Good day, everyone, and welcome to today's Ventyx Biosciences Business Update call. At this time, all participants are in a listen-only mode. Later, you will have the opportunity to ask questions during the question- and- answer session. Today's call is being recorded. I will stand by should you need any assistance. It is now my pleasure to turn the conference over to Mr. Alex Schwartz. Please go ahead, sir. Thank you, Sherri. Hello, everyone. Thank you for joining us today. Before we discuss the phase II study results in greater detail, we have some preliminary items to cover. First, I'd like to note the VTX3232 results press release is now available on our website, ventyxbio.com. Second, the slides that are being presented today are currently available on webcast. Following the conclusion of our webcast, the slides will be posted on our website. Next, on slide two, I'd like to remind the audience that during this call, we will be making forward-looking statements under the Safe Harbor Act. These forward-looking statements are based on current information, assumptions, and expectations that are subject to change and involve risks and uncertainties that may cause actual results to differ materially from those contained in the forward-looking statements. These and other risk factors can be found in our most recent Form 10-K and Form 10-Q filed with the SEC, and as such, we advise you to refer to the risks and uncertainties of our business outlined in these filings to learn more about an investment in Ventyx Biosciences. Now, with great pleasure, I'd like to turn the call over to our Chief Executive Officer and President, Dr. Raju Mohan. Raju? Yeah, thanks, Alex, and good afternoon, everybody, and welcome again to our conference call on VTX3232 phase II results. Before we dive into the data, let me introduce the Ventyx team here with me joining the call. Joining me are Mark Forman, our Chief Medical Officer, and Matt Moore, our Chief Operating Officer. Also, joining this call are Dr. Peter Libby, who is at Mass General Brigham Heart and Vascular Institute, and Dr. Antonio Abbate, who is at the University of Virginia School of Medicine. Both Dr. Libby and Dr. Abbate are world experts in cardiovascular disease. Both are clinicians and thought leaders, and they will join us in the Q&A portion of this call, as well as Antonio Abbate will present a few slides at the end of Ventyx's presentation. First, I'd like to thank you, a big thank you to the Ventyx team for all the work that has gone into the successful execution of this trial. To all our internal and external investigators, our CROs, our partners that worked with us tirelessly and closely, and were integral to the success of the program, I am truly grateful. Moreover, I would like to thank the individuals who participated in this trial and who are a constant reminder to us as to why we do and believe in what we do every day. Finally, a thank you to all who are joining this call. Turning now to slide four, please. As you're aware, and we've previously disclosed this, the phase II trial was a placebo-controlled trial of VTX3232, an NLRP3 inhibitor. This trial was both designed as a monotherapy trial and a trial in combination with semaglutide, a GLP-1 receptor agonist. As a headline, we believe that the data that we will review this afternoon and that Mark will elaborate shows VTX3232 as a potent, oral, once-daily drug demonstrating sustained reduction in NLRP3 and IL-1β-driven biomarkers that have been unambiguously associated with significantly increasing cardiovascular risk factors associated with atherosclerotic cardiovascular disease and related comorbidities. Let me briefly highlight the top-line results and key takeaways, and then Mark will get into more granular details and data in his presentation. In the first bullet, approximately 80% reduction in hsCRP was achieved within the first week of dosing and sustained throughout the 12-week dosing period in patients who remained on therapy. Second bullet, a majority of patients in this study achieved hsCRP levels below 2 mg/L, also at week 12. Now, just briefly to put hsCRP in context, Paul Ridker and others have recently shown, and we referenced the Lancet publication on this slide, that CRP levels were a strong predictor of cardiovascular risk, were a stronger predictor of CV risk than LDL cholesterol levels in more than 27,000 healthy American women followed over a mean of eight years. Additionally, patients with hsCRP greater than 2 mg/L were at higher risk of major adverse cardiovascular events and mortality. Now, moving to the next biomarker, we saw significant reductions in IL-6 levels, interleukin-6 levels, to below the threshold for cardiovascular risk. Given that IL-6 is a pleiotropic cytokine, one needs to find the sweet spot between significant reductions in cardiovascular risk while maintaining immune homeostasis, and Mark will elaborate further on this in his presentation. We also saw significant reductions in Lipoprotein(a). This is bullet number three here on your slide. Lipoprotein(a) is an independent risk factor for cardiovascular disease, and elevated levels of Lp(a) are associated with increased cardiovascular risk in both primary and secondary prevention populations, regardless of baseline hsCRP. On bullet number four, consistent with anti-inflammatory effects of our drug, VTX3232, we saw significant reductions in liver inflammation as measured by MRI CT1 imaging. As you'll see, the totality of data that we will show you demonstrates that VTX3232 also has an independent and clinically meaningful benefit on inflammation as an add-on to semaglutide. This was the cohort trial with the combination with a GLP-1 receptor agonist. Now, on the safety assessment from the study, VTX3232 was well tolerated, and all rates of adverse events were comparable to placebo, both in the monotherapy arm and in combination with semaglutide. Finally, VTX3232 showed no effect on weight loss, either as monotherapy or in combination with semaglutide, now showing conclusively that NLRP3 inhibition has no effect in humans in promoting weight loss. With this, I will hand over to Mark, who's going to walk you through the detailed data set. Actually, I have one more slide before I hand it to Mark, so let's just move on to slide five. Slide five highlights the importance of NLRP3 and its role in relationship to biomarkers that we have now highlighted or we will highlight in the results section. Inflammasomes are multiprotein complexes, as you can see on the right-hand side, that are activated in response to molecular hard marks of infection or cellular injury. NLRP3 activation results in the production of IL-1β, IL-18, and IL-1β induces IL-6, as shown in the cartoon on the right-hand side as well. IL-6, the cytokine IL-6, in turn, elicits systemic inflammation, including hepatic production of acute phase proteins such as CRP or hsCRP that I had just highlighted earlier, and other downstream reactants such as fibrinogen and other markers that Mark will also discuss. Data in the last decade has focused. In addition to the cartoon on the right-hand side, the similar pathway is now also described on the left-hand side of this slide, and I'm not going to repeat that. Data in the last decade has focused on the aberrant activation of NLRP3 inflammasome in tissues where NLRP3 is upregulated and is directly linked to a broad range of diseases, including metabolic, cardiovascular, rheumatic, and neurodegenerative diseases. By inhibiting NLRP3, we have shown with VTX3232 that we have the opportunity to significantly downregulate cytokines such as IL-1β, IL-18, IL-6, as well as acute phase reactants that have been unambiguously associated with significantly increasing cardiovascular risk factors. With that, now is my turn to hand over the presentation to our Chief Medical Officer, Dr. Mark Forman, to walk you through the data. Mark. Thanks, Raju. I'm really excited to share the results from our phase II trial with VTX3232 and cardiometabolic disease risk. I would like to start by reiterating our thanks to the participants, the trial