Greetings, and welcome to the BioAge Labs update call. At this time, all participants are in a listen-only mode. A question and answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad. As a reminder, this conference is being recorded. I would now like to turn the call over to your host, Chris Patil, Vice President, Media. Thank you. Please go ahead. Thank you for joining today's call. I'm Chris Patil, VP Media at BioAge Labs. Before we begin, I would like to remind everyone that during this call, we will be making forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements are based on our current beliefs, plans, expectations, and assumptions as of today and are subject to risks, uncertainties, and other factors that could cause actual results to differ materially from those expressed or implied by such statements. These risks and other factors can be found in our most recent annual report on Form 10-K, quarterly reports on Form 10-Q, and other filings we have made with the Securities and Exchange Commission. We encourage you to review these filings as well as the full forward-looking statements disclaimer on slide two for a more complete understanding of the risks associated with our business. We undertake no obligation to update or revise any forward-looking statement, whether as a result of new information, future events, or otherwise, except as required by law. A copy of the press release, as well as the presentation materials for today's call, are available on the investor relations section of our website at ir.bioagelabs.com. With that, I'd like to turn the call over to Dr. Kristen Fortney, our Chief Executive Officer. Kristen? Thank you, Chris. Good morning, everyone. I'm Kristen Fortney, CEO and Co-Founder of BioAge Labs. We're very excited to share our phase I results for BGE-102 today. We believe these data, showing profound hs-CRP reductions with a well-tolerated once-daily oral dose, position BGE-102 as a potential best-in-class NLRP3 inhibitor, and they've given us strong conviction to really accelerate the program. We'll walk you through the data and our plans to advance into phase II and beyond. Next slide. Next slide. At BioAge, we're harnessing the biology of human aging to develop new therapies for metabolic disease. We built BioAge on one of the world's largest longitudinal human aging datasets, and that platform, validated through ongoing partnerships with Novartis and Lilly, has produced a pipeline led by BGE-102, which will be the focus of today's presentation. BGE-102 is the company's oral brain-penetrant NLRP3 inhibitor, a potential pipeline-in-a-pill targeting efficacy in line with injectable anti-inflammatories. From a cardiovascular risk perspective, we've shown potential best-in-class profile for CRP reduction, including an 86% reduction in CRP in obese subjects. Critically, we've restored 87%-93% of patients to CRP levels below 2 mg/L. This is the critical threshold that should translate into improved cardiovascular benefits. This drug has potential beyond cardiovascular risk as well, and we're also pursuing a phase II trial in ophthalmology. We believe that therapeutic retinal exposure can enable oral treatment of multiple diseases, including DME, where IL-6 has shown potential benefits. We have a number of upcoming catalysts. Our cardiovascular risk trial will read out by the end of this year, and our DME POC trial will read out in mid-2027. Briefly, we have other programs at the company, and we're also rapidly advancing our APJ agonist program. This is a potential exercise mimetic, has the potential to increase weight loss and also restore body composition together with an incretin drug, and we're on track to submit an IND for this program by the end of 2026. Next slide. I'm going to start with a brief overview of BGE-102 and the science behind NLRP3 inhibition before handing over to our Chief Medical Officer, Dr. Paul Rubin, to walk you through our phase I results and our clinical development strategy going forward. Next slide. Chronic NLRP3 activity drives disease and predicts poor human longevity. NLRP3 is a master switch in innate immunity, and when it's chronically activated by metabolic stress, it drives sustained inflammation that's directly linked to cardiometabolic disease and shortened lifespan. It sits upstream of IL-1β and IL-6, mechanisms that have shown great potential in CRP reduction and potential cardiovascular benefits as well. It's very validated by human data, both external and internal to BioAge. There's a very nice human genetic signal. Mendelian randomization links NLRP3 expression to heart failure. Additionally, BioAge platform independently identified NLRP3. Those individuals with lower activity at mid-age live longer in longitudinal human data. Next slide. This slide summarizes our lead program, BGE-102, which is well positioned to address diseases driven by inflammation in both the CNS and beyond in the periphery. BGE-102 is a potent, structurally novel oral and brain-penetrant NLRP3 inhibitor, and our phase I data show it has the attributes needed to address inflammation-driven disease across multiple organ systems. We have potential best-in-class potency based on our phase I trial results so far, 1.8 nanomolar IC90 in the human ex vivo whole blood stimulation assay, 24-hour IC90 coverage at the 60 mg once-a-day dose, suppressing IL-1β at 90% or higher levels. Furthermore, as I mentioned, 86% CRP reduction. Really profound CRP reduction as well as normalization in line with injectable IL-6 drugs. The drug is very CNS penetrant as well. Our Kp,uu,CSF is 0.7. This is also potentially best in class, and this really enables ophthalmology as well as neuroinflammation indications beyond our cardiovascular focus. From a safety perspective, as you'll hear, we have a very attractive profile to date. All AEs mild to moderate, self-limited, and no dose dependency. Coming out of our