Amylyx Pharmaceuticals, Inc.

Good morning. My name is Carly, and I will be your conference operator today. At this time, I would like to welcome everyone to the Amelix Pharmaceuticals Third Quarter Earnings Conference Call. All participants will be in 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 1 again. Please limit your questions to one 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 third quarter 2025 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, and Jim Fradies, 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 a Vexatide AMX 35 and 114 statements regarding other development candidates, statements regarding regulatory and clinical developments, 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 statement. You are cautioned not to place any undue reliance on these forward-looking statements, and AMLEX 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. Q3 was a quarter of progress as we continue to focus on our lead program, Avexatide in Post-Bariatric Hypoglycemia, or PBH. Avexatide is our investigational, first-in-class inhibitor of GLP-1 receptor activity with FDA breakthrough therapy designation. PBH is a condition characterized by recurrent hypoglycemic events which can impose a significant and lasting burden on a person's quality of life. There is a robust body of data generated to date for vexatide, which includes five clinical trials demonstrating statistically significant and clinically meaningful reductions in hypoglycemic events. Based on those results, we designed our pivotal phase three lucidity trial with the goal of replication. We remain focused on enrolling a similar patient population collecting the data in a similar way, and executing lucidity with high quality. We continue to see high participant interest and broad engagement across clinical trial sites, which we believe supports the urgent need for an FDA-approved treatment. Our previous guidance for completion of recruitment was by the end of 2025, with top-line data in the first half of next year. Based on our most recent projections, we now expect to complete recruitment in Q1 2026, with top-line data expected in Q3 2026. We anticipated more of a ramp in the enrollment rate at this stage, but we have seen more of a steady enrollment rate in the last few weeks. Timing for potential launch remains unchanged. With early NEA preparation efforts underway, we continue to expect to be in a position to launch Avexatide in 2027, pending FDA approval. Having launched a commercial product in the past, we're focused on key areas required for successful launch. we are already laying the groundwork to be ready in 2027 if approved. We've been taking the initial steps towards building the medical affairs and commercial organizations with targeted investments in market research, insights, disease education, market access strategy, and commercial infrastructure. Our continued market research, claims analysis, and engagement in the field support our confidence in our estimate of 160,000 people with TBH in the U.S., and bolsters our understanding of the unmet need. Turning to our broader pipeline, in Wolfram syndrome, we are advancing the clinical development of AMX35, and pending alignment with FPA, we plan to initiate a focused pivotal phase 3 trial in the second half of 2026. For AMX114, our investigational antisense oligonucleotide targeting CalPain2 and ALS, We were pleased to share that in September, we fully enrolled cohort one in the phase one Lumina trial. We anticipate early cohort data later this year and plan to share the safety data at the 36th International Symposium on ALS and MND, which is being held from December 5th to the 7th. Based on biomarker collection and analysis timelines, we anticipate biomarker data will be available in the coming months and expect to present these at a medical meeting in the first half of 2026. We are excited by the potential of this novel mechanism and the fast track designation from the FDA. Across all of our programs, our team is focused on execution as we head toward a pivotal year in 2026 with top line data from Lucidity anticipated next year. Now, I'll turn the call over to Camille.

Thank you, Justin. As a reminder, TBH is a serious, persistent, and life altering condition with no FDA approved therapy. People living with PBH often experience frequent, unpredictable hypoglycemic events driven by an exaggerated GLP-1 response that can severely limit their independence and quality of life. Many people with PBH live with a constant anxiety around meals, social interactions, and basic daily activities. Individuals with these experiences are not outliers. They reflect a broader underserved population. that motivate our work. Avexatide is an inhibitor of GLP-1 receptor activity that reduces insulin secretion and stabilizes blood glucose levels. Based on the data and consistency from our five previous trials in PBH, we designed the pivotal phase three lucidity trial to optimize the potential for success by being as consistent as possible with the previous phase two trial. These studies directly informed the dose, endpoints, inclusion criteria, and surgical subtypes. Lucidity is evaluating a vexatide 90 milligrams once daily in individuals with PBH following Roux-en-Y gastric bypass surgery. The FDA agreed upon primary endpoint is reduction in the composite rate of level two and level three hypoglycemic events through week 16. Based on prior phase two data, we believe the trial is well powered to detect clinically meaningful benefit. We continue to be encouraged by the execution of the trial that prioritizes scientific rigor and operational excellence. All clinical trial sites are now activated and screening participants. There is high participant interest and engagement across our sites. Investigators continue to report that participants are highly motivated to contribute to the study. Furthermore, participants have begun to move into the open label extension portion of the trial. As awareness of PBH continues to grow, we are seeing increased recognition of the burden and the urgent need for a treatment option. We believe of Exatide, which has been granted FDA breakthrough therapy designation, has the potential to be the first approved therapy for PBH and to meaningfully improve the lives of those affected. With that, I'll turn over the call to Jim to review our financials.

