Xencor Inc — Call Transcript 2026

I'm part of the Leerink Partners Equity Research team. It's my pleasure to host the management team of Xencor. We have with us today CEO Bassil Dahiyat and Chief Strategy Officer Dane Leone. Thank you guys very much for joining us. Thank you. Thank you. Glad to be here. Would you like to first briefly introduce the company? Sure. Xencor is a company that was founded to do protein and antibody engineering, and we focus those tools on building our own proprietary pipeline of novel monoclonal antibodies and bispecific antibodies in oncology and autoimmune disease. Our goal is to become a fully integrated company by advancing our own programs through the clinic and ultimately onto the market one day. We use our protein engineering skills and our XmAb toolkit of antibody modules to build what we hope are best-in-class molecules that push the edge on addressable targets in oncology, particularly for T cell engagers, in an autoimmune disease building bespoke, highly suited for I and I applications, bispecific molecules and highly long-acting monospecific antibodies to address novel target pairs and greatly extended dosing intervals in I&I. That's kind of who we are, and we have a series of programs that we're gonna be rolling out data for this year and next, and we're glad to talk about 'em. Great. Given the breadth of potential applications for your platform, what would you say are the key priorities for the company? The key priorities are focusing on our internal clinical development we spent last year really being an execution year, advancing our two oncology programs, our XmAb819 program in renal cell carcinoma, and our XmAb541 program in CLDN6+ tumors, so specifically GYN tumors and germ cell tumors, as well as launching several programs in autoimmune disease that we'll touch on in a bit. The efforts for this year are building on that clinical base and the operational execution and delivering data from our phase I studies in for XmAb819 and XmAb541 to show the data that supports the recommended phase III doses that we hope to be disclosing in the second half of this year and setting ourselves up for pivotal trials for those molecules in 2027. For the autoimmune programs, we do expect to start an additional study this year, our XmAb412 molecule. That is a bispecific antibody targeting TL1A and IL-23p19 that we believe we've built to have best-in-class properties we're gonna be sharing the full preclinical package on XmAb412 at DDW in May. Great. Let's start with your solid tumor T cell engagers, XmAb819. This is your ENPP3 x CD3. What would you say are the key highlights from the most recent data update for this program? Yeah. Let me start by saying what XmAb819 is, XmAb819 is a bispecific antibody that targets ENPP3, a target that is very bright on clear cell renal cell carcinoma, as well as several other histologies that we're starting to study, and CD3 on the other side it's a T cell engager. We built it using our XmAb toolkit, our highly stable XmAb Fc domain that creates a bispecific structure on a very solid scaffold, so you can build different formats on it, and we used our 2+1 format to allow us to have high engagement and high cytotoxicity on high ENPP3 expressing tumor cells while avoiding the low ENPP3 expressing normal tissues that express it. There's low level expression in a variety of organs. That 2+1 design lets us use high avidity binding to ENPP3, but low affinity to do that separation and to do that potency window that hopefully gives us a therapeutic window. That's the design. That's the same design that's used in Amgen's xaluritamig that we built for them, the STEAP1 CD3 in phase III in prostate, as well as the Claudin 18.2 CD3 we built for Astellas, ASP2138. That's starting phase III they've guided this year in gastric GEJ. This format is something that we believe enables solid tumor targets to be addressed with these incredibly potent CD3-based mechanisms while avoiding the broad kind of toxicity that you might otherwise fear. The key highlights for XmAb819 in a data disclosure we did at the Triple Meeting last October are 25% objective response rate in heavily pretreated patients. The most pretreated patients that we're aware of that have ever been disclosed in clear cell renal cell, median of four prior lines, 100% IO TKI exposure. Over a third had HIF-2 alpha exposure. We had a 25% response rate. You know, we've seen a number of patients from our lower dose cohorts extend out therapy quite a long time, well past a year, still characterizing at the target dose ranges where we got that 25% response rate, still characterizing that durability. We had a safety profile that was dominated by CRS and a rash that we believe is ENPP3 mediated because of an expression on basophils you get sort of an allergic kind of rash that happens early in the first few weeks, and then after that, it's a very clean drug, and that we think sets it up well for long-term use. Those are the highlights of the data for XmAb819, and maybe Dane can now touch on what we expect to deliver this year and how that's gonna position us for later line development in monotherapy and beyond. Yeah, I mean, we just build off of the clinical momentum coming out of 2025, sorry, where our goal is to really get to the target dose ranges and trigger the dose Expansion. Towards the end of last year, we triggered recommended dose Expansion 1. We've triggered recommended dose Expansion 2. And that gives us what we need this year to characterize the target dose that we would have for RP3D, and as Bassil said earlier, will allow us to start a pivotal study in late-line clear cell renal cell carcinoma in 2027. When we entered 2026, the development pathway really moved to parallel development for this drug. We're confident in the monotherapy activity, so as we enroll those target dose cohorts to define the RP3D, in parallel with that, we're catching up on the sub-Q presentation, so we'll be able to make a decision ahead of the pivotal start on IV versus sub-Q. Also we're expanding the totality of the program on the behest of our investigators and a lot of the discussion that we even just had at the ASCO GU advisory board we hosted, and our steering committee. We're working on a sub-study in pre-TKI patients, probably intermediate to poor prognosis that have progressed on Ipilimumab and Nivolumab, to look at XmAb819 as a monotherapy. The reason for that is the clinical community is really trying to move away from the VEGF TKI axis in clear cell renal cell carcinoma and look at something that is a novel modality. You can think about it a couple different ways, right? Firstly, this is the first IO-like agent to deliver real monotherapy activity and clinical benefit for patients that progressed on IO. That is definitely revolutionary and it has caught the attention and excitement in the clinical community. Secondly, it's the first agent to show monotherapy activity for patients that progressed on IO, TKI, and a HIF-2 alpha inhibitor. I think that sub-study will be really important we're working on the protocol right now, so this year will be mostly about ramping that up, but it will define a couple things for us. First, the monotherapy potential in earlier lines, which obviously captures a lot more market, for XmAb819 if successful, and also gets us truer to that original biopsy, reading on ENPP3 positivity. 'Cause remember, we're not pre-selecting patients, but we are looking at ENPP3 H-scores on that original biopsy in clear cell. On the one hand, over 90% of patients with clear cell renal cell carcinoma have high ENPP3 positivity on their original biopsy. However, in the current cohort that we presented in October last year, where we had a 25% response rate, that's post four lines of treatment. Over 60% of patients went through two TKIs. As we all know, when you've been exposed to a TKI, that changes the clonal subpopulation, the tumor cells, and kinda the phenotype of what they're actually expressing in the oncogenic signaling pathway. This gives us a really good reading as a sub-study true to that original biopsy, what XmAb819 has potential as monotherapy for these patients. Beyond that, we're also expanding into different tumor types. We think there's other tumor types with very large patient populations, potentially ENPP3-positive, that could benefit from XmAb819. As we're looking today, we're screening patients with papillary renal cell carcinoma. We think about 50%-60% of those patients have ENPP3 positivity that could benefit from XmAb819. We're screening patients with non-small cell lung cancer. Our estimate is about 20%-30% of non-small cell lung cancer patients have ENPP3 positivity that could benefit from XmAb819. We're also looking at colorectal cancer patients, where we think about 30%-40% of those patients are ENPP3-positive. Substantial market Expansion opportunity for XmAb819 is now ongoing in parallel with the late line development pathway. Importantly, because we defined an RG1 late last year, we're using that in the Expansion tumor type cohorts, and so we already know we're starting an effective dose for those patients. It's a really exciting year for XmAb819, as a program, and we're carrying a lot of clinical momentum to really become a later stage development opportunity for patients and obviously, Xencor as a company. Understood. What do you see as the bar for the second-line plus RCC space? Has that changed with HIF-2 alpha inhibitors? Yeah, that's a good question. As I think the summary is the HIF-2 alpha inhibitors, Belzutifan, are moving earlier in line, right? I think we saw the LITESPARK-011 data at ASCO GU a couple weeks ago. On top of lenvatinib, a multi-TKI, you saw a really move in the standard of care over monotherapy TKI cabozantinib. As those classes, IO, TKI, VEGF, TKI, and HIF-2 alpha all compress earlier in line, it really clears out the later lines. In fact, there's the potential that a good number of patients are gonna be treated HIF-2 alpha frontline or adjuvant, right? Creating more room to move up with a novel mechanism. When we look at the bar, we look at studies like the TIVO-3 study for tivozanib, which had, I believe, an 18% response rate and a PFS around five months, if I'm not mistaken, as the kind of bars in that third line or second line plus setting because that's where you are these days after you've gone through these three classes. You know, when we look at our 25% response rate in a population that was significantly more heavily pretreated than the TIVO-3 study, you know, we think that's a slot that should be something that makes phase III development really amenable while we work on expanding into earlier line and into these other indications. Understood. What could a pivotal study for XmAb819 look like in RCC? It's gonna be randomized. It's gonna be against a control arm that, you know, has, there's a number with data behind them, which we haven't disclosed what we're thinking on control arm yet. It's gonna be, you know, fairly sizable, given the appetite on the clinical community for agents that are novel in mechanism and can give monotherapy activity. You know, I think it's a study that'll be well-received. I think from the powering, we haven't done the full work, but it's gonna be north of 450 patients very likely. Got it. Just touching on the other tumor types that you mentioned. Is the rationale for those Expansions primarily the target expression profile at the end? Exactly. Yeah. The target expression profile seems amenable. Obviously, even a subset of those opportunities there, the patient population. If you think about renal cell carcinoma, you know, in totality, right? It's 50,000 to 60,000 patient population opportunity, right, in the U.S. Those additional tumor types, even with kinda the cut point for ENPP3 positivity could potentially double that market opportunity. It's a very significant area that we need to invest in and start understanding the signal now. Each of those tumor types obviously is different in their own right of how they react to immunotherapy, but what I think is a true point is none of those tumor types have really ever had a good T-cell engager target developed against them. In particular, we've now seen T-cell engagers by one of our partner programs, xaluritamig, prove that T-cell engagers work differently than IO, right? Xaluritamig in late line metastatic castrate-resistant prostate cancer, classically Ipi-Nivo doesn't work. Pembro doesn't work, right? You cannot, for whatever reason, get the IO reaction to occur in those patients, but you can get a T-cell engager to work we think it's a very good opportunity for us to push the limits with good targets into these other large patient populations and really define the monotherapy potential of this drug. Right. Just double-clicking on that then, how do you view the commercial opportunity for XmAb819? We think the commercial opportunity is quite substantial in RCC, right? Again, there's really a great opportunity in late line to capture those patients by besting, you know, really pretty aged TKIs, right, in those late line settings. The opportunity to move up as those three classes of drug compress earlier on, as well as the very orthogonal toxicity profile we see with XmAb819. Really, after the priming regimen, which is CRS and rash, it's a very quiet drug. The combinability with things like IO or HIF-2 alpha or- -There's a lot of plausibility there we're doing a lot of thinking and exploration about how we might go there. These other indications, whether it's papillary renal where there's nothing or colorectal, MSS colorectal or lung, you know, these are wide open spaces, right, where there's salvage 'cause that's what everybody