Hello and welcome to the Xencor 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 Liles, 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 XmAb819 in advanced clear cell renal cell carcinoma. The press release is available at www.xencor.com. Providing comments on the call from Xencor are Bassil Dahiyat, 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 Chou, Senior Vice President and Head of Clinical Development for Xencor's Oncology Programs. We are also joined by Dr. Sumanta Pal, 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, Xencor 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 on 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 Form 10-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 Bassil.
Thanks, Charles, and thank you for joining us today. We are 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 Xencor'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 are two ongoing phase III programs, both with exciting data created by Xencor using our XmAb platform and 2+1 format for selective tumor targeting. ASP2138 at Astellas and xaluritamig at Amgen. We expect XmAb819 to be the third in pivotal studies when we start our planned trial in 2027.
We are not aware of any other TCE platform or company that has made this much progress against the enormous unmet need in solid tumor oncology. In addition to this, we are awaiting an update from our partner, J&J, for the combination of pasritamig with JNJ-9401 and XmAb CD28 bispecific. It is important to put this update into another context. We have spent the last three years focusing on excellence in clinical trial execution and strategy, trying to have Xencor realize the value from the incredibly promising XmAb 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 I-B data from plamotamab in RA in two weeks at ACR. Then phase I data from XmAb412, our bispecific TL1A/IL-23.
Then the primary endpoint of our global phase II-B study of XmAb942 in ulcerative colitis, plus further data updates from the ongoing studies of XmAb819. Now back to XmAb819. 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 is a high level in tumor cells, higher level in tumor cells than healthy cells, but these cases still have target in those healthy cells. Drugging solid tumor targets has been a compromise between high anti-tumor potency and hence impact, and high selectivity, which avoids toxicity. This 2x2 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 compromise selectivity, which you can see from ADC killing of low or even zero target tumor cells, and tox profiles reflecting their chemo ligand. For first gen TCEs, having tox challenges achieving and sustaining effective doses in solid tumor indications. With our 2+1 platform, we have 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 am going to turn it over to John Desjarlais, our longtime CSO and co-inventor of our XmAb platform, so he can describe how we did this to create XmAb819 and the other 2+1s.
Thanks, Bassil. Since the XmAb 2+1 platform has been critical to ours and our partners solid tumors T-cell engagers strategy, I like to review the general concept. First, the 2+1 format binds tumors like natural antibodies do, specifically we have bivalent targeting of tumor antigen. That provides as with the powerful engineering paradigm to create T-cell engager with improve tumor versus normal selective. The way that works is we tune the affinity tumor targeting arms 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 is a well-validated biophysical phenomenon due to the heightened ability of the second targeting arm to quickly find another target when there is lots of it around, like natural antibodies do. In contrast, when using a 1+1 bispecific, that single tumor targeting arm has to have sufficient affinity on its own to drive binding the tumor cells, meaning it is much harder to distinguish 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 XmAb 2+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+1 bispecific, then you can see the model predicts very little discrimination between tumor and normal, which of course means it will have higher potential for safety issues. In fact, the only way to recover more selectivity with a 1+1 is to reduce its affinity, which then means we would struggle to have sufficient killing of tumor cells.
Now let us focus more specifically on XmAb819, Xencor's XmAb 2+1 that we developed for the treatment of kidney cancer. From the antibody diagram, you can see that it has two arms that bind ENPP3 and a single CD3 targeting arm. Of course, it was affinity/avidity tuned to optimize for tumor normal selectivity. The middle plot shows that nicely where we could see significantly more killing of a high-density tumor cell line versus one with lower ENPP3 expression. Finally, on the right plot, we are able to see strong anti-tumor activity of XmAb819 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, but we know the target is also expressed to some extent across a wide range of histologies.
As you can see from this large IHC data set we collected, ENPP3 is strongly and uniformly expressed in clear cell RCC. We also see a good proportion of papillary RCC patients expressing strong levels, and there is also a good number of microsatellite stable colorectal cancer patients and lung cancer patients that express significant levels. We have included some representative IHC images from some of these histologies on the right. Now that we have observed compelling activity in clear cell RCC, we recently opened cohorts for papillary RCC, colorectal cancer, and lung cancer. While we do not need to pre-screen for ENPP3 expression in clear cell, enrollment in these other cohorts is contingent on seeing strong expression by IHC. Xencor 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 have been excited to see such compelling progress with many of our and our partners' clinical stage molecules. With such a strong backbone format for XmAb819, we have 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. 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 XmAb819 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 cytotoxicity of 80%. As I emphasized earlier, Xencor's platforms are built for robust stability, developability, and manufacturing. You can see from this summary table that we have a high titer cell bank for XmAb819 that scales well to 2,000 liter. Our drug substance and product are both stable for at least 60 months in liquid formulation. We are using commercially validated CDMOs for manufacturing in the U.S.
