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

Good morning. Thanks for joining our 45th Annual Healthcare Conference. I'm Stacy Ku, part of the biotech analyst team with my colleague, Vis Shah, and we're happy to be hosting Astria Therapeutics. With us today, we have Jill Milne, thank you so much, CEO of Astria Therapeutics. Thank you so much for being here today. So obviously, just a short period of time and a lot to cover. In the last couple of months, the team has reported some of, to us, the best case scenario, updates for your lead program, navenibart previously STAR-0215, an HAE prophylaxis. So maybe let's take a step back, provide some brief overview of navenibart and then recap your recent proof-of-concept results -- drill down.

Yes, for sure. Well, first, thank you for inviting us to participate. Thrilled to be here. So I'll take a step back and give a brief overview of Astria. So at Astria, we are dedicated to advancing what we call first choice medicines for patients affected by allergic and immunologic diseases. Our lead program is navenibart, which is a monoclonal antibody inhibitor of an enzyme called plasma kallikrein that we're developing as a preventative treatment for a disease called hereditary angioedema and plasma kallikrein, the target of navenibart, is a clinically and commercially validated target for the preventative treatment of hereditary angioedema or HAE, as I'll abbreviate it. And you're right, we recently reported what we also agree were best case scenario results from our Phase Ib/II trial in HAE patients with navenibart, and we reported that earlier than anticipated, this past December. And those results support our vision for the profile of navenibart for the treatment of HAE. And briefly, what we were able to demonstrate with navenibart in that trial is robust efficacy, a really good safety and tolerability profile and support for dosing as infrequently as every 6 months. And in that trial, that 6-month trial, 1 or 2 doses of navenibart led to a greater than 90% reduction in attack rate in patients and up to 67% attack freedom rate, a 95% reduction in moderate to severe attacks and a greater than 90% reduction in the use of rescue med. So together, the data, we thought, was really compelling and supports our vision for navenibart to become the market-leading product in the preventative treatment of HAE.

So you talked about the every 6-month dosing and how competitive it looks versus some of the other agents out there. But I think what's remarkable is that when you look at every 3-month arm and the every 6-month arm, the efficacy looks almost the same. So I do think that's one aspect of the proof-of-concept studies. We're kind of keen to see if that reads out in future studies. So again, recent updates as we look to January, this year, you released kind of post-FDA interactions and update for your Phase III trial. Can you just walk through what are the different updates, clinical trial design?

Yes. And so certainly, again, I'd say that was the best case scenario for us as well because, as you know, we originally anticipated running 2 Phase IIIs to support both of those dosing regimens running a Q3-month first, followed by Q6-months. But based on the regulatory interactions we had, the global interactions, we're thrilled with the final design of the pivotal Phase III study, which includes -- incorporates both the Q3-month and the Q6-month, dosing regimens in a single 6-month trial. So again, best case scenario, and thrilled to have that ongoing now. We just announced last week that, that trial is underway. It's been initiated.

Exactly. So let's talk about the every 3-month and every 6-month arm and selection of doses. What were your -- so as we look to the proof of concepts, what were the read-throughs and kind of decision-making as you selected doses?

Yes. So we -- very data-driven selection of doses for that Phase III and data driven from our clinical data to date with navenibart. And what we were aiming for, was to advance doses to support the Q3-month and the Q6-month regimens that would produce efficacy that really was best-in-class as a preventative therapy on par with what TAKHZYRO, the current market leader, could produce or better. And both dose regimens that support the Q3 and the Q6-month based on our clinical data to date and our analysis of that data should provide that level of efficacy that is at or better than TAKHZYRO.

As we think about every 6-month dose, we're taking 600 milligrams forward, no loading dose. So what are your thoughts there? And as it relates to maybe some of the dose selection for Phase III, remind us that PK/PD aspect of the proof-of-concept study is quite important as we think about the different doses, maybe even kind of cohort 1, 450-milligram dose. What we saw there as you kind of did a single dose and just tried to see what happens over time for efficacy? A bunch of different questions if you look...

Yes.

I'm just trying to understand the different dose selection for Phase III.