investigators, and study team who made this work possible. Now, turning to slide seven, I'm going to spend a few minutes reviewing the study design. This was a double-blind, placebo-controlled trial with VTX3232 as a monotherapy and add-on to the GLP-1 receptor agonist semaglutide. As VTX3232 is a mouthful, and moving forward, I'll abbreviate as 3232. Trial participants were 18 years of age with a BMI of 30 - 42 and CRP levels of at least 2 mg/L. The CRP cutoff of 2 mg/L was selected based on evidence that residual low-grade inflammation is associated with increased cardiovascular risk. Specifically, canakinumab, an antibody to IL-1β, in the CANTOS study demonstrated that reducing CRP levels to less than 2 mg/L was associated with a 25% risk reduction for future cardiovascular events. Following screening, subjects were randomized to one of four treatment arms, as Raju described, specifically 30 mg of 3232 once daily or matching placebo or a combination of semaglutide administered weekly plus 3232 or matching placebo. Study participants were not blinded to semaglutide, which was dosed per label, starting at 0.25 mg per week and reaching 1 mg per week for the last four weeks of the study. The treatment period was 12 weeks with a safety follow-up period of four weeks. Turning to the study objectives, the primary endpoint for the study was safety and tolerability. The secondary endpoint was change from baseline in hsCRP over time. Now, importantly, we're going to show data with two analysis populations. The full analysis set includes all participants who have received at least one dose of study drug. A second modified analysis set excludes participants in 3232 treatment groups with plasma levels below the limit of quantification at the end of the treatment period. The reason for this analysis is that in clinical trials to date, 3232 has predictable PK with a low coefficient of variation. Based on a half-life of 17 hours, it takes approximately four to five days for drug levels to fall below the limit of quantification. Thus, this analysis set includes only participants with objective evidence that they took study drug as intended. The modified analysis set excludes eight individuals from the VTX3232 monotherapy treatment arm and seven from the VTX3232 semaglutide combination treatment arm. Next slide, please. Slide eight shows the disposition of study participants. A total of 175 individuals were randomized and treated. Overall, 153 participants completed treatment, corresponding to about 87% of the study population. The completion rate was generally similar across treatment arms, with slightly higher rates in the semaglutide arms of the study. Primary reasons for discontinuation included subjects lost to follow-up, adverse events, and withdrawal of consent. Of note, the rate of discontinuation due to adverse events was similar across all treatment arms. Next slide, please. Slide nine shows the baseline participant characteristics and was generally balanced across treatment groups. The mean age was 45 - 50 years, and the trial participants were predominantly white and female. Black or African Americans constituted approximately 25% of the study population. As intended, the study population was consistent with an obese cohort with cardiovascular risk factors. Specifically, the mean weight was about 100 kg, with an average BMI of 36. The mean% body fat was approximately 45%, and mean liver fat was approximately 8%. Importantly, the mean hsCRP at baseline was 4.1 mg/L, above the threshold we referenced earlier for increased cardiovascular risk, which was 2 mg/L. The median IL-6 levels were 3.7 ng/L, also above the threshold for increased cardiovascular risk of 1.65 ng/L reported in the CANTOS trial with canakinumab. I'd like you to remember these thresholds as I present data subsequently later in the presentation with VTX3232. Next slide, please. Starting with safety, slide 10 summarizes our data, the primary endpoint of the study. This slide includes data from the full analysis set, but the results are essentially the same when using the modified analysis set I referenced earlier. Overall, VTX3232 was well tolerated both as monotherapy and in combination with semaglutide. A few points to highlight. First, the majority of treatment emergent adverse events, or TEAEs, were mild to moderate in severity and were balanced across treatment groups. Second, all adverse events of infection were mild or moderate in severity. There were no serious or opportunistic infections, and all TEAEs of infection were assessed as unrelated to study treatment. Third, there was one SAE in the study in the VTX3232 monotherapy treatment arm. This was an AE of major depressive disorder resulting in hospitalization in a participant with a known history of depression. This SAE was assessed as unrelated to study drug. Next, there were four AEs leading to study discontinuation, one in each of the treatment arms. Lastly, there were four grade 3 TEAEs, two in the placebo arm, including LFT increased and blood CPK increased, one in the VTX3232 monotherapy arm, the AE of major depressive disorder that was also an SAE, and one AE of neutropenia in a participant receiving both VTX3232 and semaglutide. The neutropenia resolved within one week upon discontinuation of study treatment. Overall, I'm really happy to report that VTX3232 demonstrated a benign safety profile with no evidence of increased risk of infection. Moving to slide 11. On the next few slides, I'll review data from our secondary endpoint, hsCRP. As a reminder, increased levels of CRP, a marker of inflammation, is associated with increased cardiovascular risk. Recently, the American College of Cardiology, in a 2025 scientific consensus statement, recommended measuring hsCRP in clinical practice to identify individuals at increased inflammatory risk. Here, we show that VTX3232 led to rapid and durable reductions in hsCRP over the 12-week treatment period. Let me walk you through this slide in more detail. The data in this slide is from the full analysis set, with the panel on the left showing the percent reduction change from baseline over time. The right panel shows the observed values of hsCRP over the 12-week treatment period. Semaglutide alone shows a modest reduction in hsCRP, corresponding to approximately 28% at the end of the 12 weeks. In contrast, with both presentations of the data, VTX3232 administered either as monotherapy or in combination with semaglutide resulted in deep reduction in CRP with the majority of participants below 2 mg/L at one week, the first time point that it was measured. This corresponded to a median CRP reduction of approximately 80%. The reduction in CRP was sustained over the 12-week treatment period, below the threshold for reduced cardiovascular risk at all time points. The changes from baseline are statistically significant, with P-values less than 0.0001 at all time points. Moving to slide 12, here we show the two complementary analyses of the hsCRP data. On the left, we show the full analysis set, which includes all participants who received at least one dose of study drug. This is the same data that was presented on the previous slide. On the right, we show the modified analysis set that excludes subjects with VTX3232 drug concentrations below the limit of quantification at the end of the treatment period, thus including only participants with objective evidence of taking the drug as intended. On the left, the full analysis plan shows a small decrease in the magnitude of CRP reduction over time. In contrast, with the modified analysis set, we see the impact of excluding subjects with no measurable drug in plasma. In this analysis, the decrease in CRP is stable over time, approximately an 80% reduction from baseline. Again, with both analyses, these results are statistically significant, with P-values less than 0.0001 for all time points. Turning to slide 13, this slide is focused on the CRP reductions at week 12, the end of the treatment period. As in the prior slide, both full and modified analysis sets are included. On the left, in the full analysis