Now, I would like to introduce one of our investigators and close collaborators, Dr. Monty Pal from the City of Hope Comprehensive 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 on the West Coast. I will now turn things over to Dr. Pal to review the phase I results for XmAb819 as presented yesterday at ESMO.
Thank you so much, Dr. Desjarlais. First and foremost, this is a really exciting opportunity. I am 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 will 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 are also keen on investigating the agent in the context of papillary kidney cancer, colon cancer, and lung cancer, as he had 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 are reporting today phases of dose escalation involving 100 micrograms per kilogram up to 400 micrograms per kilogram. We have completed a dose expansion at 100 and 200 micrograms per kilogram and continue to enroll at 400 micrograms per kilogram. I will 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. 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 will 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 6%- 7% of the population overall. The vast majority of patients that we enrolled were intermediate and poor risk. If we had looked at prior therapy, as I had emphasized previously, this was a very heavily pre-treated population of patients. About one-quarter of patients had received three prior lines of therapy, and in fact, 35%- 40% of patients had received four or more prior lines of treatment.
In addition to this, beyond just receiving one VEGF-TKI and one checkpoint inhibitor, we had approximately 63%- 64% of patients that had received two or more prior VEGF- TKIs. We also had about 35% of patients that had received a prior HIF-2 inhibitor as well. We will dive a little bit deeper into these subsets as we explore the efficacy of XmAb819. The next slide is a busy slide that highlights adverse events. I will 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. 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 premedication for XmAb819 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 priming 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. Just as we saw with cytokine release syndrome, you can see 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, transaminase levels, which is articulated in the graphic in the bottom right, really peaked after priming dose three. 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 antitumor 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 four point one 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 in the 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-up time of about four and a half months, you see patients that are really approaching a durable response, with some patients extending their responses to 10 months and beyond. 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%, a disease control rate of 81.8%. You can see that almost all patients had tumor shrinkage, and on the spider plot articulated below, many ongoing responses. I am keen on updating this data in the months to come. I think it is salient to point out two specific subgroups. Again, as noted, all patients in the study had to receive a prior VEGF-TKI 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%. 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. What we see here is a response rate of 45.2%. These data really, in my opinion, represent a high watermark for what we have seen in phase I clinical trials in renal cell carcinoma to date. The disease control rate in that subset was 85.7%. On the next slide is articulated the ongoing responses within this population, of which there are 19. You can see that the median time to response is relatively quick, two point seven months.
Median time on treatment within this cohort is seven months. As noted previously, we are starting to see very durable responses with some patients who have responses extending to almost two and a half years, some approaching two years. Again, very keen on extending this data. 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 have been treating for a decade. This patient is 56 years old. He was diagnosed 10 years ago, as noted, with metastatic disease incurred about five years ago. This patient had two prior lines of therapy, the first being cabozantinib with nivolumab, the second being lenvatinib and everolimus.
He was on the first therapy for a month, the second therapy for three 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 mediastinal 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, this patient 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 has had normalization of his lymph nodes.
He has had disappearance of lung and pancreatic lesions, and his response is ongoing, a complete response at 16 months. Not only that, but I'll note that his toxicity profiles have just been exceptional, and he's really had restoration of his quality of life. In conclusion, XmAb819 shows very meaningful antitumor activity in patients with advanced clear cell renal cell carcinoma. I'll emphasize that this, in my mind, represents a high watermark amongst trials that I've seen in the phase I space in this field. Antitumor activity was observed in a dose-dependent manner with an objective response rate of 30% at 100 micrograms per kilogram. That increases to 44% at 200 micrograms per kilogram and further to 45% at 400 micrograms per kilogram.
The majority of these responses are still ongoing at our last data cut. Not only that, but if we think to the triple pretreated population of patients, those that have received a checkpoint inhibitor, a TKI, and a HIF-2 inhibitor, we see a response rate of 35%. In addition, in those individuals that have received two or more VEGF- TKIs, again, very heavily pretreated, a very exciting response rate of 45%. In my opinion, these data firmly support continued development of XmAb819 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 Xencor.
