Amylyx Pharmaceuticals, Inc. (AMLX) Q2 2026 Earnings Report, Transcript and Summary

Good morning. My name is Carrie, and I will be your conference operator today. At this time, I would like to welcome everyone to the Amylyx Pharmaceuticals Second Quarter 2026 Earnings Conference Call. [Operator Instructions] Please be advised that this call is being recorded at the company's request. I would now like to turn the call over to Lindsey Allen, Vice President, Investor Relations and Communications. Please proceed.

Good morning, and thank you all for joining us today to discuss our second quarter 2026 financial results and business updates. With me on the call today are Josh Cohen and Justin Klee, our Co-CEOs; Dr. Camille Bedrosian, our Chief Medical Officer; Dan Monahan, our Chief Commercial Officer; and Jim Frates, our Chief Financial Officer. Before we begin, I would like to remind everyone that any statements we make or information presented on this call that are not historical facts are forward-looking statements that are based on our current beliefs, plans, and expectations and are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, our expectations with respect to avexitide, AMX0035, AMX0114, and AMX0318, statements regarding regulatory and clinical development, the impact thereof and the expected timing thereof, and statements regarding our cash runway. Actual events and results could differ materially from those expressed or implied by any forward-looking statements. You are cautioned not to place any undue reliance on these forward-looking statements, and Amylyx disclaims any obligation to update such statements unless required by law. Now, I will turn the call over to Justin.

Good morning, everyone, and thank you for joining us. This is an exciting time for Amylyx and the post-bariatric hypoglycemia community as we approach the pivotal Phase III LUCIDITY top-line data readout. At the beginning of the year, we outlined 3 strategic priorities for avexitide, our investigational, first-in-class GLP-1 receptor antagonist with FDA breakthrough therapy designation in post-bariatric hypoglycemia or PBH. First, advancing the pivotal Phase III LUCIDITY trial toward top-line data. The last participant has recently completed their last visit in the trial. We are on track and eagerly anticipating the top-line data readout in late August or early September. The database has yet to be locked at this time, and we remain blinded to the data. Second, in parallel, advancing NDA readiness and regulatory preparations. We are actively preparing all applicable sections of the NDA to support a potential submission. And third, strengthening our launch readiness to prepare for the potential commercialization of avexitide in 2027, if approved. We've deployed our field medical affairs team to facilitate on-the-ground HCP scientific exchange, and we've continued to build out our teams across marketing, market access, and commercial operations. At ENDO 2026 in June, we activated our disease state education campaign, 'Uncover the Mystery of Post-Bariatric Hypoglycemia,' designed to increase awareness, understanding, and action around PBH. Dan will provide more details on our launch readiness efforts later in the call. We're fully focused on execution as we work toward the potential of delivering the first FDA-approved therapy for people living with PBH. With that, Camille, I'll turn the call over to you.

Thank you, Justin. PBH is characterized by recurrent and often debilitating hypoglycemia thought to be caused by an exaggerated GLP-1 response, primarily after food intake. The American Diabetes Association recognizes hypoglycemia as a potential medical emergency because low blood glucose levels can compromise the body's ability to maintain essential physiologic processes and can result in cognitive dysfunction, seizures, or loss of consciousness. PBH is a chronic condition with no FDA-approved therapies. Many people with PBH live with the ongoing fear of hypoglycemia. Our pivotal Phase III LUCIDITY trial is a randomized, double-blind, placebo-controlled trial evaluating avexitide 90 mg once daily in adults with PBH following Roux-en-Y gastric bypass surgery. The LUCIDITY trial is anchored in the robust data generated to date from the 5 prior avexitide clinical trials in PBH that demonstrated statistically significant reductions in hypoglycemic events. The primary endpoint is the FDA-agreed-upon outcome of reduction in the composite of Level 2 and Level 3 hypoglycemic events through week 16. At the ENDO 2026 Annual Meeting in June, several case reports describing many aspects of PBH and hypoglycemia were presented, highlighting a growing recognition of PBH and the seriousness of hypoglycemia across the medical community. Dr. Colleen Craig presented a poster characterizing the clinical, economic, and humanistic burden of PBH in the U.S. and evaluating how Level 2 and Level 3 hypoglycemic events in PBH impact healthcare utilization, productivity, and overall cost. At the patient level, patients face direct medical costs, productivity loss, such as missed work, diminished quality of life, caregiver burden, and out-of-pocket non-medical costs. At the systemic level, societies face resource utilization and downstream clinical consequences in addition to direct healthcare costs, non-medical system costs, and societal productivity loss. Also at ENDO 2026, we had meaningful scientific dialogue about PBH with endocrinologists that underscored the tremendous unmet need for people living with this condition. We met many endocrinologists with whom we had not previously engaged, and many of them already were aware of PBH. They describe the challenges in managing these individuals, given the limited options for treatment and had strong interest in learning more about this condition. This interest is inspiring as our field medical affairs team furthers PBH scientific exchange and engagement with endocrinologists. In addition, in June, CMS and CDC published their 2027 ICD-10 code files, which represent the official code set to be used for patient encounters beginning October 1, 2026. This code set includes an ICD-10 code specific to PBH, also demonstrating the growing recognition of this condition by the medical community. In closing, we are encouraged by the increasing awareness and understanding of PBH, along with our informative engagements with healthcare professionals. We continue to be focused on strong execution as we approach our anticipated LUCIDITY top-line data readout. With that, Dan, I'll now turn over the call to you.

