Good afternoon, everyone. Welcome to our 37th Healthcare Conference at Piper Sandler. My name is Yaz Rahimi. I'm a Senior Biotech Analyst at Piper Sandler, and really thrilled to have BioAge Labs with us. Kristen, it's wonderful to have you. Thank you for taking time out of your busy schedule. I have lots of questions for you, but I think a great place to start off is congrats on the exciting data this morning presented.
Thank you.
So, for investors who were trapped in meetings all day, give us a recap of the data that you presented this morning?
Yeah, for sure. So we were happy to do, really excited to put out a press release on some of the first clinical results from our homegrown brain-penetrant NLRP3 inhibitor this morning. So I don't know if I should go into the high points now, or that's better done in context, but we released data on SAD cohorts and a couple of MAD cohorts, showing really everything we were hoping to show in the initial release for this compound. That 60 mg once a day gave us IC90 target coverage in the brain and the periphery. If we went higher to 120 mg, we could actually completely shut off the target, IL-1 beta, which is really interesting, safe and well tolerated to date. Yeah, really exciting data set for us.
Wonderful. And we're going to talk more about it, but maybe a great place to start is 102, which is a CNS penetrant. Help us think about how you're thinking about overall positioning of CNS penetrant and NLRP3 inflammasome inhibitor for obesity and cardiometabolic diseases. And do you envision this biology as a standalone monotherapy, or is it dual or combination therapy?
Yeah, that's a great question. Really post the Ventyx readout in October, where we're thinking firmly of obesity as upside now, it's not something that's the primary endpoint anymore, right? So instead, our POC next year will focus on it'll still be the same population, very similar to the population that Ventyx used, obese individuals with elevated cardiovascular risk factors. But the primary endpoint will be CRP reduction, because really we think in the wake of the Tourmaline acquisition, the focus on profound CRP reductions and their relevance to ASCVD, that's how we can create a lot of value for the drug. So obesity, if there is a change, we'll see it. We'll still have power to capture that as a monotherapy in the three-month trial that we're going to read out about a year from today.
But really, it's going to be more focused around cardiovascular risk factors today.
Okay. And do you think we need a CNS penetrant asset to drive brain penetration in these cardiometabolic diseases, or is it more the inflammasome systemically driven that you really don't need activity in the brain to achieve benefit?
Yeah, that's a great question. And probably for something like CRP reduction, there's no reason you would need brain penetration, right? I mean, we've seen antibodies that are peripheral have similar comparable levels of CRP reduction. What you do need, though, is potency, right? And looking at the landscape of NLRP3 inhibitors out there today, CNS and peripheral, a lot of the peripheral ones are sort of earlier generations. They are five to 10-fold less potent than our compound and the Ventyx compound. And that's likely why there's this potential for enhanced CRP reduction beyond what's been observed with the peripherally restricted NLRP3s.
Okay.
I do want to point out, though, that even if not for CRP, obese individuals who are inflamed, there are eye and brain comorbidities that are relevant to inflammasome biology. Not for that endpoint in particular, but there still could be other benefits in those populations.
Okay. How do you think about? You noted too, obviously we're going to talk about in a second about the obese population with elevated CRP reduction, which is another sort of a great POC study, but then post that you have a very robust roster of indications to pick from, and you alluded to beyond cardiovascular and metabolic potential indications that would require CNS penetrants like neurodegenerative diseases, ocular diseases. So how do you, at BioAge and the team, decide prioritization of which indications you would move an inflammasome inhibitor?
Yeah, that's a really great question. And of course, we're really investing more into the program with the recent readouts, with the recent excitement around the target and with our clinical data. So our intent is, we've already communicated we're going to be doing this CRP reduction study. We're not going to run a MACE trial after that, right? That's not something that we can go it alone as a small biotech company. And to your point, there's a lot of other promising indications for the inflammasome, many of them that have already been de-risked with human data, whether it's with IL-6 or an IL-1 beta inhibitor. So our intent is at some point to communicate another indication where we will gather some initial clinical data next year, so not too far away, which is an indication where we as a small company could go it alone through phase III.
That's the goal. And it also takes advantage of some of the more unique properties of our molecule. So our drug gets really well into the brain. It also, this might be unique, gets really well into the retina. And there's some very nice human POC data with, well, phase III data really, even with IL-6 and some types of uveitis, for example, right? So there's a few indications to choose from. Yeah. And once we have a plan, that's at that point, we'll roll it out when it's more fulfilled.
Got it. A lot of times we get questions. I think a lot of investors understand now the breadth of developing inflammasome inhibitors for a broad range of indication across almost any therapeutic area. That they understand. They also understand that it's going to require a number of assets to advance such a broad opportunity. But the question that they don't ever know the answer is, how does each of the different NLRP3 molecules that you, Ventyx, and others are developing differentiate from one another? Not that we need one drug to hit all indications, but help us understand how you think about differentiation of these assets.
