All right. Welcome, everyone, to Jefferies 2026 Global Healthcare Conference. My name is Roger Song, Senior Analyst covers SMID-Cap B iotech. It is my pleasure to have the fireside chat with BioAge Labs. We have CBO, BJ, and the CFO, Dov, here. Welcome, gentlemen.
Thank you for having us.
Thank you for having us.
Awesome. Maybe BJ or Dov, you want to give a couple minutes overview of BioAge. It's a very exciting time, so you have a lot going on, coming, and then give us some state of affairs, and then we'll have a conversation.
Sure. Sounds good. We are BioAge Labs. We're a clinical-stage biotech company founded on just the thesis that we can interrogate human aging to identify drug targets for cardiometabolic disease in particular. Our lead program is BGE-102, which I'm sure we'll speak about at length today. It's a potential best-in-class NLRP3 inhibitor that we're developing for cardiovascular disease as well as ophthalmology. We recently reported our phase I results a few months ago. We are going to be reporting results from our cardiovascular risk phase II dose-ranging study end of this year, and we'll also be initiating a POC trial in DME in the middle of this year, which we'll read out in the middle of next year. In addition to our lead program, we're developing both oral and parenteral APJ agonists, which we view as a complement to incretin therapy.
Thank you, Roger, for having us.
Absolutely. Yes. You have a aging discovery platform, and then you have a couple pipeline is coming out of that platform. I believe today we're going to mostly talk about the NLRP3. Maybe CV and the ophthalmology disease as well. We just want to emphasize that you do have the other pipeline as well. Right. Okay. For NLRP3, I think the field has been evolved over the past couple of months. What happened there? NLRP3 from a multi-target or multi-disease area target become it's more prominent in the CV space, and then how BioAge is going to capitalize this?
Yes. There's been a lot of growing excitement in the NLRP3 space. I think one of the exciting catalysts last year was Ventyx reporting results from their three-month trial showing efficacy that was approaching that we see with the biologic injectable modalities. That catalyzed a lot of interest. Obviously, they were acquired by Lilly shortly thereafter. ZEUS, the Novo IL-6 program, has their ASCVD readout in the third quarter of this year. A lot of eyes are on that catalyst as well. We're very aggressively pursuing ASCVD. We reported our phase I results a few months ago, and as part of that, we included two cohorts of obese participants who had elevated CRP at baseline, so very similar patients to those that Ventyx studied in their trial.
In those patients, 60 mg, we treated for three weeks, 120 mg QD we treated for two weeks. There we observed what we believe to be best-in-class efficacy in terms of biomarker reduction. We saw an 86% reduction in hsCRP in both cohorts. Importantly, also, we saw a normalization rate of CRP to below two mgs per liter of 87% in the 60 mg cohort and 93% in the 120 mg cohort. This is really important because what we learned from the CANTOS trial of canakinumab in ASCVD is the headline MACE reduction in that trial was 15%. If you actually look at responders, those patients who achieved hsCRP below that two mgs per liter threshold actually had a 25% benefit, whereas those that didn't had essentially no benefit.
In terms of thinking about how these early phase I results connect to long-term potential cardiovascular outcomes, we were really buoyed by that data. In addition to that, looking at these, hsCRP was supported by concordant changes in IL-6 and fibrinogen, as well as sort of what we believe to be an exceptional tolerability profile, which is critical for this indication. Furthermore, I think as we think about the NLRP3 landscape, there's efficacy, there's tolerability, and then there's also dosing and administration. We're now looking at an oral once-daily dose range of 30 mg to 90 mg, which is commercially important to have a once-daily dose, and certainly provides flexibility and potential co-formulation, thinking long-term lifecycle management strategy. Across all those dimensions, we're feeling really great about our program following these phase I results.
Excellent. NLRP3 is high interest target for some time, and then with this, the recent acquisition and then also the CV data hs-CRP reduction, probably the interest level will even go higher. Maybe tell us how unique and/or differentiated from BGE-102, and in terms of how you designed the molecule, and then what's the property to make you feel the best-in-class signal you're seeing is real?
