Great. Good afternoon, everyone. Thank you so much for joining us. I'm Selvine Richter, biotechnology analyst at Goldman Sachs, and it's a pleasure to have the BioAge team with us. With us, we have Kristen Fortney, co-founder and CEO, and Dov Goldstein, CFO. To start here, you know, in the context of the news flow that's played out since the IPO, maybe level set us with where you stand today in terms of strategy, pipeline, and your 12-month catalyst path. Yeah, sure. Happy to do that. Just by way of introduction, a reminder at BioAge, we're focused on really understanding key mechanisms in the biology of aging to find important new targets for metabolic disease. We're advancing several of those forward from the preclinical stage, our first program into the clinic later this year, and we also, for a second program, happen to have an IND on file for next year. It's just looking into the near-term catalyst over the next 12 months. Our NLRP3 inhibitor and inflammasome inhibitor, which we believe is going to have applications in many important diseases beyond metabolism. Metabolism is where we're going to look first. We're going to file IND mid-year this year, have our first SAD data by the end of this year, and then SAD/MAD data in the first half of next year, and then an obesity cohort readout by the end of next year. For our next-generation apelin approach, apelin is a target that we're really excited about at BioAge that really behaves like an exercise mimetic and is linked to improved muscle function in a metabolic context. There we have both an oral and an injectable approach, and the goal is to file IND next year. Behind those, we have earlier-stage targets we're working on as a company, some in collaboration with pharma. We have a couple of collaborations with Lilly and Novartis based on our human data platform. Maybe to start here, provide an overview in a deeper way about the platform itself and these targets, and maybe shed some light on the collaborations you have with Novartis and Lilly, particularly the therapeutic areas of interest and how they seek to kind of leverage your platform within their portfolio. For sure. The aging process is one of the biggest drivers of chronic disease, including chronic metabolic diseases. The vision at the company was that by better understanding how that process unfolds in humans at a molecular level, we might discover important new targets to treat disease. The resource that we've constructed, it's basically a biobank resource like deCODE or like UK Biobank, with one key difference, which is that we have samples going back 50 years that were collected when people were middle-aged. The follow-up of the data is a lot longer, so that we're able to understand those molecular changes that are part of aging that actually precede disease. We believe that by looking at different diseases through the window of aging biology, we can find important new targets. We like to see basically for the targets we bet on at the company that signal in the human data, right? It's kind of a de-risking signal for translation. I mean, you saw Amgen bet on deCODE, and targets with genetic validation of some sort tend to work out better. Our version of that is the BioAge platform. As you mentioned, we have collaborations on that platform now with validating collaborations with Novartis and with Lilly. The Novartis collaboration we announced in December, and it's really a target discovery collaboration. Novartis has a new division called DARE, Division of Aging and Regenerative Medicine. They're really focused on aging biology. They're very much bought into that idea like we are, that the biology of aging can help us find important new targets. They believe, too, that a lot of those targets are still unknown. That's exciting for us because it lets us work on kind of some of the earliest targets from our platform. Usually, when we're bringing something forward ourselves, it's got some validation in preclinical models or in literature. With Novartis, we're actually focused on completely novel targets that haven't been published on before. They're bringing some of their data sets to the table, too. Novartis is actually really interested in the gene changes induced by exercise that can help mediate some of the positive benefits of exercise. We're really overlaying our two data sets together, looking for those molecular pathways that change in human populations as they age, and our exercise responses can help mediate some of those benefits. Apelin is a great example, actually, of a molecular factor that declines with age that is induced by exercise that can recapitulate some benefits. We're looking to find additional targets like that. Some of those targets will be advanced by Novartis, and some of them will be advanced by us. You've touched on this broadly, but when you look at NLRP3 inhibition in your inflammation that's linked to conditions such as obesity, maybe help us understand the mechanistic rationale and how you can directly target this. For sure. We initially started working on NLRP3 a few years ago, really not thinking of obesity at all, and really having that signal in our human cohorts where NLRP3 is going up as you get older. In middle-aged people who are otherwise healthy, having high levels of NLRP3 predicted dying sooner when you look at the follow-up data, and also predicted accelerated cognitive decline. That was sort of the starting signal there. It was really interesting to see the connection to metabolism and obesity evolve. I think it was known for a few years that if you knocked out NLRP3, that could protect from weight gain. That has been established for a while, at least five years. The finding that if you took an obese animal and reduced NLRP3, and that could actually, especially a brain-penetrant