All right. Well, thanks, everyone, for coming to the Xencor panel. I'm pleased to have Dane Leone, EVP and Chief Strategy Officer. Thank you for having us at the Wells Fargo Conference. Pleasure to be here, and thanks for having us on stage. I'll let you start off with an overview to introduce those who may not be familiar with the company and then I'll go into questions. Great, thank you so much. So I'm the Chief Strategy Officer of Zenkor, which is a clinical stage biotech company advancing novel engineered proteins for the advancement of oncology and autoimmune disease. We've had a growing portfolio over the last couple of years to really harness the power of our protein engineering platform, which has been validated and differentiated through numerous partnerships and drugs that are on in commercial use over the years since its founding over twenty years ago by our CEO, Founder, Basil Dahyatt. And yes, we're getting into a clinical inflection point that's really exciting across roughly three different therapeutic verticals. If you think about how we phase the company, last September, we did what could be characterized as a strategic reset, where we trimmed some of the oncology programs to those that we really think have a higher probability of success and then unveiled a number of autoimmune programs. Two of those programs are targeting a novel target, which is very exciting for inflammatory bowel disease, which is TL1a and then two programs that are moving into the clinic this year for rare and severe autoimmune disease, which is a CD20, CD3 T cell engager and a CD19, CD3 T cell engager, pimetamab and XmAb657 respectively. So kind of on the forefront of our clinical development are our oncology programs, which are T cell engagers, XmAb819, which is the EMPP3 CD3 T cell engager that's being developed in dose escalation studies for advanced clear cell renal cell carcinoma. We will have first data from that study in the fourth quarter presented at a medical meeting of this year. And then coming up probably fast behind it is XmAb541, which is a Cloudin-six CD3 T cell engager, which we're testing in endometrial, ovarian, germ cell and other solid tumors. We started that program in the clinic in April 2024 and have been working through dose escalation rapidly. I'm very excited on our second quarter earnings release to disclose that we had started the Phase 2b of our monospecific TL1a program in ulcerative colitis, XmAb942. And that program, that global study is ramping as we speak now, and we remain on track to have kind of the killer app in targeting two different inflammatory axes for inflammatory bowel disease. Our XmAb program, bispecific, which targets TL1A and IL-23P19, and that'll be first in human in 2026. So yes, we have kind of three different verticals split between oncology and autoimmune. And really, what we're aiming for here and what we've been discussing since probably September is taking maybe targets that we think are have validation and applying our protein engineering to those targets to either make better modalities or better constructs that can maximize the benefit of what that target can do for a specific disease and those patients and clinicians and advance the standard of care. So we're very excited. We have a lot going on, definitely a busy time over at Zencore. So 2025 has been kind of heads down, execution focused, and we're looking forward to a lot of data generation going into the back part of this year and into 2026. All right. So a lot of exciting programs. I wanted to dig more into the platform that underpins this. Can you walk us through the plug and play platform and how your approach and extend technology are differentiated from competitors? Sure. So like I said, the company was founded over twenty years ago by our CEO, founder of Basil Diet, and essentially assembled a world class group of protein engineers to things with proteins that really had not been done before. And some of the earlier technologies were looking at ways to do Fc knockout on the Fc region in a stable manner to do half life extension with the LS mutation that is still under patent for us and is widely regarded as the best way of doing FCR and recycling currently to more novel ways of putting two different targets together in a bispecific format, which has emerged as our two plus one format, where there's kind of two engagement targets for any antigen and then a CD3 region or some other region that's engaging a T cell. And yes, so for example, the Xtend technology has been used in Ultomiris and the two plus one formats being used in the xioridomig program by Amgen for prostate cancer. And that goes back to the validation that I'd mentioned earlier through these partnership programs and commercial assets on what our the power of our protein engineering and what it can really differentiate to be. And so yes, there's kind of a good list of partnerships and programs that we're watching and looking forward to seeing them advance through the clinic, not just for the financial aspects of the royalties we may owe or the milestones we may be owed on those programs, but also through, to your point, validation over technology. Okay. Got it. So given some of these products on the market, is it fair to say that the Xtend platform at this point is fairly derisked? Yes. I think our Half Life extension technology is probably as well characterized as it has been for any Half Life extension technology. And there's another one that's off patent. Ours remains on patent and is used in a number of our wholly owned programs as well. So I don't think there's any debate in terms of how well the half life extension technology works. And by evidence of using it in our monospecific TL1a