Yeah. In addition to the phase I results, we can sort of bring you back in time. We discovered this program internally. It's a homegrown program. We originally identified the hit through a DNA-encoded library, and so we were looking. We blocked the binding site that to our knowledge, all other programs target, which is the ATPase pocket. We were looking for novel binding site, and so we found this hit. We've sort of optimized the molecule over several years. I think, in our detailed characterization of the structural biology, this binding site is actually accessible in all conformations, so both the inactive form as well as the active inflammasome. That may help explain both the rapid onset of action.
We're seeing hs-CRP reductions profound by day seven of treatment, as well as the magnitude or the depth of the biomarker reductions that we're observing in our clinical trial.
Got it. Okay. You give us phase I data. Now you are running the phase II and try to give a bit longer-term data and across different doses. What is the base case here? We see pretty rapid reduction for the hsCRP along with many other biomarkers. You are already pretty deep, and we don't expect you need to be even further. Durability wise, is that a kind of base case you'll be sustained kind of reduction to that end?
Yeah. That's our expectation. I think what was really interesting about the Ventyx data, again, is that they showed essentially their maximum biomarker reduction within the first couple of weeks of treatment. That's actually why we added those obese, inflamed cohorts to our phase I trial because we thought that we could actually get a lot of the answer early, and that it would be sustained with chronic treatment. We were initiating this dose-ranging phase II trial that'll read out by the end of the year. This is going to be three months of treatment.
One of the goals, the key goal is to show a stable reduction in these inflammatory biomarkers and sort of extending the results from the phase I trial both in terms of biomarkers, safety tolerability, and of course, we'll be adding incremental assessments that are only feasible with this longer treatment duration. For example, we'll be looking at MRI imaging of the liver fat content, liver inflammation. This is another area where Ventyx saw a meaningful signal in their three-month trial, and so we'll be hoping to recapitulate the same.
Okay, good. We're going to see a bit more kind of efficacy endpoints.
Yeah. Maybe an important point, too. The dose ranging here, we're exploring three doses. We're looking at 30 mg, 60 mg, and 90 mgs QD. 90 mg essentially gives us what we expect to be about 98% inhibition of the target. If you need complete inhibition of NLRP3 to get your maximal biomarker response, we think we can deliver that.
We'll be exploring 60 mg and 30 mgs as well. Based on our modeling, we expect 30 mg will give us a suboptimal biomarker response. This is really important because time is such an important value driver for this program, so we want to end the year with confident in dose selection for a potential phase III trial starting next year. As we think about the profile we have in hand, given the phase I results, we want to do these enabling activities. We expanded the study to do dose ranging. We've initiated CMC to support a phase III start next year. We want to be addressing some of these long lead time items and making sure that we're doing all of the enabling work.
Got it. Okay, good. In terms of the safety side or tolerability side, we learn from the old days from IL-1, so you see some infection risk there. That's why they haven't really gone to the forward or move forward into the cardiovascular space. The IL-6 so far is fine. At least from the Novo, they are doing the IL-6, and then they're running a large kind of main study. How are you confident about the NLRP3 safety database, and then what are key evidence to support the long-term safety for NLRP3 target?
Yeah. It's a great question. There was a small but significant increase in infections in the CANTOS trials. This was with an IL-1β neutralizing antibody. This is something we'll be looking at, of course, in the ZEUS trial. I think inflammasome inhibition is fundamentally different from cytokine neutralization. If you think about NLRP3 being sort of the key sensor of sterile inflammation and triggering this cytokine cascade of IL-1β, IL-6, ultimately CRP. When you neutralize a cytokine like IL-1β or IL-6, you do have the potential of just knocking out that node in the inflammatory pathway. Whereas, with inflammasomes, there are redundant inflammasomes. NLRP3 is the predominant sensor of sort of sterile inflammation triggers. There are a number of other inflammasomes that are not targeted by our drug and by selective NLRP3 inhibitors.
In the context of a pathogen response can certainly help mount an infection, and you have all of the downstream machinery still in place. There are certainly strong theoretical reasons why this sort of different strategy may be advantageous in that context.
From clinical perspective, how much NLRP3 inhibition we have known for the long-term safety? I know you haven't done that. Many of the other NLRP3 company haven't done that. Any like those long-term safety we should give the people a little bit more kind of comfort?
