Astria Therapeutics, Inc. (ATXS) Earnings Call Transcript & Summary

Okay. Great. Good afternoon, everyone, and welcome to the next session at the Cantor Global Healthcare Conference. Really glad -- I'm Steve Seedhouse on the Cantor biotech team. Really glad to be joined by our next participating company, Astria Therapeutics, exciting company that we launched coverage on when we came to Cantor. And it's been a privilege to cover so far and looking forward to all the upcoming progress. I'm joined on stage by CEO, Jill Milne. Looking forward to the conversation. And as has sort of been typical for me in these fireside chats at our conference, I would love to just pass you the mic to start for some introductory comments and overview of the current state of affairs at Astria and the outlook as we head into the end of the year here.

Great. Yes, absolutely. Well, thanks for having us. It's been a great conference. So at Astria, our focus is on developing medicines to improve the health and outcomes of people with allergic and immunologic diseases. Our lead program is navenibart. It's a monoclonal antibody inhibitor of an enzyme called plasma kallikrein, which is a clinically and commercially validated target for the treatment of hereditary angioedema, a rare disease. We are currently in Phase III development with navenibart. What has excited us about this program is the efficacy that we've seen to date with navenibart in our Phase Ib/II trial, which demonstrated a greater than 90% attack rate reduction in patients with HAE for both our q3-month and our q6-month dosing regimens. And so those regimens are currently being tested in Phase III. We are actively enrolling that trial and on track for top line data in early 2027. The second program in our pipeline is STAR-0310, and this is a monoclonal antibody antagonist of the OX40 receptor. We have some data coming out in a couple of weeks at EADV. We will be presenting an oral presentation in a late-breaking session on our Phase Ia healthy subject data. And so very much looking forward to that as well.

Indeed. Thanks for that overview. And we'll start with HAE. Would love to talk about OX40. And also there's been some news just recently with OX40. Yes, we can maybe come to that. But just in the Phase III, I mean, how is enrollment going? And are you satisfied with the sort of guidance you've put out there for early 2027 data? How is the progress?

Yes. We are thrilled with the progress to date, really excited about the enthusiasm that we're hearing from patients and physicians. The trial is active now in the U.S., U.K., Canada, South Africa, Hong Kong, with European sites coming up and also Japan sites coming up. So, so far, so good. So we remain on track.

Great. One thing that I wanted to clarify was -- so there's an additional cohort in the study, which is in adolescents, and that's an important segment of patients, of course, to address. Will that data be available with the initial top line data release? Or is that sort of running parallel and separate on a different time line?

It's running in the same trial, but as -- you're absolutely right, as a separate arm. And we haven't yet indicated what data will be available with that top line, but it is running concurrently with the Phase III.

Okay. Is that enrolling as well right now?

Yes.

Okay. And then just regarding dose selection. In Phase II, there was sort of the additional dose at 1 month post treatment initiation. In Phase III, you've obviously selected the every 3-month and the every 6-month dosing regimens. Just based on all the data that you're continuing to accrue, and you've presented some of that in the open-label extension study, are you comfortable with the Phase III doses that you selected? Is this tracking as expected in terms of the long-term data you're seeing? And just talk about the rationale, I guess, for doing what you did.

Yes. So we are -- we remain confident in the doses we've selected for the Phase III for the -- both to support the q3-month regimen as well as to support the q6-month regimen. And that confidence comes from the data that we've released to date from the ALPHA-STAR Phase Ib/II trial, but also importantly, from the ALPHA-SOLAR open-label extension trial as well. In addition, also our QSP, or quantitative systems pharmacology, modeling as well that supports both of the q3, q6 and the doses selected for those.

Okay. And then in the adolescent arm that I mentioned, the dosing regimen there, I think, is 600 milligrams transitioning to 300 milligrams. What was the rationale for that in that particular arm?

Yes. So we think that the q3-month regimen will really be a huge improvement for adolescent patients with HAE to go to that infrequent dosing. And that dose selection was selected based on the QSP modeling and based on previous data that led us to that as well as conversations with health authorities.

