Good afternoon, everyone. Welcome to our Piper Sandler Healthcare Conference. My name is Yasmeen Rahimi. I'm a senior biotech analyst here at Piper Sandler. Really excited to have BioAge Labs here with us at our conference. Congrats on a very successful IPO.
Thank you.
Thrilled to have you and discuss lots of great topics over the next 25 minutes. I think the first place to start off is, I think there's quite a bit of enthusiasm. We can all agree obesity has been a phenomenal therapeutic area. But maybe help us understand the differentiation of your assets, both your apelin as well as your NLRP3, of how it could be well positioned for obese patients or metabolic syndrome patients, obese/type 2 diabetes.
Yeah, for sure. Happy to go into all that. First, thanks a lot for having me here. It's great to be here despite the weather. And yeah, we have a couple of programs that are fairly differentiated. Our lead program, azelaprag, is differentiated in a few important ways. I mean, for one thing, it's an oral small molecule in the obesity space. And for another, it's not an appetite suppression mechanism. If you think of the universe of weight loss drugs, and even if you just restrict yourself to those oral mechanisms, there's really only two ways you can lose weight. You can either eat less food, which is how the incretins work, how CB1 works, or you can burn more calories, more energy expenditure mechanisms, which is true of our drug, azelaprag, also true of some of the other mechanisms like the mitochondrial uncouplers, et cetera.
So in the universe of weight loss drugs, we're in the sort of complementary oral bucket. And what's really exciting about that is that, as you're aware, the injectable drugs are super effective. You can get 20% plus weight loss at one year. And the orals, there's no clear winner yet. And just like the injectables, the orals are going to have to go multi-mechanism. GLP agonist by itself in a small molecule is not going to get you there. And when you think, what is a set of things that you can plug together with an oral GLP to amplify weight loss, improve tolerability, et cetera, it's really a very small set of things. So we're in that category that it's not competitive with the incretins. It can help improve them.
That's very helpful. Would love to also dig into the STRIDES data that's upcoming in 3Q. Congrats on success on moving it even earlier than expected. So that's always a wonderful and great problem to have. High level, what is the design of the STRIDES study and what are your expectations around the trial?
Yeah, for sure. So this is our ongoing STRIDES trial, which is a collaboration with Lilly, where they're supplying tirzepatide, which we're using in the trial. And our goal going into designing this trial was that we really want to show, in some ways, the most important value proposition for the company is to show that you can take the weight loss profile of an oral incretin and improve it by 5%. And we're combining ourselves with tirzepatide, which is not an oral because it's an approved drug. But in the STRIDES trial, we specifically selected the five-milligram dose of tirzepatide because it has the weight loss kinetics of an oral medicine. That dose of tirzepatide will give you 15% weight loss at one year.
And what we really want to show is that we can take that 15% weight loss at one year and take it to 20% plus when you combine azelaprag together with tirzepatide. It's a bit more complicated than that because we have a six-month trial, not a year-long trial. So what that means is that we want to take 12% tirzepatide alone weight loss at six months and increase it by an additional 3.3% at that point in time because that will correspond to 5% plus at one year. So our trial was really designed with that goal foremost in mind. We have 90% power to show that weight loss increment that would correspond to a real win in terms of, that's the regulatory hurdle for approval, but that's also the difference right now between oral and injectable weight loss.
What do you hope to see in the monoarm? Because there's a monoarm, there's a comboarm, where it's tirzepatide.
Yeah, that's right, so that's the combo arm where we're really powered to see a weight loss difference. We're not anticipating a very dramatic monotherapy weight loss difference. We haven't seen that preclinically. It's more from a safety perspective. This drug has not been in people for longer than a month, so it's mostly for safety reasons, so it's a much smaller arm. It's 20 patients.
Is there an opportunity to also see mechanistically differences in GI tolerability? Or do you want to be GI tolerability neutral? Basically, don't make it worse, but don't expect it to suddenly your nausea, vomiting, diarrhea is going to go away.
That's a great question. Yeah, I don't think it's going to make anything disappear. Our expectations going into that.
That would be amazing if it does.
