STIFEL 2026 HEALTHCARE CONFERENCE - BIOAGE LABS INC

Are you on? Yes. Okay. Good afternoon, everyone, and welcome to the BioAge Lab's presentation. BioAGE, as you know, is targeting NLRP3 to address diseases of aging and inflammation, and with us today is B.J. Sullivan, Chief Strategy Officer of BioAege. So why don't you come on and give us the presentation, and we'll go into Q&A. Sounds great, and thank you for having us today. We appreciate it, And thanks to you, all of you who are attending in person and virtually. So I am going to start off and give you a brief corporate presentation and an overview of our programs, and then we can go into Q&A. So BioAge is a platform company. You know, we are essentially harnessing the biology of human aging and using that as a lens for target discovery and targeting pathways associated with healthy aging. Our lead program is BGE-102. It's a potential best-in-class oral NLRP3 inflammasome inhibitor. We released our Phase I data earlier this year showing what we believe to be a best-In-Class profile with essentially 98% trough inhibition of IL-1 beta and 86% reduction of HSCRP in obese and inflamed individuals, and all of that in sort of a convenient once-daily dosing paradigm with placebo-like tolerability and really excellent tissue distribution, which enables us to go after diseases driven by inflammation, not only in the periphery, but also in protected compartments like the retina. And so with this program, we have two ongoing phase two trials. So one is QUEL-CV, which is a peripheral dose ranging study where we're looking at three doses of BG-102 and trying to understand the relationship between those exposure as well and sort of a rich set of inflammatory and metabolic biomarkers as well as MRI imaging of the liver. So that's reading out at the end of this year. And we also have the ongoing Quell DME trial, which is enrolling and is targeting data by the end next year. You know, in there we're looking at NLRP3 both as a monotherapy and as a combination with VEGF to see if we can improve visual acuity in these patients. And we see this really as a beachhead into a broader ophthalmology strategy, which takes advantage you know the fact that we we really have exceptional tissue distribution which we showed you know in the clinic getting very nice levels in the CSF and you know across non-clinical species including primates we see very high free levels in the retina and so we're we're really leaning into this sort of differentiated profile of our molecule I would also say you know that we are we're planning to announce an additional indication for for NLRP3 and plan to announce that once those plans are fully solidified, but that's also on the horizon for that program. We're also very excited to be back in the clinic soon with APJ. So this is a target that in our platform is among the most highly associated with both longevity and preservation of physical function. This is a a target when you combine APJ agonism with an incretin or actually any mechanism that causes weight loss due to appetite suppression, we've shown the ability to double weight loss and restore body composition back to that of lean control animals. You know, and actually with a first-generation compound, we were able to show in older participants at bed rest essentially full preservation of muscle size, muscle quality, and essentially muscle protein synthesis. And so we have two next-generation programs. We're working on an oral and a parenteral, and we're targeting IND submission by the end of this year and that's on track you know which point will essentially debut the program as well as our clinical development plans and so you know we're very excited to be back in the clinic with with APJ very shortly so I'm gonna give you a brief overview of the the BG 102 program so NLRP3 is essentially an inflammasome in the body that's responsible for essentially translating sterile inflammatory signals into both you know cytokine production and release So IL-1 beta and IL-18, as well as mediating the inflammatory cell death process called pyreptosis. You know, and so there are other inflammasomes in the body, but NLRP3 is really the key mediator of sterile inflammation. And by that, I mean inflammatory signals that are not associated with an infection or a pathogen. This could be, you know, metabolic stress, nutrient excess, you know, a lot of the things we associate it with creating this sort of chronic simmering inflammation. Those are mediated by NLLP3. And in our cohort, we see that NLRP3 activity is highly associated with mortality in humans. So BG102 is our lead program, and we'll get into this in more detail, but we think it has best-in-class potency with an IC90 of 1.6 nanomolar. This, in the clinic, we're seeing 98% suppression of IL-1 beta trough at the 120-milligram dose. We're getting 24 hours of essentially complete target