BioAge Labs, Inc. (BIOA) September 2026 Conference Transcript

Hello, everyone, and thanks for joining us at the Morgan Stanley Global Healthcare Conference. I'm Mike Goltz, one of the biotech analysts here, and it's my pleasure to introduce the team from BioAge Labs. To my immediate left is B.J. Sullivan. He's the chief strategy officer, and to his left is Dove Goldstein, the CFO. Just as a reminder, format for today is the 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 backslash research disclosures. If you have any questions, please reach out to your Morgan Stanley sales representative. With that, BJ and Dove, 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, so 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 one 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. You know, two was sort of the dosing paradigm, you know, with 60 milligrams able to achieve 24 hours of IC90 coverage, you know, 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 tissue distribution and ability to access protected compartments like the CSF as well as the retina. And so that certainly informed, you know, our indication strategy that we'll get into in a little bit. So that's our lead program. We have two phase twos that are ongoing with BG-102. So one is QEL-CV, which is a dose-ranging trial in obese individuals with elevated inflammation. And there we're going to be looking at cardiometabolic biomarkers, inflammatory biomarkers, teasing out a dose response, and building the safety database over an extended treatment duration, so over three 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 QEL-DME trial. And so this is a trial looking at BG-102 in diabetic macular edema, and it is similarly three months of treatment across three arms, so looking at BG-102 as a monotherapy as well as in combination with VEGF. And so there we recently actually announced that we had 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 a primary endpoint, visual acuity with 90% power to show a four-letter improvement. And so that trial is now enrolling, and we're expecting data by the end of next year. So that's our BG-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 the prior molecule, you know, very, very nice preservation of muscle integrity, you know, in bed rest and preclinically 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 bit more about your platform, how it works. Also maybe touch on your collaborations too.

Yeah, so our platform is sort of the central thesis of the company. So I think everyone's familiar with biobanking as a concept. that's, you know, taken off 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 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, and then doing serial sampling as well. So we can now go and follow those samples, apply modernomics 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 human sort of healthy aging. 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 two things. We also have a collaboration with Eli Lilly, and this is a molecule discovery collaboration. We're looking for, you know, we're building molecules against novel targets that have emerged out of our platform.

Yep. I want to dig into 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.

Yeah, we haven't disclosed the more novel targets, right? I mean, 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 a quick background there and maybe focus on sort of the mechanism of action and how it works.

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 that results in sort of maturation of IL-1 beta and further downstream IL-6. It also, importantly, controls an inflammatory cell death process called pyroptosis. And so this is a target with broad utility in a range of diseases that are driven by inflammation. And so folks have been trying to drug this target for 20 years at this point, starting with MCC-950, 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, there were 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. And what we did was we actually did a DNA-encoded library screen and blocked the existing binding site to find totally new binding domains in NLRP3. And so that's the origin of BG-102. This is a homegrown program, and we, you know, we have a differentiated mechanism of action in that it is able to inhibit both the active and inactive inflammasome that that binding site is available in all of its conformations. And importantly, too, we were we have, you know, a very broad, you know, IP estate around the around this molecule, as well as, you know, the chemistry broadly and actually have issued IP, you know, for for ligands that broadly interact with this binding site. So we think it's a really differentiated mechanism, and we feel very strongly 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 kind of where you're focused on today?

Right. So, you know, a lot of what we're doing is looking for at least sort of preliminary de-risking signals from the cytokine experience and sort of cytokine neutralization strategies. And so where have IL-1 beta or IL-1, generally speaking, strategies 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, you know, a safe and well-tolerated daily oral, or, you know, actually providing differentiated biology and going upstream and being able to capture not just the, you know, best described canonical IL-1 beta IL-6 axis, but also IL-18 and this pyroptotic cell death, right? So we think we can differentiate on both of those fronts. And so, you know, I'm sure we'll talk about Zeus and ASCD, you know, that was sort of a shock to the system, I think, for everyone and certainly the cardiovascular community and very disappointing for patients, truly. You know, we can talk about the implications of that, but the, you know, I think beyond that, we're looking at diabetic macular edema and ophthalmology indications, you know, 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, you know, 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 sort of a valuable approach. and thinking about, again, 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 the commercial opportunity, the risk-benefit makes sense for a company of our profile?

