BioAge Labs, Inc. (BIOA) Earnings Call Transcript & Summary

Good morning. I'm Sam Semenkow, one of the senior biotech analysts here at Citi, and it is my pleasure to be hosting BioAge at Citi's 2026 Biopharma Back to School Summit. I'm joined by Kristen Fortney, CEO; and Dov Goldstein, CFO of BioAge. Kristen and Dov, thank you so much for being here, and welcome.

Thanks, Sam. Great to be here.

Thank you.

So why don't we just start off? It's been an eventful year for BioAge. I think we started off with a lot of highs for NLRP3. And recently, we've had some news. So why don't we just start broadly like level setting on the NLRP landscape and also where BioAge sits today?

Yes, for sure. No, as you said, it's been a super eventful year for us and for the target. So year started in January. We were in the middle of our Phase I. We published the full -- Am I not on? Do I need that for the webcast?

Is that better? Okay. Cool.

Yes, when we started the year, we were in the middle of Phase I with BGE-102, our lead program. In April, we released the full data set showing we have a potential best-in-class inhibitor with, again, potential best-in-class brain penetration, full suppression of IL-1 beta and also CRP results, which is relevant to multiple different indications. And then we started 2 different trials, one in obese inflamed population, a Phase II. And as we announced just yesterday, a Phase II in a diabetic macular edema trial. So we've got 2 parallel indications going on. So we're really excited about that. Of course, for the target, there was a setback a month ago, and I'm sure we'll talk about that. It's not a setback for the target, but the IL-6 setback and the way that people are thinking about cardiovascular outcomes trial in particular for this target is, of course, a riskier proposition, but there's still a lot of potential that we're excited about. And by the end of the year, too, we're still on track to file IND for apelin as well. So it's a good year for us.

Yes. So we're going to dive into all of that. So maybe we do start with the ASCVD opportunity. And just maybe just help us frame how we should be thinking about NLRP3 going forward given the IL-6 failure from ZEUS and then the 2 other studies that were halted for that particular asset as well. And I think one of the major questions is we thought that the translatability of maybe CRP reduction and IL-6 reduction would translate to a reduction in cardiovascular risk factors, and that didn't seem to be the case. So when we think about the landscape for NLRP3, where does that leave us? And how confident are we that this can be a target in ASCVD?

Yes, for sure. So of course, the ZEUS news from Novo just over a month ago, a huge disappointment, right? Really, really unfortunate to see that, especially for patients. And as you mentioned, right, Novo did indicate that they saw CRP reductions on par with what they are expecting. So we're assuming somewhere in the 80% range, but that failed to translate into MACE outcomes, at least in this patient population, right? So that's really unfortunate. And there's still 2 potential explanations for what's going on, and those won't be resolved really until we have additional data. There's, of course, hopefully more data from Novo coming in November and then the other trial that they have next year, the ARTEMIS trial will read out in the first half of next year. But the 2 explanations, as people are aware is that is it a target problem or is it a patient population problem? Because of course, the inflammation hypothesis is partly anchored by some very robust data in the CANTOS trial, where an IL-1 beta antibody drove very profound reductions in MACE. And as a function of CRP, the biomarker that you mentioned, right? So amongst those people who normalize their CRP, they saw a 25% MACE benefit, which is super meaningful to patients. So it was really disappointing to see a hazard ratio of basically 1 with IL-6, right? And the 2 things to be aware of that I think are being discussed right now is one that the ZEUS trial population was a lot sicker than the CANTOS patient population. So these people have profound kidney disease. There could be a lot of events that are not related to cardiovascular inflammation that could make it challenging for this mechanism to shine. And that's why everyone is still looking to the ARTEMIS trial reading out in the first half of next year, which is IL-6, but taken to a very CANTOS-like patient population. But the second explanation is that this might be the wrong target, right? We don't really know yet because again, what worked before was IL-1 beta, IL-6, while it reduces CRP, does not affect IL-1 beta at all, right? Of course, that's different for NLRP3, right? So IL-1 beta is already validated in this population. And the entire target engagement biomarker for NLRP3 is IL-1 beta, and we showed in our Phase I that doses of our drug could fully inhibit IL-1 beta. So there's still -- so it's really like quite a different proposition. But the unfortunate thing, right, is that CRP didn't mean what it used to before we were hoping -- even no one ever thought it was a causal biomarker, right? But we were hoping that across patient populations, lower CRP would mean improved MACE outcomes, and that's not true. It's not enough by itself. It might depend on the -- a combination of the biomarker with the patient population or with a particular target like IL-1 beta, but it's just more uncertain.

And you mentioned that you can get that full IL-1 beta with your drug. You've seen that in, I think, your Phase I healthy volunteers and your obese patients so far that you have data for. I mean how should we think -- so you're already reaching the max that you need to be CANTOS-like, but you get better safety on infection risk. How do you reconcile that?

