Xencor Trial Results Webcast - XENCOR INC

Hello and welcome to the Zencore ESMO 2026 webcast. We ask that you please hold all questions until the completion of the formal remarks, at which time you will be given instructions for the question and answer session. Also, as a reminder, this conference call is being recorded today. If you have any objections, please disconnect at this time. I will now turn the call over to Charles Lyles, Executive Director of Investor Relations and Corporate Communications. Thank you and good morning. Yesterday, we issued a press release introducing the topics we plan to discuss on this webcast, including results from dose expansion cohorts of the Phase I study of XMET819 and advanced clear cell renal cell carcinoma. The press release is available at www.zencor.com. Providing comments on the call from Zencor are Basil Dahyat, President and Chief Executive Officer, John Desjarlais, Executive Vice President and Chief Scientific Officer, Dane Leone, Executive Vice President, and Chief Strategy Officer, and Jeff Cho, Senior Vice President & Head of Clinical Development for Zencore's Oncology Programs. We are also joined by Dr. Sumant DePaul, Professor and Vice Chair of Academic Affairs, City of Hope Comprehensive Cancer Center, who will join us to review his presentation at the ESMO conference yesterday. After the prepared remarks and presentation, we will open up the call for management to address your questions. Slides that we are using today should be visible here on the webcast and will be made available for download on the events and presentations page of our website around the time our remarks are concluded. Before we begin, I would like to remind you that during the course of this conference call, Zencore Management may make forward-looking statements, including statements regarding the plans and objectives of management, future product offerings and research and development programs, as well as future financial and operating results, future market conditions, future operations, the company's partnering efforts, and capital requirements. These forward-looking statements are not historical facts, but rather are based on current expectations and beliefs, and are based upon information currently available to us. The outcome of the events described in these forward- looking statements are subject to known and unknown risks, uncertainties, and other factors that could cause actual results to differ materially from results anticipated by these forward looking statements, including but not limited to those factors contained in the risk factors section of our most recently filed annual report on Form 10-K and subsequently filed quarterly reports on Form10-Q. These statements speak only as of today, and we undertake no obligation to update them except as required by law. Now, I'll pass the call over to Basil. Thanks, Charles, and thank you for joining us today. We're absolutely delighted to share the data presented at ESMO yesterday on XMAB819 Phase I Expansion Cohorts in Clear Cell Renal Cell Carcinoma and to give an update on our plans for the program. I think this data cements CENCOR's position at the forefront in targeting solid tumors with T-cell engagers. an emerging modality that we think delivers precision immunotherapy against solid tumors by bringing the immune system to bear against just the right cells. Currently, there's two ongoing phase three programs, both with exciting data created by Zencore using our XMAP platform in 2 plus 1 format for selective tumor targeting, ASP2138 and Astellas, and Zaloridamig and Amgen. And we expect XMAB819 to be the third in pivotal studies when we start our planned trial in 2027. We're not aware of any other TCE platform or company that has made this much progress against the enormous unmet need in solving tumor oncology. In addition to this, we're awaiting an update from our partner, J&J, for the combination of Pasiridamig with J&G 9401, an XNAB CD28 bispecific. Now, it's important to put this update into another context. We've spent the last three years focusing on excellence in clinical trial execution and strategy, trying to have Zencore realize the value from the incredibly promising XMAP molecules we create. You can see the accelerating pace of trials, and most critically, we expect the resulting multiple data readouts will continue through 2027, starting with initial Phase 1b data from Plumodimab and RA in two weeks at ACR, then Phase 1 data from XMAB412, our bispecific TLNA by IL-23, then the primary endpoint of our global phase 2b study of XMAP942 and ulcerative colitis, plus further data updates from the ongoing studies of XMAB819. So now back to 819. The central problem in targeting RCC or any solid tumor is the near universal issue of expression of tumor-associated antigen targets in normal tissue, very often in vital organs. The best target distribution situation is where there's a high level in tumor cells, higher level in tumor cells and healthy cells, but these cases still have target in those healthy cells. So drugging solid tumor targets has been a compromise between high anti-tumor potency and hence impact and high selectivity, which avoids toxicity. This two-by-two schematic illustrates the point with highly active but toxic chemotherapy at the lower right and at the top left, highly selective traditional monoclonals lacking potent killing mechanisms. ADCs and first-gen TCEs added very active cytotoxic functions to antibodies, chemo molecules, and T cell recruitment, respectively. But they compromised selectivity, which you can see from ADCC killing of low or even zero target tumor cells and tox profiles reflecting their chemo ligand. And for first- gen TCE, having tox challenges achieving and sustaining effective doses and solid tumor indications. With our 2 plus 1 platform, we've been attempting to move TCEs up in selectivity without compromising anti-tumor activity so we can broaden both therapeutic windows and use cases. Now I'm going to turn it over to John Desjardins, our longtime CSO and co-inventor of our XMAP platform, so he can describe how we did this to create 819 and the other 2 plus 1s. Thanks, Basil. Since the XMAS 2 plus one platform has been critical to ours and our partners' solid tumor T cell engager strategy, I'd like to review the general concept. First, the 2 plus 1 format binds tumors like national antibodies do. Specifically, we have bivalent targeting of the tumor antigen. That provides us with a powerful engineering paradigm to create T cell engagers with improved tumor versus normal selectivity. The way that works is we tune the affinity of the tumour targeting arm such that the antibody can retain high binding or avidity for high density tumor cells expressing lots of the target, while sparing normal cells that express lower levels of our target. That's a well-validated biophysical phenomenon due to the heightened ability of the second targeting arm to quickly find another target when there's lots of it around, like natural antibodies do. In contrast, when using a 1 plus 1 bispecific, that single tumor targeting arm has to have sufficient affinity on its own to drive binding the tumor cells, meaning it's much harder to distinguished tumor from normal cells. Because this is a well-understood biophysical phenomenon, we can develop QSP models to help us tune the tumor normal selectivity for a given target and its density ranges. Here on the top right plot, you can see a QSP-optimized XMAB2 plus 1 for a hypothetical target density of 30,000 and a normal density threefold lower. For this scenario, the model shows strong killing of the higher density tumor cells with significantly lower activity on normal cells. On the bottom right, if we take that same density range for a 1 plus 1 biospecific, then you can see the model predicts very little discrimination between tumor and normal, which of course means it'll have higher potential for safety issues. In fact, the only way to recover more selectivity with a 1-plus-1 is to reduce its affinity, which then means we'd struggle to have sufficient killing of tumor cells. Now let's focus more specifically on X-MAP819, Sencor's X-MAB2 plus 1 