Thank you, Camille, and good morning, everyone. We continue to make significant progress in our preparations for the potential commercialization of avexitide next year. We remain encouraged by the growing recognition of PBH among healthcare professionals. Importantly, our understanding of the PBH population continues to strengthen. We estimate that approximately 160,000 people in the U.S. are living with PBH following the 2 most common bariatric procedures, Roux-en-Y gastric bypass and sleeve gastrectomy. This estimate remains supported by our independent claims analysis, ongoing field insights, and a growing body of published prospective and retrospective literature. Together, these data continue to reinforce both the significant unmet need and the opportunity to identify and reach appropriate patients. Our market research also continues to demonstrate a high intent among endocrinologists to treat PBH with an approved therapy, providing further confidence in the commercial opportunity should avexitide be approved. We are excited to share that we recently activated our disease state education campaign, 'Uncover the Mystery of Post-Bariatric Hypoglycemia,' to address the educational need among HCPs and the PBH community. As part of this initiative, we launched UncoverPBH.com. This platform provides educational resources for both healthcare professionals and the PBH community. The HCP website is intended to help clinicians better recognize and understand PBH. The community website empowers people with PBH with information to support discussions with their healthcare teams. As Camille mentioned, engagement at ENDO 2026 was high, where we also introduced an interactive disease state education experience that generated strong engagement and positive feedback. One of our most encouraging early observations was the level of familiarity many healthcare professionals already had with PBH, reinforcing our view that awareness of the condition continues to grow within the endocrinology community. In parallel, we continue to add key talent across the organization and advance our commercial readiness efforts as we prepare for the potential launch of avexitide in 2027, should it be approved. And with that, I will now turn the call over to Jim to review our financials.

Thanks, Dan. Good morning, everyone. Our financial results for the second quarter reflect our continued disciplined execution of the Phase III LUCIDITY trial and targeted investment in advancing our broader pipeline. We ended the second quarter with $250.8 million in cash and marketable securities, compared to $279.8 million at the end of the first quarter. This capital provides us with an anticipated cash runway into 2028 to fund our operations through expected milestones, including our key focus, LUCIDITY top-line readout, potential FDA approval, and potential commercial launch of avexitide in 2027. Turning now to our results for the quarter, total operating expenses for the quarter were $45.7 million, up 7% for the same period in 2025. Research and development expenses for the quarter were $23.8 million compared to $27.2 million in Q2 2025. The decrease was primarily due to a decrease in spending related to AMX0035 for the treatment of progressive supranuclear palsy, offset primarily by an increase in spending related to the clinical development of avexitide in PBH and other costs related to avexitide. Selling, general and administrative expenses for the quarter were $21.9 million, compared to $15.6 million in Q2 2025. This increase was primarily due to increased legal expenses, including a one-time legal charge and investment in commercial strategic initiatives. We recognized $8.3 million of non-cash stock-based compensation expense for the quarter compared to $7.4 million of non-cash stock-based compensation expense in Q2 2025. With the LUCIDITY top-line data readout later this month or early September, we're entering into an exciting phase. We're investing in a disciplined manner as we prepare for the potential launch of avexitide, and we believe we're well-funded to execute. With that, I'll turn the call over to Josh.

