Amylyx Pharmaceuticals, Inc.

Good morning. My name is Kate, and I will be your conference operator today. At this time, I would like to welcome everyone to the AMELIST Pharmaceuticals first quarter 2026 earnings conference call. All participants will be in a listen-only mode. After today's presentation, there will be an opportunity to ask questions. To ask a question, please press star 1 on your telephone keypad. To withdraw your question, press star 2. Please limit yourselves to one question with one follow-up. If you have additional questions, you may rejoin the queue. Please be advised that this call is being recorded at the company's request. I would now like to turn the call over to Lindsay Allen, Vice President, Investor Relations and Communications. Please proceed.

Good morning, and thank you all for joining us today to discuss our first 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, Jim Freydes, our Chief Financial Officer, and Dan Monahan, our Chief Commercial 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 Avexatide, AMX 35, AMX 114, and AMX 318, statements regarding regulatory and clinical developments and 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 AMOX 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. The first quarter of 2026 was marked by execution across our pipelines. Most notably, we continue to progress the pivotal Phase III Lucidity Trial of Avexatide, our investigational first-in-class GLP-1 receptor antagonist with the FDA Breakthrough Therapy designation in post-bariatric hypoglycemia, or PBH. We are executing on the three strategic imperatives for Avexatide that we outlined earlier this year. First, we are advancing the pivotal Phase III Lucidity Trial toward top-line data. Randomizing and dosing the last participant in late March was a significant milestone. We have a clear line of sight toward the completion of the 16-week trial, and we remain on track for a top-line readout next quarter. Second, we are advancing NDA readiness and regulatory preparations. We are already drafting NDA sections to support a potential submission. And third, we continue to strengthen our launch readiness We are executing against a comprehensive commercial readiness roadmap to help ensure we are fully prepared for commercialization of Avexatide if approved in 2027. In addition to Avexatide, we continue to make progress across our broader pipeline. For AMX318, our long-acting GLP-1 receptor antagonist, IMD-enabling studies are underway. We are targeting a 2027 IMD filing. For AMX35 and Wolfram syndrome, we anticipate presenting longer term week 96 data from the phase two open label helios clinical trial at an upcoming scientific meeting. And for AMX114 and ALS, we fully enrolled cohort two of the phase one lumen trial in March. At the NCALS annual meeting this June, we expect to present early biomarker data from cohort one, the first and lowest of four doses being evaluated in the trial. We expect these data will provide initial information about the levels of the ALS biomarkers being assessed in the Lumina trial from the first cohort. As we continue to advance our pipeline, we are simultaneously preparing for the potential commercial launch of Avexatide. To discuss our launch readiness efforts, Dan Monaghan, our Chief Commercial Officer, is with us on the call today. Dan joined AMLEX in January 2024, bringing more than two decades of experience. He was instrumental in the commercialization of Otsuka's Rixulti, Novartis' Cosentix, and Sanofi's Lantus and Actinil, among others. With that, Dan, I'll turn the call over to you.

Thank you, Justin, and good morning, everyone. I am pleased to be on the call today to discuss how we have been refining our launch strategies as we prepare for the potential commercialization of Avexotide next year. The more we engage with the PBH community, the more we understand the profound unmet need that exists. we are operating with a deep sense of urgency. To date, our commercial efforts have been focused on gaining key insights into the PBH market. This includes gathering direct insights from people living with PBH and the healthcare professionals who are managing their condition. In addition, we are developing a deep understanding of the patient journey and continuing ongoing claims work to help us determine where patients are being treated. To enable our commercial preparations, we've made key hires across marketing, market access and commercial operations. Ahead of the potential approval and commercial launch of Avexatide, our immediate focus is on disease state education. This includes raising stakeholder awareness of PBH with an emphasis on the pathophysiology, the importance of accurate and timely diagnosis and the profound unmet need and burden of the condition. We plan to launch this disease state education campaign this summer. Looking at the market opportunity, our independent claims analysis and ongoing field engagements continue to support our estimate of approximately 160,000 people living with PBH in the U.S. who have undergone the two most common types of bariatric surgery, sleeve gastrectomy and rune-wide gastric bypass. Our estimates are firmly rooted in a growing body of prospective and retrospective published literature, including large, long-term cohort studies evaluating hypoglycemia in people who have undergone bariatric surgery. Importantly, our ongoing market research indicates that endocrinologists have a high intent to treat PBH if there were to be an approved medicine. To reach appropriate patients, we have initiated our marketplace sizing efforts and continue to identify key centers and endocrinologists that manage this condition. Building up to the potential launch, we will refine these efforts as more insights are generated. Our commercial preparations are advancing in lockstep with our clinical progress, and we look forward to sharing additional details as we move closer to the commercialization of Avexatide, if approved. With that, I'll turn the call over to Camille to provide an update on our clinical and medical affairs progress this quarter.