Yes. So there's different pathways that can turn on IL-1 beta. And what you want in your ideal profile is you want to turn off the bad constant background inflammation that's turned up too high, which we believe is through NLRP3, but you still want to, if an infection comes along, be responsive to that infection because of course, CRP, the inflammatory response can be very useful, too. It's not like universally a bad actor. So what's nice about NLRP3 is that you're turning off the NLRP3-dependent IL-1 beta, but the rest of your -- there are parallel inflammasomes that should be responsive to infection. So there's a potential for a safety advantage over an IL-1 beta.

Great. Okay. And so then, I mean, we have the CANTOS data. We know that there was a stat sig MACE reduction. With an NLRP3 doing the same thing, like how -- what is your confidence then that NLRP3 could still work in ASCVD? And how do we move forward to get confident enough to run a large study that would be required to show it?

No, that's a great question, right? And part of the challenge here is just that it's large and long, like uniquely large and long, right? It's not one of those Phase IIs that you can run in a year for $20 million. It's $500 million of spend, 5-, 6-year massive outcomes trial. So I think strategics are openly still bullish on NLRP3, right, Novo, AstraZeneca. They say, "Well, we might have to go upstream, NLRP3 is promising." But it's a big bet to make, especially for biotech, right? But I mean, that really relates to the rest of the story and for our focus at BioAge because the focus, of course, has been on ASCVD for a few months because of this readout, we were also excited about. But this is not a target that is relevant to only one narrow disease indication, right? Like there are a whole number of different indications that are derisked with human either IL-1 beta or IL-6 depending on the indication. There's a lot of other places to take it. And I think that, that for us as a smaller company, we want to have -- we want to be ready, right, in case ARTEMIS reads positive, in case things shift in our favor for ASCVD to like move quickly, but that's really upside now, right? Like we really want to focus on these opportunities that we as a small biotech can move forward that are also really big and exciting.

Great. And we're definitely going to dive into the ophthalmology piece and beyond as well. But just really quickly before we go there, for the QUELL-CV study that's ongoing, we're going to have data before the end of the year. What can we take from that? What should we be looking for in that? Because it seems like more external factors are driving some of the next steps there. But mechanistically, I think there's probably something we can learn from the study. So what should we be looking for when the data reads out?

Yes, for sure. So QUELL-CV study, and we announced as part of our ocular press release yesterday that, that one is fully enrolled, on track for top line by end of the year. So as a reminder, that's actually not in a cardiovascular disease population. That's a lot broader than that. So it's really closer to our Phase I obese, inflamed cohort. So these are people who are overweight, who have elevated CRP. And that means that they're really helpful to look at a host of different markers that are relevant in a variety of different context, right? Like, for example, we're looking at liver inflammation with MRI because Ventyx saw some really promising data there, right? Like there's a whole host of other markers and diseases that are relevant in these patients. NLRP3 has relevance in other metabolic indications beyond the cardiovascular one. So I think we're going to learn about, frankly, all of those from the biomarkers that we look at in this patient population that's at risk for numerous different metabolic diseases. Cardiovascular is one of them and a big one, but not the only one. And importantly, too, it's going to be relevant for dose selection for really any peripheral indication we take forward, right? So as a brief reminder, in QUELL-CV, we're looking at 3 different doses of our drug, 30, 60 or 90 mgs once a day. And we're looking at every biomarker you can think of, which is cardio, of course, but it's a lot broader than that. But -- and as a reminder, too, right, in our -- the reason why we're doing these 3 dose levels is because in our Phase I data, we couldn't really distinguish between the 2 top doses, like 60 milligrams once a day might already sort of max out all the inflammatory biomarkers, and we're going to learn that from this study, and it will really let us bring us select a single dose that will then carry forward into our other indications -- other peripheral indications that we're excited about.

Got it. Okay. Well, looking forward to that and maybe some additional indications from that data set in the future. So okay. Maybe we spend a good bit of time then next on ophthalmology. As you said, you initiated or you announced that you dosed the first patient in the QUELL-DME trial. Just maybe you could level set for us, you're the only one that I'm aware of going into ophthalmology with NLRP3. Just what is the rationale here for this mechanism to work?