that we developed for the treatment of kidney cancer. From the antibody diagram, you can see that it has two arms that bind EMPP3 and a single CD3 targeting arm. And of course, it was affinity-avidity tuned to optimize for tumor normal selectivity. The middle plot shows that nicely, where we can see significantly more killing of a high-density tumor cell line versus one with lower EMPPP3 expression. Finally, on the right plot, we were able to see strong antitumor activity of XMAV819 in our preclinical mouse tumor models. Notably, the same model is completely refractory to PD-1 blockade. Now, we initially developed XMAB819 for treatment of kidney cancer, specifically clear cell renal cell carcinoma. We know the target is also expressed to some extent across a wide range of histologies. As you can see from this large IHC dataset we collected, EMPP3 is strongly and uniformly expressed in clear-cell RCC, but we also see a good proportion of papillary RCC patients expressing strong levels, and there's also a good number of microsatellite-stable colorectal cancer patients and lung cancer patients that express significant levels. We've included some representative IHC images from some of these histologies on the right. Now that we've observed compelling activity in clear cell RCC we recently opened cohorts for papillary RCC, colorectal cancer, and lung cancer. While we don't need to pre-screen for EMPP3 expression in ClearCell, enrollment in the other cohorts is contingent on seeing strong expression by IHC. CENTCOR has always prioritized for the creation of modular antibody formats with high stability, developability, and robust manufacturing using straightforward purification protocols. We believe this approach has borne out very well clinically, and we've been excited to see such compelling progress with many of our and our partners' clinical stage molecules. With such a strong backbone format for XMAP819, we've been happy to see a good pharmacokinetic profile in our patients. The plot here shows our fitted population PK profile for XMAB819 as we go through the priming and step-up phases of dosing, up to 100, 200, and 400 microgram per kilogram target dose, and the model fits a terminal half-life of approximately eight days. That profile lends itself to dosing every two weeks, or we believe three-week dosing, particularly when we reach the target dose. The shaded areas of the plot show important regions for our QSP model of XMAP819 cytotoxicity, with the EC50 to EC80 range shown in light gray, and the EC80-plus range shown in dark gray. The model, built with a combination of preclinical cytotoxicity and PK data, predicts that at our highest IV dose of 400 microgram per kilogram, we are approaching the maximum activity of the drug, with trough levels at two-week dosing remaining above a predicted cytot toxicity of 80%. As I emphasized earlier, CENCORS platforms are built from robust stability, developability, in manufacturing. You can see from this summary table that we have a high titer cell bank for Expat 8819 that scales well to 2,000 lire. Our drug substance and product are both stable for at least 60 months in liquid formulation, and we're using commercially validated CDMOs for manufacturing in the U.S. Now I'd like to introduce one of our investigators and close collaborators, Dr. Monty Paul from the City of Hope Cancer Center, where he is Vice Chair of Academic Affairs and co-director of the Kidney Cancer Program and oversees one of the largest clinical trial portfolios in the West Coast. I'll now turn things over to Dr. Paul to review the phase one results for XMAP819 as presented yesterday at ESMO. Thank you so much, Dr. Desjarlais. First and foremost, this is a really exciting opportunity. I'm really pleased to be here. This is a study near and dear to my heart. We enrolled the first patient on this study at City of Hope several years ago. We can jump to the next slide here. Dr. Desjarlais really gave you a great background on XMAB819 in terms of its biology. I'll emphasize the fact that the target, ENPP3, is heavily expressed in clear cell renal cell carcinoma to a much lesser extent on adjacent normal tissues, and we're also keen on investigating the agent in the context of papillary kidney cancer, colon cancer, and lung cancer as he'd articulated on the basis of selective expression in these tissues. We can jump to the next slide here. This is the schema for the study, and you can see that we're reporting today phases of dose escalation involving 100 micrograms per kilogram up to 400 microgramS per kilogram. We've completed dose expansion at 100 and 200 microgram S per kilogram and continue to enroll at 400 micro grams per kilogram I'll emphasize this during the course of my discussion today. This was a very heavily pre-treated population of patients. A mandate in the study is that all patients must have received for clear cell renal cell carcinoma at least a prior checkpoint inhibitor and a VEGF TKI. Many patients received several lines of therapy beyond this. Patients had to have measurable disease with no prior anti-ENPP3 therapy, and shown below is the schema for the study. This involved a priming dose followed by two step-up doses followed by delivery of the target dose thereafter. On the next slide, you can see patient characteristics, and I'll emphasize that this was a fairly typical population of patients with metastatic renal cell carcinoma, except for the fact that if you look at the IMDC risk score amongst patients enrolled in the study, it was a very small proportion that actually had favorable risk. It amounted to six to seven percent of the population overall. The vast majority of patients that we enrolled were intermediate and poor risk. If we look to prior therapy, as I'd emphasized previously, this was a very heavily pretreated population of patients. About one quarter of patients had received three prior lines of therapy. And in fact, 35 to 40% of patients that received four or more prior lines of treatment. In addition to this, beyond just receiving one VEGF-TK and one checkpoint inhibitor, we had approximately 63 to 64% of patience that had received two or more VEJF-FTKIs. And we also had about 35% of patient that had receive a prior HIF-2 inhibitor as well. and we'll dive a little bit deeper into these subsets as we explore the efficacy of eczema 819. The next slide is a busy slide that highlights adverse events, and I'll just summarize the table on the left by noting there was a relatively low rate of dose reductions and treatment discontinuations on account of treatment emergent adverse events. On the right, one of the points that I'll make is that if we look across any incidence of toxicity versus those toxicities that had an onset beyond day 29, it was really that first month of therapy in which the vast majority of toxicities were incurred. We've highlighted in boxes on the next slide here several toxicities in particular, and I'll dive deeper into the management of these. These are adverse events I think of special interest, rash, cytokine release syndrome, and transaminitis. The next slide highlights our experience with cytokINE release syndrome. I'll highlight the fact that CRS was predominantly low-grade, and it occurred principally during priming, and you can really see that emphasized in the graphic on the left. The incidence of CRS really diminishes substantially as we go through priming doses and dissipates almost completely as we get to target doses of therapy. We've come up with, as an investigative team, a very, I think, reasonable regimen for pre-medication for eczema 819 to mitigate this with acetaminophen, diphenhydramine, IV normal saline. Dexamethasone is being given now prior to priming doses, and we give one dose of tocilizumab prior to priving dose one. Next slide, please. I've highlighted here two other cytokine-driven adverse events. The first is something we might anticipate, which is rash. This is an on-target effect, given the fact that ENPP3 is expressed on basophils and mast cells. We found this to be very easily managed, in my opinion, with daily antihistamines and use of oral and topical steroids. We only incurred dose delays in about 