All right. Good morning, everyone, and thanks for joining us at the Morgan Stanley Global Health Care Conference. I'm Mike Goldstein, the biotech analyst here, and it's my pleasure to introduce the team from BioAge Labs, Kristen Fortney, CEO and co-founder, as well as Dov Goldstein, CFO. Just before we get started, I need to read a quick disclosure for important disclosures. Please see the Morgan Stanley Research Disclosure website at www.morganstanley.com/researchdisclosures. If you have any questions, please reach out to your Morgan Stanley sales representative. With that, Kristen and Dov, thanks for joining us today. Maybe, Kristen, I'll hand it over to you to just make a couple of introductory comments, and then we can get into the Q&A.
Yeah, thanks for having us here today. We're pleased to be here to talk about BioAge Labs, our platform, and our programs.
Great. Maybe we can just start on the platform piece, and maybe you can talk about your focus on just metabolic aging and how you translate that into promising therapeutics.
Yeah, sure. The platform at the company is really important for us. We've invested a lot of resource and time into it over the years. It is very unique in that it comprises about 50 million molecular data points collected over decades of human aging. It is one of the largest collections of human aging data sets in the world right now with people from different, you know, ethnic backgrounds, et cetera. Also, importantly, with decades of follow-up. Aging doesn't happen overnight. It happens slowly over the course of decades. We have human samples and human medical records with up to 50 years of follow-up, which is fairly unique. We use these data sets to identify important targets for metabolic aging. That's really the focus of the company right now.
Strategically, when you look at the assets, the targets that come out of the platform where we built compounds, the ones that are in the clinic and at earlier stages, we're really focusing broadly on this area, which is the next generation of obesity therapy, so beyond weight loss. There is certainly the oral segment of the market where weight loss itself is still a need. Beyond that, there's muscle loss, there's inflammation, and dealing with other obesity comorbidities. Of course, there's the side effect profile.
Gotcha. Maybe just the uniqueness of the platform and maybe talk a little bit about some of your discovery capabilities in terms of identifying targets, et cetera.
Yeah. What's unique about our discovery platform really is the focus on aging. Like a lot of other biobanks that are useful for drug discovery, like the UK Biobank, for example, or DCODE, they don't have the same degree of follow-up. Most of their participants will maybe have 10 to 20 years of patient follow-up, and most of the samples, you're capturing people when they're already diseased or close to diseased. Aging really drives a lot of different chronic diseases as you get older. What our data enables us to do is look for those molecular changes that precede disease, so some of these sort of earliest switches that you can intervene in to improve outcomes.
How do you link the disease to the actual sort of change in the genetics or whatever data points you're looking at?
Yeah, sure. What our data set is the most useful for is finding things that predict longevity itself, so time to death. After that, you would use standard methods to find particular diseases where it might have promise, right, like Mendelian randomization with genetics or just interventional models with animals where you can't do that.
That makes sense. You recently expanded your sort of discovery platform with data from the HUNT Biobank of Norway. Maybe speak to how that sort of enhances and complements your existing database.
Yeah, this is a substantial increase in our platform's capabilities. The HUNT Biobank data set is Norway's national biobank. It's one of the largest ever health studies. They have over 30 years of health records. We're doing an additional 17,000 samples. It's a lot of new human data. It's very enriched for disease, right? Over 50% of these individuals go on to develop some kind of cardiometabolic disease. Over 33% of them, some kind of brain degeneration. It's really a rich source for novel targets and complementary to what we already have.
How big is that versus your existing database? Is it multiple times?
Not multiple times, but it's a significant chunk.
Yep.
Yeah.
Gotcha. You apply the same sort of methods to sort of interrogate that data set as well. Is there anything?
That's right. What's unique is some of the enrichment for particular diseases of interest to us. Those cases are more unique.
Gotcha. OK. You also have a number of pharma collaborations that sort of speak to the uniqueness of what you're doing and why it's important. Maybe you can sort of touch on some of those collaborations and what you're doing there.
That's right. No, that's been very validating to the platform. We announced a couple of large pharma collaborations that are different in type over the past year. Last December, we announced a collaboration with Novartis around novel target discovery. They're very interested in sort of the interface of aging biology and exercise. One of the targets that we work on at the company is exactly kind of in this intersection, which is apolin, the factor which declines as you get older, induced by exercise and can have several benefits. Novartis was really interested in leveraging our platform and our data to find other targets like that. It's really useful for us because it's cashed into the company, into the platform to keep that engine running. It also lets us bet on kind of the earliest stage of biology, right?