set, VTX3232 was associated with a 64% - 75% reduction in median CRP levels as monotherapy and add-on to semaglutide. These reductions were statistically significant, with P-values again less than 0.0001. The modified analysis set in the graph on the right demonstrates the impact of subjects with no measurable drug levels in the blood at the end of the treatment period. There's a 5% - 14% increase in the percent reduction of CRP relative to the full analysis set, with a median reduction in CRP of 78%- 80%. Furthermore, the reduction in CRP when VTX3232 was administered with semaglutide was significantly different from semaglutide alone, where a 28% decrease in CRP was observed. The observed reductions in hsCRP are comparable to those observed with biologics targeting IL-1β and approach those observed with biologics targeting IL-6. Turning to slide 14, now this is the last data set that I'm going to present on CRP. As I mentioned earlier, several landmark studies have demonstrated that reducing CRP below 2 mg/L is associated with reduced risks for future cardiovascular events. The American College of Cardiology scientific consensus statement recommends targeted anti-inflammatory approaches in primary and secondary CV prevention, with the goal of reducing CRP levels as a biomarker for cardiovascular risk. On this slide, we show the responder analysis of the proportion of subjects achieving the target threshold of hsCRP. In the modified analysis set shown here, 69% and 82% of study participants receiving VTX3232 as monotherapy and combination with semaglutide respectively achieved CRP levels less than 2 mg/L. These results were statistically significant, with P-values less than 0.0001. In contrast, only 38% of study participants achieved this level of reduction on semaglutide alone. To summarize the CRP data, once-daily VTX3232 reduces inflammatory risk with CRP levels below 2 mg/L in the majority of study subjects. Moving now to slide 15. Now, I'm going to pause for a moment to frame up the next set of data. As Raju reviewed earlier, the NLRP3 inflammasome regulates inflammation through a well-defined cascade of cytokines and acute phase reactants. Specifically, NLRP3 activation mediates the release of IL-1β and IL-18, and IL-1β, in turn, leads to increased levels of IL-6. IL-6 stimulates generalized inflammation, including acute phase reactants in the liver and systemic inflammatory changes. In this study, we measured several biomarkers within this NLRP3 axis as markers of activation of the innate immune system. First, I'll start with IL-6. High IL-6 levels correlate with greater risk for cardiovascular events, including mortality, both in the general population and among individuals with existing coronary syndromes. In the CANTOS study with canakinumab, reducing IL-6 below 1.65 ng/L was associated with reduced cardiovascular risk. In the current study, we measured IL-6 levels at baseline and at the end of treatment. In the full analysis set shown on the left, VTX3232 was associated with significant reductions in median IL-6 concentrations to 1.6 ng/L. In the modified analysis set on the right, IL-6 concentrations were further reduced to a level of 1.35 ng/L. These IL-6 levels at the end of treatment are below the threshold of 1.65 ng/L that, again, we've discussed, has been associated with reduced cardiovascular risk and is comparable to biologics targeting IL-1. Furthermore, the reduction in IL-6 complements the action of semaglutide that was not associated with changes in IL-6 levels. Targeting inflammation in cardiovascular disease needs to balance benefit-risk for patients. We need to find the sweet spot for reducing inflammation while limiting infection risk. To date, VTX3232 reduced both CRP and IL-6 to target levels associated with reduced cardiovascular risk without evidence of increased risk of infection. Next slide, please. On slide 16, we extend the data with a panel of additional biomarkers in the NLRP3 pathway, including Lipoprotein(a), the acute phase reactant fibrinogen, and the systemic inflammatory biomarker ESR, or erythrocyte sedimentation rate. This slide shows a time course for change in these biomarkers from the full analysis set. VTX3232, both as monotherapy and add-on to semaglutide, was associated with significant reductions in fibrinogen, shown in the middle panel, and ESR on the right. These data are consistent, again, with VTX3232 inhibition of the NLRP3 pathway. Turning to Lipoprotein(a), as Raju mentioned earlier, it is an independent genetically determined lipid factor distinct from cholesterol and lipids that is associated with increased cardiovascular risk. The left panel shows that VTX3232 was associated with rapid and durable decreases in Lipoprotein(a), up to approximately 20%, both as monotherapy and add-on to semaglutide. The magnitude of the observed reduction in Lipoprotein(a) is similar to that observed with therapeutic antibodies to IL-6. These reductions in systemic inflammatory biomarkers complement the biological activity of semaglutide, which showed only modest or no change in Lipoprotein(a), fibrinogen, and ESR. Turning to slide 17, we also assess the effects of VTX3232 on lipid profiles. Cholesterol and lipid levels may be reduced in patients with chronic inflammation. Conversely, increases in non-fasting lipids have been reported in patients treated with therapeutics targeting IL-1β, such as Relanosib. Following treatment with VTX3232, no clinically meaningful changes were observed in lipid parameters, including LDL, HDL, total cholesterol, and triglycerides. These data are consistent with the overall safety profile of VTX3232. Now, moving to slide 18, an exploratory objective of the study was to determine if the preclinical findings of VTX3232-associated weight loss in the diet-induced obesity mouse model translated into use. In this slide, we show the change in participant body weight over time. First, we show that semaglutide alone results in an approximately 4% - 5% weight loss at 12 weeks, consistent with prior publications. Second, VTX3232, when administered as monotherapy, was not associated with change in body weight. Furthermore, there was no incremental weight loss when VTX3232 was administered in combination with semaglutide relative to that observed with semaglutide alone. As Raju mentioned earlier, these data unambiguously demonstrate that NLRP3 inhibition has no effect on weight loss. Next slide. The last piece of data I will share is an assessment of the effect of VTX3232 in the liver. There's extensive data linking NLRP3 activation in liver inflammation and fibrosis. We assess liver steatosis in this study using MRI PDFF, or proton density fat fraction, a quantitative measure of liver fat. We assess liver inflammation with the corrected CT1 imaging, or CT1, a highly sensitive state-of-the-art technology for assessing liver inflammation and fibrosis. It provides an objective measure of liver tissue health and serves as a non-invasive surrogate to liver biopsy. In our study, CT1 and PDFF were assessed at baseline in all participants. Individuals with baseline liver fat on PDFF greater than 5% were scanned again following completion of treatment. First, the results show that VTX3232 had no effect on liver fat. Second, both VTX3232 and semaglutide were associated with statistically significant reduction in liver inflammation on CT1 imaging. Furthermore, there was an additive effect on liver inflammation when VTX3232 and semaglutide were administered together, with the level of reduction exceeding a clinically significant threshold of 46 milliseconds, an observation that certainly merits additional follow-up. These data suggest that VTX3232 was reducing liver inflammation through a distinct mechanism or pathway that is orthogonal to that of a GLP-1 receptor agonist, which reduces both liver steatosis and, to a lesser extent, inflammation. Now, turning to slide 20. In summary, VTX3232 is a potent, oral, once-daily NLRP3 inhibitor with the potential to target inflammation in cardiovascular disease while balancing benefit-risk for patients. Specifically, we showed