Okay. Just to follow up on the recent announcement of the Kaken partnership. First of all, I guess, what role will Japan sites and enrollment of Japanese patients play in the overall study that has some implications also for the reimbursement as part of that partnership, I think? So maybe just recap the structure there and the expectations for how big of a role that region will play in the trial.

Yes. So Japan is obviously a region that we're very interested in. It's the third largest market behind the U.S. and Europe. And it's actually a really interesting market in that it's really early in development. So we think it's important to be there, and we are really pleased with the partner that we've selected to do that with. And so from a Phase III trial perspective, one important aspect of having a partner for us is really to raise awareness of the trial and also to engage the KOLs and treating physicians in Japan. Now that partnership included support for the Phase III, so with regard to the percentage of patients we enroll in Japan. And just to give some color, I guess, if we -- probably the best measure there is to look back at other trials that have run Phase III and had sites in Japan. And the most recent one, ANDEMBRY, that was reported had about 9% of patients coming from Japan. And so there'll be a proportional cost that Kaken will cover as part of that.

Got it. Is that -- will that be recognized just as revenue like cost reimbursement? Or...

So we haven't indicated how it will be recognized yet, but by our next Q, we'll have that assessment.

Okay. And then how are you thinking about Europe? I mean we've seen some strategic transactions in the HAE space in Europe, ORLADEYO recently. I mean is that a market that you think more amenable to a partnership as well like Japan? Or is that a region you think you can commercialize at Astria?

Yes. So what we've stated is we plan to commercialize on our own in the U.S. and are considering our strategy outside of the U.S. And clearly, we've now revealed that strategy in Japan. Certainly, there's a lot of interest in the space. So I think for us, we'll further explore what we think is right for the program and for patients and make a decision about that. But yes, a lot of interest in the space.

Yes. And then back to the Japan deal, I mean, what was unique about that, of course, is you haven't even completed your Phase III study yet. You're already licensing commercial rights at economics that match drugs that were pending approvals. I mean how were you able to get that done on those terms?

Yes. We were -- and you're absolutely right because you'd most typically think, wait until you have your Phase III data because that will drive the best economics. We were really pleased with the process that we ended up running in Japan and how competitive it was and to secure the economics that we did get for a pre-Phase III. But I think I chalk it up to the confidence in the program and the data that we've produced to date and I think also the interest that the Japanese partners had detected in the physician and patient population there for navenibart.

Yes. That's great. As you think about this market, I mean, it's a large market, HAE. A lot of patients have shown a propensity to want prophylaxis. That's a growing opportunity. But there are some new launches recently in the space. You mentioned one, ANDEMBRY, also DAWNZERA. Different mechanism there, a different approach from a knockdown standpoint. Just what are you looking for in these launches? I mean, obviously, sort of the willingness of patients to switch to a new therapy is one metric that would be critical to Astria down the road. The longer-acting sort of nature of those antibodies relative to their predecessors is another. But how -- I mean, what's going to be important for you to see? What are you sort of hoping to see? Does any of this matter? Or do you think in a vacuum, navenibart is going to succeed on its own merit? I would love to get your perspective.

Yes. Well, to start with the latter, I do think navenibart is going to succeed on its own merit. And I think what we continually hear from patients and physicians is they want a therapy, a preventative therapy that has robust efficacy and can be dosed infrequently, so with low treatment burden. We obviously are watching both of these launches closely, and I can talk sort of out of both sides of my mouth. If their launches go well, yes, it does speak to the switch population. I think if they go moderately well or not well, you could argue, is there enough differentiation from an every month dosing to what we have right now with the market leader, TAKHZYRO, which can be dosed in some patients every month. And so we'll obviously be watching the dynamic and seeing which type of patients are switching.

So personally, I mean, I am expecting them to struggle a little bit for that reason because when we -- the differentiation reason. When we've talked to KOLs and when we were doing our work on the space, it was amazing to hear -- well, maybe not surprising to hear that once monthly is not so differentiated from every 2 weeks, not enough to sort of overcome the stickiness of this market. But the KOLs were aware of Astria and aware of navenibart, and this is before you had even initiated your Phase III study. I mean how have you been -- what have you been doing as a company? And how have you been able to sort of prep the experts in this space already years in advance of a potential launch? I'd love to sort of unpack the strategy there. And is it just the product profile speaking for itself? Or how have you tackled it?