Jim? Thanks, Camille. Our financial position is strong as we focus on careful execution of lucidity and preparing the company for a launch in 2027 should Avexatide be approved by the FDA. We ended the third quarter with a strong cash position of $344 million. compared to $181 million at the end of the second quarter. This reflects the recent completion of our public offering in early September. This financing provided approximately $191 million in net proceeds, and together with our existing cash, positions us to support the potential launch of Avexitide in 2027, and provides us with an anticipated cash runway into 2028. Turning now to our results for the quarter, Total operating expenses for the quarter were $36 million, down 53% from the same period in 2024. The decrease is primarily due to the one-time expenses related to the acquisition of Avexatide that we incurred in the third quarter of last year. Research and development expenses were $19.9 million, compared to $21.2 million in Q3 2024. This decrease was primarily due to decreases in spending on AMX 35, for the treatment of PSP and ALS. The decrease was offset by increased spending related to the clinical development of abexetide in PBH. Selling general and administrative expenses were $16.2 million, compared to $17.8 million in Q3 2024. This decrease was primarily due to a decrease in consulting, professional services, and other expenses. We recognize $7.1 million of non-cash stock-based compensation expense for the quarter compared to $6.8 million of non-cash stock-based compensation expense in Q3 2024. In summary, the more work we do, the more we learn about the patients and providers, the more we believe that there is a major unmet need for people living with PBH. The key for us operationally is to execute the lucidity study well and prepare for a positive outcome. We believe we have the scientific, operational, and financial resources we need to execute on our goals. With that, I'll turn the call over to Josh.

Thanks, Jim. Our conviction in inhibiting the GLP-1 receptor as a therapeutic approach remains strong. While lucidity remains our primary focus, we also view it as a starting point, both for vexatide and for advancing research into GLP-1 receptor antagonism more broadly. For instance, our research collaboration with Gubra continues to show encouraging proof-of-concept data with new molecules demonstrating strong potency in vitro and in vivo, along with extended half-lives. We are very pleased with how the partnership is progressing to develop a novel long-acting GLP-1 receptor antagonist. We expect to make a decision on a potential development candidate in the next few months, and pending a candidate nomination, we are preparing to initiate our IND-enabling studies. Before we open the call up for Q&A, I would like to reflect on the urgent opportunity driving our work in post-bariatric hypoglycemia. PBH affects an estimated 8% of people in the U.S. who have undergone the two most common types of bariatric surgery, sleeve gastrectomy and Roux-en-Y gastric bypass. That translates to approximately 160,000 individuals living with PBH. many of whom experience frequent, unpredictable hypoglycemic events that disrupt daily life and limit independence. Multiple lines of evidence support a belief in the significant unmet need in this market, including several robust published prospective and retrospective studies and our ongoing claims-based work. Most compelling is what we are hearing directly from the field, which has continued to corroborate the substantial burden in PBH. We continue to be excited by the data generated to date in the five clinical trials of vexatide and PBH. These findings, together with new analyses we shared last quarter at Endo 2025, reinforce the robust body of evidence and give us confidence as we advance lucidity towards top line results next year. We are committed to executing lucidity and preparing to be launch ready following FDA approval, and we look forward to keeping you updated. Now I would like to open the call up for questions.

We will now begin the Q&A session. To ask a question, please press star 1 on your telephone keypad. To withdraw your question, press star 1 again. Please limit your questions to one with one follow-up. If you have additional questions, you may rejoin the queue. At this time, we'll pause momentarily to assemble our roster. Your first question comes from Seamus Fernandez with Guggenheim.

