管理層發言
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. 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 three 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 five 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 described 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 two 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% from 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 three 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.
分析師問答
We will pause momentarily to assemble our roster. Your first question will come from Seamus Fernandez of Guggenheim.
I have a couple of questions. Could you update us on when the last patient visit was? What are the key factors that need to be completed to lock the database? Are there specific areas of core focus, or do you need all of the sites fully aligned to lock the database? Second, I realize you may not be able to provide specific numbers, but can you provide color on how the Early Access Program is progressing? Are patients being recruited into the EAP, and how would you characterize demand for that program at this point?
Great, Seamus. For the last patient visit and preparations for database lock and top-line data: we announced we completed enrollment in mid to late March. The study has a 16-week double-blind period, which brings us to about mid to late July for last visits. The team is executing a number of activities, including data cleaning and verification to ensure everything matches up, because the database is locked once for the core double-blind period. The team is being very diligent in that regard. As we said, we expect top-line data in late August or early September. Regarding the Early Access Program, we are excited to have an EAP for people living with PBH. The initial phase of the EAP is for those individuals in LUCIDITY who have completed the double-blind period and the open-label extension and then had the opportunity to roll into the EAP. It is also open to individuals who participated in prior avexitide trials, many of whom are at other centers that need to be activated to participate in the EAP. The EAP is a separate study with its own protocol. We are still in early days, enthusiasm to participate is strong, and we will provide updates as the program progresses.
Your next question will come from Joseph Thome of TD Cowen.
I'm not sure if you can answer this, but regarding the patient population enrolled in Phase III, does it look similar to the prior Phase II experience? Any comments on that? Second, can you remind us what mechanisms were in place during the study to monitor compliance with injections to ensure patients received recommended doses throughout the study?
Thank you. We designed LUCIDITY with the Phase II studies in mind, which showed highly successful and statistically significant outcomes. Participants enrolled in LUCIDITY are very consistent with the populations from the Phase II and Phase IIb trials. Our Amylyx team conducting the study rigorously assessed eligibility before enrollment, and we are very confident and pleased with execution from day one. Regarding study drug compliance, compliance was monitored throughout the study, and we are pleased with those metrics.
I'll add that trial conduct and compliance start with selecting the right clinical trial sites. We were rigorous in choosing sites that could recruit appropriate participants and had strong clinical trial experience. We paid particular attention during the run-in period to ensure participants met inclusion and exclusion criteria—especially the requirement of three events in three weeks including one Level 3 event—and that they would be reliable study participants. Throughout the study, our team maintained close oversight and monitoring with the clinical sites to ensure continued compliance with the protocol and dosing.
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? Does LUCIDITY have enough sleeve gastrectomy patients to support a compelling subgroup analysis? If the FDA restricts the label, what study design, enrollment size, and timeline would be needed to add sleeve patients? Second, on commercial opportunity: how does the 160,000 prevalence estimate translate into a realistic five-year treated population?
Mike, thank you. Regarding the label, since we have not yet seen the Phase III results or submitted an NDA, it's early to know specifics. Our view today is that PBH has a common pathophysiology regardless of the surgery that led to it—an exaggerated GLP-1 response driving hypoglycemic events. Most avexitide studies, including LUCIDITY, enrolled people with PBH after Roux-en-Y gastric bypass surgery; that was an inclusion criterion in LUCIDITY. The Phase IIb trials allowed other surgeries and showed avexitide appeared to work regardless of surgery type. As we prepare the NDA and discuss with FDA, two paths could emerge: one where the label covers PBH regardless of surgery, which is what we will strongly advocate for, and another where the FDA could restrict the label to Roux-en-Y patients if it focuses on the Phase III population. If the latter occurs, we would consider an efficient supplemental study to demonstrate efficacy in other surgery types; showing similar effects should not be overly burdensome because avexitide can show effects in a single dose. On the prevalence breakdown, Stanford prevalence work estimates that of the 160,000 people with PBH in the U.S., about 120,000 had Roux-en-Y gastric bypass leading to PBH. So even in a narrower label scenario at launch, the population would be substantial. We would aim to run an efficient study to broaden the label if needed. I'll pass the commercial question to Dan.
Thanks, Justin. On the commercial front, our market research and claims-based analyses have identified centers—academic and other settings—with concentrated PBH patient populations. Some centers report 50 to 60 patients, some up to 70, and others potentially 100 patients. We will focus on those centers at launch because we know patients are already there and have been identified by KOLs and endocrinologists who have expressed intent to treat. As our educational efforts scale and we engage the broader endocrinology community, we expect uptake to continue to grow. The prevalent population estimate remains 160,000, and we are confident in that number.
Your next question will come from Geoffrey Meacham with Citi.