Yes. I think Ventyx to date has the largest safety database with their three-month trial, where there didn't seem to be any on-target safety or tolerability issues. NodThera will have two readouts this year as well that'll build on that. We'll be looking for evolution in this space. Thinking about our molecule in the phase I results that we had an exceptional tolerability profile, and certainly AEs as well as looking carefully at clinical chemistries and just saw no adverse changes of any kind. When we think about that, when we think about the 50x-100x safety margin we have based on our three-month GLP tox to date, we feel really good about the safety tolerability profile of the molecule.
Got it. Okay. One of the component of your compound is brain-penetrant. Understand this is not CNS indication, but how much it will help the overall profile, even you're going after the cardiovascular disease?
Yeah. One of the differentiators of BGE-102 is it does have exceptional CNS penetration. We showed a Kp,uu,CSF of 0.7 i n our phase I trial. What that enables is us to address the broad range of diseases driven by NLRP3. There may be benefits even if you're talking about things, the indications that appear on the surface to be peripheral. For example, ASCVD.
Neuroinflammation is thought to be the result of even psychological cognitive stress, right? That triggers a beta-adrenergic response that promotes peripheral inflammation. Even in something that appears peripheral on the surface, having CNS exposure may actually, even when you're solving for the peripheral sort of inflammatory biomarker, may actually be advantageous.
Okay. That's interesting. Okay, good. All right. I think all eyes is on the ZEUS, and particularly related to the NLRP3 IL-1, IL-6. We know we have quite a few acquisition happen, in the NLRP3 and then also IL-6. What is your base case for ZEUS? What would the MACE reduction considered to be validating, very good for the space, and then what would be, you think it's either worse or more bullish case?
Yeah, no, all eyes on that trial, for sure. I think we remain cautiously optimistic about that. Any significant MACE reduction, I think, is going to be really exciting for us, and I think validates the overall thesis that you can target this inflammatory axis and have that result in meaningful MACE benefits. I think we'll be looking at the headline number as well as what's the relationship between inflammatory biomarkers and those patients that benefit the most. I think CANTOS certainly provided rich substrate for subgroup analyses and really understanding those relationships. We'll be looking to ZEUS for the same.
Yeah. By the way, ZEUS is IL-6. It's not necessarily direct to NLRP3. You just mentioned you have a few other biomarkers also beneficial, right? When we look at, let's say MACE 15%, that seems to be the bar usually for the cardiovascular benefit. If they get to 15, that's certainly validating this class. Would you say NLRP3 with a slightly different kind of approach, maybe you can get higher MACE reduction?
There's certainly that possibility. I think the way we look at it, what excites us about this program is in our phase I, we're achieving reductions in CRP that are essentially on par with what the ziltivekimab dose showed, the dose that was carried into the ZEUS trial. On that just sort of raw anti-inflammatory horsepower on that central axis, we feel like it's quite comparable. There are also aspects of NLRP3 biology that are not captured by IL-6 that are independent. For example, NLRP3 also regulates the cytokine IL-18.
That in CANTOS was shown to independently predict MACE in that trial, baseline levels. There are Mendelian randomization or human genetic signals that support a causal role in ASCVD. There's the sort of pyroptotic inflammatory cell death that NLRP3 regulates that there's work to support that may contribute to plaque destabilization as well. There's a lot of NLRP3 biology that overlaps with IL-6, but by going upstream, we're able to address incremental biology as well.
Okay. Very good. All right. Just like you said, if the top line hits, great. We can go into the details later. If a top line, for some reason, didn't get to the level people want to see, still you have a chance to look at the details and then see, okay, how this will translate to NLRP3. That's a little bit more nuanced, but I think that's probably the scenario you also want to do.
Yeah. No, of course, we're going to be looking far beyond the headline number.
Yeah. Okay. All right. In terms of your clinical strategy, you are running phase II, that's a 12 weeks, three months trial, you're going to read out maybe after ZEUS. It will be very interesting. By the way, what's the timing of that? When that data read out, along with ZEUS, I think the timing should be pretty close. What's next?