NLRP3 inhibitor, that could reduce body weight, that's newer, really. It was really Nodthera who first published that data a year and a half ago, which we've replicated with ours. We just, a week and a half ago, did a press release on our BGE-102, our potential best-in-class brain-penetrant NLRP3 inhibitor. We see, as we published in that press release, very potent monotherapy efficacy with this inhibitor on par with semaglutide, and also very nice additivity when you combine it with semaglutide, which is really exciting when you think about an oral strategy in obesity is going to have to be a multi-mechanism to really compete with the injectables. It's a really nice--these are sort of two potential things you could plug together to have that efficacy. Just to return to the original question, I think a lot of the science is still being worked out. What's very clear is that in the obese context, sort of the nutrient excess context, you have a lot more inflammation peripherally and in the brain. In the brain, that's been linked to appetite dysregulation. Of course, the peripheral inflammation is also linked to all these comorbidities of obesity, whether it's cardiovascular disease, et cetera. You're expected to present the phase I SAD data by year-end this year. That's right. The MAD next year, as you mentioned. What do you expect to see in these data sets that would inform your go/ no-go? Yeah. The SAD/MAD data is just a standard SAD/MAD study. What's nice with NLRP3 inhibitors is there is an ex vivo assay that can teach you a lot about your drug is doing what it's supposed to be doing and also help you select that dose. That's the ex vivo IL-1 beta assay. You basically take blood from people who've been taking the drugs. You can stimulate it and see how much of the signaling is inhibited with your drug. That's really important because it'll tell us where we are in the human. It'll help us select our dose as we go forward into that obesity cohort. I should mention, too, that phase one we're doing, that will inform all future trials of NLRP3. This is a mechanism promising for many different indications. We're excited to go into the metabolism first because, for one reason, the preclinical models have been very translational to date. We're really excited about the effect size that we see in the data and the translational potential there. We really think that by going to that population, you're also going to a population where we'd expect this mechanism to have benefits beyond weight loss, right? Especially when you think about cardiovascular disease in that cohort with canakinumab and IL-1 beta, there's a lot of reasons to believe this mechanism will be efficacious. Sure. Walk us through the trial design of the phase one proof of concept study in obesity as you move forward with the 1B. Yeah. This will be reading out at the end of next year. It'll be around 100 patients, three months in duration. The goal is really just as a monotherapy to show a semaglutide-like effect. Single-digit weight loss% on its own as a once-a-day therapy. This is a once-a-day therapy with a predicted pill size below 50 mg. The goal there is just to show that first. Of course, we'll look at a bunch of relevant biomarkers as well, collect as much data as we can, but weight loss is the primary endpoint. What is the target profile here? I'm saying this in the context of what you want to see from the drug, right, clinically, but also it's such a changing field, and you can assume injectables are going to be improved upon over time, but there is a need for orals to widen the opportunity. What else can you solve for here? Yeah, that's a great question. I mean, I think the needs are very different on the injectable side versus the oral side. We probably have as much weight loss efficacy as we need on the injectable side, right? It's more about maybe improving the AE profile or having additional benefits in different patient populations. In contrast with orals, it's still, I think, first and foremost about weight loss, right? If we had a pill that you could take once a day that behaved like tirzepatide in terms of its efficacy, I think that would be really exciting. We think the most valuable opportunity here is to pair together an NLRP3 inhibitor with a GLP-1 or another appetite-suppressing mechanism to achieve that best-in-class efficacy in a pill. Because of the mechanism, it's really weight loss plus, right? There could be other benefits, too, but that's the key part of the TPP. Is the strategy here, evaluate the profile monotherapy, then look to a combination therapy? That's right. That's right. Yeah, no, if the monotherapy shows nice efficacy, if that translates from the mouse, it'll work with a combination. It would be very just de-risking for any combination. Yeah. What about with other mechanisms like amylin? Yeah. We have not generated that data ourselves, but you would expect from the mechanism that this would be additive with appetite suppressants, or with NLRP3 inhibitors themselves are also appetite suppressants. I want to just point out that our other mechanism is going to be an oral APJ agonist, which we have previously shown is additive on top of appetite suppressants. We are excited about potentially having that combination within the company as well as the APJ program matures to have the APJ with the NLRP3 together. From a tolerability standpoint, do you have any understanding, at least on the sema side, what that combinatorial aspect looks like? How do you--I guess it just takes time with the studies to be able to. Yeah. I mean, the hope, of course, is that it will be better, right? NLRP3 inhibitors have been in a number of phase one studies. There have not been AEs like with sema, like nausea, et cetera, have been noted. It will be different, of