Yes. So I'm really proud of the work our team has done here, and that work has started from day 1. When we first started working on this project in this area was to really understand what patients wanted and what physicians wanted in a product. And so we've had a very active open dialogue throughout the evolution of Astria from the time this asset became ours. And I think that's paid off well. But I think importantly, the target profile that we have for navenibart is something that's pretty unique and special in this space to have something that is a trusted mechanism, a trusted modality that so far has produced efficacy that is on par with the market-leading products and also with a very low treatment burden. That's really a step change from anything that's out there right now, I think helps support the interest.

I think saying efficacy is on par with the market leader is maybe a little too humble because the efficacy to us looks quite a bit better from Phase II. So hopefully, that can be replicated in Phase III. Speaking of Phase II, I mean, what future updates are we going to get from the long-term extension study that's ongoing? We've gotten one, the data looked great. On what cadence and when would be the next update?

Yes. We haven't indicated yet when the next update will be, but I can tell you we'll be taking data cuts from that ALPHA-SOLAR extension trial on an annual basis. And so I would expect to continue to share data from that. And we agree that data has been great, and it's really great to see patients engage in that trial and staying in that trial. And I think it speaks to the benefit that they're getting from navenibart.

In addition to the efficacy and the convenience, also the injection site reaction profile looks very mild for navenibart compared to at least TAKHZYRO. Can you just maybe walk through -- I mean, what is that reaction and the burden on patients and sort of how important is it in your experience in talking to the experts in the field? Why is it so much more mild for navenibart? Is that a feature of the drug that was sort of built in? And how much impact do you think that could have ultimately on patient preference?

I think that's really important from a patient experience perspective. And I can tell you when we first started this program back in early 2021, when we were talking to patients just to understand the HAE landscape, one thing we were surprised to hear is about how painful injections were with TAKHZYRO. And so it's something that struck us. We hadn't anticipated to hear that. And so when we started to work on navenibart and work on the formulation, we would ultimately take forward -- we took that into consideration, how could you improve this to improve that patient experience? Because I can tell you hearing some patient stories about how they have to psych themselves up to give the injection. And it probably speaks to why there's only a prefilled syringe in the U.S. for TAKHZYRO. So patients can control the rate of injection where an auto-injector would be a faster uncontrollable rate that you're injecting if it's a stinging sensation. That's not a pleasant experience. And so we believe that could be due to the citrate buffer that's in the formulation for TAKHZYRO. We actively worked to develop a formulation that was very patient-friendly and could support a no-pain injection. And that's sort of what our mantra was as we were developing that formulation, and it seems to have played out.

That's great. And so that's on the tolerability front. On the safety front, just thinking about the DAWNZERA label in particular and some of the sort of class labeling features, have you guys seen any effect on platelets? Have there been any hypersensitivity reactions or anaphylaxis in any of your studies?

So no effect on platelets, no hypersensitivity, anaphylaxis. We -- and also no elevation of liver enzymes as was also in the label.

Okay. I mean do you think that just by virtue of that, the data will speak for itself and that will afford you a differentiated label if you replicate that in Phase III? Or is the FDA kind of a stickler on some just class labeling?

If you look across the different labels, there are differences. So I don't think it is a class label. And of course, DAWNZERA has a different mechanism, different modality as well. So we don't anticipate that would be something unless we see something from a safety perspective in our Phase III.

Okay. Maybe we can talk about OX40 as well. It's an exciting space. And the amlitelimab Phase III AD results were just announced. So I would love, if you're comfortable, just to get your perspective on sort of the outlook for OX40 as a mechanism in AD and beyond and maybe updated thoughts post that data. Maybe we can start there, and then we can discuss the asset and the history of the asset and your plans for it.