Yeah, that would be magic. Yeah.
I would like that.
One of the nice things about azelaprag is that it is pretty clean from a tolerability perspective. Some of the other complementary mechanisms have similar tolerability issues to the incretins, which might amplify when you combine them. But what that means, though, is that you might have strictly superior tolerability for the weight loss. So because we're going into this trial with the low dose of tirzepatide, if we come out of the trial and we're achieving the same weight loss as the 10 or 15-mg dose of tirzepatide, but we haven't moved the needle on tolerability, that's a big deal. Because then it's sort of like a better it's very much a function of the dose and of the weight loss.
That's helpful. And then I think we all understand that rebound of weight has to do with our ability to lose lean mass because when we're using weight with the incretins, we're losing both fat and lean mass. It's a combination. Given the mechanism and apelin receptor agonist, there's a lot of data supporting muscle mass preservation. Could you talk about what is built into STRIDES in terms of measurements for assessing lean mass preservation? And what do you hope to gain there?
Yeah, we're really excited about the implications for body composition too with this mechanism. We don't have power for that in this trial. So these are firmly in the exploratory category. But we can at least learn about variability to properly power future trials. But we are going to be using DEXA to look at lean muscle, fat, bone as well. Everyone will have wearables as well. So we'll have activity measures. We'll look at a handful of functional measures too. Though same story there, we're probably not powered to see a difference. But that's another really important differentiator for this mechanism. And to your point about rebound, again, we're not powered. But this is a six-month weight loss study, and then we're going to follow them for three months afterwards. Because people usually do rebound a lot.
Again, you would need a larger trial to be properly powered for that kind of effect. We think that's really interesting to consider for the future. We will start to learn about that from this initial trial.
At the top line data in 3Q, will you have the rebound data or not really? Because based on enrollment completion, it would be tough to get that.
Yeah, top line data will be weight loss. Weight loss all around the primary endpoint.
Got it. That's helpful. I think we all know that in terms of lean mass, we lose at least with tirzepatide, all of them. It's like we lose about 50% of our weight loss is coming from lean mass. Is there a certain expectation of what do you have to want to see what type of lean mass preservation is? 30%, obviously 30% versus 50% is better. But I don't know if you have communicated a line of thought.
Yeah, we haven't communicated an ideal expectation there. I'll say too for other incretins, it's kind of all over the map. We've seen it as bad as 50%. But for tirzepatide and some of the large studies, it's more like 25%-30%, which is fairly healthy. My expectation is that this is going to matter more for different populations that are predisposed to muscle loss, especially older populations, sarcopenic obesity. Because these people, it's nothing specific to the incretins. When they lose weight for any reason, bariatric surgery, for example, they lose too much muscle. So I think maybe it's in those populations that we have to worry about more. But that's, again, one reason why this is exploratory, because we want to learn about the variability with this drug in this population.
So, fast forward. Third quarter comes around, we get the data. You achieve the bar that you just said, an additional weight loss. Let's say we get also lean mass preservation. Let's fast forward, we wait three months, we get, let's say, also a trend of less rebound. What will you do then? What is your vision in terms of starting a registered phase III study? Do you want to do it on your own? Partner? Yeah, I would love to hear your thoughts around the three downs.
No, that's a really great question, and there's really a couple of parallel futures for this drug, because this isn't a monotherapy weight loss drug, so there's really needs an appetite suppression mechanism like an incretin to shine, so the go-it-alone strategy for the company, which is really our base case, what we're building for, is we would pursue an incretin agnostic label, so there's a lot of precedent for this if you look, for example, at PCSK9 on the background of statins, and what you'll need to show in phase III is that combined with those agents that at the time are approved for obesity.
Getting additional benefit of weight loss on top.
Yeah, you hit that incremental 5% as part of your 3,000, mostly safety-motivated database build-out.
I didn't ask why 5%. Is that like a regulatory?
That's the FDA guidance.
FDA guidance that you need to get 5% weight loss.
Yeah, that's sort of very clear guidance from the FDA that an incremental 5% is required for approval. We think it's also interesting because it happens to be the gap today between oral weight loss and injectable weight loss performance. So if you really had a pill performed on par with the injectables, that would really change the story too.