4.5% of subjects, and there are no treatment discontinuations. And just as we saw with cytokines, we found that the incidence of rash really diminishes substantially as we go across priming doses. Most events, again, were low-grade. Transaminase elevations are highlighted on the right, and these were asymptomatic. They were transient and largely self-limited. The median time to resolution was just seven days, and there really appeared to be no significant clinical sequelae in the vast majority of patients. Dose delays due to transaminase elevations occurred in about 15% of subjects. There were no treatment discontinuations. As you can see, transaminese levels, which is articulated in the graphic in the bottom right, really peaked after priming dose 3, but you can see that these were quick to resolve. And as we got to subsequent target doses, the incurrence of these was relatively low. I'm very excited to present to you the data related to anti-tumor activity. What we see at the lowest dose that we'll report here today, 100 micrograms per kilogram, is a very, very reasonable and, I think, exciting response rate of 30%. You can see a disease control rate of 86.7%. With a median time to follow-up of just 4.1 months, I'll still emphasize that there are some patients who actually had responses that were durable, as you can see in the spider plot below, extending to almost two and a half years. What we'll see inthe next slide here as we go to 200 micrograms per kilogram is a step-up in response rate to 44%. The disease control rate here was 64%. You can see that the vast majority of patients had tumor shrinkage. Again, with a median follow-op time of about four and a halftime, you see patients that really approaching a durable response with some patients extending their responses to 10 months and beyond. And finally, we report on the next slide the 400 microgram per kilogram dose. Again, very exciting. We see a response rate here of 45.5 percent, the disease control rate of 81.8 percent. You can see that almost all patients had tumor shrinkage, and on the spider plot articulated below, many ongoing responses, and I'm keen on updating this data in the months to come. I think it's salient to point out two specific subgroups. Again, as noted, all patients in this study had to receive a prior VEGF-TK and checkpoint inhibitor, and we have a cohort of triple-treated patients who have also received a HIF-2 inhibitor in addition. These patients have frankly exhausted all of the classical mechanisms of action that we utilize for therapy for metastatic renal cell carcinoma. What we see in this cohort is a response rate that approaches 35% and a disease control rate of 78 percent. In addition, we have a subset of patients that have received not just one but two prior VEGF TKIs. Again, these patients all received an additional checkpoint inhibitor beyond this, and what we see here is a response rate of 45.2 percent. These data really, in my opinion, represent a high watermark for what we've seen in phase one clinical trials and renal cell carcinoma to date. The disease control rate in that subset was 85.7 percent. On the next slide has articulated the ongoing responses within this population, of which there are 19. And you can see that the median time to response is relatively quick, 2.7 months. Median time on treatment within this cohort is 7 months. But as noted previously, we're starting to see very durable responses with some patients who have responses extending to almost two and a half years, some approaching two years, and again, very keen on extending this data. And I have a very special example on the next slide to share with you. This is a patient very near and dear to my heart that I've been treating for a decade. This patient's 56 years old. He was diagnosed 10 years ago, as noted, with metastatic disease incurred about five years ago. Thispatient had two prior lines of therapy, the first being cabizantinib with nivolumab, the second being lenvatinib and everolimus. He was on the first therapy for a month, the 2nd therapy for 3 years, and he was really mired by the toxicities of these regimens. He suffered from a great deal of gastrointestinal symptoms from the VEGF TKI. He began on protocol with two enlarged mediastinal lymph nodes, both more than two centimeters in long diameter. You can actually see the figures posted on the right of his baseline images there, so bulky mediastional adenopathy. Now, this patient also had multiple small lung and pancreatic lesions. Notably, his membrane expression of ENPP3 was actually less than 25% on tumor cells. Despite that, thispatient actually had a partial response that was incurred very early on, at just six weeks, and this deepened to a complete response at week 42. He's had normalization of his lymph nodes, he's had disappearance of lung and pancreatic lesions, and his response is ongoing, a complete respons at 16 months. Not only that, but I'll note that his toxicity profiles have just been exceptional, and it's really had restoration of his quality of life. In conclusion, XMAB819 shows very meaningful anti-tumor activity in patients with advanced clear cell renal cell carcinoma. I'll emphasize that this, in my mind, represents a high water mark amongst trials that I've seen in the phase one space in this field. Anti-tumor activity was observed in a dose-dependent manner with an objective response rate of 30% of 100 micrograms per kilogram. That increases to 44% to 200 microgramS per kilogram and further to 45% at 400 microgram S per kilogram, the majority of these responses are still ongoing in our last data cut. Not only that, but if we think to the triple pre-treated population of patients, those that have received a checkpoint inhibitor, a TKI, and a HIF-2 inhibitor. We see a response rate of 35%. And in addition, in those individuals that have perceived two or more VEGF TKIs, again, very heavily pretreated, a very, very exciting response rate of 45%. In my opinion, these data firmly support continued development of eczema 819 as monotherapy for advanced clear cell kidney cancer. I think it makes sense to look at rational combinations and certainly explore this in earlier lines of treatment. I'll pass it back now to the team at ZenCorp. Thank you, Dr. Paul, for your collaboration and leadership. And thanks to the entire City of Hope team and patients that have supported eczema 819 as a potential breakthrough therapy for advanced renal cell carcinoma. We want to take the opportunity now to provide some slightly updated data with one additional month relative to our data cut for the ESBO presentation, which helps provide more details for our development decisions as we move into late phase development in 2027. Our pooled swim reply here for the expanded target dose cohorts of 100, 200, and 400 micrograms per kilogram IV remains immature with a 7.9-month median time on treatment as of October 1st. We're pleased with the high response rate, numbers of patients remaining on treatment and encouraging durable disease control as fall continues. We have one patient at the very top of the swim plot who elected to dose escalate to 100 micrograms per kilogram when that dose was cleared back in 2025. This patient experienced a deepening of response after the dose escalation, and though having some progression with new lesions after 28 months, continues on treatment today. Looking now at our spider plot of every IV responder across expanded dose levels as well as a couple at lower doses, we provide some additional insights around deepening of responses over time, which can be seen with powerful immune-based therapies. In about 25% of patients, time to response is more than four months on treatment, but even in the majority of patients with more rapid time to respond, we see those responses continue to deepen over time. Following the step-up dosing period of XMAB819, the tolerability has been very good, which limits interruptions in treatment over the long term and allows the drug to continue directing an immune attack against tumors. For the purposes of planning our next stage of clinical development, inclusive of a registration-enabling study expected to start