Makes a lot of sense. Maybe we can dig into the ASCVD, Maybe 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...

Yeah, so the phase 1 data that we shared earlier this year, there was sort of a standard SADMAD component, and then we also did two 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, sort of a systemic inflammatory marker, 86% in actually both cohorts, and sort of concordant reductions in IL-6 and fibridogen. And importantly, we saw, you know, at 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 one, which actually corresponds on an exposure basis to the 90 milligram dose we're testing in this longer duration trial. You know, you get essentially 98% target inhibition at trough. And so, you know, 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 one was exquisitely well-tolerated, right? So I think we see really nice alignment across, you know, all of those dimensions coming out of the phase one. And we also did lumbars on those patients and saw, you know, exposures at the 120-milligram dose that were 3x the IC90, right? So we're able to really potently inhibit the target, you know, know, 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 QL-CV later this year. Maybe just talk about what's the key goal of that study and what you're hoping to learn And there are several goals.

So QL-CV is our dose-ranging trial for peripheral inflammation. It's a similar patient to the Phase I obese, inflamed individuals. We're testing three doses of BG-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, by contrast, the 30 milligram dose we think will give us sort of a suboptimal biomarker response. So we're really trying to tease out, you know, the dose response in terms of the expected panel of inflammatory and metabolic markers. We will be adding additional assessments compared to the phase one. 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 monotherapy and additive to GLP-1. We'll be looking at A1C and just a variety of inflammatory and metabolic markers there. You know, and importantly also looking at safety and tolerability over this three-month treatment duration, right, so really hoping to extend the findings that we observed in Phase I and that profile over a longer treatment period.

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

Yeah, 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, you know, a 15% MACE benefit is the headline number, you know, in patients who achieved CRP reductions through IL-1 beta, you know, below a sort of a normalization threshold, there was a 25% benefit. You know, so we know that intervening in inflammation, targeting inflammation can work. It's a matter of, like, what is the right target, you know, 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 0.99, so essentially no treatment effect on MACE. And so there were some questions, you know, 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, 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. You know, 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, it's 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 these will be presented as 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 SGLP-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. And so I think that there's certainly more that we'll learn from the full Zeus readout, hopefully later this year. You know, Novo terminated the two half-half trials that they were running, so one outcomes trial, one functional trial. Athena and Hermes were those two trials so the DSMB thought that it was unlikely it was going to achieve a different outcome to Zeus but there is another trial ongoing which is the acute post-MI trial this is Artemis 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 will give us a window in helping us understand was it not the right patients or was it not the right target. So more on the horizon, although it's interesting, the strategic posture, even Novo in the immediate aftermath of that news was 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. And what does it mean for us? We were preparing for a Phase III outcomes trial initiation in the second half of next year. Given this news, we've put that on pause for now. And so we're looking at additional different indications that, again, have been, And do you risk 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 one additional indication by year-end. Now, all of that preparedness is we can turn that back on should there be a de-risking signal and we get more, you know, confidence and clarity on the go forward in ASCVD. But, you know, the net of it is we actually think that, in a way, the negative result very much supports the upstream biology. But we'll know more with the full Zeus data and then Artemis data in the first half of next year. Gotcha.

Great. Maybe we can shift now just to ophthalmology. You talked a bit about it earlier, but maybe to start, just the rationale for going into sort of DME, you know, the unmet need and sort of the advantages of your approach there. Yeah.

