Good afternoon, everyone. Thank you for joining the 25th Annual Needham Virtual Healthcare Conference. My name is Joey Stringer, and I'm one of the biotech analysts at Needham & Company. It's my pleasure to introduce our next presenting company, BioAge Labs. Joining us from the company is Chief Financial Officer, Dov Goldstein, and Chief Strategy Officer, BJ Sullivan. For those of you joining on the webcast, if you would like to ask a question, please do so at any time. You can submit a question using the chat box feature at the bottom of your screen. With that, we'll get started. Dov and BJ, thank you so much for joining us today.
Our pleasure. Thank you.
Yeah, thank you so much for having us.
Certainly, 2026 is looking to be a transformational year for BioAge, but before we get into the pipeline, can you provide a brief overview of the company? What are the top priorities, and can you touch on some of the key milestones and catalysts this year?
Yeah. With pleasure. So we are a clinical stage biotech, and we are applying human aging biology as a lens for therapeutic development in cardiometabolic disease. We're a platform-based company. We have one of the world's largest collections of human aging data, and we use this to inform all of our discovery and development activities, including ongoing collaborations with Eli Lilly and Novartis. On the pipeline side, BG-102 is our lead program. It's an NLRP3 inflammasome inhibitor with novel chemistry and a novel binding site. We're really excited about the emerging potential best-in-class profile that we've shared from our phase I to date, where we're seeing anti-inflammatory effects that are really in line with the IL-6 injectable modalities. We're advancing this molecule into two therapeutic areas, where NLRP3 sits really at the key node of disease biology and where there's significant clinical unmet need.
And so our lead indication is cardiovascular risk reduction, which I'm sure we'll talk about extensively in this chat. The second area that we announced in January is ophthalmology. This is an area where there's very strong rationale for NLRP3, and we can take advantage of the really exquisite tissue penetration of our molecule. There we're going to be running a POC in diabetic macular edema and really using that as a beachhead into broader development. In addition to NLRP3, we are advancing two APJ agonist programs, both an oral and a parenteral program. APJ is the receptor for the endogenous apelin. We've shown in pre-clinical studies that agonizing that receptor in combination with an incretin can double weight loss and fully restore body composition to that of lean controls. We're really excited about those programs as well.
From a catalyst perspective, this will be an exciting year for us. In the first half, we're going to be completing our phase I. There, we'll share details from our second obese inflamed MAD cohort at 60 mg, as well as sharing unblinded AE data and speaking more about the safety tolerability profile. A really exciting update there. We'll be initiating a dose-ranging CV risk POC trial, looking at three different dose levels of BGE-102 in the middle of this year with data by end of year. We'll also be initiating a POC trial in diabetic macular edema in the middle of this year with data anticipated in the middle of next year. Those are the catalysts on the horizon for BGE-102, and we're also anticipating filing our first IND for APJ by the end of this year.
Great. Well, BJ, you mentioned the lead asset, BGE-102 NLRP3 inhibitor. Can you give us a brief history of that target, the mechanistic rationale for BGE-102, and why has there been so much recent interest from investors in pharma in the NLRP3 space?
Yeah. Great question. NLRP3 is an inflammasome, and so it is a key part of the innate immune system. What is interesting about NLRP3, it's sort of a critical mediator of sterile inflammation. You can think about the inflammation that's downstream of things like nutrient excess or cellular stress, things that are sort of non-pathogenic, right? What NLRP3 does in response to these stress signals is secrete cytokines like IL-1 beta and IL-18. Again, like a really critical mediator of sterile inflammation. In cardiovascular disease in particular, there's very strong human genetic evidence supporting the benefits here, right? I think we can all appreciate how important inflammation is in broad disease biology. Where BGE-102 is really differentiated, so people have been trying to drug this target for a long time. We started from scratch, essentially.
We ran a DEL screen, and identified the precursors to BGE-102. They're novel chemistry. They actually have a novel binding site. BGE-102 is really quite differentiated from that perspective from other inhibitors in development. Critically, we've characterized the structural biology of the inhibitor in complex with NLRP3, and really interestingly, it can inhibit both the inactive and the active form of NLRP3. That may be part of the reason why we see what's emerging as sort of potential best-in-class efficacy in terms of its anti-inflammatory effects that we've seen so far in the phase I.
I think that you asked a question like what's generating a lot of investor and strategic interest in the target, and I think that really is part of the crux of it is we're seeing reductions in hs-CRP that are really not just approaching but totally in line with the IL-6 modalities that are currently in development for ASCVD. You've got all the anti-inflammatory horsepower in the presentation of a well-tolerated oral medicine. I think that's part of it, the intrinsic excitement there.