during 2027, we have selected 400 micrograms per kilogram IV target dose as the putative IV recommended phase 3 dose for XMAB819. Even though we've only recently finished enrolling the 400 micrograms per kilogram expansion group to give us a little over 20 patients total treated at this dose level, the follow-up for the full group is less mature than the full 100 or 200 microgram per kilogram target dose cohorts. Data are clear to us that there could be an increasing response to the dose at 400 micro grams per kilograms and importantly an increasing dose response for disease control. The shape of the waterfall plot tells most of the story here with a left shift of the inflection point compared to lower target doses. But the new unconfirmed PR at week 42 and the treatment durability itself also look encouraging with over 70% of patients still receiving ongoing treatment with over six months medium follow-up and an 82% six-month PFS Kaplan-Meier estimate. Importantly, the safety profile for the 400 microgram per kilogram target dose looks largely consistent with the 100 or 200 micrograms per kilogram of target doses. So based on the strength of both the efficacy and safety profile for eczema 819 at our chosen target dose cohorts, we're optimistic we're in a favorable position to use an active standard of care control tovosinib for our registration enabling study supporting full approval of eczemab 819 monotherapy for use in advanced clear cell RCC following prior exposure to one PD-1 or PD-L1 inhibitor and one VEGFR TKI. This label could support broad access to eczema 819 largely as a second or third line monotherapy drug of choice. We plan to power for a clinically meaningful PFS hazard ratio of 0.7 based on our expectations of tibozumab in this treatment setting. We view the third-line subgroup analysis from Tenevo2 to be the most contemporary dataset for our expectations of tivozinib in a post-IO and VEGFR TKI patient population. By the numbers in this setting, treatment with tivonzinib has achieved a 10.5% ORR 6-month PFS Kaplan-Meier estimate of 41% and a medium PFS estimate of 5.4 months. While these numbers are an unfortunate representation of current therapeutic options in the third line for patients with advanced clear cell RCC, it's also why we think there's a compelling opportunity for XMAP819 to make an impact for patients and caregivers as our first indication for full approval. And now I'll turn it over to my colleague, Dane, to discuss the broader strategy with XMAT819 development. Thank you, Jeff. Setting the background of what has been achieved is important context. As we presented earlier, XMAP819 has demonstrated a clear dose-response relationship for our selected 100, 200, and 400 microgram per kilogram target dose cohorts, with a still maturing response rate for our putative recommended phase 3 target dose of 400 micro gram per kilogram. Shown on the slide, for illustration purposes, as they were not head-to-head studies, the 45% confirmed overall response rate of the XMAP819 putative RP3D cohort in the fourth-line treatment setting represents an unprecedented level of antitumor activity reported for monotherapy drugs that are currently a part of the advanced clear-cell renal cell carcinoma treatment armamentarium. Even cross-comparing to monotherapy treatment-naive frontline studies of VEGFR TKIs currently within NCCN guidelines, the confirmed response rate of XMAB819 compares favorably. But response rate alone is not the defining feature of the strength of monotherapy outcomes for XMABA819 in our study. IMDC risk is highly prognostic for response to therapy, and as you can see, our 400 microgram per kilogram cohort enrolled a primarily intermediate to poor risk patient population where unmet clinical need remains high. For patients and caregivers, the choice to use treatment is often driven by the perceived balance between the patient opportunity for a meaningful clinical response versus the potential they do not respond to therapy at all and experience primary progressive disease. As you can see, once again for illustration purposes only, XMAB819 has reported a very favorable clinical balance of response to primary progressive diseases relative to the most recent monotherapy-approved agents, divaznib and belzudifan, but also to the current dominant standard-of-care mono and combination therapy, cabizantinib, in a post-VEGFR TKI treatment line. Importantly, the safety profile of XMAP819 is well-tolerated, with a rate of discontinuations due to treatment-emergent adverse events lower than those reported in studies of the VEGFR TKI class of drugs or per-label monotherapy nivolumab. Importantly though, XMAT819 excellent tolerability profile post the priming period has allowed us to avoid the common dose reductions or interruptions required by the VEGFR TKI class, allowing XMAP819 to achieve long-term consistent target coverage above EC80, which is the biology behind the durable disease control and continued deepening of response we see over time. The strength of our data supports our enthusiasm to begin engaging with global health authorities. We aim to have our end-of-Phase I meeting with the US FDA during the first half of 2027, which aligns with the maturing data for both our putative RP3D IV dose of 400 microgram per kilogram, along with our dose escalation data for the subcutaneous presentation of XMAP819. We plan to discuss an accelerated approval pathway with health authorities. Given the robust analysis we have around two key subgroups, patients that have progressed on prior IO and at least two prior VEGFR TKIs, which represented over 60% of the patient population enrolled into our phase one study, and or patients that have progressed on all three current standard of care mechanisms, IO, VEGRTKI, and HIF2-alpha inhibitors, which represented 30% of our enrolled patient population. As you can see from the confirmed response rate confidence intervals, our lower bounds of response exceed what could be expected to be achieved with the current available treatments that we previously discussed. From a market perspective, we view the post-IO and two prior VEGFR TKI market largely representative of a third-line indication in advanced clear cell renal cell carcinoma, and in the U.S. alone would represent more than 9,000 eligible patients annually based on a claims database analysis. The market for triple class exposed patients is currently limited, but expected to grow substantially, as a combination of Belzutafan and Levatmib has now been approved in the U.S. as a new treatment for patients who have progressed on prior PD-1 or PD-L1 therapy. Overall, we are very excited that XMAP819 has demonstrated breakthrough potential for patients with high NMET need who have exhausted standard of care options and could benefit from accelerated access to treatment with the drug. Our comprehensive development plan for XMAB819 continues to accelerate, with a focus on moving 819 as a monotherapy drug into earlier lines of treatment, optimizing clinical convenience for commercial use, and also exploring rational combinations with current standard of care for future frontline studies. We expect the breadth of our development activities in renal cell carcinoma to continue expanding as we view the development pathway going forward as a parallel effort to ultimately maximize the number of regulatory approvals that can be rapidly achieved across the treatment landscape, which we hope to start by 2030. The commercial market opportunity in renal cell carcinoma is significant. With the current addressable global market over $11 billion currently, expected to continue growing through 2030, our near-term focus for regulatory approval and commercial launch is to reduce clinical reliance on recycling of VEGFR TKI therapy across lines of treatment, with the introduction of XMAB819 as a powerful, novel, first-in-class XMAV2 plus 1 T-cell engager. We feel good that an initial approval in the later line setting as a monotherapy can support XMABA819 exceeding potential blockbuster status ahead of approval in earlier line settings. Longer term, we view the frontline therapy where PD-1, PD-L1 inhibitors are the anchor