tox studies, both our three-month and our one-month tox, we have very high safety margins of 50-97-fold to the 60 mg dose. We also have a strong IP position and composition of matter through 2045. Next slide. Importantly, our NLRP3 inhibitors are unique in terms of their chemistry, but also their binding site. BGE -102 was discovered independently of the original MCC950 scaffold. In fact, we have a binding site different to that of other NLRP3 inhibitors. The typical binding site of other inhibitors is indicated in purple here on the left. That's where MCC950 and other compounds bind. In contrast, BioAge compounds bind at the green site. We've shown this, we published this structure, together with Matthias Geyer. There's a couple of very interesting features of our novel binding site. One of the critical ones is highlighted here on the top right. The BioAge binding site is available when NLRP3 is both active and inactive in both forms. In contrast, the purple binding site is only available in inactivated NLRP3. There's a theoretical advantage to our binding site that could translate into greater efficacy. On the bottom right of the slide here, we've listed three key publications that BioAge has put out in the past few years describing our chemistry, our biology, and also our structural biology. Now I'm going to hand it over to Paul Rubin, our Chief Medical Officer, to walk you through our latest clinical data. Next slide. Thank you, Kristen. I'll start with the overall trial design and key objectives, and then I'll move into the detailed results. Next slide. Our phase I program is a comprehensive dose escalation study where we initiated in healthy volunteers, but then we expanded it into obese participants, which represent a class of individuals that are more consistent with the ultimate population that we'll be studying in future studies. We were looking within this trial to characterize the pharmacokinetics, the pharmacodynamics, and perhaps more importantly, relevant inflammatory biomarkers, including hs-CRP. The study had three components. We started with a single ascending dose, and that involved 36 volunteers plus nine obese subjects. We then moved to multiple ascending doses, and that was 18 per cohort, or 18 total, sorry, 60 and 120 mg, and we treated those subjects for 14 days. We moved into the MAD obese subjects, which was a total of 41 subjects, looking at 60 mg for a 21-day period and 120 mg for 14 days. Our obese MAD cohorts, as I mentioned, are probably the most clinically relevant population in that with obesity comes an increase in inflammation and potential risk factors that certainly are correlative with what you would see in patients that ultimately develop heart disease. Therefore, the study in phase I was designed to mirror what phase II eligibility might be. Next slide. Our data very fortunately met all of our key trial objectives. It was clear from this study that the drug was safe and well-tolerated. We showed that the pharmacokinetics was dose proportional with ascending dose, and it's clear that PK supports a once-a-day daily dosing. We showed that we have very potent and consistent suppression of IL-1β, which is the key activity of the inflammasome. Even more importantly, we showed that we can get up to 86% reduction in CRP in these obese patients. We'll talk a bit in the ensuing slides as to how relevant that is in terms of potential for therapeutic benefit. From a safety perspective, all of our adverse events were mild, moderate. They were self-limited, and there was clearly no dose-limiting toxicities. The PK, as I mentioned, dose proportional. With ascending dose, you saw a linear increase in exposure. As mentioned, the half-life is clearly amenable to a once-a-day daily dosing. Then in our B subjects, we got up to 86% reduction of CRP at both the 60 and 120 mg dose. 87% of subjects at 60 mg and 93% at 120 saw that their CRP was reduced to below 2 mg/L, which is considered normal and decreases the risk of potential outcomes related to cardiovascular disease. Next slide. As mentioned in this study, BGE-102 was very well tolerated across the subjects. We had an adverse event profile that we believe was similar to what is known for placebo-treated subjects. We only saw mild to moderate treatment emergent adverse events. They were all self-limited. There was no dose dependency. There was no drug-related discontinuations, as well as no serious adverse events. The rate of adverse event was comparable active to placebo, 61% versus 59%. We saw no clinically meaningful changes in the vital signs, in laboratory analyses, or electrocardiograms. Next slide. Moving to the obese MAD cohorts. This slide represents what our baseline characteristics were. You can see that they're pretty consistent across the various dose groups, including placebo. We had two active cohorts, the 60 mg as well as 120 mg group. There were 19 subjects in the 60, 14 in the 120, and eight in the placebo. The CRP, by design, was elevated at baseline, and that ranged from 4.85-6.3 mg/L, which is well above the 3 mg/L high CV risk threshold. We also had a diverse population with racial representation across the spectrum. Next slide. In the obese cohorts, the safety and tolerability was consistent with what we saw in the healthy volunteers, in that there was clearly no signal that would preclude what we believe would be aggressive development of this compound. There were no treatment-related discontinuations, no serious adverse events, or severe treatment emergent adverse events. Importantly, we did not see significant effects on neutrophils. There was no neutropenia observed, no thrombocytopenia, or no infections, which is a hypothetical concern with any immunosuppressant agent, including one that might block IL-1β or IL-6. Next slide. We're now going to go through the PK and the pharmacodynamic data from our healthy volunteer cohorts, which then