inhibition, and so we feel that we're able to really inhibit this target almost completely with essentially placebo-like tolerability and a high degree of CNS penetration. So we did lumbars in our phase one and showed a KPU-UCSF of 0.7, which we think is best in class. I would also note here that we'll get into a little bit of the unique binding site, which we've characterized. And the IPs around that and around this molecule are out to 2045 with claims not only for the specific structures, but also broadly covering ligands that interact with this binding site. And so NLRP3 has been a target of interest for drug development for 20 years. The original compound that Pfizer took into the clinic was MCC950. This targeted the ATPase pocket on the molecule, to our knowledge, all of the other programs in development are essentially derivations of that structure or novel chemotypes targeting that binding site. So we did a sort of a de novo approach. We did a Dell screen. We blocked that binding site, intentionally looking for novel binding sites. And so we were able to sort of characterize this with a collaboration with Matthias Geier at the University of Bonn, and we've published on this extensively. This binding site is distinct, and what it enables is the ability to inhibit the inflammasome both in its active and inactive form. So what we see is that we're really able to completely inhibit the target. The inflammasom in NLRP3 has a monomeric form, and then it assembles into a decamer in this really big sort of scaffolded inflammasome assembly that that is required to sort of process the cytokines and initiate pyroptosis once that complex assembles it you know it appears that the being sort of the original binding site is blocked and so we think that this this binding site may in part explain why we're able to achieve you know the depth of target inhibition that we've we've shown in the clinic so to go over our phase one results. So these are the results that we shared in April of this year. So this included essentially a standard SAD-MAD with healthy volunteers. And we also included two cohorts of obese and inflamed individuals. And essentially, this was informed by the VENTIX trial, which had read out and essentially showed that in patients, some similar patients, you basically achieve maximum biomarker reductions within a couple of weeks. And so we think we were, the goal was to show, okay, what is the depth of the biomarker reductions that you're able to achieve, you know, with the expectation that we'll be able to sustain those over chronic dosing. And so the highlights here are basically, you know, safety tolerability was really placebo-like, you know, excellent in, you know, across the phase one. Nice dose proportionality with clearly supporting, you know, once daily dosing, you know, and from a biomarkER and pharmacodynamic perspective, again, we were able to achieve essentially 24 hours of complete target inhibition. You know, and in both of the doses we tested in these obese and inflamed individuals, we were able to achieve a 60% or an 86% reduction in CRP. So I'm just going to walk you through some of the key findings here. So this is the CSFPK from lumbar punctures in healthy individuals, and you can see that this is basically a steady state level. at the 60 milligram QD dose, we were able to achieve essentially IC90 coverage in the CSF, which rose to about 3x the IC90 at the 120 milligram dose. So very nice tissue distribution into the CSf. This is essentially showing the magnitude of target inhibition. So this is an ex vivo stimulation of blood from these patients, healthy volunteers, 60 and 120 milligrams QD. And we're basically able to show up to 98% suppression of the target. This basically tells you the same thing, but I think it illustrates it in a very visual way. You can just see here, this is the 120 milligram dose group at day one, day eight, and day 14. And what we're able to is that by day eight you're basically getting 24 hours of complete target inhibition. So we're really knocking the target down for that full 24-hour period. This is one slide just summarizing the data from the obese inflamed MAD cohorts. You can see here in the 60 milligram and the 120 milligram MAD cohort, we were able to achieve an 86% reduction in CRP. You know, and so as we go into the QUAL-CV trial, that, you know, the dose ranging trial that's reading out at the end of this year, you know one of the goals of that is to really understand what is the dose-response relationship between BG102 and then these metabolic and inflammatory biomarkers, you may not need to have 98% trough inhibition of IL-1 beta to have maximal effect on some of these downstream markers. So that's one of the key goals of the ongoing study. So to briefly touch on therapeutic areas, we think we have the ability to address inflammation very broadly across compartments. So