Thanks, Jim. In addition to avexitide, we continue to advance our broader pipeline and our commitment to the communities we serve with high unmet needs. For AMX0035 and Wolfram syndrome, we presented week 96 data from the Phase II open-label HELIOS clinical trial in the spring, which continued to show stabilization or improvement in measures of glycemic control and vision, consistent with week 24 and week 48 data. Under AMX0114 and ALS, we continue to advance the Phase I LUMINA multiple ascending dose clinical trial in people living with ALS. We are progressing through the dose cohorts given the favorable safety profile AMX0114 has exhibited in LUMINA so far. We are currently enrolling cohort 3. And for AMX0318, our long-acting GLP-1 receptor antagonist, IND-enabling studies are underway, and we are targeting a 2027 IND filing. Additionally, we are pleased to share we entered into a second research collaboration with Gubra in July, following the collaboration that identified AMX0318. This new collaboration will screen and develop peptide candidates for another rare endocrine disease of high unmet need. We're looking forward to sharing additional updates on this program as it advances. In closing, we are executing against our 3 strategic priorities for avexitide, including delivering top-line data from LUCIDITY, advancing our NDA readiness, and strengthening our commercial launch preparations. Guided by the profound unmet need of the PBH community, we are working with urgency to bring this potential treatment to people living with PBH. Before we turn it over to the operator for Q&A, I want to reiterate that this is an exciting time for Amylyx as we are eagerly awaiting Phase III top-line data. Because we are getting close to locking the LUCIDITY trial database, we will be entering a quiet period after this call.

[Operator Instructions] We'll pause momentarily to assemble our roster. Your first question will come from Seamus Fernandez of Guggenheim.

So I just have a couple here. You know, I believe maybe you guys could just update us on when the last patient visit was. And what are the, kind of, key factors that, kind of, need to be completed to lock the database? Where are the areas of, kind of, core focus, or is it the, sort of, need to get all of the sites, kind of, fully aligned to be able to lock the database? And then the second question is, I'm guessing you won't be able to update us on specific numbers, but maybe you can provide us a little bit of color on how the Early Access Program is progressing at this point. Are patients actively being recruited into the EAP? And, how would you kind of characterize the demand for that program at this point? It's obviously an opportunity to really put the company commercially on a very strong footing going forward.

Great. Seamus, Hi. Thanks for the questions. So your first question revolved around last patient visit and what efforts need to continue to be ready for the database lock and then top-line data. If we start with when our last patient's first visit was, we announced we completed enrollment late March or mid-March, I would say. And so it's a 16-week double-blind period. So advance toward that. We get to about mid-late July. And there are, as you point out, rightly so, there are a number of activities that the team is working on, and they're continuing to execute beautifully and the enthusiasm continues very strong by the trial participants as well. There is data cleaning, making sure that everything matches up, dotting all the i's, crossing all the t's, because we only lock a database once in this instance for the core study, double-blind period. So the team is being very diligent in that regard. And as we said, we expect, you know, top-line data late August, early September. With regard to the Early Access Program, yes, we're so excited to have an Early Access Program for people living with PBH. The initial phase, if you will, of the EAP as we abbreviate it, is for those individuals in LUCIDITY who have completed the study, double-blind period, of course, and then the open-label extension. And then they had the opportunity to roll over into the EAP. And also, at this period of time, it's open for those individuals who have been in prior avexitide trials. Many of those individuals are at other centers, so they have to be activated as well in order to participate in the EAP. It's a separate study, separate protocol. So we're early days yet. The enthusiasm is great about being able to participate in the EAP, and we'll continue to give you updates along the way.

Your next question will come from Joseph Thome, TD Cowen.

I'm not sure if you can answer this, but I guess in terms of the patient population that you did enroll for the Phase III, I guess, does it overall look similar to the prior Phase II experience or any sort of comments you can make on that? And then second, can you just remind us what sort of mechanisms were in place during the study to monitor compliance with the injections, just to make sure that patients were getting all the recommended doses over the study period?