established the foundational PK/PD profile for BGE-102. Next slide. As you can see here, with ascending dose, we saw dose proportionality observed in the single ascending dose cohorts, very nicely linear in nature. Was dose proportional across the spectrum from 10-120 mg, which obviously makes it much simpler for dose selection, especially as we have a good PD marker to look at the PK analysis and to correlate. Next slide. In the MAD cohort, because of its longer half-life, we did see accumulation, but it started to approach steady state by the 14-15-day time points. We saw trough concentrations that were well above the IC90 for inhibition of IL-1β, which obviously was gratifying. This confirms the fact that 24-hour target coverage, translated as being able to inhibit IL-1β across a 24-hour period, is clearly possible with once daily dosing. Both doses, both the 60 mg and the 120 mg, consistently showed levels above the IC90, and as I mentioned we are at 14 days, we were near the steady state level. This allows us, because not only did we see this nice effect on pharmacodynamic effects, but these doses were safe. This allows us to test complete or near complete inhibition, and if that is necessary for optimal efficacy, we believe we can achieve that. Next slide. We also looked at the kinetics in the CSF as we did lumbar punctures and were able to measure or quantitate the amount of drug seen in the cerebrospinal fluid. What we found was that the 120 mg dose showed mean CSF levels that were well above the IC90, and the 60 mg dose was also above the IC90. Even at 60 mg, if we're interested in having an effect on central nervous system inflammation or control of, we have the ability to show at least a 90% inhibition in IL-1β. With this CNS access, obviously it expands the potential of this drug and confirms this idea that this drug is a mechanism in search of a disease, or another way to approach it is, it's a pipeline in a pill. We also showed that the drug can not only address neuroinflammation, but we've shown that there's therapeutic levels in the eye which will allow us to pursue retinal disease as well. Next slide. When we go from kinetics to pharmacodynamics, you can see that at both the 60 and 120 mg doses, you have over 90% inhibition at trough levels of IL-1β. It's a very potent inhibitor, and it's demonstrated by actually measuring IL-1β in these subjects. You can see at 60 mg, we had an average, a trough of 90% inhibition, and at 120 mg, we got as high as 98% inhibition. Next slide. At day eight, we looked across a 24-hour period, at day eight as well as day 14, as well as day one for that matter. What we saw is that with the first dose administered, the day one dose, we did get to a peak inhibition that approached a maximum of 90%, but you could see that it reversed with time. This provides evidence that the effect on IL-1β is reversible. However, by day eight, where the levels, obviously the drug is accumulated and the levels are increased, you can see we have virtually complete inhibition across a full 24-hour period. This is measured as opposed to hypothetical. We've documented that with a single dose of drug on a daily basis, you can get complete inhibition of the main dynamic endpoint, IL-1β, across a full 24-hour period, which obviously was gratifying and I think will give us high flexibility as to how we develop this drug. Next slide. Now we'll move on to the subjects with obesity. Go on to the next slide. Now, obese subjects represent a more extrapolatable population when we think about the indications that we'll be pursuing in the future, especially cardiovascular disease. Obviously, subjects with obesity have a risk factor for cardiovascular disease. They're hyperinflamed, which is similar to what you'll see in patients with cardiovascular disease, and have a risk of getting these particular diseases. In the obese MAD cohorts, we had two, the 60 and 120 mg that we studied. We documented in the design, we assured that these patients had BMIs between 32-42. Their baseline CRPs were greater than three. They weren't allowed to have concomitant incretins during the course of this trial. They had to be off incretins for the duration of this study. In fact, we believe this population will mirror and provide a very relevant example of what we might see in the phase II cardiovascular study. Next slide. This slide shows the actual reduction of CRP across both cohorts in our obese populations. As you can see, we have very significant and profound decreases in CRP that get to pretty close to maximum by day seven and are continued throughout the course of the drug exposure. We're getting approximately 85% inhibition across the full duration of the study, which as far as we can see, is the best in class to date. This is significant from a clinical perspective. Obviously, the lower the CRP, the better in terms of cardiovascular risk. We were impressed and very gratified and happy with these data. This, with an oral medication, I think, puts us in a very good position to compete with the injectables, as when you look at the magnitude of the effect, it's as good as it gets. Next slide. In both MAD cohorts, you see that the trajectory of the decrease or the inhibition is similar, that by day seven you're at essentially maximum inhibition, and this is maintained throughout the full dosing schedule. For up to 21 days, it maintains at this maximum inhibitory rate. Now, looking at the fact that you're down below 1 mg/L is very important in that when you look at data from previous trials, if you can get the level of CRP below 2 mg/L, you get a significant benefit in outcomes from MACE data. The fact that we're showing on average a very favorable inhibition and we're well below this two level, which should be very important clinically. Despite the fact that the baseline levels in the two cohorts were slightly different and that the lower dose