For sure. So you're absolutely right that for that dose selection for Phase III, we took into account the PK, the PD and the efficacy produced in patients that we had seen to date. And you're right, from the Phase Ib/II trial that cohort 1 data that was produced with 450-milligram single dose that led to a greater than 90% attack rate reduction in patients through 6 months of treatment, that was pretty compelling to us. In the PK and PD, what that showed us is that we had a very rapid onset of activity and durable activity through 6 months. And so certainly, all of those were taken into consideration as we selected the doses going into the Phase III. And I think that's one aspect that's pretty compelling about navenibart at least as we see it is this rapid onset of activity and you said no loading dose for the Q6-month, and that's right. And that's because that 600-milligram dose gives a very rapid onset of inhibition of plasma kallikrein. Within 24 hours, we're inhibiting plasma kallikrein to levels that we believe are important for driving attack rate reduction.

Okay. And as we talk to our KOLs, they think that every 6 months is a total game changer, but they do expect some patients will actually still prefer the every 3-month arm. So I believe there are 2 arms for a 3-month dosing, just walk through your decision-making there. And what you're trying to achieve in terms of kind of patient flexibility around doses?

Yes. That's one thing that's been very important to us and certainly is built into the design of the Phase III is that concept of offering flexible dosing for patients and physicians. And we agree that the Q6-month is a game changer, but equally so, from what we've heard from patients and physicians that Q3-month is as well that some patients just going to feel more comfortable with in every 3-month dosing regimen. And so we want to be able to provide both of those dosing regimens to patients so that they can select what works best for them. Did I answer the whole?

Yes. Think about the 2 different Q3 arm doses, selection of kind of maybe the higher, I think it's one arm is going to be a lower dose, the second arm is going to be higher dose.

That's right. So in our Phase III, we have 3 navenibart arms for the adult patients. The first one is a Q3-month, it's a 600 mg dose followed by 300 milligrams every 3 months. The second arm is the 6 month, it's 600 milligrams every 6 months. And then there's a third arm that's 600 milligrams every 3 months. We believe that those first 2 cohorts are -- the first 2 doses, dose regimens are going to cover the majority of patients sufficiently. That's going to put them at the TAKHZYRO plus efficacy level. That third dose, the 600 milligrams every 3 months is for patients that may need a higher dose for a number of reasons or may feel more comfortable at the highest dose possible. So that's why that was incorporated. And again, to give that flexibility to the patient and the physician to choose what works best for the patient.

Okay. I understand that we're spending a ton of time on the Phase III design, but I do think it was really thoughtfully designed and as we think about patient flexibility, we also have a unique open-label extension trial. So maybe talk about Part 1, Part 2, what are you trying to achieve in kind of each aspect?

Yes. I certainly will give a shout out to Chris, our CMO and our clinical team for the innovative design of the Phase III program for navenibart. We are incredibly thrilled with the design we've ended up with and that long-term extension for the Phase III called ORBIT expansion. And you're right, that has 2 parts, which I think are incredibly interesting and hopefully going to really support what we hope to achieve with patients in HAE with navenibart. So part 1 of that extension trial, patients from ALPHA-ORBIT Phase III have the opportunity to move into that extension. And in Part 1, which is 6 months in duration, they'll go on to the same dose of navenibart that they were on in the Phase III. The placebos will go to the highest dose, so that 600 milligrams every 3 months. So that's part 1. We'll continue to collect efficacy data, safety, tolerability data. Part 2 is where it becomes interesting. So at part 2 -- after 6 months in Part 1, they move on to Part 2, where the patient and physicians choose which regimen works -- they think will work best for them going forward with their particular lifestyle and disease. And so that's where the dosing flexibility is introduced. And again, that will go on for another 6 months or longer as long as the patients want to stay on.

Okay. So remind us, when are we going to get data? And then from there, when would your expected NDA filing be based on the safety data that we're grabbing from the open-label extension?

Sure. So we are anticipating having top line data from the Phase III trial in early 2027. And of course, we're going to do everything in our power to work as efficiently as possible to execute upon this trial, and we'll see if we can beat those -- exceed those time lines. In terms of the long-term extension, that data is not critical path to a filing. Really, it's the top line data from the pivotal Phase III, the ALPHA-ORBIT trial. We will certainly -- the long-term extension data will be incorporated into registration filings for navenibart and will be an important component of that, but won't be rate limiting as we've laid out the plan to date.

Okay. So it would be helpful for the label, but you could always add it on as data progresses.

Yes, it will be certainly important for the label to collect more efficacy data and more safety data. But based on our projections of enrollment, won't be rate limiting.

And again, at the beginning, you did mention plasma kallikrein inhibitor, high familiarity, given TAKHZYRO mechanism of action. Very, very similar type of, let's say, target. Not the same, but they're very similar. So what do you think about enrollment? What are you -- I know it's very, very early days, but are you seeing a lot of excitement from kind of investigators? Are you seeing patients very willing to try something that they already know?