Sure, sure. Thank you. So just to reiterate, we designed LUCIDITY with the Phase II studies in mind, the highly successful statistically significant outcomes for those Phase II studies. And we're enrolling participants who are very consistent with the populations that were enrolled in the Phase II and Phase IIb. Furthermore, while I can't give you specifics. Furthermore, our Amylyx team conducting the study were those who decided at the end of the day whether an individual was eligible or not. We went through a very rigorous assessment of eligibility before patients enrolled. So we're very confident and very pleased with how the study has been executed from day one, actually. Your second question is about study drug compliance. Yes, that is monitored throughout as well. And, you know, we're also pleased with those metrics and parameters also.

And I'll just add in terms of the trial conduct and sort of compliance, I'd say first it starts with the right clinical trial sites. So we were very rigorous in finding clinical trial sites who not only could recruit the right participants, but also were good clinical trial sites with good experience. Second, we paid particularly close attention during the run-in period to see that not only were participants meeting inclusion and exclusion criteria, in particular the 3 events in 3 weeks, including one Level 3 event, but also that they were good study participants, that they were consistent, and we thought would be good trial participants for the study. And then all throughout the study, our team had very close oversight and monitoring in partnership with the clinical trial sites to make sure that people stayed compliant with all study protocol needs as well as drug, as you were mentioning.

Your next question will come from Michael DiFiore with Evercore ISI.

What evidence package would be required for an initial broad label encompassing all PBH? Like does LUCIDITY have enough sleeve patients to make for a compelling subgroup analysis here? And if the FDA restricts the label, potentially, what study design, enrollment size, and timeline would be needed to add sleeve patients? That's my first question. And the second's on a commercial question. Hoping you could bridge the 160,000 patient prevalence estimate into the commercial funnel better. What percent of these 160K patients represent a realistic 5-year treated population?

Hi, Mike. Thank you for the question. So, the first in terms of label, I'll start with that, you know, given that we have yet to see the Phase III trial results, we have yet to submit the NDA, it's, you know, it's early to know too much about what the label will be. I'll give you the context as we see it today. So first and foremost, we believe PBH is PBH, regardless of the surgery that leads to PBH, we believe the pathophysiology is the same and that the primary driver of hypoglycemic events is this exaggerated GLP-1 response. Now, looking through the clinical studies of avexitide, the majority of people with PBH studied with avexitide have had Roux-en-Y gastric bypass surgery leading to PBH, and that includes the Phase III LUCIDITY trial. One of the inclusion criteria was Roux-en-Y gastric bypass surgery that led to PBH only. Now, in the Phase IIb, different surgery that led to PBH were allowed in for inclusion criteria, and avexitide appeared to work just as well regardless of the surgery that led to PBH. So as we submit our NDA and have the discussions with FDA, we think there's sort of two paths that could emerge. What we will strongly make the case for is that we believe avexitide should be for people with PBH, regardless of the surgery led to it due to the same pathophysiology and due to the evidence that we've generated to date. FDA could of course take the stance that the Phase III trial was studied only in Roux-en-Y gastric bypass PBH patients. And so could say, you know, that would be the indication in the label. If that's the case, then I think you're right. The question would be what additional evidence would we need in order to show that avexitide should be applicable regardless of the surgery that led to PBH. And so we're working through those, various scenarios right now. I'd say the way we view it, it should be pretty efficient. You're just trying to show that, you know, that these are not different and that avexitide works regardless. We're able to see the effects of avexitide in a single dose. So we think that that should not be an overly burdensome study. And maybe last piece I'll say on the sort of commercial side of things, if we go back to the Stanford prevalence work, their estimate is that of the current 160,000 people with PBH in the United States, about 120,000 had Roux-en-Y gastric bypass leading to their PBH. So I'd say at launch, we're already talking, if we were in that narrower label scenario, we're already talking about a very substantial population. And so our goal would be then to run an efficient study to show that avexitide should work regardless of the surgery that led to PBH. And for your second commercial question, I'll pass to Dan.