was a bit higher, they had the same landing point, showing again, attesting to the potency and consistency of the response to this drug. Next slide. Previous trials, specifically the CANTOS trial has demonstrated that if you can reduce CRP to below 2 mg / L, you'll get up to 25% benefit below 2 mg/L, and that will be increased even more if you can get it below 1 mg/L. What we're showing in our study is that at the 60 mg dose, 87% of subjects landed below this threshold of 2 mg/L. At 120 mg, we get 93% of subjects. The overwhelming majority of subjects are below this threshold, at least in our trial, which should translate into very significant clinical benefit in patients that have the potential for developing cardiovascular disease in the future. Next slide. Now in looking at IL-6 this is a known mechanism that by inhibiting the NLRP3 inflammasome, not only will you inhibit IL-1 β, but that will result in significant inhibition of IL-6. And this was verified in this particular trial where you could see at both the 60 and 120 mg dose, we got significant inhibition of IL-6 up to 70% or 78%. You're getting a very significant, and the magnitude effect is clinically relevant. It just suggests that you can get effects on IL-6, which is a known inducer of cardiovascular risk, and you can get significant inhibition at a magnitude that it should be very clinically relevant. Next slide. Now, although the study was not designed to look at inhibition of IL-6 in CSF because it's impractical, obviously, to screen all these subjects and then only enter those trials with elevated IL-6. We did have two subjects that had elevations in baseline, and in both cases, the IL-6 was brought down significantly. This attests to the fact that this drug does get into the brain, especially when you look at their plasma IL-6 levels, and the levels in the brain were higher than the plasma. We believe that this supports the fact that our drug is brain penetrant and it can inhibit a significant biomarker in the brain independently of what's going on in the plasma. This obviously supports looking at this for the treatment of inflammatory brain disease, cognitive dysfunction among them. We look forward to exploring that in the future as well. Next slide. We also looked at fibrinogen, which is an independent predictor of cardiovascular risks. As you can see, we get up to a 30% inhibition of fibrinogen as well. You're getting an effect on another important marker of cardiovascular disease. It just also shows that this drug is pretty potent. It doesn't have an effect on a single marker, but at multiple markers that are all relevant in terms of providing risk or causing risk as it pertains to cardiovascular disease. This should also, I think, provide an increased chance of an important benefit especially due to the fact that we're not only looking at a single risk, but multiple. Next slide. With the phase I data validating what we think the effects of 102 on these dynamic markers, which we know are correlative with cardiovascular disease, we're now going to turn to how we're going to develop this particular compound. We are going to initially focus on cardiovascular, as we've mentioned, and we have increased the size of our planned phase II-A study as part of our prioritization of enabling phase III start by the end of next year. Next slide. As mentioned, the overwhelming majority of subjects had their CRP reduced below this threshold level of two. This mechanism is through IL-1β and as suggested here, and as a result of the CANTOS trial, if you can drive it below two, you can drive a 25% MACE benefit. Now the CRP, we believe, and data cited in the Women's Health Study, the quintile data, showed that this CRP reduction is more predictive than LDL or Lp(a). The fact that we do have this effect is probably more beneficial and more predictive of ultimate cardiovascular risk. As mentioned, this was documented in the CANTOS trial, which did produce a 25% MACE reduction in those patients that had a less than 2 mg/L. This provides clinical proof of concept for an anti-inflammatory cardiovascular therapy here. Now, the 25% MACE reduction was observed in patients that had a high severity rate. These are patients with diagnosed atherosclerotic heart disease plus chronic kidney disease. Other studies suggest that if you can treat people, and this is a compound that's both safe and potentially effective and practical, and you could treat people at earlier stages of diseases, you can actually have a greater effect than the 25%. We believe this compound might expand the population that are amenable to this type of therapy. Interestingly, there was an American College of Cardiology scientific statement that suggested that inflammation, regarding inflammation, atherosclerotic vascular disease is no longer exploratory, but it's compelling and clinically actionable, and we intend to exploit that. Next slide. Present therapies with IL-6 are all injectable, and NLRP3 inhibitors provide the potential for oral reduction in IL-6 with comparable benefits, including decreases in CRP. Now NLRP3 inhibitors, like BGE-102, are at the apex of the inflammatory cascade. They're upstream of IL-1β, IL-6, and CRP. We are now seeing that these oral NLRP3 inhibitors can achieve reductions comparable to injectable IL-6 antibodies. With this particular mode of therapy, they can be as good as or better than what's personally out there related to IL-6. When you look at comparable data with the IL-6 inhibitors that are out there, NLRP3 inhibitors can provide benefit far greater than what they're achieving. Now, the oral format is not just a convenience advantage, it also makes this broad population coverage possible. Injectables, we don't think will ever reach primary care at scale. Oral inflammatories can be prescribed alongside statins by the same PCPs who manage CV risk today, and inflammation treatment could be