Yeah.
There's also some more sort of external factors that I think are generating interest. Lilly obviously acquired Ventyx. They're thought to be the kingmaker in the cardiometabolic space now, and has sort of, I think, generated excitement around the target. They obviously also did a licensing deal with CSL for their IL-6 antibody, so obviously committed to that axis. Novartis acquired Tourmaline, similarly, a longer acting IL-6 asset. There's been a lot of interest, obviously, in this inflammatory axis. Then, lastly I would just point out people are really focusing on the inflammatory ASCVD opportunity with the ZEUS readout. This is Novo's IL-6, and we're expecting that data presumably at some point in the second half of the year.
We think that this could be really exciting for NLRP3, in addition to the CANTOS trial, which sort of demonstrated a MACE benefit targeting IL-1 beta, which is directly downstream of NLRP3. This could add further evidence for selective anti-inflammatory strategies in ASCVD. Generally, we think it could be a very positive thing to have an injectable on the market first to create market development. If you think about physician awareness, routine testing, and screening for hs-CRP, could be a really fertile ground to launch a follow-on oral medicine.
The company announced some initial phase I data late last year in healthy volunteers and some CV risk patients. Can you just summarize the trial design and key takeaways from that dataset?
Yes. The trial essentially has three parts. It's a healthy volunteer SAD/MAD. In the MAD, we tested two dose levels, 60 and 120 milligrams, QD. We extended the trial, and we are running two obese MAD cohorts. This is looking at obese individuals who have elevated CRP above 3 mg per liter at baseline. There we'll be looking at those same dose levels, so 60 and 120 milligrams. The 120 milligrams we've reported, that was 14 days of treatment. The 60 milligram dose group we'll report in the first half of this year, and that'll be for 21 days of treatment. What I think is exciting about this is the, what we learned from the Ventyx readout is that reductions in hs-CRP happen rapidly and are sustained.
We think that actually we're getting 80% of the answer from our longer three-month CV risk POC trial that we're about to run just from this short treatment period in the phase I setting. We're really excited about that sort of early look at the anti-inflammatory efficacy of the molecule.
In terms of the data that we can expect from the phase I MAD readout, the upcoming readout here, what do you plan to disclose? I'm sure CRP will be part of that, but anything else that we should be aware of, and what are the goals of the trial?
Yeah. I think we've safely established that this clearly has the PK to support a once daily oral administration. The safety tolerability for the chronic indications we're looking at is paramount. To date, we've seen only mild moderate AEs, no dose dependency, no DLTs, strong target engagement, right? In the healthy volunteer MADs, we're seeing 90%-98% suppression of IL-1 beta. In the 120 mg obese MAD cohort that we reported, we see anti-inflammatory effects in hs-CRP, IL-6, and fibrinogen that we think are potential best-in-class. What we'll see from the 60 mg cohort is really the beginning of a dose response exploration, right?
Yeah.
Seeing what is the lowest dose where we can see maximum anti-inflammatory effects.
What can you tell us about the types of patients that are in the obese MAD cohorts? What types of patients were enrolled, their background CRP levels, and how relevant are they to a potential CV indication moving forward?
Right. These patients were critically obese and had hs-CRP above 3 mg/L at baseline. The baseline values in the active group were 4.85 mg/L, and this is in the 120 mg cohort. That's actually very comparable to what Ventyx enrolled at baseline, and also actually what we saw in the CANTOS trial. It's a highly comparable baseline. When we do the dose ranging three-month trial that's initiating in the middle of this year, it'll be very similar eligibility. We'll just be requiring an additional CV risk factor, so think of hyperlipidemia, hypertension, in addition to what we've described.
I want to kind of zoom in on the CRP biomarker here. Can you discuss the importance of CRP, and also percent reduction versus hitting normal levels, and what is a normal level? What's considered clinically meaningful here?
Yeah. No, great question. We're obviously looking at the percentage reduction in CRP, and that's helpful for benchmarking across dose levels and-
Yeah
... across different baselines and programs. What we think is actually the most clinically meaningful is the percent of participants who achieve normalized levels, and that's below 2 mg/L. The reason for that is, this really comes from the CANTOS trial. In that trial, they showed that in participants who achieved that below that threshold had a 25% MACE benefit, whereas those who didn't essentially had nothing. If we think about what is really the level, where clinical benefits-
Yeah
... can accrue, it's in that subset. I would also say, lower is better, like lipids. It's like we're not just going to hang our hat on less than 2 mg/L and say there's
Yeah
No more work to do. We're also seeing a substantial proportion of participants in the 120 mg group who achieved less than one. Right?