Yes, I think that's a huge advantage for navenibart is it's a trusted mechanism already, plasma kallikrein inhibition and a trusted modality of monoclonal antibody. So it's very much like the market-leading products. So a very easy conversation to have with patients and physicians. So I think that certainly plays to our favor, and we've heard a lot of excitement and interest from both patients and physicians, who are participating in the trial.

Do you expect similar level of ease to enroll both adults and adolescents?

I think -- so we have 135 adults that we anticipate enrolling in the trial and 10 adolescents. So certainly a different order of magnitude. I think there is a lot of interest. I could imagine from an adolescent perspective, being on a drug that's dosed as infrequently as navenibart could be a really attractive proposition for young patients.

Okay. Understood. So as the Phase III progresses, we are going to get additional information from the Phase IIb aspect of your proof-of-concept study. So maybe to the extent that you can, number of patients that you might disclose from the ongoing open-label extension trial, the redosing, how many redosing, I guess -- doses will you get? And what kind of efficacy should we expect?

Yes. So that's our long-term extension trial from our Phase Ib/2, which is called ALPHA-SOLAR. We anticipate sharing an interim read from that middle of this year. So what that will include is long-term data from patients who've been in the ALPHA-STAR Phase Ib/2 and opted to go in -- and I should point out that all patients who've been in that Phase Ib/2 trial have opted to go into ALPHA-SOLAR. So I think that's a vote of confidence for the profile. We'll have patients and will report data for patients who've been dosing for 12 to 18 months on navenibart. And in that ALPHA-SOLAR data set, we'll have patients who've been on the Q3-month, 300 milligrams Q3-month and patients who've been on the 600-milligram Q6-month. So that will be nice data to take a look at to look at durability of the efficacy and also, of course, safety tolerability as well.

Okay. Are you expecting similar level of efficacy as what we saw in proof-of-concept?

That's certainly the expectation. And I think it's certainly a vote of confidence from patients and physicians to have all of the patients who were in the ALPHA-STAR trial opt to go into that and stay in it. So I think that's a good sign.

Okay. So I guess we're expecting around 15, maybe, plus patients then. Is that a fair estimate?

So we had -- in the original set in ALPHA-STAR, there were 16 patients who enrolled, yes.

Perfect. Wonderful. And as a reminder, I believe the efficacy hurdle that you've discussed in the past is 80% to 90% reduction of Dyax.

That's right.

Okay. Wonderful. As we think about the HAE prophylaxis competitive landscape, there are obviously multiple agents that are in development. But obviously, to us, the KOLs tell us that every 3 months and every 6 month should lead to meaningful adoption versus maybe every 1 month dose. So maybe talk about your market research, what the KOL feedback has been so far to your proof-of-concept results? And how do you think those 2 different treatment frequencies will be used, so 3 months versus 6 months because you've done a lot of that work.

Yes. So we've done market research both in patients and physicians. Most recently, we did a market research study in 50 physicians, treating physicians from the United States. And I'd say what we tested was a product with a profile like navenibart that was offered as both a Q3-month and a Q6-month regimen. And we asked how that would be utilized in their practice. And I think we were thrilled with the responses. It was those 50 -- physicians said that in 53 -- they would use navenibart in 53% of their patients who are newly diagnosed, and in 46% of their patient population that was already on a preventative therapy. So that was pretty compelling to us that perhaps we could be looking at a market share in the 50% range, which we agree with the potential of navenibart and the excitement around it based on the profile we've generated clinically to date and what we think it can offer for patients.

Okay. Understood. And then maybe in the discussions you've had with KOLs, HAEGARDA still remains a fairly sticky market, but it's twice a week dosing. It's pretty onerous. So what are they saying for these patients? Like what's really going to kind of shake these patients out from switching?

Yes. I think the market has really changed. If you think about the HAE market, 15 years ago or so, there were no mechanism-based therapies. And so I think patients who all of a sudden had a HAEGARDA or CINRYZE, it was, I'm not going to change anything because I finally have something that is controlling my disease. I think that's changing. And I think a good example of why we think the market is not as sticky as everyone talks about is you look at the success of Orladeyo which had half the Phase III efficacy from TAKHZYRO but has certainly had a lot of uptake in the market because I think it offers something that TAKHZYRO couldn't offer to patients, a much more patient-friendly approach. And so we're pretty optimistic. And from the market research we've done, both the patients and physicians that the market isn't as sticky as I think we all believed.