Thanks, Justin. Mike, thanks for the question on the commercial front. And just to build on what Justin had shared on the 160,000 patient population in the prevalent market. So we are aware through market research and through our claims-based analyses of centers and academic centers or different settings of care that have 50 to 60 patients. Some settings even have informed us that they have potentially 100 patients in their care. So now that we know where those patients are, we'll certainly focus there at our launch, and then as our educational efforts take shape and we have more and more education with our commercial colleagues and alignment with our medical colleagues, we look to see that launch trajectory continue to grow. But again, the prevalent population is 160,000 and we remain confident in that number.

Your next question will come from Geoff Meacham with Citi.

Just had a couple of quick ones. The first is, when you look at pricing reimbursement sort of guidelines, do you think that, I get it that it's a completely unmet medical need, PBH is, but do you think there'll be differentiation between Level 2 and 3 events that you'll see in the study? So that's the first question. The second one is just beyond the Phase III. Are you totally done with other elements of the filing on preclinical, CMC, et cetera, et cetera?

Sure. Yes, I'm happy to maybe take part of that and maybe pass to my colleagues as well. So for Level 2 and Level 3, I think it, kind of, bears noting that usually these travel pretty closely together. The reason the ADA selected less than 54 mgs per deciliter as a level for a Level 2 event is because once you're less than 54 mgs per deciliter, that's when your brain is really starved of glucose. So people often begin experiencing, below 54 mgs, serious glycemic events, whether that's loss of consciousness, seizures, severe confusion, et cetera. So it's not often the case that you have a patient that has Level 2s but not Level 3s or vice versa, these things really do tend to travel together. I guess in terms of the NDA preparation as well, we have been working throughout the year to be prepared as possible, and we do believe that the 16-week double-blind outcome from the LUCIDITY Phase III trial, which we're very excited for, is, kind of, the last piece of the NDA that we need to, kind of, put together. Regarding pricing guidelines, I guess I would pass over to Dan.

Sure. Thanks, Josh. And Geoff, thank you for the question. I would just add, PBH, as we all know, is a very dangerous condition without any approved medications for these patients living with post-bariatric hypoglycemia. So, when we go down the pricing journey, we will certainly take a look at and consider various analogs across both rare as well as rare endocrinology. And again, following top-line data and the LUCIDITY results, we'll then initiate our pricing research.

Your next question will come from Marc Goodman with Leerink Partners.

Yes, as you have done this review of where the patients are, can you help us understand just the concentration of patients? You just started to mention there were some sites over 100, some 50 to 60. I mean, if you think about the 160,000 patients, are 50% of them at concentrated sites or is it only 20%? Just give us a sense of that. And then one question that we just keep getting, I just want to make sure we hear it from you guys now, and that is, what should we expect the placebo response to be in this study?

Sure, I'll start with the first question just on where patients are, and we continue to do more and more research using really the claims-based analyses from multiple databases that continue to point us in the direction as to where these patients are. So yes, I've mentioned earlier that there's some settings of care where there's 50 to 60. Some have 70, some have 100, and the more research we do, the more confident we get in those conversations. This is something our medical affairs colleagues have also begun to validate as our MSL team has engaged with various customers to understand and validate some of our claims-based analysis. And again, as we get closer to a potential launch, we will share what our go-to-market plans are in terms of how we'll engage these various centers.

Great, and thanks for the question regarding placebo. I'll start by reiterating that we've had 5 highly successful trials of avexitide in PBH to date, with the Phase II trials showing statistically significant and clinically meaningful reductions in both Level 2 and Level 3. And at ENDO 2025, we shared an ad hoc analysis of the composite as well, which was also highly statistically significant. LUCIDITY is designed to replicate those Phase II studies and we have powered the study very conservatively even in the face of those very highly significant studies. So even with, we're powering at least at 90% with a very modest effect size and with a placebo rate as well. We don't know specifically what the placebo effect is going to be. This is the first Phase III pivotal study of people living with PBH. You know, so that's an important consideration. And finally, as we've been discussing this morning, PBH is a devastating condition. And people already are doing whatever they can to control or mitigate their events. Clearly those who are enrolling in our study continue to have events, but they -- and they continue to do whatever they can to minimize it, given that there is, you know, much fear of hypoglycemia that these patients experience.