Yeah, we were anticipating and guiding two results from the phase II dose-ranging trial by the end of this year.
We're expecting ZEUS results in the third quarter of this year. I think our position will be materially advanced, hopefully, by end of year given these internal and external catalysts. What comes next? We are, I think, at end of phase II meeting, and really revving the engines for a phase III trial. We're targeting enablement for a start next year. It would be full speed ahead on ASCVD, and we're also working on ophthalmology, of course. We have a POC trial in DME that we're initiating in the middle of this year, and we're guiding to data for that in the middle of next year. That's a totally orthogonal indication area that we're really excited about.
Yeah. No, we will touch on the ophthalmology, DME, for sure. In terms of ASCVD, obviously you're open for any kind of a partnership or any potential BD situation. If that's in parallel, you also committed to do on your own, then what will be the next kind of trial look like if you go by yourself, like a MACE or a certain subpopulation, and how you think about this as of now?
Yeah. I think in terms of a trial perspective, the base case would be a MACE trial, right? This is an enormous clinical opportunity. We think an oral, well-tolerated, once a day anti-inflammatory could be the next statin. This is a major risk factor that's currently unaddressed. To unlock that opportunity requires an outcomes trial. What that could look like? It could look more like the ZEUS trial on one end. It could look more like the NewAmsterdam Pharma PREVAIL trial, where you're looking broadly at the secondary prevention setting with elevated CRP as sort of the key eligibility criteria as a biomarker. We're looking at the full range of possibilities at this point. Dov, I don't know if you want to speak to add anything there.
Yeah. One of the questions that was raised by investors this week was, go it alone or go it with a partner?
Yeah.
Which is obviously an important question, and the short answer there, Roger, is we have to be prepared to go it alone and go fast. We're already making investments in things like CMC for the MACE study today. Those are longer lead time items, not huge capital commitments, but gets us in a position to start that trial at the end of 2027. Then as well as financial resources, we're very well-funded to date, about $385 million at the end of the first quarter, which gets us a long way there in funding a potential MACE study. This will eventually go to a big company in a commercial setting. Quite frankly, it may be advantageous if the right deal is struck for it to go in the clinical stage and for them to run the MACE study.
We need to be prepared to do it on our own, we feel.
Yeah. No, honestly, you have to run the company not just a beautiful sale, but on the other side is it makes a lot of sense for big partner to take on this kind of a massive MACE, particularly if they have the capital to run multiple trial in parallel. That's always maximize the value here.
Yeah.
On the other side, you do have the DME and then ophthalmology. I think that's a very smart strategy because we know NLRP3 or hsCRP, IL-6, SHP works in many other different indications. This DME ophthalmology, is that something you think BioAge as a biotech company potentially can take this a little bit further and then maybe even towards the approval, if you launch it?
We're very excited about ophthalmology. I think it takes advantage of, again, the ability of the molecule to access these privileged compartments. We get really nice CSF exposure in our trial. We see therapeutic retinal exposures across preclinical species, so rodents, rabbits, NHPs. I think the ability to target the inflammasome specifically and inflammatory drivers generally with an oral is a huge opportunity across a range of indications. We're prioritizing DME as our POC for a variety of reasons. One, the IL-6 drugs have shown a benefit here. I think specifically vamikibart recently released monotherapy data at ARVO. They saw a nice monotherapy effect. They've previously shown incremental benefit on top of VEGF. At a high-l evel, it shows that selective anti-inflammatory strategies can be efficacious in this setting. They also showed the maximum efficacy at around two months of treatment.
This enables us to, sort of within a relatively short treatment period, ideally demonstrate proof of concept. The trial that we're running is going to be three arms. It's going to be BGE-102 monotherapy, VEGF monotherapy, and then VEGF plus 102.
We'll be able to look at the pharmacodynamic effects in both of those treatment settings. The goal of this study is really to show a clear PD in the eye. We want to show that the drug gets there and hits its target in the eye as sort of a way to stage gate further work in ophthalmology. Our primary endpoint is intraocular IL-6. We'll be doing aqueous taps on these patients, so removing the aqueous humor. We can look at biomarkers there as sort of the primary outcome of the trial. We'll be doing a variety of functional assessments like BCVA. We'll be doing OCT imaging, so we'll be able to look at CST and other anatomical endpoints.
