All right, we'll get started with our next fireside discussion. My name is Derek Archila. I'm one of the Wells biotech analysts here. Our next discussion is with Ventyx Biosciences. From the company, we have Raju Mohan, the CEO. We also have Marty Auster, the CFO. Gentlemen, thanks so much for joining us for the discussion. Our pleasure. Thanks, Derek. All right. Well, maybe, you know, Raju, you can kind of set the table here in terms of, you know, what you guys have been working on, the state of the business. Obviously, you know, you got some major readouts coming up, so maybe just again, set the table for those, and then we can kind of dig into the questions. Yeah. So the state of the business is healthy. That's it. In terms of. Well, in terms of the, you know, the, the, the main, the main catalyst for everybody, the, the main data points, milestones, whatever you want to call them, we have two phase 2 readouts coming out Q4. I'm, you know, super excited about both of them, each of them. First one is the readout in UC with the S1P1 modulator, VTX002, and the second one is the phase 2 psoriasis readout with our TYK2 compound, VTX958, right? I think that's sort of the main data points we have, and that's where the company goes. You know, obviously, we've grown now from, I would say, what? 15 people when we first started with Series A in 2021 to close to 100 plus folks right now. We built out, obviously, the clinical side, so ClinDev, ClinOps, Regulatory, QA, QC, CMC, obviously, Marty's group, the G&A group, and we're even looking at some commercial input right now. So the company has really grown, evolved, matured to some extent. And, and then behind all the phase 2 readouts is we have a phase 1 for our CNS compound, VTX3232. And then all the housekeeping that continues, all the support work to keep these trials on track. We're planning for phase 3 start for both of the, molecules, and that's independent of the data readout. We plan ahead, so the CMC regulatory work all initiates. So, you know, we've got, you know, things that now are, I would say, the die is cast to some extent with the, with the data readouts, but all the other work the team continues to build for the future, for the other compounds, for the Phase 1 that will move with the Phase 2. So that's where we are. Got it. Well, let's get to it. So maybe starting with VTX958, your TYK2, I mean, obviously, you know, we've seen good validation of the class. Can you just maybe provide, you know, kind of the differentiating features of your molecule and ultimately, again, where you think you guys can, I guess, really do better than what's currently out there, and what's also coming with some of these other agents that are, you know, also in development? Yeah. So, you know, we've laid out the profile of 958 systematically over the last couple of years. You know, obviously, we've laid out the in vitro profile, the preclinical profile of the compound, the selectivity for TYK2 versus any of the JAK family members, exquisite selectivity. The fact that we are targeting the 3 cytokines of interest, which is interferon alpha on one side, 12 and 23. More importantly, for near term, it's a 23-driven biology. We showed in our phase 1 data unmatched coverage of the cytokines, again, of 23, so that we could cover 24 hours of IC90 with the higher doses in our phase 2 trial. We showed a differentiated safety profile in the phase 1 study as well. So all those learnings from Phase 1 then led to the design of the Phase 2 trials, and we have three trials running for Phase 2. So we have the psoriasis trial that'll read out in the Q4. We have the psoriatic arthritis trial, and then we have the Crohn's trial that will read out, both will read out in 2024. And for each of these trials, in particular for psoriasis, which is the near-term interest, we made sure that our dose ranges that we use in the trial not only cover a wide dose range, but our top dose in the trial is also modeled to cover IC90 for 24 hours. And that, as you know from what you've seen from other drugs that have come out, has not been matched by any other molecule in the class. So, you know, I hate to call it an experiment, but since we are focused on biology here and coverage and translation into efficacy, it sort of is an experiment because, you know, we have laid it out and, you know, and we, you know, we'll see now what happens in terms of the readout, be it on PASI 75, PASI 90 or PASI 100. And in terms of, you know, what our expectations are, you know, again, it's, it's the trial is designed to cover IL-23. I think the base case scenario, you know, for us to be excited about this drug would be, you know, in the sort of the data shown by Takeda Nimbus drug. Mm-hmm. But again, we believe there's a delta out there between that drug and the 23 that still needs to be bridged. Mm-hmm. The question is, you