Attovia Therapeutics, Inc. (ATTO) Earnings Call Transcript & Summary

Thank you. Good morning, everyone. Welcome to this session of the Morgan Stanley Global Healthcare Conference. I'm Judah Frommer, one of the Morgan Stanley Biotech analysts. We're very excited to have Tao Fu, President and CEO from Atovia with us. Let me just get through a quick disclosure, Tao, before we get started.

For important disclosures, please see the Morgan Stanley Research Disclosure website at www.morganstanley.com/researchdisclosures. All right. So with that out of the way, I told you we had an exciting IPO in August. Congrats to the team on that. Thank you. Before we dive in, can you maybe give the audience a quick intro with a bit of background on how the team came together and the company formation?

Sure. Well, Judah, thanks for having me here. It's a real pleasure. Thank you.

So Atovia was founded just a little bit over a few years ago in June of 2023 and really with a simple thesis of trying to change the paradigm for immune-mediated disease treatment with our autoantibody platform-based biologics. So we started with a small group of highly experienced drug developers and scientists with early backing from Frazier Life Sciences, and you know, van Vile, and really there was two shared beliefs between the teams, our investors, that first the autoantibody platform can really have the potential to deliver breakthrough efficacy for I&I treatment. And having a small and highly focused and integrated team can deliver exceptional speed. So that's what we have done over the last three years. Our lead program ATO-1310 from concept to clinical proof of concept in patients. We have built a sustainable pipeline of near development stage multi-specifics and also completed an upsized IPO. So we're very proud of that speed and execution, but we also think it's very important.

repeatable.

Right. It's been busy. So I want to spend a little more time on the platform. Maybe just walk us through the capabilities of the platform, how candidates are screened and developed. What advantage does the autoantibody platform provide over other approaches to antibody or biologic development?

Yes, so the autoantibodies are a bi-topic

modality, which means it has two VHH or nanobody binding arms, and each of them binds to a separate epitope on the same protein target, and they're connected by a linker. So our proprietary linker technology basically enables each of the VHH arms to interact ultimately with the target. So, autoantibody-based therapeutics have several unique attributes which make them ideally suited for complex biologics. I can give you a few examples. The bi-topic binding will give you ultra-high affinity and often best-in-class potency. So ATO-1310, as an example, those highly potent mono-specifics against IL-31 ligand, and antibodies are highly modular. So they're like Lego pieces. They can be put together in multi-specific formats and retain potency against individual targets. So we can also easily extend the half-life. So great for building multi-specifics. We can also tune the affinity of our binders to create truly conditional and-gate bispecifics. We can use high affinity to target a specific cell type and then lower affinity to activate the effector function when the drug is in the tissue. So, so far, we have done over 15 campaigns. We have 100% success rate against all the targets we selected. Great. And like you said, this modular nature of the platform, the building blocks are nanobody pairs. Maybe talk about the rationale for using nanobody binders over other formats. What have we learned about nanobodies from other programs? Yes, so nanobodies are really validated commercially, right? So there are multiple FDA approved products. There are multiple products containing nanobodies in late stage clinical development with success. So it's very validated. It's very small and it's very flexible, highly engineerable. So it gives us the binding domain that's ideal for a bi-topic binder, but also it has generally low immunogenicity risk in humans. So I think our experience with ATO-1310 so far is we have seen low immunogenicity.

Right. Okay.

Great. So maybe moving to that lead candidate, ATO-1310, it's a biologic targeting IL-31, like you said, you're about to move into Phase 2 for chronic itch. But before we get to some of the data and development plans, maybe frame the opportunity in chronic itch for us. It encompasses a lot of different conditions, but broadly, what's the unmet need?

what's the rationale for targeting IL-31? Yes, so chronic itch or pruritus is a major, but underappreciated disease burden. So it really spans through dermatological to systemic conditions. These patients really suffer from persistent debilitating itch that, you know, ranging for, you know, skin damage, to loss of sleep, depression, and sometimes suicidal ideation, right? So it's a major disease burden. And those are highly prevalent. So we have over 15 million patients in the U.S. being impacted and just between high-itch AD and chronic pruritus of unknown origin, the two indications we're trying to take ATO-1310 to late stage development, we have over 10 million patients. So IL-31 has been now widely recognized by the medical community to be the primary driver of itch, right? Sometimes it's called the itch cytokine, and it was really found to be elevated in a variety of these chronic itch conditions.