Oh, great. Thanks for the question and appreciate all the updates. Wanted to just get a quick sense of the enrollment, you know, update. With regard to a couple of things, as we've been speaking with physicians, there were a couple of dynamics in play here. One was the very careful decisions on the part of the company to ensure that there is a broad enough participation from a wide enough array of sites that, you know, it would take some time to basically start up those sites. So just trying to get a better sense of the impact here. Is it site startup that has resulted in the, you know, estimated modest delay of a quarter? Is it the run-in period that is potentially impacting the enrollment, because again, a three-week with the requirements for level three events, I could envision having an impact on enrollment just given the careful design there. And then another factor would be just ensuring that the patients that are enrolled are actually fully dedicated and committed to limiting any potential changes in diet over the 16-week period. That could negatively impact the study. So just wanted to get a better sense of, you know, some of the operational dynamics that could be coming into play as it relates to the study. And then just a very quick follow-up on the Gubra comments. You know, the DC development candidate selection to IND, can you just give us a sense of the timeline that might come into play there? Thanks so much.

Great. Yeah, thank you so much, Seamus. Great, great questions and important points on operations. Yeah, so I think first just to say at a high level, you know, I think we're pleased with how the study is being executed, how it's progressing. The first participants are going into the open label extension. And, you know, you raise really important points as well, which is our real focus is on quality, enrolling the right participants, ensuring the right data collection, you know, especially in view of the five prior trials of Avexacide and PBH, which demonstrated very statistically significant and clinically meaningful reductions in hyperglycemic events. So the update is on the timeline based on our most recent enrollment projections and estimates. And I would say that, you know, certainly in every trial I've been a part of, As you have all of the sites up and running, recruiting participants, you tend to see a ramp in the enrollment rate. Now, that could still happen, but so far it's been a steady enrollment rate. And so that's why we're updating the projections to now estimated completion of recruitment in the first quarter. So I hope that helps, but I really appreciate your points on the quality of the operations, that's definitely where our team is focused as well. And, you know, we're pleased with our team's focus.

And maybe just touching on your other questions too, included in that quality certainly is maintaining the dietary guidance throughout the whole trial. So just as a reminder, at every clinic visit, patients do receive dietary guidance. And, you know, the goal of that is to keep everybody following closely with the recommended PBH diet. And we have heard that patients are, you know, quite engaged, quite, you know, excited to participate in the study and wanting to be, you know, to follow the protocol as best as they possibly can. You also asked about the drug candidate nomination from Gubra and a sense of the timeline. So first I'll say we've been quite excited about the data from Gubra. We've seen really encouraging data both in vitro and in vivo, you know, both on kind of efficacy outcomes as well as outcomes related to half-life and kind of the duration of the drug. We'll probably give more granularity on timeline as we, you know, do nominate or as we get to the point of making the decision, you know, to nominate a drug candidate. But certainly our goal will be to move as expeditiously as we possibly can.

Your next question comes from Joseph Thorne with TD Cowan.

Hi there, good morning, and thank you for taking my questions. Maybe the first one, just on the phase three study, do you have a general idea of how long patients have trialed dietary therapy and still are not able to respond to that before entering the study? And maybe related to that, what's your kind of current screen failure rate for patients maybe not meeting the necessary events in the observation period? And then follow if I can on the ALS program. Can you just clarify a little bit what you're going to present later this year? Will you have early biomarker data from that first cohort already in this presentation? Or are you going to present all the biomarker data next year when you have a larger set? Thank you.

Sure. So probably, you know, within an ongoing trial, we don't necessarily kind of give interim data or interim updates. But what I can share is when you look at past studies with vexatide, It was often the case that people had had PBH, you know, six, seven, eight years. And, you know, the usual standard in PBH is certainly the dietary therapy. So most of these patients will, you know, we do expect that most of the patients, if not all of the patients, will have been on dietary therapy, you know, many years prior to entering. And we do require that the bariatric surgery was at least a year prior to entering the study. So everybody's had, you know, the bariatric surgery well in their past as well. You know, in terms of screen failure rates, similarly, we don't kind of report interim data as we're going through our study, but certainly our goal, as Justin suggested, is to enroll the right patients in the study and to, you know, focus on quality throughout, you know, getting patients who have the appropriate level of severity and who, you know, hopefully will be able to complete the study also. In terms of the 1-14 presentation in early December, that will focus on safety at this time. We will have biomarker later. We expect to report on that in the first half of the coming year at a medical conference. The biomarker work just takes a little bit longer, you know, hence that coming in the first half.