That's fair, especially as we think about kind of other entrants -- recent entrants in the market. Okay. Last question on competitive landscape. There obviously are maybe some ways away, but there's always going to be kind of new investor fears of longer-acting agents. So maybe talk about gene therapy approaches with Intellia's NTLA-2002. I don't know if anyone else pronounces it that way. And maybe ADARx's HAE approach?

I think those are coming in the future as well. I think navenibart has something that's pretty unique and special among all of the therapies that are either on the market or in development. And that's -- it's a trusted mechanism. It's a trusted modality in the form of monoclonal antibody. So that gives a lot of comfort to patients and physicians. Also the efficacy profile we've generated to date with navenibart shows that it has efficacy on par, if not better than the market-leading product, TAKHZYRO. Also, as we look at the Intellia's and the potential of ADARx, safety, tolerability profile with navenibart has been clean. And I think this modality has been associated with a very clean safety profile as well. In addition, the time to onset of efficacy, I think, is going to be something that continues to be important for patients. And there's a much faster onset with a product like navenibart and what we've been able to demonstrate already compared to those products as well. And so I think all together, and also the concept for us of the YTE modification of the antibody to allow this very infrequent dosing as infrequently as every 6 months, makes a pretty compelling case when you put all that together for navenibart having the potential to be the market-leading product.

Okay. Understood. And 6 months seems to be at a bit of a sweet spot. I think once you get 12 months and you think about the patient population, there may be some hesitation, especially as we think about patients that clearly are telling their clinicians that they would want 3-month dose.

That's right.

Okay. You mentioned the YTE technology. So we do want to make sure we cover that distinction versus TAKHZYRO. This is an entirely different binding site to our best understanding. So just maybe a quick reminder on the patents that are filed, what type of exclusivity you might expect?

Yes. So it's definitely a different antibody than TAKHZYRO. It incorporates that YTE as well as different sequences. We filed for composition of matter IP, which, if granted, would provide coverage out through 2042. And we also have filed for dosing patent coverage as well, and if grandad, would cover us through 2043. So a nice length of time left on our potential patent state.

Okay. Wonderful. So we do want to make sure we spend some time on your second asset, STAR-0310. So maybe briefly talk about the distinctions between your asset, rocatinlimab and amlitelimab.

Yes. So STAR-0310 is a monoclonal antibody antagonist of the OX40 receptor so more like rocatinlimab from that perspective of mechanism. I will start by saying this is a place where we have incorporated the learnings from both the amlitelimab program and the rocatinlimab program in our STAR-0310 program, and I think we've greatly benefited from the work that they've all laid out ahead of us. What we -- both antagonists or antibodies against the ligand and the receptor have shown good efficacy in Phase II in atopic dermatitis. And for us, we think that the receptor is the way to go because the receptor is only expressed on activated T cells and it's the activated T cell that you want to target in the diseases like atopic dermatitis or other T cell mediated diseases and hence, how we got there. What we chose to do was to design an antibody that we thought would have high potency, high affinity for the receptor, competitive efficacy and good safety and tolerability and low treatment burden. So again, we've introduced the YTE to allow for infrequent dosing, different than rocatinlimab, which also targets the receptor. Rocatinlimab was engineered to have high ADCC, so to kill T cells. And what that appears to have led to, is a high rate of AEs in their trial, so fever and chills that are typically associated with ADCC-like activity. And I think what that has done is limit the therapeutic window under which they can operate. We took that learning into our program and have dramatically reduced ADCC in our approach. So the idea being that we can open up that therapeutic window, go to doses without the potential for that ADCC-like fever chills effects and really drive efficacy.

Okay. And within atopic dermatitis, I think it's interesting. The hurdle is obviously post-dupilumab, but what gets KOLs most excited is the infrequency of treatment. So I do think the YTE technology should be an interesting thing to look out for. And unfortunately, or not, the value for 0310 has been entirely washed out, I would say, of the valuation. So with that in mind, maybe talk about rocatinlimab, the Phase III data. What, I guess, publicly disclosed information that we have that might be unfairly attributed to kind of the class?

Yes. So rocatinlimab reported their first Phase III readout late last year and that was disappointing efficacy in comparison to what they reported at Phase IIb. It still showed efficacy in atopic dermatitis that statistically significant, they hit their end points, but it was just less than what they saw in the Phase IIb. There's still a lot to learn from that Phase III that they reported on. They've yet to report the dose that was used in that trial, the patient -- the characteristics of the patient population and also details of the safety tolerability. One hypothesis that's been floated is that they lowered the dose going into Phase III to try to get around the fever chills AEs that have been associated with that program to try to have a better profile. And that could have led to lower efficacy. It's also possible that, that, in addition to a different patient population led to a different in efficacy. And so I think we felt that a little bit, people -- confusing people about the potential of targeting the receptor.