Yep
We're really encouraged by that metric in particular.
What about the durability of effect here? Should we anticipate to see sustained levels of CRP reduction at longer time points? How important is it to show that the levels stay down over time?
Yeah, no, that's critical. Obviously we're addressing chronic diseases right now, and so-
Yeah
You're not going to prevent cardiac events in a two-week treatment period. This is likely to be a chronic therapy, and so the durability of effect is really important. A key goal for the POC trial and the dose ranging that we're doing is over three months sort of confirming that the reductions in these inflammatory biomarkers are in fact stable.
Yeah.
We're encouraged by the Ventyx data where they did show these biomarkers were reduced quickly, and then they pretty much were stable, and so we're hoping for the same.
Yeah. IL-6, another important biomarker, I believe you showed some of that data in your previous phase I readout. Similar to the CRP questions, how important is it to show durability of response on this one? I think it was around 58%-69% in the phase I SAD. Could this be driven to even greater reductions with some of the MAD data, or what are the expectations for the IL-6?
Yeah. I think like CRP, we're looking for one thing, concordant changes. We've looked at and reported IL-6. We've also reported fibrinogen, and those change in concert with hs-CRP, and we're going to be looking in the three-month trial to see consistent reductions in those biomarkers. Right? We want to see concordance, and IL-6 is downstream of IL-1 beta, and so our expectation would be that that effect would be sustained.
In terms of potential effects on liver data, will you be looking at any biomarkers of liver health here, and how reliable and/or important are these at the time points that you'll be looking at?
Yeah. We'll be looking at liver in the three-month study. Similar to Ventyx, we're going to include MRI imaging of the liver, so to look for liver fat content, look for liver inflammation. We're not going to require it as part of the eligibility criteria, but for participants who have deficits that are correctable, at baseline, we'll be doing subgroup analyses to look at our effect there.
Right.
I don't think that directly informs what our go-forward strategy would be in ASCVD, but I do think it broadly supports benefits of this mechanism in cardiometabolic disease.
BJ, you've mentioned it earlier, but in terms of the Ventyx readout from last year, can you just describe the importance of that phase II data readout? Is this a good comp to what investors should be looking for with BGE-102, and what are the read-throughs to the phase I MAD data coming later this quarter? What are the read-throughs also to how you design your planned phase II trial?
Yeah. No, it was a really informative readout. There were two things that I think were really impactful for the way we're thinking about BGE-102. One is just the magnitude of anti-inflammatory effect. They were approaching what we're seeing with the IL-6s cross-trial comparison sort of caveated, et cetera, but which we're now seeing in line with those compounds. I think that the magnitude was surprising to the upside, and then I think the fact that the changes were rapid and sustained. As a result, we added these obese, inflamed MAD cohorts because we thought actually we can get a pretty strong first look at the anti-inflammatory effects of the molecule in the phase I setting. Very informative from that perspective. Our POC trial, our three-month trial is going to be very similar to theirs. We want to generate a comparable data set.
Looking at what we're trying to accomplish, we want to confirm over a broader treatment period or a longer treatment period, what we hope to be best-in-class anti-inflammatory efficacy.
How relevant is Novo's IL-6 program for your development plan for 102? Could the results from Novo's program, and the learnings from it, could it preclude the need for a full CVOT? The thought being what could use CRP as reliable surrogate endpoint for, say, accelerated approval?
Yeah. I think it's too early to speculate or to comment on the potential impacts of ZEUS on the regulatory path. I would say just. More generally on how to think about ZEUS, we think it could be really positive for a variety of reasons if they were to show us a strong MACE benefit. I think despite CANTOS being more directly downstream of NLRP3, and we think more de-risking from the biology perspective, it would broadly validate, okay, you can target this inflammatory axis, and that'll yield cardiovascular benefits. That's important. As I mentioned, just the physician awareness, making testing for CRP more routine. I think that there's a lot of sort of market development that would be helpful with injectable launches prior to an NLRP3 inhibitor.
In terms of the safety profile so far for BGE-102, can you summarize the data that you've seen? Just given that the drug is CNS penetrant, how do you frame the risk benefit of BGE-102 versus a drug that is not CNS penetrant?