as routine as cholesterol treatment by virtue of these orally well-tolerated compounds. Next slide. The pharmacodynamic effects of NLRP3 inhibition reach beyond IL-6 and IL-1β in that it can also reduce IL-18, which is a known risk factor, and also cell death or pyroptosis, which is another risk factor that contributes to plaque destabilization. Again, the pluripotency of this effect can have a broader potential benefit than simply modulating a single mediator such as IL-6. Next slide. The cardiovascular opportunity of an oral anti-inflammatory is substantial. Existing data suggests inflammation is an independent risk factor that's equivalent or on par with cholesterol. In the U.S., the addressable population is 15 million patients. The channel dynamics strongly favor oral therapies. In fact, these 15 million patients is 60% of the 25 million ASCVD patients, and they have elevated CRPs. BioAge is pursuing not only secondary prevention, but as mentioned, potentially high-risk primary prevention. As mentioned, like statins, which started in secondary prevention and expanded to much larger primary prevention population, we believe we could do the same thing with these oral NLRP3 inhibitors. Next slide. We are intending to initiate a CV risk proof of concept trial, and we've designed this trial to characterize the full dose response as it pertains to CRP, with arms specifically chosen to support optimal dose selection for later development. This particular trial will be a 4-arm study where we have placebo 30, 60, and 90 mg once a day. We have 160 patients total, approximately 40 per group, and the subjects will be exposed for a 12-week period. Eligibility includes BMIs between 30-42, a baseline CRP greater than three, and at least one cardiovascular risk factor beyond obesity. The primary endpoint, as mentioned, will be percent change in CRP with key secondary endpoints, including normalization rate. That means the number of subjects whose CRP goes below 2 mg/L and below 1 mg/L. In addition, on an exploratory basis, we'll be looking at Lp(a), fibrinogen, IL-6, MRI of both the liver as well as total body, various metabolic parameters looking at glucose and insulin, and body weights. We have chosen placebo, 30, 60, and 90 mg, in that we believe it provides a range based upon our pharmacodynamic exploration. The 90 mg dose, we believe, will provide exposures that are comparable to 120 mg doses, and we know that the 120 mg dose exposures cause maximal inhibition of the important pharmacodynamic endpoint. 90 mg should provide equivalent when it reaches steady state. As you know, as shown, 60 mg has already shown maximal hs-CRP reduction, including 90% IL-1β inhibition, and the 30 mg dose does show some reduction, but it's not as robust as the other two doses. We think this provides a reasonable spectrum. Next slide. BGE-102, being an anti-inflammatory compound, has the potential to address a large range of indications. Characteristics of the drug, including good brain penetration and reasonable penetration into the eye, allows us to look specifically at ophthalmology. Our intention is to initiate a trial looking at diabetic macular edema. That's planned for mid-2026 with results in mid-2027. This will be an oral therapy, and we will look at it in combination with injectable VEGFs. We believe that an oral therapy could provide clear benefits versus the present injectable burden. We're optimistic about the acceptability of this particular compound and its potential utility. Neurodegeneration is also possible as this drug gets into the brain, as we showed in some of the data. We have not yet announced a program, but we are certainly exploring the possibility of advancing this in those indications. Next slide. What I'd like to do now is walk through the DME study design briefly, and we'll go into more depth at our upcoming R&D day. At that particular day, we'll feature presentations from leading retinal disease experts in addition to internal experts. We've designed our DME proof-of-concept study to answer the key translational question whether oral BGE-102 can suppress intraocular IL-6, the same target that intravitreal IL-6 antibodies have already validated in diabetic macular edema. The study will have three arms, 30 per arm. One will be anti-VEGFs plus oral placebo. Another will be VEGF plus oral BGE-102. That's our combination arm. We'll also have a sham plus BGE-102, which is a monotherapy arm, which will test whether or not oral NLRP3 inhibition alone can suppress ocular inflammation. In this instance, our primary endpoint will be the ability to suppress intraocular IL-6. This is a pharmacodynamic study as opposed to a true efficacy trial, but we believe by proving that systemic administration can have a significant effect on an important inflammatory marker, that we can expand this drug to multiple ophthalmology indications. While we'll be looking at visual acuity outcomes as secondary endpoints and as exploratory endpoints, that is not the primary endpoint in this particular study. We will be looking at BCVA as well as CST. Both structural and functional signals will be obtained. This will be eight-week treatment, and then we'll follow up after the eight weeks. Next slide. Okay. Thank you. I'm now going to pass this on to Kristen for the conclusion. Thank you, Paul. I'll close now with a summary of our pipeline and our near-term catalysts. As you've heard, BGE-102 is marching forward in two different therapeutic areas. Our APJ agonist is moving toward IND as well. Also, our platform partnerships are continuing to generate additional programs. To briefly go through the milestones here on the slide. For BGE-102, our cardiovascular risk POC, those results will be here soon in the second half of 2026. For our DME study, we're initiating that study in the middle of this year. We'll have results the middle of next year. With our APJ agonist