Yes. So of course, the amlitelimab first Phase III data was reported in our press release this morning. So we saw that. So I think from an OX40 perspective, what that data showed is both dose groups hit their endpoints, so showed efficacy in atopic dermatitis. There was a decrease in signal compared to their Phase IIb trial. And so obviously, we're looking forward to learning more about the patient population and how that might have been different from the Phase IIb. But also understanding -- I'm sure there are going to be later time points from that trial. If you saw the data, it appeared that they hadn't reached maximal efficacy, which was something we anticipated for them. And this was, of course, replicated by rocatinlimab as well. We know the OX40 mechanism has a slower onset. And so you can see that there, the data -- the efficacy hadn't plateaued on either dose group in this data released today. And so we'll be interested to see that. I think it -- this for me, I think OX40 is a really intriguing mechanism that has a lot of potential. I think being first-in-class has -- comes with challenges in a new mechanism in disease areas such as this that are highly competitive. I think learning from rocatinlimab and amlitelimab and how these trials have run and the learnings from these trials can help influence in a positive way those of us like STAR-0310 and how we design a proof-of-concept trial.

I mean I think the -- we can all appreciate the premise in immunology that we've seen time and time again, whether it's TNF or IL-17 -- I mean, there's another -- it's like the third- or the fourth-generation IL-17, big data coming this month in HS. It shouldn't be surprising that the first movers are going to leave something on the table from a molecular design standpoint that the Astrias of the world can improve on. Can you just recap the -- what are the features of 0310 that you've built into that molecule and why you think it will be better than some of those first-generation molecules?

Yes. So to start, we decided when we got interested in the OX40 space to target the receptor. Amlitelimab is targeting the ligand. And the reason we targeted -- chose to target the receptor was we believed that targeting the activated T cells was the place to go because it's the activated T cells that only express the receptor. And those are the cells that are driving the pathology in the disease state, whether it be atopic dermatitis or another disease where OX40 plays a part. So just out of the gate, that was important to us. We thought there'd be potentially lower sort of off-target, off-T cell effects that could lead to safety or tolerability. Next, we designed a molecule that had low ADCC. As we know, rocatinlimab was engineered to kill T cells. And we believe that has translated to the fever, chills, the ADCC-like effects that they're seeing in the clinic and has, we believe, caused them to leave some efficacy on the table. Our goal was if we had no to low ADCC, we could open up that therapeutic window, drive dose, drive efficacy to greater levels. And we've also engineered this antibody to have a very long half-life. And so the idea of being the combined potentially improvements in efficacy and that long half-life could allow us to really drive the potential of the molecule. And we have our Phase Ia healthy subject data coming out in a couple of weeks. And hopefully, that data will read on some of these aspects.

Yes. I mean, typically, with Phase Ia data, maybe there's not much to learn. But here, I think there is -- there are other instances, I think, in I&I recently where there's been a lot to learn from Phase I studies because the mechanism is validated, right, and you have the late-stage efficacy data from some precedent. So I want to just walk through some of the different maybe potential aspects of the data that we could see and just get your perspective on whether I'm thinking about it reasonably and maybe how you would frame some of these data points. So first on PK, obviously. Based on preclinical data -- so there was a 26-day half-life in nonhuman primates. That would be expected to be longer in humans, maybe up to fivefold longer. So do you think that you'll be able to establish that the PK could support like every 6-month dosing in humans? And is that -- or what do you think you could establish already in Phase Ia in terms of potential dosing intervals?

Yes. So we believe the data will give us an indication of whether we can support every 3-month or every 6-month dosing.

Okay. And then on PD, is there a way to assess pharmacodynamics in this study in healthy volunteers and maybe even from the standpoint of just sort of piecing together PK/PD from other OX40s and what levels were needed to be reached? And can you adjust for the potency of your antibody? Just would love your perspective on how you're thinking about extrapolating this Phase Ia data to knowing if you're at therapeutic levels.