So I think that there's one aspect that I want to highlight, which is just that we have the molecule that can address this indication. And so, as I mentioned, we have really nice tissue distribution, and we've shown that in a range of preclinical species. We've sort of validated the CSF exposure in our phase one. And so going after ophthalmology generally is our way of taking advantage of that distribution profile and the ability to address these indications in these protected compartments, right? So I think that that was important for us as we think about the development plan for BG-102. In thinking about DME specifically, it's initiated by hyperglycemia, right? It's diabetic macular edema. So, you know, hyperglycemia and metabolic stress in the retina actually activate the NLRP3. That's sort of a canonical stimulus for NLRP3. And, you know, and not only induce a cytokine cascade that culminates in IL-6 in the retina, you know, but also controls this inflammatory cell death process. And so, you know, what we've observed in preclinical species is that, you know, when you induce hyperglycemia in a mouse, you sort of recapitulate the DME phenotype. And not only – and when you treat with oral NLRP3 inhibitor, you know, an analog of BG102, you get complete rescue of retinal vascular permeability, so just sort of fluid leakage into the retina, as well as, you know, total rescue of the integrity of the microvasculature and endothelial cell type junctions and the integrity, which is compromised by hyperglycemia. And so we think that, you know, again, we were motivated by the IL-6 experience in DME, that, you know, targeting inflammation corresponds with benefits and visual acuity. But we think that there is value and there's incremental biology to targeting NLRP3 and going upstream in addition to being an oral. And there's data with kinikinamab. There's data with mouse genetics suggesting that NLRP3 inhibition or targeting this pathway. can improve glucose control, actually. So you're not just getting – it's not just a convenient way of getting to the eye, but it may actually benefit, you know, the key risk factor for DME as well. So we think that there's really a nice alignment there with our approach. So our trial now, QL-DME, it's a three-month trial, and, you know, we're looking at both BG-102 monotherapy as well as on top of VEGF. And this is really informed by the IL-6 experience in DME. You know, we're powered now at 90% for a four-letter improvement in BCVA, and we think about, you know, that is clinically meaningful and would support advancement in DME, you know, especially if you think about delivering that benefit in a safe and well-tolerated oral. I mean, the DME landscape is one where half the patients are sort of in a watch-and-wait category where they have edema but they don't have sufficiently compromised visual function that they want to go and get monthly or quarterly intravitreal injections. I mean, these are often working-age people, and it's a huge patient burden. And even patients who have initiated intravitreal therapy are often noncompliant with the dosing schedule. And so the real-world treatment outcomes differ substantially from what you see in a trial. And so I think a really exciting opportunity would be for those early patients, can you delay initiation of intravitreal therapy, you know, and then on the other end of the patient journey, for patients who are on an intravitreal therapy but don't have sort of sufficient disease control, can you add this mechanism to give you better, you know, sort of correction of visual acuity, right? And so we think about QLDME specifically as a proof of concept in this indication, you know but also more broadly as a sort of a beachhead into ophthalmology generally and you know we want to we were looking for bcda improvements but we're also doing a variety of exploratory endpoints oct imaging we're looking at intraocular biomarkers and so we want to demonstrate more broadly a clear pharmacodynamic effect in the eye because there are you know indications like geographic atrophy you know where where nlrp3 we think has a very important role and so this will inform DME specifically but also the broader ophthalmology strategy more generally I guess assuming you get positive results in DME what would be the next steps there like a full phase 3 yeah absolutely as well as sort of expansion into other indications in ophthalmology and I think it's attractive because we feel that we can develop, you know, through NDA here and potentially commercialize as well. And so we think it's a therapeutic area that lends itself well to a company of our scale.

Yeah, that's something you would consider sort of commercializing on your own, or you think a partnership is the way?