program, which in April, we disclosed a greater than seventy one day half life, which allows us to do Q12 week dosing and our maintenance period for a Phase IIb relative to the first gen TL1a drugs, which are Q4 weeks. So yes, no, very differentiated approach, very highly stable way of doing the mutations to affect the FcRn recycling that gives the ampide to long half life and proven numerous times to be effective in the clinic. Got it. And so I wanted to talk more about the next gen anti TL1A XBAP-nine forty two. Can you talk about the design of this and then how it's differentiated from the other TL1As in development that we see from like Merck, Appy, Teva, etcetera? Yes. Great question. So when we sought out to make a next gen T01a, really, the concept to us, which took some risk because the clinical data from the first gen Phase II programs had not really played out yet as they have today was through superior potency coupled with better half life than some of the first gen molecules, you'd be able to affect greater drug exposure, more consistent drug exposure for patients with ulcerative colitis and Crohn's disease. It's been heavily debated but increasingly proven that for whatever reason, a high percentage of patients that have ulcerative colitis and Crohn's disease end up with lower drug exposure than what's effective clinically. Now there's numerous reasons for that. That can be due to the drug or the patient themselves. But what's been clear to us through numerous studies now, not even just with the TL1a class, but better defined standard of care class like the IL-twenty three class in IBD is if you ramp up the drug exposure, especially in the induction period, you will have better outcomes for these patients. So you've seen reinduction studies prove that kind of rule of thumb about fifty percent of patients that didn't respond to the original induction period on reinduction or extended induction will then respond. We want we designed a molecule that we hope can capture that in the first induction for these patients. And we think that would be clinically differentiated, and that's what we've designed to do. And we presented some of the QSP modeling off of the XmAb942 first in human dataset that we presented in April right ahead of DDW to show that in the induction period, what we're using for the Phase IIb induction regimen really gives you that reduction in soluble TL1a in the gut compartment and maintains that suppression of soluble TL1a throughout the maintenance period. And we think, especially on the back of Pfizer Phase 2b Tuscany publication, that did show great variability in outcomes that were related to drug exposure even though they didn't have dose response in their studies when reported is getting at that aspect. So we feel highly encouraged that we took the right thesis upfront at risk. That's being proven out in the clinic through all these studies in TL1A and IL-twenty three class, and we've designed the right molecule to solve for that. And so the Phase IIb global study is ongoing, ramping up as we speak, and hopefully, we'll give some more clarity on the timelines of that study as we get closer to the end of this year. Okay. I wanted to ask about the study design, but to get some context for how we got there, can you talk about the Phase I data? What kind of dosing schedule, the estimated terminal half life supports, and then perhaps also the impact of ADAs on the PK profile? Yes, sure. So we've been happy with the Phase I data. We reported out interim Phase I data, which included the SAD portion of the study along with an early cut on the MAD portion of the healthy volunteer study. The database will lock in the back half of this year. So technically, the study is not completed yet. So what we do know from the study and the totality of data that we have in hand is that the molecule's potent suppressor soluble TL1A for extended period of time and the half life of greater than seventy one days, we haven't put a fine point on it, but greater than seventy one days very clearly supports a Q12 week dosing schedule, which again differentiates versus the first end class, which is a Q4 week schedule at best. And we can do that with a single subcutaneous injection, which is obviously highly valued in the maintenance period for biologic drugs and IBD. The rationale for us in terms of the development pathway is with the confirmation that what we characterize preclinically has been now confirmed clinically, going into a Phase IIb design that does the proper dose characterization of multiple induction doses compared to placebo and induction phase fall by a maintenance phase that allows efficient transition to pivotal testing. That actually is a little bit different than I think what the first gen TL1a programs have experienced, where they're having to do more dose characterization in the pivotal studies because those were not done on a more traditional manner in the Phase II. So we want to get to market as fast as possible. We're pushing the Phase IIb to be efficient and as effective while answering regulatory questions as possible to then move into pivotal study and commercialization thereafter. We feel confident that if, again, the clinical characterization matching the preclinical characterization will transfer to the patient population and also colitis, we will have a differentiated clinical profile that will convert the market. Okay. And then within the TL1a program, you also have seen p53, a TL1a, IL-twenty three bispecific. Can you talk about the advantages of this bispecific design over combining an anti TL1a with an IL-twenty three? Sure. Yes, happy to. So as I said, kind of at the start, our clinical development pipeline is powered by the