Good afternoon, everyone. Thank you for joining us. Really pleased to have with us the BioAge team. We have BJ Sullivan, Chief Strategy Officer, and Dov Goldstein, CFO. To start here, the company's developing its NLRP3 inhibitor, BGE-102, in cardiovascular risk and ophthalmology, and also advancing a pipeline of APJ agonists. Can you walk us through the portfolio strategy, where the assets stand today, and the data expected over the next 12 months? Yeah. One, thank you for having us. Great to be here. We are a clinical stage biotech company, and we are applying human aging biology as a lens for target discovery and development of therapies for cardiometabolic disease. As you mentioned, our lead program is BGE-102. It's potential best in class NLRP3 inhibitor. We recently released our full phase I data, which included two cohorts of obese subjects with elevated inflammation at baseline. And there we showed CRP reductions of 86% in both cohorts, which was really exciting for us because that essentially is on par with the CRP reductions that have been shown with the injectable modalities, IL-6 in particular, that's currently in development for ASCVD. We have an oral modality where there's really no trade-off now in anti-inflammatory sort of horsepower. I'm sure we can go into those results in more detail, but we're developing this. Our anchor therapeutic area is cardiovascular disease. We're doing a cardiovascular risk proof of concept dose-ranging phase II study that'll read out by the end of this year. Our second therapeutic area, which we introduced earlier this year, is ophthalmology, and we're doing a DME proof of concept study to really demonstrate target engagement in the eye. We're going to initiate that study in the middle of this year and have results in the middle of next year. Again, BGE-102 is our lead program. We're also developing both an oral and a parenteral APJ agonist. This is the target for the exerkine apelin, and that's one of the strongest signals in our platform. It's associated not only with longevity but also preservation of physical function. This is an exerkine that is secreted by muscles during exercise. What we've shown pre-clinically is that you can essentially double weight loss and fully restore body composition back to that of lean control animals when you add it to an incretin. When thinking about the obesity market as it's evolving, the unmet needs on the oral side, probably still more the quantity of weight loss and getting that quantum on par with what we're seeing in the injectables. In the injectables, now we're seeing bariatric surgery like weight loss. Perhaps the sort of predominant value proposition there is body composition. We're developing both an oral and a subcutaneous agonist to complement both sort of ongoing segments of that market. Right. You have collaborations right now with Novartis and Eli Lilly, specifically. Elaborate maybe on the therapeutic focus here and how partners leverage your platform in the financial terms? Right. We had a target discovery partnership with Novartis, this is looking for targets that sit at the intersection of healthy aging and exercise. What we've built at the company is one of the world's largest collections of human aging data, which really look at healthy middle-aged people and then track them essentially to death with very detailed phenotyping and health records. We can look and actually do apply multi-omics now to biobank samples and ask the question, what is the biology that predicts not only longevity but sort of very granular health outcomes and phenotypes? That's the data set that we contribute to the collaboration, Novartis has exercise interventional data sets that they're contributing. We're really looking for targets that sit at the intersection of those two things. We also have a collaboration with Lilly, and that's really focused on molecule discovery, and so we're building drugs against targets that we've identified in our platform. Starting with 102 here, can you explain the role of NLRP3, the inflammasome pathway in your inflammation in cardiovascular disease? You've talked about a novel binding site versus other drugs in this class. How does this translate to differences in efficacy and safety? Yep. NLRP3 is one of the inflammasomes in the body, and essentially it is a sensor and a transducer of signals that contribute to sterile inflammation. If you think about in the ASCVD context, this is cholesterol crystals, oxidized LDL, metabolic stress, hyperglycemia. All of those are essentially sensed by NLRP3 and then converted into sort of a cytokine cascade. Right. NLRP3 regulates the production of IL-1 beta, of IL-18. It also controls pyroptotic cell death and atherosclerotic disease progression. In the eye, DME, hyperglycemia is the key trigger, right? That's then converted into sort of a cytokine cascade that drives the disease forward. Yes, again, this is one of several inflammasomes in the body, but it is the primary contributor to sterile inflammation. People have been trying to drug this for 20 years now. Originally, the MCC950 was the original tool compound. It bound in the ATPase pocket. Groups have been creating derivatives of that compound, novel chemotypes that target the same binding site. What we did was we took a step back and actually did a DNA-encoded library where we blocked that binding site to identify novel binding sites. What we have is not only totally novel chemistry, but a novel binding site that we've characterized and detailed structural biology of it. As a result, we have issued IP that includes not just the specific structures described, but broadly speaks to ligands that interact with that binding site. What's interesting about it is that it can bind NLRP3 in any conformation. Whether it's active or inactive, our pocket is accessible, which is unlike MCC950 