They're specifically interested in using our data to find novel targets, targets that nobody else is working on today, and take those forward. The way that it works, too, is that we're going to bring our aging data to the table. Novartis has some exercise genomics data that they're going to bring to the table. We're going to look at the intersection together. They'll advance some targets, and we'll advance some targets.
OK, great. You also, I think, have a partnership with Eli Lilly as well. Maybe you can just touch on that.
Yeah. The Lilly partnership is great, too. It is different in kind. This is more for a couple of targets that we're excited about from our human data that we want to build molecules. We're using their expertise in building molecules. They're building drugs for us that the company would then license and bring forward ourselves, which is great because it really helps us expand our earlier stage bandwidth and then commit at a later stage. Yeah.
You mentioned with the Novartis agreement that leverages your database and platform to bring in some cash. Are you thinking about other partnerships? Is that something you continue to think about? How do you or other ways that you can leverage the platform?
That's something we continue to be very interested in and exploring with other potential partners. What we have is fairly unique, can be applied to different disease areas, and there's a lot of interest.
Yeah. Can you talk about some of the other disease areas? I mean, what the limitations of the platform are? How broad can you sort of interrogate this data?
Yeah. Internally, we've really been focused on metabolics. That's, I would say, where we have the most expertise. There is, I would say, probably the second most largest area of outside interest around the brain, right? If you think of diseases like Alzheimer's, you really want to intervene earlier. People are looking into aging biology, and that has sparked interest in the platform.
Yeah, very interesting. OK. Maybe we can sort of shift to your lead platform, BGE-102. Maybe you can just start by talking about the mechanism there and why it's sort of well-suited for obesity.
For sure. BGE-102 is a brain-penetrant NLRP3 inhibitor. That's a drug that we built ourselves, we believe has best-in-class potential. We just kicked off the phase 1 study in August. NLRP3 goes up with aging. It's a very nice signal in our human data. It also goes up with nutrient excess and can drive both appetite dysregulation and obesity, as well as general inflammation, which can worsen cardiovascular outcomes, for example. What's been shown preclinically in the hands of other companies, as well as ours, is that if you inhibit NLRP3 and specifically inhibit neuroinflammation with NLRP3, that can lead to weight loss.
Can you maybe dig a little bit into some of your preclinical data that sort of drove you to advance the program?
Yeah, sure. Basically, if you give this as a monotherapy to the standard diet-induced obesity mice, you do see weight loss on par with semaglutide, so a very nice monotherapy effect driven by appetite suppression. It's not an energy expenditure mechanism. It's reducing their hunger to more normal levels. You also see very nice additivity on an incretin background. If you co-treat with semaglutide plus our drug, you do get very substantial additional weight loss. That's what we think is really exciting because this is an oral drug. As you look to the weight loss landscape today, there's clearly a need on the oral side to have improved weight loss performance. I think drugs like tirzepatide probably already give us all the weight loss we need in an injectable format.
As you can see with the Orpho package, etc., GLP-1 agonism alone in a pill is not going to get you there. It's not going to be competitive. There's a lot of interest on the part of pharma and complementary mechanisms that you could have together in the same pill, like a GLP-1 NLRP3, that could drive additional weight loss.
How is your molecule maybe different from another molecule in this space?
Yeah. There are two other molecules that are a bit more advanced by about a year, not Thera, and also Ventex. The key differentiators, we believe, are best-in-class potential in terms of both the potency and the degree of brain penetration. Our KPUU is basically one, so you get the same amount of drug in the brain and the periphery. Drug in the brain is what you need for the weight loss efficacy, as we've seen in others' work. We're also best-in-class in terms of the preclinical package. We do see very nice monotherapy, as well as additive efficacy, superior to what's been seen with some of the other molecules. As a more scientific point, we also discovered a novel binding site to NLRP3. We have very differentiated chemistry in binding. We recently published a couple of papers on that just a few weeks ago.
Great. I think you recently initiated a phase 1 study, right? You're advancing that nicely. Maybe just talk about the design there and the doses you're looking at, if you can.
We didn't say which particular doses we're using, except what we did say is that from everything we know in animals, we do predict a once-daily dose of around 50 mg, so a very sort of reasonable dosing paradigm. Study-wise, it's very typical in terms of a SAD-MAD design with one important difference, which is that you can learn about PD in phase 1 with the NLRP3 mechanism. That's because of this ex vivo whole blood assay you can do where you take blood from patients, stimulate with LPS, and look at IL-1 beta inhibition. That's really nice because you can come out of your trial knowing what dose suppresses IL-1 beta to the right extent.