Great. Thank you very much.

Your next question comes from Jeff Meacham with Citi.

Hi, guys. It's Ross on for Jeff. I guess, thanks for taking our question. We're curious about your sense of PDH and kind of the addressable market and how has that continued to evolve?

Yeah, thank you. And I would say, you know, as we've done more and more commercial preparations, you know, looking forward, I'd say it only increases in our confidence in both the unmet need in the market So we've looked at multiple claims-based analyses now, as well as there's been independent work out of Stanford looking at the total population. And our estimates continue to be that there are about 160,000 people today who have PBH. And we expect more to come as well. Bariatric surgery rates continue to be quite significant. And with that, we would expect the population to only continue to grow from already quite a substantial unmet need. You know, the other thing that I think has really come out from being out in the field is the unmet need. It's severe hypoglycemia as defined by level two, level three events. These are frequent occurrences. for people with PBH. To put it in context, severe hypoglycemia, according to the American Diabetes Association, a single event is a medical emergency. And these are people who are having frequent hypoglycemic events. So it's highly, highly debilitating. And what we hear from clinics is that they're very worried for their patients because, one, they really have very limited options to help them, and two, that these hypoglycemic events can occur often without warning and, again, so frequently. So I think all of our research just continues to bolster our confidence in the unmet needs and the opportunity here that we have with Avexotype.

Thank you.

Your next question comes from Corinne Johnson with Goldman Sachs.

Hi, this is Kevin. I'm for Corinne. Good morning. Just wanted to follow up on the addressable market question in terms of the, you know, 160,000 PBH patients. As you do more work on that, what percentage of those patients do you think would be, you you know, uncontrolled on, you know, on diet? And what percentage of those patients do you think would be eligible for your phase three? Thanks.

Yeah, good question. So maybe starting with kind of uncontrolled on diet. So in coming up with the 160,000 estimate, which, you know, as a reminder, is based on published prospective and retrospective data, as well as claims-based work and, you know, direct work with physicians treating PBH, we tried to eliminate up front those who were controlled on diet. So the 160,000 is intended to be those who are not controlled on diet and who are continuing to experience unacceptable and clinically problematic hypoglycemic events. In terms of direct eligibility for the phase three, that's not an analysis we've done directly through the 160,000 But again, we do view the 160,000 as people who are having, as Dr. Colleen Craig calls it from Stanford, medically important PBH, PBH which is significantly impacting their daily life. And as Justin said, even a single significant hypoglycemic event is considered a medical emergency. So these are patients who, in effect, are having frequent medical emergencies.

And just to give a picture of what we believe is going on from a pathophysiology perspective, we believe that PBH is caused by the body dramatically upregulating the production and secretion of GLP-1. So people will have up to 10 times normal levels of GLP-1. And so the reason that we think, we hear from both clinics and patients, that kind of no matter what they do, they continue to have these drops in blood glucose is because of this GLP-1 effect. So, you know, if you think no matter what they do, their body is producing up to 10 times normal levels of GLP-1, their blood glucose is going to plummet. And that's also why we think vexatide has such potential because really to get to the heart of PVH, we believe that you need to blunt that GLP-1 bolus, which is ultimately what's causing the hypoglycemia.

Thank you.

Your next question comes from Mark Goodman with LeeRank Partners.

Yeah, just to kind of come back to this delay in the timeline, can you help us understand like Someone asked the question, but I wasn't sure if the answer was given about, I mean, we're talking about 75 patients and 20 sites, right? And this is three to two random. I mean, what, help us understand what's going on here. Like, do we need to add more sites? Do we have the right sites? Like what, help us just understand what that issue is. And then you talked about these patients moving into the open label extension trial. Talk about the side effects that that you've seen? Is everything generally the same as what we've seen in the phase two studies? Anything unusual? Thank you.

Sure. Thanks, Mark. So first, I wouldn't, you know, characterize this as an issue. I'd say that, you know, as we continue to go along the study, we've updated our timeline, you know, to expect a complete recruitment in the first quarter of next year with data coming out in Q3 of next year. We have seen a lot of excitement across the trial. I'd remind that, you know, that timeline would still be recruiting a, you know, phase three study in under a year. And, you know, phase three studies entail, you know, not just finding the patients, but also all the work that goes into activating sites, you know, everything else. So we actually do see that as a very good timeline, you know, for a phase three as well. We probably won't report at this point. on, you know, side effects or otherwise. We don't report, you know, interim data from a trial, but I think as we mentioned, we are excited to see, you know, quite a lot of participant engagement and patients moving into the OLE as well. So, you know, excited overall about the, you know, execution of the study and our team's great efforts in this space.