as the largest market, currently split between use of pembrolizumab and nivolumab depending on the specific frontline indication or combination. Our ongoing proof-of-concept basket study for EMPP3-positive tumors, papillary renal cell carcinoma, microsatellite-stable colorectal cancer, and non-squamous non-small-cell lung cancer have the potential to greatly expand the scope and benefit of XMAP819. Each of these tumors have high unmet need for patients that have failed frontline therapy. Our EMPP3 positivity rate on screening for each of these tumor types supports clinical development, and we expect that our early promising results in clear cell renal cell carcinoma could energize engagement with oncologists specializing in thoracic and gastrointestinal cancers. Overall, we are thrilled with the momentum of the XMAP819 program building into 2027, a pivotal year of clinical milestones that we expect to support our confidence around XMAP819 as potentially the first commercial stage program wholly owned by Zencore as we approach 2030. And with that, I will turn it over to Basil for a look at our broader pipeline and concluding remarks. Basil? Thanks, Dane. We're grateful everybody could join us today for a demonstration of what Zencore strives to do, engineer novel molecules to address really hard clinical problems like precisely directing T-cells to solid tumors, and prosecute these molecules in the clinic so patients can benefit as quickly as possible. This 819 data release is just the beginning of a series of planned clinical updates across our portfolio over the next year, and I hope you can join us for those too. Now I'd like to thank the team at CENCOR with their perseverance and incredibly broad range of talent spanning engineering, protein chemistry, pharmacology, manufacturing, non-clinical, and clinical development. And I want to thank our wonderful clinical study teams and investigators around the globe. Most important, I want to thank our patients and their families and caregivers for their courage and commitment and hope in bringing new medicines forward. We'd be happy to take questions now. Operator? Thank you. At this time, if you'd like to ask a question, please click on the raise hand button, which can be found on the black bar at the bottom of your screen. When it is your turn, you will receive a message on your screen from the host allowing you to talk, and then you will hear your name called. Please accept, unmute your audio, and ask your question. If you're dialing in by phone, please use star six to unmute. Our first question comes from Steve Seedhouse with Cantor. Please go ahead with your question! Thanks so much, good morning, congrats obviously on terrific data. I wanted to first just ask about what you think you'll need in terms of a number of patients or additional study for that accelerated approval pathway in the weight-line patients. Yes. Thanks, Steve. And a great question. So, you know, we'll obviously state first and foremost, the go-forward path needs to be defined in proper discussions with global health authorities. We plan to have a meeting with FDA at the end of phase one in the half of 2027. Pending those discussions, I think our expectation going in is your normal rule of thumb kind of primary analysis set that you would want to have for review of accelerated approval and any indication. And that's going to be somewhere around that ballpark 100 patients for a safety analysis. And then your primary analysis for efficacy would really be powered to that lower bound at the confidence interval so um you know in in those subgroups that we presented uh based on the strong uh response rate we've observed um in in this group and across the 100 200 and 400 microgram per kilogram uh target doses uh we feel pretty good about um that uh powering assumption uh being even less than 100 that we need for the safety pool um so i think think we have a strong data set to really have a productive and hopefully collaborative conversation with health authorities going into the early part of 2027. Basil? No, I think you said it all. I think as our data matures for the 400 mic per gig cohort, you know, we've sorted out the enrollments essentially done. We're going to have about the same number of patients there as we did for our 100 and 200 cohorts to support our dose selection and um you know as the cohort is mature we're excited to see what we we can see you know we know we just had in a one month um incremental data cut from our september data cut for the presentation yesterday at the conference we added in our press release an extra month and there was an additional person who responded who was a stable disease and responded i think on their fourth scan much like we see in in the rest of of the study is continuing deepening of anti-tumor activity as patients are on the agent longer. So I think we're going to have a robust package. It's going to be very well supported. And I think our analysis of the prior therapies is such that the end for an accelerated approval is something very achievable. Thank you. And I wanted to ask specifically on, so as you think about the first line opportunity here and first just generating the data of combining 819 with a PD-1 inhibitor, what gives you confidence that that will be viable, that there won't be any overlapping toxicity. Do you have any insights already from the study or just working with the molecule to suggest that that's going to be okay from a safety tolerability standpoint? Sure, Steve. So I guess there's two points. One is from our own study. We've had a lot of patients come on study that have had recent prior PD-1 checkpoint exposure, and we don't have much of washout period, right? These patients are progressing rapidly. So we start treating them very quickly. So there's a number of folks who have significant exposure to anti-PD-1 and significant anti- PD-1 on board when they come onto our study. And there've been nothing notable about that group. And I think that that gives us a lot of comfort that having significant PD-2 inhibitory activity, you know, from whether it's a NEVO or a PEMBRO from a few weeks prior therapy didn't cause any untoward drive in our AE profile. In fact, it seems the same as whether they hadn't had recent checkpoint. So that, I think, gives us a lot of confidence going into our quick safety cohorts to combine with PD-1 that that ought to be something quite feasible. I think there's another line of evidence just from the class of CD3 T-cell engagers, one of which then core design that have been combined with PD-1 inhibitors. So, for example, ASP2138 is no longer called an XMAP. Our partnership with Astellas for the CloudM18-2 CD3, same 2 plus 1 format as XMAB819, that had quite a big data set of phase 1 data being combined with PEMBRO plus chemo in frontline gastric TEJ. And that data was quite positive, very well tolerated. it didn't really exacerbate or change the AE profiles of chemo or PD-1 or of 2138, the CD3 bispecific, and that's in phase three right now. And then you see additional evidence, tarlatumab, beautiful data presented a couple of days ago here at ESMO in Delphi 305 combined with DERVA. And we also have the experience from Chemtrax. So I think both our experience with patients with lots of anti-PD-1 on board, not having anything different in their AE profile, as well as the growing experience now with T cell engagers being combined with checkpoints, you know, really to great positive effects. You know, it really encourages us to want to explore the opportunity for 819 to be combined with PD-1 inhibition as we think about how to get to that frontline setting. I'll make a quick point in terms of combinations more broadly. I think there's a, You know, unique aspect of what we've seen from a safety perspective of XMAP819, where the drug does not have cumulative toxicity, right? You see the priming period has a toleration of a couple of weeks, and then at target dose, there's no, the drug's very clean. every other drug, PD-1, VEGFR, TKIs, alpha inhibitors that would be, you know, combinable standard of cares all have cumulative toxicity that actually emerges in the later cycles of treatment, kind