program, which we didn't discuss today, we are advancing both oral once-a-day as well as injectable once-a-week formulations on track for IND by the end of this year. Our partnerships based on our platform with Novartis and with Lilly are also marching ahead and delivering earlier milestones. We have a great cash position to bring our programs forward. Next slide. With that, we're happy to open the floor to questions. Thank you. If you'd like to ask a question, please press star one on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star two if you'd like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. Our first question comes from the line of Yasmeen Rahimi with Piper Sandler. Please proceed with your question. Good morning, team. Thank you so much for the thorough presentation and congrats on the data. Two questions for you. The first one is, help us understand what obviously between 60 and 120, both look very, very good. The rationale for selecting 90 mg dose group in your POC cardiovascular study. And what do you hope to see? Question number two is, do we have a good understanding what matters more? Is it the magnitude of CRP reduction? Or is it getting the percentage of patients to normal CRP? Sorry, maybe the last one is, I know the study wasn't designed to look at other comorbidities, but is there an opportunity to look if there were any improvements in liver manifestation, whether it's liver enzyme improvements or MRI-PDFF. Any liver-related assessments would be also appreciated, and I'll jump back in the queue. Hi. Yes. Thank you for those questions. As pertains to the rationale for the 90 mg dose, what we based on was the fact that at 120 mg at the seven-day period, we essentially saw maximal inhibition. Now, the exposures achieved at seven days with 120 mg are equivalent to the exposures that will be received with 90 mg at steady state. In terms of achieving concentrations that will get maximum inhibition, we think that we'll get that at a lower dose at steady state, so there's no need to go to the higher dose from that perspective. Does that make sense? Yes, very much. Just to briefly add too, right? As you've seen, basically the two doses we tested were indistinguishable in terms of the CRP performance. We'll try them out, both of them for, 60 and 90 for the full three months and see if there's further differentiation. Yeah. What was the second question? As pertains to percent change in CRP, and this is my understanding of it, you can kind of look at it sort of like cholesterol. In actuality, lower is better. You're trying to achieve it to get to your CRP level as low as possible. Now, the 2 mg/L threshold was determined from previous studies that suggested that until you get below, you don't see these decreases in risk. The decreased risk can get even greater if you can get it below, even further below 2 mg/L. It's kind of both is your question. Lower the better, but 2 mg/L has been documented to be a threshold beyond which you start to see additional risk benefit. Yeah, we are doing in our study, our phase II proof of concept trial, we will be doing liver MRIs. We'll be able to look at inflammation and look at similar outcomes that have previously been looked at to determine whether or not this mechanism has an effect on the inflammation in the liver. Yeah, there could be nice benefits there from the other data that's been put out. Great. Thank you so much, and congrats again, team. Sure. Thank you. Our next question comes in line of Roger Song with Jefferies. Please proceed with your question. Hi, this is Fiona on for Roger. Congrats on the data, and thanks for taking our question. My question is also somewhat related to the dose response between the 60 and 120. Is it possible that you're hitting an efficacy ceiling even at 60 because both response seems to be good? And I recall that you said the CRP response with the 30 mg is not as robust. Is that from the SAD study or some other measurements that you have collected? And I have a follow-up. Yeah. To your point, we could be hitting an efficacy ceiling, but frankly, it's too early to tell, right? These are small n, and they were not distinguishable, though they saw very profound normalization rates. That's exactly why we're going to carry forward two doses into the dose ranging, just to make sure that we're capturing the full effect and the durable effect as well over a longer period. Yeah. The 30 mg dose, obviously we didn't look at it in terms of multiple dosing. We're really basing it on effects on the pharmacodynamic marker on IL-1β. You're seeing significantly less of an IL-1β effect, which we think will translate to a lower effect on CRP. That's how we've made the determination. Thanks. Yeah, that makes a lot of sense. I have another one on, how do you think about the hierarchy between these biomarkers like CRP, IL-6, fibrinogen? It seems like the response over time does not necessarily go in the same direction. Just curious how you think about where to place these. CRP, we'd expect that to be profound and durable as we've shown so far, and has been shown with the mechanism so far as well. Some of the other biomarkers, like IL-6 or fibrinogen, the effects are not as profound, right? You're seeing maybe like a 30%-50% reduction versus the close to 85%-90% reduction you see with the CRP. There you'd expect to see less error, less noise in a larger cohort. Yeah, I think those findings also suggest that the effect on CRP could be driven by multiple things, not just IL-6. You're seeing kind of an additive effect of these effects on pyroptosis, on IL-18, on IL-1 β. You're seeing effects on multiple potential risk factors related to inflammatory markers. Yeah, it's really interesting that this class of drugs seems to reduce IL-6 levels by around 50%, and that's been shown with other mechanisms, and yet you're achieving similar profound CRP reductions to the