Thank you, Dr. Pal, for your collaboration and leadership. Thanks to the entire City of Hope team and patients that have supported XmAb819 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 ESMO presentation, which helps provide more details for our development decisions as we move into late-phase development in 2027. Our pooled swim plot here for the expanded target dose cohorts of 100, 200, and 400 micrograms per kilogram IV remains immature with a seven point nine-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 follow-up 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 response, we see those responses continue to deepen over time.
Following the step of 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 III dose for XmAb819. Even though we've only recently finished enrolling the 400 microgram 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 micrograms 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. 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 median 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 microgram per kilogram target doses.
Based on the strength of both the efficacy and safety profile for XmAb819 at our chosen target dose cohorts, we're optimistic we're in a favorable position to use an active standard of care control tivozanib for our registration-enabling study, supporting full approval of XmAb819 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 XmAb819 largely as a second or third-line monotherapy drug of choice. We plan the power for a clinically meaningful PFS hazard ratio of 0.7 based on our expectations of tivozanib in this treatment setting. We view the third-line subgroup analysis from TIVO-3 to be the most contemporary data set for our expectations of tivozanib in a post-IO and VEGFR TKI patient population.
By the numbers in this setting, treatment with tivozanib has achieved a 10.5% ORR, a six-month PFS Kaplan-Meier estimate of 41%, and a median PFS estimate of five point four 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 XmAb819 to make an impact for patients and caregivers as our first indication for full approval. Now I'll turn it over to my colleague, Dane, to discuss the broader strategy with XmAb819 development.
Thank you, Jeff. Setting the background of what has been achieved is important context. As we presented earlier, XmAb819 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 III target dose of 400 microgram per kilogram. Shown on this slide, for illustration purposes, as they were not head-to-head studies, the 45% confirmed overall response rate of the XmAb819 putative RP3D cohort in the fourth-line treatment setting represents an unprecedented level of anti-tumor 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 XmAb819 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 disease relative to the most recent monotherapy-approved agents, tivozanib and belzutifan, but also to the current dominant standard of care mono and combination therapy, cabozantinib, in a post-VEGFR TKI treatment line.
Importantly, the safety profile of XmAb819 is well-tolerated, with the 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, XmAb819's 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 XmAb819 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 U.S. 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 XmAb819. 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 I study, and/or patients that have progressed on all three current standard of care mechanisms, IO, VEGFR TKI, and HIF-2α 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 2 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 belzutifan and lenvatinib 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 XmAb819 has demonstrated breakthrough potential for patients with high unmet 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 XmAb819 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, and 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 XmAb 2+1 T-cell engager. We feel good that an initial approval in the later line setting as a monotherapy can support XmAb819 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 ENPP3-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 XmAb819. Each of these tumors have high unmet need for patients that have failed frontline therapy. Our ENPP3 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 XmAb819 program building into 2027, a pivotal year of clinical milestones that we expect to support our confidence around XmAb819 as potentially the first commercial stage program wholly owned by Xencor as we approach 2030.
And with that, I will turn it over to Bassil for a look at our broader pipeline and concluding remarks. Bassil?
Thanks, Dane. We're grateful everybody could join us today for a demonstration of what Xencor 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 XmAb819 data release is just the beginning of a series of planned clinical updates across our portfolio over the next year, and hope you can join us for those too. Now, I'd like to thank the team at Xencor with their perseverance and incredibly broad range of talents spanning engineering, protein chemistry, pharmacology, manufacturing, non-clinical and clinical development. 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 are dialing in via 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. Wanted to first just ask about what you think you'll need in terms of number of patients or additional study for that accelerated approval pathway in the late line patients.
Yes. Thanks, Steve, and great question. 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 end of phase I in the first 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 in any indication. That's going to be somewhere around that ballpark of 100 patients for a safety analysis. Then your primary analysis set for efficacy would really be powered to that lower bound at the confidence interval.
In those subgroups that we presented, based on the strong response rate we have observed in this group and across the 100, 200, and 400 microgram per kilogram target doses, we feel pretty good about that powering assumption being even less than 100 that we'd need for the safety pool. I 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. Bassil?
No, I think you said it all. I think as our data matures for the 400 microgram per kilogram cohort, 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. As the cohort continues to mature, we're excited to see what we can see. We know we just had a one-month incremental data cut for 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 the rest of the study, this continuing deepening of the antitumor activity as patients are on the agent longer.