of cycle one, cycle two, cycle three, which makes our unique ability to have truly orthogonal toxicity to these other agents. So I think we have, you Know, a bright future ahead of maximizing the potential of the drug in some of these different settings and indications with current standard of care. So we're very excited about that. Great insights. Thank you so much. Congratulations. Thank you. Your next question comes from Matthew Fitz with Blair. Please unmute to ask your question. Hi, guys. Congrats. Let me offer my congrats as well. Two quick questions. One, And I'm just curious how the prior HIF-2 alpha exposure compared across those target dose levels. I wonder if there's any differences in the number of patients who had HIF2 there. And I know sub-Q is ongoing, and you set a data update in the first half, but any kind of early read on how the CRS profile compares IV to sub-q? Obviously, I have seen some other TCEs get a little bit easier on sub-qu as you move to subq. Thank you. Hi. So, Matt, can you hear me? Yeah, you're a little in and out. So on the sub-Q point, so, you know, we did have some sub-q data in our data cut last year. It was in a blended cohort that we disclosed. And we're still dose escalating, and we'll present that data sometime in the first half of next year. But, you You know, historically, sub-Q dosing of CD3 bispecifics has reduced or blunted the side effect profile, the CRS-related side effects, because you do have a slower onset of drug action and you do have a lower C-max. So, you know, that's something that we're certainly looking for. We really can't comment yet on our specific data. And then there was a little bit of a stutter in the the audio feed but i thought i heard you say the prior hip 2 alpha exposures were you asking about differences across our dose levels yeah any differences in prior exposure i don't think there is i mean you can actually uh um look at the waterfall plot in the presentation we just gave and we actually provide the dots on prior therapy there for both of those subpopulations. And, you know, very consistent, very strong signal, especially at 400 microgram per kilogram. Great. Thanks. Congrats again. Thank you. Your next question comes from Sean McCutcheon with Raymond James. Please go ahead. hi guys thanks for the the question um maybe kind of uh building off of steve's question earlier uh dr paul uh noted some mechanistic data indicating that enpp3 is associated with an angiogenic phenotype which is intuitive biologically but how are you thinking about you know rational combinations and earlier lines you already disclosed that you'll be combining the PD-1, but does a VEGFR-TKI combo make sense in this setting, or does it make more sense to avoid multi-kinase-related cardiotoxin and other adverse events? Thanks. Yeah, I think, you know, we think of 819 as a drug that activates the immune system in a way that kind of short-circuits the usual considerations of, is this an angiogenic phenotype? Is this an immune phenotype, like it's typically done when you're only profiling the tumor cells. So CD3 engagement works around the standard way a T cell would normally engage with the target cell and turn on. That would be through MHT-TCR complex formation. We just short circuit that entirely. So we're less concerned about that point, though we certainly do follow Dr. Paul's work very closely in that area. I think you hit the nail on the head, though, about combination with VEGFR TKI, I think we'd like to start exploring ways to avoid that kind of the inherent toxicities that come with that class to open up the door to potentially an entirely immunotherapy-based treatment regimen, which could have completely different AE profile, potentially more beneficial. And so the mechanistic rationale for a PD-1 inhibitor with XMAP819 is excellent. We have plenty of preclinical data that shows that PD-1 inhibition only amplifies the activity of EXMAP 819. I think the selectivity of 819 for tumor cells and the really good long-term tolerability profile post-priming period gives us a good rationale for why a PD-2 combination would be, you know, top of the list? I think from a, you know, clinical utility perspective, one, obviously avoiding VEGFR TKIs would improve quality of life and health related activities of the patients as they're maintained on therapy. But in the case of 819, specifically going back to where we talked about time to response, 75% of patients have a VEGR TKI like time to respond to this therapy. We're very encouraged that we're able to blunt primary progressive disease, even in a severely intermediate to poor risk heavily pre-treated patient population as we enrolled into the study, yet also retain some of the features of IO-based mechanism where 25% of the patients have deepening responses over time. And as I said in the prepared remarks, that deepening response over time is because we have such good tolerability at the target dose, it allows consistent EC80 plus coverage as we're not dose interrupting, we're not dose reducing, as you get with many standard of care therapies, especially in combination. Excellent. Congrats on the great data, guys. Your next question comes from Gregory Renza with Truist Securities. Congrats to the team again. Really good data. Maybe let's start with a quick clarifying questions. Do you intend to use that phase three study to support accelerated approval, or is there a possibility to expand the current phase one and use a single-arm cohort to support accelerated approval? Thanks, Subha. So the global RCT with the proposed control arm of Tavaznib, that would be a full approval study. Obviously, when you go accelerated approval, it's considered a conditional approval. That would be an confirmatory study under the current plan that we'd like to propose to health authorities. We think using an active control of VEGFR TKI that is currently standard of care monotherapy in the later lines or post-VEGFR TKI is a really strong position to be in. And we obviously have the data, we think, to do very well in that comparison in that study. That's where you see, I think, a lot of the strength of the labels. And, you know, it's been a while, I thinks, since there's been a monotherapy developed that I think has the potential to advance standard of care beyond these VEGF RTKIs. So we're very confident in our design that we're going to propose against Fosnib. And yes, that would be full approval. And hopefully, based on the strength of the data, we could go in front of that with an accelerated approval pathway in a more select patient population. Got it. Thank you. And just a quick follow-up. On durability, the initial six-month landmark PFS looks quite favorable. I'm just curious, what levels of PFS or other durability metrics do you expect or need to be supportive of accelerated approval consideration? Thanks so much. Yes. So accelerated approval, because it's a single arm study, that is the primary analysis set. Survival metrics are not considered generally by health authorities. The metrics they're looking at are the lower bound of your overall response rate and the median duration of response, or the percentage of responders that have six months or greater response, and essentially the lower bound of that. So that's when you look at our data. Our DOR is still maturing, yet highly encouraging, with over 70% of responders remaining in response with a median follow-up of seven months, but also the very high response rate with the lower bounds exceeding any known responses that could be achieved for current standard of care. either in a triple-class exposed population or patients that progressed on one IO, PD-1, PD-L1 therapy, and at least two VEGFR TKIs. So we think we're in a very strong position here to have those discussions. And yes, generally, the metrics that are going to be used for efficacy are OR and MDR. Got it. Thanks so much. Congrats again. Thank you. Your next question comes from Dana Greenbush with Learing Partners. Hi. Congratulations on the exciting data set. I think we all know and have learned from Amgen about how important it is to get the right dose for a T cell engager. And, you know, with