We'll be looking at the totality of the data here to show a clear pharmacodynamic effect and ideally trends, at least in some of these clinical and anatomical endpoints that are concordant with biomarker reductions. That's the setup of that trial. I think we do think IL-6, that data is at a high- level of de-risking, but the biology, it's not one for one. I think thinking of this as an oral IL-6 is simplistic. Especially in this context, we're going upstream also enables you to capture biology that's of IL-1β, for example, that's independent of IL-6, so that directly induces VEGF. Activation of NLRP3 in endothelial cells actually causes degradation of the microvasculature in the retina, and so there are aspects of NLRP3 biology that are not captured by IL-6 that we think are really exciting here.
Makes sense. The one thing I want to emphasize is your brain penetrant is the best among all the NLRP3, the retinal penetration is nearly one-to-one, which means you also is highest penetration into the retina. The ophthalmology may makes you also best-in-class among the NLRP3.
Yeah. We're really excited about our differentiation here and ability to address a range of indications where NLRP3, we think, plays a major role, and that includes DME. Another indication of high priority for us is geographic atrophy. Those are the terminal stage of dry AMD, where the disease is characterized by the accumulation of this cellular debris that is highly pro-inflammatory, and there's a lot of nice preclinical work and some important clinical work showing that if you block NLRP3, you may have a very meaningful impact in slowing the growth of lesions that cause central blindness.
Got it. Your benchmark, obviously, you have the standard of care, but also a couple IL-6 drugs is in the indication. That's also you want to make sure you're at least comparable, if not better than the IL-6.
Yeah. IL-6 is being developed in DME, especially IL-6 VEGF bispecifics. We see a few interesting segments where BGE-102 could play really well here. There's the 40% of patients who are in the watch and wait category, where they have edema, but they don't have sufficient compromise of visual acuity to initiate intravitreal therapy. If you can treat those patients and delay that, these intravitreal therapies are a huge patient burden, and as a result, there's a major disconnect between what's shown in trials and what's shown in the real world in terms of disease control. That's one highly addressable patient segment where you're really not competing with VEGFs. You're trying to delay initiation. On the opposite side of the patient journey here, patients who are on VEGFs but are refractory and have imperfect disease control with VEGF alone.
This is another group where initiating BGE-102 on top of VEGF could be highly effective. Those are the priority segments and positioning for us right now.
Makes sense. Okay. I think I went through quite a lot of things here and then touched both CVD and then the ophthalmology. Anything else you want to discuss, highlight to people before we wrap up?
Yeah. I would just touch on we are developing, again, we have two APJ agonist programs, an oral small molecule and a sub-Q. This is a target that we're really excited about in our platform. It's a target that is among the most highly associated with not only longevity, but preservation of physical function. It's a target where we've previously shown really nice preservation of muscle size and quality in a bed rest situation, and we think that there's a lot of potential for interesting incretin combinations in obesity to increase both the quantity and the quality of weight loss. We're guiding to filing our first IND here by end of year.
I have one more question for you, and maybe the last one. Your NLRP3 initially is also just like a Ventyx, thinking about the obesity space as well. In preclinical, you're probably the only one show the weight loss compared to other NLRP3. I know this is a two-week study. You're not supposed to show anything, and we're going to see your poster at the ADA. I don't expect you will see the weight loss there. When the 12-week study with Thumberin Richmond on the hsCRP, how likely we're going to see some weight loss signal there? That would be the huge upside if you can show this.
Yeah. It would be a surprise upside. Our view is that the likelihood is low, and that there's a translational gap here, given Ventyx showed nothing on that front. The three-month study will be powered for that, and it will be sufficient duration of therapy. If for whatever reason there was something idiosyncratic about that molecule, we'll have ou data there by end of year.
What's the BMI cutoff for the phase I, phase II?
It'll be patients with BMIs between 32 and 42.
Okay. It's potential. Okay. Got it. All righty. Thank you so much, BJ, and then thank you, everyone.
Thanks, Roger. Thank you for having us.
Thank you.