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. I wanted to ask specifically on, as you think about the first-line opportunity here, and first just generating the data of combining XmAb819 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. 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 a washout period, right? These patients are progressing rapidly, so we start treating them very quickly. 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. I think that gives us a lot of comfort that having significant PD-1 inhibitory activity, from whether it's a nivo 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.
That I think gives us a lot of confidence going into our quick safety cohorts to combine with PD-1 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 Xencor designed that have been combined with PD-1 inhibitors. For example, ASP2138, it's no longer called an XmAb, our partnership with Astellas for the claudin 18.2 CD3, same 2+1 format as XmAb819. That had quite a big data set of phase I data being combined with pembro plus chemo in frontline gastric GEJ, 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 ASP2138, the CD3 bispecific, and that's in phase III right now.
You see additional evidence, tarlatamab, beautiful data presented a couple of days ago here at ESMO in DeLLphi-305 combined with durva. We also have the experience from KIMMTRAK. 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, really to great positive effect. It really encourages to want to explore the opportunity for XmAb819 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 unique aspect of what we've seen from a safety perspective of XmAb819, where the drug does not have cumulative toxicity, right? You see the priming period has a tolerization of a couple of weeks, and then at target dose, the drugs very clean. Every other drug, PD-1, VEGF R TKIs, HIF-2α inhibitors that would be combinable standard of cares all have cumulative toxicity that actually emerges in the later cycles of treatment, cycle one, cycle two, cycle three, which makes our unique ability to have truly orthogonal toxicity to these other agents. I think we have a bright future ahead of maximizing the potential of the drug in some of these different settings and indications with current standard of care. We're very excited about that.
Great insights. Thank you so much. Congratulations.
Thank you. Your next question comes from Matthew Phipps with William Blair. Please unmute to ask your question.
Hi, guys. Congrats. Let me offer my congrats as well. Two quick questions. One, just curious how the prior HIF-2α exposure compared across those target dose levels. Just wondering if there's any differences in the number of patients who had HIF-2 there. I know sub-Q is ongoing and you've set a data update in the first half, but any early read on how the CRS profile compares IV to sub-Q? Obviously, I've seen some other TCEs get a little bit easier on sub-Q as you move to sub-Q. Thank you.
Hi. Matt, can you hear me? Yeah.
Yes.
You were a little in and out. On the sub-Q point, we did have some sub-Q data in our data cut last year. It was in a blended cohort that we disclosed. We're still dose escalating, and we'll present that data sometime in the first half of next year. 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 Cmax. That's something that we're certainly looking for. We really can't comment yet on our specific data. There was a little bit of a stutter in the audio feed, but I thought I heard you say for the prior HIF-2α exposures, were you asking about differences across our dose levels?
Yeah, any differences in prior exposure if they're across like [crosstalk].
I don't think there is. You can actually 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 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 question. Maybe building off of Steve's question earlier. Dr. Pal noted some mechanistic data indicating that ENPP3 is associated with an angiogenic phenotype, which is intuitive biologically, but how are you thinking about rational combinations in earlier lines? You already disclosed that you'll be combining with PD-1, but does a VEGFR TKI combo make sense in this setting, or does it make more sense to avoid multi-kinase-related cardiotoxic and other adverse events? Thanks.
Yeah, we think of XmAb819 as a drug that activates the immune system in a way that short-circuits the usual considerations of, is this an angiogenic phenotype? Is this an immune phenotype like is 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 a target cell and turn on. That would be through MHC-TCR complex formation. We just short-circuit that entirely. So, we're less concerned about that point, though we certainly do follow Dr. Pal'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. The mechanistic rationale for a PD-1 inhibitor with XmAb819 is excellent. We have plenty of preclinical data that shows that PD-1 inhibition only amplifies the activity of XmAb819. I think the selectivity of XmAb819 for tumor cells and the really good long-term tolerability profile post priming period gives us a good rationale for why a PD-1 combination would be top of the list.
I think from a 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. In the case of XmAb819 specifically, going back to where we talked about time to response, 75% of patients have a VEGFR TKI-like time to response with 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. 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 quick clarifying questions. Do you intend to use that phase III study to support accelerated approval, or is there a possibility to expand the current phase I and use a single arm cohort to support accelerated approval?
Thanks, [uncertain]. The global RCT with the proposed control arm of tivozanib, that would be a full approval study. Obviously, when you go accelerated approval, it's considered a conditional approval. That would be a confirmatory study under the current plan that we'd like to propose to health authorities. We think using an active control of a VEGFR TKI that is currently standard of care monotherapy in the later lines or post-VEGF 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 it's been a while, I think, since there's been a monotherapy developed that I think has the potential to advance standard of care beyond these VEGFR TKIs.