Tarla, they did some very large dose finding studies. And I wonder if you could talk more about landing on the 400 dose in terms of PK, PD, efficacy, and what more you want to see from that dose before you would confirm that that's definitely the dose you want to take forward. Thank you. Yeah, thanks, Dana. So for us, the early indicators that 400 is the right dose is are the very consistent AE profile between 200 and 400. In fact, they use precisely the same priming regimen. So the priming dose 1, 2, 3 are identical for the 200 and400. And that's where the AEs are almost entirely. and we have in the follow-up period, you know, greater than 29 days, identical profiles. So I think on the tolerability side, we don't see any real differences that would change our thinking. On the activity side, one of the slides we just presented shows that it does take about a quarter of patients continue to have deepening of anti-tumor activity and a quarter of our responders happen after about four months. And so if we just had an additional response start, it's still unconfirmed, but we're optimistic it'll confirm in this 400 cohort. So now we're above 50% of the 55% unconfhirmed ORR. And I think that we've enrolled more patients and our early indicators from that additional enrollment is very consistent with what we've seen so far with 400. So I think the drive of efficacy is trending upward. It's showing a continued dose response and the tolerability is excellent. And I would note that this really matches well with the modeling we did based on our quantitative systems pharmacology work from our preclinical characterization and early human PK is matching up beautifully that this is the top end of that sigmoidal dose response curve. And so all the pieces align. Of course, we're going to confirm it when we've got a little over 20 patients. Like I said, they're all enrolled. The first patients came on, I think, a week or two ago. So by early in the new year, we should have data. We've put it together at the end of phase one package. So that's really the sort of coincidence of factors that makes us feel really excited about 400 and of course i'll note 200 had a you know 44 response rate by itself and really strong durability showing so i think we're in a good spot yeah just to directly answer the regulatory aspect of it um yeah i we we think between 100 200 and 400 uh dose characterization would fully support and satisfy project optimus great thank you our next question comes from david nearing garden with weblish securities please go ahead with your question hey thanks for taking the question i had um a couple one on the baseline characteristics of the patients um they appear to have dropped significantly from a higher level of favorable risk scores from your last data update to now. I was just wondering if patients were reclassified or if there's just a function of more patients getting enrolled that were at worse prognostic indicators. And then just on the pretreatment or additional treatment to prevent CRS, I mean, what that was, could you remind us when that was initiated? And, you know, if you notice the changes in effects on the patient's levels of CRS and adverse events. Thanks. okay thanks david um i think i'll tackle the the baseline and maybe basil you tackle pre-treatment um so on on the baseline i think you're referring to a comparison of the uh the pooled data we presented um at the triple meeting last year in 2025 versus uh this year um so the triple meaning last year, A1 was blended between IV and sub-Q versus IV only this year, and obviously a much different data set. But your observation is correct. Actually, last year those IMDCs were at diagnosis, not baseline. And I think there were a number, a lot of missing data points that were not collected at diagnosis. This year, to be proper, because IMDC is a very important component of characterizing your patient population, we actually calculated IMDC at baseline for all the patients in these cohorts presented. It is notable, however, that we had to derive the Karnofsky performance score using ECOG, which is validated by IMDC, stringently using ETOG2. That said, around probably 30% of ETOGs ones actually are 70 on a KPS score. So we're actually probably more skewed towards poor and intermediate on a true baseline IMDC than what we're presenting. So a very difficult and poor prognosis patient population, which is, again, I think, as you heard from the clinical community, a good basis for the excitement of the response rates that were presented. Basil? Yeah. And so I'll touch on the pretreatment. So starting a little over a year ago, we started using prophylactic antihistamines, Zyrtec, you know, Siderazine, to help manage the rash. And that certainly helped. Um, we'd always been doing a pretreatment dexamethasone and Benadryl and, you know, IV saline, just make sure they're hydrated, um, before our priming doses and our first target dose. So every time you introduce the drug at a new dose level, a new dosamount, when you're doing your priming, we added the prophylactic, um...the prophylacticosalizumab on only priming dose day one, which has the highest CRS rate and the highest, um..you know, rash and all that we started introducing that really um i would say late last year right around when we we did our last data presentation and yes it's absolutely had a beneficial effect at easing the day one and day eight um crs rate so i think i think it's worked out really nicely and it's simplified things for the doctors and it'S really part of a setup for peeling back the inpatient monitoring period, this hospitalization period, that's been a trend now for all the solid tumor TCEs and even the ones in myeloma and lymphoma, I should say. It just, as you gain experience with the drug through development, you start reducing the amount of hospitalization days and overnight stays, starting with the sort of first target dose and your later priming doses and then bringing it back in. Just beautiful data on xyloridamide, another exmap two plus one that Amgen is developing in prostate cancer against steep one, that guy, they've a really nice poster with a no, no hospitalization, uh, through any of their priming, um, demonstrating feasibility for that for them. And of course, charlatanab is down to, I think a couple hours of inpatient. Um, so this is all part of our plan to make this a drug that is really easy to use in the community, which we're, I Think making great progress on And the prophytosy was just part of that. Got it. Thank you. The next question comes from Brian Chang with J.P. Morgan. Hi, this is Sarah on for Brian. Thanks for taking our question. Just one from us. Can you talk about the plan to peel back the overnight stays required during the primary period? And how do you envision that or the requirements for the phase three? yeah so we take the precedent from again how folks have done it before us you start with um you start by peeling back the later days so the cohort we've opened or just about to open i should say in our phase one study we call it our reduced monitoring cohort that's about to start enrolling and we're peeling backthe overnight stays on the target last priming dose priming goes three and we're going to gather some data from a modest size cohort there. And then we'll follow the lead as we proceed in development. We continue gathering data with reduced monitoring. And you saw with Amgen, they introduced it during phase three for charlatanab and have started to do that for xaloridamide as well. So you can do it as you roll forward through development. You don't need to delay development to get that to the point where you're getting a lot reduced, a lot of reduced hospitalization by the time of approval. And how far we can get is just going to depend on specifics. We'll certainly update. Again, we're optimistic from the success our peers and our partners have had. It's definitely an important consideration for the market opportunity. We're very optimistic that we've got a good start. Thank you. Our next question comes from Derek Artillo with Wells Fargo. Please go ahead. Hey, good morning, and thanks for taking the questions. Congrats on the