Right. Good morning, everyone. Welcome to this session of the Morgan Stanley Global Healthcare Conference. I'm Judah Frommer, one of the SMID Biotech analysts. We're very excited to have Tao Fu, President and CEO from Attovia with us. Let me just get through a quick disclosure tab before we get started. For important disclosures, please see the Morgan Stanley research disclosure website at www.morganstanley.com/researchdisclosures. All right, with that out of the way, Attovia had an exciting IPO in August. Congrats to the team on that. Thank you. Before we dive in, can 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. Attovia 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 ATTOBODY platform-based biologics. We started with a small group of highly experienced drug developers and scientists with early backing from Frazier Life Sciences and venBio. And really there was two shared beliefs between the teams, our investors, that first, the ATTOBODY platform can really have the potential to deliver breakthrough efficacy for IMI 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 two years. We moved our lead program, ATTO-1310, from concept to clinical proof concept in patients. We have built a sustainable pipeline of near development stage multi-specifics. And also complete an upsized IPO. We are very proud of that speed and execution, but we also think it is very repeatable. Right. It has been busy. 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 ATTOBODY platform provide over other approaches to antibody or biologic development? Yeah. The ATTOBODYs are a biparatopic 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. Our proprietary linker technology basically enables each of the VHH arms to interact ultimately with the target. ATTOBODY based therapeutics have several unique attributes which make them ideally suited for complex biologics. I can give you a few examples. The biparatopic binding hold give you ultra high affinity and often best in class potency. ATTO-1310, as an example, builds highly potent monospecific against IL-31 ligand. ATTOBODYs are highly modular, so they're like Lego pieces. They can be put together Right. In multi-specific formats and retain potency against individual targets. We can also easily extend the half-life. Great for building multi-specifics. Right. We can also tune the affinity of our binders to create truly conditional and gate bispecific. 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. Right. So far, we have done over 15 campaigns, and we have 100% success rate against all the targets we selected. Great. Like you said, this modular nature of the platform, the building blocks are nanobody pairs. So maybe talk about the rationale for using nanobody binders over other formats. What have we learned about nanobodies from other programs? Yeah. Nanobodies are really validated commercially, right? There are multiple FDA-approved products. There are multiple products containing nanobodies in late-stage clinical development with success. So it is very validated. It is very small, and it is very flexible, highly engineerable, so it give us the binding domain-. Right. that's ideally for a biparatopic binder. It also has generally low immunogenicity risk in humans. I think our experience with ATTO-1310 so far is we have seen low immunogenicity. Right. Okay, great. Maybe moving to that lead candidate, ATTO-1310. It's a biologic targeting IL-31, like you said. You're about to move into phase II for chronic itch. 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? Yeah. Chronic itch or pruritus is a major but underappreciated disease burden. It really spans through dermatological to systemic conditions. These patients really suffer from persistent debilitating itch that ranging from skin damage to loss of sleep, depression, and sometimes suicidal ideation. Right. It is a major disease burden. Right. It is also highly prevalent. We have over 15 million patients-. Right. In the U.S. being impacted. Just between high itch AD and CPUO, the two indications we are trying to take ATTO-1310 to late stage development, we have over 10 million patients. Right. Right. IL-31 has been now widely recognized by the medical community to be the primary driver of itch, right? Sometimes it is called the itch cytokine. Sure. And it is really found to be elevated in a variety of these chronic itch conditions. We really think it's the best target-. Okay. For itch. Yeah. Okay. Excellent. The precedent product here is going to be Nemluvio, which investors will be familiar with, which targets the IL-31 receptor. ATTO-1310 targets the IL-31 ligand, like you said. What might be the potential advantages of targeting the ligand as opposed to the receptor? Yeah, I think nemolizumab is a great analog for us. It clearly validated the role of IL-31 pathway in itch. We believe ATTO-1310 by targeting the ligand has several advantages. Specifically to a question about the ligand versus receptor, 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 II trials. Right. Dr. Brian Kim published on this. Basically, the hypothesis is because IL-31 receptor dimerizes with OSMRβ for IL-31 to signal. If you hit IL-31 receptor really hard with nemolizumab, you release the free pool of OSMRβ, which has