Amylyx Pharmaceuticals 2026 Q3 Earnings Call

Good morning, and thank you all for joining us today to discuss our third 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 developments, the impact thereof and the expected timing thereof, and statements regarding our cash runway.

Actual events and results could differ materially from those expected 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.

Thank you, and good morning, everyone. It has been a momentous period for Amylyx. In the third quarter, we reported positive top-line results from the phase III LUCIDITY trial of avexitide, an investigational first-in-class GLP-1 receptor antagonist in participants with post-bariatric hypoglycemia, or PBH, following Roux-en-Y gastric bypass surgery. Fueled by the strength of this data, we completed an equity offering to support our launch readiness efforts to potentially deliver the first-ever approved therapy for PBH in 2027. Our pipeline development efforts with avexitide and our other programs remain strong as well, which Josh will talk about later in the call. As we reflect back on what has already been a milestone year for Amylyx, we are proud of our team's strong execution across the three key objectives for avexitide that we outlined in the first quarter.

In the third quarter, we continued to make substantial progress toward achieving each of them, and we now look ahead to another potential milestone year in 2027. Our first objective for 2026 was to execute on the phase III LUCIDITY trial of avexitide in people with PBH following Roux-en-Y gastric bypass surgery. in August, we reported positive top-line results from the pivotal phase III LUCIDITY trial. Avexitide demonstrated consistent, highly statistically significant, clinically meaningful reductions in hypoglycemic events across all endpoints, with a favorable safety profile. We were pleased to learn that these data were accepted as a late-breaking oral presentation at the upcoming ObesityWeek 2026 annual meeting on November 15.

As we have spent more time engaging with the PBH community and sharing the top-line data, our conviction in the significant unmet need and market opportunity has grown, with many physicians reacting positively to the strength of the LUCIDITY data. Our second objective was to execute on our NDA submission efforts. Our team has been actively preparing the submission, and we remain on track to submit our NDA to the FDA by the end of this year. Our third objective was to execute on our launch readiness efforts for avexitide, anticipating a potential 2027 approval and launch as the first-ever approved treatment for PBH. We have an experienced commercial and medical affairs leadership team in place, and our efforts this year have given us a strong understanding of the patient journey for people with PBH and the healthcare professionals who care for them.

Building on the momentum generated from the LUCIDITY results, and supported by the additional capital we recently raised, we are investing in the capabilities, infrastructure, and team needed to support a successful launch. We believe we have the opportunity to potentially change practice in PBH, a debilitating disease which to date has had no approved therapies. It is this opportunity, informed by the stories of the many people with PBH we have heard from, that will continue to drive our team to execute on our objectives with precision and urgency. We look forward to an exciting year-end and another potential transformational year in 2027. With that, I'll turn the call over to Camille to discuss the LUCIDITY results in more detail, our NDA submission, and our field medical team efforts.

Thank you, Justin, and good morning all. PBH is a chronic metabolic condition characterized by recurrent and often debilitating hypoglycemia that can lead to cognitive impairment, confusion, and in some cases, seizures or loss of consciousness. The condition can have a profound impact on daily life, with patients often structuring their lives around the constant risk of a hypoglycemic event and facing challenges maintaining their independence, employment, and family responsibilities. In one study, more than 90% of individuals with PBH describe themselves as living with a disability, underscoring the profound impact the condition can have on quality of life. Endocrinologists consistently describe PBH as one of the most challenging conditions they manage. Despite this burden, there are currently no FDA-approved therapies.

LUCIDITY met its pre-specified primary endpoint, demonstrating a 55% reduction in the composite rate of level 2 and level 3 hypoglycemic events compared to placebo, with a P-value of 0.000003. The study also met all secondary endpoints with consistent, highly statistically significant, and clinically meaningful reductions across level 2 events measured by self-monitoring of blood glucose, level 2 events measured by continuous glucose monitoring, and independently adjudicated level 3 events. Importantly, for people living with PBH, preventing even one level 2 or level 3 hypoglycemic event can have a meaningful impact on daily life. Furthermore, the American Diabetes Association recognizes hypoglycemia as a potential medical emergency. Against this backdrop, we believe the consistency, statistical strength, and clinical meaningfulness of the LUCIDITY results show its potential. LUCIDITY is the sixth clinical trial of avexitide in PBH, and all of those trials generated statistically significant results.

In addition, LUCIDITY is the largest and longest study of avexitide conducted to date. Alongside the efficacy results, avexitide demonstrated a favorable safety profile, consistent with that observed across the clinical development program to date. Avexitide was generally well tolerated, the majority of adverse events were mild to moderate, and there were no serious adverse events deemed related to avexitide treatment. More than 90% of the participants completed the 16-week double-blind treatment period, and all eligible participants entered the ongoing open-label extension portion of the trial. Additionally, our expanded access program is ongoing. Our field medical team has been focused on actively facilitating scientific exchange around the LUCIDITY data. They have established a strong presence, engaging directly with a substantial number of healthcare professionals to answer questions about the data and gain insights regarding the unmet need and patient journey in PBH.

Across these interactions, they continue to hear that awareness of PBH among specialists is high, recognition of the serious consequences in PBH is growing, and endocrinologists see a significant need for an FDA-approved treatment option, given that there are currently no approved therapies. These discussions reinforce our belief that avexitide has the potential to be the first FDA-approved treatment to address a significant unmet need in PBH. In addition, we are pleased that the LUCIDITY results will be presented to the medical community on November 15 at ObesityWeek, results that we believe will continue to demonstrate the consistency and strength of the dataset and the overall potential of avexitide to change practice in PBH. Our team remains focused on executing our planned NDA submission by year-end. As a reminder, avexitide has both Breakthrough Therapy and Orphan Drug designations from the FDA.

With that, I'll now turn over the call to Dan.

Thank you, Camille, and good morning, everyone. Bolstered by the strength of the phase III LUCIDITY data, and with additional capital, we have transitioned from launch planning to executing on our launch readiness roadmap. Our continued engagement with the PBH community has reinforced our belief that this indication represents a significant market opportunity with a substantial unmet need. We are investing in the team and capabilities needed to realize the long-term potential of avexitide if approved. As we prepare for a potential launch in 2027, our efforts are focused on three key areas. First, we are applying our growing understanding of the PBH market and the patient journey to inform our go-to-market plans. This includes our ongoing claims analysis work, additional market research, and direct engagement with healthcare professionals as well as patients.

These efforts help validate the patient population size and provide valuable insights into where patients with PBH are being treated. Second, we are expanding our disease state education campaign, uncoverpbh.com, with the goal of increasing recognition and understanding of PBH across the broader clinical community. This campaign has been well received and reached a broad number of endocrinologists, bariatric surgeons, and people living with PBH. Third, we are scaling our commercial organization and infrastructure. The full commercial leadership team is now in place, and we are making key hires across marketing, market access, patient services, and commercial operations. We are also investing in capabilities needed for a successful launch. More broadly, we continue to see increasing recognition of PBH across the medical community and healthcare system. Just last month, a PBH-specific ICD-10 code went into effect, which reflects the growing awareness of PBH within the medical community.