antibodies, right? Which is exciting. Yeah, that's very helpful. Thank you. Congrats again. Thank you. Our next question comes from the line of Samantha Semenkow with Citi. Please proceed with your question. Hi, good morning, and congratulations on all the progress here. A couple questions from me. First one also on dosing. I'm wondering if you think you'll need to go even further lower than 30 mg. Is that a possibility that you would need to go lower to see a dose response? Apologize if I missed this, the dose in the ophthalmology study, is that going to be in line with what you're planning to use for the cardiovascular risk study, or could you need, I guess, higher doses for that indication? I have a follow-up. I think, yes, it's possible to go even lower, but there's just so much we can do from a practical perspective. Again, we're basing that on the effects that we're seeing on IL-1β. When you look at 30 mg and you look at the PK/PD relationship, it definitely has a suboptimal effect compared to the higher doses, where 60 and 90 seem to be close to equivalent at a much higher level. That's the best we can do. Yes, it's possible that we get great effects at 30 mg, but I think that's a good problem to have. The dose in the ophthalmology study, is that going to be in line with what you're planning for the cardiovascular risk study? When we look at the relationship between IL levels and plasma levels. Well, we're not actually out of the study yet. We haven't disclosed that yet. Yeah, we haven't disclosed the study yet. We believe we're choosing a dose that will provide maximal inhibition in the eye. Yeah. Will be similar range. Yeah. Okay. All right. Understood. I noticed that you're going to be looking at Lp(a) in the cardiovascular risk study. I just wanted to get your thoughts on that for this mechanism. What is really driving the Lp(a) reduction that we've seen in some of your competitor datasets, and how do you think about the magnitude that you could see with BGE-102? Yeah. Lp(a) is one that where the presence of Lp(a) drives inflammation, and then inflammation in turn drives elevations in Lp(a). There is clearly a relationship, but it kind of goes in two directions, so it's hard to know what happens in a short period of time. What we're going to do is look at this for a longer period of time, and hopefully we'll be able to reduce the variability by more patients and for a longer period of time and be able to show what should be an effect. Again, we'll measure it to find out. Yeah. More moderate than CRP, for sure. Got it. One last question, if I could just squeeze one more in. You put a bunch of indications up on a slide that NLRP3 inhibition could be addressable in, and I don't think it was exhaustive. Can you just talk a little bit about how you're thinking about prioritizing where to go next and the capacity that you have with your cash runway to do so? Thank you. Yeah. We're well-financed to take the program forward, and really it's more about having indications that we're sure about, right? We're very excited about the opportunity in ASCVD and cardiovascular, and we're also very excited about the ocular opportunity for a number of reasons. One of them is that they're very much de-risked by existing data with IL-6. There's a very clear value proposition for a molecule like ours. Like in cardiovascular, we have potential best-in-class CRP reductions. In the ocular indication, it's a very unique feature of our molecule that we have great penetration into the eye and very nice pre-clinical efficacy. We'll have a similar bar for any additional indications that we consider. Thank you. Our next question comes from the line of Salveen Richter with Goldman Sachs. Please proceed with your question. Morning. Thanks for taking my question. Could you speak to the anticipated read-through from some Novo’s ziltivekimab data that's coming later this year as you think about cardiovascular outcomes in relation with CRP? There clearly are a lot of questions about the dose work here. Can you just maybe walk through the thoughts about exploring 120 mg in other indications or the likelihood even in the study for higher efficacy with that dose? If the ZEUS trial is positive, obviously I'd very welcome this mechanism because there's overlap in terms of ultimately what biological effect it has in the body. In this case, it would be with an oral medication, so there's obviously advantages as we've outlined from that perspective. In a positive scenario, obviously it's very favorable for what we're doing. If the ZEUS trial were negative, well, there's already confirmatory data for blocking IL-1β in the CANTOS trial, which we know that our drug is very potent in doing. There is already evidence that this mechanism can be beneficial from the canakinumab studies looking at cardiovascular risk and outcomes. I think either way, there's a rationale to continue. Yeah. We're excited for that readout. Your other question was around the 120 dose. Again, in terms of the cardiovascular effects, we basically saw identical effects so far at 60 and 120. The one point of differentiation is that you get a lot more brain penetration with the 120 mg dose, as you saw in our CSF data, we're basically four-fold above the IC90. There could be potential for. Yeah. Yeah. Also in the eye study, what we are doing, part of the study will be looking at both drug concentrations and effect on inhibiting IL-6 in the aqueous humor. We're actually doing taps. That will give us a PK/PD relationship that can guide us in terms of future dose selection. Thank you. Our next question comes from the line of Jay Olson with Oppenheimer & Co. Please proceed with your question. Oh, hey. Congrats on these impressive results, and thank you for hosting this event. For your phase II study protocol, what sort of background therapies will be allowed, such as statins or GLP-1s? In that study, should we be looking