basically ends up in after front line. It could be quite substantial we'll to focus our work on the monotherapy phase III initially, and then go from there. Yeah. Well, I mean, we'll give you a hyper-specific on clear cell renal cell carcinoma because I think we have the numbers now, right? We would pursue a very similar label strategy as Belzutifan and tivozanib in clear cell, where our late line study, call it, post-IO, post-TKI, would afford a label in the U.S. and in Western Europe where you would just need to be exposed to a PD-1 and need to be exposed to one VEGF-R TKI. Belzutifan actually has some handcuffs on getting reimbursement in Europe, so the adoption there has been a bit slower. Even in the U.S. alone, really driving the adoption of the drug as it currently stands, it's on track to become a billion drug with that label as used. I think that goes to the point that there's a lot of flexibility for the clinical community, and especially as Bassil said, that front-line compression of doublet and triplet agents leaves open a really big need for second, third line novel agents, where you can actually get to a blockbuster drug status, with a late line pivotal study in clear cell. Understood. How do you view the competitive landscape for XmAb819? It's limited. In clear cell specifically, it's very limited. There's very few novel agents, and I'm not, you know, trying to take a specific shot at it, but it was specifically commented to us in our ad board at ASCO GU, "This is a good target. This is a different target. We like this target better than some of the other targets being explored, like CD70, for example. And based on what we're seeing clinically, there's a lot of potential of this drug." You know, that was a key test for us when we presented in October and what we've seen with the enrollment into our study to date, where these patients have maxed out VEGF TKI exposure they've maxed out IO exposure, and they've also had HIF-2 alpha. We're in a little bit of a different spot where if this monotherapy profile, clinical profile, which we think it will, holds up for the RP3D data set, this is a very exciting drug with a lot of opportunity to help advance the standard of care for patients. Understood. Do we know any updates from the J&J in PD-? We haven't heard a word. No, we you know, again, kind of going back to some of the original comments Bassil made, we do think for this target, the two plus one format would be superior to a one plus one format. We obviously always let different formats compete when we're choosing the molecule we make, and for the expression profile of ENPP3 to bias it towards the tumor cells, we really like that play.... more technically- Yeah -gifted than I, so maybe you- Yeah -Wanna add some comments. No, I think that's exactly right we think we picked the right format given the expression profile for this target, and we have not heard a word about that program, and we're off to the races. Understood. Let's maybe switch over to XmAb541, your CLDN6 x CD3 bispecific. What are the key highlights from the most recent update on that program? The update was very terse. We just wanted to show that we had advanced our dose escalation to the point where we were at active doses we showed just a little waterfall plot, I think about a 30% response rate across a basket of GCT and ovarian tumors. Right now, we are nailing down our dose level and characterizing efficacy and safety in both GCT and ovarian cancer. Again, we expect to have our dose locked down and a recommended phase III dose later this year. The program started almost two years, actually two years, after XmAb819, so we're really excited about the progress we've learned a lot about how to escalate CD3 bispecifics in solid tumors, about how to manage things, and we're not quite as far along on planning for later line, but we'll have a lot more to say later this year when we roll out all the data that establishes the phase three dose, and we can talk a lot more about it then. Got it. Remind me, where are you in dose optimization for this program? We haven't given detailed specifics, but we are characterizing target doses, and we have been since last fall. We're at the point where we expect to have sufficient data, you know, Expansion cohort data by the end of this year at least one, if not two doses, and should be able to make decision then. Yeah. It's a different track than XmAb819. XmAb819, the RP3D data set on the target dose that we would potentially take forward into pivotal into 2027, that'll be at a medical meeting in the back half. XmAb541, we expect to be at a corporate update a little, maybe later in the year, towards the end of the year, because there's a lot more complex decision-making there. The dose escalation is a basket study of ovarian, endometrial and germ cell. As you know, once you make the choice to the next stage of development, each of those are separate pathways that have to be evaluated separately. That's part of the decision-making that we'll have to make in the back half of this year when we start seeing more characterization with bigger cohorts, bigger N's of the patients and really understand the clinical profile better. I think you touched on my next question, but just in case, what could a future development path of this program look like? It's you know, we think of it in kind of three buckets, right? You have germ cell, really nothing for these patients, extremely high unmet need, very small market, right? Endometrial, some things available, still very high clinical unmet need, bigger market. Ovarian, really busy clinical activity, in the landscape of novel drug development, large market, right? And so in a certain sense, we have to be somewhat dispassionate on what the numbers tell us to do, right? In each of those different buckets, is the clinical activity something that will drive monotherapy activity with an efficient regulatory pathway, to commercial market? What can we prosecute in that commercial market as Xencor or would we need a partner? That's a part of the decision-making process, and we kind of apply it to all those three buckets and come up with a game plan. We'll let the numbers. We're not ready yet. [crosstalk] Yeah. We'll tell you. We'll tell you later. Yeah. We'll let the numbers drive the decision-making there. But I think we have a good handle, and we have very stringent internal hurdles for what the target product co-profile needs to look like, from the data we'll be seeing this year. Understood. How do you see the competitive landscape for XmAb541? I think there's two ways to look at that. The competitive landscape in ovarian cancer is quite dense. There's a lot of ADCs, a lot of different targets. We are the first-in-class CLDN6 out there or CD3. First-in-class T-cell engager, in fact, and we hope that we can separate ourselves. We obviously have to have an active enough molecule we have to have the right kind of response rates and larger patient numbers. But separate ourselves by that immunotherapy-like durability that's starting to show from CD3 bispecifics. We've seen it with tarlatamab that led to its really excellent pivotal data in its confirmatory study, DeLLphi-304. We're starting to see it with xaluritamig. That's the hope for this modality, right? It's a very dense competitive landscape, too dense to go into an ovarian. In germ cell, there's really not a lot of activity, right? Understood. Maybe with the time left, we'll switch to the immunology efforts on XmAb942 and XmAb412. How do you view the opportunity for the anti-TL1A class and for those two programs specifically? I think for TL1A, it's probably the most exciting autoimmune target that's emerged in the last, you know, five or six years, the best in disease activity in ulcerative colitis and in Crohn's. It's led to a flurry of activity. We think that emerging data from newer and different indications, I should say, for TL1A could create that pipeline in a product we're waiting to see we've got our own ideas for us starting studies. Our approach for nine four two was to take what has made TL1A promising, maximally leverage the existing data out there to build our molecule and our program. Our molecule's about high potency and long half-life, which gives us maximal exposure. When you look at the induction phase data from the various phase II out there, it was clear that patients with higher exposure, just the variability naturally in PK, had higher response rates. We designed our molecule to have that high potency, long half-life, and our Phase 2b study, which is a very rigorous three dose level characterization Phase 2b, to maximize exposure in the induction phase. We show this from all of our comparisons against precedent programs from our large company peers. Our three-month dosing interval, we believe would really distinguish us from the pack. We're the first to start a phase I, first to start a phase II, and we hope to be the first to have data for a long-acting TL1A. Our outside of IBD development plan will go from there. We do expect to have an opportunity to update on progress by the end of the year or around year-end for that Phase 2b study and talk about our further plans for that program. The really sort of next step is how do you hit two targets at once, right? People are talking about combinations we think bispecifics are where it's gonna go. We have a very potent molecule that blocks TL1A and IL-23p19. That's XmAb412. Again, it's gonna be at DDW with the preclinical characterization. We'll also have the full phase one data from XmAb942 i always think of it as a phase two program, but I forget we haven't even presented the full phase one data that'll be at DDW. That's about having the killer app in IBD, the two best targets combined in a molecule that can be given conveniently, single injection, right? That was a really difficult engineering feat, and we'll go into the details at DDW, why we think we have the best-in-class design using Xencor's protein engineering tools to make the same kind of potency with blocking each of those two targets as the monospecific antibodies delivered at high dose. We think this is gonna be a very much simpler development path than combination agents, much simpler manufacturing than combination agents. We're ready to start that phase I in healthy volunteers this year for XmAb412. We see it as potential broad use with long-acting molecule that can combine with all the other therapies that are coming off patent you know, the combination world's gonna be about biosimilars for IL-23 and integrin inhibitors, et cetera. Those bispecifics, we think, are gonna change the landscape when they come along. Understood. Can you help set expectations for the two updates that we're expecting at DDW? Sure. Dane, you wanna go on that? for DDW Yeah We'll have the final results from the healthy volunteer study of XmAb942. We obviously provided an interim look in April 2025. This will be the full result, full follow-up, PK/PD, TL1A target engagement, and immunogenicity. The totality of the package, I think, will give everyone a clear sense of why we're so excited about the Phase 2b study and the opportunity to deliver better drug exposure, especially at the top dose level, and see if that can really break through that ceiling of efficacy for biologic therapies in patients with ulcerative colitis. On XmAb412, expect a normal Xencor quality on preclinical characterization. Very good characterization with non-human primate half-life, what we think of the dosing, what we think of the potency, stability of the molecule, and why we're obviously excited, to Bassil's point, of this killer app that could be for IBD, could be for a couple other areas where there's implications of IL-23 and TL1A, like psoriatic arthritis, for example. We'll really look to get that program going as quickly as we can in the clinic. You know, I'll take a quick second for what we can do now as a clinical organization. We were first in clinic with XmAb942 in November 2024. We had a global Phase 2b study up and enrolling less than a year later. We'll run that same game plan clinically with XmAb412 to make sure we're on the competitive edge because we think we have the best-in-class molecule, and there's a lot of potential for what we can do here. The final point of this is, and we get asked a lot on the decision-making, we'll have a nice convergence of data between XmAb412, the healthy volunteer study, to effectively know do we make the molecule we thought we did, right? In that kinda 2027 timeframe, along when we're getting some of that data really from the Phase 2b study to know was our hypothesis correct. We'll be able to make really rational decisions on dollars spent internally, how we prosecute each of those programs, potentially from, you know, partnership strategies and other strategies, to maximize the value for all of our stakeholders, the patients, the clinicians, and obviously our shareholders. Understood. Maybe I can just squeeze in one last question on exactly that last point. BD's been an important part of Xencor's history. How are you thinking about business development opportunities from here? I'll take that. BD is gonna be about what advances our pipeline. If there's an opportunity, like maybe for TL1A, where there is a broad set of late phase clinical trials that we wanna make sure we can address, that's when partnering might come in, right? Our goal is to take our programs all the way through by ourselves, but we know that sometimes the way to move fastest is with a partner. It's gonna be driven by the pipeline's needs and when we need that resource boost. Understood. Thank you guys very much for taking the time. We appreciate it. Thank you. Great questions. Thank you.