I assume since you have a partner of Lilly with tirzepatide and orforglipron is coming out next year.
We probably include them in phase III.
That could be also another.
That will probably be.
Probably the strategy moving forward.
I mean, for this agnostic label, we would combine with injectables and orals. But yes, that will be the first oral to be approved. So we would likely include it as part of the phase III design.
Could you talk about sort of the feasibility of the FDC or just in terms of manufacturability and scalability if you combine as one fixed dose combo or one pill? Because that could be very attractive.
Yeah, that's right. I mentioned before there's these two parallel paths. And this is kind of the go-it-alone path if you don't have an incretin. But if you're a pharma company and you're trying to build the best weight loss pill, then you might want to bring this in and co-formulate one pill with two different components that together.
Sounds very logical.
Sounds very appealing. So from the work we've done so far, there's no barriers to that kind of co-formulation.
Perfect. Now let's move on to the azelaprag and semaglutide data that's expected end of 2026. So that's your 52-week up to 64-week study in 300 patients. I guess is there the thought process you just wanted to see? What do you want to see in that study versus STRIDES? Are you just wanting to see the differences in weight loss curves between tirzepatide versus semaglutide or what?
Yeah, there's a few key differences comparing the two studies. Our STRIDES trial, which is ongoing now, it's kind of an off-the-shelf obesity trial with one key difference, which is it is going into an older patient population. We are looking at 55-plus. The rationale for that is just simply that that's the population where we already have clinical data. Our phase 1b was in that population. We see a very nice monotherapy benefit. We're stacking the deck in our favor. Mechanistically, you would expect weight loss additivity in younger people too, obesity in younger animals. The semaglutide trial will have the full spectrum. It'll just be like a normal obesity trial, age 18-plus. That's one key difference. The other key difference is that, as we touched on, the tirzepatide trial is six months long.
Then we're going to be projecting out to a year. The semaglutide trial will capture a full year of weight loss kinetics. And in that sense, could be part of the pivotal package. That's the FDA-mandated length. And we have power for that 5% incremental difference. So it could check the box for semaglutide as well. So those are the really key differences. Oh, and I should mention too, we're using the high dose of semaglutide. In both cases, we wanted to choose a dose of the injectable that behaved like an oral. But high dose semaglutide also gives you around 15% weight loss at one year.
But there, it's an all-comer group. So you're not capping a certain percentage of patients over the age of.
That's right. It'll be the similar distribution to other obesity trials.
But based on biology, there's no reason to believe that the effect size should be the same between younger.
Yeah, but most obesity studies, I mean, we don't have these long tables that we do have seen. But the average age in these obesity studies are in like 50s.
About a third of them are in that age group. Because we've looked in Lilly's data for.
Yeah, exactly. Yeah, so distribution-wise, about a third of people are in that 55-plus bucket. And the other two-thirds are below. Yeah, so it's a large segment, but it's not all of it.
Is the distribution of both, and I didn't ask that? Are both studies going to have diabetics too, or are they pure obesity?
They're pure obesity. That's usually what you start with because that's going to give you a cleaner signal. Diabetics don't lose as much weight, so they can noise up your. Yeah, so we would want to look at that separately.
The doses are the same between STRIDES and the semaglutide studies.
Correct. That makes it easy.
I think you guys also have communicated to think about doing a type 2 diabetes STRIDES study, which is going to start in 1H25 as well. With top line data in 2H, are you wanting you don't want to see the data before you start the Phase 3 ?
This is going to be different because this is going to be a monotherapy study. So we're interested in. There's obesity as that's a lot of people. But there's also specifically very interesting patient subpopulations where we think azelaprag can really shine. And a couple of those populations are diabetes and also heart failure. But diabetes, there's very nice animal data. Knock-out animals, for example, have much worsened insulin resistance, much more visceral fat. So we think that as you go into the diabetic obese, you might have the benefits of additional weight loss, but you also might have some azelaprag-specific benefits that are independent of weight loss altogether. So we wanted to have a look at that as a monotherapy. So it's really a different value proposition there, but could be additive.
