Good evening, everybody. My name is Ted Tenthoff. I'm a Senior Biotech Analyst at Piper Sandler. And before I begin, I am required to point out certain disclosures regarding the relationship between Piper and Xencor that are posted at the back of the room and also at the registration desk. So we just upgraded Xencor on Monday to overweight ahead of what we expect to be a really exciting 2025 with multiple clinical readouts. Beyond oncology, Xencor is expanding XmAb development into autoimmune diseases. And beyond its wholly owned pipeline, Xencor has strong partnerships with Amgen, J&J, Roche, Astellas, and others. Hear from Xencor's Co-founder, President, and CEO, Bassil Dahiyat, and also SVP of Corporate Strategy, Dane Leone. Great to see you guys, and thanks for being with us. Thank you, Ted. Thank you, Ted. I mentioned in my prepared remarks, my opening remarks, that you're expanding into antibody development in autoimmune disease. Maybe we can start, like, what went into this decision and what's Xencor's overarching strategy? So our overarching strategy is how can we use what we are best at, protein engineering, building molecules that can address very specific clinical needs. And how can we do that in a way that's going to create best-in-class molecules? The emergence of new opportunities in autoimmune disease is really what led us back into autoimmune disease. You know, we've been working in that area with partners and ourselves for over a decade. And I think with the autoimmune disease pull that really got cooking at Xencor about 18 months ago, we only unveiled in September. I think there were two main threads. One was the emergence of some new targets that could benefit from best-in-class antibody design with ultra-long half-life, like our extended technology offers, with high affinities and high selectivities. And that led to our long-acting TL1A program. And that meshes beautifully for the next generation of TL1A with other targets like IL-23 with our bispecific platform. So, new autoimmune targets that create opportunities that were emerging. Clinical data positions our platform well as one. And then two, the really exciting data that came out of CAR-Ts for very, very deep and potent depletion of B-cells to treat autoimmune disease, where we think a bispecific T-cell engager, you know, therapy in a bottle, well-validated, could be a much more amenable approach. So that upswing of data where the really deep, potent killing of B-cells could give you even better outcomes than older therapies like RITUXAN also pulled us in. So we pulled it all together and unveiled it a couple of months ago. We're talking about autoimmune disease. Maybe we'll keep going there and come back to the oncology stuff if that works for you. You just presented some data on your anti-TL1A antibody XmAb942 at United European Gastroenterology Week. Maybe you can walk us through this data. And I know you guys just started the phase I study there. Tell us about that study and when we could get data. Yeah, I'll touch briefly on the molecule design, and then Dane, who actually was at UEGW, can comment further. So we engineered that molecule. It was a fully internally developed molecule optimized at Xencor for high, high affinity to the target, high potency for both membrane and soluble TL1A, with our Xtend long half-life Fc domain on it that's been in multiple marketed products and is in over 20 product candidates right now. We had a 23-day half-life in non-human primates. We got into the clinic about a month ago. We're advancing well in healthy volunteers. And it's the first, to our knowledge, long-acting TL1A in the clinic. And then maybe, you know, Dane can comment on the context. Sure, yeah. UEGW was a great conference for us to gain exposure with the investigator community and really understand the excitement around having a best-in-class TL1A monospecific. And as we walked through, you know, our partners and investigators in what we're bringing to clinical development, it was really clear to us that we have an opportunity to try and bring best-in-class drug exposure. And there really is a clear sense that the first-generation molecules might not be adequate with drug exposure for patients and that a best-in-class next-gen would have the opportunity to maybe push the clinical efficacy of the entire TL1A drug class a bit higher if you really are getting that better drug exposure across patients. And so that's really been the cornerstone of the program for us, of trying to deliver added efficacy by building on the first gens into what our next gen is going to bring on not just the half-life, but the potency, and really think about the long-term ceiling of IBD and trying to break through that. And, you know, we're not just doing that with monospecific. We also have a TL1A IL-23 bispecific that's rapidly advancing, hopefully into the clinic in 2026, and really is looking for that next wave of drugs for the clinical community to say, "Okay, I