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

Thank you. Whenever you are.

Hello everyone, and thanks for joining us at the Morgan Stanley Global Healthcare Conference. I'm Mike Goltz, one of the biotech analysts here. It's my pleasure to introduce the team from BioAge Labs. To my immediate left is BJ Sullivan. He's the Chief Strategy Officer. And to his left is Dov Goldstein, the CFO. But just as a reminder, you know, for today is a fireside chat, but if anyone in the audience has a question, please raise your hand and we can try and address it in our discussion. But before we get started, I just need to read a quick disclosure. For important disclosures, please see the Morgan Stanley Research Disclosure website at www.morganstanley.com/researchdisclosures. And questions, please reach out to your Morgan Stanley sales representative. With that, BJ and Dov, thanks for sharing your time with us today and maybe to kick things off, I'll just hand it over to BJ who can make some introductory comments, and then we can get into the Q&A.

Sounds great. Thank you for having us. So just to introduce the company briefly, BioAge is a platform biotech company. We apply the biology of human aging to identify targets for cardiometabolic disease. Our lead program is BGE-102. It's a potential best-in-class NLRP3 inhibitor. We shared data earlier this year from an extended Phase 1 that we ran where we were thrilled with the profile that emerged across several key dimensions. So one was the magnitude of biomarker reductions that we saw in obese, inflamed individuals. Two was sort of the dosing paradigm. With 60 milligrams, able to achieve 24 hours of IC90 coverage, and at 120, achieving essentially complete target inhibition at trough, 98%. The safety tolerability profile that we observed really, you know, we thought it was exceptional. And lastly, you know, one of the key differentiators of this molecule is its, you know, its ability tissue distribution and ability to access protected compartments like the CSF, as well as the retina, and so that certainly informed our indication strategy that we'll get into in a little bit so that's our our lead program we have two Phase 2s that are ongoing with BGE-102. So one is QUELL-CV which is a dose ranging trial in obese individuals with elevated inflammation and there we're going to be looking at, you know, cardiometabolic biomarkers, inflammatory biomarkers, teasing out a dose response, and building, you know, the safety database over an extended treatment duration, so over 3 months, and we'll have that top-line data at the end of this year. And we also recently dosed the first patient in our QUELL-DME trial. And so this is a trial looking at BGE-102 in diabetic macular edema, and it is similarly 3 months of treatment, you know, across 3 arms, so looking at BGE-102 as a monotherapy, as well as in combination with VEGF. And so there we, uh, we recently actually announced that we had, um, increased the size and the scope of the trial to power for best corrected visual acuity. And so this is now, you know, we're now looking at that as the primary endpoint, visual acuity, with 90% power to show a 4-letter improvement. And so that trial is now enrolling, and we're expecting data by the end of next year. So that's our BGE-102 program. We also, behind that, are developing a family of APJ agonists. And so this is, APJ is a target that was derived from our platform. It's one of the most strongly correlated with both longevity as well as preservation of physical function. We showed with a prior molecule, you know, very, very nice preservation of muscle integrity, you know, in bed rest and pre-clinically with APJ agonism we see, you know, a doubling of weight loss on top of a GLP-1 and complete restoration of lean body composition. And so, you know, we're developing both an oral small molecule as well as a parenteral APJ agonist with the goal of addressing both segments of the GLP-1 market.

Great. Thanks for that introduction. A lot to sort of dig into there, but maybe just start at a high level, maybe talk a little more about your platform, how it works. Also, maybe touch on your collaborations, too.

Yes. So our platform is sort of the central thesis of the company. So I think everyone's familiar with biobanking as a concept. It's, you know, taken off in, in, in recent decades. I think, you know, we're very focused on human aging and the key variable there is time. And so we partnered with some of the world's leading biobanks that have been, um, following patients for decades, starting from healthy middle age through in many cases death and then charting, you know, doing sort of detailed phenotyping along the way, you know, physical function, cognitive function, you know, and then doing serial sampling as well. So we can now go and follow samples, apply modern omics technology, and ask the question, what is the biology that's predictive of good outcomes, and vice versa, right? And that really informs a lot of our therapeutic hypotheses. Maybe just to touch on the collaboration. So on the platform side, we have a collaboration with Novartis. This is really around target discovery where we're looking at, you know, the intersection of of human sort of healthy aging as well and that's our contribution to the collaboration and they have some very rich exercise intervention data sets and so we're trying to identify targets at the intersection of those 2 things. Um, We also have a collaboration with Eli Lilly, and this is a molecule discovery collaboration. We're looking for, we're building molecules against novel targets that have emerged out of our platform.

I want to dig into BGE-102, but maybe just a follow-up question just on the platform and targets. I don't know if you can talk about pipeline or other maybe targets you're considering looking at sometime in the future or how you think about that.