Your next question comes from Rami Katkata with LifeSci Capital.

Hey guys, thanks for taking my questions as well. I guess in lucidity, are you measuring diet adherence via the blinded CGM and can you intervene based on blood glucose levels if the patient is kind of liberalizing their diet as they start to feel better?

Yeah, hi Rami, great question. So I would say that Our team, as well as the monitors, are looking at all of the, you know, available blinded data, including CGM, as you mentioned, which we get in virtually real time. And the goal there is really to make sure that, one, yes, people are adhering to diet, and two, that people are collecting events as we would expect in the studies. So, yes, our teams are continuing to do that. And if we see, you know, significant, you know, deviations that we think need addressing, then our team will indeed reach out to the site and retrain as necessary.

Got it. Makes sense. And then I know I'm jumping the gun a little, but a number of KOLs are excited to use a vexatide for hypoglycemia associated with other GI surgeries as well. I guess, have you talked to the FDA on the regulatory path forward there? Would you have to run a study in each population, or is there potential for kind of a basket study across a number of these surgery types?

Sure. So, the phase three study is in people with Roux-en-Y gastric bypass. You know, it's early to, you know, label discussions happen later in the process, so it's early to say, you know, what an FDA label would or wouldn't be. But, you know, given that the study is in Roux-en-Y, that is, you know, that is a potential risk that we, you know, that element finds its way into a label or otherwise. That being said, we do believe both physiologically based on the biology of these different surgeries that the pathophysiology is similar or the same for why people are getting PBH across them. And in addition, our phase 2B study included people with multiple surgical types, and the effects look similar, you know, across those surgical types as well. So it's certainly something that we want to pursue. We do exactly as you suggested, get a lot of interest. from academics and otherwise with surgeries, you know, beyond Roux-en-Y, including people have had gastrectomy for gastric cancer, nissen fundoplication for gastroesophageal reflux disorder and otherwise. So it's definitely an area where we're quite excited to pursue. And yeah, I'd say stay tuned in that regard.

Sounds great. Thank you.

Your next question comes from Greg Souvenive with Mizuho Securities.

Hi there. This is Sam with On4Greg. Thanks for taking our question. Can you just remind us of the manufacturing and CMC processes for vexitide in terms of the commercial doses and the process there, and if you anticipate any snags moving forward? Thank you.

Hi, Sam. Yeah, and important question. So, I would say, you know, we're doing all of the expected work as we move toward commercialization, or hopefully with commercialization on the CMC side. So, I'd probably touch on a number of points. So, first, as you may expect, we have manufactured our registration batches, and they're up on stability. I'd say second, the suppliers that we're working with, both on the drug substance being the peptide and the drug products being, you know, the final finished product are manufacturers that have multiple commercial products and have very good inspection histories as well. And I would say then on the internal side, we're focused on all of the quality parameters, inspection readiness activities, as you might expect with the anticipated approval in 2027. So I'd say, you know, our team is laser focused on all of the things that would be required for both NDA submission and then eventual approval.

That's very helpful. Thanks for the color.

Your next question comes from Chris Chen with RW Baird.

Good morning, team. Thanks for taking my questions. Just going back to the lucidity and the clinical sites, have you noticed any differences in the ramp between sites? And are you kind of maybe learning from those sites that maybe are enrolling faster to kind of overall just make the ramp increase across those sites?

Yeah, thanks, Chris. And I would say, you know, in a clinical trial, of course, you know, you always have differences across sites. And, you know, that's why we have 21 sites. All sites are activated. And I would say, again, in my experience, as you have all the sites, and you go into the latter part of the study, that's when you tend to see an increase in the enrollment rate. So that could still come, but so far in the last few weeks, we've seen more of a steady enrollment rate. Again, our goal is to conclude enrollment as expeditiously as possible, but of course, making sure that we're enrolling the right participants, we have the right clinical oversight as well. I'd say on a sort of site engagement level, The main message I would say is that the unmet need here is very real. I think we have high engagement from the sites. They're very eager to have potential treatment options for their patients. So that's really come through in all of our engagements.