And I'll say...Sorry, go ahead, Marc.

No, I was just going to say, should we be thinking, you know, placebo has a 20% response and the drug does 55%, you know, and we have that 35% delta, like, is that a realistic, you know, and a good scenario?

Well, I think there are 2 different ways, I think, to look at it. I think the first is, what does the prior data tell us? And so the best placebo-based data we have comes from the first Phase II PREVENT study. If you look at the crossover design, so if you look at the run-in to placebo to active on the means, there's a difference of about 30%. If you look at the median, though, there's no difference. So I would say then looking at the Phase III study, our goal was to be conservative in our assumptions. We believe avexitide should work for PBH. That's what the prior studies tell us. And so conservatively powering the study, we thought was the right thing to do. So, we powered the study to be 90% powered to detect a 35% treatment effect with even an up to 50% placebo effect. We have not seen any evidence of such a placebo effect in prior trials, but again, we thought that the right thing to do is to power conservatively. And going back to the Phase II trial, if you look at those very statistically significant results, including for example, 55% reduction in Level 2, Level 3 composite hypoglycemic events, that's against the placebo. So again, if we're powering to 35% difference versus placebo, you can see why we're saying we're using conservative assumptions.

Your next question will come from Rami Katkhuda with LifeSci Capital.

I guess for LUCIDITY, what secondary endpoints will be included in the top-line release and which do KOLs view as the most important? And maybe more broadly, can you provide any additional color on the second research collaboration with Gubra and the type of endocrine indication or target that you're ultimately going after?

Sure. So, we're very excited and eager to see the top-line data, as I expect all of you are as well. And we plan to share the data that is consistent with other rare diseases that present Phase III top-line data. So stay tuned. We're very eager as well.

Absolutely. And maybe I just add on the second collaboration with Gubra as well. So yes, we really quite enjoyed working with Gubra. I think they have a particular peptide expertise that we certainly saw with AMX0318, where we tried to develop as optimized a GLP-1 receptor antagonist as we possibly could. We are looking at another rare endocrine disease here of significant unmet need. I think it's, you know, it, kind of, fits with, kind of, our focus on focusing in rare diseases of really serious unmet need, where there are either no or really inadequate treatments as well. But we'll share more details there as maybe it gets further along as well. And I think just to Camille's earlier point as well, we are quite excited for the top line. I think you can expect us to share, kind of, typical data that you'd expect for a top-line data release. And I'd say in talking with KOLs as well, our primary endpoint really is quite a meaningful endpoint here. Level 2 and Level 3 hypoglycemia are viewed as very significant clinically meaningful events. Physicians describe that they have nothing for these patients and any impact on what they basically describe as medical emergencies, these Level 2 and Level 3 events would be quite significant. So I really think that's where people are mostly focused. But we are evaluating in our secondaries, things like the individual Level 2 and Level 3 rates, as well as, you know, kind of, other patient-reported outcomes and otherwise, you know, in the study as well.

Our next question will come from James Condulis with Stifel.

On the commercial front, as you've done more work here, curious if you have any more thoughts on, sort of, what the right analogs are here, specifically as it relates to what a launch trajectory may look like and, essentially do you worry at all about a bolus in the sense of getting a lot of traction at those centers that have 50, 60, or 100 patients, but it's taking longer to kind of get to the next layer or next rung of patients? Or, you know, do you think it'll be more steady because there's so many patients here? Just like curious how you're starting to think about that as you've done more work.

Sure. Thanks for the question, James. And on the launch trajectory, the first thing I'd say and just reiterate is, again, that there's -- for these patients with post-bariatric hypoglycemia, there are no approved therapies. And we continue to stand behind the 160,000 prevalent population. We're very confident in the market size there. This is a market we continue to see building over time. A point that we haven't emphasized yet is just the research that we've done with our endocrinologists. They have a very high intent to treat these PBH patients. So, on the trajectory, again, we will be focused on these centers at launch because that's where we know there are existing patients from the KOLs and endocrinologists who have already communicated to us that they've raised their hands and identified patients. So we'll focus there. But then again, as that educational effort takes shape, as we continue to engage with the marketplace, we do see this building over time. So we'll start with those key centers, educate the centers, and then expand broader into the endocrinology community. And we're certainly looking forward to this educational opportunity with the endos.

