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

Good morning, everyone, and welcome back to Oppenheimer's Annual Health Care Conference. I'm Jeff Jones. I'm one of the senior analysts here at Oppenheimer on the biotech team. And I'm delighted to be joined by Astria Therapeutics and their CEO, Jill Milne; as well as the Chief Medical Officer, Chris Morabito. So Jill, just to start off, why don't I have you get a little bit of a background and an overview of Astria Therapeutics, and then we can dive into the programs.

That's great. Thanks, Jeff. So as many of you know, our focus at Astria is to develop first choice products that improve the health outcomes of patients with allergic and immunologic diseases. Our strategy for our pipeline is to transform science that works into medicines that patients want. In our lead program, which sits very well with this strategy, navenibart, is a monoclonal antibody inhibitor of an enzyme called plasma kallikrein. Plasma kallikrein is a clinically and commercially validated target for the treatment of hereditary angioedema or HAE. We're in the process of initiating our Phase III ALPHA-ORBIT trial for navenibart this quarter with top line results anticipated in early 2027. We also expect to have long-term open-label data from the ALPHA-SOLAR trial midyear this year. Our second program, STAR-0310, is a potential best-in-class OX40 program for atopic dermatitis and potentially other indications as well. We received IND clearance in December for STAR-0310 and have initiated a Phase IA healthy subjects trial with the result anticipated in Q3 of this year.

Okay. Great. So diving in on navenibart. As you mentioned, you're starting your Phase III. But if you could remind us what you showed in Phase II and really how this program is set apart from some of the other options in this space really TAKHZYRO as a prophylactic?

Sure, Jeff, I can take that. As Jill said, we've developed navenibart with first choice mentality in mind and at Astria, we have been very deeply focused on taking trusted science and turning it into medicines that patients want. Jill highlighted a couple of very important attributes of this navenibart. First is that it's a monoclonal antibody as a trusted modality. We have a lot of experience with, growing experience with monoclonal antibodies. We understand how they work, we understand how they're eliminated and we understand how patients respond to them in general terms. The second is that is an anti-plasma kallikrein antibody, and this is a core enzyme in the pathway that generates bradykinin that causes these attacks in hereditary angioedema. Lanadelumab, the current market leader, is also a plasma kallikrein inhibitor. In vitro, where at least, if not more potent than lanadelumab. And clinically, it looks like be may in fact be more potent. What takes this one step further there and informed by listening deeply to the clinical community is that we've modified this navenibart such that it has a prolonged half-life. And its prolonged half-life allows for Q3-month and Q6-month administration, and I'll get to some of the data in just a second that further inform that. We've also changed the formulation so that it is well tolerated and low risk of pain. And to date in our clinical program, we haven't seen any injection site reactions of pain, which already differentiates it for lanadelumab and TAKHZYRO. The formulation also lends itself nicely to an auto-injector, which is, again, different from what lanadelumab currently offers. And we do intend to bring forward an auto-injector and a prefilled syringe for commercialization after the Phase III trial. So that's a little bit about what makes us feel navenibart is special. The clinical data that we've developed so far from the Phase I and the Phase II further affirm our confidence in our conviction in navenibart as a potential market-leading therapy for hereditary angioedema. In Phase I, in healthy subjects, we saw that this has a good PK that's associated with the potential for Q3 and Q6 months half-life as well as strong pharmacodynamics. In the Phase Ib/II ALPHA-STAR trial that we just reported final data from the original 16 target enrollment population in December, we're seeing a very strong efficacy. We're seeing over 91% reduction in HAE attacks after just 1 or 2 doses in the patients who have participated this, and that reduction is compared to baseline. Up to 2/3 of the participants are attack-free. And for a small study, attack rate by the way, is 6 months. And for a small study, that's a very encouraging number. And again, this gives us conviction that this will be a potential differentiator when we get into Phase III. We're seeing over 95% reduction in moderate and severe attacks. We're seeing over 91% reduction in attacks requiring rescue medicines and appears to be safe. And as I mentioned, we're not seeing any evidence of tolerability concerns. We're not seeing any evidence of pain. So as we think about moving into Phase III, we're doing so in a position of strength and with a lot of conviction.

That's great. And just for reference, the 90% to 95% reductions in be they attack rates, use of rescue therapy and things like that, how does that compare to TAKHZYRO as we think about setting a bar here?