Yes, we haven't disclosed the more novel targets, right? I mean, those are, you know, I think as those programs mature, we'll share more information.

Yep, makes sense. Now if we just shift to BGE-102, as you mentioned, your lead asset, maybe just give us, you know, a quick background there and maybe focus on sort of the mechanism of action and how it works.

Yep. So NLRP3 is an inflammasome, and so this is really the key mediator of sterile inflammation in the body. And so you can think of that as, you know, in the absence of a pathogen. And so in the context of, for example, metabolic stress or nutrient abundance, hyperglycemia in the case of DME, these all activate the NLRP3 inflammasome, and that triggers an inflammatory cascade with, you know, the the results in sort of maturation of IL-1 beta and further downstream IL-6. It also importantly controls a cell, an inflammatory cell death process called pyroptosis. And so, you know, this is a target with broad utility in a range of diseases that are driven by inflammation. And so, this is, you know, folks have been trying to drug this target for 20 years at this point, starting with, you know, MCC950, the Pfizer compound, and we really feel like we're able to reach escape velocity now with this probably fourth-generation approach that we have. I think if you think about the evolution of this space, there was the original molecule, subsequent generations of compounds trying to remove the alerting structures and improve the safety profile, then entirely new chemistry going after the same binding site. You know, and what we did was we actually did a DNA-encoded library screen and blocked the existing binding site to, you know, find totally new binding sites, sort of domains in NLRP3. And so that's the origin of BGE-102. This is a homegrown program, and we, you know, we have a differentiated mechanism of action and that it is able to inhibit both the active and inactive inflammasome that binding site is available in all of its confirmations. And importantly, too, we have, you know, a very broad, you know, IP estate around this molecule as well as, you know, the chemistry broadly and actually have issued IP, you know, for ligands that broadly interact with this binding site. So we think it's a really differentiated mechanism and we feel very strongly about it about our sort of IP position around it.

Great. Just given the mechanism of action and, you know, kind of the inflammation piece, like can you talk about the opportunities and where you can go with that and sort of, you know, how you came to deciding, you know, your current pathways and kindulate where you're focused on today? Right.

So a lot of what we're doing is is looking for at least sort of preliminary de-risking signals from the cytokine experience and sort of cytokine neutralization strategies. IL-1 beta or IL-1, generally speaking, strategy's been efficacious or IL-6 inhibition, and then where do we think that those cytokines are primarily attributed to NLRP3 activation, you know, in that disease context, and then, you know, where do we think we can provide, you know, differential value, whether it's through, you know, a more attractive route of administration, a safe and well-tolerated daily oral, or actually providing differentiated biology and going upstream and being able to capture not just the best described canonical IL-1 beta, IL-6 axis, but also IL-18 and this pyroptotic cell death. So we think we can differentiate on both of those fronts. So I'm sure we'll talk about Zeus and ASCVD. That was sort of a shock to the system, I think, for everyone, and certainly the cardiovascular community, and very disappointing for patients, truly. We can talk about the implications of that, but the I think beyond that, we're looking at diabetic macular edema and ophthalmology indications, where there's been success with cytokines. And again, we think we can provide incremental value. And I think that the biology, for example, in DME, the inciting event is hyperglycemia, and that's sort of a canonical activator of NLRP3. So we think the biology, you know, harmonizes very nicely. And, you know, we're certainly exploring a variety of other indications where this could be, this could be sort of a valuable approach and thinking about, again, the sort of the framework we're applying is, where has there been de-risking cytokine experience, where do we think that that experience is downstream of NLRP3, and where do we feel that the development opportunity and the feasibility and then the commercial opportunity, the risk benefit makes sense for sort of a company of our profile.

That makes a lot of sense. Uh, maybe we can dig into the ASCVD, um, the Phase 1B data you shared earlier this year, you touched on it already, but maybe just, you know, what were the key findings there and how does that, you know, sort of translate into your thoughts moving forward?

Yes, so the Phase 1 data that we shared earlier this year, there was a sort of a standard SADMAD component. And then we also did 2 cohorts of obese individuals with elevated inflammation. And so we treated those individuals for 14 to 21 days. You know, and there we saw rapid reductions in hsCRP, you know, a sort of systemic inflammatory marker, 86% in actually both cohorts, and sort of concordant reduction in IL-6 and fibrinogen. And importantly, we saw, you know, at the, the 60 milligram dose, you get 24 hours of IC90 coverage. So really nice target inhibition, you know, at the 120 milligram dose in Phase 1, which actually corresponds on an exposure basis to the 90 milligram dose we're testing in this longer duration trial. You get essentially 98% target inhibition at trough. And so if we need to completely inhibit the target, we feel that we can do that. And we can do that with a very tractable once daily dose. And a dose that then in Phase 1 was exquisitely well tolerated. So I think we see really nice alignment across all of those dimensions coming out of the Phase 1. And we also did lumbars on those patients and saw exposures at the 120 milligram dose that were 3x the IC90. So we're able to really potently inhibit the target across compartments and do that in a way that's very well tolerated.