We're very confident in our design that we're going to propose against tivozanib. Yes, that would be full approval. Hopefully, based on 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. Just a quick follow-up. On durability, the initial six-month landmark PFS looks quite favorable. I am 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. Accelerated approval because it is a single-arm study that is the primary analysis set. Survival metrics are not considered generally by health authorities. The metrics they are 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. 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. Also, the very high response rate with the lower bounds exceeding any known responses that could be achieved with 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.
We think we are in a very strong position here to have those discussions. Yes, generally, the metrics that are going to be used for efficacy are ORR and mDoR.
Got it. Thanks so much. Congrats again.
Thank you. Your next question comes from Daina Graybosch with Leerink 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. 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, Daina. For us, the early indicators that 400 is the right dose are the very consistent AE profile between 200 and 400. In fact, they use precisely the same priming regimen. So, the priming dose one , two, three are identical for the 200 and 400, and that's where the AEs are almost entirely. We have in the follow-up period, 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, we note that one of the slides we just presented shows that it does take about a quarter of patients continue to have deepening of antitumor activity, and a quarter of our responders happen after about four months.
So, we just had an additional response start. It's still unconfirmed, but we're optimistic it'll confirm in these 400 cohorts . Now we're above 50% at a 55% unconfirmed ORR. 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. 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. 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 will be putting together the end of phase I package. So that is really the sort of coincidence of factors that makes us feel really excited about 400. Of course, I will note, 200 had a 44% response rate by itself and really strong durability showing. So, I think we are in a good spot.
Yeah, just to directly answer [crosstalk].
Thank you.
The regulatory aspect of it. Yeah. We think between 100, 200 and 400 dose characterization would fully support and satisfy Project Optimus.
Great. Thank you.
Our next question comes from David Nierengarten with Wedbush Securities. Please go ahead with your question.
Hey, thanks for taking the question. I had a couple, one on the baseline characteristics of the patients. 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. Then just on the pre-treatment or additional treatment to prevent CRS, could you remind us when that was initiated and if you noticed the changes and effects on the patients' levels of CRS and adverse events? Thanks.
Okay. Thanks, David. I think I'll tackle the baseline and maybe Bassil, you tackle pre-treatment.
Yeah.
On the baseline, I think you are referring to a comparison of the pooled data we presented at the Triple Meeting last year in 2025 versus this year. The Triple Meeting last year, A1 was blended between IV and SubQ 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. I think there were 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 ECOG 2.
That said, around probably 30% of ECOG 1s actually are 70 on a KPS score. We are actually probably more skewed towards poor and intermediate on a true baseline IMDC than what we are actually presenting. 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. Bassil?
Yeah. I will touch on the pre-treatment. Starting a little over a year ago, we started using prophylactic antihistamine, Zyrtec, cetirizine, to help manage the rash, and that [crosstalk].
Yep.
Certainly helped. We had always been doing pre-treatment dexamethasone and Benadryl and IV saline, just make sure they are hydrated, before our priming doses and our first target dose. Every time you introduce the drug at a new dose amount when you are doing your priming. We added the prophylactic tocilizumab on only priming dose day one, which has the highest CRS rate and the highest rash and all that. We started introducing that really, I would say, late last year, right around when we did our last data presentation. Yes, it has absolutely had a beneficial effect at easing the day one and day eight CRS rate.
I think it's worked out really nicely, and it's simplified things for the doctors, and it's really part of the setup for peeling back the inpatient monitoring period, this hospitalization period that's been a trend now for all the solid tumor TCEs and e ven the ones in myeloma and lymphoma, I should say. It's 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 xaluritamig, another XmAb 2+1 that Amgen is developing in prostate cancer against STEAP1. That guy, they've a really nice poster with no hospitalization through any of their priming, demonstrating feasibility for that for them. And of course, tarlatamab is down to, I think, couple hours of inpatient. 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 prophy toci was just part of that.
Got it. Thank you.
Your next question comes from Brian Cheng with JPMorgan.
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 priming period, and how do you envision that for the requirements for the phase III?