You're still in the SAD portion currently. Maybe you can talk about how many patients you're enrolling or plan to enroll for that portion of the study.
Yeah, we didn't release the exact number of patients, but it's basically typical in size. We will announce the SAD results when they're done. We will share that.
Maybe talk about when you might do that and sort of what data you might include in that sort of update and how to think about those results.
Yeah, sure. We previously shared end of year. We're on track for that to have that data in hand by end of year. That should include basically the PD marker as well, right? We're still going to learn more from the MAD portion. That could also inform our dose choice. We're going to learn a lot from the SAD portion in terms of the sort of extent of IL-1 beta inhibition with a single dose.
Will the venue just be sort of a press release, something like that?
Yeah, that's right.
Obviously, the key piece of data we're going to be looking at is this PD effect. Is it just.
That's right. Of course, the safety that you get out of the SAD, yeah.
Are we just looking for a trend on this endpoint? How do we know if that effect is a good effect or a marginal effect?
Yeah, our goal is to have 90% inhibition, which is something we've seen.
That's pretty good.
We've seen that in primates with a single dose. That's what we're looking for in people as well.
OK. The long-term vision here is a fixed-dose oral combination. The 50 milligrams once a day is very important. That plus or minus allows you to combine it very easily with a drug like semaglutide to a single pill once a day. That's the long-term vision of what you could do with the drug. It has monotherapy potential as well. The fixed-dose oral combination is particularly interesting. Yeah, that makes sense. Maybe going back to the preclinical data, when you do the combination, do you see just additive, or are you seeing synergistic effects on the weight loss?
I would say additive. It's not an energy expenditure mechanism.
The phase 1 update we'll get, you mentioned also safety is important. Are there any sort of key safety or adverse events that you'll be looking for that are notable with this sort of mechanism?
Not specifically. A number of these have been in phase 1 trials before, and we know they can be well tolerated. We want to have a competitive profile there, too.
Yeah. If we just think about you'll share your SAD data, what's the next step, and maybe how many combination doses are you sort of considering? What does that MAD study look like?
Yeah. It's just a typical MAD study as well. We're not doing combinations of drugs yet. This is more like NLRP3 too has a lot of potential in other diseases. This is a standard phase 1 package that will enable further development in obesity, but also in other indications. As soon as the MAD reads out, we'll go immediately into a monotherapy obesity trial, which will read out by the end of next year, so not too far in the future. That will be sort of precisely designed around looking for weight loss in a patient population.
Gotcha. In terms of the strategy, Dov, you mentioned combo is pretty important. Would you also consider a registrational path for a monotherapy first or something like that? How do you think about, or can you do it combined maybe or something like that?
Yeah, no, that's a great question. I mean, this is nice because the mechanism already has very great monotherapy potential, right? We do think what is going to be most attractive commercially is going to be a combination. If it behaves on par with GLP-1 agonism, then it might also not be competitive enough to compete with an injectable, at least as a first-line therapy. It could still be a maintenance therapy, right? There's still other potential utility. The combination development will be an important part of what we do. Right after the monotherapy study reads out end of next year, we would go into a longer study. You do need six months to have good power to look at the combination with a GLP.
OK. This PD effect that you're going to see by the end of this year, you said you're looking for 90% reduction. How does that, is there a way to translate that into sort of like a weight loss outcome in some way? What's the thinking there?
I can tell you that preclinically, the extent of IL-1, like sort of target coverage in the brain, was very relevant for the weight loss effect that we saw. Here, of course, we're looking at peripheral blood.
OK. We talked about competitors earlier, you mentioned two. I think one will have some data later this year. Is there anything in particular you might learn or learn from that study, or any read-through to your program or how you're thinking about that?
Yeah, I mean, we're really excited to see that readout. That would be really meaningful. This is a novel target in obesity. They have a well-powered monotherapy look at their drug, hopefully coming in October. We're very interested to see how that reads out.
Gotcha. Targeting NLRP3, you're focused on obesity, but there's other opportunities for that target. Do you have any plans to potentially expand into those disease areas? Would you partner or something like that?