know, with the coverage we get, how much of that delta can we actually bridge between the... what's been shown with, with, Takeda Nimbus and what's left out there? And I'm talking about the whole composite picture, not just PASI 75- Right. N ot just PASI 90, but PASI 100, sort of a full spectrum there. L ike, would you, again, if, let's say, you know, there's always this, again, I don't know if it's a fair thesis or just, like, commentary, but about, like, are you kind of at a ceiling, or is the class at a ceiling, you know, at PASI 75, and the only way you can really win is maybe PASI 90, PASI 100? Like, how do you feel about that? And again, does that, is that suggested by the Nimbus Takeda data, like, that there's a ceiling, or why, why or why not? Look, when the data are the data- Right. It's what you take away from that data. And I think they're really small trials. Small numbers, cross-trial comparisons are really difficult among these trials. I think as you get to more sensitive endpoints, I think these, the differentiations start to be more apparent, right? So, you know, you need more data points in terms of coverage versus efficacy. I think we provide that data point. Mm-hmm. And so we'll see whether we actually can break through, break through this barrier or the bare thesis that, you know, you'll plateauing out on 75. Got it. I'm gonna ask, I don't know if I'm gonna get any sort of answer, but obviously, you know, with the Alumis data, like, coming fairly soon, allegedly, I guess, how would you interpret the data, depending on... I mean, we have no idea what we will actually hear or learn. It could just be like, "It's positive," or we don't learn anything. So, like, I guess, how would you interpret that and is it really relevant to, like, you know, how we should be thinking about your program? I think it's relevant because it's just another drug in the class, right? Yeah. Appropriately dosed, I would expect that compound to be active and positive, right? Again, the devil's in the details. Yeah. So again, what coverage are they getting for IL-23? Right. We've seen some bits and pieces of their data come out in some reports, and it's a bigger focus on interferon alpha. Yeah I n 2023, so it's really hard to tell. Mm-hmm. But again, you know, it's another drug in the class, and the more drugs from this class that are active, the more sort of the comfort you have, similar to what we've seen with the 23s or, or p19s or p40s or S1P1s, you know, in the class of compounds. Yeah. And then just can you remind us the range of doses you're testing in the phase 2 in terms of coverage, also in terms of IC50, IC90? Yeah. So we haven't, we haven't disclosed the doses. Okay. Obviously, we will, once we show the data later this year. So we've got four actives in the trial and one placebo, so it's a five-cohort trial. And the top dose in the trial is modeled to cover IC90 for 24 hours, and then from there, we go down doses to a minimally effective dose. And we've also kept the two doses in the psoriasis trial the same as in the PSA and the Crohn's trial as well. Mm-hmm. So again, we'll have a good, good, degree of data coming out from the coverage versus efficacy across three different trials, as well as, of course, the safety package across these doses as we build towards registration and approval. Got it. And one of the doses, if I recall, is a QD, and, like, is there any expectation around... Like, what, again, what are you trying to prove with that dose? Is it more just to kind of creating that curve or what? Well, you know, again, there's so little known about... Yeah exposure, dose response, coverage, both magnitude of the coverage, IC90, IC50, IC80, as you know, as well as the duration of coverage. Mm-hmm. We thought the QD dose would be a good dose to look and see what happens in terms of PASI 75 and higher scores- Mm-hmm V ersus the coverage we get on a QD dose for the IC50, IC90 coverage. Got it. And then just on the safety perspective—like, you know, component of, you know, kind of that acneiform rash and, like, neutropenia seen maybe with some of the other TYK2s, I guess, I don't think you've seen any of that. But again, why is that? Is it just more selectivity, or why, or again, maybe you just have to dose it incredibly high? Yeah. I don't know. Yeah, the neutropenia, you know, the numbers were small. They were seen in placebo. Mm-hmm. And obviously, I don't think there was concern to Takeda on, on the neutropenia side. I don't think... You know, I think a consistent grade three would have not been a good, good outcome for a psoriasis drug. But let's focus on the acne for a second. Yes, it's been seen across both drugs. We don't believe it's a class effect of TYK2. In fact, we don't even think predominantly the acne is driven by crossover into JAK1 as well. It's possible both drugs have a different MOA for what's