Yeah, for sure. So there's a few points of differentiation with our assets. I should say too, we published three papers on our mechanism, on our binding site. So we do have a novel binding site to NLRP3, which has really enabled novel chemistry for us, which has led us to our potential best-in-class potent molecules and most of our best-in-class brain penetrant molecules. We actually published the crystal structure over the summer. And some of the theoretical potential advantages there are that this could block both the active and inactive forms of NLRP3. And in fact, in one of the papers that we published, we showed that certain CAPS mutations, NLRP3 mutations that were not inhibited by MCC950 were, in fact, inhibited by our drug. So there are some mechanistic differences there that are potentially of interest.
Then if you look at the landscape of what gets really well into the brain and is in the clinic today, there's really only three programs, right? There's us, Ventyx, and NodThera. NodThera is likely a twice-a-day. So it's different from a dosing perspective, right? I think we're going to see growth in this area. I know there's some preclinical programs coming along, but there's not that many today with those attributes.
Okay. Perfect. And then, Kristen, now, so at the time that you're going to announce the obese patient with elevated CRP, will that be also the same time of the opportunity to think about what are the indications you're pursuing, or is it these are two isolated disclosures?
Yeah, it'll be when we're ready. Actually, I forgot to say one of the other key announcements we made in the press release, right? Because the other one is that we're going to be doing a couple of obese MAD cohorts as part of the phase I. We think this is really exciting because what the Ventyx data showed was that you could have these profound CRP reductions get their maximal effect after only a week, really, right? So we are going to be doing two different MAD cohorts, obese individuals with elevated CRP levels, and that's going to read out in the first half of next year. So that's actually the first data coming along, and then, of course, some of these other really interesting biomarkers really unfold over a longer time scale.
And so the three-month monotherapy look will look at a broader set of biomarkers in a larger population, but we now expect to have that sort of CRP information pretty soon.
Yeah. Okay. Perfect. And then obviously, today with the initial SAD data, the full SAD/MAD cohort is expected mid-2026. So maybe just kind of contrast sort of today with the SAD and two MAD cohorts today.
Two MAD cohorts, yes. That's right.
What were the doses you disclosed? What will the mid-2026 readout include?
Yeah. So what we've done so far is everything we've done in healthy volunteers, which is a full sort of SAD dose ranging up to 120 mg, and two MAD cohorts in healthy volunteers only. One at 60 mg per day, one at 120 mg per day. And as we showed, the 60 milligrams once a day was already achieving over IC90 for the target in both the periphery and in terms of the CSF levels. And the 120 was actually completely shutting off IL-1 beta in the ex vivo assay, which we thought was really interesting. Another potential point of differentiation that we can dose to the level where you're not just heavily suppressing, but really just switching that off for at least the IL-1 beta that you can ascribe to NLRP3, right? So that's sort of the healthy portion of the phase I is done now.
What we're going to be doing is two additional cohorts. I should mention too, so this isn't in our press release, but it's in our corporate presentation, right? Most of these people so far have not had elevated CRP. They were healthy. There were a handful of people who did. There were, in fact, a grand total of three people, so very small.
These are healthy volunteers that somehow have elevated CRP levels.
Yes, that we got lucky.
Elevated.
Above two, right? So we had to have that threshold. But in the two different MAD cohorts we did, there were three individuals, and they experienced an average of 79.5% reduction in their CRP, right? So they're very early, but promising.
What are we, like 0.2 or something? Normal?
Below two. But yeah, usually below one even, right? So yeah, exactly. Two is the typical threshold. But what we're going to do now is have a whole population of people like that, right? Where they're obese, BMI 32 and above, CRP above three, right? And then look at what happens over the course of a couple of weeks of treatment with a 120 mg dose that completely shuts off IL-1 beta. And then we have to choose the second dose. We're either going to choose the IC90 or a lower dose that also totally shuts it off. That's still TBD.
Okay, and that's separate from your 12-week study that is.
Correct. Yeah. This is basically ongoing now, and we'll read out in the first half of next year. Yeah, and could inform release the three-month study.
Given the safety profile, what is the rationale for going higher beyond 120 in this process?
Oh, there's no reason you'd want to go beyond 120. There's no reason to go beyond 100, actually. We should be able to show a completely shut-off IL-1 beta, even at lower doses.
Okay. And that's coming out, so that's great. So concurrently, you also are running a 12-week study, right?
This will be more sort of starting in the middle towards the middle of next year.
I see. Got it.
Once the phase I is complete.
Okay. Then you would be actually thinking about a longer duration.
The three-month one.
The three-month. And this would be how do you think about what is the current tox package for 102?