Yes. So certainly, this -- so unfortunately, not all programs have reported healthy subject PD data. So it's hard to compare directly across to that. But as you say, because this -- there are molecules ahead of us that have clinical efficacy, we have a good understanding of and we know potency of our molecule in vitro. We know potency of those molecules as well in vitro. And we can -- you can make -- build models that will give you a read of have we achieved drug levels that we think will drive efficacy to levels that are important. And so we'll certainly -- this data is going to be used to build a QSP model to hopefully inform on dosing regimens and where we think we can drive efficacy in terms of every 3 months or every 6 months.

Great. And then, of course, the ever important safety and tolerability. So you mentioned some of the potential areas of differentiation given the molecular design, the enhanced ADCC of rocatinlimab and the impact I think you mentioned on chills. Is that something you can tease out already in Phase Ia? Or are we going to have to wait [indiscernible]?

Yes, for sure in Phase Ia. So in fact, that is an easy thing you see upon dosing is if a molecule has ADCC, you will see that, fever and chills. And in rocatinlimab Ia healthy subject trial, they saw greater than 50% of subjects had experienced fever or chills.

Okay. And then I guess the big question, which is assuming these data support the product profile that you're hoping for, what's the next step? So I mean, even after this morning, how are you thinking about atopic dermatitis maybe strategically or other potential indications for this drug?

Yes. So that's a great question. So for us, it's getting our data, looking at the external landscape and determining what the best path forward is for STAR-0310 and in what indication. I think it's clear that there is efficacy of this mechanism in atopic dermatitis. Is there a way to drive that efficacy deeper and faster? And I think our team has some ideas about that.

Okay. And just to close, I want to go back to HAE. And it's a market that we have a lot of data on. Historically, there's a lot of drugs approved, and these new launches will be tracking. Do you think there's going to be big changes in that market over time in terms of proportion of patients on prophylaxis? Pricing is maybe a big one. Anything else? Or do you think you have a handle that, that market is pretty predictable and stable and what you see today will sort of be a similar landscape to when navenibart launches?

Yes. So I think the market is going to evolve. Clearly, with the other products coming to market, we're going to see some evolution and movement of patients. I think some of the older drugs potentially will begin to take less and less market share. Some of the more burdensome drugs that are dosed 2 or 3 times a week, I think, become probably less interesting in the marketplace. I think as we see it, the market will likely evolve to the agents that have the best efficacy and the lowest treatment burden, and we see navenibart playing a big part in that. I think in the U.S., there are probably about 70% of patients on preventative therapies. That will probably continue to grow. Certainly, there's more room for growth in Europe and a lot of room for growth in Japan in terms of patients going on to preventative therapies. And quite frankly, in Japan as well, our understanding of the patient population there is there's only about 20% to 25% of patients have been identified. And so we think there's a lot of growth that's going to happen in that market.

Do you think -- so I'm expecting there'll be another oral on the market. There's no oral on-demand therapies. Intellia's gene editing product could very well be on market. Do you think those will have sort of large transformative impacts on the market, particularly on gene editing? Or does that feel like it could be a niche product for the most part?

Yes. I think it will be -- my guess, it will be a more niche product. And the reason I say that is this -- HAE is a place where there are trusted modalities that work really well. And what we haven't seen from gene editing yet is -- it is not a cure. So I think the question will be, is it worth -- is the risk/benefit there for gene editing? I think the orals -- there'll always be a place in the market for orals. I think we firmly believe that when you have an agent that can be dosed as infrequently as every 3 or 6 months, you probably start to think about patients who are going to an oral for convenience might be better served by something they can think about 2 or 4 times a year.

Yes. Anything we didn't cover that you'd flag that would be sort of important to highlight for investors that you'd be expecting either away from Astria or anything you have sort of cooking in the oven at Astria that you'd be announcing or updating folks on in the next 6 to 12 months?

Yes. I think for us, it continues to be about execution and doing what we say we're going to do. And we've done a good job at that so far and, I think, advancing 2 high-quality programs.

Great. Well, we really appreciate you being at the Cantor conference this year. Thanks so much for the discussion. We're looking forward to the Phase Ia OX40 data that's upcoming and all the progress that you'll be making in the years ahead. So good to have you here.

Well, thank you for having us.

You bet.