Yes. So TAKHZYRO in this Phase III trial, which was also 6 months long, had between 83% -- sorry, 87% reduction at the 300-milligram Q2 week dose level, and that was the highest dose level and the highest efficacy achieved in that trial. And that's placebo-controlled data. So it's different from what we have. It is a Phase III trial, so it's just bigger. We've done our own work here. We've amplified our small data set from ALPHA-STAR using model-informed drug development, quantitative medicine techniques from sample in patients of 16 patients to a virtual sample of 10,000 patients. And in that modeling and simulation exercise, we're seeing, again, a reiteration of this efficacy profile. So in a 6-month trial, where we continue to be in a position where we expect to see very robust potentially market-leading efficacy with 0310 -- sorry, with navenibart.

Now obviously, you're moving into your Phase III. But in the meantime, you have the ALPHA-SOLAR program running. And could you give us -- just walk people through the ALPHA-SOLAR program and how that builds the bridge between the Phase I and Phase II as well as the dosing interval?

Yes. So ALPHA-SOLAR is our long-term open-label extension. And patients who completed ALPHA-STAR, which is a 6- to 9-month treatment duration proof-of-concept trial, how the ability to roll into ALPHA SOLAR. And in ALPHA-SOLAR, the patients get either 300 milligrams every 3 months subcu, or 600 milligrams every 6 months. And this turns out to be the doses essentially that we've tested for -- that we plan to test in the ALPHA-ORBIT trial, and we can talk about that trial in a minute, I suppose. So we're already beginning to collect long-term safety and efficacy data with 300 milligrams every 3 months and 600 milligrams every 6 months to further support the value proposition of navenibart in HAE. And we look forward to sharing those data, initial data from the ALPHA-SOLAR trial in mid-2025.

Great. And I guess just given the limitations of timing from the Phase I, the open label as you said, you've already initiated your ALPHA-ORBIT Phase III. And it has really interesting design allowing you flexibility to look at these doses and schedules. So maybe share a little bit about how you arrived at that strategy and the benefit of that flexibility.

Yes. So ALPHA-ORBIT is our single Phase III pivotal trial. And it's that trial plus a long-term extension trial that will provide ultimately safety and efficacy data that will support applications for market authorization, assuming that the data are positive. What we've done is build together a very strong case to design an innovative Phase III pivotal trial, ALPHA-ORBIT. And it's innovative in that it's a single 6-month trial that will assess Q3-month administration as well as Q6-month administration. In this trial, we're testing navenibart in adults and adolescents. Adult patients will be randomized to 1 of 3 active arms; 600 milligrams followed by 300 milligrams every 3 months, again, this is a 6-month trial; 600 milligrams every 6 months and 600 milligrams every 3 months. Those first 2 doses, 600 and 300 and at 600 Q6 months, we expect to be the doses that will work well for the majority of patients. But there might be some patients who, based on the severity of their disease or based on their patient preference, would need more drug. And for that, we're testing 600 milligrams Q3 months. And what we anticipate out of this trial and ultimately out of a long-term extension trial is data that would inform the ability for patients and clinicians to work together to find a regimen that works best for their disease and their expectations. As we've done a lot of work here, we know that some patients are going to prefer every 3-month drug. Some patients are going to prefer every 6-month drug. And here, we've built away that in the real world, patients could get 600 milligrams on the first day they start therapy, wait and see how their response to the medicine is and then based on that response, based on preference based on discussions at the patient level, medical population level, which is what most drugs do, but at the patient level, make a determination about what that next dose is. Would you go to 600 every 6 months? Do you want to stay at 300 milligrams every 3 months? Might you need more drug, 600 milligrams every 3 months, because maybe you have a life stressor coming up or your disease is just so severe that you just need a bit more drug. So this is -- we're really excited about this. It's all set to kick off this quarter on track to deliver data in '27. And like I said, all cylinders are on fire to get this trial up and running.

Great. Do you guys have a feel yourselves for the likelihood that this ends out 3 months versus 6 months?

In terms of -- our goal is to bring both the Q3-month and the Q6-month regimen to market and make available for patients. And I suppose maybe what you're asking is what will be the patient preference. And I'd say there's strong interest in both the 3-month and the 6-month regimens. And so I think -- we think there'll be good uptake of both. You might imagine that patients may feel more comfortable starting on the Q3-month regimen and making a decision to go to the Q6 once they have established that navenibart is a drug that works well for them.

Okay. Yes. And I think it's a good segue into the market. And as you look at some of the other options that are out there, you look at sort of TAKHZYRO in the market as a dominant leader in the space and the adoption of ORLADEYO as an oral option. I guess are there lessons to be learned from what you've seen in the uptake of ORLADEYO in terms of efficacy preferences, convenience and just patient unmet needs?