not only do we think, we have potential best class performances for an NLRP3 inhibitor full stop, but because we have demonstrated very high penetration to the CSF, we think obviously that that compartment is highly addressable. And then across non-clinical species we've looked at, including primates, we see excellent exposure in the retina, and so that's obviously one of the anchor therapeutic areas for us as well. So we think we're able to address inflammation broadly regardless of the compartment. So this is the design of the QUEL-CV trial, which is currently ongoing and going to read out at the end of the year. This is a, you know, it's dose ranging. We're looking at three doses of BG102 and placebo, so we're looking 30, 60, and 90 milligrams QD. 90 milligrams essentially is the pharmacokinetic equivalent at steady state to the 120 milligram dose we tested in phase one, where we expect, you, know, similar 98 percent trough suppression of IL-1 beta. You know, we expect 60 and 30 milligrams are going to give us, you know, lower levels of IL-1 beta suppression, and so we're trying to interrogate really, again, the dose response and relationship to downstream markers like CRP, which is the primary endpoint, as well as a variety of other inflammatory and metabolic markers that we're looking at. We'll also be looking at MRI imaging of the liver, so we'll look at liver fat as well as liver inflammation, which actually Ventix showed a benefit in their, you know, in their three-month trial. So we'll be able to look at a much richer set of these markers and looking at markers that take longer to change than would have been feasible to measure in the context of the phase one. So this sort of broadly supports cardiometabolic indications. We'll beable to really look at this rich set of data to understand where within the cardiometabolics base this drug might play. So to touch on HSCRP as the primary endpoint, we think it is a very important PD marker to help us understand and benchmark the anti-inflammatory activity of the molecule. I think the elephant in the room is sort of Zeus, and how do we interpret those results? I think what we can glean from that is it's certainly not a surrogate marker for cardiovascular benefit, but we still think it's a very strong PD marker. This slide really essentially illustrates how both pathways converge on CRP. So NLRP3 inhibition really happens at the level of the plaque, you know, in the context of cardiovascular disease where cholesterol crystals or oxidized LDL, other inflammatory stimuli, stimulate NLLP3, it secretes IL-1 beta, which is a local cytokine, and that sort of ultimately translates into this sort of systemic alarm signal of IL-6. You know, sort of that converges on CRP, you know, as well as, you know, just, you know, blocking much further downstream and, you know, just blocking IL-6 directly, you know, so both of those can similarly impact CRP despite capturing very different biology, if that makes sense. And so, you know, in looking at the Zeus, you know, results, in our view, it actually really strongly points to NLRP3 being a good target here. You know it's much further upstream. If you think about what's worked in inflammation, colchicine certainly, IL-1 beta in the CANTOS trial, and so if you harmonize that and reconcile it with Zeus, it really, in our view, seems to point upstream, much more so than it being the other hypothesis that maybe the patients were too sick or was too far gone. The fact that there was sort of no subgroup signal in the full Zeus data, in my view, seems to strongly suggest it's actually the upstream biology that may be more relevant for cardiovascular disease. That said, as a company, this isn't a priority for us. I think we're shifting in other directions, and we're really leaning into our ophthalmology program and, again, can announce an additional indication for the program at a later date. And so I think the key message here for us is that it's on pause. It's no longer a priority. That said. We've done a lot of preparatory work from a CMC perspective and sort of planning for phase three enablement. And so if there's a surprise, for example, in Q1, in Artemis, the other Novo trial reads out in the acute MI setting, we're ready to respond to new information very quickly. So to just sort of close out on cardiometabolic, obviously atherosclerotic disease is an area where we think NLRP3 is very relevant. There are a number of other facets of cardiometabolics disease, including insulin resistance, MASH, kidney disease, where NLLP3 may be relevant and we'll be able to sort of interrogate the rich data set that we're generating in the Quell-CV trial to understand where this may play. Ophthalmology is our other sort of anchor therapeutic area for BG102. We think that this is an incredibly attractive target for ophthalmologists, not only with the potential to deliver