Yeah, so we take the precedent from, again, how folks have done it before us. You start by peeling back the later days. So, the cohort we've opened or are just about to open, I should say, in our phase I study, we call it our reduced monitoring cohort. That's about to start enrolling, and we are peeling back the overnight stays on the target and last priming dose, priming dose three, and we're going to gather some data from a modest-sized cohort there. Then we'll follow the lead as we proceed in development. We continue gathering data with reduced monitoring. You saw with Amgen, they introduced it during phase III for tarlatamab, and have started to do that for xaluritamig 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 of reduced hospitalization by the time of approval. 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 Archila with Wells Fargo. Please go ahead.
Hey, good morning, and thanks for taking the questions. Congrats on the data. Just quick question. How does the SubQ development align with the timing of the XmAb819 phase III? Any consideration of using that presentation for the trial? Thanks.
Thanks, Derek. Good question. 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. SubQ, where we're at is on track to present data from SubQ in the first half of 2027. That data set will obviously align with our end of phase I meeting. There's really three paths here, right? Path one, we use SubQ for the next phase of clinical development as the preferred presentation. Path two, we go forward with IV, SubQ becomes a life cycle play for clinical convenience, as has been done with many biologics, including the PD-L1 class. Or three, we just feel that SubQ 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. I would say, we're encouraged by what we're seeing in SubQ. 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 2027. I think have some great regulatory interactions and keep moving this program forward.
Great. Thank you.
Our next question comes from Leonid Timashev 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. I guess, how should we think about the read-throughs on the efficacy and safety side from today's data? 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, Leo. We just got rolling a few months ago, in the sub-study doing papillary renal 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 is well over half of patients express ENPP3 at a high enough level. Then you have your colorectal and lung a little bit below that, maybe between a third and a half, we expect, based on our pre-work. So, these are really, really big opportunities. Now, what is 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 are running the study to look at the data.
There is not a huge amount of experience with solid tumor CD3s of a given molecule against different tumor types. So, I think we are going to be really building that data set ahead of any of our partners or peers. But I think, we are really optimistic that the tolerability should be very similar, and that is 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 are going to learn a ton about how each of these behave. I will 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.
Then you go through papillary renal, much less known, and MSS colorectal, been a tough nut to crack, but a huge unmet need. There's just such an opportunity once you have a drug that's showing outstanding activity in its first indication, like XmAb819 in clear cell, with a profile that we can 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 trying to leverage it. Stay tuned. We haven't guided on timing for that, but 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 XmAb819.
Thank you. Our last question comes from Tara Bancroft with TD Cowen. Please go ahead with your question.
Hi, this is Danny on for Tara Bancroft. 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? Then perhaps any color or framing that you guys can give on the expected sequence of milestones for XmAb819 in 2027 or first half 2027. Thank you so much.
Yeah. 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. The general rule of thumb is people tend to scan in that 8-1 0-week range. We haven't really decided on or disclosed really all the details of our pivotal studies. But we definitely think we want to keep people on drug because it's working really well as you go forward. Remember, scans keep going on during study for a year or two. I think we've got plenty of time to capture all the responses. You want to talk about maybe the sequence of our milestones for XmAb819 as we go into 2027, Dane?
Sure. Yeah, happy to. I actually think we would be remiss because we talked about actually last year, too, in terms of scan timing. In this study, we had week six for scan. There's actually, I would say, I don't know, Bassil, 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 the next scan, had complete resolution of those new target lesions and deep responses to the target lesions from baseline, but forever are marked as PD. It's our theory that, again, only in a handful of patients, if the scan timing was more to standard practice today, which is around somewhere between eight and 10 weeks, those would actually be PRs.
Obviously under careful consideration as we go forward, but yeah, expect a kind of normalized scan timing cycle. In terms of milestones, we have a big year ahead for this program. Again, I'd emphasize that this is what we consider to be the first potential commercial program for Xencor as a company. Our focus, our allocation of resources is matched to that goal and focus. 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 evaluable for the IV 400 microgram per kilogram dose that we think is a potential RP3D.
We'll 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 tivozanib. That obviously doesn't include the number of sub studies that we talked about today that are starting to ramp up right now. Still a little TBD on a lot of the things that will be percolating as we head into 2027. I think the first half of the year is going to be some continued excitement on the momentum of this program.
Thank you very much.
We have no further questions at this time. I will now turn the call back over to Bassil Dahiyat for closing remarks.
Hey, thanks everyone for joining us today to review these results and plans for XmAb819, which you can see we are extremely excited about. This is just the beginning of several planned updates for XmAb819, 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. For now, have a wonderful rest of your day. Take care.