XmAb protein engineering platform. And bispecifics are something that Xencor has been known for through many partnerships and efforts in oncology and outside of oncology for years and years. And we think there's specific cases where you can fix the stoichiometry between two targets in autoimmune disease autoimmune and inflammatory disease to essentially create one molecule that's going to be just like your average monoclonal antibody for development purposes into something that could have truly game changing clinical outcomes. And so what we liked about IL-twenty three is that it to date, when you saw the outcomes of the risankizumab studies and emirikizumab studies and the gazelkumab studies as well. These are this is a class that has produced the best clinical results clinical benefit along with lowest toxicity and adverse event rates that we've ever seen in ulcerative colitis and Crohn's disease. Given the safety profile that we've seen with IL-twenty three and a I think a reasonable understanding of the translational biology between IL-twenty three signaling pathway and the TL1A signaling pathway, there would be synergy and also perhaps a somewhat orthogonal nature between the two signaling pathways where you could then combine IL-twenty three inhibition with the safety profile that we're seeing for TL1A And creating a bispecific that can affect both of these in one drug delivery, right, very clean CMC, very clean regulatory pathway would be something that we could rapidly progress through the clinic to commercial and for IBD and probably another select set of autoimmune inflammatory disease, really be something truly differentiated. So we're very excited about that program. We'll be first in human in 2026. And that's hopefully going to be a flagship program showcasing the power of our protein engineering. Okay. And can you share if you've learned anything about the profile so far from preclinical data? And then how you're thinking about the development strategy for ZNP53 versus XmAb942? Sure. So what we've shared on the preclinical profile of our bispecific, TL1A IL-twenty three bispecific, is we have been able to engineer into a bispecific construct two monovalent arms that are equipotent to their a parental monospecific where you obviously have two arms binding. That's not a small feat to do either on the TL1a side or the IL-twenty three side. So that took a lot of engineering work from the Xencor team. But being able to do that means that without kind of a loss of potency, we can dose effectively, hopefully at very reasonable drug concentrations, and simulate giving each of those drugs an IL-twenty three and a potent TL1A individually. That gives you a lot of flexibility in terms of working with the clinical regimen, doing the formulation, getting it into subcutaneous delivery and bringing the power of the two best autoimmune targets we've seen for inflammatory bowel disease together in one bottle. Okay. Got you. So I wanted to talk about the B cell depleting T cell engager side of the INI franchise. Can you discuss the data that you've seen so far for plamotamab? So the plamotamab study is getting up and running right now. In the second quarter, we disclosed that had regulatory authorization outside The U. S. We're continuing to ramp up the clinical sites. So a little early to be discussing data, but we'll provide some time lines as we get a better handle on the cadence of that study as it kind of rolls out in the back half of this year. And then for XmAb657, which is the CD19 and CD3, we're working through regulatory authorization in the back half of this year to then kind of get both of these studies up and going in earnest during 2026. Okay. And then for the CD19CD3 bispecific, where do you think that this can win over CD20 T cell engager? And then is targeting CD19 differentiated in autoimmune indications? Yeah. We think, you know, across the spectrum of B cell targeted antigens, CD20, CD19 are both quite interesting and potentially differentiated. So we've publicly announced that for piplotamab, we'll be looking at advanced rheumatoid arthritis patient population with the initial study. And we thought targeting CD20 in rheumatoid arthritis was fit for purpose. So there's kind of the factors that everyone knows, right? Rituximab is approved for RA. Rituximab is monoclonal antibody that could target CD20, has been proven effective for patients that have gone through probably earlier lines of biologic or targeted synthetic therapy and need something a little bit more powerful. What we also know is that rituximab is not able to really consistently affect deep enough B cell depletion to have durable clinical outcomes in RA. So there's been studies where you see whether the B cells come back replete in a way within the first four months can actually signal their clinical outcomes. T cell engagers notably get much deeper into the tissues than a monoclonal antibody. And especially in a B cell driven disease, T cells co locate with B cells much more frequently in resident tissue than you do with NK cells, which is kind of the dependent mechanism of a monoclonal antibody on ADCC. So yes, there's a lot of reasons to think that you have a high level proof of concept that targeting CD20 and RA can be effective and also why a T cell engager against that same CD20 antigen would be substantially more effective. And then you layer in some of the nuance that in RA specifically in the synovial tissue, that's kind of the manifestation a lot of the clinical assessments and outcomes, even though it is a systemic disease. And plamotamab or any T cell engager is going get into that synovial tissue. We saw that through some of the academic studies where there were risk biopsies