And given that the studies are sort of staggered, you're going to get STRIDES in third quarter, and you're going to get the semaglutide large study by end of 2026. But of course, you can meet with the agency and start already discussing the sort of phase III. So then the phase IIIs would potentially start while the semaglutide studies are ongoing.
Potentially some of that work would start before that readout. And as I mentioned too, that STRIDES trial could contribute toward that data package.
Oh, because it's like all these.
The full year of weight loss kinetics, the right.
How do you figure out to what? What is the safety requirement?
3,000.
3,000.
So that's a lot of people. So a lot of different patient subsets to look at.
Then at the end, between the STRIDES study and the semaglutide study plus your phase I studies, where are you in total patient? Like almost like.
Oh, sure. In terms of total patient exposure. So the STRIDES II is about 300. Similar size for STRIDES I. It's a bit lower, probably similar size for III. So there's still a long way to go, basically.
But kind of getting there.
Getting there. No, it'll be a healthy chunk.
It'll be a healthy chunk.
It's a good amount that you'll get, and we're making all the clinical supply at risk, so we'll be ready to do the additional work. For a year, though, 3,000 per year. Actually, I misspoke, so it's really only the semaglutide trial that'll count towards that.
Given that you have a partnership with Lilly, how does this collaboration work in terms of especially when we get to phase III, post the readout? Yeah.
Sure, so I mean, we're basically independent after phase II, so this is really more of a clinical collaboration with Lilly.
Yeah, they're supplying the drug.
They're supplying drug. They helped us design the trial, which was very helpful. They're helping us run the trial as well. Most of our sites are sites that have recruited really well and developed quality data to Lilly in the past. And we're working with their group. It's called Chorus right now. So there are some people who are really extended members of our clinical team. And they're also investors in the company. And in exchange for all of that, they have a right of first negotiation after this particular trial reads out.
Oh, STRIDE.
Correct. Yeah, STRIDES I. So we're public. The top line data will be released immediately. But they'll basically be able to, for a period of time, be able to go first into the data room. So that's what they get in exchange. But after that, that's the only right.
So there could be a scenario by which we wake up, we don't see STRIDES, and Lilly.
Sorry. If you've never done a fireside chat, I go off script because I just go with the flow of my brain things. You know what I mean? I'm just thinking, aren't we all thinking that? Yeah, there could be that situation. Is that a possibility?
I mean, the top line data will be out there in the world. So everybody will know. All the other companies will know.
They're going to be in the data room before that.
They'll be in the well, no. The top-line data comes out at the same time.
I see.
But no one will be able to get additional detail.
Oh, I see. OK, got it. OK, so it will be after the release that they can.
That's right.
They'll see the data release when we all see it.
Exactly. Everyone will see that at the same time, but they're going to be able to go deeper.
For a certain period of time that they have to see more to make a decision and refusal.
That's right.
It's not a right of first refusal. It's a right of first negotiation, which is softer.
Oh, OK.
Yeah.
OK. Well, that's good to know. Have you publicly disclosed what the time frame of that negotiation is?
I don't think we have. No.
OK, got it. I look at Dov Goldstein. No, absolutely not. We have not discussed that.
Yeah.
No, that's great. I think that from investors' perspective, I think the question that people are wanting to see, I think, is just making sure execution-wise is going to be critically important. I think we learned quite a bit over the last two years, making sure that there are no hiccups.
It seems like it can go wrong.
Yeah. So it seems like you guys have really a great CRO. You have a great team. You have the help of Lilly as well to be part of recruiting high-quality sites. So everything is sort of set up for success.
No, the Lilly collaboration for us is all about the executional data staying. That's been really helpful.
Before we go into NLRP3, I think there's also quite a bit of depth of understanding how the different mechanisms have an effect on lipid profile, maybe other comorbidities of MASH, whether it's MASH or whether it's elevated lipids. Have you guys seen is there a reason to believe that apelin also has additional metabolic syndrome benefits that have been observed in preclinical models?