Okay. Understood. I do believe they did disclose that they essentially extended the dosing frequency from every 2 weeks to every 4 weeks. You covered all the other aspects.

That's exactly right.

Okay. Understood. So as a reminder to the audience, we are getting a lot of competitive read-through to the OX40 class this year. We're going to get Sanofi's amlitelimab, at least asthma and hidradenitis suppurativa results, proof-of-concept results and in the first half and potentially atopic dermatitis results by year-end. So there are a number of different indications. You all have started your Phase I in healthy volunteers in January, and we could get potential results in Q3. So what kind of disclosures could we expect in healthy volunteers that would help us have read-through to atopic dermatitis. And again, as we're getting all of these different other potential indications where OX40 could be useful or could be pursued, how quickly could you move into some of these other indications?

Yes. So I'll start with the Phase Ia and the Q3 data that we intend to share. So that Phase Ia will be important for us in looking at the potential profile of STAR-0310 and also helping us select doses to go into the first patient trial. What we will clearly be looking at is certainly safety tolerability and looking for differentiation from programs like rocatinlimab and that aspect and also looking at PK for sure, to demonstrate that we could support a less frequent dosing regimen. And we'll use all of that information to help us select doses that we believe will produce robust efficacy in patients. When we started to get interest in the OX40 mechanism, it was because of the broad potential in diseases like atopic dermatitis, but in a broad range of other T cell mediated diseases. And we internally have been looking at potential opportunities for the OX40 mechanism and other diseases, and we're very eager to see the outcomes of this Sanofi data in HS and asthma in the first half of this year. I think that will be compelling. And I think in atopic dermatitis, just to make the distinction from DUPIXENT is, this mechanism, OX40 has the potential to have a broader effect than just a TH2-mediated mechanism like dupilumab. And I think that's why there's so much excitement in it to have that broader potential to hopefully reach a broader set of patients.

Yes. And it's interesting when we talk to KOLs, obviously, they're very comfortable with using kind of JAK inhibitors, which is not necessarily the case for most dermatologists treating atopic dermatitis. So we do think that there's greenfields in between the two, but unfortunately JAK inhibitors do influence efficacy expectations. So we'll have to see how all the different agents back up -- stack up among the KOLs but also among kind of the community treating dermatologist. Okay. In the last few moments, maybe just -- I know we hopped around all the different catalysts, but just remind us for this year and maybe the beginning of next year, what's the catalyst pathway for you all?

Yes. So 2025 is going to be an exciting year, and we're off to an amazing start. I'll start with the navenibart program, an important milestone this year was to initiate the Phase III trial with navenibart. And of course, we announced that last week that, that is now up and running and ongoing. For navenibart, we also anticipate releasing ALPHA-SOLAR long-term extension data which will -- we hope will show a read-on durability of the efficacy of navenibart in patients on a Q3-month and a Q6-month regimen. And so that will be midyear. And then for the STAR-0310 program, we're off to a fast start there as well. We initiated the Phase Ia trial earlier this month. That trial is ongoing and on track to allow us to deliver interim results in Q3, which will be important for assessing the potential in selecting doses for the first patient trial.

Wonderful. So to us, it sounds like a catalyst-rich next 6 to 12 months. In the last few moments before we end, this is obviously a unique scenario where the KOL feedback could not be more overwhelmingly effusive and no investor debates the likelihood of a navenibart success or the ability to reach $1 billion in peak sales, but the stock is trading close to -- last we looked, $50 million EV. So we get a lot of inbounds on HAE and this is one that we think is underappreciated. So if there's any last comments you'd like to make about kind of our open-ended discussion. I'd appreciate it.

Yes. I mean we also agree, underappreciated, I think, high potential for success with navenibart and based on the profile we've been able to support clinically I think, is there. I think having the Phase III clarity, we hope we'll turn the tables on how people view this program that now we have a trial design in a single pivotal Phase III that can support both that Q3 and Q6-month regimen. I think the macro environment has been a little crazy. But -- and for us, it's getting out there and explaining the potential of navenibart and continuing to execute as we have been.

Okay. Wonderful. Well, thank you so much for your time. Really, really appreciate it.

Thank you.

Thank you.