Thank you, Dan. To start, PBH is a chronic metabolic condition driven by an exaggerated GLP-1 response, primarily after food intake. resulting in persistent, recurrent, and often debilitating hypoglycemia. These events cause an inadequate supply of glucose to the brain known as neuroglycopenia with potential clinical consequences such as cognitive dysfunction, seizures, and loss of consciousness. For people living with PBH, this can create a life of perpetual vigilance where a meal with friends, or a drive to work carries the risk of debilitating hypoglycemia and its ramifications. This fear can disrupt independence and compromise safety, nutrition, and overall quality of life. Currently, there are no FDA approved therapies. Our pivotal phase three lucidity trial is evaluating Avexatide 90 milligrams once daily in individuals with PBH following Roux-en-Y gastric bypass surgery using the FDA agreed upon primary outcome of reduction in the composite of level 2 and level 3 hypoglycemic events through week 16. Lucidity was designed with the goal of replication. Five prior Avexatide trials in PBH, which demonstrated statistically significant results, including reductions in hypoglycemic events, directly informed the dose, the primary endpoint, inclusion criteria, and surgical subtype for lucidity. Echoing Justin's earlier remarks, our clinical team remains deeply focused on the execution of the lucidity trial, and we continue to work closely with our investigators as we approach our anticipated data readout next quarter. In parallel with our clinical trial execution, We are actively ramping up our field medical affairs team to facilitate on-the-ground engagement with KOL. I also am pleased to share that we recently launched a U.S. expanded access program to provide a vexatide for up to 250 adults with PBH following rule-on-lie gastric bypass surgery. This program is a direct response to the urgent need we are hearing from individuals who are struggling with the devastating daily realities of PBH. and the physicians who treat them. Initial eligible patients include individuals who have either completed lucidity or participated in previous clinical trials of Avexatide in PBH. As a reminder, Avexatide is an investigational drug and has not been approved by the FDA for any indication. Working directly with the PBH community and seeing the everyday impact of this devastating condition drives our continued commitment to our clinical and medical efforts. And with that, I will now turn over the call to Jim to review our financials. Jim?

Thanks, Camille. Our financial results for the first quarter were in line with our plans and reflect our focus on the Phase III lucidity trial and targeted investments in advancing our broader pipeline. We ended the fourth quarter with $279.8 million in cash and marketable securities, compared to $317 million at the end of the fourth quarter of last year. This capital funds our anticipated cash runway into 2028, including our key expected milestones, the lucidity top line readout expected in Q3 2026, potential FDA approval, and potential commercial launch of Avexatide in 2027. Turning now to our results for the quarter. Total operating expenses for the quarter were $43.8 million. up 16% from the same period in 2025. Research and development expenses were $27.6 million, compared to $22.1 million in Q1 2025. The increase was primarily due to an increase in spending related to the clinical development of Avexatide and PBH. This quarter, we also recognized a milestone payment of $4 million to Gubra, following the identification of AMX318 as a development candidate for PBH and other rare diseases. The increase was offset by decreased spending related to the clinical development of AMX-35 for progressive supernuclear pulses. Selling general and administrative expenses were $16.2 million, compared to $15.7 million in Q1 2025. This increase was primarily due to an increase in consulting and professional services as we prepare for the potential commercial launch of Avexotide. We recognize $6.1 million of non-cash stock-based compensation expense for the quarter, compared to $6.8 million of non-cash stock-based compensation expense in Q1 2025. Turning to our balance sheet, our cash usage was slightly higher in Q1 compared to Q4 because of our group or milestone payments and the payment of our annual corporate bonus during the quarter. We're in the midst of a pivotal year for Amilex. with the top-line data readout for lucidity expected in Q3. The team will continue to focus on scaling our business with discipline, and we're actively laying the groundwork for a potential commercial launch. This focus positions us well, particularly for our work with Avexatide. We continue to believe Avexatide has the potential to be a breakthrough treatment for PVH. With that, I'll turn the call over to Josh.