have something that looks different in terms of clinical remission and induction period. I have something that's going to be more effective for these patients in the maintenance period." So, yeah, lots of excitement. We're thrilled. We'll be moving forward rapidly, and we'll have the first interim data in the first half of 2025 for the monospecific TL1A. Great. Now, you guys got rights back to your CD20 x CD3 bispecific, plamotamab from J&J. What are your plans for this in autoimmune disease? Yeah, we had the collaboration with them in lymphoma, and just the commercial landscape and lymphoma shift got Janssen to the point where they thought they didn't want to pursue lymphoma. We encouraged them to revert the rights. We knew we wanted to position that molecule. Plamo is an 18-day half-life. We've got a really good, well-tolerated priming step-up regimen, subcutaneous delivery already for lymphoma. And we're going to start a trial in RA in the first half of next year. We think RA is a great indication for a CD20 x CD3. It's a very, very safety-first indication where long-term infection risk, even at low rates, is something that people strive to avoid, even though all the known therapies have some incidence, even the good old TNF blockers and methotrexate. So CD20 is expressed on a narrower band of B-cells, and some of the other popular B-cell targets people are using as an anchor to kill that population. It's fewer B-cells than the CD19s or the BCMAs. And so we thought that was a great fit that might really help us differentiate, plus the speed edge we have with a dosing regimen for oncology worked out that positions us to really, hopefully, very quickly port it in an optimal way to autoimmune. Yeah. And you mentioned in your prep remarks or in your discussion about sort of the transition that you're making about CD19 CAR-T resetting the immune system to treat lupus and other autoimmune diseases. We just got an update from a bunch of those approaches at ACR just a couple of weeks ago. Tell us what your plans are for XmAb657, which is your CD19 x CD3 bispecific. And, you know, again, how important is safety with these bispecifics in autoimmune disease? Let me comment on the design of the molecule and the positioning, and then, you know, Dane can jump in on how we're going to build the clinical approach. So that molecule was designed specifically for use in autoimmune disease. We picked a 2+1 format to give us killing of even fairly low CD19 expressing cells because we have a good affinity there. And we have our long half-life Xtend Fc domain in there. So even in non-human primates, we had about a 15-day half-life with a single dose of non-human primates ablating all detectable B-cells in lymph nodes, bone marrow, and in the periphery better than 99.9% for over a month. So one shot, just crushing it down. We believe that durable action for an agent that showed very good tolerability in monkeys, no CRS symptoms, though we don't know, obviously, how that's going to port to humans. We can't predict. That durability is important for two reasons. CAR-Ts give you about two months - four months of killing of the B-cells. That's how long they persist. That has correlated with very, very deep B-cell killing and good efficacy in hard-to-treat lupus and systemic sclerosis. We don't know whether it's necessary, but it certainly correlates. We think 657 can mimic that with a very short regimen of a few weeks, and, you know, that's a very attractive profile. Furthermore, having that drug level maintained means as you step into your target dose, as you do your priming and step-up, your drug level is maintained up there, and you run less risk of recurrence of CRS. So it's a double win. Now, how we use that, that's an interesting question. Yeah, it's been an exciting year for B-cell targeted therapy in autoimmune. Building on a lot of different studies, it's become clear that with deep depletion, not just in the periphery, but in the B-cell compartments, you can get repletion of the B-cell population towards more of a naive subset that seems to have this durability of remission across a number of very hard-to-treat autoimmune disorders. And so when we think about the landscape, we think about what's fit for purpose on a clinical basis, right? And so plamotamab, which we just disclosed, is going into the clinic for rheumatoid arthritis in the first half of next year. That's a patient population that's very sensitive to infection risk, right? A CD20 is probably not going to deplete the plasma cell subsets as much as other targets. You know, the extreme case would obviously be target, which onset of infection is very fast in a recent academic study, but you can also get something beyond what's been seen with the classical B-cell depleter, which is rituximab, right? A T-cell engager is going to deplete in those B-cell compartments, and that's really fundamental to the synovial inflammation that you see in these RA patients, right? You clear out