course, in an obese population, but we think that is an exciting potential value add here, right, that you can have more weight loss but maintain. I do not think it is going to improve the side effects that you are already having with the GLP-1-1 component of your pill, but they should not get any worse, right? You should have the same side effect profile for more weight loss. As the field starts thinking about weight maintenance as well, there are opportunities to do two things. One, have GLP-1-sparing medications, either totally sparing or reduce the GLP-1s in combination with NLRP3 or an APJ agonist, or have the APJ agonist and NLRP3 together, as Kristen mentioned, alone. Yeah. That's true. We touched on this, but I guess with regard to market opportunity, where do you feel—I guess, where do you see the oral space evolving into? Because I think we have an understanding of injectables. Yeah, for sure. I mean, I think right now people are thinking of orals more as maintenance. I think that's driven largely by the fact that they don't perform on par with the injectables. I think that changes. For a couple of reasons. One of them, a big one, is cost. These are very expensive drugs. Having a small molecule oral would be a huge change, especially when you think about reimbursement for the larger populations that need these drugs. We think that a superior weight loss profile could really drive huge gains for an oral strategy. With regard to this class, we're going to see data from Ventyx in the second half of the year and potentially Nodthera as well. Could you help us understand what we need to see to validate this class, but then also how you might be differentiated in terms of both the assets? Yeah. No, we're really excited to see those readouts. I think Ventyx is coming later this year and Nodthera next year because this is a new target, right, a new mechanism. I believe I would like to see weight loss efficacy as a monotherapy, right, in both of these studies. I will say that we are differentiated in a few ways. First, actually, I'll mention just the scientific way. We do have a—we'll publish a paper on that later this year, which could lead to some novel biology. Knowledge of that novel binding site really did enable our chemistry. We think we do have potentially a best-in-class profile. The brain penetration to the brain-to-plasma ratio is close to 1, so very similar levels in brain and in the periphery, which is what we believe you need for the weight loss effect. The potency is very high. We're excited about that profile. We saw very nice efficacy as well in the animal model. They're also being evaluated, this class, in Parkinson's disease and essentially neurodegenerative diseases. What are your thoughts there with regard to investigating that? If not by yourself, would you look to partner? I mean, I guess that's tough because you can't partner out an indication always, but yes. Yeah. No, that's a great question. I mean, we have a backup program, too, of course. We believe this is an important aging target. Like any target, it's really like it's driving this inflammation that accumulates as you get older that underlies really a lot of different diseases, neurodegeneration, and that spectrum of diseases among them. We're watching those readouts with a lot of interest, right? Those can be challenging trials, but I think that it is a promising mechanism for those indications. When you went public, your value proposition was centered around a different drug, right, which obviously had some hiccups. What is the learning that you took from that that you are now going to apply to your portfolio and strategy? Yeah, for sure. Just for those of you who do not know, we discontinued azelaprag earlier this year with our APJ agonist in phase II after some unexpected liver tox events, which is incredibly disappointing. It is a very, very promising mechanism. We still believe in the biology and hope to be back in the clinic with that mechanism next year. Learnings-wise, I guess I wish we had a backup that was closer. That is probably the biggest one. That one had been in a bunch of phase one studies already, so we thought we were good, but yeah. You do have a backup, and you've filed IP for obviously these novel agents here. Just tell us how you're kind of parsing out the toxicity signal that played out in the context of these next generations. Yeah. We believe from everything we looked at that it's structure-related. The novel compounds, and we just did a press release on this last week, they're incredibly potent, picomolar potent, and they bear zero structural similarity to azelaprag. At the same time, we also announced last week that we in-licensed an APJ agonist nanobody, which is a really cool modality developed by the work of Fei Xu, who was a professor at Shanghai Tech and founded a company called Ji kang. She was actually the scientist who first published the crystal structure of APJ. That was in collaboration with Amgen showing that it bound to one of their peptides. Her lab has been the leader in APJ biology there. They built this incredibly potent, tenfold more potent than the endogenous peptide nanobody that we're hoping to also advance to the clinic to really address the injectable segment of the market as well. How does this differ from some of your other programs in terms of it being a nanobody? That's a great question. Yeah, we usually stick to oral for our other targets. This is, if you look at obesity, part of our thesis is, as we discussed earlier, that if you have an oral that behaves like an injectable, that's going to be preferred for a lot of people. I think probably especially long-acting injectables will still continue to be an important part of the market. Of course, with an antibody agonist, that's something you can