Speaker 3: I'm part of the Leerink Partners Equity Research team. It's my pleasure to host the management team of Xencor. We have with us today CEO Bassil Dahiyat and Chief Strategy Officer Dane Leone. Thank you guys very much for joining us. I'm part of the Leerink Partners Equity Research team. i'm part of the leerink partners equity research team It's my pleasure to host the management team of Xencor. it's my pleasure to host the management team of xencor We have with us today CEO Bassil Dahiyat and Chief Strategy Officer Dane Leone. we have with us today ceo bassil dahiyat and chief strategy officer dane leone Thank you guys very much for joining us. thank you guys very much for joining us

Speaker 2: Thank you. Thank you. thank you

Speaker 1: Thank you. Glad to be here. Thank you. thank you Glad to be here. glad to be here

Speaker 3: Would you like to first briefly introduce the company? Would you like to first briefly introduce the company? would you like to first briefly introduce the company

Speaker 1: Sure. Xencor is a company that was founded to do protein and antibody engineering, and we focus those tools on building our own proprietary pipeline of novel monoclonal antibodies and bispecific antibodies in oncology and autoimmune disease. Our goal is to become a fully integrated company by advancing our own programs through the clinic and ultimately onto the market one day. Sure. sure Xencor is a company that was founded to do protein and antibody engineering, and we focus those tools on building our own proprietary pipeline of novel monoclonal antibodies and bispecific antibodies in oncology and autoimmune disease. xencor is a company that was founded to do protein and antibody engineering and we focus those tools on building our own proprietary pipeline of novel monoclonal antibodies and bispecific antibodies in oncology and autoimmune disease Our goal is to become a fully integrated company by advancing our own programs through the clinic and ultimately onto the market one day. our goal is to become a fully integrated company by advancing our own programs through the clinic and ultimately onto the market one day We use our protein engineering skills and our XmAb toolkit of antibody modules to build what we hope are best-in-class molecules that push the edge on addressable targets in oncology, particularly for T cell engagers, in an autoimmune disease building bespoke, highly suited for I and I applications, bispecific molecules and highly long-acting monospecific antibodies to address novel target pairs and greatly extended dosing intervals in I&I. That's kind of who we are, and we have a series of programs that we're gonna be rolling out data for this year and next, and we're glad to talk about 'em. We use our protein engineering skills and our XmAb toolkit of antibody modules to build what we hope are best-in-class molecules that push the edge on addressable targets in oncology, particularly for T cell engagers, in an autoimmune disease building bespoke, highly suited for I and I applications, bispecific molecules and highly long-acting monospecific antibodies to address novel target pairs and greatly extended dosing intervals in I & I. we use our protein engineering skills and our xmab toolkit of antibody modules to build what we hope are best-in-class molecules that push the edge on addressable targets in oncology particularly for t cell engagers in an autoimmune disease building bespoke highly suited for i and i applications bispecific molecules and highly long-acting monospecific antibodies to address novel target pairs and greatly extended dosing intervals in i & i That's kind of who we are, and we have a series of programs that we're gonna be rolling out data for this year and next, and we're glad to talk about 'em. that's kind of who we are and we have a series of programs that we're gonna be rolling out data for this year and next and we're glad to talk about 'em

Speaker 3: Great. Given the breadth of potential applications for your platform, what would you say are the key priorities for the company? Great. great Given the breadth of potential applications for your platform, what would you say are the key priorities for the company? given the breadth of potential applications for your platform what would you say are the key priorities for the company

Speaker 1: The key priorities are focusing on our internal clinical development we spent last year really being an execution year, advancing our two oncology programs, our XmAb819 program in renal cell carcinoma, and our XmAb541 program in CLDN6+ tumors, so specifically GYN tumors and germ cell tumors, as well as launching several programs in autoimmune disease that we'll touch on in a bit. The key priorities are focusing on our internal clinical development w e spent last year really being an execution year, advancing our two oncology programs, our XmAb819 program in renal cell carcinoma, and our XmAb541 program in CLDN6+ tumors, so specifically GYN tumors and germ cell tumors, as well as launching several programs in autoimmune disease that we'll touch on in a bit. the key priorities are focusing on our internal clinical development w e spent last year really being an execution year advancing our two oncology programs our xmab819 program in renal cell carcinoma and our xmab541 program in cldn6+ tumors so specifically gyn tumors and germ cell tumors as well as launching several programs in autoimmune disease that we'll touch on in a bit The efforts for this year are building on that clinical base and the operational execution and delivering data from our phase I studies in for XmAb819 and XmAb541 to show the data that supports the recommended phase III doses that we hope to be disclosing in the second half of this year and setting ourselves up for pivotal trials for those molecules in 2027. The efforts for this year are building on that clinical base and the operational execution and delivering data from our phase I studies in for XmAb819 and XmAb541 to show the data that supports the recommended phase III doses that we hope to be disclosing in the second half of this year and setting ourselves up for pivotal trials for those molecules in 2027. the efforts for this year are building on that clinical base and the operational execution and delivering data from our phase i studies in for xmab819 and xmab541 to show the data that supports the recommended phase iii doses that we hope to be disclosing in the second half of this year and setting ourselves up for pivotal trials for those molecules in 2027 For the autoimmune programs, we do expect to start an additional study this year, our XmAb412 molecule. That is a bispecific antibody targeting TL1A and IL-23p19 that we believe we've built to have best-in-class properties we're gonna be sharing the full preclinical package on XmAb412 at DDW in May. For the autoimmune programs, we do expect to start an additional study this year, our XmAb412 molecule. for the autoimmune programs we do expect to start an additional study this year our xmab412 molecule That is a bispecific antibody targeting TL1A and IL-23p19 that we believe we've built to have best-in-class properties w e're gonna be sharing the full preclinical package on XmAb412 at DDW in May. that is a bispecific antibody targeting tl1a and il-23p19 that we believe we've built to have best-in-class properties w e're gonna be sharing the full preclinical package on xmab412 at ddw in may

Speaker 3: Great. Let's start with your solid tumor T cell engagers, XmAb819. This is your ENPP3 x CD3. What would you say are the key highlights from the most recent data update for this program? Great. great Let's start with your solid tumor T cell engagers, XmAb819. let's start with your solid tumor t cell engagers xmab819 This is your ENPP3 x CD3. this is your enpp3 x cd3 What would you say are the key highlights from the most recent data update for this program? what would you say are the key highlights from the most recent data update for this program

Speaker 1: Yeah. Let me start by saying what XmAb819 is, XmAb819 is a bispecific antibody that targets ENPP3, a target that is very bright on clear cell renal cell carcinoma, as well as several other histologies that we're starting to study, and CD3 on the other side it's a T cell engager. Yeah. yeah Let me start by saying what XmAb819 is, XmAb819 is a bispecific antibody that targets ENPP3, a target that is very bright on clear cell renal cell carcinoma, as well as several other histologies that we're starting to study, and CD3 on the other side i t's a T cell engager. let me start by saying what xmab819 is xmab819 is a bispecific antibody that targets enpp3 a target that is very bright on clear cell renal cell carcinoma as well as several other histologies that we're starting to study and cd3 on the other side i t's a t cell engager We built it using our XmAb toolkit, our highly stable XmAb Fc domain that creates a bispecific structure on a very solid scaffold, so you can build different formats on it, and we used our 2+1 format to allow us to have high engagement and high cytotoxicity on high ENPP3 expressing tumor cells while avoiding the low ENPP3 expressing normal tissues that express it. There's low level expression in a variety of organs. That 2+1 design lets us use high avidity binding to ENPP3, but low affinity to do that separation and to do that potency window that hopefully gives us a therapeutic window. We built it using our XmAb toolkit, our highly stable XmAb Fc domain that creates a bispecific structure on a very solid scaffold, so you can build different formats on it, and we used our 2+1 format to allow us to have high engagement and high cytotoxicity on high ENPP3 expressing tumor cells while avoiding the low ENPP3 expressing normal tissues that express it. we built it using our xmab toolkit our highly stable xmab fc domain that creates a bispecific structure on a very solid scaffold so you can build different formats on it and we used our 2+1 format to allow us to have high engagement and high cytotoxicity on high enpp3 expressing tumor cells while avoiding the low enpp3 expressing normal tissues that express it There's low level expression in a variety of organs. there's low level expression in a variety of organs That 2+1 design lets us use high avidity binding to ENPP3, but low affinity to do that separation and to do that potency window that hopefully gives us a therapeutic window. that 2+1 design lets us use high avidity binding to enpp3 but low affinity to do that separation and to do that potency window that hopefully gives us a therapeutic window That's the design. That's the same design that's used in Amgen's xaluritamig that we built for them, the STEAP1 CD3 in phase III in prostate, as well as the Claudin 18.2 CD3 we built for Astellas, ASP2138. That's starting phase III they've guided this year in gastric GEJ. This format is something that we believe enables solid tumor targets to be addressed with these incredibly potent CD3-based mechanisms while avoiding the broad kind of toxicity that you might otherwise fear. That's the design. that's the design That's the same design that's used in Amgen's xaluritamig that we built for them, the STEAP1 CD3 in phase III in prostate, as well as the Claudin 18.2 CD3 we built for Astellas, ASP 2138. that's the same design that's used in amgen's xaluritamig that we built for them the steap1 cd3 in phase iii in prostate as well as the claudin 18.2 cd3 we built for astellas asp 2138 That's starting phase III they've guided this year in gastric GEJ. that's starting phase iii they've guided this year in gastric gej This format is something that we believe enables solid tumor targets to be addressed with these incredibly potent CD3-based mechanisms while avoiding the broad kind of toxicity that you might otherwise fear. this format is something that we believe enables solid tumor targets to be addressed with these incredibly potent cd3-based mechanisms while avoiding the broad kind of toxicity that you might otherwise fear The key highlights for XmAb819 in a data disclosure we did at the Triple Meeting last October are 25% objective response rate in heavily pretreated patients. The most pretreated patients that we're aware of that have ever been disclosed in clear cell renal cell, median of four prior lines, 100% IO TKI exposure. Over a third had HIF-2 alpha exposure. We had a 25% response rate. The key highlights for XmAb819 in a data disclosure we did at the Triple Meeting last October are 25% objective response rate in heavily pretreated patients. the key highlights for xmab819 in a data disclosure we did at the triple meeting last october are 25% objective response rate in heavily pretreated patients The most pretreated patients that we're aware of that have ever been disclosed in clear cell renal cell, median of four prior lines, 100% IO TKI exposure. the most pretreated patients that we're aware of that have ever been disclosed in clear cell renal cell median of four prior lines 100% io tki exposure Over a third had HIF-2 alpha exposure. over a third had hif-2 alpha exposure We had a 25% response rate. we had a 25% response rate You know, we've seen a number of patients from our lower dose cohorts extend out therapy quite a long time, well past a year, still characterizing at the target dose ranges where we got that 25% response rate, still characterizing that durability. You know, we've seen a number of patients from our lower dose cohorts extend out therapy quite a long time, well past a year, still characterizing at the target dose ranges where we got that 25% response rate, still characterizing that durability. you know we've seen a number of patients from our lower dose cohorts extend out therapy quite a long time well past a year still characterizing at the target dose ranges where we got that 25% response rate still characterizing that durability We had a safety profile that was dominated by CRS and a rash that we believe is ENPP3 mediated because of an expression on basophils you get sort of an allergic kind of rash that happens early in the first few weeks, and then after that, it's a very clean drug, and that we think sets it up well for long-term use. Those are the highlights of the data for XmAb819, and maybe Dane can now touch on what we expect to deliver this year and how that's gonna position us for later line development in monotherapy and beyond. We had a safety profile that was dominated by CRS and a rash that we believe is ENPP3 mediated because of an expression on basophils y ou get sort of an allergic kind of rash that happens early in the first few weeks, and then after that, it's a very clean drug, and that we think sets it up well for long-term use. we had a safety profile that was dominated by crs and a rash that we believe is enpp3 mediated because of an expression on basophils y ou get sort of an allergic kind of rash that happens early in the first few weeks and then after that it's a very clean drug and that we think sets it up well for long-term use Those are the highlights of the data for XmAb819, and maybe Dane can now touch on what we expect to deliver this year and how that's gonna position us for later line development in monotherapy and beyond. those are the highlights of the data for xmab819 and maybe dane can now touch on what we expect to deliver this year and how that's gonna position us for later line development in monotherapy and beyond