Yes, sure. Yes, starting with ORLADEYO. ORLADEYO clearly has had a very strong launch and continued success with their sales, and we see this as really an opportunity for navenibart. ORLADEYO's success demonstrates to us that the HAE market may not be as sticky as many originally anticipated and reinforces that patients are willing to try a product with half the efficacy in Phase III as the market leader, TAKHZYRO, in exchange for convenient dosing. And so we believe that navenibart can become the market-leading HAE therapy because of its robust efficacy, but importantly, because of the reduced treatment and administration burden and comparable efficacy to TAKHZYRO.

And I think you had mentioned briefly in the introduction on navenibart some of the issues around injection site pain on administration of TAKHZYRO. So in addition to that high treatment burden in terms of every 2 occasionally 4-week injection, the injection site pain. How is that -- in your market research, how is that impacting patients and the benefit for what you guys are able to demonstrate so far?

Yes. I mean from what we hear that the pain associated with injection is something is quite significant to patients. And in the design of navenibart and the formulation that we selected to use with navenibart, that was top of mind for us, is to make navenibart the most patient-friendly prophylactic therapy that we could. And that was partly to reduce the frequency of dosing, so going from that 26 times a year with TAKHZYRO for the Q2 week dose to 4 times a year or 2 times a year. But importantly, along with that less frequent dosing is to also make the injection more friendly for the patient. And so we've chosen a formulation that we believe would not be associated with pain, and that has played out very well in our clinical trials to date. And we think from what we hear from patients, that is something significant to them and meaningful.

Okay. And you mentioned you were exploring 2 different formulations, a prefilled syringe as well as an auto injector. Where do those stand in terms of development? What will you use in your Phase III? And any challenges as you look to get those formulations approved?

Yes. So from -- you're right. So from a device perspective, we've made the decision that we would like to launch navenibart with both a prefilled syringe and an autoinjector. And we think that's important, to allow the patients to choose which device is best suited to their lifestyle. And in fact, the reason while I would anticipate great uptake with the autoinjector, we know that patients who are currently on TAKHZYRO using a prefilled syringe. So making that transition potentially even easier for those patients is important. So the work on both the prefilled syringe and the auto-injector is going well. It's on track, and we are working diligently to ensure that we can launch with both of those devices. And so that is our strategy and our plan for the launch.

Okay. And for the Phase III, is that a prefilled syringe? Or I guess it doesn't really need to be for your Phase III, but what is your formulation going to be there?

So we're using a vial and syringe for the Phase III. However, we will be incorporating a device in the Phase III program to help with establishing those devices and collecting data in patients.

Okay. And I guess on navenibart, what is, as we look into 2025, what is the pace of sort of updates and clinical data on ALPHA-SOLAR? Any follow-on data maybe on laryngeal attacks or things like that and what you're seeing out of these patients? So what should we expect as we look into 2025 in terms of updates for the program?

Yes. So the first big update we'll have, we hope, is this quarter, we are on track to initiate the Phase III ALPHA-ORBIT trial. And so that's first milestone. In terms of navenibart as well, as Chris had mentioned, we plan to share results from the ALPHA-SOLAR long-term open-label trial middle of this year, which we think will be an important update for the program as we expect that, that update will show durability of effect of navenibart when administered chronically at 300 milligrams every 3 months or 600 milligrams every 6 months. And so those are the major milestones for the navenibart program.

So perfect segue into talking about the OX40 program and STAR-0310. And I guess, OX40 has been a target with mixed results. And really -- so let's talk about STAR-0310 and how it's differentiated from your perspective from some of the other programs in the space? And what gives you confidence here?

Yes. So I'll start there. So yes, I agree with you some of the data that we've seen from some of the competitor programs has been mixed. But I will say we've intentionally designed STAR-0310 to capitalize on the learnings from the OX40 receptor and OX40 ligand programs with the goal of having the best overall OX40 program. We believe we have confidence that STAR-0310 has the potential for a best-in-class profile. And that includes competitive efficacy low, treatment burden with infrequent dosing, potentially as infrequent as every 6 months and the potential for disease modification. In addition, and I think what might be important area as well is we're exploring options to optimize dosing to really drive rapid onset of activity and sustained efficacy. And so certainly more to come on that. Additionally, in the design of STAR-0310 and what we've been pursuing with this program is combining reduced ADCC activity alongside robust against cytokine modulation to provide STAR-0310 with potential for a more favorable safety profile and, importantly, a wider therapeutic window. And we think that balance really minimizes -- could minimize the side effects of unwanted immune overreaction but maintain very strong efficacy, which we think the OX40 mechanism can deliver.