causing the skin effects. You know, I worked on Exelixis. I'm familiar with some of the kinase inhibitors, the EGFRs do it. Again, it could be that there's a metabolite in each of these drugs that's interacting with a pathway that's affecting the microbial defense system, the lipid composition, the barrier integrity, the inflammatory signaling. It's really hard to tell. I mean, the data are there. Mm-hmm. We don't believe they're coming through our TYK2 pathways. You don't see that level with any kind of IL-23s, and even, even the JAK inhibitor, like Rinvoq, don't have that level of acne. So it's, it's clearly a pathway that may be common, it may be different, but it's not TYK2. Got it. So assuming positive data readout, kind of like discuss the move into, like, a Phase 3, and obviously, this, it sounds like it does depend on some of the QD formulation work that you've been doing. So maybe you can kind of, you know, tie that in as well. Yeah. So the QD formulation is very important to us, and we're, you know, we want to nail it, and we'll show you the data in the Q4 to make sure we absolutely nail it. It's not linked to it. It's It's obviously, it's for phase 3, but it's not getting to the timing of it. The phase 3 timing is literally the planning that goes on from a phase 2 to a phase 3, and that timing is typically 6-9 months for most companies, and there's a lot of work involved in the phase 2 meetings. And so working on the QD formulation, we'll present the data in the Q4. We'll have the data from the phase 2 studies in the Q4 as well. Mm-hmm. And then you bridge the QD formulation with your phase 2 exposure response, and you actually build your QD tablet, and then all the work that's behind goes into manufacturing and packaging, labeling, regulatory work that goes on. That's, again, all that is. There's enough buffer in there. It will not have anything to do with the start of the phase 3 trial. In terms of phase 3 planning, we started the planning early this year. A lot of work goes into it. Obviously, you have to build large quantities of the drug substance for phase 3. You often change manufacturers because now you're planning for phase 3 and commercial. Mm. A lot of reg work goes into it. Obviously, the drug product work, the ER work goes on in here, and all that work is, again, going on. And once the Phase 2 data are out, then that'll gear up to making sure we don't have any hiccups to start with the trial. Yeah. I mean, is there anything inherently challenging of going from that, like, to get to that QD formulation? Is it... You know, I know you've kind of used, I mean, I think Rinvoq is one of the examples, but again, are there any challenges with the type of formulation that you're trying to- Not really. I think the key is that when a bar is high, we wanna make sure we get- Mm ... coverage for 24 hours. You end up fine-tuning towards the end, and that, fine-tuning literally is a build and test in humans, right? And, you know, I think most people know that sometimes that particular cycle can take a little bit longer, but there's nothing... These are standard, true, and tried technologies, right? Mm. You just wanna make sure that you nail the target profile for this drug, given the fact that, you know, our Phase 3 trial is gonna be with the QD. Got it. And obviously, it sounds like you're putting a lot of emphasis here, but clearly it's important. But, I mean, again, can you just kind of elaborate on the importance of QD in the class and maybe just in these kind of types of autoimmune indications in general? Yeah, I mean, I think with any drug, a QD drug is always preferable, right? If you can get the coverage exposure, oftentimes you have the BID or TID drugs that, you know, just don't have a sustenance for that long, and you have to repeat the dosing of the drug, so that's obviously preferred. Now, especially with psoriasis, a very competitive area, and we think a QD drug is, it's what's going to be preferred if things are equal or semi-equal. I think beyond that, in terms of IBD, and I've talked to plenty of IBD people, Bill Sandborn included, depending on your efficacy, a BID drug would be completely acceptable for an IBD indication. I think psoriasis is just a much more competitive area for us right now, and that's where we're determined to get this thing nailed. Got it. And maybe just to, you know, end on the, on the, you know, psoriasis point, just commercially, you know, now we have, we have one TYK2 that's approved, you know, multiple, you know, kind of focusing on psoriasis. Not that psoriasis is everything, for the class, but I guess, again, what do you think kind of being potentially a later entry into that, into that market, how that will evolve depending on, you know, different scenarios for your efficacy? Marty? Go ahead. You're on. Derek, answer the question. So, I mean, I think the