taken. And the T cell engagers were able to clear out the autoreactive B cells. And that's been a characterized feature of something like rituximab not being able to do for whatever reason, right? And so on clinical benefit, I think there's a very clear thesis of why pimetomab could be interesting. The other side of this, though, is that in RA, there's really a low acceptance of added toxicity or infection risk, right? Safety is pretty paramount. It's a high bar in RA. And so CD20 with kind of RA defined safety profile of rituximab kind of gives us a sense of where we could come in with pipotamab. CD19, which is going to target some of the subsets of plasma cells more directly, would be expected to have maybe more of a pronounced incidence of infection risk, right? And so we think for XmAb657, which targets CD19 as a T cell engager, there's probably going to be a different set of autoimmune inflammatory disease where there might be more of a plasma cell subset component driving the disease relative to what you see in RA, but also maybe a severity that the acceptance level of a little bit more potential risk to the patient on infection risks or what would need to be clinically managed would be more tolerant than something like RA. So we think CD20 and CD19 are kind of fit for purpose and different indications. Even though, yes, there is kind of an overlap of some of the B cells that both of them target, there's also enough of a difference of the striatum of B cell lineages that CD20 and CD19 are expressed on to think that there will be somewhat of a differentiated clinical profile between the two. Okay. And then for pimonimab, can you run us through the development plan and when we can expect an initial data readout? Yes. I think probably towards the end of this year and to early next year, we'll be able to give more time lines. Again, we're just kind of getting the study open, up and running. And the data that we've seen from muslinetuzumab, which is the Roche CD20, CD3 in lupus, which was reported at EULAR, was highly encouraging for the class. You saw a good clinical response, a reasonable cytokine release safety profile and nothing really else unexpected with very good B cell depletion. So I think for us, it's kind of getting a handle of the cadence of the clinical enrollment and the pace that we're going to be going at for both of these programs and then kind of predicting when we'll have something meaningful to say. Because I think there's been a lot of good academic work done, and I think people believe in the proof of concept. Now I think it's more on the companies such as Zencore to come out with real clinical data sets that maybe prove take the next step beyond the academic step. But you know, that said, both of the studies will obviously be open label. As, you know, data cards are flipped, for us internally, we can figure out whether is there something meaningful to say externally. Okay. Moving on to the oncology franchise with the XmAb819 program, can you talk about the rationale for targeting ENPP3 in CCRC patients? And then also just provide more color on this antigen target, how de risked it is. Yes. XmAb819 is our lead oncology program. Like I said earlier, we're going to have first data from the ongoing dose escalation study in advanced clear cell renal cell carcinoma, which unfortunately for patients has not had a lot of innovation as has been seen in other areas of oncology and has a very high unmet need for differentiated modalities. We chose ENPP3 to study one on our own internal work and data around expression of EMPP3 on these tumor cells, but also had some third party validation from older ADC studies that had been run and also did good characterization of the MPP3 on the tumor cells and did show some activity, although there was kind of dose limiting toxicity associated with those agents due to the warheads and the conjugates. So we think ENP3 with probably fairly high and consistent age score expression in clear cell renal cell carcinoma allowed us to run a dose escalation study where we don't have to preselect the patients, which is kind of paramount and makes the study more run faster. So basically all comers, any clear cell renal cell carcinoma patients can ID for the study. And also give us a real clear definition of how this target works and XBAP-eight nineteen works and dialing in the regimen to get these patients to the target dose levels while trying to minimize the CRS, but maximize the dose exposure upfront to control the progression of the disease, which is obviously paramount when you're dealing with salvage line patients. So we've been working hard on this program for a number of years now. We kind of gave a qualitative disclosure last September that, yes, we felt like we had an active drug. We had seen anti tumor activity. And now it's on us at a medical meeting to present that data as we continue to dose escalate around what we've really seen on anti tumor activity in some of these early target dose cohorts and then kind of the duration of those responses they've occurred for those patients that have had clinical response. So we're really excited about where the program is moving to. I think we want to obviously, after this presentation, really work to accelerate the development going forward and bring a novel modality to these patients that really have nothing else and continue to cycle through multiple lines of VEGF TKIs that unfortunately do not do a great job of extending survival. Okay. And can you walk us through the latest update on 08/19? Have you seen any responses yet in Phase I? And does any of the early data suggest that safety is manageable here? Yes. So we actually disclosed last September that we had seen