those autoreactive B-cells in the synovial tissue, and that should really correlate some of the clinical scales that are used to measure tender, swollen, joint counts, etc., and that drives better outcomes, right, and you hope you have these durable outcomes for these patients on a naive switch in the repletion of B-cell subsets. So, you know, taking that, we were then going to look with 657 on the CD19 side and say, "Okay, well, what's fit for purpose here," right? As Bassil laid out, right, we have clear depletion in our NHPs on plasma cell subsets. Looks really good, really strong, nice, beautiful, long half-life, where we could match the B-cell aplasia window really easily that we've seen in some of these CD19 CAR-T studies. But this is an off-the-shelf drug product, right? We're not using fludarabine or cyclophosphamide, which is becoming a little hard to digest for the clinical community, as we heard at ACR. And this is a stable drug product, right? We give a dose to a patient. We know what dose they're getting. With CAR-T, you have no idea what dose is going to vary patient to patient. That's just become increasingly problematic of replicating some of these early academic studies. That said, these early academic studies have shown that there's real clinical response across really difficult autoimmune diseases, systemic sclerosis, myositis. So we've played CD19 close to the chest, and we're going to be first in human in the back half of next year. You can think of that as a differentiated build versus what plamotamab. We think there's definitely a clinical spectrum going on here. What we feel good about with having a CD20, CD19 in our portfolio is that these seem to be the right targets now, right? We've seen the academic data come out again on BCMA. It's a little tough, right? There's real infections, even with prophylactic antivirals and antibiotics. We feel like we're in a good position. We'll definitely disclose more as we get in the first in human. But we think there's kind of two different pathways to build the clinical portfolio of plamotamab and 657. Would the approach here be a chronic therapy, or would it be really this reset of the immune system? It's an interesting question. I mean, the evidence that we have now is across, and we can just pool CAR-T experience from the academic and the early commercial efforts and along with some of the now academic studies and T-cell engagers. Even look at, you know, some of the CD20s, next-gen CD20s like obinutuzumab that have been tested in autoimmune as presented at EULAR this year. There's really a clear spectrum, right? You know, so you'll have a percentage of patients that have this durable remission, right, where the repletion is enough with a naive subset that, you know, they're out beyond a year. They could be out beyond two years, right? Then there's some that might need repeat therapy on a yearly basis. So we don't know, you know, which patient is going to respond why, but it seems clear that if you have a good drug that's doing the right and deep B-cell depletion, you know, you'll get that subset that's going to be the long-term responders. And then you have patients that might need periodic treatment. Yep. Great. And that's one of the advantages of bispecific is you can go back in and treat again. So I'm going to transition to some of the stuff in oncology, which I do think provides a lot of validation for what you're doing just across the XmAb platform in so many patients at this point. Vudalimab targets CTLA-4 and PD-1. We could get some data in the first half next year in prostate cancer. This is an area checkpoint inhibitors really haven't shown that much activity. So why do you think vudali can work here, and what should we be expecting? We've seen, you know, we had our data update in February with vudalimab in patients with visceral mets, very heavily pretreated, where we had, I believe, it was a 25% PSA90 rate and objective responses in four patients as well. Because these were all RECIST measurable. That was clear activity, right? I think the challenge is making sure we understand how it fits into the landscape. So that was a small N. We've run the study now further. We're going to have the ability to sort of look at the cards in a short order, certainly in the first half of next year, and be able to say, "Have we maintained that level of activity? Do we have what it takes to go forward," right? Because prostate cancer is an area that's been changing rapidly, and we want to make sure we can fit into that landscape and be competitive. So that's a card flip, right? We want to see if a checkpoint inhibitor can break into prostate cancer, in this case, a dual bispecific. We'll see. We're also running our non-small cell lung study frontline in combination with frontline chemo, where there's a safety run-in at two doses to pick a dose, and then we would go into a randomized portion if everything goes well, head-to-head against pembrolizumab chemo. So we're