So we really think it's the best target for it.

Okay. Excellent. And, you know, kind of the precedent product here is going to be Nemolizumab, which investors will be familiar with, which targets the IL-31 receptor. ATO-1310 targets the IL-31 ligand, like you said. So what might be the potential advantages of targeting the ligand as opposed to the receptor?

Yes, I think Nemolizumab is a great analog for us. It's clearly validated the role of IL-31 pathway in itch, and we believe ATO-1310 by targeting the ligand has several advantages. So specifically to your question about the ligand versus receptor, so Nemolizumab actually suffers from this known reverse dose efficacy issue. Basically, their highest dose performed worse on efficacy than the lower doses in three separate Phase 2 trials. And Dr. Brian Kim published on this, you know, basically the hypothesis is because IL-31 receptor dimerizes with OSMAR beta for IL-31 to signal. So if you hit IL-31 receptor really hard with Nemolizumab, you release the free pool of OSMAR beta, which has an alternative binding partner called GP 130, and that's an alternative pro-inflammatory pathway. So this paradoxical loop basically contributes to it starting to lose efficacy. And obviously, if you target the ligand, you are completely free and clear from that pathway. We also believe we can potentially achieve faster itch relief, and there is a validation from a canine drug called Cytopoint. Basically, it's a highly effective anti-IL-31 monoclonal antibody, and if you inject Cytopoint into dogs, sometimes you get itch relief in minutes to hours. It's very fast onset. So we're also hoping to see that in humans with ATO-1310.

Okay. Are there any other aspects of molecular design for ATO-1310 that differentiate versus Nemolizumab besides the particular target?

Yes, I think there's a couple. In addition to the reverse dose issue we just talked about for IL-31 receptor, you know, we're using the autoantibody, the bi-phasic binding mode, which gives us really almost no off-rate and we can achieve higher potency with our binder. And our PK and target engagement data so far also suggest we have full suppression of IL-31 for at least 12 weeks, which supports quarterly dosing. And Nemolizumab, as you know, is primarily a monthly injection drug.

Sure, yeah. Yeah. Excellent. Some Phase 1 data for ATO-1310 in healthy volunteers and patients maybe. Tell us about the design of your Phase 1 study. Give us the kind of the highlights on what's been reported thus far. You know, what was behind your decision to include placebo patients in the trial?

Yeah, so the Phase 1 study really has three parts. You know, in healthy volunteers, we have single ascending dose, IV and sub-Q, and also MAD, sub-Q only. So, part three is really in, uh, it's a randomized placebo-controlled study for both chronic pruritus of unknown origin and the high-itch AD population. And participants are followed up for 12 to 16 weeks. But we give only one single subcutaneous dose. So the clinical profile we have seen so far has been very encouraging. So really excellent safety, great target engagement. We've been able to show full suppression of IL-31 to support the quarterly dosing. And we have increased the dose and dosing. Encouraging clinical signals from both patient cohorts, very fast and deep itch relief for both populations and specifically for AD, we're also seeing pretty rapid and meaningful lesion improvements in terms of both EASI and IGA.

Right, great. Maybe just a little bit more on the targeting engagement data supporting that potential for quarterly dosing. Maybe just discuss the data we've seen for that.

So we have an ultra-sensitive assay for IL-31. So in healthy volunteers, we are being able to show that we have full suppression of free IL-31 at the 95% level for at least 12 weeks. And the early patient experience we have so far is also consistent with us. And we have other ways to really triage this. For example, we can look at IC90 levels based on our animal models, the effective dose, and QSP modeling based on Cytopoint efficacy. All these data points consistently point to we can actually achieve quarterly dosing.

Yeah. Okay, great.

You said, you saw encouraging responses in both patients with chronic pruritus and atopic dermatitis, and I know it's a single dose and a short study, but maybe frame the magnitude and the kinetics of those responses versus approved biologics if you can.

Yes, we have seen very deep and rapid release.