Speaker 2: Yeah, I mean, we just build off of the clinical momentum coming out of 2025, sorry, where our goal is to really get to the target dose ranges and trigger the dose Expansion. Towards the end of last year, we triggered recommended dose Expansion 1. We've triggered recommended dose Expansion 2. And that gives us what we need this year to characterize the target dose that we would have for RP3D, and as Bassil said earlier, will allow us to start a pivotal study in late-line clear cell renal cell carcinoma in 2027. Yeah, I mean, we just build off of the clinical momentum coming out of 2025, sorry, where our goal is to really get to the target dose ranges and trigger the dose Expansion. yeah i mean we just build off of the clinical momentum coming out of 2025 sorry where our goal is to really get to the target dose ranges and trigger the dose expansion Towards the end of last year, we triggered recommended dose Expansion 1. towards the end of last year we triggered recommended dose expansion 1 We've triggered recommended dose Expansion 2. we've triggered recommended dose expansion 2 And that gives us what we need this year to characterize the target dose that we would have for RP3D, and as Bassil said earlier, will allow us to start a pivotal study in late-line clear cell renal cell carcinoma in 2027. and that gives us what we need this year to characterize the target dose that we would have for rp3d and as bassil said earlier will allow us to start a pivotal study in late-line clear cell renal cell carcinoma in 2027 When we entered 2026, the development pathway really moved to parallel development for this drug. We're confident in the monotherapy activity, so as we enroll those target dose cohorts to define the RP3D, in parallel with that, we're catching up on the sub-Q presentation, so we'll be able to make a decision ahead of the pivotal start on IV versus sub-Q. When we entered 2026, the development pathway really moved to parallel development for this drug. when we entered 2026 the development pathway really moved to parallel development for this drug We're confident in the monotherapy activity, so as we enroll those target dose cohorts to define the RP3D, in parallel with that, we're catching up on the sub-Q presentation, so we'll be able to make a decision ahead of the pivotal start on IV versus sub-Q. we're confident in the monotherapy activity so as we enroll those target dose cohorts to define the rp3d in parallel with that we're catching up on the sub-q presentation so we'll be able to make a decision ahead of the pivotal start on iv versus sub-q Also we're expanding the totality of the program on the behest of our investigators and a lot of the discussion that we even just had at the ASCO GU advisory board we hosted, and our steering committee. We're working on a sub-study in pre-TKI patients, probably intermediate to poor prognosis that have progressed on Ipilimumab and Nivolumab, to look at XmAb819 as a monotherapy. Also we're expanding the totality of the program on the behest of our investigators and a lot of the discussion that we even just had at the ASCO GU advisory board we hosted, and our steering committee. also we're expanding the totality of the program on the behest of our investigators and a lot of the discussion that we even just had at the asco gu advisory board we hosted and our steering committee We're working on a sub-study in pre-TKI patients, probably intermediate to poor prognosis that have progressed on Ipilimumab and Nivolumab, to look at XmAb819 as a monotherapy. we're working on a sub-study in pre-tki patients probably intermediate to poor prognosis that have progressed on ipilimumab and nivolumab to look at xmab819 as a monotherapy The reason for that is the clinical community is really trying to move away from the VEGF TKI axis in clear cell renal cell carcinoma and look at something that is a novel modality. You can think about it a couple different ways, right? Firstly, this is the first IO-like agent to deliver real monotherapy activity and clinical benefit for patients that progressed on IO. The reason for that is the clinical community is really trying to move away from the VEGF TKI axis in clear cell renal cell carcinoma and look at something that is a novel modality. the reason for that is the clinical community is really trying to move away from the vegf tki axis in clear cell renal cell carcinoma and look at something that is a novel modality You can think about it a couple different ways, right? you can think about it a couple different ways right Firstly, this is the first IO-like agent to deliver real monotherapy activity and clinical benefit for patients that progressed on IO. firstly this is the first io-like agent to deliver real monotherapy activity and clinical benefit for patients that progressed on io That is definitely revolutionary and it has caught the attention and excitement in the clinical community. Secondly, it's the first agent to show monotherapy activity for patients that progressed on IO, TKI, and a HIF-2 alpha inhibitor. I think that sub-study will be really important we're working on the protocol right now, so this year will be mostly about ramping that up, but it will define a couple things for us. That is definitely revolutionary and it has caught the attention and excitement in the clinical community. that is definitely revolutionary and it has caught the attention and excitement in the clinical community Secondly, it's the first agent to show monotherapy activity for patients that progressed on IO, TKI, and a HIF-2 alpha inhibitor. secondly it's the first agent to show monotherapy activity for patients that progressed on io tki and a hif-2 alpha inhibitor I think that sub-study will be really important w e're working on the protocol right now, so this year will be mostly about ramping that up, but it will define a couple things for us. i think that sub-study will be really important w e're working on the protocol right now so this year will be mostly about ramping that up but it will define a couple things for us First, the monotherapy potential in earlier lines, which obviously captures a lot more market, for XmAb819 if successful, and also gets us truer to that original biopsy, reading on ENPP3 positivity. 'Cause remember, we're not pre-selecting patients, but we are looking at ENPP3 H-scores on that original biopsy in clear cell. First, the monotherapy potential in earlier lines, which obviously captures a lot more market, for XmAb819 if successful, and also gets us truer to that original biopsy, reading on ENPP3 positivity. 'Cause remember, we're not pre-selecting patients, but we are looking at ENPP3 H-scores on that original biopsy in clear cell. first the monotherapy potential in earlier lines which obviously captures a lot more market for xmab819 if successful and also gets us truer to that original biopsy reading on enpp3 positivity 'cause remember we're not pre-selecting patients but we are looking at enpp3 h-scores on that original biopsy in clear cell On the one hand, over 90% of patients with clear cell renal cell carcinoma have high ENPP3 positivity on their original biopsy. However, in the current cohort that we presented in October last year, where we had a 25% response rate, that's post four lines of treatment. Over 60% of patients went through two TKIs. On the one hand, over 90% of patients with clear cell renal cell carcinoma have high ENPP3 positivity on their original biopsy. on the one hand over 90% of patients with clear cell renal cell carcinoma have high enpp3 positivity on their original biopsy However, in the current cohort that we presented in October last year, where we had a 25% response rate, that's post four lines of treatment. however in the current cohort that we presented in october last year where we had a 25% response rate that's post four lines of treatment Over 60% of patients went through two TKIs. over 60% of patients went through two tkis As we all know, when you've been exposed to a TKI, that changes the clonal subpopulation, the tumor cells, and kinda the phenotype of what they're actually expressing in the oncogenic signaling pathway. This gives us a really good reading as a sub-study true to that original biopsy, what XmAb819 has potential as monotherapy for these patients. As we all know, when you've been exposed to a TKI, that changes the clonal subpopulation, the tumor cells, and kinda the phenotype of what they're actually expressing in the oncogenic signaling pathway. as we all know when you've been exposed to a tki that changes the clonal subpopulation the tumor cells and kinda the phenotype of what they're actually expressing in the oncogenic signaling pathway This gives us a really good reading as a sub-study true to that original biopsy, what XmAb819 has potential as monotherapy for these patients. this gives us a really good reading as a sub-study true to that original biopsy what xmab819 has potential as monotherapy for these patients Beyond that, we're also expanding into different tumor types. We think there's other tumor types with very large patient populations, potentially ENPP3-positive, that could benefit from XmAb819. As we're looking today, we're screening patients with papillary renal cell carcinoma. We think about 50%-60% of those patients have ENPP3 positivity that could benefit from XmAb819. We're screening patients with non-small cell lung cancer. Beyond that, we're also expanding into different tumor types. beyond that we're also expanding into different tumor types We think there's other tumor types with very large patient populations, potentially ENPP3 -positive, that could benefit from XmAb819. we think there's other tumor types with very large patient populations potentially enpp3 -positive that could benefit from xmab819 As we're looking today, we're screening patients with papillary renal cell carcinoma. as we're looking today we're screening patients with papillary renal cell carcinoma We think about 50%-60% of those patients have ENPP3 positivity that could benefit from XmAb819. we think about 50%-60% of those patients have enpp3 positivity that could benefit from xmab819 We're screening patients with non-small cell lung cancer. we're screening patients with non-small cell lung cancer Our estimate is about 20%-30% of non-small cell lung cancer patients have ENPP3 positivity that could benefit from XmAb819. We're also looking at colorectal cancer patients, where we think about 30%-40% of those patients are ENPP3-positive. Substantial market Expansion opportunity for XmAb819 is now ongoing in parallel with the late line development pathway. Our estimate is about 20%-30% of non-small cell lung cancer patients have ENPP3 positivity that could benefit from XmAb819. our estimate is about 20%-30% of non-small cell lung cancer patients have enpp3 positivity that could benefit from xmab819 We're also looking at colorectal cancer patients, where we think about 30%-40% of those patients are ENPP3 -positive. we're also looking at colorectal cancer patients where we think about 30%-40% of those patients are enpp3 -positive Substantial market Expansion opportunity for XmAb819 is now ongoing in parallel with the late line development pathway. substantial market expansion opportunity for xmab819 is now ongoing in parallel with the late line development pathway Importantly, because we defined an RG1 late last year, we're using that in the Expansion tumor type cohorts, and so we already know we're starting an effective dose for those patients. It's a really exciting year for XmAb819, as a program, and we're carrying a lot of clinical momentum to really become a later stage development opportunity for patients and obviously, Xencor as a company. Importantly, because we defined an RG1 late last year, we're using that in the Expansion tumor type cohorts, and so we already know we're starting an effective dose for those patients. importantly because we defined an rg1 late last year we're using that in the expansion tumor type cohorts and so we already know we're starting an effective dose for those patients It's a really exciting year for XmAb819, as a program, and we're carrying a lot of clinical momentum to really become a later stage development opportunity for patients and obviously, Xencor as a company. it's a really exciting year for xmab819 as a program and we're carrying a lot of clinical momentum to really become a later stage development opportunity for patients and obviously xencor as a company