Your next question will come from Graig Suvannavejh with Mizuho.

Just trying to anticipate that in the case that you do get positive data and then you do end up getting the drug approved, could you just remind us how you're thinking about the competitive landscape? There aren't all that many companies that are focused on PBH, but I think it would be good as we think about our uptake curves over whether it's a 5-, 10-year period, how we should be thinking about the competitive landscape?

Yes, great question Graig. I'd say, maybe first our view of the kind of pathophysiology of the disease is that this is really driven by an exaggerated GLP-1 response and that's why we believe that avexitide is sort of on target and, a really appropriate way to, try to, ameliorate or significantly impact the disease. So I think, based on the, I mean, obviously we got to get the top-line data and we're quite excited for that. But, we don't really see, much else that has shown, close to the profile of avexitide to date. So we really do believe this will sort of be the first and only, if pending an approval would be the first and only therapy, and we don't really see other things that, have shown the same profile.

And I would just add and underscore the point that, because we really believe in this mechanism of, exaggerated GLP-1 driving hypoglycemic events in PBH, that's why we started development on our long-acting AMX0318 early as well. That's still in IND-enabling studies. Our focus right now is on avexitide, but we really do intend to continue to innovate. And we think AMX0318 may be a very nice way to do so.

Can I just quickly follow up just on 318? I know it's still early days, but what are the different types of formulations that are being considered for 318?

Yes, great question. So maybe first just to say on 318, kind of came out of the collaboration with Gubra where our goal was to -- and what we did was screened a large number of peptides to try to find as optimal a GLP-1 antagonist as we possibly could. And this is really sort of Gubra's bread and butter. It's their kind of main focus is on peptide drug development. And we do believe based on our preclinical data that we were able to arrive at a very strong GLP-1 receptor antagonist. I'd say from a formulation perspective, I think all the options for injectables are certainly available to us, whether that's a vial and syringe or more advanced formulation such as autoinjectors or pens or otherwise. Luckily, I think both with avexitide and with how we've been designing AMX0318, at this time, we don't really see technical hurdles to being able to do that.

Your next question will come from Jason Gerberry with Bank of America.

Hi, good morning. This is Dina on for Jason. In your filings, I believe you disclosed a total of $35 million in CMO payment commitments throughout 2028 for avexitide and in the event of a positive Phase III readout is your current manufacturing scale sufficient for a commercial launch? Or would a positive readout trigger additional CMO capacity obligations? And then just a quick question on AMX0035 for Wolfram. Any guidance on when we can maybe expect the update on regulatory interactions regarding the Phase III trial design and just maybe openness to that accelerated approval pathway?

Yes, I'd say great question. So I'd say we're certainly kind of proceeding with our manufacturing, in line with, prepping for commercial launch as well. And so we do from time to time make commitments to secure supply and capacity. And I think we expect to continue doing so, as we get towards our launch. And then I guess on your question on Wolfram as well. Yes, so I mean, we are quite excited about our week 96 data, which continued to show stabilization or improvement across glycemic measures as well as visual measures. This would be the first Phase III trial conducted in Wolfram syndrome, and it is a multifactorial disease. People have not only diabetic symptoms, but also visual symptoms, sensorimotor symptoms, kind of, vestibular symptoms of, kind of, balance and otherwise. And patients ultimately usually pass away from respiratory or swallowing difficulties in their early 30s. So there is thought about what is kind of the best design that kind of most efficiently can show, efficacy in the Wolfram population. So that's what we're continuing to work on, but we remain quite excited, including from our week 96 results.

Your next question will come from Ananda Ghosh with H.C. Wainwright.

A couple of questions from me. Can you tell me, like from our KOL discussions, use of avexitide has been always highlighted in certain surgeries, especially the gastric cancer or upper GI surgeries. So I just wanted to get your thoughts on what you are hearing from the KOLs on that. Now, the second question is, what is the development plan for the long-acting avexitide vis-a-vis the avexitide when you are thinking from a commercial point of view? The third is, does a dedicated ICD-10 code change the payer conversation and given the diagnosis is a barrier to penetration of avexitide, what are the efforts from the company on that end?