obviously we see this from the rapidity of enrollment of our trial, and you see that across the other phase 2 trials for TYK2s recently. You see it with the comments that Bristol Myers has made since the launch of TYK2 and their attainment of, you know, 40%+ oral market share within a couple quarters of launch. But there's clearly a strong appetite for orals and new oral agents in this class. The only sort of systemic oral option now is, you know, prior to TYK2 was Otezla, which, you know, I think obviously the TYK2 class appears to be significantly ahead of them on efficacy. And the second wave of drugs coming through now, including ours, you know, with greater target coverage than the first gen drug, deucravacitinib, you know, hopefully, we can continue to iterate on that efficacy and improve that and, and continue to drive that enthusiasm. But I think this is something that's going to play out over the course of several years and ultimately become a very important, part, part of the treatment armamentarium. It's a, it's a $24 billion global market right now. There's six or seven different blockbuster, unique drugs in psoriasis. There's, you know, three or four different blockbuster classes within that. I think TAK-2 is clearly poised to become a significant player within that kind of realm. Got it. I mean, do you also think about, like, JNJ-2113 or the oral IL-17? Like, we're... I mean, are we all kind of competing for the same spot, or like, again, do you think TYK2s will ultimately kind of be maybe the preferred oral? Well, I'll maybe add to that, but I think the- Mm The IL-17s and IL-23s have a, you know, similar and different opportunities. Mm-hmm. You know, clearly in IBD, the IL-17s are not gonna have an option, and we're- Sure Running a Crohn's trial. We're pretty bullish on, you know, the possibility of getting a first-in-class oral. Right? I think beyond that, yes, there's the... It's a big market, and anything that builds an oral market is good for everybody else. I think that's really the key, right? It's been so dominated by biologics. Any oral penetration is gonna help. N ot just the front, the front runner, the second, the third, as Marty said, the big markets. The patient preference is clearly to, you know, take oral therapies over injectables, and that's been proven out time and time again in pharmaceuticals. You know, when you look at psoriasis, but, I mean, all these markets, IBD, even Crohn's, which is a pretty serious disease in most patients, you're looking at a minority. In the case of psoriasis, a pretty small minority of moderate severe patients who are actually being treated with systemic therapy. There's a lot of opportunity for growth. There's a lot of opportunity to sort of convert off patients who aren't happy with taking biologics, taking injectables. But, I think there's just gonna be a lot of, a lot of new patient flow and a lot of, lot of market growth overall. Got it. Okay. Wanna shift gears to S1P, 'cause that's actually the first catalyst that's coming. Right. So I think you guys had said, you know, sometime, maybe early Q4. Again, S1P, another validated class. People aren't so hot on the class, maybe 'cause of ozanimod, but maybe you kind of just talk to the differentiation you guys have with that molecule, and, you know, ultimately, you know, should we get more bullish on this class? Is ozanimod like a bad analog, you know, in terms of what it's done and you see? Well, absolutely, you should be bullish on this class, honestly, right? And, and we believed in this, in this class from day one. When, when we, when we started with this program, it's pre-TYK2. We've stayed on message. We've made sure we execute, and we're, we're super excited about the data coming out in the early Q4, for sure. I don't think ozanimod is a bad compound. That's not a fair thing to say. I think the way ozanimod has been handled, both in the development of that molecule, as well as how Bristol has handled, has been a disservice to the compound. First, people think it's less efficacious than etrasimod. That's not the case. I think if you were to actually manage to run these head-to-head in a similar sort of timeframe, I think you'd get pretty similar efficacies for both molecules, that's for sure. And we can go more into that at some point as to why ozanimod was short-changed in its efficacy relative to etrasimod. First runners often don't have the luxury of a second and third to learn from the mistakes, so I think Receptos did a great job in building the compound. And, obviously, you know, it led to the excitement with etrasimod and then us going into the space. I think in terms of. And I just don't think it's gotten the attention from Bristol like it should have, both in terms of the initial pricing, which were the MS, and their overall sort of the impetus and drive that we expect Pfizer to have