Speaker 3: Understood. What do you see as the bar for the second-line plus RCC space? Has that changed with HIF-2 alpha inhibitors? Understood. understood What do you see as the bar for the second-line plus RCC space? what do you see as the bar for the second-line plus rcc space Has that changed with HIF-2 alpha inhibitors? has that changed with hif-2 alpha inhibitors

Speaker 1: Yeah, that's a good question. As I think the summary is the HIF-2 alpha inhibitors, Belzutifan, are moving earlier in line, right? I think we saw the LITESPARK-011 data at ASCO GU a couple weeks ago. On top of lenvatinib, a multi-TKI, you saw a really move in the standard of care over monotherapy TKI cabozantinib. As those classes, IO, TKI, VEGF, TKI, and HIF-2 alpha all compress earlier in line, it really clears out the later lines. In fact, there's the potential that a good number of patients are gonna be treated HIF-2 alpha frontline or adjuvant, right? Creating more room to move up with a novel mechanism. Yeah, that's a good question. yeah that's a good question As I think the summary is the HIF-2 alpha inhibitors, Belzutifan, are moving earlier in line, right? as i think the summary is the hif-2 alpha inhibitors belzutifan are moving earlier in line right I think we saw the LITESPARK-011 data at ASCO GU a couple weeks ago. i think we saw the litespark-011 data at asco gu a couple weeks ago On top of lenvatinib, a multi-TKI, you saw a really move in the standard of care over monotherapy TKI cabozantinib. on top of lenvatinib a multi-tki you saw a really move in the standard of care over monotherapy tki cabozantinib As those classes, IO, TKI, VEGF, TKI, and HIF-2 alpha all compress earlier in line, it really clears out the later lines. as those classes io tki vegf tki and hif-2 alpha all compress earlier in line it really clears out the later lines In fact, there's the potential that a good number of patients are gonna be treated HIF-2 alpha frontline or adjuvant, right? in fact there's the potential that a good number of patients are gonna be treated hif-2 alpha frontline or adjuvant right Creating more room to move up with a novel mechanism. creating more room to move up with a novel mechanism When we look at the bar, we look at studies like the TIVO-3 study for tivozanib, which had, I believe, an 18% response rate and a PFS around five months, if I'm not mistaken, as the kind of bars in that third line or second line plus setting because that's where you are these days after you've gone through these three classes. When we look at the bar, we look at studies like the TIVO-3 study for tivozanib, which had, I believe, an 18% response rate and a PFS around five months, if I'm not mistaken, as the kind of bars in that third line or second line plus setting because that's where you are these days after you've gone through these three classes. when we look at the bar we look at studies like the tivo-3 study for tivozanib which had i believe an 18% response rate and a pfs around five months if i'm not mistaken as the kind of bars in that third line or second line plus setting because that's where you are these days after you've gone through these three classes You know, when we look at our 25% response rate in a population that was significantly more heavily pretreated than the TIVO-3 study, you know, we think that's a slot that should be something that makes phase III development really amenable while we work on expanding into earlier line and into these other indications. You know, when we look at our 25% response rate in a population that was significantly more heavily pretreated than the TIVO-3 study, you know, we think that's a slot that should be something that makes phase III development really amenable while we work on expanding into earlier line and into these other indications. you know when we look at our 25% response rate in a population that was significantly more heavily pretreated than the tivo-3 study you know we think that's a slot that should be something that makes phase iii development really amenable while we work on expanding into earlier line and into these other indications

Speaker 3: Understood. What could a pivotal study for XmAb819 look like in RCC? Understood. understood What could a pivotal study for XmAb819 look like in RCC? what could a pivotal study for xmab819 look like in rcc

Speaker 1: It's gonna be randomized. It's gonna be against a control arm that, you know, has, there's a number with data behind them, which we haven't disclosed what we're thinking on control arm yet. It's gonna be, you know, fairly sizable, given the appetite on the clinical community for agents that are novel in mechanism and can give monotherapy activity. You know, I think it's a study that'll be well-received. I think from the powering, we haven't done the full work, but it's gonna be north of 450 patients very likely. It's gonna be randomized. it's gonna be randomized It's gonna be against a control arm that, you know, has, there's a number with data behind them, which we haven't disclosed what we're thinking on control arm yet. it's gonna be against a control arm that you know has there's a number with data behind them which we haven't disclosed what we're thinking on control arm yet It's gonna be, you know, fairly sizable, given the appetite on the clinical community for agents that are novel in mechanism and can give monotherapy activity. it's gonna be you know fairly sizable given the appetite on the clinical community for agents that are novel in mechanism and can give monotherapy activity You know, I think it's a study that'll be well-received. you know i think it's a study that'll be well-received I think from the powering, we haven't done the full work, but it's gonna be north of 450 patients very likely. i think from the powering we haven't done the full work but it's gonna be north of 450 patients very likely

Speaker 3: Got it. Just touching on the other tumor types that you mentioned. Is the rationale for those Expansions primarily the target expression profile at the end? Got it. got it Just touching on the other tumor types that you mentioned. just touching on the other tumor types that you mentioned Is the rationale for those Expansions primarily the target expression profile at the end? is the rationale for those expansions primarily the target expression profile at the end

Speaker 1: Exactly. Exactly. exactly

Speaker 2: Yeah. The target expression profile seems amenable. Obviously, even a subset of those opportunities there, the patient population. If you think about renal cell carcinoma, you know, in totality, right? It's 50,000 to 60,000 patient population opportunity, right, in the U.S. Yeah. yeah The target expression profile seems amenable. the target expression profile seems amenable Obviously, even a subset of those opportunities there, the patient population. obviously even a subset of those opportunities there the patient population If you think about renal cell carcinoma, you know, in totality, right? if you think about renal cell carcinoma you know in totality right It's 50,000 to 60,000 patient population opportunity, right, in the U.S. it's 50,000 to 60,000 patient population opportunity right in the u.s Those additional tumor types, even with kinda the cut point for ENPP3 positivity could potentially double that market opportunity. It's a very significant area that we need to invest in and start understanding the signal now. Each of those tumor types obviously is different in their own right of how they react to immunotherapy, but what I think is a true point is none of those tumor types have really ever had a good T-cell engager target developed against them. Those additional tumor types, even with kinda the cut point for ENPP3 positivity could potentially double that market opportunity. those additional tumor types even with kinda the cut point for enpp3 positivity could potentially double that market opportunity It's a very significant area that we need to invest in and start understanding the signal now. it's a very significant area that we need to invest in and start understanding the signal now Each of those tumor types obviously is different in their own right of how they react to immunotherapy, but what I think is a true point is none of those tumor types have really ever had a good T-cell engager target developed against them. each of those tumor types obviously is different in their own right of how they react to immunotherapy but what i think is a true point is none of those tumor types have really ever had a good t-cell engager target developed against them In particular, we've now seen T-cell engagers by one of our partner programs, xaluritamig, prove that T-cell engagers work differently than IO, right? Xaluritamig in late line metastatic castrate-resistant prostate cancer, classically Ipi-Nivo doesn't work. Pembro doesn't work, right? You cannot, for whatever reason, get the IO reaction to occur in those patients, but you can get a T-cell engager to work we think it's a very good opportunity for us to push the limits with good targets into these other large patient populations and really define the monotherapy potential of this drug. In particular, we've now seen T-cell engagers by one of our partner programs, xaluritamig, prove that T-cell engagers work differently than IO, right? in particular we've now seen t-cell engagers by one of our partner programs xaluritamig prove that t-cell engagers work differently than io right Xaluritamig in late line metastatic castrate-resistant prostate cancer, classically Ipi- Nivo doesn't work. xaluritamig in late line metastatic castrate-resistant prostate cancer classically ipi- nivo doesn't work Pembro doesn't work, right? pembro doesn't work right You cannot, for whatever reason, get the IO reaction to occur in those patients, but you can get a T-cell engager to work w e think it's a very good opportunity for us to push the limits with good targets into these other large patient populations and really define the monotherapy potential of this drug. you cannot for whatever reason get the io reaction to occur in those patients but you can get a t-cell engager to work w e think it's a very good opportunity for us to push the limits with good targets into these other large patient populations and really define the monotherapy potential of this drug

Speaker 3: Right. Just double-clicking on that then, how do you view the commercial opportunity for XmAb819? Right. right Just double-clicking on that then, how do you view the commercial opportunity for XmAb819? just double-clicking on that then how do you view the commercial opportunity for xmab819

Speaker 1: We think the commercial opportunity is quite substantial in RCC, right? Again, there's really a great opportunity in late line to capture those patients by besting, you know, really pretty aged TKIs, right, in those late line settings. The opportunity to move up as those three classes of drug compress earlier on, as well as the very orthogonal toxicity profile we see with XmAb819. Really, after the priming regimen, which is CRS and rash, it's a very quiet drug. The combinability with things like IO or HIF-2 alpha or- We think the commercial opportunity is quite substantial in RCC, right? we think the commercial opportunity is quite substantial in rcc right Again, there's really a great opportunity in late line to capture those patients by besting, you know, really pretty aged TKIs, right, in those late line settings. again there's really a great opportunity in late line to capture those patients by besting you know really pretty aged tkis right in those late line settings The opportunity to move up as those three classes of drug compress earlier on, as well as the very orthogonal toxicity profile we see with XmAb819. the opportunity to move up as those three classes of drug compress earlier on as well as the very orthogonal toxicity profile we see with xmab819 Really, after the priming regimen, which is CRS and rash, it's a very quiet drug. really after the priming regimen which is crs and rash it's a very quiet drug The combinability with things like IO or HIF-2 alpha or- the combinability with things like io or hif-2 alpha or- -There's a lot of plausibility there we're doing a lot of thinking and exploration about how we might go there. These other indications, whether it's papillary renal where there's nothing or colorectal, MSS colorectal or lung, you know, these are wide open spaces, right, where there's salvage 'cause that's what everybody basically ends up in after front line. It could be quite substantial we'll to focus our work on the monotherapy phase III initially, and then go from there. -There's a lot of plausibility there w e're doing a lot of thinking and exploration about how we might go there. -there's a lot of plausibility there w e're doing a lot of thinking and exploration about how we might go there These other indications, whether it's papillary renal where there's nothing or colorectal, MSS colorectal or lung, you know, these are wide open spaces, right, where there's salvage 'cause that's what everybody basically ends up in after front line. these other indications whether it's papillary renal where there's nothing or colorectal mss colorectal or lung you know these are wide open spaces right where there's salvage 'cause that's what everybody basically ends up in after front line It could be quite substantial w e'll to focus our work on the monotherapy phase III initially, and then go from there. it could be quite substantial w e'll to focus our work on the monotherapy phase iii initially and then go from there