Thanks, Jim. To close, we are focused on the execution of the lucidity trial as we track toward our anticipated top-line readout next quarter. PBH is a chronic, lifelong condition with symptoms that often emerge one to three years following bariatric surgery. Many people who receive bariatric surgery are in their 40s, suggesting that if they develop PBH, they may have decades of life impacted by this condition. The broader medical community continues to recognize this critical need in PBH. In March, Dr. Colleen Craig and her colleagues at Stanford published the first U.S. prevalence model for PBH in Surgery for Obesity and Related Diseases, the official peer-reviewed journal of the ASMBS. And in April, CMS published their annual list of ICD-10 codes to be potentially effective October 1, 2026. which includes an ICD-10 code specific to PBH. The planned adoption of an ICD-10 code shows the growing recognition of this condition by the medical community. We believe that a vexatide, if approved, could play a meaningful role in addressing this highly underserved patient population. In parallel with lucidity, we are actively preparing for a regulatory submission following top-line results. while simultaneously scaling our commercial and medical teams to support a strong commercial launch of Avexatide in 2027, if approved. With that, I would like to now open the call up for questions.

We will now begin the Q&A session. To ask a question, please press star one on your telephone keypad. To withdraw your question, please press star two. Please limit yourselves to one and with one follow-up. If you have additional questions, you may rejoin the queue. At this time, we will pass them entirely to assemble a roster. Your first question comes from the line of Seamus Fernandez with Gogginham. Your line is open.

Oh, great. Thanks for the question. I hope you'll bear to for me quickly. You know, the first question is really on the initiation of the EAP. You know, typically we see companies sort of waiting for the completion of their phase three. And then, you know, the announcement of an EAP in the wake of a positive phase three. Just wanted to get a better sense of obviously, you know, how you were able to execute this. and get it approved, and then also, you know, how you were really responding to the community with the implementation and announcement of the EAP. And then just a quick follow-up question. I wanted to get a sense of just sort of that relative impact that working on the NDA now could actually have from a filing perspective. Typically, when we see biotech companies with positive phase three data. It'll take as much as, you know, six to nine months to see that file. So just wanted to get a sense of how working on the NDA now might advance that ahead of those types of timelines. Thanks so much.

Thank you very much, Seamus. This is Camille. So for the EAP, indeed, we are responding to the community where there is currently no approved therapies for PBH, and we recognize and have received several requests and demands. Importantly, we're starting the EAP now because we want to be sure there's continuity of treatment for people in the lucidity study who are completing the OLEB portion of the lucidity trial. So that drives the timing for the EAP. Now with regard to your question about NDA preparation, yeah, we're sort of not typical for sure. And we are working, as noted, on NDA preparations. And we do hope that that will, you know, allow us to be most efficient as we reach top line data next quarter. And because there is a great sense of urgency, there are no treatments for people with PBH. And if positive, we want to be sure that we're providing the opportunity for access as promptly as possible.

Yeah, and I'd just maybe underscore from Camille as well. I think both of these activities both underscore, too, the unmet need in PBH. We know that patients urgently need a new therapy and also our excitement about Avexotide. You know, we've had five prior trials of Avexotide. all which showed, you know, very strong results. We have breakthrough therapy from FDA. So we want, you know, both to get patients access as quickly as possible, which, you know, of course is reflected with the EAP, but also pending positive results to be able to submit as soon as we possibly can, which is, you know, reflected by our ongoing work on the NDA.

And just one more thing to add, thank you, Seamus, is we also have a very experienced team here. Our team has experience with global regulatory approval, certainly a lot of experience with FDA as well. And so that allows us to start working on the NDA documents now. Again, everything is driven by the urgent unmet need for people with PBH, but I think coupled with the strong experience we have here both for regulatory submissions and process as well as commercialization process.

Your next question comes from the line of Joseph Fong with TD Common. Your line is open.

Hey, this is Jacob on for Joe. Thanks for taking our question. We were wondering how the baseline for the enrolled Phase III population would compare to the patients in Phase II studies, and then what the expected placebo response in Phase III might be versus what we know about the patients in phase two and the differences in the run-in periods. Thanks.