a novel mechanism of action, but also very importantly for patients, reducing the treatment burden, which can really, you know, there's a huge disconnect between, I think, you know, clinical trial, treatment outcomes, and real-world outcomes, and a big part of this is sort of, you know, patient willingness to undergo treatment. This also enables us to treat both eyes simultaneously. A lot of patients who have retinal disease have bilateral involvement, which means often two injections and two visits, and so, you know, again, a huge value proposition in streamlining care for for patients and I think also importantly for us like this this presents the opportunity to address both the local retinal inflammation as well as the upstream drivers of disease so in DME for example you know we know that you know NLRP3 is involved and may have benefit for you know this sort of metabolic syndrome broadly and so you're you're able to potentially address and improve the underlying disease and sort of the key risk factor for for DME as well as addressing the specific local inflammatory biology. So just briefly, DME and GA are sort of the two priority indications for us. We also think this is highly relevant in MESI and UME. So DME, this is sort of a leading cause of vision loss in younger individuals, so less than sort of 65 years of age. The key risk factor is obviously hyperglycemia and diabetes. The way it's treated right now is really focused on anti-VEGF and steroids and laser for more recalcitrant disease. So the goal here is really to reduce the injection burden. There are a number of patient segments we think are highly addressable here, one being the 40% that are in this, quote unquote, watch and wait, who are, their maculas are wet, but they don't, they have sufficiently compromised vision to initiate intravitreal therapy or they just don't want to. And then on the other end of the spectrum, there are patients who are on VEGF therapy but having incomplete disease control. And so we'll be able to interrogate both of those patient segments really in the ongoing Quell DME trial. I'm going to skip GA just for the interest of time. But the inspiration for the Quell DME trial was we're being – the high-level motivation is really the IL-6 experience. And if you think about the Roche, the Mickey Bar program, they're able to show essentially a line of BCVA improvement in two treatment settings. So one is a monotherapy as well as in combination with VEGF. And they're are able to that relatively quickly. So they're were able to sort of maximum separation of the groups in about a month or two. So regardless of intervention point and within a relatively short period of time, they've demonstrated that an anti-inflammatory can have benefits in visual acuity. So that at a high level inspired the design of quality ME, but I would point to important distinctions and differences in the biology of NLRP3. So it's much further upstream, and so you're capturing IL-1 beta, IL-18, as well as pyreptosis, which affects and compromises the microvasculature in the retina, and there's a lot more biology here than just IL-6. Our preclinical models certainly support strong potential benefits in this indication. So this is a diabetic retinopathy model, and so you can see in the mice when you treat with BG102 orally, you're able to essentially completely rescue retinal vascular permeability. So this just fluorescein angiography and measuring leakage into the retina. And then on the right, this is sort of zooming in and looking at the integrity of the microvasculature. So both on the left, it's really the macro. On the right it's the micro, but you're able to almost completely correct this phenotype with BG102 monotherapy. So this is the design of the Quell DME phase two trial. So we're looking at center-involved DME, and these are either naive or washed-out patients. we're looking at essentially two comparisons. One is monotherapy to its baseline, and then we're also comparing VEGF to VEGEF plus BG102. So those are the key comparisons. We're powered for essentially a four-letter improvement in both of those comparisons. And again, the primary endpoint is visual acuity. We'll obviously be looking at a variety of exploratory markers, including retinal parameters, as well as systemic biomarkers to really try to understand the full picture in these patients. So in terms of the goals of the study, obviously, first and foremost, we want to demonstrate a benefit in visual acuity. But we also see this trial as essentially a beachhead into ophthalmology more generally. And as I mentioned, there are other highly addressable indications like GA, MESI, and UME, which could follow on from this trial with a clear demonstration of pharmacodynamics and target engagement in the eye. And again, this trial is gonna read out at the end of next year. So I'll briefly touch on this. This is sort