Excellent. So, I'm happy to start with the first. So, yes, I appreciate your mentioning the potential use of avexitide in other surgery-induced hypoglycemias. That's certainly something we hear a lot about from key opinion leaders. There are many gastric surgeries, as you mentioned, for example, gastrectomy for gastric cancer, that can lead to this same hypoglycemic condition. And in fact, in the Phase IIb trial, there were people who had a gastrectomy or esophagectomy due to cancer-induced hypoglycemia who responded very well to avexitide as well. So we do believe that the mechanism there is very similar, that it's this exaggerated GLP-1 response that is primarily driving the hypoglycemic events so that is certainly something we're interested in studying in the future. And I'll add that while this is certainly an unmet need in the United States, it's a very substantial unmet need in most countries in Asia due to their very high rates of gastric cancer and esophageal cancer, and one of the risks is that people develop this hypoglycemic condition. As far as the 318 development plan, I'd say, please stay tuned. We're in IND-enabling studies now. I'd say, as Josh was mentioning, we really screened for molecules that would meet all of our criteria, including good drug-like properties and good sort of manufacturing qualities. So we, as we go through the IND-enabling studies, we'll outline our development plan. But we really do believe that the primary driver of events in PBH, in surgery-induced hypoglycemia, is this exaggerated GLP-1 response. And so that's why we're investing in 318 as well as investing in avexitide because we really believe that there's a substantial unmet need and opportunity here. For the ICD-10 code, maybe I'll pass to Dan to share more on that.

Sure. Thanks, Justin. And as Camille mentioned earlier, in June, CMS and the CDC, they did publish their 2027 ICD-10 code files. So beginning October 1st, this is when we will have a specific code for post-bariatric hypoglycemia. First thing I would say is this new code really recognizes PBH within the broader medical community. ICD-10 codes, they are certainly helpful for tracking and diagnosing patients. And oftentimes the coding, the ICD-10 codes are used for epidemiology. From a payer perspective, an ICD-10 code is not necessary for reimbursement. And this is again, just back to the claims analysis. Patients can still be identified today through the claims analysis. You don't need an ICD-10 code to identify them. But again, this is really a recognition of PBH in the broader community, and we're excited that a code is going to be effective October 1st.

And on your last question, in terms of diagnosis, so I think the first thing I'll say is I think PBH awareness and diagnosis is high. We've certainly seen that in all of our market research. But as Dan was saying as well, this is also a condition where there had not been FDA-approved treatments. There are many education gaps. And so I think starting on the education front is why we were so excited to launch our disease state education campaign. We've been very pleased with the feedback on that so far. So those efforts will continue.

Your final question will come from Christopher Chen with Baird.

Two for me. Can you characterize just the nature of recent interactions, if any, with FDA surrounding the NDA? And do you plan on having any additional interactions before submission? And then just one for Dan. I know it's still somewhat early days, but assuming positive data and approval, how soon do you think you can launch following approval? And what would you say are the primary factors gating a launch?

Great. So, thank you, Chris. With regard to our FDA interactions, as we don't really discuss the details of the interactions. We have had, as part of avexitide's breakthrough therapy designation, we have had consistent interactions with the agency throughout this period of time. Not starting with but one of course was, reviewing the LUCIDITY protocol and throughout this time. So we're very excited about the potential to submit an NDA. We have a tremendously experienced team working on the NDA elements and they're making great progress. Obviously, when we have the core 16-week data set, those will be included in the NDA and we'll go from there. And we continue to plan for a launch in 2027.

Chris, I'll just jump in on the launch date and the launch timing. We're certainly excited about the Phase III LUCIDITY results. At this point in time, we've guided towards a launch in 2027. From a launch preparation perspective, as we've mentioned, we've made key hires across the organization within medical affairs and across the commercial side in market access, marketing, as commercial operations. So our launch plans are on track and certainly underway as we prepare for a successful launch.

There are no further questions at this time. I'll turn the call back over to Mr. Klee for any closing remarks.

Thank you, operator, and thank you all for your time. We're looking forward to connecting when we report the top-line data after final database cleaning and lock. We're excited about what these results could mean for people with PBH. We hope you have a great rest of your day.

Thank you for your participation.