right now accruing the patients in that safety run-in, and we'll also have a card flip in the next couple of months to see how does the safety stack up, right? Because dual checkpoints have been tough with chemo. Does our bispecific get us where we need to be in, again, a rapidly changing landscape in frontline lung where pembrolizumab alone with chemo might have pretenders coming, where the bar might be raised? So we're going to be really stringent and make sure we pursue those programs, you know, if the data really supports it. Yep. Great. And both of those data readouts are in the first half of next year on vudalimab. Yep. Exactly. Exactly. And then in the third quarter press release, you guys announced two DLTs for your B7-H3 x CD28 bispecific, XmAb808. Maybe you can describe these and how are you planning on advancing 808? Sure, sure. So they were both at a dose level well into our target dose levels. One of them was just an infusion reaction upon first exposure. Hadn't seen infusion reactions before, unclear whether it was idiosyncratic or not. Nonetheless, the patient was taken off. It was considered a DLT. The second one was LFTs with bilirubin increase that has resolved. The patient's fine now. And again, that was the first time we'd seen any kind of bilirubin increase. So what we did is we stepped back, accruing more patients, still in our target dose ranges. And so it just made us say, "Okay, we could go back to that target dose, by the way. We're not prevented based on our dose escalation rules, but we want to be really thoughtful, having seen a lot of safety challenges bedevil some of our competitors. We wanted to get out ahead of those. So we're accruing patients now at active dose levels, and we should have the data by first half of next year to give us the key understanding whether to go forward with a PD-1 combo with this agent. Yep. Again, a lot going on in the first half. And then one other agent is XmAb819, which is a 2+1 bispecific. Maybe you can describe how you're using this construct for kidney cancer here with the target ENPP3. Sure. Sure. So we're very excited about 819. It's a program that's been really advancing rapidly in the last year. ENPP3 is a target very highly expressed in renal cell carcinoma, particularly the predominant clear cell type, about 85% of patients. It has low expression on a few healthy tissues. We used our 2+1 format to dial in that selectivity to the high tumor antigen-expressing cells, the cells that have high ENPP3. That's tumor cells. And to have it avoid activation of T-cells around the low-expressing healthy tissue. We've been advancing. We're now just getting into our target dose levels. We've already seen objective RECIST responses. We have patients at lower dose levels that have been out on therapy for over a year. These are, again, very advanced RCC patients. And so we're very encouraged by that. We'll expect to have some characterization from escalation of activity and safety. We've been managing CRS, which has been the predominant AE, with a priming and step-up regimen, so all the pieces coming together for a somewhat selective target like ENPP3 to be really addressed with this 2+1 format, and, you know, we're, of course, we've used it in other molecules as well, so that program is really going well. Yeah. And there's still a huge need there, so that's important. At ESMO, partner Amgen presented data on xaluritamig, which is a STEAP1 CD3 bispecific for prostate cancer. Walk us through, and what are their plans? Because it seems like this is moving along pretty quickly now for them. It is. It is. So the molecule was designed the exact same way as XmAb819. Of course, the details of the affinities have to be customized for each target. But same 2+1 design, really promising data at ESMO 2023, updated 2024 in very late-line prostate cancer patients, high PSA90 rates, RECIST response rates, and durability starting to look very interesting now. So the initial data has been great. They're starting phase three. They've announced it. It should be any day now. And, you know, they've got a broad range. So outside of their phase three, which is a monotherapy in late-line metastatic castrate-resistant prostate cancer, I think post-taxane, they've got a whole range of other studies going as early as you can. Maybe, Dane, you're better at tracking all of that. Yeah, sure. Yeah, it's a comprehensive program. Obviously, they're in charge of it. What's encouraging is, again, as Bassil mentioned, in those very late-line, metastatic, castration-resistant prostate cancer patients, they had a really good PFS, impressive PFS. That's what you need to beat something like docetaxel or a taxane or move even in front of chemotherapy. In a patient population that I think was 86% prior taxane, if not higher, beating that kind of six-month mark on docetaxel is really important on PFS. This is a real drug. It's very exciting. Especially with the move to Q2 weekly, that's going to make the