I mean, I think all options are on the table, but I think, you know, a go-it alone is certainly feasible from our perspective. Yep. Makes sense. maybe we can shift now to just the APJ agonist you talked a little bit, you gave us a little bit of it in your prepared remarks but I guess what's different this time maybe let's start there and kind of what are the next steps so as a reminder APJ is the receptor for an exerkind called apolin and so it's secreted by the muscle during exercise this peptide is, again, one of the strongest signals in our cohort for longevity and preservation of physical function. We had licensed an APJ agonist from Amgen, and there demonstrated very profound muscle preservation at bedrest, right? We did a trial in obesity, and there was, you know, idiosyncratic DILI-related, you know, from all expert feedback we got to the compound, So we have very high conviction in the target, and so right now we're pursuing both an oral small molecule as well as a parenteral approach to APJ agonism. And so the oral small molecule is a totally distinct chemotype. We're targeting the same biology with a totally different chemistry and a low oral dose. And then with the parenteral, we've disclosed a collaboration with G. Kang Therapeutics on an APJ agonist nanobody. Right. And so we think what we're trying to accomplish here is improving with a GLP-1, both the quantity and quality of weight loss. And, you know, in our preclinical data, again, you get a doubling of weight loss with a GLP-1 and you get, you know, complete restoration of lean body composition. And so in looking at where the market stands now with GLP-1s and the unmet needs there, you know, in the oral small molecule space, I think that there's certainly, you know, Orpho disappointed, I think, in terms of the headline weight loss number not really being in line. You know, it's a compromise in terms of weight loss. And so, you know, they're having incremental weight loss is probably value proposition number one, and body composition is value proposition number two. I think on the parenteral side, you know, it's the opposite now that we've achieved bariatric surgery like weight loss, you know, but the body composition element, I think, remains an unmet need. You know, and importantly here, too, the, you know, our prior experience suggested that there's no tolerability issues associated with ABJ agonism. And so if you think about that in combination with GLP-1, I would think that's really important. You know, in looking at some of the more anabolic mechanisms that have tolerability profiles that are more similar to GLP-1s, you know, as monotherapies, you know, the prospect of combining may be a lot to ask of a patient, and so, you know, our experience certainly supports really no tolerability issues of any kind, you know, and certainly not any GI issues, and so we think the complementarity, you know, of these mechanisms is very high.

Yeah, very interesting. Maybe in the last couple minutes here, we can just fire off some of our survey questions we've been asking all our biotech companies. These questions are in sort of key theme areas. I guess the first one is just, you know, China, you know, what's your thought on innovation coming out of China or how does it impact your R&D approach or BD playbook?

Yeah, so from a BD perspective, we have a global view. I mean, as we've talked about, we have a collaboration with Chi Kang Therapeutics, you know, out of China, and so we're certainly, again, you know, we have a global view. You know, in terms of competition, we, you know, at least on the BG-102 side, I think, you know, one of the key advantages of this program is, again, because it was, you know, a totally novel chemistry, a novel binding site, and we have a really broad IP state around that. You know, we have issued IP that, you know, for broadly covering ligands, sort of interacting with the binding site. And so, you know, we feel like we're really well positioned from a competitive perspective there as well.

Yeah, great. And the second question is in an area that keeps getting more interest by the day. It's just AI, implementing AI and kind of where you've used it and kind of where you might use it in the future. Yeah, no, this is definitely a question of great personal interest.

But the, you know, AI for the company has been part of our DNA since our inception. You know, I think on the data science side and the platform side, it's always been there, right? I mean, I think this is not a novel. I think the LLMs, and this has been a huge area of focus for us. And for us, it's not, you know, that any process or activity, There's not going to be sort of a magic bullet, but it's more about how do we incorporate this and incentivize this as part of our ways of working. You know, and it's a change management thing, more, you know, question as much as it's a technical question. And so how do we encourage sort of aptitude here, you know, and incorporate this again into our ways of working? And I think we've been, we've made great strides here. And so, you know, really across the company. So it's not just the platform, it's every function now. we're, you know, encouraging and certainly promoting use of, you know, a variety of AI tools.

And then maybe the last one here is just which policy variable, whether it's FDA, Medicare negotiation, MFN, tariffs, or global pricing sort of matters most to you? I think it really depends week to week. Great. So why don't we, we're just about out of time, so why don't we end it there? BJ and Dove, thanks so much. Really appreciate your time. Thank you very much. We appreciate it.