design for. It could be part of your injectable once-a-month amylin or once-a-month GLP-1 regimen. Maybe, Dov, we can talk about the cash outlook here for the company. Sure. At the end of the first quarter, we had more than $330 million. We've guided that that's more than three years of cash runway for the company. It will deliver all the milestones that Kristen has mentioned. The POC monotherapy data for NLRP3, the SAD, the MAD data, advancing to DC both of the APJ programs, the injectable, as well as the oral program. Just going back to the NLRP3 target, can you just give us more history here on the program, not just from your side, but from the space as a whole and the work that's been done around this? Yeah. Just so we can put it in context. Definitely. I mean, there were a few big acquisitions on the peripheral NLRP3 side just a few years ago, right? My ears perked up this morning when Fiona Marshall was being interviewed because they were asked about Novartis's metabolic strategy, and she brought up the inflammasome, and its key importance in a lot of different comorbidities there, which is something, of course, we're paying a lot of attention to. There are at large pharma some programs and readouts that we're keeping an eye on, too. Like Novartis, I think their lead indication is still osteoarthritis. AstraZeneca is actually doing a small obesity trial as well, just a one-month study. We'll see if we get to see that data or not. There's also a small Parkinson's study as well, right? I think the question, too, most of these early-stage NLRP3 inhibitors from a few years ago are peripherally restricted, or they have some brain penetration, maybe like 30% brain penetration. What's sort of driven the newest crop, which is us and Ventyx and Nodthera, of course, ahead of us, are the promise of brain penetrance for neurodegeneration and also for obesity. This is a newer strategy to get these drugs into the brain at sufficient quantity. One other important point to mention is I think the very first NLRP3 inhibitor to hit the clinic, MCC950, Pfizer, had some liver tox issues that were related to the structure, right? That's also been important for everybody to sort of work away from that structure. So far, so good for the other programs. That was one reason that we at BioAge started off with a DNA-encoded library approach. We wanted totally different chemistry and then landed on this different binding site. That's the key differentiator, is the different binding site here. Different binding site and also different chemistry. That's right. And as I mentioned, a potential best-in-class profile in terms of potency in the brain, which we believe is what we need to achieve for metabolic indication. What should we be thinking about overall with next steps here? Really, I guess the readouts, right? We're looking forward to being back in the clinic later this year. We will have that SAD data set by the end of this year. I mean, it's not too far away. It's going to be the second half of next year when we have our obesity readout for what we think could be a really exciting oral strategy. Those are the catalysts that are coming up. Great. Any questions from the audience? I think one quick question for me. When we look at the NLRP3 inhibitors, there has been a lot of discussion around whether the mechanism is more suited for obesity or more suited for Parkinson's. Just in that perspective, and I'm trying to have some comments even though there are multiple motives there. Just from that perspective, what do you think about this debate around where this mechanism is best suited? Yeah. That's a great question. I think there's a lot of compelling preclinical data. I think the clinical readouts are going to tell us, right? I think we do not quite know yet. There's a compelling case to be made for neurodegeneration. There's a very compelling case to be made for obesity. The answer, of course, might be more than one, right? I mean, I think we're seeing surprising benefits with the GLP-1s, for example, right? Novo is running a big Alzheimer's trial. There are different benefits beyond the weight loss. I think that NLRP3 is one of those targets that has multiple effects that could be promising for different diseases. I'm unbiased. I'm the son of an immunologist. This is an I&I target, right? We've seen those class of drugs be implicated in many, many different disease types for single agents. This has the possibility of working in multiple areas. I think the field is having data drive those decisions. Any comment on the Lilly R&D Agreement? Oh, sure. Yeah, I didn't comment on that. That one's a little bit different than the Novartis collaboration. The goal with the Lilly collaboration is really to continue to bring forward exciting targets at BioAge. Here, it's a case of where we found a couple of exciting new targets from our data platform. We're collaborating with Lilly, where they're building antibodies against those targets. It's really leveraging their expertise and building drugs. Who else is in the space outside of Ventyx and Nodthera with regard to the? There's a lot of earlier programs. There's Eventus. We used to confuse those two all the time. There's a couple others that I'm forgetting. There's a spin-out of a company. There's a spin-out of company. There's a spin-out of Denali called Tenvie? Yes. Tenvie that we don't know how, we don't know what stage they're at. It's unclear. It's not their lead compound. Presumably, given the Denali history, it'll be used for neurologic indications. Great. Anything you want to highlight that we didn't talk about or just regarding kind of the outlook for this upcoming readout? We probably covered the big stuff. Anything else, Dov? No. No. Thank you. Great. Thank you. Thank you so much. Thank you. Thank you.