larger coming pivotal studies more easy to execute. I think you'll see it move up in earlier lines, look in combinations with some of the standard of care, pre-taxane. You know, we're excited. It's a molecule that, you know, is demonstrative proof of our technology. Yeah. Yeah, for sure. And what are you guys' retained economics there? Mid- to high single-digit royalties. And I think we've got another $255 million in milestones remaining, some of which we expect to take down in the next quarter because of the phase III start. Yep. Awesome. Nothing wrong with that. Speaking of the balance sheet, we estimate you guys now hold pro forma cash of over $750 million, so $754 million. How long does this fund the company? And what's it enable you to accomplish? It gets us well into 2028. What it lets us do is for all of our clinical programs, it lets us get to that key proof-of-concept card flip, expansion cohort data for our T-cell engagers, whether it's 808, 819, or our claudin- 6, XmAb 541, which just got into the clinic. It helps us have clarity on vudalimab, as well as the phase II data we expect from our TL1A and the readouts from plamotamab and initial readouts from 657 in the B-cell depleting areas. I don't imagine, I'm not so arrogant to think all of those are going to work, but we want to maintain those options so we can have the drugs that Xencor is going to take all the way and be our own. So it gets us all of that, which is it's a great position to be in from a cash standpoint. And you guys have been very successful partnering. How does partnering fit into the strategy with such a big pipeline? It's really about how those card flips turn out. Are there programs we can't or don't want to prosecute ourselves? Because it's not something we want to build our company around. That's how I view it. We want to keep our own programs and have it an escape valve, right? But we're not compelled to partner now. And so let's see the data. Yep. Great. Well, thank you guys very much for being with us. It's going to be an exciting 2025, and we're pleased to be back at an overweight. Thank you so much. Take care. Yeah, you too. See you guys. My name is Ted Tenthoff. I'm a Senior Biotech Analyst at Piper Sandler. And before I begin, I'm required to point out certain disclosures regarding the relationship between Piper Sandler and Arvinas that are posted at the back of the room and also at the registration desk. Arvinas is a leading protein degrader play developing vepdegestrant, formerly ARV-471, to treat breast cancer with Pfizer. And they're also conducting phase I studies of ARV-393 targeting BCL6 for B-cell malignancies and ARV-102 targeting LRRK2 for Parkinson's disease. And earlier this year, the company partnered androgen receptor degrader ARV-766 with Novartis for prostate cancer. Here with us today from Arvinas are Chief Medical Officer Noah Berkowitz and also Andrew Saik, the CFO. Great to have you both here, and nice to get to meet you in person. It's a pleasure. Great to be here with you. I'll start off with vepdegestrant. You guys are conducting a broad clinical development plan here in metastatic breast cancer. Maybe you can start by reminding us of the phase II VERITAC monotherapy data that you reported and really why you selected the 200-mg vepdegestrant dose? Yeah, thank you for the question. So we reported out some of the results from that expansion last year. This was on the heels of work we did in phase I to look at different doses. In the end, we were also looking at a 500-mg dose. But when we looked on balance at the exposure response relationship we were able to model and also the safety profile of the drug, we decided that we could get just about all the benefit we were at a slightly lower dose than that 500 mg. So we decided to move ahead with 200 mg, not dissimilar from how most, I think, all companies would make a decision. And we were pleased with our decision because, as we reported out last year, the 200-mg monotherapy dose was able to prove itself in patients with hormone receptor positive metastatic breast cancer in the second-plus line setting. So when we were looking at patients that had been heavily pretreated, they were really mostly third, fourth, fifth line treatment. We observed that with the 200-mg dose, they were able to achieve median PFS of about 3.5 months in wild-type patients and 5.7 months in patients with ESR1 mutations. When we looked at how heavily pretreated these patients were, that benefit was seen despite the fact that patients had prior CDK4/6 therapy and 74% of patients had prior fulvestrant therapy as well as chemotherapy. So it was a very compelling data set for demonstrating that monotherapy can have impact in the setting. Yeah. On the basis of that, we chose to move ahead with that dose and schedule in the second-line setting. I'm sorry, in a phase III study called VERITAC- 2. That sounds about that. Yeah. Tell us about the trial design, and we should be getting data out. I think.