Yes, for sure. So this is a unique feature of our molecule, too, which is that as an oral agent, it penetrates the eye really well, right, which is -- can come along with brain penetration. The blood-brain barrier and the blood-retina barrier are not dissimilar. But we don't know if others are even positioned to go there should they choose to, but we're really excited [indiscernible] indication is that there is already human derisking data with IL-6. So unlike in cardiovascular disease, IL-6 significantly improves what is the approvable endpoint in that indication, like it improves BCVA and Roche and Kodiak have bispecific programs with VEGF and with IL-6 they're taking forward. And we really see as IL-6 is more of a potential floor when you think about all the things that NLRP3 is doing. It has the potential additionally to suppress pyroptosis, to have other addition -- there's even, I think, a VEGF drying effect preclinically. So we can see full correction basically of the DME deficits in preclinical models. So we're really excited to bring that to patients. And of course, that's even ignoring the fact that this is a pill, right? Like typically, these patients -- it's an injection into your eye. So they don't even start treatment until they're quite severe because patients don't want an injection into their eye. So there's that whole sort of early patient population that isn't addressed at all. There's a number of them that aren't VEGF responders as well, right, where another mechanism can make sense. So we're really excited about the potential there. And as a final point, too, I'll mention that DME happens in the context of diabetes, right? And preclinically, there's evidence that NLRP3 inhibitors can have numerous benefits in diabetic animals. We're waiting for more data from NodThera to see what they saw in patients as well. But -- so the body is not just like a convenient way to get to your eyes -- there could be benefits there as well in the diabetes that is really driving the DME.

Are you looking for that in the study, the more systemic effects?

I look at peripheral biomarkers as well, yes.

Okay. And does that include, I guess, glucose tolerance and things like those?

No, all the usual just biomarkers, not like specific sort of challenge tests of biomarkers.

Yes. Okay. So you'll get, I guess, early feel for potentially what impact you could have in a broad diabetic population.

Yes, additional benefits that could be relevant to the eye as well.

Yes. And then going back to IL-6 in the eye, when you talked about the validation that we've seen from there. When you think about the IL-6 reduction you get from BGE-102, is that on par with the dedicated agents? Or is it like a little bit less of an IL-6 reduction plus some other benefits of -- like how do you delineate like the IL-6 specific effects of 102 versus some of the other effects that it's possibly having?

Yes, for sure. So basically, our NLRP3 inhibitor like others reduces IL-6 by about 50% peripherally. We would expect a similar amount in the eye. That's about comparable to what we saw in the brain as well when you look in the CSF. So it's not like a full ablation of IL-6. But again, this is one of many inflammatory cytokines that are relevant in DME. So we think it's important to go upstream and hit all of those as opposed to like IL-6 being a special cytokine there.

And we've seen some difficulty in some of these trials with agents in combo with VEGFs trying to improve upon VEGF monotherapy. I guess how do you think about that dynamic? And what gives you confidence that NLRP3 inhibition in combo can perform better than VEGF monotherapy? I think we've all recognized that VEGF is a very effective target.

No, part of that is the data we've already discussed, right? Like there already is a significant improvement when you add IL-6 on top of VEGF. And then, of course, there's also this huge patient segment that doesn't get VEGF because they're not ready for eye injections yet, right, where a monotherapy oral that has a significant effect would be very meaningful. So both of those are exciting opportunities for us.

Is the study designed to test both combo and monotherapy for 102? Maybe just walk us a little bit through the design.

Yes, for sure. So this is -- as we announced when we -- the last time we spoke about this, we were probably thinking about it as a biomarker trial, right? So it's a true efficacy Phase II now, about 180 patients. There's patients who are getting our drug alone. There are patients who are getting VEGF alone and then there's patients getting the combination. So we're going to basically be able to learn about all of those in the same study. And the primary endpoint is BCVA, where we have good power to see a clinically meaningful difference.

And is this population on the more severe side, more typical DME population, not the earlier stage that you were alluding to as that's a potential future population?

Yes. It's a typical Phase II DME design. So it will include both naive patients as well as ones who've had experience with VEGF and who have washed out.

Okay. And so then -- yes, so I guess, what do you need to see just improvement on BCVA? I'm sure that there's a statistical -- and remind me how many letters do you generally have to gain to make a clinically meaningful.

[indiscernible] would be really... yes.

[indiscernible]?

And that's what's been shown with the IL-6 as well. Yes.

Okay. Got it. So if you have that in any of your monotherapy and/or combo arms, that's enough for you to want to move this forward?

That's right. That would be really exciting. So that data is going to come before the end of next year. We could potentially go into a pivotal trial after that, right? This is the clinically relevant endpoint. So that's going to be a really meaningful readout for us. And as a reminder, too, right, we see this as really the first ocular indication for 102. We're really excited as well about geographic atrophy. We went for DME first because we could see proof of concept faster. But we're also going to be looking at target engagement biomarkers in the eye and some exciting data there could support broadening to look at not just DME, but also GA, also MESI, right? There's a number of opportunities where inflammation plays a really important role in the disease.

And of course, it will be like totality of data as you're making those decisions. But let's call it one line on BCVA plus you're saying some biomarkers. Is there anything specific to GA that you are particularly watching that would give you confidence to move forward in GA?