and the derivatives thereof, which the pocket's only available when it's in the inactive form. That may contribute to either onset of action as well as the magnitude of the anti-inflammatory effect that we're observing. Essentially, all of the NLRP3 in the body is open to our inhibitor. With regard to your phase I data that you've shown here, you reported up to 86% reduction in CRP within two to three weeks in obese subjects with high baseline CRP. How does that compare with other inhibitors or inflammasome-targeting therapies in development? I think we looked at the sort of differentiation across three key dimensions. One is efficacy in terms of biomarker reductions, safety and tolerability, as well as dosing. To speak first to the bio In both of the cohorts that we tested in our phase I, we were able to normalize CRP below the 2 mgs per liter threshold in 87%-93% of those participants. That's really important because we learned from the CANTOS trial, which Novartis ran with their IL-1 beta antibody, showing that essentially the headline number in the MACE trial was 15%, which is a good result. It was concentrated in the patients who achieved this 2 mgs per liter threshold where they had a 25% benefit, and those that didn't had essentially none. We think that that's the really meaningful outcome, and regardless of baseline, in the two cohorts who were able to normalize them to these, the vast majority of patients to this important goal. We're thrilled with the biomarker efficacy. The safety tolerability was, in our view, exceptional coming out of the phase I trial, really no observations of any kind. Importantly, dosing, I think. We have a clear low-dose QD profile, which is not only commercially very important when you think about the ASCVD opportunity in particular, where it's dominated by orals, it's mostly PCPs prescribing. People are used to taking a statin every day. It's commercially very important, and then also in terms of ultimately strategic interest, there's a lot of value potentially in fixed-dose combinations and the sort of lifecycle management strategies and the ability to combine NLRP3 with an oral PCSK9, a statin, and again, drive value for across a franchise, but also maximize patient acceptance and convenience. Given these phase I data, what are expectations for phase II proof of concept data that's coming by year-end? The proof of concept is really first and foremost going to extend the phase I data. Right? The primary outcome is CRP reductions. What we're looking to see here is a sustained decrease in CRP and other inflammatory biomarkers. We're hoping to extend the safety tolerability findings from the phase I, and we're also adding additional assessments like MRI imaging of the liver, where Ventyx previously showed, for example, a benefit as a monotherapy in liver inflammation. There will be additional assessments there. The key outcome beyond that is really dose selection. We think about the profile coming out of phase I, we're feeling really bullish about it, and we want to maintain an aggressive timeline going forward to enable a phase III start next year. Part of that was expanding the phase II POC to include exploration of multiple doses, have confidence in what we ultimately carry forward into phase III. You talked about the dosing work that you've done, and you're looking at the 90 mg in phase II versus the 120 mg in phase I. What gives you confidence in achieving similar biomarker outcomes with the lower dose in the phase II? Right. The top dose in the dose-ranging study is 90 mgs QD, and we are expecting on an exposure basis that that's really going to give us 98% target suppression. The drug does have a relatively long half-life and reaches steady state at about a month. The difference between the 120 mg and 90 mg dose is really an adjustment for that PK profile. Right? In the phase I with 120 mgs, we saw 98% suppression of IL-1 beta at a week. We'll achieve that level at a month in the phase II trial, but this is really a chronic medicine. Again, it's sort of a pharmacokinetic extrapolation. The endpoint for the study. Right. The key read through this year, we were just talking about this, but is the phase III CV outcomes data for Novo Nordisk's IL-6 inhibitor in the ZEUS trial. What level of MACE reduction would bode well for your drug and for the class overall? Right. We're really looking for any significant MACE benefit here. I think typically clinicians view 15% MACE benefit as sort of the threshold at which there's excitement. We're looking obviously for a meaningful MACE benefit here. I would say that the way we think about this is actually the biology is probably more de-risked by the CANTOS trial that we were talking about earlier, which is targeting IL-1 beta, which is directly downstream of NLRP3 and where patients who achieved target CRP levels had a 25% MACE benefit. Of course, if IL-6 shows a significant benefit here, you're saying that no matter where you are in this inflammatory cascade, that blocking that provides clinical benefit for patients. That is, of course, broadly. The way we think about this program in particular and the value of success in ZEUS is really anticipating a launch of an IL-6 drug in this space. I think right now, physicians only have low-dose colchicine, which is approved for inflammatory cardiovascular risk, has a lot of tolerability, drug interactions that make its use in clinical practice virtually. The prospect of having a selective anti-inflammatory launch in the space, have growing physician awareness of inflammation as a treatable risk factor, and have CRP routinely tested as part of your annual workup, we think all of those would be very powerful and market development for subsequent launch of an oral that can provide similar benefit in a more convenient sort of format. if the ZEUS study is unfavorable