for etrasimod as well, right? Why should people be bullish about the class? Because there's hundreds and thousands of patient safety data for these compounds, not just across UC, but across the MS world as well, starting from fingolimod or Gilenya. I think our thesis is that if you can maximize the PD activity for this drug, which in this case is lowering of absolute lymphocyte counts, very similar to the thesis we have for TYK2, which is IC90 coverage of the cytokine. If you can maximize the PD effect, you should be able to get the maximal efficacy or close to maximal efficacy that you can elicit beyond what's been shown with these compounds, the other two. Because where the disservice has been is suboptimal dosing and what we think is suboptimal PD effects for these two drugs, right? And that's why we're bullish, because we've shown our PD data to you folks in the R&D day, and we believe that that is clearly a different PD magnitude than what's been shown with these two drugs. And based on what has been shown with MS drugs, that- Mm-hmm L evel of PD calibrates into a higher level of efficacy, be it in MS. We believe that's gonna translate into UC as well. Like, in MS, is that a linear relationship pretty much? Or, like, how do you- Well, yeah. Yeah, I think, I think making a mathematical model for human clinical data is very hard, right? What I would argue is there's a dose-response relationship that we've seen within drug classes that clearly correlates with higher efficacy, higher PD response correlates with higher efficacy, right? Mm-hmm. Now, I think to have it linear, you're gonna have to have multiple data points on this set, and you draw a regression- Yeah L ine. I just don't think that's a fair thing to say. Yeah. There's a clear, unambiguous dose response for PD versus efficacy, and that's our thesis, that we will... You know, our goal is to demonstrate that PD response with differentiated efficacy. Yeah. I guess, you know, as you think about the bar for that trial, in UC, I mean, people kind of go back and forth between, you know, etrasimod phase 2, or is it etrasimod phase 3? Maybe just based on your trial design, enrollment criteria, I guess, where would you kind of put in terms of, like, where we should be benchmarking, you know, VTX002? Yeah. Why don't you take that one? Sure. I think, so when you look across the landscape, and this is gonna be a little bit long-winded, and I'll circle back -... or force me back if you want. When you look across the treatment landscape in ulcerative colitis, you've got a, you know, the first waves of drugs, the biologics, you're looking at clinical remission deltas from placebo in the 10%-15% range. More recently, you've seen a couple drugs, Rinvoq, the TL1A, antibodies, have pushed into the 20%+ range. I think you're seeing a differentiated response from clinicians. You're seeing excitement about that, kind of pushing that efficacy- Mm-hmm R ange higher. And I think what we think is with the S1P class, if you sort of, you know, kind of flatline out the, the PD response and kind of maximize that, this class of drugs has potential to be in that ballpark of efficacy, where you're looking at a very competitive profile relative to earlier generation drugs. Now, etrasimod is a, you know, admittedly a very challenging drug to compete against. Mm-hmm. Obviously, when you're looking at studies across trials and different timelines, and different populations, and different, you know, and it's always difficult, and it's always a little bit misleading to try to do that. With etrasimod, it's unusual in that you have this 20% response delta, 10% response delta, a north of 20% response delta in phase 2. It's, it's pretty inconsistent, and it's, it's an outlier. When we've looked through every successfully developed, ulcerative colitis drug, it's really the only one where you see this kind of deviation from trial to trial. So it's a very difficult one to kind of pinpoint yourself against. But what I do feel confident about is that if you get in that 20% ballpark, that's efficacy that speaks pretty loudly to people. Mm-hmm. And again, the fact that we're running a trial that has, like, a mid-dose, high dose, we can really tie it to that differentiated lymphocyte effect, and we'll also be looking to sort of, you know, look at that depth of remission and look at histopathologic subscores and really understand both the dose and the PD effect, but also sort of what that's doing to the, to the underlying, you know, histopathology in the, in the colon. I think that's all gonna put a picture together that's pretty clear. Got it. Obviously, we always plan for success, but we also have to plan for other things. What if you kind of, you know, in that trial, you're a little bit short-changed, you're more high teens, mid-teens in terms of the delta? What's kind of the development plan? You