Okay. And in terms of -- well, as you said, you're getting ready to start your Phase I trial. So can you shed a little light on what that looks like in terms of the Phase I and as you move from a healthy volunteer to an atopic derma-type population?

Yes, sure. I'll be happy to get that, Jeff. As Jill said, we purposely designed this to differentiate from the other therapies that are currently in this space. And she highlighted the ADCC appropriately. Whilst reducing ADCC means is that we have the potential for a wide therapeutic window, meaning that we have the potential to optimize the dose without side effects that lead to discontinuations that lead to fevers and to chills, which I think is plaguing the rocantinlimab program. They have a narrower therapeutic window because of safety concerns. We've designed 0310 in a way that opens this up and we expect in our Phase I healthy subject trial to explore this. So that's ongoing right now, healthy subjects are getting 0310 now. And later this year, we'll be able to share some early proven concept data that we'll talk about the pharmacokinetic profile, talk about the safety profile. We're looking for some PD effects as well from that clinical trial in some healthies, so there are some limitations on pharmacodynamics. And then based on that, we should get a very good idea of what ultimately the potential of this is compared to the other OX40 antagonist for AD right from the back, from early proof-of-concept data. The next clinical trial that I should point out is proof-of-concept trial, and that will be in patients. We're working through the details now. We anticipate that this will start before the end of this calendar year and provide data by Q2 2026. That ultimately should show some effects on clinical outcomes like the [ EZ 75 ] score and give some sense of not just the slope of the impact on this clinical outcome assessment. But ultimately, how high can we go, how can we drive efficacy with 0310 to provide some framework reference to its potential effects or effects themselves versus rocatinlimab and versus amlitelimab, which we view as right now the more significant players in the OX40 space for atopic dermatitis.

And as we look ahead to that Phase I data, what particular signals should folks be looking at to differentiate it versus roca and the other OX40s?

Yes. It's an important question because it is in healthy subjects and healthy subjects don't bind their age or have activated T cells don't therefore have lots of OX40 expression. Having said that, from a PK perspective, we want to be able to demonstrate that we have the ability to drive PK in a way that optimizes efficacy and as Jill said, be able to maintain efficacy with infrequent dosing. Already just based on nonclinical data, our projected impact of this drug on maintenance dosing is that we could dose this as infrequently as once every 6 months and that would be a tremendous benefit for patients. Our vision for this is that we can drive remission and then maintain clinical remission in patients with infrequent dosing. And we've already seen evidence that the OX40 mechanism is disease modifying. We would expect the same for 0310 in its ability to modify this disease and look forward already from early proof-of-concept data with PK information to be able to inform on that potential.

Okay. And so would you -- in terms of your dose schedule in your Phase I, do you then look at higher doses for induction of remission and then longer-term dosing? How do you balance sort of those 2 objectives in the Phase I? Is it purely PK/PD based or how do you then think about that as you look to that data to inform design for Phase II?

So the Phase I healthy subject trial was single ascending dose, and we're testing a wide range of doses. We have lots of experience now through navenibart, especially about Phase I trials with YTE-modified antibodies and how to use PK data with model-informed drug development, sort of quantitative medicine methodologies in mind to inform future dosing strategies. So we're going to leverage our experiences here, our unique knowledge in this space to be able to come up with, we think, dose regimens for proof-of-concept trial in patients that would drive to induce efficacy in the patient trial and ultimately maintain it as well.

Okay. And I guess just as we wrap things up here, just to talk about where you stand from a corporate perspective in terms of financials and runway to the clinical programs in hand?

Yes. Sure. I'll take that. So I think as a company, we're in a strong position as we enter to 2025. So we ended 2024 with just over $320 million in cash, and that supports our runway into mid-2027. And as we've previously shared, this puts us past top line Phase III results with navenibart in early 2027 and puts us in a good position as the program reaches that Phase III and ending of that Phase III.

Okay. Is there anything else we haven't asked that you'd like to highlight?

Well, I think you covered -- I mean I think 2025 for Astria is going to be important year for both of our programs in our portfolio. Navenibart, we expect that Phase III to initiate this quarter and very excited about the interest so far that we've received in that trial. And importantly, this is going to be the year of OX40, I think, for us internally with our STAR-0310 program. But importantly, we're going to see a lot of other data points in the OX40 space from competitor programs, which I think will be really interesting as we advance ours.

All right. Fantastic. Well, guys, thank you very much for the time this morning. Operator, I think you can take us clear.