an alternative binding partner called GP130, and that is an alternative pro-inflammatory pathway. This paradoxical loop basically contributes to them starting to lose efficacy. Obviously, if you target the ligand you are completely free and clear from that pathway. Right. We also believe we can potentially achieve faster itch relief. There is the validation from a canine drug called Cytopoint. Right. Basically, it's a highly effective anti-IL-31 molecule antibody, and if you inject Cytopoint into dogs, sometimes you get itch relief in minutes to hours. Yeah. It's very fast onset. We're also hoping to see that in human with ATTO-1310. Okay. Are there any other aspects of molecular design for ATTO-1310 that differentiate versus Nemluvio besides the particular target? Yeah, I think there's a couple. In addition to the reverse dose issue we just talked about for IL-31 receptor, we're using the ATTOBODY, the biparatopic binding mode. Right Which give us really almost no off rate. And we can achieve higher potency with that binder. And our PK and target engagement data so far also suggest we have full suppression of IL-31 for at least 12 weeks. Yeah. Which support quarterly dosing. Nemluvio, as you know, is primarily a monthly-. Sure. Injection drug. Sure. Yeah. Yeah. Excellent. You have reported some phase I data for ATTO-1310 in healthy volunteers and patients. Maybe tell us about the design of your phase I study. Give us the highlights on what has been reported thus far. What was behind your decision to include placebo patients in the trial? Yeah. The phase I study really has three parts. Yeah. In healthy volunteers, we have single ascending dose IV and sub Q, and also MAD Sub Q only. The part three is a randomized placebo controlled study for both chronic pruritus or CPUO and high AD population. Right. Participants are followed up for 12 - 16 weeks. We give only one single subcutaneous dose. Right. The clinical profile we have seen so far has been very encouraging. 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 encouraging clinical signals from both patient cohorts, very fast and deep itch relief for both populations and specifically for AD. We are 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 target engagement data supporting that potential for quarterly dosing. Maybe just discuss the data we have seen thus far for that. Yeah. We have an ultra sensitive assay for IL-31. In healthy volunteer, we are being able to show that we have full suppression of free IL-31 at a 95% level for at least 12 weeks. The early patient experience we have so far is also consistent with us. Right. 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 the QSP modeling based on C ytopoint efficacy. All these data points consistently point to we can actually achieve quarterly dosing. Yeah. Okay, great. Like you said, you saw encouraging responses in both patients with chronic pruritus and atopic dermatitis. 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. Yeah. We have seen very deep and rapid itch relief with I would say one single unoptimized dose really compare quite favorable to the benchmarks we have. Right. For CPUO, our pooled PP-NRS4 responder rate for ATTO-1310 is about 65%. Yeah. At week four. That's versus about 18%-. Yeah. For dupilumab in the Part 3 of their phase III study. Yeah. At similar time point. For high AD, our PP-NRS4 responder rate is about 44% at week four, which versus nemolizumab is about 28% they've shown in their phase III study, and that's also in the high itch group that is same as our study. I think we basically showed really two active doses. Yeah. In two indications that compare pretty favorable to benchmarks from the itch standpoint. As I mentioned earlier, in the AD cohort, we also showed pretty meaningful-. Yeah. And fast and easy. Sure. Reduction-. Okay. For lesion. Yeah. Excellent. We will dive into this a bit more later, but I guess just maybe upfront, in what ways do the data provide positive read-through to the platform, other candidates that are behind ATTO-1310, maybe just from a high level to address that? Yeah. I think the ATTO-1310 data is the first human validation of our platform. Yeah. We are basically able to demonstrate that an antibody-based therapeutics can be dosed subcutaneously. We can have very strong and durable suppression of the target, favorable PK, [PD], and immunogenicity profile. Broadly speaking, basically the design principle or the criteria we have for the ATTOBODY-based therapeutics pre-clinically translated into human pharmacology and create encouraging clinical activities. Right. That really bodes well for our platform. Yeah. Okay. Excellent. Like you said, you are going to report full phase Ib results for ATTO-1310 in the fourth quarter. Can you tell us what data we are going to be getting? What do you hope to see in that update? It is a single dose again, so where should investors be careful not to read too much into the data that you will share? The Q4 update will include the full follow-up for the two patient cohorts for up to 12-16 weeks. So 16 weeks visit is an optional visit. Okay. The data will include obviously safety, target engagement. 