Yeah, no, that's something we think about a lot. There are a lot of experiments ongoing right now in the hands of others, right? Novartis should have an osteoarthritis readout by end of year. There are a number of Parkinson's experiments going on, right? As I mentioned earlier, our phase 1 package will enable us to quickly go where we think it has potential. That is going to be data-driven. Yeah.
OK. Maybe just one last question on 102 here. We talked about the path and next steps. Is this, when you start to get to commercialization or thinking about commercialization, I know it's way down the road, but would you plan to build your own sales force and launch it on your own? Do you partner? I know you kind of have to see the data to figure this out. What's the general thought?
Yeah, in obesity, you're probably not our own sales force. Do you want me to comment? Yeah.
I think what's important for investors at this stage of the company is you can take it all the way to approval. It's about 3,000 patients in a safety database of the dose that gets approved is needed for approval. That's something with public equity dollars. Some people, we've been asked about royalties. There are multiple different ways to finance it. A little company can hold on to the value until we get the right deal quite well in the development of the program.
Yeah, makes sense. OK. Maybe we can move to just the APJ agonist. You've got a few programs or a few products in development. Maybe just talk first about the mechanism of action to kind of set the stage.
Sure. Apolin is a mechanism we've done a lot of work for preclinically as well as clinically. Apolin is a factor that is induced by exercise. If you go for a bike ride or a run, your body makes a lot more apolin. It seems to mediate some of the positive benefits by increasing energy expenditure. We've seen in obesity models that this is not a monotherapy weight loss drug, but when you combine it with an appetite suppressant, whether that's GLP or another mechanism, you do see this very nice synergistic weight loss, not driven by reduced food consumption, just increased energy expenditure. You can see that in metabolic cages. You also see relative improvements in body composition as well. This is a mechanism that we believe could have the potential to help you retain more muscle.
In fact, we did a phase 1B clinical trial in an older population at bedrest, and we saw more muscle preserved in those that were taking an apolin agonist. It's a mechanism we're really excited about. We have a couple of programs that we made announcements about in the summer. They're preclinical. They're both on track for filing IND by end of next year. The target we have a lot of conviction in, so we have both a biologic strategy and a small molecule strategy. We announced recently that we have an option agreement to work with an APJ agonist and antibody, which is a really exciting program. This was a program developed by Zhiqang Therapeutics in China. The founder of that company is actually one of the foremost experts in APJ structural biology. She first published the crystal structure.
She's built this very potent antibody agonist that we're hoping to take forward. We also have a small molecule program here as well where we filed novel IP for very potent compounds. Again, hope to file IND next year.
You have had previous experience with an APJ agonist. Maybe just talk about some of the learnings there and how you apply that going forward.
Yeah, the first APJ agonist we brought to the clinic, Azalipreg, unfortunately had some liver liabilities from the obesity study that we did. The data set that we gathered in the clinic, especially in our elderly bedrest cohort, gave us a lot of conviction in the mechanism. It will help to retain muscle. We want to stay very far away from the Azalipreg chemistry with our next-gen compounds.
You mentioned you have both an oral and injectable approach. I don't know if you can talk about any sort of preclinical findings or interesting things you've seen there.
Yeah, only with the tool, the Azalipreg tool, not with these novel ones. We would anticipate similar benefits. We would anticipate additive weight loss on top of an agonist or other appetite suppressing background. We would expect more retention of lean body mass, which is a need especially for the older cohort of patients that are losing weight. This has the same potential with NLRP3 where you have more weight loss in a pill. We think especially the oral segment is really interested in obesity. This is the one program where we also have an injectable drug. As we think about the long-term future of obesity therapies, we think it's going to go to orals and long-acting injectables, right? Here we have a bet in both areas.
You mentioned you're going to be working towards filing INDs. What's kind of the next steps in sort of the oral and injectable? Are they kind of in the same sort of time frame or is one ahead of the other?
Yeah, it's hard to say given that they're not at IND stage yet, right? There could be all sorts of surprises along the way. They're both on track for IND next year.
OK. You kind of have two options there, oral and injectable. What do you think might be the preferred method going forward?
That's hard to say. That's kind of projecting the whole future. I think if you had an oral drug that performed on par with tirzepatide, that would be a first-line choice for people, right? There's, of course, a lot of cost advantages, too, right?
Yeah. Maybe talk about what you saw on tolerability with the APJ agonist. Obviously, the ingredient has a lot of GI concerns. What are you seeing on that side?
Yeah, that's another edge with this mechanism. There are really no GI issues of note with APJ agonism. They have extensive phase 1 data conducted by Amgen with the drug that we previously worked with.