Speaker 2: Yeah. Well, I mean, we'll give you a hyper-specific on clear cell renal cell carcinoma because I think we have the numbers now, right? We would pursue a very similar label strategy as Belzutifan and tivozanib in clear cell, where our late line study, call it, post-IO, post-TKI, would afford a label in the U.S. and in Western Europe where you would just need to be exposed to a PD-1 and need to be exposed to one VEGF-R TKI. Belzutifan actually has some handcuffs on getting reimbursement in Europe, so the adoption there has been a bit slower. Yeah. yeah Well, I mean, we'll give you a hyper-specific on clear cell renal cell carcinoma because I think we have the numbers now, right? We would pursue a very similar label strategy as Belzutifan and tivozanib in clear cell, where our late line study, call it, post-IO, post-TKI, would afford a label in the U.S. and in Western Europe where you would just need to be exposed to a PD-1 and need to be exposed to one VEGF-R TKI. well i mean we'll give you a hyper-specific on clear cell renal cell carcinoma because i think we have the numbers now right we would pursue a very similar label strategy as belzutifan and tivozanib in clear cell where our late line study call it post-io post-tki would afford a label in the u.s and in western europe where you would just need to be exposed to a pd-1 and need to be exposed to one vegf-r tki Belzutifan actually has some handcuffs on getting reimbursement in Europe, so the adoption there has been a bit slower. belzutifan actually has some handcuffs on getting reimbursement in europe so the adoption there has been a bit slower Even in the U.S. alone, really driving the adoption of the drug as it currently stands, it's on track to become a billion drug with that label as used. I think that goes to the point that there's a lot of flexibility for the clinical community, and especially as Bassil said, that front-line compression of doublet and triplet agents leaves open a really big need for second, third line novel agents, where you can actually get to a blockbuster drug status, with a late line pivotal study in clear cell. Even in the U.S. alone, really driving the adoption of the drug as it currently stands, it's on track to become a billion drug with that label as used. even in the u.s alone really driving the adoption of the drug as it currently stands it's on track to become a billion drug with that label as used I think that goes to the point that there's a lot of flexibility for the clinical community, and especially as Bassil said, that front-line compression of doublet and triplet agents leaves open a really big need for second, third line novel agents, where you can actually get to a blockbuster drug status, with a late line pivotal study in clear cell. i think that goes to the point that there's a lot of flexibility for the clinical community and especially as bassil said that front-line compression of doublet and triplet agents leaves open a really big need for second third line novel agents where you can actually get to a blockbuster drug status with a late line pivotal study in clear cell

Speaker 3: Understood. How do you view the competitive landscape for XmAb819? Understood. understood How do you view the competitive landscape for XmAb819? how do you view the competitive landscape for xmab819

Speaker 2: It's limited. In clear cell specifically, it's very limited. There's very few novel agents, and I'm not, you know, trying to take a specific shot at it, but it was specifically commented to us in our ad board at ASCO GU, "This is a good target. This is a different target. We like this target better than some of the other targets being explored, like CD70, for example. And based on what we're seeing clinically, there's a lot of potential of this drug." It's limited. it's limited In clear cell specifically, it's very limited. in clear cell specifically it's very limited There's very few novel agents, and I'm not, you know, trying to take a specific shot at it, but it was specifically commented to us in our ad board at ASCO GU, "This is a good target. there's very few novel agents and i'm not you know trying to take a specific shot at it but it was specifically commented to us in our ad board at asco gu "this is a good target This is a different target. this is a different target We like this target better than some of the other targets being explored, like CD70, for example. we like this target better than some of the other targets being explored like cd70 for example And based on what we're seeing clinically, there's a lot of potential of this drug." and based on what we're seeing clinically there's a lot of potential of this drug." You know, that was a key test for us when we presented in October and what we've seen with the enrollment into our study to date, where these patients have maxed out VEGF TKI exposure they've maxed out IO exposure, and they've also had HIF-2 alpha. We're in a little bit of a different spot where if this monotherapy profile, clinical profile, which we think it will, holds up for the RP3D data set, this is a very exciting drug with a lot of opportunity to help advance the standard of care for patients. You know, that was a key test for us when we presented in October and what we've seen with the enrollment into our study to date, where these patients have maxed out VEGF TKI exposure t hey've maxed out IO exposure, and they've also had HIF-2 alpha. you know that was a key test for us when we presented in october and what we've seen with the enrollment into our study to date where these patients have maxed out vegf tki exposure t hey've maxed out io exposure and they've also had hif-2 alpha We're in a little bit of a different spot where if this monotherapy profile, clinical profile, which we think it will, holds up for the RP3D data set, this is a very exciting drug with a lot of opportunity to help advance the standard of care for patients. we're in a little bit of a different spot where if this monotherapy profile clinical profile which we think it will holds up for the rp3d data set this is a very exciting drug with a lot of opportunity to help advance the standard of care for patients

Speaker 3: Understood. Do we know any updates from the J&J in PD-? Understood. understood Do we know any updates from the J&J in PD-? do we know any updates from the j&j in pd-

Speaker 1: We haven't heard a word. We haven't heard a word. we haven't heard a word

Speaker 2: No, we you know, again, kind of going back to some of the original comments Bassil made, we do think for this target, the two plus one format would be superior to a one plus one format. We obviously always let different formats compete when we're choosing the molecule we make, and for the expression profile of ENPP3 to bias it towards the tumor cells, we really like that play.... more technically- No, we you know, again, kind of going back to some of the original comments Bassil made, we do think for this target, the two plus one format would be superior to a one plus one format. no we you know again kind of going back to some of the original comments bassil made we do think for this target the two plus one format would be superior to a one plus one format We obviously always let different formats compete when we're choosing the molecule we make, and for the expression profile of ENPP3 to bias it towards the tumor cells, we really like that play. ... more technically- we obviously always let different formats compete when we're choosing the molecule we make and for the expression profile of enpp3 to bias it towards the tumor cells we really like that play more technically-

Speaker 1: Yeah Yeah yeah

Speaker 2: -gifted than I, so maybe you- - gifted than I, so maybe you- - gifted than i so maybe you-

Speaker 1: Yeah Yeah yeah

Speaker 2: -Wanna add some comments. -Wanna add some comments. -wanna add some comments

Speaker 1: No, I think that's exactly right we think we picked the right format given the expression profile for this target, and we have not heard a word about that program, and we're off to the races. No, I think that's exactly right w e think we picked the right format given the expression profile for this target, and we have not heard a word about that program, and we're off to the races. no i think that's exactly right w e think we picked the right format given the expression profile for this target and we have not heard a word about that program and we're off to the races

Speaker 3: Understood. Let's maybe switch over to XmAb541, your CLDN6 x CD3 bispecific. What are the key highlights from the most recent update on that program? Understood. understood Let's maybe switch over to XmAb541, your CLDN6 x CD3 bispecific. let's maybe switch over to xmab541 your cldn6 x cd3 bispecific What are the key highlights from the most recent update on that program? what are the key highlights from the most recent update on that program

Speaker 1: The update was very terse. We just wanted to show that we had advanced our dose escalation to the point where we were at active doses we showed just a little waterfall plot, I think about a 30% response rate across a basket of GCT and ovarian tumors. Right now, we are nailing down our dose level and characterizing efficacy and safety in both GCT and ovarian cancer. Again, we expect to have our dose locked down and a recommended phase III dose later this year. The update was very terse. the update was very terse We just wanted to show that we had advanced our dose escalation to the point where we were at active doses w e showed just a little waterfall plot, I think about a 30% response rate across a basket of GCT and ovarian tumors. we just wanted to show that we had advanced our dose escalation to the point where we were at active doses w e showed just a little waterfall plot i think about a 30% response rate across a basket of gct and ovarian tumors Right now, we are nailing down our dose level and characterizing efficacy and safety in both GCT and ovarian cancer. right now we are nailing down our dose level and characterizing efficacy and safety in both gct and ovarian cancer Again, we expect to have our dose locked down and a recommended phase III dose later this year. again we expect to have our dose locked down and a recommended phase iii dose later this year The program started almost two years, actually two years, after XmAb819, so we're really excited about the progress we've learned a lot about how to escalate CD3 bispecifics in solid tumors, about how to manage things, and we're not quite as far along on planning for later line, but we'll have a lot more to say later this year when we roll out all the data that establishes the phase three dose, and we can talk a lot more about it then. The program started almost two years, actually two years, after XmAb819, so we're really excited about the progress w e've learned a lot about how to escalate CD3 bispecifics in solid tumors, about how to manage things, and we're not quite as far along on planning for later line, but we'll have a lot more to say later this year when we roll out all the data that establishes the phase three dose, and we can talk a lot more about it then. the program started almost two years actually two years after xmab819 so we're really excited about the progress w e've learned a lot about how to escalate cd3 bispecifics in solid tumors about how to manage things and we're not quite as far along on planning for later line but we'll have a lot more to say later this year when we roll out all the data that establishes the phase three dose and we can talk a lot more about it then

Speaker 3: Got it. Remind me, where are you in dose optimization for this program? Got it. got it Remind me, where are you in dose optimization for this program? remind me where are you in dose optimization for this program

Speaker 1: We haven't given detailed specifics, but we are characterizing target doses, and we have been since last fall. We're at the point where we expect to have sufficient data, you know, Expansion cohort data by the end of this year at least one, if not two doses, and should be able to make decision then. We haven't given detailed specifics, but we are characterizing target doses, and we have been since last fall. we haven't given detailed specifics but we are characterizing target doses and we have been since last fall We're at the point where we expect to have sufficient data, you know, Expansion cohort data by the end of this year at least one, if not two doses, and should be able to make decision then. we're at the point where we expect to have sufficient data you know expansion cohort data by the end of this year at least one if not two doses and should be able to make decision then

