is that something that's a bit more arbitrary and maybe not as well utilized? Dr. Posadas, do you want to try that? Can you repeat the first part of that again? Just the variability in PSA that we observed at baseline in those 10 patients, and how we could think about that, if it could potentially inform their outcomes in second line and beyond, or if we maybe shouldn't pay too much heed to that. Oh, yeah. You need to be careful when you ask me to speculate. Dr. Lee and Dr. Bhowmick are oddly familiar with me speculating. PSA secretion is regulated by a number of factors, including androgen dependence and also any kind of escape mechanisms that may be evolving within the tumor cell and its microenvironment. One could postulate that the amount of PSA relative to tumor burden, because remember, there are two confounding factors. It's the amount of PSA that a cell produces and how many cells are present. Looking at the absolute value is a little bit difficult because you can't separate out those two factors without some kind of tumor burden normalization. You can have folks that are very, very sensitive to hormonal therapy, even with PSAs that are up around 200 or 300. That's because their disease is progressing slowly enough, their symptoms are slowly enough that they don't really move from their current form of therapy. The kinetics, we think, also kind of point towards something. I think it's really difficult to use a PSA threshold. People have tried to look at PSA as a predictor of mortality risk. It oddly doesn't show that. We also know that dedifferentiated prostate cancers becoming resistant tend to lose PSA and PSMA expression. With all those factors coming to this, it's hard to know how to interpret that. We report it in almost all trials as a way of representing the patient population that we treat. What's kind of wild is, I think, the numbers that you're seeing with PSAs that are below one to PSAs that are over 200, unfortunately, it's not unusual to see quite a range in a CRPC study. I think that's important as other investigators and physicians look at it to say, oh no, my patient's PSA is too high or too low to benefit from all this. We will likely go back and look at some of these things. For example, now we know that low PSMA expression or low SUVs on a PSMA PET/CT tends to not correlate so well with response to the PSMA radioligands. As Dr. Bhowmick mentioned, the biomarker work here that we think will help us to better identify that. I doubt it would be PSA solely that would filter into that, but it may be part of the answer. OK. Thanks. That's helpful. For my second question, since that safety profile you're seeing at this point seems pretty favorable, only one grade 3 and no grade 4 or 5 toxicities were observed. If you could at this point give any color or other plans to dose escalate, or is that current dose that you're at considered kind of the maximum tolerated or as biologically active dose that these patients are being given? Yeah. I'll speak as the old man on the call in terms of experience. I've been using this agent now through a number of different settings, including kidney cancer. I think this is the most we could utilize. In fact, if you look at our dosing regimen compared to any other previous studies of carotuximab, we've actually reduced the dose for two reasons. One is it became kind of a tradition. It's something that we were not tradition, but something that we were having to do routinely on earlier studies with carotuximab because of the angiogenic or blood-vessel-related toxicities. Plus, as Neil pointed out, this is an antibody. Its residence time is quite long. The repeated dosing didn't kind of make sense after enough of it was in the system. We see this routinely in clinic. The PDL1 inhibitors we're using, we're not dosing them every two weeks or three weeks anymore. It's more standard. We see these every four to six weeks. This seems to improve tolerability for patients. That's the other thing. You've got to find that space where you can thread the needle between toxicity and benefit. This seems to be a better window. Would we revisit this again in the future going forward? These are some of the longest exposures I've had to the CD105 therapy because I think the patient selection and the partnering that we're doing, so that may be revisited again in the future. It may go even further in order to minimize long-term toxicity. OK, great. Thank you so much for taking the questions. Thank you for those questions, Sara. Our next final question is from Dr. Chad Yahn. Dr. Yahn is Equity Research Associate, specializing in the biotechnology sector at Maxim Group. Please go ahead, Chad. Hi. Thanks, guys. As more patients come onto the study, are you seeing any early signals, like baseline CD105 levels, for instance, that seem to line up with how long patients are staying on treatment? Yeah. One thing, this is Neil. I'll let Dr. Posadas answer this. We're not measuring CD105 in the tumor or in the blood at this stage. Dr. Posadas could probably. Yeah. We are collecting both circulating tumor cells and plasma. Plasma will be used both for extracellular vesicle characterization studies as well as serum protein or plasma protein analysis. It's something that we've talked about doing. There's certainly Neil's work with endoglin. We know that there's elevated endoglin expression in these patients. It's likely to be variable to some extent. We think it's probably almost too high in some of the more resistant patients. One of the problems that we face in prostate cancer, and Dr. Lee and Dr. Swamy are very familiar with this, is getting tissue specimens, contemporary tissue specimens from prostate cancer is really hard. They tend to have their skin crawl when they hear the drill that we want to use in order to collect bone cores from them. We were not able to mandate that as part of the study. That would be almost cruel and unusual to make that happen. Where we can, the study is designed to collect tissue whenever it is possible. Dr. Bhowmick was careful in his selection of co-investigators to choose those that have experience in acquiring specimens. We hope to be able to shed some insight into that as we go forward. We just haven't been able to get there quite yet, not in the first 10 patients. Thank you very much to our analysts for their important and thoughtful questions. I would also like to thank our KOL panel, Dr. Posadas, Dr. Swamy, and Dr. Lee, for their insights and time today. Lastly, I want to thank everyone who joined us. I will now turn it over to our operator to conclude the call. Thank you. The conference is now concluded. Thank you to everyone that attended today's webcast presentation. You may now disconnect your line and have a pleasant day.