Thank you. Your next question comes from Tim Anderson with Bank of America Securities.

Hi, good morning. This is Susan on for Tim. I have a couple questions. First question, given that you now have a timeline estimate for the pivotal Wolfram Syndrome trial, what can you tell us about the potential trial parameters and just how have your discussions with the FDA gone? And I'll follow up with my second question. Thanks very much.

This is Camille. As, you know, we have indicated, based actually on the Helios data in AMX35 for Wolfram syndrome and the very encouraging results out to 48 weeks, we are advancing the clinical development of 35 for Wolfram and plan to initiate our focus pivotal trial second half of 2026. pending, of course, FDA alignment. And we're actively seeking that alignment now, not only with the FDA, but also we are engaging a number of additional stakeholders, clinicians who treat people with Wolfram syndrome, researchers who study the disease, as well as the Wolfram community itself. And we're seeking alignment across all those stakeholders.

Thank you. Sorry to keep coming back to this, but you've mentioned a couple times already that you typically see a ramp in enrollment when all trial sites are activated, but rates have been steady. Why do you think this is? Would you characterize this more as a system-wide issue or specific to the lucidity trial?

Yeah, I don't think I would characterize this as a system-wide issue or an issue, really. I think just as we're updating our projections, we're trying to be as accurate as we possibly can. And given the current rate, we expect Q1 of the coming year. I'd remind that still enrolling a phase three trial in less than a year, which, you know, I think is a good timeline for a phase three overall.

Your final question comes from Ananda Ghosh with HC Wainwright.

Hi, guys. Thanks for taking my question. I have two, one from Lucidity and the other from the ALS program. So maybe the first question, you know, how is the level two or three weighed in for the composite scale? And, you know, is there a way to kind of like the nocturnal and the diurnal rates differ? And how is that kind of taken care of? And the other question you might have discussed beforehand, but Just to reiterate, how are prior therapies handled like GLP-1 agonist?

Yeah, thank you, Ananda. So two important questions. So first, coming off of five prior trials of the vexatide in people with BVH that showed statistically significant and clinically meaningful reductions in hypoglycemic events, the goal really here is replication. So to try to enroll a similar patient population, collect the events in the same way, etc., So, for the primary outcome, level two events are done by finger stick blood glucose, and level three is an e-diary that's adjudicated by an expert committee. So, that's how the data are collected. People can collect those during the day or during the night. Now, people also have CGMs on, which have continuous monitoring. And so, you know, obviously we will be looking at both. In the Phase 2b trial where they used the 90 milligram dose that we're using in the Phase 3, there were significant reductions both as measured by the finger stick as well as by the CGM day and night. But again, our goal really here is with replication, so we're trying to keep things as consistent as possible. In terms of use of GLP-1 receptor agonists or really any therapeutic that could alter blood glucose, we have a washout period before people can be randomized into the study so that we don't have things that could affect people's blood glucose levels, given that, of course, that is a key part of this study.

Great, thanks. Maybe just one question on this is that how are those level two or three weighed in the composite scale? How are they weighted? Are they weighted equally?

Yes, they're weighted equally.

The next question on the ALS program, how are you measuring the CalPAN and NFL levels in terms of, and also given the short trial length, what magnitude of NFL change might be practically feasible?

Yeah, so the calpain, I'd say we're measuring kind of different points in the pathway. So we're certainly working to measure mRNA, you know, in the CSF. You know, we are also looking at measures of calpain activity, including things like Spectrum Breakdown Product 145 or SBDP 145, which is a specific protein cleavage fragment that calpain makes and is, you know, an element of, you know, calpain activity. And then as you mentioned downstream, looking at markers of axonal degeneration like neurofilament, you know, to kind of see that downstream effect of potential calpinic inhibition. I'd say in initial study, we don't quite know yet what the kinetics of changes in those markers, you know, might be. In our preclinical work, we've seen, you know, changes on multiple of those markers, which certainly makes us encouraged, but we'll have to see clinically, you know, how that bears out.

Great. Thank you, Liz.

There are no further questions at this time. If you have any follow-up questions, please reach out to the company. This concludes today's conference call. Thank you for joining. Have a great rest of your day.