Sure. So the study is ongoing and blinded, and so we will not really comment on the details of this ongoing study. Having said that, we are very much looking forward to top-line data next quarter where we'll share the top-line data with you and hope you're sharing our excitement as well for this possibility. With regard to the placebo, remind as well, we've had five prior highly successful trials. The phase two trials showed statistical significance and clinically meaningful reductions in the composite as we presented at endo. In the PREVENTS study, 55% reduction with a highly statistically significant value. And in the phase 2B with a 90 milligram dose, the dose and lucidity, 64% reduction with p-value 0.0031. Those p-values do take into account all aspects of the trial, including the possibility of any placebo effect. We designed lucidity with the goal of replicating these prior successful trials. So, and we powered, we're highly powered, 90%. to detect a clinically meaningful reduction in events, even under the most conservative circumstances.

So yeah, you're welcome.

Your next question comes from the line of Corinne Johnson with Goldman Sachs.

Your line is open.

Good morning. This is Kevin on for Corinne. Could you just talk about the steps that you've taken beyond the event rate quota to ensure patient quality in the study for lucidity, and then also to ensure sort of as much as possible adherence to study protocols for the full 16-week treatment period? Thanks.

Sure. So we, again, we're replicating as much as possible the way lucidity is being conducted, mirroring what was done in the successful Phase II and Phase IIb studies. We have training, extensive training of the clinical sites at the onset of the clinical trial. That training is reinforced throughout the conduct. And we also have materials for the participants to guide them on the study procedures throughout the study as well. And we also do, you know, have quality checks on the data overall to be sure that things are moving along well.

Yeah. And I just add to, you know, we have a very experienced team at Amelix and, you know, quality starts from selecting great sites, having strong oversight. And I think throughout the whole course of the study, I've been quite proud of the team's efforts, just kind of continually keeping close and making sure that, you know, quality is kind of built in from the start and continues through the whole study.

Your next question comes from the line of Michael LaFleur with Evercore ISI.

Your line is open.

Hey guys, thanks so much for taking my questions and congrats on all the continued progress. First one for me is, now that Lucidity is fully enrolled, can you help us think through what the top line disclosure will actually look like, what it will contain, beyond whether the primary endpoint is met, What do you think will be the most important aspect of the data for people to understand, again, beyond the primary endpoint in that initial release? And secondly, you know, since you're already preparing for NDA, since the last update, can you share more light on what work remains to be done between top line and potential submission, maybe in terms of QC, any additional studies, et cetera? Thank you.

Yeah, thank you, Mike. So I think first in terms of, you know, top line disclosure, you know us well. We're a transparent company, so our goal is always to present things as they are. I think what's important in this study is probably two things to remind. The first is that the primary outcome, which is level two, level three hypoglycemic events, not only is it the primary outcome, it's in FDA guidance, But it's also very well known by endocrinologists, and it's inherently clinically meaningful. Level 2 events being less than 54 milligrams per deciliter of blood glucose, which is the blood value at which neuroglycopenia occurs. Level 3, of course, means that the clinical manifestations of hypoglycemia have already occurred. So those are inherently clinically meaningful. And then I think a second important point is that there are currently no treatments for PBH And so, what we have heard consistently, not just from people with PVH, but from physicians as well, is that any reduction in hypoglycemic events is meaningful. Each one of these events is a medical emergency. And so, what we hear from physicians often is that they are worried for their patients, and they have really very few tools to help prevent these medical emergencies. So, any reduction in these hypoglycemic events is meaningful. In terms of the NDA, we're working hard on everything we can now. I think the goal would be that the last really substantial piece of work would be everything associated with the Phase III trial. So we're trying to write everything in advance that we can. As I said, we have a very experienced team who's been through many regulatory submissions before, so they're hard at work as we speak.

Your next question?

comes from the line of Mark Goodman with Learing Partners. Your line is open.

Yes, good morning. This process of adjudicating the claims data, can you give us an example or two of just some of these efforts and just so we understand what you have done so far and how confident you are that you're finding these patients in the places that you think they are based on the claims data? Thank you. And are you only counting like the moderate to severe ones. You're not counting the benign ones, right?

Thanks, Mark. Appreciate the question. Just to talk a little bit about the claims analysis. So within the claims databases, we start with identifying patients that have a presence of bariatric surgery. And then we look at patients who also have documented hypoglycemia, so non-diabetic hypoglycemia. And then after that, we'll then apply, and we have applied, additional signs and symptoms associated with PBH, such as fatigue, dizziness, seizures, even blood glucose tests, or even ER visits. And then to add to that, we can look at it from how many of those type of events they've also had within the claims databases. So that's really how we've continued to look at the databases. I'll say we've done it several times, and each time we do it, we are confident in the 160,000 patient population that we've mentioned a few times.