Yeah. In terms of the safety tolerability data to date, it's been very well tolerated. In all the cohorts we've evaluated, all the AEs have been mild to moderate. Again, no dose dependency, no dose-limiting toxicities. We also, as part of our 10-K update, we actually expanded our tox margin. We have three-month GLP tox results and now giving us a 50x-97x safety margin on the 60 milligram dose. A little bit of a bump up and I think the totality here is really exciting for us. In terms of the CNS penetrance and the trade-offs there, we see the ability to access the CNS and across the blood-retinal barrier as well, which is critical to our ophthalmology strategy, is maximizing the optionality and the degrees of freedom on the table for this molecule.
We just don't see real trade-offs here in terms of safety or tolerability. Nothing's come up in any of the talks that
Yeah
In our experience and with the Ventyx program, there's nothing to sort of suggest a CNS liability. We think it's upside for the program. Honestly, I would point out that there are indications like ophthalmology where obviously crossing into protected compartments is required. Even if you look at something like ASCVD, there's evidence to suggest that actually it's neuroinflammation that coordinates or links psychological stress to actually cardiac-
Yeah
outcomes and sort of coordinating this sort of beta-adrenergic response. Even if things that are maybe notionally seem peripheral, there could be benefits to having central exposure.
Right. Well, that's a perfect lead-in to our next segment on ophthalmology, and you answered my next question on why this drug, you believe it will work in an ophthalmology indication like DME, which is quite different than a CV type indication. There are a lot of relationships there and factors that are highly related, so very interesting. I guess in terms of the points of differentiation from standard of care, let's say in DME and potentially geographic atrophy, which is an indication you've indicated that you could potentially look into, how would BGE-102 address the unmet need in each of those indications?
Yeah. No, it's a great question. In DME, it's managed now mostly with anti-VEGF injections, so intravitreal injections. Among the key unmet needs there are really non-compliance, so there's a disparity between clinical trial results and real-world results. Then there's a big segment of patients who are actually partially or fully refractory to anti-VEGF therapy. In thinking about it, okay, you can introduce a new mechanism of action, and an oral, so you could address essentially three different patient segments. One is the watch and wait. Patients who have some edema, they don't have meaningfully compromised vision, so you're going to delay or watch and wait before you initiate therapy with VEGF. You could treat those patients and delay the onset of VEGF. You could think about VEGF sparing, in a co-treatment setting.
You could also think about using it to treat those who are refractory to VEGF. There are a lot of different ways to position it in DME, and I think, what's interesting about DME as well as GA is, obviously, you're using an oral, and systemic administration is a way to access the local inflammatory milieu, where we think NLRP3 is very relevant. There are also potential systemic benefits. It's not just a convenient way to access the eye, but there are actually also systemic benefits. We've shown with BGE-102 improvements in insulin resistance in just sort of a diet-induced obesity model.
That's sort of concordant with NLRP3 knockout mice that have improved insulin sensitivity, and so you think in that case, you're able to potentially address the systemic risk factor, as well as the local disease biology in the retina as well. Yeah. In geographic atrophy, there's enormous unmet need, right? Complement inhibitors are approved.
Yeah.
They were approved on the basis of a slowing of lesion size growth. They haven't shown visual acuity benefits yet. It's pretty modest efficacy. Just bringing forward a new MOA that can either, as monotherapy or in combination, improve the disease control for these patients would be enormous. I think, having an oral that can do it, and convenient, that's nice. The most pressing unmet need is just slowing disease progression.
I guess to our knowledge, you're the only one with an NLRP3 program in ophthalmology. I think most of the other programs are going after neuro type indications as their secondary indication. What's the basis for this? Is this based on something that you believe is differentiated about your drug, or is it kind of the company's appetite for differentiation here?
Yeah. I think part of it is just the intrinsic properties of BGE-102. We have really nice penetration of the retina. We're able to address that local inflammatory context with an oral systemic medication. I think that we want to lean into that profile. There's also been sort of adjacent clinical validation, right? There are a number of companies who are developing VEGF, IL-6 bispecifics, and those have shown incremental efficacy over VEGF. It's not the same obviously, but it broadly validates the idea that addressing inflammation can actually result in sort of meaningful improvements in efficacy. We're looking both where there's signs of clinical evidence and where can we really lean into the differentiation of our compound.
You mentioned you plan to start a trial in DME this year. Can you describe trial design, what are the goals and some of the key endpoints?