with regard to that outcome here, what is the read-through for you? Yeah, again, I think we map the biology more closely to the CANTOS trial, but we won't swim upstream if it's a very catastrophic negative result. The primary focus of the CV risk market has been LDL lowering with PCSK9s and statins, with increasing focus on Lp(a) as a target coming up. Where do therapies targeting residual inflammation fit, and what is the market opportunity in that context? Yep. There was actually a really compelling paper in "The New England Journal of Medicine," I believe, last year by Paul Ridker, showing that hsCRP was actually the most predictive risk factor for MACE in the 30-year longitudinal women's health study. It's a strong risk factor, it's an independent risk factor, and it's one where there's actually about 60% of ASCVD patients today have residual inflammatory risk, which is to say they have not achieved that target CRP level of 2 mgs per liter. We're hoping that this will become a routine part of care where those patients who do have elevated CRP, despite whatever background therapies they're on, will be initiated on a drug that can address that risk. Again, it's highly predictive, and it is independent of these other sort of lipid biomarkers. You plan to start a phase III by year-end 2027. Do you plan to advance independently or seek a partner here? I think right now our focus is on enablement, I would say. All of the long lead time activities that we need to feel confident with this aggressive timing. That includes doing dose ranging, it includes initiating a CMC campaign to support the initiation of a trial of that size. Of course, aligning on a design and all of the preparation for an end-of-phase II meeting. Dov, do you want to speak to the partnership aspect? Yeah, sure. My pleasure. As far as partnership, we strongly believe the best way to form a partnership potentially is for the company being in a strong position to go it ourselves. That means, as BJ mentioned, preparedness, but also financial preparedness. This is an asset that makes sense already in the late-stage clinical setting to be done by a larger group, but we are prepared as a company. Anything else we need to touch on with regard to this program? I think we've covered the bases in ASCVD. Perfect. Let's switch over to ophthalmology here with 102. With regard to diabetic macular edema and geographic atrophy, maybe speak to the mechanistic rationale behind moving into these disease areas. Right. I think that there's one driver of our therapeutic area strategy here is just the differentiation of the molecule and the ability to access these privileged compartments and the distribution profile of the molecule. In our phase I data, we show that we get excellent CSF penetration. We've shown in a range of preclinical species that we get therapeutic exposure in the retina, and we're leaning into this property of the molecule to expand the scope of indications that we can address, and ophthalmology is sort of our second anchor therapeutic area. To speak to the biology of it, the NLRP3, again, is a sensor of sterile inflammatory triggers. In DME, it's really responding to hyperglycemia, and that's what activates NLRP3. Geographic atrophy is a little bit different. It's almost like a neurodegenerative condition of the retina, where you get accumulation of the cellular debris like drusen, which has these amyloid components. You get deposition of all of the cellular debris, and it's sort of a canonical pro-inflammatory trigger. NLRP3 actually sits at the core of both of those diseases, but with different upstream drivers. Any read-through from Roche's data for their IL-6? Yep. The Vamikibart program has been sort of informative for us in thinking about our next steps here, I think. First and foremost, this is an IL-6 in an intravitreal injection. They've shown efficacy now as a monotherapy with Eylea. They released that data at ARVO a few weeks ago. They had shown incremental efficacy on top of VEGF. I think on a very fundamental level, it tells us that selective anti-inflammatory strategies can provide incremental benefit in this patient population. It also showed that essentially the maximum benefit was achieved by two months of treatment. For us thinking about a tractable POC indication where we're trying to first and foremost demonstrate target engagement in the eye, that this is a tractable indication for us versus geographic atrophy, which is an area of enormous unmet need, but it does progress more slowly. In thinking about IL-6, though, it's one aspect of NLRP3. It's not the totality of the picture. I think NLRP3 does induce IL-6. VEGF is induced by IL-1 beta. You've got this sort of pyroptotic cell death when NLRP3 is activated and the retinal microvasculature. There is potential to have efficacy beyond what was demonstrated with these IL-6 modalities. Without the sort of the complications that come with that route of administration. For the DME study, we were looking forward to results in mid-2027 here. What% change in intraocular IL-6 will be clinically meaningful? Maybe talk about both the monotherapy in combination with anti-VEGF therapy and the incremental BCVA in each of those cases. Right. Our POC study, it's going to have three arms. We're looking at BGE-102 as a monotherapy. We're also looking at VEGF as a monotherapy and VEGF combined with BGE-102. There are three arms we're going to treat for two months. The primary endpoint is the percentage change in IL-6, intraocular IL-6. We're going to be doing aqueous taps on these patients, so we can measure biomarkers in the aqueous fluid. We're powering the study for about a 40% change in IL-6, but I think it's going to be important for us to look at the totality of the data. It will be a biomarker primary, but we're going to be doing functional assessments