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. What we are hoping to see is whether the early clinical signal is sustained. Right. Whether we have durable target engagement to continue to support quarterly dosing. Yeah. Also the favorable safety and low immunogenicity we observe so far carry through to the full follow-up period. Okay. But I do want the investor to remember, this is a relatively small phase I study. Right. The primary objective of the study is to assess safety, PK/PD-. Right. And the initial clinical signals. It really doesn't define the dosing regimen or even the duration. Right. We also allow rescue therapy after week four. Right. Therefore, the available and it's one single dose, so the available week four data we already have-. Right. Really is the most important data set for this trial, which we already demonstrated we have two active doses in two different populations. I think the right way to use the full phase Ib data, is really to confirm our biological thesis-. Yeah. But also inform our phase II dose and regimen selection. Right. Okay. I think I would also like to mention in our phase II studies, we also plan to give multiple doses-. Right In the induction phase. Right. We can maximize efficacy before we start maintenance. Yeah. Okay. Speaking of the phase II, you will be advancing ATTO-1310 into phase II studies in, like we said, chronic pruritus of unknown origin, CPUO, and high atopic dermatitis in the first half of next year. There are no approved therapies in CPUO and not many development precedents. I guess with that in mind, how are you approaching the design of the CPUO phase II, and any learnings from other studies that you are planning on incorporating? Yeah. CPUO is a real and now widely recognized disease. As you point out, there is no-. Yeah. FDA-approved therapy. We really believe the trial design and execution matter. CPUO is diagnosed by exclusion, and it can have meaningful placebo responses. Our phase II design is really trying to mitigate those risks. Right. We are planning to conduct a very large, 300 patients global study that will be the largest study to date for this indication. Yeah. Two active dosing strategies and one large placebo group. Given the large effective size we see in our phase Ib-. Right. We really overpowered the study to really maximize our chance to win. Okay. That makes sense. You have engaged with FDA on the phase II design, submitted the protocol to the agency. Maybe talk about any feedback you got from the agency, any surprises within that feedback, or maybe just elements of the conversation. Yeah. We have very constructive dialogue-. Yeah. With the FDA, and really their feedback are broadly consistent with our phase II design. Okay. Because CPUO is obviously no approved therapy, FDA provide meaningful feedback-. Yeah. On inclusion, exclusion criteria, study endpoints, and how do you characterize a dose response. We have submitted our protocol to the-. Yeah. FDA after incorporating all those feedbacks. I would also say that we have learnings from other later-stage CPO-. Right. Studies, like the LIBERTY study. Sure. There will be regulatory pathways they establish which could-. Yeah. Benefit our program. Okay, excellent. Just touching on the phase II in atopic dermatitis. Maybe just elaborate on the decision to pursue development in mild to moderate patients with high itch specifically. Yeah. Our thesis there is that the disease burdens for AD is not fully captured by lesion severity. Yeah. There is this distinctive clinical phenotype where a patient can have more moderate lesion, its EASI score in the sort of 7-16 range, but they have very severe itch. Okay. It is a very large and underserved segment, where I think a systemic therapy, specifically focused on itch like ATTO-1310-. Right. With also infrequent dosing could be very attractive compared to branded topicals. Sure. Because there's no biologics approved-. Right In that segment. It also give us a very differentiated development pathway-. Yeah. Versus the more, lot more crowded. Yes. Moderate to severe EASI above 16 Dupixent market. On the more severe spectrum, we do think IL-31 pathway could play an important role-. Yeah. Either as a standalone therapy for certain high itch patients or in combination with other drugs. We have also a bispecific-. Sure. Which incorporate both IL-13 and-. Sure. IL-31 to address itch and inflammation simultaneously. Okay. Yeah. And maybe just to follow up on that, I guess, what you've heard in terms of Nemluvio utilization and efficacy within that mild to moderate high itch population. It is not approved for that. Right. The Nemluvio has a label for EASI 16 and above. There might be some off-label use. Yeah. But for us, this is a true expansion opportunity. Okay. Yeah. Excellent. Then maybe briefly just touch on development plans for ATTO-1310 in other pruritic indications. I think you recently received IND clearance for a study in cholestatic pruritus. What are kind of go forward plans for this molecule beyond these two indications? Yes, we did receive IND clearance to study ATTO-1310 in China for-. Cholestatic pruritus associated with PBC and PSC patients, and we actually received this approval within 22 working days-. Oh, wow. Based on their new innovative therapy paradigm. It is our first foray into the systemic itch outside of