rapid and sustained reductions in hsCRP versus placebo, comprehensive inhibition of the NLRP3 pathway, clinically meaningful benefit on inflammation as an add-on to semaglutide, and an excellent safety profile. With that, I'd like to turn things back to Raju for some closing comments. Yeah, thanks, Mark, and thanks for making a very comprehensive presentation on the data set for VTX3232, both on the efficacy in terms of the biomarkers that are associated with cardiovascular risk and also highlighting the safety profile of VTX3232. Moving on to the last couple of slides before I wrap up and bring in the experts. As you can see on the charts in this slide, there are over 25 million patients that fall into the broad category of elevated CV risk, shown here with the three pie charts, first with atherosclerotic cardiovascular disease, second with atrial fibrillation, and the last with the broad category of heart failure patients there, all of whom share a common risk factor of elevated CRP of greater than 2 mg/L, and that's how they have been dissected in this pie chart. There's clearly a vast opportunity, as you can see here, and an unmet need to treat these patients with a safer oral drug such as VTX3232 that robustly and safely targets hsCRP lowering, as we have shown you in this data set in a number of different formats. I will let our experts speak further on this topic in their section. Finally, on my last slide, which is slide 23, we believe that VTX3232 has the potential to be the first-line therapy in targeting patients whose cardiovascular risk factors are inadequately controlled, such as with lipid-lowering therapies. Those three aspects of this drug are highlighted there. First, the potential for first-line therapy, an oral, once-daily drug representing the next generation of anti-inflammatory therapies, and its targeting cardiovascular risk factors independent of lipid lowering, as I mentioned before, really shows significant anti-inflammatory effects in the NLRP3 cascade and pathway, reduction in CRP, reductions in IL-6, reductions in fibrinogen, reductions in ESR, and a complementary pathway in the liver with significant reductions in liver inflammation, as shown by MRI PDF-F and CT1. Again, as in the last slide, I highlighted a vast cardiovascular opportunity as inflammation has emerged as a pivotal factor in a wide range of CV diseases. We have seen a number of highlights in the last couple of years highlighting the role of what's called simmering or residual inflammation in a number of diseases, including cardiovascular disease. Finally, I'm not going to belabor this, but you can look at the blurb on the bottom. This is from, as Mark referenced before, this is from a scientific statement from the ACC in Inflammation and Cardiovascular Disease, a very recent statement. What it says is summarizing what we said before, and I'm going to read it here, which says, "In aggregate, the evidence linking inflammation with atherosclerotic CVD, cardiovascular disease, is no longer exploratory, but compelling and clinically actionable. The time for taking action has now arrived." With that, I'm going to hand this over to our experts. I believe there's a set of slides that have been prepared, and please take over. Let me just introduce one more time Dr. Peter Libby, Dr. Antonio Abbate. Gentlemen, the podium is yours. Thank you, Dr. Mohan. Perhaps I can start if Dr. Libby allows me. You can go to the next slide, number 26. It is very exciting for me as a Clinical Cardiologist and a researcher in the field. You can go to the next slide, 27. Here, I'm showing you a graph that I've obtained from one of Paul Ridker's publications. This has been used in many, many presentations. You already referred to this earlier. I just wanted to show how central the NLRP3 inflammasome is in this schematic here. We have known for now some time through experimental studies in cells and animals that this NLRP3 inflammasome can be activated by a variety of stimuli, including cholesterol crystals, but also other physical factors. We have been focused on this NLRP3 IL-1β IL-6 axis now for some time, and we have seen some clinical trials along this axis. This is the first presentation of actually a targeted NLRP3 inflammasome in patients at risk for atherosclerotic cardiovascular disease. Just as a reminder, we talked a lot about C-reactive protein. We talked a lot about interleukin-6. You can see how interleukin-6 is downstream of this axis, downstream of the inflammasome of interleukin-1β. CRP is an easily measurable, widely available, reliable marker of risk. On the right here, from the same publication, you can see how the risk increases linearly with CRP levels. We've heard that the level of 2 or a level of 3 predicts a very high risk, but we should remember that this risk is linear, and higher is worse. In the subjects that we've seen in this presentation, it started with certainly higher levels between 4 and 5. Just to give you an idea, a level of 3 is uniformly identified as very high risk. In this presentation, this meta-analysis by Paul Ridker, that level of 3 mg/L was associated with a 220% increase compared to a level that was in the lowest group of 0.5 - 1. If you go to the next slide, this is actually the same slide Dr. Mohan has showed you earlier. This statement just came out a few weeks ago. I think actually it's not even in paper print yet. It is a wonderful overview. The final words of the abstract really are remarkable for what we heard today. There are several guidelines in this statement. I'm not going to go through all of them, but I do want to show you how using C-reactive protein to identify patients at risk and treating patients with levels more than 3 is mentioned several times in the recommendation of this statement. Here we are. We're talking about a phase II study with the first targeted NLRP3 inhibitor in patients with elevated C-reactive protein. If you allow me to show one more slide, the next one here, you can see here on the left is again the schematic from Paul Ridker that I modified some to show you what drugs have been explored in this space. I'm now showing you VTX3232 as the targeted NLRP3 inflammasome, so upstream in this cascade. I'm showing again the slide that Dr. Mark Forman showed here that the levels of C-reactive protein start elevated and rapidly go below in the low-risk area. On the right, you can see that in this analysis, 79% had reached a level of 3 mg/L. That's what we would identify definitely at high risk. I can predict that's why I'm very excited today that I can predict that a reduction of C-reactive protein like this will translate in a reduction of clinical events, and I'm very excited to see more studies with this drug. With this, I would like to stop and let Dr. Peter Libby talk more about this because he's the world expert on this field. Thank you. That's a bit of an exaggeration, Antonio. Why don't we leave that slide up? I'd like us to have a little bit of a dialogue about the utility and acceptability of an oral agent. You have the agent that we were discussing today on top of this cascade as a direct NLRP3 inflammasome inhibitor. Colchicine is also an oral drug, but it's one which has not had uptake even in the wake of the studies: COLCOT study, the LUPIL-2 study. First of all, there's some controversy because of the Clear Synergy study, which was a null study. We don't have time to go into all of the reasons why that might have been. Also, you know, Antonio, when I was on the inpatient cardiology service a couple of times ago, I did a back-of-the-envelope survey of the renal function of my inpatients with cardiovascular disease, and the EGFR, the estimated glomerular filtration rate, was 45. That gets to be a level where I'm concerned about giving colchicine because colchicine is disposed of in a renal fashion, and it is associated with toxicities and intolerability due to gastrointestinal side effects if it accumulates. Really, the therapeutic margin of colchicine is not great, and there's a lot of reasons why there may not have been uptake by the community despite there