have a drug, but, like, what's the development plan maybe for the S1P in, in that type of scenario? Yeah. Look, our base case is we for this drug to be super competitive out there, and given the history with these drugs and the fact that we believe in the S1P1 class- Mm-hmm. You know, base case here is in the upper teens to 20 and higher. As Marty said, the bar has been set by TL1A, and that's what we're aiming for. I think anything below that, it's not gonna be, you know... I mean, we look, we look at every option, obviously, but, you know, we're, we're going for the PD here and giving us differentiated efficacy and, and, and again, upper teens, 20s to the bar being set by TL1A. Obviously- Yeah You plan for success, and if it's not where we want to be, then we'll rethink it, but that's not where our mindset is right now. Got it. I would say, Derek, we're going to have two substantial readouts, right, in Q4. Yeah. So there's an element of, we have to kind of step back and look at the totality of the portfolio. You know, the time difference between the two trials is not going to be particularly great. Yeah. So we'll be able to kind of look at this in its totality and think about, you know, what's the right capital use going forward? Where should we be focusing our resources? And obviously, we recognize, you know, that there's- Yeah T here's a finiteness to resources- Got it - both in personnel as well as capital. For sure. I want to touch on a couple other things before getting to NLRP3, but just, you know, staying within IBD, you know, Crohn's disease and also looking at 958 there. I mean, obviously, we've seen some data for Sotyktu there. Maybe just walk us through kind of like, again, your kind of continued confidence that, you know, you'll be able to be active in Crohn's and, you know, ultimately, the kind of the plan there. Yeah. Our confidence is really based on the biology of the target, right? And IL-23s and the success efficacy of IL-23s is unambiguous, unmatched across all the different 23s that are out there, right? And so there is no reason why a drug that has the coverage that is, you know, close to the biologic, assimilates the biologic, approaches the biologic-like coverage, which we've always maintained that we can with 958, shouldn't be efficacious in Crohn's disease, right? And the corollary is, if you don't have biologic-like coverage, if you cannot cover IC90 for a substantial part of the dosing cycle, you couldn't, shouldn't expect efficacy in IBD, where you know, based on small molecules, based on biologics, you need much higher coverage. Mm-hmm T han you do for non-IBD indications. Like in the case of Rinvoq for RA, we've shown the type, the calibration with Skyrizi IL-23. So if you don't, if you drop below that coverage of your target, you wouldn't expect to see a minimal to no efficacy, and that's our hypothesis. Mm-hmm F or what's happening with Sotyktu. Mm-hmm. So we're, again, going in with our, like I said, our top dose there is the same, same top dose in this rise style. IC90 covers a beta part of the day, and let's see. Got you. Yeah, maybe just shifting gears to NLRP3. So, always interesting target. We haven't seen a lot of, you know, data from programs externally from other companies. A lot of these, you know, private companies get sold, and we never see the program again. But, just kind of your enthusiasm around not only just peripheral, but maybe more so on the CNS side, you know, with this target, and again, kind of your plans there. Yeah. So excitement around this target is really sort of the undeveloped biology of, for not just IL-1 beta, for IL-18, right? And the NLRP3 is the inflammasome that sort of sits right smack where you can actually target IL-1 beta and IL-18. And then you've got, of course, a readout from the CANTOS trial across- Right A spectrum of indications. We think here that whether it's peripheral or CNS, right, not only the drug has to cover IL-1 beta, right? But the efficacy of these small molecules has been unproven. I'll come to the CNS compound in a second, but I think what happened with the first generation NLRP3s, right after the CANTOS data came out, everybody scrambled to build a NLRP3 small molecule drug. They all knocked off compounds outside of this MCC950, which is an old Pfizer drug- Right G lipizide. It's, there's nothing intrinsically wrong with the sulfonylurea, it's more the drug itself, the other pieces to it, right? I don't know if you recently saw the Jecure molecule was published in a phase 1 study, and they had tox, which was molecule-specific and nothing to do with sulfonylurea, nothing to do with NLRP3. So I think this is the sort of exuberance to get into this space and take suboptimal molecules into development. I think all the players sort of pulled back and said, "Let's go back now. We believe in the biology. We've got to