Speaker 2: Yeah. It's a different track than XmAb819. XmAb819, the RP3D data set on the target dose that we would potentially take forward into pivotal into 2027, that'll be at a medical meeting in the back half. XmAb541, we expect to be at a corporate update a little, maybe later in the year, towards the end of the year, because there's a lot more complex decision-making there. The dose escalation is a basket study of ovarian, endometrial and germ cell. Yeah. yeah It's a different track than XmAb819. it's a different track than xmab819 XmAb819, the RP3D data set on the target dose that we would potentially take forward into pivotal into 2027, that'll be at a medical meeting in the back half. xmab819 the rp3d data set on the target dose that we would potentially take forward into pivotal into 2027 that'll be at a medical meeting in the back half XmAb541, we expect to be at a corporate update a little, maybe later in the year, towards the end of the year, because there's a lot more complex decision-making there. xmab541 we expect to be at a corporate update a little maybe later in the year towards the end of the year because there's a lot more complex decision-making there The dose escalation is a basket study of ovarian, endometrial and germ cell. the dose escalation is a basket study of ovarian endometrial and germ cell As you know, once you make the choice to the next stage of development, each of those are separate pathways that have to be evaluated separately. That's part of the decision-making that we'll have to make in the back half of this year when we start seeing more characterization with bigger cohorts, bigger N's of the patients and really understand the clinical profile better. As you know, once you make the choice to the next stage of development, each of those are separate pathways that have to be evaluated separately. as you know once you make the choice to the next stage of development each of those are separate pathways that have to be evaluated separately That's part of the decision-making that we'll have to make in the back half of this year when we start seeing more characterization with bigger cohorts, bigger N's of the patients and really understand the clinical profile better. that's part of the decision-making that we'll have to make in the back half of this year when we start seeing more characterization with bigger cohorts bigger n's of the patients and really understand the clinical profile better

Speaker 3: I think you touched on my next question, but just in case, what could a future development path of this program look like? I think you touched on my next question, but just in case, what could a future development path of this program look like? i think you touched on my next question but just in case what could a future development path of this program look like

Speaker 2: It's you know, we think of it in kind of three buckets, right? You have germ cell, really nothing for these patients, extremely high unmet need, very small market, right? Endometrial, some things available, still very high clinical unmet need, bigger market. It's you know, we think of it in kind of three buckets, right? it's you know we think of it in kind of three buckets right You have germ cell, really nothing for these patients, extremely high unmet need, very small market, right? you have germ cell really nothing for these patients extremely high unmet need very small market right Endometrial, some things available, still very high clinical unmet need, bigger market. endometrial some things available still very high clinical unmet need bigger market Ovarian, really busy clinical activity, in the landscape of novel drug development, large market, right? And so in a certain sense, we have to be somewhat dispassionate on what the numbers tell us to do, right? In each of those different buckets, is the clinical activity something that will drive monotherapy activity with an efficient regulatory pathway, to commercial market? Ovarian, really busy clinical activity, in the landscape of novel drug development, large market, right? ovarian really busy clinical activity in the landscape of novel drug development large market right And so in a certain sense, we have to be somewhat dispassionate on what the numbers tell us to do, right? and so in a certain sense we have to be somewhat dispassionate on what the numbers tell us to do right In each of those different buckets, is the clinical activity something that will drive monotherapy activity with an efficient regulatory pathway, to commercial market? in each of those different buckets is the clinical activity something that will drive monotherapy activity with an efficient regulatory pathway to commercial market What can we prosecute in that commercial market as Xencor or would we need a partner? That's a part of the decision-making process, and we kind of apply it to all those three buckets and come up with a game plan. We'll let the numbers. What can we prosecute in that commercial market as Xencor or would we need a partner? what can we prosecute in that commercial market as xencor or would we need a partner That's a part of the decision-making process, and we kind of apply it to all those three buckets and come up with a game plan. that's a part of the decision-making process and we kind of apply it to all those three buckets and come up with a game plan We'll let the numbers. we'll let the numbers

Speaker 1: We're not ready yet. We're not ready yet. we're not ready yet [crosstalk] Yeah. We'll tell you. We'll tell you later. [crosstalk] Yeah. [crosstalk] yeah We'll tell you. we'll tell you We'll tell you later. we'll tell you later

Speaker 2: Yeah. We'll let the numbers drive the decision-making there. But I think we have a good handle, and we have very stringent internal hurdles for what the target product co-profile needs to look like, from the data we'll be seeing this year. Yeah. yeah We'll let the numbers drive the decision-making there. we'll let the numbers drive the decision-making there But I think we have a good handle, and we have very stringent internal hurdles for what the target product co-profile needs to look like, from the data we'll be seeing this year. but i think we have a good handle and we have very stringent internal hurdles for what the target product co-profile needs to look like from the data we'll be seeing this year

Speaker 3: Understood. How do you see the competitive landscape for XmAb541? Understood. understood How do you see the competitive landscape for XmAb541? how do you see the competitive landscape for xmab541

Speaker 1: I think there's two ways to look at that. The competitive landscape in ovarian cancer is quite dense. There's a lot of ADCs, a lot of different targets. We are the first-in-class CLDN6 out there or CD3. First-in-class T-cell engager, in fact, and we hope that we can separate ourselves. We obviously have to have an active enough molecule we have to have the right kind of response rates and larger patient numbers. I think there's two ways to look at that. i think there's two ways to look at that The competitive landscape in ovarian cancer is quite dense. the competitive landscape in ovarian cancer is quite dense There's a lot of ADCs, a lot of different targets. there's a lot of adcs a lot of different targets We are the first-in-class CLDN6 out there or CD3. we are the first-in-class cldn6 out there or cd3 First-in-class T-cell engager, in fact, and we hope that we can separate ourselves. first-in-class t-cell engager in fact and we hope that we can separate ourselves We obviously have to have an active enough molecule w e have to have the right kind of response rates and larger patient numbers. we obviously have to have an active enough molecule w e have to have the right kind of response rates and larger patient numbers But separate ourselves by that immunotherapy-like durability that's starting to show from CD3 bispecifics. We've seen it with tarlatamab that led to its really excellent pivotal data in its confirmatory study, DeLLphi-304. We're starting to see it with xaluritamig. That's the hope for this modality, right? It's a very dense competitive landscape, too dense to go into an ovarian. In germ cell, there's really not a lot of activity, right? But separate ourselves by that immunotherapy-like durability that's starting to show from CD3 bispecifics. but separate ourselves by that immunotherapy-like durability that's starting to show from cd3 bispecifics We've seen it with tarlatamab that led to its really excellent pivotal data in its confirmatory study, DeLLphi-304. we've seen it with tarlatamab that led to its really excellent pivotal data in its confirmatory study dellphi-304 We're starting to see it with xaluritamig. we're starting to see it with xaluritamig That's the hope for this modality, right? that's the hope for this modality right It's a very dense competitive landscape, too dense to go into an ovarian. it's a very dense competitive landscape too dense to go into an ovarian In germ cell, there's really not a lot of activity, right? in germ cell there's really not a lot of activity right

Speaker 3: Understood. Maybe with the time left, we'll switch to the immunology efforts on XmAb942 and XmAb412. How do you view the opportunity for the anti-TL1A class and for those two programs specifically? Understood. understood Maybe with the time left, we'll switch to the immunology efforts on XmAb942 and XmAb412. maybe with the time left we'll switch to the immunology efforts on xmab942 and xmab412 How do you view the opportunity for the anti-TL1A class and for those two programs specifically? how do you view the opportunity for the anti-tl1a class and for those two programs specifically