being some positive clinical trials. The other drugs that you have listed there in the lower two boxes are injectables. Anakinras, as you've done many studies with Anakinra, have to be injected rather frequently, and some of the other monoclonal antibodies are there for a long time. Of course, if you do have an intercurrent infection, you can't get rid of it quickly. I think the idea of an oral agent that is efficacious and that might be safe to use in those with renal dysfunction will be really something very attractive to the practitioners and to the patients. I wonder what your reflections are about that issue. Yeah, no, I fully agree. I welcome the colchicine trials. I think they have shown that acting on this axis works and it's helpful, but colchicine is not a targeted NLRP3 inflammasome inhibitor. It has multiple other actions. As you mentioned, it has toxicity. It could actually be deadly if you take it in an overdose, and likely not the ideal anti-inflammatory drug. We are building on the successes of the earlier trials with colchicine. In terms of the other inhibitors, I think what I'm most excited about today as a scientist is that we are really showing that acting upstream on this cascade, we can measure the inflammation downstream with high-sensitivity C-reactive protein, and there's no interaction here, no interference. The VTX3232 is not inhibiting high-sensitivity C-reactive protein production. It's inhibiting the inflammatory cascade, and that really proves that this cascade that Paul Ridker and others had shown is actually active in patients, and therefore now we can use it to reduce cardiovascular risk. Yeah, Antonio, as you know, the IL-1 induction of IL-1 is something that my lab showed back in the '80s, and the induction of IL-6 by IL-1β is something that my lab showed in the end of the '80s and early '90s. What's referred to as the canonical cascade, actually the bottom part of that figure comes from my lab. One of the things about going upstream is concern about deviating from that sweet spot. Are we going to impair host defenses by going upstream? I don't know if everyone in the audience knows that there's a family of inflammasomes, not just NLRP3. There's NLRP1, NLRP1B, NLRP2, NLRP6, PYRIN. There's a whole family. We might be able to hone in on the sweet spot by targeting the inflammasome. Actually, I think that the evidence that colchicine is an inflammasome inhibitor is very weak. I think it may interfere with its microtubular functions with the assembly of the inflammasome, but it's not an inflammasome inhibitor. I think the evidence for that is very weak. Absolutely. You know, your lab and other labs have shown that NLRP3 is really the link to the cholesterol crystals. Seeing this in patients, that the NLRP3, this one specific form of the inflammasome, one where the sensor is NLRP3, can affect systemic inflammation is confirmation of what we've seen in experimental models and a good way forward. You're right, this may not interfere at all with other immune responses, so it could potentially have a significantly lower infectious risk. Yeah. Peter and Antonio, I think we're going to transition to the Q&A section because I'm sure folks want to hear from you in the Q&A side as well. Peter, I always thought of you as a cardiovascular guru. I'm going to add you as the inflammasome guru now as well in your reminder of the inflammasome and the family. Again, both of you, thank you for your comments, and thanks to everybody who was on this call. Thank you for the team, KOL. Let me hand it back now over to the operator for the Q&A session. Thank you. As a reminder, if you would like to ask a question, please press star one on your telephone keypad. Our first question is from Andrew Tsai with Jefferies. Please proceed. Hey, good afternoon. Interesting set of findings today. Thanks for these updates. My questions are more big picture today. The first one is more about how you're exactly positioning this drug going forward. It's definitely not a weight loss drug. What cardiovascular indications are you most interested in pursuing next? Do you have desire to move it forward yourself, or should we be assuming a strategic partner? Thank you. Yeah. Thanks, Andrew. First, you're right. This is not a weight loss drug. We have absolutely nailed this hypothesis, which was a mouse study. In terms of the study, we've shown benefits beyond weight loss here. When you have oral GLP-1 receptor agonists, for example, or even with injectables and the whole family of integrins, you can clearly see the benefit of VTX3232 as an orthogonal add-on to the benefits of semaglutide in the family, a drug in that space. Let's not lose sight of what the combination trial has shown us. Even if there was no weight loss, there's this clear benefit on inflammation, clear benefits on inflammatory markers, clear benefits in the liver. All of these add to the totality of overall adding to a benefit of a GLP-1 receptor agonist. Your second question of, I guess, what's next with this drug. We have to be sensitive to the fact that we have a right of first negotiation agreement with Sanofi. That is public knowledge. While we are extremely excited about this, the results of VTX3232, where and how we develop this will play itself out. The first thing is to be sensitive to the agreement we had with Sanofi. As you can clearly see, this drug is positioned as a first-line therapy for atherosclerotic cardiovascular disease. You've seen our experts comment on this. Clearly, there's a number of ways you can design the trial, and we will come back to you with next steps once we play out, like I said, our relationship with some of the strategics here, including Sanofi. Stay tuned for that. Great. Maybe as a follow-up for the doctors, perhaps, if an investor were to say, you know, these hsCRP, IL-6, Lp(a) data reductions are all great, but so far, there hasn't necessarily been a cardiovascular drug that's been approved yet by lowering these markers to benefit cardiovascular outcomes. What would you say to that exactly? Correct me if I'm wrong in that thinking too. Thank you. Yeah, Peter or Antonio? Peter, do you want to start? Colchicine has received approval by the FDA. It's a very broad label. I told you that it is controversial after the Clear Synergy study and that it has limitations and that despite the FDA approval, it hasn't gained traction with the community for some of the reasons that I outlined. I can speak quite clearly about the canakinumab. When I pitched the CANTOS trial to Novartis in February of 2009, one of my slides said, "We're looking for the sweet spot." I chose that because Paul Ridker, who was with me, my wingman, we worked together on that trial, is a tennis player, and I showed a picture of a tennis racket in the sweet spot. Canakinumab didn't exactly hit the sweet spot because we did see a signal for infection. We learned a lot about what kind of infections and who gets infections, and we think we can mitigate some of that with some of these biologicals that target the downstream cytokines. I think that's one of the reasons that is public anyway that canakinumab has not been approved for use for cardiovascular. We also showed, by the way, a striking benefit for cancer in the CANTOS trial in exploratory analyses. There's good rationale for that, and the sponsor of the CANTOS trial was much more interested in pursuing it as a cancer therapeutic when we presented the data. Let me just add, Andrew, on top of what Dr. Libby said, there is a drug approved that has shown CRP lowering in efficacy, and that drug is rilonacept, right? The Arcalyst drug for recurrent pericarditis. We look forward to sharing our results on this trial in the fourth quarter. The mechanism by which rilonacept lowers or has efficacy in recurrent pericarditis is clearly through reduction of high-sensitivity C-reactive protein(hsCRP). That is one of the primary endpoints in the trial, and rilonacept is an approved drug, right? There is a lot of work to be done in the cardiovascular field. Excitement is now beginning, and the time is now, as you've seen. In