Two quick questions. First, in pricing and reimbursement discussions, do you expect differentiation between Level 2 and Level 3 events shown in the study? Second, beyond Phase III, are you done with other filing elements such as preclinical and CMC?
For Level 2 and Level 3, these events often travel together. The ADA defined Level 2 as less than 54 mg/dL because below that threshold the brain is significantly deprived of glucose and patients may experience serious events such as seizures, loss of consciousness, or severe confusion. It's uncommon to see Level 2 events without Level 3 events and vice versa. We have been preparing the NDA throughout the year and view the 16-week double-blind LUCIDITY outcome as the final piece of the NDA that needs to be completed. Regarding pricing, I'll pass that to Dan.
Geoff, PBH is a dangerous condition with no approved medications. When developing pricing strategy, we will review relevant analogs across rare and rare endocrinology conditions. Following the top-line LUCIDITY results, we'll initiate formal pricing research and consider those data and peer analogs to shape our approach.
Your next question will come from Marc Goodman with Leerink Partners.
As you have reviewed where patients are, can you help us understand the concentration of patients? You mentioned some sites have 50 to 60, some have 70, some up to 100—what percent of the 160,000 are concentrated in those sites? Also, what should we expect the placebo response to be in this study?
We continue to refine our understanding using claims-based analyses from multiple databases, which point us to centers with concentrated patient populations. Our medical affairs colleagues, including MSLs, have engaged customers to validate the claims-based analyses. As we get closer to potential launch, we will share our go-to-market plans for how we will engage these centers.
Regarding placebo expectations: we have had five highly successful avexitide trials in PBH to date, with Phase II trials showing statistically significant and clinically meaningful reductions in both Level 2 and Level 3 events. LUCIDITY is designed to replicate those Phase II studies and we powered the study conservatively, at least 90% power, using modest effect size assumptions and a conservative placebo rate assumption. We do not know the specific placebo rate in LUCIDITY—the Phase III is the first pivotal study in PBH—but prior trials have not demonstrated a large placebo effect. Patients enrolling in the trial continue to experience events despite doing everything they can to minimize them, given the fear of hypoglycemia.
To provide additional context, the PREVENT Phase II crossover data suggest about a 30% difference on means between active and placebo, though medians in some analyses showed less difference. We chose conservative assumptions for LUCIDITY. The study was powered at 90% to detect a 35% treatment effect with the ability to accommodate up to a 50% placebo effect, though we have not seen evidence of such a placebo effect in prior trials. For reference, Phase II results included a 55% reduction in the Level 2 and Level 3 composite hypoglycemic events versus placebo in some analyses, which illustrates why we feel the study is well powered even using conservative assumptions.
Your next question will come from Rami Katkhuda with LifeSci Capital.
For LUCIDITY, which secondary endpoints will be included in the top-line release and which do KOLs view as most important? Also, can you provide additional color on the second research collaboration with Gubra and the type of endocrine indication or target you are pursuing?
We are eager to share top-line data. We plan to release data consistent with typical rare disease Phase III top-line presentations. Please stay tuned for the specific secondary endpoints included in the top-line release.
We enjoyed working with Gubra on AMX0318 and appreciate their peptide expertise. The second collaboration will screen and develop peptide candidates for another rare endocrine disease with significant unmet need. This aligns with our focus on rare diseases with serious unmet needs. As top-line data are shared, you can expect us to present typical data for a top-line release. KOLs view the composite endpoint of Level 2 and Level 3 hypoglycemia as clinically meaningful; both levels are significant medical events, and any impact on these events would be substantial clinically.
Your next question will come from James Condulis with Stifel.
On the commercial front, as you've done more work, what analogs are you using to shape a launch trajectory? Do you worry about a concentrated initial bolus of patients at key centers and then a slower expansion to other centers, or do you expect more steady uptake given the patient numbers?
For launch trajectory, we'll focus on centers with known patients at launch because that's where existing patients are concentrated and where KOLs and endocrinologists have identified patients. Our research shows high intent among endocrinologists to treat PBH. We expect to educate and align both medical and commercial colleagues at these centers, and then expand into the broader endocrinology community as our disease-state education progresses. We see a building market over time rather than a single one-time bolus that exhausts demand.
Your next question will come from Graig Suvannavejh with Mizuho.
If you get positive data and approval, how should we think about the competitive landscape over a five- to ten-year period? There aren't many companies focused on PBH today, but how should we expect uptake curves and potential competition to evolve?
We view the pathophysiology of PBH as driven by an exaggerated GLP-1 response, which makes avexitide a well-targeted approach. To date, we have not seen other agents demonstrate a similar profile. If approved, avexitide would be the first therapy specifically approved for PBH, and we do not currently see other programs that have demonstrated comparable efficacy profiles.