of, this is a model of geographic atrophy, which again is a high priority indication for us. There's a robust literature here showing that essentially NLRP3 knockout in mice can prevent the rapid and profound degradation of the retinal pigment epithelium. And we're able to essentially recapitulate that with oral delivery of a BG102 analog. So we think we're able to access the retina and really prevent this tissue deterioration that is triggered by the bicellular debris, essentially, in the retinal, lipofuscin and drusen, which are the hallmarks of the disease and highly pro-inflammatory. This is another naturally aged model, which we think is really exciting. We have an outbred mouse strain in our lab, which we've developed to study natural aging processes. And on the left, this is really just a characterization of the model, which is you get an AMD phenotype over time. And with age, you get, essentially, deposition of lipofuscin granules in the retina. And when we treat with a BG102 analog, we're essentially able to completely prevent further accumulation of that lipo-fusin. So that is another high priority indication for BG-102 and one we would certainly be interested in exploring after establishing clear pharmacodynamics in the eye and Quell DME. There is also interesting sort of human data to support this hypothesis as well in GA. So in Flamazon Therapeutics, for example, they're running a pilot trial right now with an RTI that they're delivering as an implant to deliver high concentration in the retina. And in some of their early data, they've shown sort of slowing of lesion size in excess of 50%, which compares very favorably to the complement inhibitors right now, which showed approximately 15% slowing of legion size growth in their pivotal trials. So we think that this is early data, but certainly very supportive and very exciting in our view. So I'll touch quickly on APJ. So this is the target we're very excited to be back in the clinic with. this year, or rather at the beginning of next year. Apolin is one of the, which is the ligand for APJ, it's one of strongest signals in our platform associated with longevity as well as the preservation of physical function, and is associated with a whole variety of cardiometabolic benefits on a proteomic level. We show preclinically that when you combine APJ agonism with an incretin, you can essentially double weight loss as well completely restore body composition to that of lean controls. And with our first generation APHA Agnes, which we licensed from Amgen, we were able to demonstrate essentially complete preservation of muscle size, muscle quality, as well as muscle protein synthesis in older individuals at bed rest as sort of a proof of principle, this muscle-preserving activity. And so we just reported a cash balance of just over $350 million in the last quarter. And so that essentially funds all of the activities that you see here. So QWEL-CV, reading out at the end of this year. QWel-DME, reading at the beginning of next year. Reading out at end of next. It also funds an additional indication for BG-102 through proof of concept, and that is to be announced. It also fund APJ programs through proof-of-concept. So again, the next milestone here is IND submission by the end the year. At that point, we're excited to announce, essentially debut the program, as well as share clinical development plans for that program. And so, you know, again, we're very excited to be back in the clinic with APJ very shortly. And that is it. So I'm happy to take questions. Great. Well, I am going to ask you one question about the cardiovascular indication. What do you need to see from Artemis to give you confidence that you can move forward in that indication or whether it's worth moving forward in that indication? Yeah, I mean, it's like a clear signal. I think, you know, whether it's stat-sign or just a magnitude that, you know, is decisive, right? I mean I think that if it's, you know, gray area or, you know, you think that there's some benefit and NLRP3 might be stronger, you know. I think we're very, you know, excited about the plans where, you know, we had the studies we have ongoing and some plans we're yet to announce. And so I think it would have to be a very decisive win in order to sort of change the, change our tune on ASCVD. And would you say that Artemis has the most similar patient population to what you're looking at in the QUEL study? You know, it's a little bit different. So the QUAL-CV study is sort of a, you know, to obese individuals, cardiovascular risk, elevated inflammation. The acute MI, patients are like hyper-inflammatory, so this is right after an event. It's not that dissimilar from the CANTOS trial where there was the, you You know, the IL-1 beta was studied and did show a very meaningful benefit. But there, you know, each population is a little bit different. And so I