Yeah, and I might just add to, you know, some added work that the team's done too is both speaking, you know, to many of the sites and doing kind of market research with many of the sites to validate what we're finding in claims. You know, for example, if the claims are saying, you know, a site has 50 patients, you know, actually checking with the site and seeing if they do have 50 patients. And so far, those have been quite confirmatory as well. And I'll also just add from a call today, we also, you know, received notification, you know, kind of through the CMS manual list that there's likely to be an ICD-10 code for PBH going live in October, which will provide, you know, an additional tool kind of to track the claims data as well.

Yeah, and to directly your point, too, on excluding benign, you know, based on the coding, both on hypoglycemia as well as the signs and symptoms, these are people who have severe hypoglycemia.

Thank you.

Your next question comes from the line of Jeff Meacham with Citibank.

Your line is open.

Great. Morning, guys. Thanks for the question. I have two quick ones. So ahead of Lucidity Topline, I know the primary outcome measure is level two or three events as a composite, but is there a thought of looking at, you know, each one of those separately, in particular level three, just to have a cleaner, you know, look at the profile from maybe a more commercial context? And then the second question, as you guys begin to focus on commercial and further evaluate the PBH prescriber base, you know, how has your thinking evolved in terms of size and scope of Salesforce and MSL teams? Thank you.

Hi, Jeff. I'll take your first question and then pass it down for your second. So, as you say, our primary endpoint, which is FDA agreed upon, we were looking at the reduction in the composite of level two and level three events. And that is well established in the ADA Diabetes Association literature and community as well. We do intend as well, our secondary endpoints are looking separately at level two, which is by finger stick, blood glucose level of less than 54 grams per deciliter, and separately level three, which is independent of glucose level, signs and symptoms that require individuals to have another individual health or signs and symptoms that would have required someone else to help them if no one else is around. And that is adjudicated by an independent group of experienced endocrinologists who are blinded to the data as well. And they do that adjudication on an ongoing basis.

And I'll just add, too, from the sort of commercial point of view. So you're right. Absolutely, level three means the person has had the manifestation of hypoglycemia. And so, of course, that's important. But level two being less than 54 is very well established, too. So I think endocrinologists will be interested in both. And if you think about the outcome, it's really a nice mix. You have a blood value, which indicates severe hypoglycemia, so you kind of know what's happening in the body. And then you have a clinical outcome in level three, where you know the person has had the impact of severe hypoglycemia. And then for your question on prescriber-based, I'll pass it to Dan.

Sure. So Jeff, thanks for the commercial question. So on the Salesforce sizing, we are initiating the go-to-market efforts at this moment. I would say this is a rare endocrine launch, so from an expectation, you can expect that the Salesforce would reflect this particular size of a Salesforce. I'd also add that on Camille's team in the medical affairs function, we have initiated hiring our regional scientific director team, also known as an MSL team, but those hires are in place.

Your next question comes from the line of Ramik at CUDA with Lifeslide Capital. Your line is open.

Hi, Jane. Thanks for taking my questions as well. I guess, can you touch on the degree of natural variability there is in level 2 and level 3 hypoglycemic events for PBH patients? Do you expect a massive difference from one week to another? And then secondly, from a commercial perspective, are these PBH patients generally managed at centers of excellence, or would you need to target endocrinologists more broadly?

Sure. Maybe starting with the variability. So, you know, all of that's taken into account in our powering analysis. And I think we were quite conservative in our powering, both on the effect size and on the placebo effect, you know, whereas we saw a 50 and 64% effect size at the 60 and 90 mcdoses, you know, we powered to a 35% effect. And then, of course, you know, retaining power up to a 50% placebo effect, even though I, you know, I don't think we expect that, you in this condition. You know, you can certainly look at the, you know, variability kind of from previous studies, but again, that's all kind of accounted for, you know, in our powering analysis. And generally, it's a chronic condition. Generally, people, you know, are not able to, you know, prevent these events from occurring. So often, if people are having events, that will be a continuous thing. You know, they don't kind of come in fits and starts, you know, so to speak, all that often. In terms of the question of, you know, how we'll target centers of excellence versus the broader endocommunity, I'll pass over to Dan.