We believe in the mechanism, which is why we started development on the long-acting AMX0318. That program came out of our collaboration with Gubra. Our primary focus is avexitide, but we plan to continue innovating with AMX0318 as a potential longer-acting option.
Can I quickly follow up on AMX0318? What formulations are being considered?
AMX0318 resulted from screening many peptides to identify an optimized GLP-1 receptor antagonist with strong preclinical properties. From a formulation perspective, typical injectable options are available, such as vial and syringe, autoinjectors, or pens. Based on formulation design for avexitide and AMX0318 to date, we do not see technical hurdles to implementing those delivery options.
Your next question will come from Jason Gerberry with Bank of America.
In your filings, I believe you disclosed a total of $35 million in CMO payment commitments through 2028 for avexitide. In the event of a positive Phase III readout, is current manufacturing scale sufficient for commercial launch, or would a positive readout trigger additional CMO capacity obligations? Also, any guidance on when we might expect an update on regulatory interactions regarding the Phase III trial design for AMX0035 in Wolfram syndrome and openness to accelerated approval?
We are proceeding with manufacturing preparations in line with commercial launch planning. We do make commitments to secure supply and capacity and expect to continue doing so as we move toward launch. Regarding AMX0035 for Wolfram syndrome, we are encouraged by week 96 data showing stabilization or improvement across glycemic measures and vision, consistent with earlier timepoints. Wolfram syndrome is multifactorial, involving diabetes-like symptoms and visual and sensorimotor deficits, and patients often face life-limiting complications. We are continuing to work on Phase III design considerations to determine the most efficient way to demonstrate efficacy in this rare, complex disease. We remain excited by the data and will share updates on regulatory interactions as appropriate.
Your next question will come from Ananda Ghosh with H.C. Wainwright.
From KOL discussions, avexitide use has been highlighted in certain surgeries beyond bariatric procedures, such as gastrectomy or upper GI surgeries related to cancer. What are you hearing from KOLs about those uses? Second, what is the development plan for a long-acting avexitide relative to avexitide from a commercial perspective? Third, does a dedicated ICD-10 code change the payer conversation, and what are the company's efforts to address diagnosis as a barrier to penetration?
Great questions. On avexitide use in other surgery-induced hypoglycemias, KOLs have noted cases such as gastrectomy or esophagectomy for cancer leading to similar hypoglycemic conditions. In the Phase IIb trial, individuals with gastrectomy or esophagectomy due to cancer responded well to avexitide. We believe the mechanism is similar—an exaggerated GLP-1 response—so these surgical etiologies are of interest for future study. This is also a significant unmet need in many Asian countries due to higher rates of gastric and esophageal cancers. For AMX0318, we are in IND-enabling studies; as that progresses, we will outline the development plan. We selected molecules with favorable drug-like and manufacturing properties. For diagnosis and the ICD-10 code, I'll pass to Dan.
As Camille mentioned earlier, CMS and CDC published the 2027 ICD-10 code files in June. A specific code for post-bariatric hypoglycemia becomes effective October 1st, which recognizes PBH in the broader medical community. ICD-10 codes are helpful for tracking and epidemiology. From a payer perspective, an ICD-10 code is not required for reimbursement, and patients can be identified today through claims analyses without a specific code. However, the new code will support broader recognition, epidemiology, and awareness, which we view as positive.
On diagnosis, our market research indicates PBH awareness and diagnosis are already relatively high among endocrinologists. Nonetheless, there are education gaps, in part because there have been no FDA-approved treatments. That is why we launched our disease state education campaign. These educational efforts will continue and are an important part of our strategy to improve diagnosis and awareness ahead of potential approval.
Your final question will come from Christopher Chen with Baird.
Can you characterize recent interactions with FDA surrounding the NDA? Do you plan additional interactions before submission? And for Dan: assuming positive data and approval, how soon could you launch following approval, and what are the primary gating factors to launch?
Thank you, Chris. We do not discuss detailed contents of our interactions with FDA publicly. As part of avexitide's breakthrough therapy designation, we have had consistent interactions with the agency, including review of the LUCIDITY protocol. We are making great progress preparing the NDA elements, and when the core 16-week data set is available, those data will be included in the NDA. We continue to plan for a potential launch in 2027.
On launch timing, we are excited about the Phase III LUCIDITY results and have guided toward a launch in 2027. We have made key hires across medical affairs, market access, marketing, and commercial operations and our launch preparations are on track. Primary gating factors will include final database lock, regulatory review and approval, manufacturing readiness and supply, pricing and reimbursement planning, and continued education and engagement with the endocrinology community and specialty centers.
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.