With, I would say, one single unoptimized dose really compares quite favorably to the benchmarks we have. For chronic pruritus of unknown origin, our pooled PPRS4 responder rate for ATO-1310 is about 65% at week four. That's versus about 18% for Dupixent in the part three of their Phase 3 study at similar time point. And for high-itch AD, our PPRS4 responder rate is about 44% at week four, which versus Nemolizumab is about 28%. They showed in their Phase 3 study, and that's also in the high-itch group. That is same as our study. So I think we basically showed really two active doses in two indications that compare pretty favorably to benchmarks from an itch standpoint. And as I mentioned earlier, in the AD cohort, we also showed pretty meaningful.

Fast, EASI reduction for lesion.

Excellent. And we'll dive into this a bit more later, but I guess just.

Maybe up front, you know, in what ways did the data provide kind of positive read-through to the platform, other candidates that are behind ATO-1310, maybe just from a high level, address that?

Yeah, I think... of the all of ATO-1310 data is the first human validation of our platform.

We're basically able to demonstrate that an autoantibody-based therapeutics can be dosed subcutaneously. We can have very strong and durable suppression of the target, you know, favorable PK and, you know, safety and immunogenicity profile. And and broadly speaking, basically the design principle or criteria we have for the autoantibody-based therapeutics pre-clinically translated into human pharmacology and create encouraging clinical activities. And that's that really bodes well for our platform.

Yeah, okay, excellent. And like you said, you're going to report.

Report full Phase 1b results for ATO-1310 in the fourth quarter. Can you tell us what data we're going to be getting? What do you hope to see in that update? It's a single dose again. So where should investors be careful not to read too much into the data that you'll share?

So the fourth quarter update will include the full follow up for the two.

Patient cohorts for up to 12 to 16 weeks. So 16 weeks visit is an option visit, optional visit. So the data will include, you know, obviously safety, you know, target engagement. You know, we want to see whether the target engagement is durable. You will have the full time course of the clinical responses for both populations and obviously the completed assessment of immunogenicity. So what we're hoping to see is, you know, whether the early clinical signal is sustained, whether we have durable target engagement to continue to support quarterly dosing, and also the favorable safety and low immunogenicity we observed so far kind of carry through to the full follow-up period. I do want the investor to remember this is a relatively small Phase 1 study, and the primary objective of the study is to assess safety, PK/PD, and the initial clinical signals, it really doesn't define the dosing regimen or even the duration, right? And we also allow rescue therapy after week four. Therefore, the available, and it's one single dose so the available week four data we already have really is the most important data set for this trial which we already demonstrated we have two active doses in two different populations. So I think the right way to use the full Phase 1b data is really to confirm our biological thesis, but also inform our Phase 2 dose and regimen selection. I think I would also like to mention in our Phase 2 studies, we also plan to give multiple doses in the induction phase. We can maximize efficacy before we start maintenance.

Yes. Okay. So speaking of the Phase 2, so you'll be advancing ATO-1310 into Phase 2 studies in, like we said, chronic pruritus of unknown origin and high atopic dermatitis in the first half of next year. So there are no approved therapies in chronic pruritus of unknown origin and not many development precedents. I guess with that in mind, how are you approaching the design of the chronic pruritus of unknown origin Phase 2 and any learnings from other studies that you're planning on incorporating?

Yes.

Chronic pruritus of unknown origin is a real and now widely recognized disease. And as you point out, there's no FDA approved therapy. So we really believe the trial design and execution matter. And, you know, chronic pruritus of unknown origin is diagnosed by exclusion and it can have, you know, meaningful placebo responses. So our Phase 2 design is really trying to mitigate those risks. So, you know, we're planning to conduct a very large 300 patients global study that will be the largest study to date for this indication. Active dosing strategies and one large placebo group. So given the large effective size we see in our Phase 1b, we really kind of overpower the study to really maximize our chance to win.

Okay. Yes, we have very constructive dialogue with the FDA and and. Okay, that makes sense. And you've engaged with FDA on the Phase 2 design, submitted the protocol to the agency. Can you talk about any feedback you got from the agency? Any surprises within that feedback or maybe just elements of the conversation?