Sure. Thanks, Josh. I'd appreciate the question on the potential launch, Rami. On where the patients are potentially treated, so we have initiated that work, and we are aware, and Josh mentioned this earlier, but there are centers of excellence. There are also key opinion leaders, and that's likely where we'll start from a launch perspective. We know that there's, you know, potentially 50 to 60 patients at certain centers, and some centers have even mentioned even more. But we'll start there. We know there's a concentration, and then as our disease state education efforts take a foothold, we'll expand into the broader endocrinology community.

Your next question comes from the line of James Candales with CFIL. Your line is open.

Hey, this is Mark on for James. Thanks for taking our question. One for me on a record Dottie, I believe we should be getting some data this quarter. And just curious your thoughts here as it relates to potential placebo effect and you know what the implications are for acidity and whether really this is something that can actually be sort of, you know, read through onto your trial. Thanks.

Yeah, thank you, Mark. So, I would say, no, I wouldn't think there should be any read-throughs. They're very different studies, and of course, we're conducting our study, and Recordati is conducting their study. As I understand it, I think their study is a phase two, looking at mixed meal tolerance tests, and ours is based on the prior phase twos, which is a much more real-world type approach looking at level two, level three hypoglycemic events, which of course is within FDA guidance to support a potential registration. So, no, I don't think there should be any read-through between the studies.

Plus the mechanisms of the drugs are very different as well.

Your next question comes from the line of Greg Zivanovich with Mizzou. Your line is open.

Hi, this is for Greg. Thanks for taking questions.

Maybe switching over to 0114 with the ALS data coming up shortly. Just remind us of the specific biomarkers to potentially look out for. I know there was some prior analysis done by you guys highlighting certain biomarkers. But maybe just a reminder, and then also some of the expectations you guys have. Or we should be thinking about going ahead into the data. Thank you.

Sure. Thanks very much. So just to remind, our ALS study with AMX114, which is an ASO against CalPain 2, is ongoing. We announced that we completed enrollment of cohort one in March and that we are recruiting cohort two at the moment. And earlier this year, we reported on the safety data for cohort one. And we do anticipate, as you point out, reporting on the biomarker data. Actually, it will be this June at NCALS in Madrid, Spain. So the biomarkers that we're studying are related to the mechanism of the CalPain2 ASO blocking this protease, as well as biomarkers that are related also to the ALS disease process. And we look forward very much to sharing those data with you.

And just to... that as well. You know, as Camille said, study's proceeding incredibly well. So, you know, I think as Camille was mentioning, we've completed enrollment in cohort two, and, you know, we're now recruiting for, you know, cohort three as well.

Your next question comes from the line of Jason Gerberry with Bank of America. Your line is open.

Hi, good morning. This is Dina Ramadan on for Jason. Thank you for taking our question. Maybe just a couple of commercial questions on Invexatide. I think you've mentioned before that the ICD-10 code was not necessary for successful commercialization, but just curious how ultimately having an ICD-10 code kind of alters your confidence in identifying and capturing patients at scale. I know you've outlined the centers you're targeting and what your commercial strategy is, but just curious if it impacts how you're you're approaching your commercial plan. And then, just a second quick follow-up. I believe you plan to physician of exercise as a chronic therapy. I'm just curious what assumptions you're making around expectations for persistence and adherence in the real world.

Thank you.

Great. Thanks, Dina.

So, on the ICD-10 question, so in April, Well, CMS, they published a list of ITD-10 codes to be effective October 1st. These codes demonstrate a recognition of PBH in the broader medical community. The ITD-10 code, yes, it is helpful for diagnosis and tracking of patients. However, it's not necessarily, it's not a necessity. ITD-10 codes are often used for epidemiology. So in implementation of the code, this will enable patients to be tracked across the various electronic medical record systems. It's also important to note that patients today, they still can be identified via the claims analysis, and that's how we validated the 160,000 patient population.

And then to your other question, too, about kind of chronic therapy and persistence, it's probably early to comment there. You know, we're quite excited, you know, about Avexetat and, you know, PBH is a chronic condition where the needs do not go away over time.

So, certainly, we do think that, you know, patients will have an ongoing need for therapy.

Your next question comes from the line of Chris Chen with Baird.

Your line is open.

Good morning. Thanks for taking my question and congrats on the progress. Just a quick one on the OLE. Can you just remind us what the setup is specifically for that? And, you know, are you able to kind of share high level how enrollment in that is going?