think we don't want to over-read at this point. And so we would be delighted if there were a surprise to the upside and there were huge benefit in these patients. And it really was that it was the wrong population in Zeus. I'm a little skeptical just because none of the subgroups in Zeus moved. And so the idea that this group was too far gone. We didn't see any sort of directional benefit in, you know, higher EGFR patients, for example. And so, you now, I'm skeptical, but would be delighted to be surprised. Okay. All right. I'll leave it at that. Okay. DME now. Maybe you can talk to us about the patient population that you specifically want to go after in DME. Obviously anti-VEGFs work pretty nicely, but not everyone is getting treated. So are you looking for that earlier patient population? I think that that is an incredibly attractive population. So this is essentially 40% of patients are in the watch and wait category where they have edema in the eye, but don't have sufficiently compromised vision or they don't want therapy. When you speak to investigators and sites, these are patients who are working. It's a huge inconvenience. No one wants to get a needle in the eyes. And so I think everyone appreciates that an oral here would be an incredible unlock for these patients. That is a very attractive opportunity, and we're obviously looking at that in the monotherapy group. Otherwise, even on top of VEGF, if it can give you better disease control between doses or it can improve disease control for patients who are refractory, and that's sort of the highly inflammatory phenotype of those refractory patients. And so, you know, we're trying to understand in this trial, you know, the benefit in those different treatment settings. And would you say that DME has more of an inflammatory component or is it dependent on VEGF? Because obviously VEGs have been developed here, but how much of this disease is driven more by the inflammatory cascade behind the disease? Yeah, I mean, it is a highly inflammatory disease. And so hyperglycemia is an inflammatory stimulus, right? So it's one of the classic activators of NLRP3, the metabolic stress that results from it. And so we think that there's multiple aspects in which inflammation, in this sense, can contribute to the DME pathology. It's not just through the cytokine cascade, although IL-1 beta directly induces VEGF. And so you do certainly get that pro-inflammatory classical milieu, but you're also getting that, at the level of the endothelium, you're getting this sort of compromised integrity of these cells because you're getting this pyreptotic cell death that further contributes to the edema and essentially the lack of tissue integrity in the retina. Okay. And then just you mentioned earlier that obviously this is, you're dealing with a diabetic population, so they have a whole host of things going on. So are there any other biomarkers that you're looking at beyond just the eye to look at how it might be impacting the rest of their disease? Absolutely. And so this is a huge thing. I mean, in terms of, you know, just the glucose control, kidney function, the whole range of sort of cardiometabolic comorbidities, right, with type 2 diabetes, we're going to be looking at, you know, in sort of the standard, you know, set of systemic labs that accompany this, I think it's a huge part of the value proposition, in addition to a new mechanism, in addition to, you know, being oral, but the ability to actually address systemic cardiometabolic disease as well, at the same time, I think is, you know, incredibly important. Metabolic markers, just as a secondary exploratory. Totally, yeah. Okay, and then just on the arm that is monotherapy, we're looking at earlier stages of disease. What are you actually measuring there? Is it going to be harder to show any kind of separation? Are you measuring progression to DME or first vision-threatening event, or what is it that you're measuring? Yeah, so in all of the groups, the primary endpoint is visual acuity, right? And so while these are treatment-naive patients or washed-out patients, we're looking for those who do have sufficiently compromised vision that we can show a benefit, right? So these are not patients who are a little bit wet, but their vision is intact. You know, we do need to have, you know, the eligibility requires some compromise in vision so we can show a benefit. Okay. And so you mentioned that you had started enrolling your first patient. Yes. How's that going? I know it's really early, but... No, it's, you know, going well. We're off to the races. It's maybe easier to enroll a patient when you're offering them an oral than needles in the eye. So I'm hoping maybe it'll speed things up. Yeah. Yeah. No. So we're maintaining our guidance for Topline at the end of next year. Okay. All right. Well, great. Thank you very much. I appreciate you having us.