heart failure and in recurrent pericarditis, there is clear evidence both from colchicine and from rilonacept, which is an IL-1αβ trap, but the endpoint of that study is measuring hsCRP. that has shown CRP lowering in efficacy, and that drug is rilonacept, right? The Arcalyst drug for recurrent pericarditis. We look forward to sharing our results on this trial in the fourth quarter. The mechanism by which rilonacept lowers or has efficacy in recurrent pericarditis is clearly through reduction of high-sensitivity C-reactive protein(hsCRP). That is one of the primary endpoints in the trial, and rilonacept is an approved drug, right? There is a lot of work to be done in the cardiovascular field. Excitement is now beginning, and the time is now, as you've seen. In heart failure and in recurrent pericarditis, there is clear evidence both from colchicine and from rilonacept, which is an IL-1αβ trap, but the endpoint of that study is measuring hsCRP. that has shown CRP lowering in efficacy, and that drug is rilonacept, right? The Arcalyst drug for recurrent pericarditis. We look forward to sharing our results on this trial in the fourth quarter. The mechanism by which rilonacept lowers or has efficacy in recurrent pericarditis is clearly through reduction of high-sensitivity C-reactive protein(hsCRP). That is one of the primary endpoints in the trial, and rilonacept is an approved drug, right? There is a lot of work to be done in the cardiovascular field. Excitement is now beginning, and the time is now, as you've seen. In heart failure and in recurrent pericarditis, there is clear evidence both from colchicine and from rilonacept, which is an IL-1αβ trap, but the endpoint of that study is measuring hsCRP. that has shown CRP lowering in efficacy, and that drug is rilonacept, right? The Arcalyst drug for recurrent pericarditis. We look forward to sharing our results on this trial in the fourth quarter. The mechanism by which rilonacept lowers or has efficacy in recurrent pericarditis is clearly through reduction of high-sensitivity C-reactive protein(hsCRP). That is one of the primary endpoints in the trial, and rilonacept is an approved drug, right? There is a lot of work to be done in the cardiovascular field. Excitement is now beginning, and the time is now, as you've seen. In heart failure and in recurrent pericarditis, there is clear evidence both from colchicine and from rilonacept, which is an IL-1αβ trap, but the endpoint of that study is measuring hsCRP. that has shown CRP lowering in efficacy, and that drug is rilonacept, right? The Arcalyst drug for recurrent pericarditis. We look forward to sharing our results on this trial in the fourth quarter. The mechanism by which rilonacept lowers or has efficacy in recurrent pericarditis is clearly through reduction of high-sensitivity C-reactive protein(hsCRP). That is one of the primary endpoints in the trial, and rilonacept is an approved drug, right? There is a lot of work to be done in the cardiovascular field. Excitement is now beginning, and the time is now, as you've seen. In heart failure and in recurrent pericarditis, there is clear evidence both from colchicine and from rilonacept, which is an IL-1αβ trap, but the endpoint of that study is measuring hsCRP. that has shown CRP lowering in efficacy, and that drug is rilonacept, right? The Arcalyst drug for recurrent pericarditis. We look forward to sharing our results on this trial in the fourth quarter. The mechanism by which rilonacept lowers or has efficacy in recurrent pericarditis is clearly through reduction of high-sensitivity C-reactive protein(hsCRP). That is one of the primary endpoints in the trial, and rilonacept is an approved drug, right? There is a lot of work to be done in the cardiovascular field. Excitement is now beginning, and the time is now, as you've seen. In heart failure and in recurrent pericarditis, there is clear evidence both from colchicine and from rilonacept, which is an IL-1αβ trap, but the endpoint of that study is measuring hsCRP. that has shown CRP lowering in efficacy, and that drug is rilonacept, right? The Arcalyst drug for recurrent pericarditis. We look forward to sharing our results on this trial in the fourth quarter. The mechanism by which rilonacept lowers or has efficacy in recurrent pericarditis is clearly through reduction of high-sensitivity C-reactive protein(hsCRP). That is one of the primary endpoints in the trial, and rilonacept is an approved drug, right? There is a lot of work to be done in the cardiovascular field. Excitement is now beginning, and the time is now, as you've seen. In heart failure and in recurrent pericarditis, there is clear evidence both from colchicine and from rilonacept, which is an IL-1αβ trap, but the endpoint of that study is measuring hsCRP. that has shown CRP lowering in efficacy, and that drug is rilonacept, right? The Arcalyst drug for recurrent pericarditis. We look forward to sharing our results on this trial in the fourth quarter. The mechanism by which rilonacept lowers or has efficacy in recurrent pericarditis is clearly through reduction of high-sensitivity C-reactive protein(hsCRP). That is one of the primary endpoints in the trial, and rilonacept is an approved drug, right? There is a lot of work to be done in the cardiovascular field. Excitement is now beginning, and the time is now, as you've seen. In heart failure and in recurrent pericarditis, there is clear evidence both from colchicine and from rilonacept, which is an IL-1αβ trap, but the endpoint of that study is measuring hsCRP. Dr. Mohan, if I can add one more thing, this is Antonio. I would say that the agreement is that elevated CRP is bad, and you know that's coming also for this ACC statement. There's also one more example. Give another credit to Dr. Ridker that a few years ago, he did the JUPITER trial that showed that in patients with elevated CRP, rosuvastatin reduced risk. On the label of the rosuvastatin, there's CRP as an indication. I think what we have now is an opportunity of a very much more powerful reduction of CRP and risk with targeted drugs. That's what I would add to the question. Okay. Thanks, Andrew. Anything else? Thanks for clarifying. No, all set. Thank you. My pleasure. Our next question is from Sam Slutsky with LifeSci Capital. Please proceed. Hey, good afternoon, everyone. Thanks for taking the questions, and great to see the strong biomarker data. For me, I guess, I wanted to hear your view on the read-through from these data to recurrent pericarditis as you look at the biomarker results and then think about the PKPD profile, VTX3232 versus VTX2735. Also, is there anything you can do to ensure that patients in the recurrent pericarditis study are compliant with taking their treatment, or is that less of a risk since they're symptomatic? I have one follow-up. Yeah, I think the latter question is, I think, pretty straightforward, which is, yeah, expectations here for folks who want to be on semaglutide or weight loss drugs. You know, they're not getting an injectable. Some of them just get out of the trial. I think that's sort of the simple answer, right, Mark? Yes, that's correct. We don't expect that. People who are getting onto the RP trial, folks that are committed, they want an oral drug. They come in with extreme pain and with elevated CRPs, and they want an oral therapy. That's the unambiguous answer I can give you there. In terms of read-through, look, independent of structure, right, the body doesn't care whether it's VTX2735 or it's VTX3232. What it wants is a safe compound that lowers, in this case, lowers hsCRP, and both drugs do that. We have shown that amazingly with VTX2735 in the CAPS trial and the phase I data. We will share some more data in the fourth quarter on our QD drug. The read-through is if you have a safe therapy, in this case, oral, that reduces CRP levels to your target levels, you will have an efficacious drug, right? We hope to show that in the RP trial. Different disease populations, different starting thresholds in the RP trial, as you know, one of the criteria for a set of patients is to have hsCRP greater