at placebo-adjusted hs-CRP reduction or just focusing on absolute hs-CRP reduction? Finally, recognizing that it's early to talk about a registrational clinical plan, can you talk about the potential use of hs-CRP as a surrogate biomarker for a Subpart H accelerated approval contingent upon outcomes? Thank you. I'll start with the last one first, and obviously we don't know for a fact what's going to happen from a regulatory perspective, but when you look at the use of cholesterol as a surrogate, for example, it required validation studies. Until those validation studies exist, and they might come out of these very large, long outcome studies, that's when they'll allow us to use CRP as a surrogate. You have to look at what had to be done for lipid-lowering agents to get the same consideration. Oh, yeah. If people are on cholesterol-lowering agents or antihypertensives, those would be allowed as part of the study, as long as they're on a stable dose. GLP-1s? GLPs are not allowed. Yeah. GLPs are not allowed. In terms of hs-CRP reduction, should people be focusing on placebo-adjusted or just the absolute reduction? Yeah. Yeah. I mean, likely the absolute, right? You wouldn't expect in a phase II there to be much of a placebo response there. Yeah. In a short period of time. We'd be looking at, yeah, absolute effects. Obviously in the secondary endpoints, we're looking at essentially response rates. You'll obviously be comparing that to placebo response rates. Yeah. Exactly. You don't really see placebo normalization below two. Great. Congrats again. Thanks for taking the questions. Thank you. Our next question comes from the line of Joseph Stringer with Needham & Company. Please proceed with your question. Hi, good morning. Thanks for taking our questions. Just curious, in general, how did the CRP reductions look based on baseline CRP levels? And I guess for the few subjects that did not hit the CRP threshold levels of less than 2 mg/L Yeah. There's nothing out of the ordinary in the ones that didn't respond, and some of them came very close. It could just be the time of exposure. There was nothing unique about the ones that didn't respond. Oh, yeah. To your question about how CRP changed depending on baseline, the percent was similar. Right? If you're starting at a higher baseline CRP, you're losing more absolute CRP. Right? The percent was fairly similar. Great. Thank you. Thank you. Our next question comes from the line of Mike Ulz with Morgan Stanley. Please proceed with your question. Good morning. Thanks for taking the question, and congratulations on the data update as well. Maybe just a quick one around safety. Looks like both the 60 and 120 mg doses are very well tolerated. Just curious if you can characterize some of the mild to moderate adverse events you're seeing, and then more specifically, if you're noticing any differences between the 60 and 120 mg doses so far. Thanks. Yeah. I'd say that in general, the side effects are fairly typical of a phase I study. We did see headaches as one of the relatively more commonly reported, but these seem to be directly due to the fact that these patients had two lumbar punctures during the course of the trial. In fact, we had a cohort that didn't have lumbar punctures, and the rate of headache was much less. Yeah, no dose group differences. Nothing dose dependent. Nothing dose dependent. In fact, there were some opposite effects. It was lower, it wasn't higher. Great. Thank you. Thank you. Our next question comes from the line of Andy Hsieh with William Blair. Please proceed with your question. Thanks for taking our questions. I'm looking at the brain penetration study that you did. It suggests that probably 50% of the drug is actually going into the brain, and I'm just curious if you can extrapolate that data into some ocular indications if you're hoping to start shortly. I'm also curious, from a previous question, in terms of headache, you talked about 6 patients experiencing that, no dose response, but I'm curious across the active treatment arms and the placebo, are they mostly balanced? Yeah. There's balance across it, but we had much fewer placebos in the study than we had actives. It wasn't a 50/50 split. As I mentioned, the headaches themselves seem to be, the majority are not related to drug and are related to lumbar puncture. Got it. Now- In terms of the ocular extrapol- Yeah. There are some similarities between blood-brain barrier and blood-retinal barrier. In this case, it would be dangerous to extrapolate one to the other. We've done some studies in animals to determine what the levels are in the eye and the free drug in the eye, and that's where we're kind of extrapolating from animal data. I see. Okay. Last one for me, looking at the IL-6 reduction. If you look at across two doses, there's actually a diminishing reduction over time, 7, 14, 21 for the 60 mg dose and then day seven, day 14 for the 100 mg dose. There's a diminishing reduction over time. I'm curious if that's kind of a small number, a function of small numbers, or maybe there's a biological rationale that you can explain. We think that's most likely to just be a small N. If you look at the placebo response, that also bounces up from day seven to 14 and then down again a lot by day 21. It's likely driven by the N as opposed to anything biological. Of course, we'll look at this in our larger study next. I see. Thank you so much for all the answers. Thank you. Ladies and gentlemen, this concludes our question and answer session. I'll turn the floor back to Dr. Fortney for any final comments. Thank you, everybody, for joining us today and for your thoughtful questions. We're excited to continue advancing BGE-102 and our other programs, and we look forward to sharing our next update with you soon. Thank you. This concludes today's conference. You may disconnect your lines at this time. Thank you for your participation.