dermatology. Yeah. If we're successful there, I think systemic itch conditions like cholestatic or CKD-related pruritus could represent a very meaningful upside in addition to CPUO and high itch AD. Okay. Excellent. I want to make sure we cover some of your pre-clinical programs, too. So maybe first starting with ATTO-2306, this is a bispecific targeting IL-31 and 13. These targets have obviously been individually validated for atopic dermatitis and prurigo nodularis. But if these targets are inhibited simultaneously, should we expect better outcomes? How distinct and complementary are these two pathways? Yeah. We believe IL-13 and IL-31 are two complementary and non-overlapping pathways. IL-13 obviously is the key driver for TH2 inflammation and skin lesions, where IL-31 is the primary driver of itch. It also impacts barrier dysfunction and neural inflammation. IL-13 can have indirect effect on itch, but those effects tend to be slow and not complete. Right. So really if you look at also the two pathway, these are the only two clinically validated pathway that independently give you lesion control efficacy. Right? They are also the only two commercially validated pathways to get approval by the FDA. Right. Specifically for lesion control. As I mentioned, the 1310. We have demonstrated we have lesion efficacy potentially without TCS. The two pathways really make a lot of sense to combine together. Hopefully that can help address both inflammation and itch simultaneously. Yeah. Also give you very fast, deep, and durable responses. Okay. That's the thesis we have. Sure. Okay. It's no secret the bispecific development landscape is becoming increasingly more crowded, with I would say certain arms, certain IL-31 targeting arms, then the IL-4/13 pathway being another target. How might ATTO-2306 be differentiated from those other programs? If you could include some commentary on differentiation versus IL-4 targeting and the choice on IL-13. Yeah, I think our thought has always been that the target selection within these two pathways are actually quite important and also nuanced. First IL-13 targeting therapies like lebrikizumab or zumilokibart has essentially similar or identical efficacy like Dupixent. Yeah. But by avoiding IL-4 receptor, it also avoid a risk of target-mediated drug disposition, or TMDD. Which results in basically poor exposure and dosing frequency. So any IL-4 receptor containing bispecific, for example, like the Bambusa. BPT 001 molecule will suffer from TMDD. So you will likely have poor PK and will be struggling with commercially viable dosing. Right. I believe the Bambusa molecule is currently being studied in IV only. Got it. once every couple weeks. There is the IL-31 versus IL-31 receptor. Right. We talk about the reverse dose efficacy issue associated with IL-31 receptor. If you think about it, that could be more problematic in a bispecific format, because if you limited dosing for the IL-31 receptor arm, you will likely impact the dosing on the IL-13. Right. I think the Chugai molecule target IL-31 receptor, and as we understand, it's also being studied in IV only right now. Right. Okay. Interesting differentiation. You'll be starting a phase I healthy volunteer study for ATTO-2306 in the first half of next year. I think you've said results mid 2027. What should we be looking for in terms of PK/PD from that study? I think we'll be looking for three things in that study. Yeah. We're looking for a favorable PK profile. Specifically, the very long PK half-life we have been predicting from based on our NHP half-life-. Sure. To really support quarterly or even longer dosing. We are looking for robust target engagement for both pathways, for both IL-13 and IL-31, and favorable safety and immunogenicity profile. I think if we can confirm all three things, our plan is to really move ATTO-2306 to a large dose-ranging phase II study directly-. Right. In moderate to severe atopic dermatitis. Right. Okay. We have a high concentration subcu formulation ready to go. For that study. Yeah. Okay, excellent. I think investors have been conditioned to look at biomarkers within these early AD studies. Maybe any benchmarks we should have in mind for STAT6 inhibition or TARC reduction or any other biomarker you'd point to? Yeah. I think for IL-13, probably the best marker for healthy volunteers is the phospho-STAT6. I think the data on TARC is pretty inconsistent if you look at-. Yeah. The data from most of the approved TH2-. Right. Therapies. phospho-STAT6 is probably the most important, and obviously we'll be looking at IL-31-. Sure. Inhibition, and for us looking for that long PK half-life we're predicting based on our preclinical model. Okay. Yeah. Excellent. I want to make sure we touch on your trispecific ATTO-1091. Similar to our discussion on the other assets, maybe just talk about the target selection for this asset, and what have we seen preclinically thus far for ATTO-1091. Yeah. ATTO-1091 is our global first-in-class trispecific targeting TL1A. IL-23, P19, and integrin alpha 4 beta 7 simultaneously in one single molecule, right? Sort of a trifecta. Yep. We really think those three pathways are really distinctive complementary to each other, and really a molecule that it can inhibit all three