Yeah. So we haven't looked at the combination in those specific models. Certainly, apelin has been described as anti-inflammatory. It's had these insulin benefits. So there are, I think, additional features that could give it an outcome's edge, but we don't have that specific data in those models.
Got it. OK, but you're measuring all of those things.
We're measuring everything we can. Yeah. I mean, one advantage of going into this older population in the initial phase II is that they are going to have some more, not overt morbidity at that point in time, but they'll have more pathology. Yeah.
And I don't remember seeing this, but when you articulated the weight loss of tirzepatide as a monoarm, there is data of just that 55 and above population. So that's the curve that you're basing it on.
That's what we were able to get from the Lilly collaboration. So they were able to go into their database, cut the data with just that age group, and use that to power the study. But that was important for us, for sure.
Yeah, because that's a tough population to gain. OK, now that we have four minutes, we'd love to talk about your oral NLRP3. I guess the first question is, where are you in terms of development?
Sure. So we've provided guidance that we're going to file IND in the second half of next year. So that's where that program stands.
And then now, I think I cover Ventyx. We know NodThera, that's in the space. Are you able to share a little bit how you differentiate versus those programs? What do you see in preclinically?
I mean, preclinically, we think we have a shot at best-in-class potency by a large edge. We think we're an order of magnitude more potent than the relevant assays. We do have a novel binding site, which we've shown with our collaborator, Matthias Geyer. We'll publish a paper with him. We've got the structure. Knowledge of that binding site has really enabled the chemistry. That's where we have the clearest edge. It's very highly brain penetrant, close to parity in terms of brain-to-body basically exposure. Yeah, we're excited about this too because, I mean, it's early days yet, but NLRP3 could be an appetite suppressant mechanism. It seems to be in NodThera and Ventyx's hands. If that translates to humans, then this could also be a potential complement to azelaprag. We're excited about bringing that forward.
Have you done preclinical work on the combination of the two?
We're going to talk more about that program and what we've seen preclinically after we're through GLP-1.
I think the nice part also is by the time that you will have second half of 2025, we'll have data sets from the CNS penetrant and NLRP3.
That's right. We're really excited to see Ventyx's readout and maybe NodThera's too. So some de-risking for the target. Yeah.
And also thinking about, do we use this? And I don't know if you have any thoughts around developing this for a pure obese population or potentially other metabolic indications that we have seen, like obese plus high risk, whether it's cardiac related, et cetera. But I think by the time you would enter the clinic, we'll have a lot of.
Yeah, we'll be learning a bit more from some of the other programs. So we're very actively looking at this, but don't have any sort of concrete decisions on that yet. Yeah, right now we're still thinking the first clinical look will be like obesity monotherapy. But that could evolve.
The NLRP3 program has not. That negotiation has nothing to do with the NLRP3s. It's an unpartnered, uncombined.
That's right. No, this is our company's first in-house discovery compound. Yeah.
For both of these assets, are there other generation compounds that one could also develop and optimize for?
Sure. So the azelaprag, which we licensed from Amgen, we also have their entire backup portfolio of compounds. So there's a whole spectrum of other interesting matter and interesting backups we could bring forward. And with NLRP3 as well. So there's a lot of different chemistry enabled by this new site. So we were looking at a few different compounds there too.
And then, cash ending as of the end of the fundraising post-IPO and runway.
Yeah. From our last Q, we have $360 million. So that gives us runway for all these three different phase IIs, azelaprag, a couple of phase IIs, phase I's with NLRP3, all our platform work, et cetera, and runway into 2029. So we're pretty comfortable from a cash perspective. But we would do a big raise following STRIDES to really fund the phase III program.
Perfect. Well, team, congratulations. It's been very exciting, like two different mechanisms, really well-designed studies with a lot of great data that's upcoming. And I guess this will be the first combo study, if you think about it, in obesity to read out.
Sure. Yeah. Especially with the orals, we'll see more of that. Yeah, this is the sort of paving new ground too.
Paving the ground, but even the orals, they're just monoarms. Yeah, this could be quite exciting. What a great 2025 that we have. I'm excited, so I want to say thank you for being part of our conference. Thank you so much, and let's thank the team for their thoughtful comments.