Yeah, the tox package is great, so from the chronic tox studies, we have margins of over a 40-fold, actually, at the 60 milligram dose, 40-fold to 80-fold, depending on the different tox species, and we cleared our highest dose, so there was no dose-limiting toxicity in the work we've done to date, and the AEs we've done, we haven't locked the database yet, but all the AEs we've seen in everybody have been mild to moderate, nothing of concern.
So the thought process is, let's see, in this particular longer duration study at the highest dose, what you're getting in this population that you would be studying for 12 weeks before then embarking sort of on the design of a 12-week.
The two-week means?
Yeah, the obese population. And when you go to that obese population with high risk, such as high CRP, I assume that would be greater than two. Would you want to do similar to Ventyx, sort of like testing monotherapy as well as combination with it? Because I think the key finding here is that there's definitely an additive effect of the mechanism when it's combined with current GLP-1. So would love to talk about how you're thinking about that.
I think that's a great question. I mean, looking at their dataset, we saw, for example, very nice additivity with the liver marker, right? Where it was sort of like a very straightforward additivity, right? Like one plus the other. So we're actually planning to focus just on the monotherapy. We think that's the most unknown, right, and then similarly, most of those effects should be similar in how they combine with the incretin.
Yeah. Perfect. So in terms of sort of the cadence of disclosures, then if I can summarize, it's going to be like the additional MAD cohort from disease patients and obese patients sometimes in the first half of this year and next year. And then you will be communicating, kicking off your 12-week study in obese patients. And then at the same time, sometime in 2026, you'll come back and help us understand sort of what are the indication selection that you're pursuing for 102. But it seems like you are interested broadly in metabolic diseases, right? Or maybe ocular diseases given this high brain penetration that you're seeing in neurodegenerative, which is also an opportunity, right? Is that sort of a fair way to?
Yeah, I think that's very fair, right? So the first half of the year, we're going to get a couple of important things. We're going to get that initial CRP readout, how much can we reduce it in a couple of weeks. And we'll be able to sort of guide more to our indication strategy, right? And then second half of the year, we'll have that very meaningful, sort of more wholesome dataset of three-month exposure with a lot of different biomarkers that are relevant more broadly.
Got it. Perfect. And what if the company is like your current cash runway, and kind of getting you to some of these important inflection points?
Yeah, we've guided in our most recent quarterly update to around $300 million cash balance and runway of around three years, right? So that includes the studies we discussed. That also includes for our APJ programs, taking them through phase I. Of course, we did just discuss adding additional indication. So that would bring in the runway, but we're comfortable from where we stand today.
Are you interested in how far along? One of the things we're learning too is that it's important to have a portfolio of NLRP3 therapies because drugs are available, so given you can build an entire pipeline. Where is the status of the second follow-on compound when it comes in terms of versus 102? Like how far behind are they? How soon could you file an IND?
Because of the multi-indication potential, this is something we're definitely investing in. We have another brain penetrant compound that is pretty close behind this first one, and then our peripheral, we also have ones that are purely peripherally restricted, which we were deprioritizing, but they were at an earlier stage, like incredibly potent though, right? Which is still an unmet need in the NLRP3 space, so those are all going to be resourced.
What are the capabilities that led to the discovery really rapidly of this entire portfolio?
Yeah. I mean, we have been working on it for a few years, I guess. As you know, until these things hit the clinic, they're sort of a bit more below the radar. But we did publish three papers over the past couple of years sort of outlining the discovery process. We actually got our initial hits from doing a DNA encoded library screen. So we worked with HitGen, a great company in China. It's one of these things where they immobilize the protein. They use literally billions of molecules. We got to some very novel compounds, very different chemistries. And then we worked together with Matthias Geyer at the University of Bonn, who's the NLRP3 structural biology expert. And he showed that they were binding somewhere new, right? And then we optimized those compounds. So it's been a discovery process, all homegrown.
Wow. That's pretty. What is the ultimate strategy? Is the thought process to really get these agents to full development on your own? Are you thinking to take 102 on your own and build a pipeline and maybe partner some of the additional assets that could give you guys further non-dilutive capital access and runway?
Yeah. As you touched on earlier, it's very indication dependent, right? Like ASCVD is very much necessarily a partnered indication. We don't have, I mean, some companies are bold enough to, but yeah, that would be likely to be the way to get the most value the most rapidly in that situation, right? There's a lot of pharma, for example, also interested in Alzheimer's disease and the inflammasome in Alzheimer's. And again, that's not really an indication for us. But that said, it's very important to us to also have some indications and assets that we do own and can bring through phase III.
Is RP one of the indications that is on your list?
We're investigating a whole bucket of things right now, so yeah.
Kristen, it's wonderful to have you at our conference. Really, it's just been a whirlwind of a year, right? of a lot of setbacks, but successes. Really, really remarkable to see sort of the transition of the company very quickly. So very much looking forward to 2026. And thank you so much for being part of our conference.
Thanks for having me.
Big congrats and applause to Kristen.
I think I already did great.