Yes. We are initiating the DME trial this year. There are going to be three arms. With about 30 patients per arm. The treatment duration is going to be eight weeks. The two key arms are VEGF placebo and VEGF plus BGE-102. This is essentially the same paradigm as some of the bispecifics where they're looking at that versus VEGF alone, right? Have shown pretty rapid separation of those two treatment groups. Then we'll have a third arm, which is just BGE-102 monotherapy. We've seen in preclinical models very strong efficacy as a monotherapy, and so we're very interested to just play that forward and see how changes in baseline in our key biomarker, which is intraocular IL-6. We really want to demonstrate PD in the eye, right? That it gets into the eye and has a pharmacodynamic effect there.
We're going to be measuring, of course, on an exploratory basis, BCVA, CST, and we'll be looking to see what is the totality of the picture here. Are there numerical changes in those endpoints as well? Given the treatment duration and the sample size, it's not powered for those endpoints.
Yeah
We'd be very happy with sort of directionally consistent outcomes there.
Are there, in terms of the biomarkers, certain reductions or levels of, say, IL-6 that you'd be looking for, absolute or relative, that would give you confidence? Then just as a follow-up, you mentioned BCVA, certainly an important registrational endpoint in DME. You mentioned directional changes, but is there a bar for success there on BCVA, just given the short duration, or anything else that we should be aware of?
Yeah. I mean, in terms of the biomarker reductions, we're looking for a clear pharmacodynamic effect. That can be just looking at IL-6 and looking at the totality of that plus exploratory biomarkers and what is the full picture telling you. It's really hard to just benchmark a number there.
Yeah.
I would say in terms of BCVA, it really depends on ultimately where you advance the molecule and how you want to differentiate it. As I mentioned, there are really sort of three different patient segments, so like the watch and wait early patients, VEGF sparing, essentially in combination, and then the refractory patients. It just depends on ultimately where we would go, and how we would position the molecule.
Great. Well, I want to leave time for APJ and some of the rest of the pipeline, so maybe a question or two on that. Next gen NLRP3 and preclinical development. How different is this drug from BGE-102, and how do you plan to position it going forward?
Yeah. With that, I think it's too early to get into the specifics on how we're positioning the next-gen program. We'll share more details on that as we get closer into the clinic.
In terms of the APJ obesity program, anything that investors should know about that? Any updates and development plans there?
Yeah. We're advancing both an oral and a parenteral APJ agonist. We're anticipating submitting the first IND for APJ by the end of the year. Just as a reminder, this is a target where, in preclinical models, we've shown a doubling of weight loss when you combine it with an incretin, as well as complete restoration of body composition back to that of lean controls. We're really excited about, you know, developing this as an incretin adjunct. I think that there's obviously in the market, there are going to be established oral and parenteral segments going forward.
I think the unmet need around, I think that we've really seen a shift or an evolution in our thinking about what the treatment goals are in obesity, away from, quote-unquote, "The Weight Loss Olympics," where we're sort of benchmarking overall weight loss down to a significant figure, and more around body composition, looking at the clinical picture with a little bit more granularity and what actually impacts quality of life, ultimate health outcomes. I think that there are certainly tailwinds in our thinking about body composition and in the obesity context, yeah.
Current cash position, where do you stand there and what are your expectations on cash runway?
We had $285 million at the end of last year. We raised, on a net basis, about $125 million in the first quarter. All the milestones that BJ's laid out for you, plus some proof of concept work in the APJ programs, as well as some CMC to support later trials, especially with BGE-102. It's part of the phase III preparedness, will result in a budget that forecasts us having more than three years of cash from this point.
Got it. I guess, lastly, the stock, certainly it's performed well over the past six months. In your view, what's been the primary driver for this? For investors that are still on the sidelines, can you recap what's kind of the biggest disconnects in your view, and what offers potential for upside here on the stock?
Yeah. The stock's been on a journey in the past year, and I think a lot of the positive momentum that we've seen was really around the BGE-102 data and our evolving strategy there. Really in January we announced the results from the first obese MAD cohort, the 120 mg dose level. They're showing the potential for best-in-class efficacy. I think that's created a lot of excitement around it, right? That's sort of the intrinsic factors. I think there's, of course, growing awareness of an NLRP3 and the opportunity, and I think, of course, Lilly's acquisition and in-licensing of the IL-6, the Tourmaline acquisition, and certainly anticipating the Novo ZEUS readout on the horizon. There's sharpened interest and focus in this opportunity.
Great. Well, BJ and Dov, thank you so much for the excellent discussion.
Yeah. Thank you so much for having us.
Thank you, Joey.
Thanks, everyone, for joining us on the webcast. Have a good rest of your day.