data. Just a quick question. So how does the sub-Q development align with the timing of the 819 phase 3? Any consideration of using that presentation for the trial? Thanks. Thanks, Derek. Good question. So subcutaneous development has been going staggered parallel dose escalation to what we've accomplished in IV. Given the dose characterization we've done in IV, I think we're fairly robust in understanding exposure response analysis. So SubQ, where we're at, is on track to present data from SubQ in the first half of 2027. And that data set will obviously align with our end of phase one meeting. And there's really three paths here, right? You know, path one, we use sub-Q for the next phase of clinical development as the preferred presentation. Path two, we go forward with IV. Sub-Q becomes a lifecycle play for clinical convenience, as has been done with many biologics, including the PD-1 L1 class. or three, we just feel that sub-Q is inferior for whatever reason to IV and go purely with IV. But it's on us as a company to explore that. I think we'll wait for the data to play out to actually present, but I would say we're encouraged by what we're seeing in sub-q. So stay tuned on that front. We'll present the data alongside the full cohort analysis of 400 microgram per kilogram IV in the first half of 27, and I think have some great regulatory interactions and keep moving this program forward. Great, thank you. Our next question comes from Leonid Timisha with RBC. Please go ahead with your question. Hey, guys. Thanks for taking my question. I want to ask maybe an open-ended one just on the other tumor types you guys are exploring, small cell, colorectal. How should we think about the re-throughs on the efficacy and safety side from today's data? And I guess any opportunity to accelerate those studies and any differences in ENPP3 expression that we should think about as you guys move into those tumor types? Thanks. Oh, yes. Hi. Thanks. Great question, We just got rolling a few months ago in the study doing papillary venal cell, adeno non-small cell lung, and MSS colorectal cancer. Those are all tumor types that express high amounts of ENPP3 in varying populations. For the papillary, it's well over half of patients express ENPP4 at a high enough level. and then you've got your colorectal and lung a little bit below that, maybe between a third and a half, we expect, based on our pre-work. So, you know, these are really, really big opportunities. Now, what's the read-through? On the safety side, we just started treating these patients at our expected go-forward dose of 400 micrograms per kilogram with the same priming regimen. We do expect to see pretty similar tolerability profiles. Obviously, we're running this study to look at the data. There's not a huge amount of experience with solid tumor CD3s of a given molecule against different tumor types. So I think we're going to be really building that data set ahead of any of our partners or peers. But I think, you know, we're really optimistic that the tolerability should be very similar. And that's why we started with our target dose. As for efficacy, these are very different tumor types. They have different susceptibilities to being killed. Just generally, their T-cell distributions are different. So we're going to learn a ton about how each of these behave. You know, I'll note that on the top end, non-small cell lung is considered a generally pretty immune susceptible tumor, right? Certainly outstanding checkpoint inhibitor data there. And then you go through papillary renal, much less known and mss colorectal been a tough nut to crack but a huge unmet need so you know there's there's just such an opportunity once you have a drug that's showing outstanding activity in its first indication like axmab 819 and clear cell with a profile that we can you know really pretty readily give it and an excellent long-term tolerability this is when you really start putting the pedal to the metal and examining other indications and really try to leverage it so you Know stay tuned We haven't guided on timing for that, but, you know, we just started enrolling a few months ago, but there's no escalation. So things should move really quickly with these additional tumor types to really give us insight on just how broad the opportunity is for 819. Thank you. Our last question comes from Tara Bancroft with TD Cohen. Please go ahead with your question. Hi, this is Danny on for Tara Bacoff. Thank you for taking our questions and congratulations on the data set. I think you guys noted that about 25% of responses emerge after more than four months and that the responses can continue to deepen over time. How would that influence scan timing treatment beyond progression rules and progression adjudication randomized study? And then perhaps any color or framing that you guys can give on the expected sequence of milestones for 819 in 2027 or first half 2027? Thank you so much. Yeah. So I think with scan timing, you want to use scan timing that makes sense relative to the expected deltas you're going to have in whatever durability metrics. So the general rule of thumb is people tend to scan in that eight to 10 week range. We haven't really decided on or disclosed really all the details of our pivotal studies. So, but we definitely think we want to, you know, keep people on drug because it's working really well as you go forward. And remember, scans keep going on during study for a year or two. So I think we've got plenty of time to capture all the responses. You know, do you want to talk about maybe the sequence of our milestones for 819 as we go into 27, Dan? Sure. Yeah, happy to. I actually think we would be remiss because we talked about actually last year too, in terms of scan timing. So in this study, we had week six first scan. There's actually, I would say, I don't know, Basil, a handful of patients that on their week six scan actually had an emergence of new target lesions, were marked as a PD, and then on next scan had complete resolution of those new target lesions and deep responses to the target lesions from baseline, but forever marked as PD. You know, it's our theory that, again, only in a handful of patients, if the scan timing was more, you know, to standard practice today, which is around, you Know, somewhere between eight and 10 weeks, those would actually be PRs. So obviously, under careful consideration as we go forward. But yeah, expect to kind of normalize scan timing cycle. In terms of milestones, we have a big year ahead for this program. Again, you know, it emphasized that this is what we consider to be the first potential commercial program for Zencore as a company. And our focus, our allocation of resources is matched to that goal and focus. And as we go into 2027, you're going to see that cadence. We're going to present the first sub-Q data in the first half of 2027. We'll provide the confirmatory analysis set of at least an N of 20 efficacy of valuable for the IV 400 microgram per kilogram dose that we think is the potential RP3D. We will obviously have regulatory interactions in the first half that will clearly define our path forward, both from a potential accelerated approval pathway, but also from the confirmatory or full approval study that we're proposing versus Tavaznib. And that obviously doesn't include the number of sub-studies that we talked about today that are starting to ramp up right now. So, you know, still a little TBD on a lot of the things that will be percolating as we head into 2027. But I think the first half of the year is going to be, you know, some continued excitement on the momentum of this program. Thank you very much. We have no further questions at this time. I'll now turn the call back over to Basil Dayat for closing remarks. Hey, thanks everyone for joining us today to review these results and plans for XMAP 819, which you can see we're extremely excited about. This is just the beginning of several planned updates for 819, as well as other elements of our portfolio in the next year. And we look forward to catching up with you again about those in the coming months. And for now, have a wonderful rest of your day. Take care.