give us the real potential to break through the efficacy ceiling of existing. Yeah. IBD treatment. Preclinically, we have shown we can very potently inhibiting all three pathways at the same time without interference. Also in a YTFCE contained format that has very good developability. Our preclinical in vivo models also support that inhibiting all three pathway is actually a better activity than just one or two. We obviously need to confirm that in the clinic. But it's a really highly differentiated and unique molecule which will allow us to test this hypothesis of whether we can break through the efficacy ceiling. Right. Yeah. Right. Then maybe just a strategic question on this asset. How are you thinking about progressing development in IBD while also pursuing these dermatological indications? Do you think about partnering? Is this something that Attovia could do themselves, or decide down the line with more data? Yeah. ATTO-1091 is a very important internal value driver for us. Yeah. I think in addition to the trispecific concept, there are some very unique differentiating features like our TL1A binder, for example. Right. It is not only more potent than some of the monoclonal antibodies in phase III, but also avoid this high molecular weight aggregate issue which could result in high ADA. Yeah. We think it's a very differentiated asset, it's a very important value driver for us. And our IPO give us the full ability-. Right. To really fund the study into early clinical proof of concept. Okay. But that being said, we recognize IBD as complex. Yeah. It's going to be very costly to conduct large global studies. If there are partners that have deep development and commercial expertise, they could add value, right? Right. Yeah. So I think our strategy is really maintain optionality. We'll continue to unlock the strategic value while we're evaluating different alternatives, and the goal is to deliver the best value for our shareholders. Sure. Then maybe just quickly, with that upsized IPO, what is your cash runway fund in terms of operational activity that we've discussed? Yeah. The IPO, we raised over $300 million, and we still have about $150 million at the end of Q2. Right. Combined the financial resources, we can fully fund our operating plan into 2030. Great. It funds the two large phase II studies for ATTO-1310 and all the other activities like ulcerative colitis. We will fund the ATTO-2306 programs through a phase II atopic dermatitis study, and also fund ATTO-1091 through early clinical proof of concept as well. Great. I think we are in a very strong position. I think the strategic point is we actually have multiple near-term value inflection points-. Right. For investors that are independent of each other. Right. Yeah. Right. Excellent. Okay. In the last couple of minutes, we will just tick through a mini survey we are asking all the management teams at the conference. The first is on China's rise in biotech innovation. How are you thinking about your competitive position? Will this influence R&D or business development strategy, potentially? Yeah, I think the Chinese competition is real. Yeah. But we really see that both as a threat and an opportunity. Internally for the pipeline we had, I think so far we saw a limited or nonexistent competition. For example, the ATTO-1091 program, we have not seen another trispecific program that is advanced to our stage. And we have certainly strategic interest from pharma on these programs. Yeah. So we know we are creating value there. Right. But our overall strategy with respect to China is to really raise our innovation bar. Yeah. Right? Really try to work on those concepts that are unique to our platform. I talk about the conditional bispecifics. Sure. We haven't disclosed the targets, but both novel targets plus what our technology platform can uniquely do that's very difficult to be repeated. Okay. Really, that's our strategy. Okay. Yeah. Great. Is there a way that Attovia is leveraging AI or thinking about the potential for AI to disrupt the broader industry? Yeah, that is also real. Yeah. For Attovia, we're trying to incorporate AI into how we evaluate science and how our scientists are doing science and think about maximizing or optimizing our workflow. For a core discovery, I think a lot of experts would agree that the true bottom line is biology. Right. That's where AI is still having to catch up. Yeah. Okay, excellent. Lastly, just on the regulatory side of things, maybe it's a bit early for you guys, but do you think about whether it's an evolving FDA, pricing for drugs or anything on the regulatory side that garners particular focus from you? I don't think it has a direct impact-. Yeah. On Attovia because we're still-. Yeah. Relatively early stage. For example, MFN. Sure. One thing we have done is because of MFN really trying to be conservative on our commercial forecast. Right. Like for ATTO-1310, for example, we included U.S. revenue only. Right. Also making very conservative pricing assumptions. That being said, we still get to an $11 billion peak sales. So it is still-. Still pretty good. Yeah. Excellent. All right. Thank you again, Tao. This was great. We appreciate you being here. Yeah. Thank you, Judah, for having me. Yeah. Appreciate it.