than 10 mg/L, right? These people are coming in with extreme pain as well as elevated CRP, and we have shown the ability to drop CRP rapidly. We show first week here, but in many cases, we look in the first day and the second day. We've done that again, and we'll show some more data when we talk about the RP trial. Obviously, we have not read out the trial. We are hoping to put all that in the context that you will understand, and we promise to have that in the fourth quarter. We expect with the profile of our compounds, whether it's VTX3232 or VTX2735, the robust CRP lowering of this drug, rapid, robust, sustained, will result in efficacy, hopefully, in the RP as well. Okay. Just a quick follow-up. Anything you were able to measure or see as it relates to IL-1 levels in the study? IL-1β levels are, and I'm not an expert in that, but as we've talked about before, historically, they're very hard to measure. They're low basal levels. You're really measuring the downstream products of IL-1β. We can certainly look at IL-1β ex vivo and we know it completely slams it, right? There's no ambiguity about our level to block NLRP3 and to block the cascade of Caspase-1, IL-1β, IL-6. Measuring some of these biomarkers is a little tricky, so you have to settle on something that's stable and measurable, and high-sensitivity C-reactive protein(hsCRP) is one of them. Yeah, IL-1β, as Peter is speaking, IL-1β is a terrible analyte, and it's very, very difficult. There are no standardized assays. IL-6 became much more standardized in the wake of the SARS-CoV-2 pandemic when it became a standard test. IL-1β is just a laboratory measurement, and it's a terrible analyte for clinical trials. Yeah. Thanks, Peter. Thanks, Sam. Our next question is from Yasmeen Rahimi with Piper Sandler. Please proceed. Good afternoon, Raju and team. Congrats, really, on these great data. You have this hypothesis, and you've proven it with really a thorough presentation. I guess the question, I have a couple for you. One is, I went back to the IL-6 data that was reported by Tourmaline earlier in the year, and they found, you know, they measured at month one and saw, you know, CRP reductions, but you're getting that within one week. I guess the question to you here is, is the rapid onset driven team because of sitting upstream? That's sort of question number one. If you could maybe talk about that, maybe start there, and then I have like two additional ones. I think that's a fair assumption, right? I'll let Mark speak to that. Mark, the question is, is the rapid reduction because you're sitting upstream? There are two parts to your question. One of the things is in Tourmaline, they didn't look early, so we don't know how fast they dropped CRP. In fact, we don't really have an apples-to-apples comparison there. I don't think we can answer it, but I think given the mechanism of action of both IL-6 therapeutics, which are biologics, and ours, we would expect these, you know, because they're immediately, you know, IL-6 is immediately upstream of CRP, we would expect to see CRP reducing pretty quickly in Tourmaline as well. We don't have an apples-to-apples comparison because they didn't measure it at one week. Perfect. Second question is, I mean, I think we all know that the cardiovascular studies with IL-6 are ongoing, and we're hoping to see data next year. Now with this data on hand with NLRP3 driving CRP reductions profoundly, can maybe the physicians talk about, you know, once that data is out, how we could map out sort of an outcome study with, you know, VTX3232? How do you think about that given that, again, it sits upstream? We'd love to hear their thoughts, right, sort of forward-looking into next year and on the heels of potential very positive data. Obviously, the Tourmaline acquisition illustrates, right, that there's maybe a possibility of high POS of success there. Sorry. Like maybe we'll tackle that. Who wants to take that? This is Peter. I just would like to say that what we just saw was a factorial study with a GLP-1 receptor agonist. GLP-1 receptor agonists are going to become standard of care pretty soon for people who have high cardiovascular risk. I think that the idea that you could combine what this study showed was at least in the dataset that we just saw, that the word used was orthogonal. You're going to get an additive effect. It would be wonderful to see a study that actually had an active therapeutic that worked by a different mechanism that showed, as we saw here, some additivity. That would be my if I were I congratulated Ventyx when I saw the design in going head-to-head and actually showing that it was additive to a therapy that, you know, is going to be inevitably gaining much more traction going forward. Okay. Thanks, Peter. Thank you. Maybe one last question. My apologies. Team, this is for the Ventyx team. Were you able to see differences in CRP reduction based on where patients started, like a baseline 2 versus a baseline 3 versus a 4? Is there a different degree of reduction based on where you start off? Thank you again for answering my question. The simple answer is no, we haven't seen a difference. I think there's a lot more analyses that we need to do on the data. The data is really just hot off the press. I think the percent reduction, one of the things that we've talked about in the past, and I would want to emphasize again, the percent reduction is in some ways more of an arbitrary distinction because if you start at 10 and you go to 1 or 2, you have a 90% reduction. If you start at 3.5 and go to 1 or 2, you have a 50% reduction. It's really not the% reduction that you really want to focus on, but the level of reduction. As you heard from Antonio, CRP is a continuous variable as a risk factor. The lower, the better. We're going to get some of that data as the question that was asked about the RP trial where patients are starting at much higher levels. We're going to start getting some information about how this mechanism distinguishes with people with low-grade inflammation versus really high-grade inflammation. A quick more add pretty quickly is in the CAPS trial, you had a much higher dynamic range, yes. You went from folks that came in at 2 all the way to 30- 40 mg/L. In all cases, we dropped it down to the same levels we talked about today, which is below 2, below 1 in some cases. It is really independent of where you start out because you're completely blocking the pathway. It's not like we have a partial NLRP3 inhibition. We're completely blocking it. What we've seen, at least from studies where we've had a much larger dynamic range, it doesn't really matter. As Mark said, it's going to have to be barred out in more studies. It really doesn't matter. The drug works independent of where the starting levels are. Can I make another comment on the mechanisms, Antonio? I know we may be running out of time, but I do think the IL-6 trials and the Ventyx trials are going to be complementary because you're inhibiting the cascade at different levels. We know the CRP is a marker, and it's not really a mediator. IL-6 is upstream, and it may be a mediator, but we have to prove that. We have to show that blocking IL-6 is actually beneficial. We know that IL-1β blockade has been beneficial in other trials. What really may be affecting the plaque is really the inflammasome, the pyroptosis, the events that are more linked to the inflammasome at the plaque level and destabilizing those plaques and causing atherosclerosis. I'm looking forward to all of these results because they're going to be complementary. Awesome. Thank you, Yas. Let's be fair to the other folks. Let's move quickly. Operator. Our next question is from Derek Archila with Wells Fargo. Please proceed. Hey, good afternoon, and congrats on the data. Just two quick ones from us. In terms of the Sanofi and in terms of first negotiation rights, I guess when does the clock start for them? Is it now that the data is reported? Just remind us of the logistics there. How do you think this data kind of further validates 3232's Parkinson's data? Were there any key neurobiomarkers