rebuild these compounds and go back." So you'll see now more molecules going to phase 1, and you'll see data coming out in phase 2. You've seen some of our competitors we're in that space. So I think really a disservice done by suboptimal drugs for the peripheral molecule. But CNS is a very exciting part of the inflammasome. Again, there's a lot of biology that links NLRP3 assembly, activation, right, effect on a number of diseases, in particular, motor neuron diseases, Parkinson's in particular. Again, a lot of it is animal biology and in vitro biology, but I think it's now getting folks excited about getting a compound they can actually test in humans, albeit initially in biomarkers, but eventually take this not just for Parkinson's, but for other neuroinflammatory drugs. And we believe VTX3232, which is a CNS compound, is a balanced molecule. It's got a good balance of CNS versus plasma exposure. Running a phase I trial. We're gonna show biomarkers. We're gonna look at CSF. CSF levels of drug are a good surrogate for what you... the free fraction expect in the brain, and that data will come out early next year. And so between the peripheral compound and the CNS molecule, by the Q1, we would have two phase II-ready molecules, and with multiple options, broad indications. Mm-hmm. We own all of the IP rights to all our drugs, and again, as Marty said, there's a number of decisions we'll have to make depending on how this whole thing plays out. Right. NLRP3 will be a clear factor in how we develop those compounds. Got it. I mean, obviously, not knowing yet, you know, your 2 readouts and how that turns out, as you said, might be in a different place, but, you know, would there be, you know, opportunities to maybe out-license or at least, like, some of the larger, you know, neuro indications? Do you want to go into those larger ones, or would you more focus on smaller ones? I mean, obviously, you know, again, you could be in a completely different place, and you could do maybe everything. Yeah. You know, how are you kind of currently thinking about that? Well, let's say we're thinking about it. Again, it's all gonna depend on the data readouts. Yeah. Look, it's obvious some of the indications you look for NLRP3 may be beyond where we want to go, but we would position these compounds to be Phase II ready. Right. We're doing all the prep work to support that, and then we'll decide whether we do some of these, or it belongs better in a partner that can accelerate this. It'll all play itself out, right? Got it. I mean, what biomarkers for you, I mean, maybe beyond kind of just like the CSF stuff that you just talked about, like, are good, you know, kind of at least de-risking to a certain degree for a CNS penetrant, you know, NLRP3? Yeah, I mean, that's a great question, right? It's... There's very little known from the NLRP3 pathway itself, but there's biomarkers that have been shown, for example, with some of the LRRK2 molecules Mm-hmm T hat have come out in patients, and these are longer, longer studies. And so it's more about consistent change in biomarkers than actually running a noisy experiment, right? Right. So I think it's gonna be a combination of looking at inflammatory markers, looking at hs-CRP, neurofilament light chain. I mean, I can rattle a whole slew of these, alpha-synuclein, but there's got to be a consistent readout on these markers that'll show up in a patient trial, biomarker trial. On the other side, there's really a lot of belief in the biology of NLRP3 and CNS, but someone's gonna have to run that experiment, an efficacy experiment, and actually prove it. Yeah. Right. Maybe just last question. Just on the peripheral NLRP3, I guess, how do you think about indications there and, you know, in terms of just other inflammatory diseases, and, again, trying to generate, you know, good proof of concept early? I know you think you're doing- Yeah ... CAPS, but, you know, other than that. Yeah, CAPS is a proof of mechanism trial for us- Yeah A nd obviously, we are currently enrolling the trial, and we'll read that out early next year. I think, again, the biology of IL-1 beta is very compelling across a number of cardiovascular indications, cardiometabolic indications, right? There's other areas like osteoarthritis, obviously, gout is an indication. My personal belief, for what it's worth, is that this eventually an IL-1 beta is gonna be a very powerful add-on to a, as a adjunct co-therapy, especially in the metabolic space right now. Mm. Perhaps with GLP molecule, you know, really controlling the inflammatory signaling around the central signaling, adipose fat. So I think we have to just stay tuned to who and how that experiment is done. Sure W ith that molecule. All right, sounds good. Well, let's leave it there. Thanks, Raju. Thanks, Marty, for joining us today. Thanks for the question. I appreciate it.