Is the view more combination also with this approach? Is there opportunity monotherapy?
Unlike NLRP3, this is more of a combination therapy for weight loss because we wouldn't expect monotherapy weight loss. You do see as a monotherapy protection from weight gain, so it could be used as part of a maintenance regimen as a monotherapy. We see the clearest value proposition as a combination for weight loss.
Anything else in the pipeline to talk about?
The other programs we're working on at an earlier stage, we mentioned yet a couple of targets we're working on with Eli Lilly, et cetera. We continue to advance exciting targets for metabolic aging from the platform.
OK. Maybe I can ask sort of a last question here about just you're pushing your programs forward. That costs money. Maybe just talk about where the cash position is now, what that covers, and how far that goes.
At the end of June, we had told investors that we had a little over $310 million of cash on the balance sheet with the milestones we've told you about. The SAD-MAD monotherapy cohort and the IND enabling studies for the two programs in APJ, we still have over three years of cash from today.
OK. Great. Maybe just one last question before I get into a couple of the macro questions. Maybe just walk us through the next year or two in terms of the catalysts that are coming and what we should be sort of paying attention to. I know we talked a lot about this already, but just.
There are internal catalysts and there are external catalysts. I'll walk you through both. Importantly, what's coming next, as Kristen mentioned, is the SAD data by the end of this year that will come with PD as well as a sense of dose. We'll have the MAD data in the first half of 2026. By the end of the year, we'll have quite a robust monotherapy experience looking at NLRP3 as a single agent. The APJ agonist programs, and we're currently thinking of advancing both of them. The macromolecule and the small molecule are on target for an IND filing by the end of 2026. That's the guidance we've given externally. There are two milestones or multiple milestones. I'll just tell you a couple of them. We've talked about Ventex. Their data is coming in, we think, October. That's a study that's well-powered for monotherapy.
Unfortunately, it is probably not powered for combination therapy. We're focused on the monotherapy result there with their drug. Thera has data coming with just monotherapy, but in diabetes as well as non-diabetic patient population. That's coming in Q2 of next year. Novartis has AOA readouts that we're expecting in the fourth quarter of this year, probably towards the end of the year. The OA is particularly interesting because about 50% of OA patients are obese. The Novartis drug is a peripheral drug. It would treat only the OA and wouldn't treat obesity, which you need a central mechanism. We could come behind a positive result with them with the drug that treated both the aspects of the disease process. Obesity is causative for OA as well.
Great, thanks for that. A lot to look forward to and continue to make progress. Looking forward to that. Maybe we can ask some macro questions. We've been sort of asking all the companies at the conference for some perspective on these. I'll start maybe with the first one, just with China's rise in biotech innovation. How are you thinking about your competitive position here? Will this influence your R&D strategy?
Yeah, sure. That's a very important question for us and everybody else. We try to use China really as an internal accelerant. As we mentioned, we have a recent option deal where we're with Zhiqang Therapeutics where they have something close to the clinic, we hope, that is an APJ agonist. We've also worked on the discovery side. Like our novel NLRP3, for example, started off with a DNA encoded library screen with HipGen, which is a great company. The separate point is that we do focus with our platform on novel targets. I think China and other players have an edge where it's like a validated target. It can go with the next gen. We are trying to keep our novel targets under wraps.
OK. Great. Maybe the second question is just how you're currently leveraging artificial intelligence or thinking about AI's future disruption potential for the industry.
Yeah, no, that's a really fun question. That's, of course, always been part of our platform. It's really nice to see the capabilities grow. We can build all that into the platform around target discovery, which we think is still a very hard piece, right? Like which new targets do you bet on? I think it's also been very useful so far in accelerating molecule identification, right? I mean, like I just mentioned HipGen. DNA encoded libraries are a perfect use case for AI. We are right now, as I think many companies are, going through the exercise of trying to apply it across departments, especially on the clinical side, the regulatory side. There's a lot of paperwork where LLMs can be really helpful. Yeah. Any thoughts?
No, that was well said.
Yeah, OK.
It is built into the DNA of the company to begin with because of the platform. It is exciting and very easy to integrate it into different aspects of the business. It is integrated into finance, if you can believe that. We are doing things with LLMs to help us with filings and stuff like that. We take it very serious.
Great. All right, we'll end it there. Thanks so much, Kristen and Dov. Really appreciate your time today.
Thank you.
Yeah.