looked at in this trial? Thanks. We didn't look at any neurobiomarkers in this trial. We didn't look at CSF. You know, we don't need to torture folks in here because we did that in the CNS trial. We're not going to get into details of specific timelines in terms of the ROSEN. Stay tuned, right? The key point is, with this data set, we now start the cycle of our right of first negotiation with Sanofi. I am sensitive, we are sensitive to how much we get into it, but that'll play itself out, and we will disclose things at the appropriate time, Derek? Got it, thank you. Operator? Our next question is from Jeff Jones with Oppenheimer & Company. Please proceed. Thanks, guys, and great update and detailed presentation. Most of mine have been asked, but just, I guess, one quick one. As you look at VTX3232 versus VTX2735, any differences in potency between the two, and could either of these molecules be applied here in this indication or as we think about cardiovascular indications here? Yeah, so the converse is 2735 is a peripherally restricted compound, so you cannot apply it in the same pathways as we did with the CNS cascade, which was affecting neurodegenerative diseases, right? That we showed in the 3232 biomarker trial. In terms of potency and of the two compounds, without getting into details here, you've seen the numbers. They're both very potent compounds. They're both very selective. They both are now QD drugs, so we can hit the target with QD doses that are in a highly tractable range. We haven't decided on the QD doses that we will actually take into phase III trials because, as you know, these trials have all been one single dose, whether it was the biomarker for CNS, whether this was an obesity trial, and the same thing with the RP. We're very confident in the safety margins of these drugs, right? 3232 has a very wide safety margin over and above the highest exposure tested that we had showed with the 40 mg dose, right? In blood, it's somewhere between 40 -5 0 fold towards the NOEL. Wide safety margins, good potencies of both compounds, two distinct chemotypes, so they're distinct chemotypes, both with safety profiles that we have shown you. Yes, there's a clear option for 3232 in cardiovascular disease. There's not an option for 2735 in CNS. Appreciate it. Thanks, guys. Of course. Our next question is from Kaveri Pohlman with Clear Street. Please proceed. Yes, good evening. Congrats on the great results and thanks for taking my questions. Can you tell us how does this data look like to you based on your expectations and perhaps Sanofi's expectations? Does weight loss data change any of your thinking or your plans about the drug? My second question is about the safety profile. If you can tell us how the safety profile looks like in comparison with IL-6 targeting agents, one of which was already discussed, and some of the other NLRP3 inhibitors in the clinic. Thank you. Yeah, I mean, I think there's at least four different questions on that, Kaveri. Let me first talk about what does Sanofi think of this data. We'll have to see their reaction. This is the first time we're publicly disclosing this data, and so they have not had a chance to see it. I'm hoping some of them have seen it today, and they will see it in the course of our interactions with them as part of ROFIN, right? How do we see this weight loss data? We went in with little to no expectations on weight loss. There was no human biology, but given three or four trials in the mouse, we put this to rest and then showed the benefit, as we've highlighted and Peter said, over and above the GLP-1 receptor agonist, number two. In terms of how this compares to other NLRP3, obviously anything I tell you is going to be biased, but we have a portfolio of safe, potent compounds with QD dosing. What we've done is shared the life of these compounds. We've shown you the exposures, we've shown you biomarkers, we've shown you safety, shown you efficacy in the CAPS trial, we've shown you phase I data, we've shown you the CNS trial, exhaustive data here on VTX3232. I just don't think there's any, and you can look, there's any other compound out there that has shown such depth of data and such a clean safety profile. That's as much as an objective answer I can give you. That's very helpful. Thanks for the color. Of course. Our final question is from Alex Thompson with Stifel. Please proceed. Hey, great. Congrats on the data and thanks for taking our questions. I guess on the brain penetrant aspect of VTX3232, without this sort of neuroinflammatory thesis related to weight loss, how are you thinking about that, you know, when you're thinking about the path forward for VTX3232 here versus VTX2735, potentially, in cardiovascular disease? Maybe any hypotheses as to why the DIO mouse model did not translate in this context. Thanks. We have no hypotheses as to why the DIO mouse doesn't translate or not. The answer is there are many more instances of mouse models not reproducing, especially when you have something that has to do with as complex as feeding behavior. You know, mice will eat themselves to death, literally, right? I have been in vivariums and watched from a distance these models. On the other side, there was no human biology linking feeding behavior with NLRP3 as opposed to what we've seen in the CNS studies with links to microglia, inflammation, the astrocytes. While the story is not complete there, at least you have links that are being formed. There was nothing here, right? This was really a human experiment in the absence of in vitro biology as opposed to mouse studies where there was at least three or four studies that had shown this, and they're all consistent. There is no doubt in my mind that in mice there's weight loss. It's not working through NLRP3, at least in a human for sure. The good news is that you put it to rest now, and you move on to all the benefits that we've shown you with this compound, both with GLP as ones, but also standalone that we've highlighted that Peter and Antonio showed the excitement for, right? I think you had a second part of that, Alex? Yeah, I guess with the brain penetrance here, if you don't need that for the cardiovascular context, how are you thinking about prioritization of Parkinson's node diseases versus cardiovascular disease when you think about VTX3232 versus VTX2735? Yeah, so VTX2735 is right now in recurrent pericarditis, and I guess we're looking forward to sharing those results this quarter on that compound. For now, that compound is committed to that trial, and, you know, it's got tremendous potential of lowering CRP, and we are hoping that translates into efficacy, as you've seen with ARKLIST. VTX3232, we've shown biomarkers in the CNS, we've also shown effects you saw today. VTX3232, again, I'm not being cagey, but VTX3232 has a relationship in the form of a right of first negotiation agreement with Sanofi. We can come back and decide where we position these compounds, but let us play this out. We've obviously got internal planning now. We've been planning for multiple scenarios with an incredible team. We have all the drug product ready to go. We're at the starting gate, but let's just play out the right of first negotiation agreement and stay tuned for next steps with compounds that we have in the portfolio. Yeah, fair? Yep, got it. Thank you. Of course. We have reached the end of our question and answer session. I would like to turn the floor back over to Dr. Raju Mohan for closing remarks. Yeah, my closing remarks are to thank everybody who was on this call. Thank you for the questions, thanks to the KOLs, thanks to all the analysts who took the call, thanks to our investors, who I'm sure we'll interact with in the future. Really, thanks to the subjects who've been with not just on this trial, but on our previous trials, and really thanks to my team. I have an amazing team here. Thank you, Dr. Abbate. Thank you, Dr. Libby. We will continue our relationship, and again, this call is now done. Thanks. Thank you. Thank you. This concludes our call for today. Thank you, everyone. You may now disconnect.