Sure. So, are you speaking of the OLE or the EAP? Just so that I'm clear, please.

The OLE for Lucidity, the Open Label Extension. Yep, yep.

Yes. So, you know, while I will not comment on details of our ongoing blinded trial, I am pleased to share that Lucidity is proceeding well, including participants transitioning from the double-blind period to the OLE portion of the study. We're confident that we're running the right study, and we're very pleased on how the team has been executing on the trial. We have such an experienced team. and they're overseeing the trial with great focus and care.

Yeah, and you asked the OLE setup, so just to add there as well. So, you know, we expect the randomized double-blind study is the study that, you know, we expect to use in our NDA, you know, to support potential commercialization. The OLE itself, though, also has a Part A and a Part B. During the Part A, we keep the study very similar to how it's conducted during the double-blind. That allows, you know, to look at, you know, kind of data, you know, in a similar way to we look at as the double-blind. And then later, they enroll in the OLE-B after eight weeks in the OLE, at which point it's a little more, you know, there's less burden, some kind of trial participation at that point. But overall, just to kind of reiterate what Camille said as well, We're very pleased with the context of the study. You know, there's a lot of excitement, you know, from sites and otherwise as well. And we'll look forward to reporting our data in Q3.

And I think it's obvious, but just to say also for the open label extension, I think it's very important when you work in rare debilitating conditions like post-bariatric hypoglycemia that you always try to think about the people we're trying to help. And so for an open-label extension, if you're on treatment and you believe that you're benefiting, an open-label extension allows you to continue. And if you're randomized to placebo, then it allows you to take active medication. So that's something that we always really try to think about in our programs.

Your next question comes from the line of Ananda Ghosh with HSC Winwright. Your line is open.

Hi, good morning, guys. Thanks for the question. Maybe one question, you know, people have been focusing on U.S. opportunities. So one question would be, have you done work with respect to Avexatide on ex-U.S. opportunities? You know, what are you hearing from the KOLs or stakeholders? And then I have one follow-up question on Lumina.

Absolutely, yeah. Thank you, Ananda. So there's a tremendous unmet need globally, right? for post-bariatric hypoglycemia. Now, our focus is very much on the U.S. right now. With 160,000 people in the U.S. with PBH today, that's a substantial unmet need and people to help and address. But our, first of all, bariatric surgeries occur globally. And also, as we've mentioned before, virtually any gastric surgery, has the potential to cause the same debilitating hypoglycemia. So, for example, in major Asian countries, gastric cancer rates, esophageal cancer rates are very high. And so gastrectomy or esophagectomy is often indicated. And so for people with those surgeries, they also have the potential of developing this same debilitating hypoglycemia. And we have data from the Phase IIb study of Avexatide, that Avexatide may be beneficial for people who had those surgeries leading to this debilitating hypoglycemia as well. The pathophysiology is the same regardless of the surgical intervention. So our focus is really on the U.S., really on the U.S. population of post-bariatric hypoglycemia. But absolutely, there's a huge unmet need internationally. We get compassionate use requests from people around the world constantly.

Got it, great, thanks. One question on Lumina. I know there was a question on biomarkers. So given that it's the lowest dose, can we expect the preliminary NFL data or target engagement data with respect to CalPEN2 levels or other downstream markers like SBDP 145 in the data readout? Or that is for later?

Yeah, I mean, it's hard to know. Sorry to interrupt. It's hard to know until we have the data. I'd say, you know, we do preclinically believe we have a potent ASO. As you look at past ASOs that have been in clinic, usually they've been studied, you know, between the range of generally about 10 mg to 100 mg for CSF injection, and we're at the very low end of that range. So we may see signals, but it also may require us to go to a higher dose before we, you know, start significantly moving the biomarkers.

But I'll add to, Anand, to your point. We really are, our goal is to have a picture of first, are we replicating the biology that we saw in the preclinic to the clinic? Are we seeing the implications of CalPain2 knockdown? And then are we seeing effects on biomarkers that we believe to be agnostic for ALS as well? So that is indeed the goal of the biomarkers in all of these cohorts is to try to get a picture of are we seeing the impacts of CalPain2 and are we seeing potential impacts on ALS as well.

Thank you. There are no further questions at this time. I'll turn the call back to Mr. Klee.

Thank you, operator, and thank you all for your time. If you have any follow-up questions, please reach out to Lindsay, and we hope you have a great rest of your day.