Speaker 1: I think for TL1A, it's probably the most exciting autoimmune target that's emerged in the last, you know, five or six years, the best in disease activity in ulcerative colitis and in Crohn's. It's led to a flurry of activity. We think that emerging data from newer and different indications, I should say, for TL1A could create that pipeline in a product we're waiting to see we've got our own ideas for us starting studies. I think for TL1A, it's probably the most exciting autoimmune target that's emerged in the last, you know, five or six years, the best in disease activity in ulcerative colitis and in Crohn's. i think for tl1a it's probably the most exciting autoimmune target that's emerged in the last you know five or six years the best in disease activity in ulcerative colitis and in crohn's It's led to a flurry of activity. it's led to a flurry of activity We think that emerging data from newer and different indications, I should say, for TL1A could create that pipeline in a product w e're waiting to see w e've got our own ideas for us starting studies. we think that emerging data from newer and different indications i should say for tl1a could create that pipeline in a product w e're waiting to see w e've got our own ideas for us starting studies Our approach for nine four two was to take what has made TL1A promising, maximally leverage the existing data out there to build our molecule and our program. Our molecule's about high potency and long half-life, which gives us maximal exposure. Our approach for nine four two was to take what has made TL1A promising, maximally leverage the existing data out there to build our molecule and our program. our approach for nine four two was to take what has made tl1a promising maximally leverage the existing data out there to build our molecule and our program Our molecule's about high potency and long half-life, which gives us maximal exposure. our molecule's about high potency and long half-life which gives us maximal exposure When you look at the induction phase data from the various phase II out there, it was clear that patients with higher exposure, just the variability naturally in PK, had higher response rates. We designed our molecule to have that high potency, long half-life, and our Phase 2b study, which is a very rigorous three dose level characterization Phase 2b, to maximize exposure in the induction phase. When you look at the induction phase data from the various phase II out there, it was clear that patients with higher exposure, just the variability naturally in PK, had higher response rates. when you look at the induction phase data from the various phase ii out there it was clear that patients with higher exposure just the variability naturally in pk had higher response rates We designed our molecule to have that high potency, long half-life, and our Phase 2b study, which is a very rigorous three dose level characterization Phase 2b, to maximize exposure in the induction phase. we designed our molecule to have that high potency long half-life and our phase 2b study which is a very rigorous three dose level characterization phase 2b to maximize exposure in the induction phase We show this from all of our comparisons against precedent programs from our large company peers. Our three-month dosing interval, we believe would really distinguish us from the pack. We're the first to start a phase I, first to start a phase II, and we hope to be the first to have data for a long-acting TL1A. Our outside of IBD development plan will go from there. We do expect to have an opportunity to update on progress by the end of the year or around year-end for that Phase 2b study and talk about our further plans for that program. We show this from all of our comparisons against precedent programs from our large company peers. we show this from all of our comparisons against precedent programs from our large company peers Our three-month dosing interval, we believe would really distinguish us from the pack. our three-month dosing interval we believe would really distinguish us from the pack We're the first to start a phase I, first to start a phase II, and we hope to be the first to have data for a long-acting TL1A. we're the first to start a phase i first to start a phase ii and we hope to be the first to have data for a long-acting tl1a Our outside of IBD development plan will go from there. our outside of ibd development plan will go from there We do expect to have an opportunity to update on progress by the end of the year or around year-end for that Phase 2b study and talk about our further plans for that program. we do expect to have an opportunity to update on progress by the end of the year or around year-end for that phase 2b study and talk about our further plans for that program The really sort of next step is how do you hit two targets at once, right? People are talking about combinations we think bispecifics are where it's gonna go. We have a very potent molecule that blocks TL1A and IL-23p19. That's XmAb412. Again, it's gonna be at DDW with the preclinical characterization. We'll also have the full phase one data from XmAb942 i always think of it as a phase two program, but I forget we haven't even presented the full phase one data that'll be at DDW. The really sort of next step is how do you hit two targets at once, right? the really sort of next step is how do you hit two targets at once right People are talking about combinations w e think bispecifics are where it's gonna go. people are talking about combinations w e think bispecifics are where it's gonna go We have a very potent molecule that blocks TL1A and IL-23p19. we have a very potent molecule that blocks tl1a and il-23p19 That's XmAb412. that's xmab412 Again, it's gonna be at DDW with the preclinical characterization. again it's gonna be at ddw with the preclinical characterization We'll also have the full phase one data from XmAb942 i always think of it as a phase two program, but I forget we haven't even presented the full phase one data t hat'll be at DDW. we'll also have the full phase one data from xmab942 i always think of it as a phase two program but i forget we haven't even presented the full phase one data t hat'll be at ddw That's about having the killer app in IBD, the two best targets combined in a molecule that can be given conveniently, single injection, right? That was a really difficult engineering feat, and we'll go into the details at DDW, why we think we have the best-in-class design using Xencor's protein engineering tools to make the same kind of potency with blocking each of those two targets as the monospecific antibodies delivered at high dose. That's about having the killer app in IBD, the two best targets combined in a molecule that can be given conveniently, single injection, right? that's about having the killer app in ibd the two best targets combined in a molecule that can be given conveniently single injection right That was a really difficult engineering feat, and we'll go into the details at DDW, why we think we have the best-in-class design using Xencor's protein engineering tools to make the same kind of potency with blocking each of those two targets as the monospecific antibodies delivered at high dose. that was a really difficult engineering feat and we'll go into the details at ddw why we think we have the best-in-class design using xencor's protein engineering tools to make the same kind of potency with blocking each of those two targets as the monospecific antibodies delivered at high dose We think this is gonna be a very much simpler development path than combination agents, much simpler manufacturing than combination agents. We're ready to start that phase I in healthy volunteers this year for XmAb412. We see it as potential broad use with long-acting molecule that can combine with all the other therapies that are coming off patent you know, the combination world's gonna be about biosimilars for IL-23 and integrin inhibitors, et cetera. Those bispecifics, we think, are gonna change the landscape when they come along. We think this is gonna be a very much simpler development path than combination agents, much simpler manufacturing than combination agents. we think this is gonna be a very much simpler development path than combination agents much simpler manufacturing than combination agents We're ready to start that phase I in healthy volunteers this year for XmAb412. we're ready to start that phase i in healthy volunteers this year for xmab412 We see it as potential broad use with long-acting molecule that can combine with all the other therapies that are coming off patent y ou know, the combination world's gonna be about biosimilars for IL-23 and integrin inhibitors, et cetera. we see it as potential broad use with long-acting molecule that can combine with all the other therapies that are coming off patent y ou know the combination world's gonna be about biosimilars for il-23 and integrin inhibitors et cetera Those bispecifics, we think, are gonna change the landscape when they come along. those bispecifics we think are gonna change the landscape when they come along

Speaker 3: Understood. Can you help set expectations for the two updates that we're expecting at DDW? Understood. understood Can you help set expectations for the two updates that we're expecting at DDW? can you help set expectations for the two updates that we're expecting at ddw

Speaker 1: Sure. Dane, you wanna go on that? Sure. sure Dane, you wanna go on that? dane you wanna go on that

Speaker 2: for DDW for DDW for ddw

Speaker 3: Yeah Yeah yeah

Speaker 2: We'll have the final results from the healthy volunteer study of XmAb942. We obviously provided an interim look in April 2025. This will be the full result, full follow-up, PK/PD, TL1A target engagement, and immunogenicity. We'll have the final results from the healthy volunteer study of XmAb942. we'll have the final results from the healthy volunteer study of xmab942 We obviously provided an interim look in April 2025. we obviously provided an interim look in april 2025 This will be the full result, full follow-up, PK/PD, TL1A target engagement, and immunogenicity. this will be the full result full follow-up pk/pd tl1a target engagement and immunogenicity The totality of the package, I think, will give everyone a clear sense of why we're so excited about the Phase 2b study and the opportunity to deliver better drug exposure, especially at the top dose level, and see if that can really break through that ceiling of efficacy for biologic therapies in patients with ulcerative colitis. On XmAb412, expect a normal Xencor quality on preclinical characterization. The totality of the package, I think, will give everyone a clear sense of why we're so excited about the Phase 2b study and the opportunity to deliver better drug exposure, especially at the top dose level, and see if that can really break through that ceiling of efficacy for biologic therapies in patients with ulcerative colitis. the totality of the package i think will give everyone a clear sense of why we're so excited about the phase 2b study and the opportunity to deliver better drug exposure especially at the top dose level and see if that can really break through that ceiling of efficacy for biologic therapies in patients with ulcerative colitis On XmAb412, expect a normal Xencor quality on preclinical characterization. on xmab412 expect a normal xencor quality on preclinical characterization Very good characterization with non-human primate half-life, what we think of the dosing, what we think of the potency, stability of the molecule, and why we're obviously excited, to Bassil's point, of this killer app that could be for IBD, could be for a couple other areas where there's implications of IL-23 and TL1A, like psoriatic arthritis, for example. Very good characterization with non-human primate half-life, what we think of the dosing, what we think of the potency, stability of the molecule, and why we're obviously excited, to Bassil's point, of this killer app that could be for IBD, could be for a couple other areas where there's implications of IL-23 and TL1A, like psoriatic arthritis, for example. very good characterization with non-human primate half-life what we think of the dosing what we think of the potency stability of the molecule and why we're obviously excited to bassil's point of this killer app that could be for ibd could be for a couple other areas where there's implications of il-23 and tl1a like psoriatic arthritis for example We'll really look to get that program going as quickly as we can in the clinic. You know, I'll take a quick second for what we can do now as a clinical organization. We were first in clinic with XmAb942 in November 2024. We had a global Phase 2b study up and enrolling less than a year later. We'll really look to get that program going as quickly as we can in the clinic. we'll really look to get that program going as quickly as we can in the clinic You know, I'll take a quick second for what we can do now as a clinical organization. you know i'll take a quick second for what we can do now as a clinical organization We were first in clinic with XmAb942 in November 2024. we were first in clinic with xmab942 in november 2024 We had a global Phase 2b study up and enrolling less than a year later. we had a global phase 2b study up and enrolling less than a year later We'll run that same game plan clinically with XmAb412 to make sure we're on the competitive edge because we think we have the best-in-class molecule, and there's a lot of potential for what we can do here. The final point of this is, and we get asked a lot on the decision-making, we'll have a nice convergence of data between XmAb412, the healthy volunteer study, to effectively know do we make the molecule we thought we did, right? In that kinda 2027 timeframe, along when we're getting some of that data really from the Phase 2b study to know was our hypothesis correct. We'll run that same game plan clinically with XmAb412 to make sure we're on the competitive edge because we think we have the best-in-class molecule, and there's a lot of potential for what we can do here. we'll run that same game plan clinically with xmab412 to make sure we're on the competitive edge because we think we have the best-in-class molecule and there's a lot of potential for what we can do here The final point of this is, and we get asked a lot on the decision-making, we'll have a nice convergence of data between XmAb412, the healthy volunteer study, to effectively know do we make the molecule we thought we did, right? the final point of this is and we get asked a lot on the decision-making we'll have a nice convergence of data between xmab412 the healthy volunteer study to effectively know do we make the molecule we thought we did right In that kinda 2027 timeframe, along when we're getting some of that data really from the Phase 2b study to know was our hypothesis correct. in that kinda 2027 timeframe along when we're getting some of that data really from the phase 2b study to know was our hypothesis correct We'll be able to make really rational decisions on dollars spent internally, how we prosecute each of those programs, potentially from, you know, partnership strategies and other strategies, to maximize the value for all of our stakeholders, the patients, the clinicians, and obviously our shareholders. We'll be able to make really rational decisions on dollars spent internally, how we prosecute each of those programs, potentially from, you know, partnership strategies and other strategies, to maximize the value for all of our stakeholders, the patients, the clinicians, and obviously our shareholders. we'll be able to make really rational decisions on dollars spent internally how we prosecute each of those programs potentially from you know partnership strategies and other strategies to maximize the value for all of our stakeholders the patients the clinicians and obviously our shareholders

Speaker 3: Understood. Maybe I can just squeeze in one last question on exactly that last point. BD's been an important part of Xencor's history. How are you thinking about business development opportunities from here? Understood. understood Maybe I can just squeeze in one last question on exactly that last point. maybe i can just squeeze in one last question on exactly that last point BD's been an important part of Xencor's history. bd's been an important part of xencor's history How are you thinking about business development opportunities from here? how are you thinking about business development opportunities from here

Speaker 1: I'll take that. BD is gonna be about what advances our pipeline. If there's an opportunity, like maybe for TL1A, where there is a broad set of late phase clinical trials that we wanna make sure we can address, that's when partnering might come in, right? Our goal is to take our programs all the way through by ourselves, but we know that sometimes the way to move fastest is with a partner. It's gonna be driven by the pipeline's needs and when we need that resource boost. I'll take that. i'll take that BD is gonna be about what advances our pipeline. bd is gonna be about what advances our pipeline If there's an opportunity, like maybe for TL1A, where there is a broad set of late phase clinical trials that we wanna make sure we can address, that's when partnering might come in, right? if there's an opportunity like maybe for tl1a where there is a broad set of late phase clinical trials that we wanna make sure we can address that's when partnering might come in right Our goal is to take our programs all the way through by ourselves, but we know that sometimes the way to move fastest is with a partner. our goal is to take our programs all the way through by ourselves but we know that sometimes the way to move fastest is with a partner It's gonna be driven by the pipeline's needs and when we need that resource boost. it's gonna be driven by the pipeline's needs and when we need that resource boost

Speaker 3: Understood. Thank you guys very much for taking the time. We appreciate it. Understood. understood Thank you guys very much for taking the time. thank you guys very much for taking the time We appreciate it. we appreciate it

Speaker 2: Thank you. Great questions. Thank you. thank you Great questions. great questions

Speaker 1: Thank you. Thank you. thank you