like BCVA. We'll be making anatomical OCT measurements like CST. We're going to be looking to see that the totality of the data sort of tracks that biomarker change, right? Thinking about that pharmacodynamic effect. Where would this drug be positioned within the market? I think that there are multiple compelling segments here. If you think about DME, I think the obvious segment is the watch-and-wait patients. They're about 40% of DME patients who have edema, but they don't have sufficiently compromised vision that ophthalmologists have initiated intravitreal therapy. If you can treat these patients with an oral and delay the onset of initiation of that therapy, that could be incredibly meaningful. I think, for context, VEGF does work well in a lot of patients, especially in trials. I think in the real world, that picture becomes more complicated because you're talking about monthly or quarterly dosing that's challenging for sort of working average people to follow. That's one highly addressable segment. On the other side of this, you sort of got early patients, and then I think also late patients where you've got, they've been on a VEGF, they're refractory in terms of the amount of disease control, even when they're compliant. Adding on this mechanism to regain disease control would be very meaningful, and I think there it's really just the clinical benefit first and foremost, the convenience of it secondary. For geographic atrophy, this has been a much harder indication historically than DME, particularly with regard to BCVA. What is the expected profile for your drug in geographic atrophy, and can the drug deliver functional improvement, noting the absence of approved assets, as we just mentioned, showing that? Right. That's, of course, the truth call. Geographic atrophy, this is essentially the terminal stage of dry AMD. It causes central blindness in the vast majority of patients. There are approved complement inhibitors. Syfovre and Izervay, these are blockbuster products, but right now they slow lesion size by about 15%, right? They require monthly injections. They haven't shown visual acuity benefits yet. There's a ton of unmet need here. The clinical need is really enormous. In thinking about the positioning of this molecule, yes, an oral is convenient, especially with this sort of majority elderly population. Just getting disease control of any kind, however you measure it, I think is a major step forward for these patients. You've also talked about going into CNS-related chronic inflammatory conditions. Speak to the rationale there and the indications that may be of most interest. Yeah. As we demonstrated in the phase I, we do get really nice CNS exposure with the drug. Right now we're very focused on ophthalmology as our way to lean into the sort of differentiated distribution of the drug. Thinking long term and the applicability of this mechanism, really the range of neurodegenerative conditions in particular are exciting because those are ones where you get accumulation of debris like alpha-synuclein or amyloids, those are canonical, again, pro-inflammatory triggers. It's a lot for a small biotech to block and tackle, there's a lot of promise in this mechanism for this sort of broader range of CNS disease. Finally, apelin, where it all started. Yeah You do have an agonist here under development, one in collaboration with Jingang Therapeutics. In terms of therapeutic areas in focus, speak to expected profile and key near-term milestones. Yeah. We are developing two APJ agonists, one for an oral small molecule, and then a subcutaneous agonist as well. As you mentioned, we have a collaboration with Jingang Therapeutics developing agonist nanobody. The profile here again is we're looking to increase both the quantity and quality of weight loss. We think that even as the obesity market evolves, I think a lot of key unmet needs remain. Thinking about the oral space where incremental efficacy to really make it a competitive alternative to an injectable, it would be commercially valuable with body composition as sort of a nice upside. I would say too, with limited increase in GI tolerability, I think our experience with this target is that it shouldn't lead to any sort of untolerability issues that would make combinations with incretins challenging, and I think that that's in contrast to other sort of mechanisms focused on certainly anabolism. On the parenteral side, injectables have achieved remarkable amounts of weight loss, I think body composition, and especially addressing that in a well-tolerated way remains a major unmet need. This is again, the optimal profile for a sub-Q would be to complement the injectable incretin. You could even think about dose sparing too, to sort of take advantage of some of the synergistic weight loss. Either of those, I think, would be highly valuable. Right. Maybe just here as a final question, walk us through your cash position and cash runway and maybe just in the context of all these programs that you're advancing. Yeah. My pleasure. At the end of the first quarter, we had $385 million in cash. All the programs we've outlined are included in the guidance I'm just about to give you. The only thing we haven't talked about is we're actively working on a backup compound for NLRP3 to potentially one of these two indications will be another molecule to split the commercial opportunity. With all the programs we've talked about, we have cash runway into 2026. Just maybe the rationale for the second follow-on NLRP3 and the need to split the commercial. Yeah. Just thinking about if we partner the ASCVD, the asset with someone and want to price it at a certain level, and want to keep ophthalmology for ourselves and price it at different, gives us that flexibility. Perfect. Well, with that, thank you so much. Thank you very much. Thank you so much.