Makes sense. And you're going to be sharing, I think, you know, updated Phase 2 data from QUELL-CV later this year. Maybe just talk about what's the key of that study and what you're hoping to learn there.

Yep. And there are several goals. So QUELL-CV is our dose ranging trial for peripheral inflammation. It's a similar patient to the Phase 1, obese, inflamed individuals. We're testing 3 doses of BGE-102, so 30, 60, and 90 milligrams. 90 milligrams, you know, at steady state is going to give us, we expect 98% target inhibition at trough, so complete pathway shutdown. You know, um, by contrast, the 30 milligram dose, we think will give us sort of an, um, a suboptimal biomarker response. So we're really trying to tease out, you know, the dose response in terms of, um, of the sort of the expected panel of inflammatory and metabolic markers. You know, we will be adding additional assessments compared to the Phase 1. So, for example, we'll be doing MRI imaging of the liver and looking for the inflammation CT1 signal, for example, where Ventix showed a benefit that was, you know, as a monotherapy and additive to GLP-1. We'll be looking at A1C and, you know, just a variety of inflammatory and metabolic markers there. You know, and importantly also looking at safety and tolerability over this 3-month treatment duration, right, so really hoping to extend the findings that we observed in Phase 1 in that profile over a longer treatment period.

Understood. And you mentioned earlier, you know, Zeus and kind of, you know, maybe talk about your thoughts on what happened there and then how that impacts how you think about your program.

Yes, so I think importantly we do think NLRP3 is a very distinct target from IL-6 and it would have been fabulous if the, you know, there's for context there was the IL-1 beta experience in the CANTOS trial with canakinumab there. There was a 15% MACE benefit as the headline number in patients who achieved CRP reductions through IL-1 beta below a sort of a normalization threshold, there was a 25% benefit. So we know that intervening in inflammation, targeting inflammation can work. It's a matter of what is the right target and potentially which are the right patients. And so, Zeus obviously, this was the Novo IL-6 agent in CKD patients with ASCVD had a hazard ratio of .99, so essentially no treatment effect on MACE. And so, there were some questions going into the trial, is it the right target? You know, IL-6 is downstream of IL-1 beta, you know. So if you think about the context, NLRP3 is activated in a plaque, um, and induces a local IL-1 beta signal and that translates into sort of a systemic IL-6 signal, you know, is the relevant biology at the plaque level and not at the systemic level? So that's a question. Within the trial itself, there were questions of, are these patients too severe, essentially, to have a benefit? Is the risk not modifiable at that stage? So these are patients with, you know, in some cases, very severe CKD, and so at that point, as the train left the station, so to speak, and so by targeting inflammation, it's just not modifiable at that point. So that question remains and we may know more when we anticipate Zeus will be presented at AHA. The other question was, you know, would, you know, between, you know, Cantos 10 years ago and now, there's been introduction of GLP-1s and SGLT-2s and would the drop-ins reduce the residual risk and without having seen the data, Novo did, include in their press release with the trial, that that wasn't the case and that didn't impact the result. So I think that there's certainly more that we'll learn from the full Zeus readout, hopefully, later this year. You know, they, Novo terminated the 2 HFpEF trials that they were running, so one outcomes trial, one functional trial. Athena and Hermes, those 2 trials. So the DSMB thought that it was unlikely it was going to achieve a different outcome to Zeus. But, you know, their, um, there is another trial ongoing, which is the acute post MI trial. This is Artemis. And so that one is they reiterated guidance that we're going to get that data in the first half of next year. And that's a very different patient population from Zeus. And so I think it'll give us a window in helping us understand is this, is it was it not the right patient? Or is it not the right target? So more on the horizon, although it's interesting, the strategic posture, even Novo in their sort of in the immediate aftermath of that news was very, who is proactively touting NLRP3 as potentially a better target for the reason that it is capturing the upstream biology that IL-6 may be missing. So I think that there are questions to be answered in the coming months on that front. What does it mean for us? We were preparing for a Phase 3 outcomes trial initiation in the second half of next year. You know, given this news, we put that on pause for now. Right, and so we're looking at, you know, you know, additional different indications, you know, that again have been derisked by cytokine neutralization experience that we think are predominantly downstream of NLRP3, you know, and have an attractive sort of, you know, risk benefit profile. You know, and so that's our focus now, and we've indicated, you know, we intend to share at least 1 additional indication by year end. Now all of that preparedness we can turn that back on should there be a de-risking signal and we get more confidence and clarity on the go forward in ASCVD but the net of it is we actually think that it in a way, the negative result very much supports the upstream biology, but we'll know more with the full Zeus data and then and then Artemis data in the first half of next year.