clinical responses in the program. What's different now is kind of getting into the target dose levels, looking at the patient subsets that we think are getting the adequate drug exposure and kind of more of what is an emergent response rate, right, for those patients. And at those levels where we're getting an emergent response rate, what's the toxicity profile? How tolerable is the regimen? And are we able to manage through the CRS, right, which is the class effect of T cell engagers. And so yes, where we've been at in setting expectations is there's pretty good precedent for what you see of a monotherapy anti tumor activity for salvage line, clear cell renal cell carcinoma that's been indicative of the potential of a drug or drug program to move forward eventually into commercial use. And so when you break it down in kind of the patient populations that we've been looking at, rechallenge with a VEGF TKI, you'll get kind of somewhere between a fifteen percent to twenty percent response rate at best. The most novel agent that we've seen, which is belzutafan recently approved, affected about a twenty five percent response rate in their dose escalation cohort, and then that stayed relatively steady at to around a twenty two percent response rate in their pivotal study. So kind of above twenty percent is probably the hurdle that you're looking at to say there's enough antitumor activity here, if there's a manageable safety profile to think that this could have potential through optimization and all the work that goes into coming up with that final regimen ahead of a pivotal study to be something that's really effective for these patients and exciting for clinical use. And I think that's probably the best characterization of how to interpret an early data set and bring something to the table that is going to be orthogonal to, again, hitting those patients over and over with the VEGF TKI. And we've already proven that rechallenge with PD-1s does not work. And PD-1s or nivolumab or pembrolizumab or standard of care frontline. All right. Elsewhere in the oncology franchise, can you provide an overview of XmAb XmAb541, the CLDN6 and CD3? Sure. We started in clinic with XmAb541, which is a CloudN6 CD3 T cell engager in April 2024 and have been working through dose escalation with that program as fast as possible. We publicly disclosed that. We hope to start characterizing target dose levels this year. And quite honestly, applied a lot of the learnings that we went through with XmAb819 to make that program run faster, be more efficient with how we tackle it and keep on the edge as kind of the first in class CLDN6 CD3 T cell engager. So what we've seen is CLDN6 is a good target in ovarian endometrial germ cell tumors. There's been a number of ADCs that have reported out data from their programs. And I think for the T cell engager class, it's can you get to the drug exposure level, work through CRS that allows you to hit a response rate that's like the ADCs, but not having the accumulated toxicity of being exposed on a cycle by cycle basis to those warheads, which can include neutropenia, which is managed with G CSF or neuropathy, which is accumulating and debilitating. So we think T cell engagers have a clear opportunity to differentiate. Now it's just getting to dose levels where they start having response rate and antitumor activity that's on par with the other modalities targeting Cloud N6. Okay. And then what do you see as a potential advantage for XmAb5R1 being so highly selective for Cloud N6 over other family members? Yes. I think I mean, I think that's the ticket to admission, right? There's different CloudEnd family members that have kind of a high homology, if you will, where it takes a lot of thought around the design, and we also use our two plus one format to be selective over the other family members that would have potentially problematic on target toxicity. So I think that's just that's, again, the price of admission here. I think when we think about the design of XmAb541, we were going for something that could be dosed conveniently and also give us the fidelity to work through any kind of CRS toxicity type issues getting to the patients to the target dose where we know T cell engagers become a lot cleaner once you start cycling through the target dose, and it's easy to keep the patients on those drugs. Okay. Then wanted to leave the audience with a parting takeaway statement. As you think about over the next year, what would you say are like the top one or two developments that would make for a successful year? Yes. I guess I'm going to one, we love all of our children in the portfolio and pipeline and are proud every day of what our protein engineers have been able to achieve in the design and development of these molecules. But on us and as a management team, I think in the coming year, it's paramount to kind of bring the story together, right? So in September 2024, we did the strategic reset. Now we need to kind of bring out the clinical data, the clinical time lines, the catalyst calendars as we worked hard over the last twelve months to grind through regulatory approvals to start these studies, get the studies ramped up, do all the clinical operations work to make sure we have well thought out tactics in the clinic. And now kind of come back to the investor community and say, okay, this is how it all fits together. This is the grand plan here between our wholly owned programs, the partnerships that we have that are starting to mature and how, at the end of the day, Xencor becomes a commercial stage biotech. All right. Well, thanks so much, Dane, for that fantastic dive through Xencor. And thanks, everyone, for being here. Thank you. It was a pleasure.