Amylyx Pharmaceuticals (NASDAQ:AMLX) executives told investors the company entered 2026 with a focus on advancing avexitide toward what could become the first FDA-approved therapy for post-bariatric hypoglycemia (PBH), while continuing early-stage work across its pipeline and maintaining a cash runway management said extends into 2028.
Avexitide’s pivotal trial: timeline, endpoint, and powering assumptions
Co-CEO Justin Klee said the company’s “top priority” is advancing avexitide, a GLP-1 receptor antagonist, in PBH. Management outlined three 2026 objectives: delivering top-line data from the Phase 3 LUCIDITY trial in Q3 2026, advancing NDA readiness, and strengthening launch readiness for a potential 2027 commercialization if approved.
Bedrosian said LUCIDITY is evaluating avexitide 90 mg once daily in individuals with PBH following Roux-en-Y gastric bypass surgery. The trial uses an FDA-agreed primary outcome: a reduction in the composite of level 2 and level 3 hypoglycemic events through week 16.
She said LUCIDITY was designed for replication based on five prior PBH trials with avexitide, which management said demonstrated statistically significant reductions in hypoglycemic events. Bedrosian highlighted a prior result in which avexitide 90 mg once daily led to a 64% least squares mean reduction versus baseline in the composite rate of level 2 and level 3 events (p=0.0031), and noted that a Phase 2 trial showed no placebo response. Despite that, the company modeled up to a 50% placebo effect and a 35% effect size versus placebo in its Phase 3 assumptions, which Bedrosian said was intended to be conservative and keep the study well powered.
Klee also said the recruitment phase of LUCIDITY is complete and the company expects to “fully complete enrollment this quarter,” with the final potential patients in screening and the last eligible participants expected to be randomized and dosed this month.
Open-label extension and study execution comments
Bedrosian said the trial’s open-label extension (OLE) is underway and that participants may enter the OLE immediately upon completion of the double-blind phase. When asked how many participants had rolled into the OLE, she said the company does not report details of an ongoing study, but added that management was pleased with participation and that participants are rolling over into the extension.
In response to analyst questions about trial execution and the run-in period, management emphasized that LUCIDITY’s inclusion criteria and design were informed by prior successful Phase 2 studies. Executives said discussions with sites have reinforced the severity and unmet need in PBH, describing hypoglycemic events as medical emergencies and highlighting physicians’ limited tools beyond medical nutrition therapy.
On trial duration and dietary factors, Bedrosian said participants receive training and are asked to reaffirm adherence to dietary guidelines intended to maintain consistency in medical nutrition therapy throughout the study. Management added it did not expect a waning drug effect and said avexitide’s safety profile has been “very good” across clinical and non-clinical studies.
Commercial and market preparation: prevalence estimate and ICD-10 discussion
Alongside clinical execution, management discussed ongoing commercial and medical affairs buildout. Klee said the company is making key hires, conducting market research with clinicians and people living with PBH, and developing disease education and market access strategies.
Based on published literature and claims analysis, management reiterated an estimate of approximately 160,000 people living with PBH in the U.S., out of more than 2 million people who underwent sleeve gastrectomy or Roux-en-Y gastric bypass over the last decade. Executives said claims work has also been used to better understand where patients are treated and to corroborate patient counts with centers.
When asked about patient concentration, the company said its data suggest a pattern typical of an orphan disease, with some centers caring for a concentrated pool of PBH patients and others seeing fewer. Management said this informs future deployment strategies if avexitide is approved.
Klee also noted growing awareness of PBH, citing that PBH is now on endocrinology board exams and that the company expects to “hear on a potential ICD-10 code this year,” with more expected in April. He said an ICD-10 code could help with identifying PBH patients in claims data and within health systems, while adding the company does not view an ICD-10 code as necessary for future reimbursement if avexitide is approved because it would be a take-home product covered through the pharmacy benefit.
Pipeline updates: AMX0318, AMX0114, and AMX0035
Management also provided updates on pipeline programs beyond avexitide.
- AMX0318: Klee said Amylyx and Gubra nominated AMX0318, a novel long-acting GLP-1 receptor antagonist, as a development candidate in January. Co-CEO Josh Cohen said IND-enabling studies are underway and an IND filing is targeted for 2027. Executives also discussed broader interest in GLP-1 antagonism beyond bariatric surgery, including hypoglycemia following surgeries for gastric or esophageal cancer and other gastrointestinal procedures, noting potential relevance outside the U.S. as well.
- AMX0114 (ALS): Cohen said AMX0114 received Fast Track designation and showed a favorable safety and tolerability profile in cohort 1 of the Phase 1 LUMINA trial, enabling progression to the next cohort. The company expects to present biomarker data from cohort 1 in the first half of the year and said cohort 2 enrollment is expected to be completed this month.
- AMX0035 (Wolfram syndrome): Cohen said the company continues to work with the FDA on a Phase 3 trial in Wolfram syndrome following long-term data from the Phase 2 HELIOS trial presented last year.
On avexitide tolerability, executives said tolerability has been “quite excellent” across studies to date, with few dropouts. They said injection site reactions, when they occurred, were generally mild and at a rate similar to placebo, and that anti-drug antibodies were rare and not associated with notable issues.
Financial results and cash runway
Chief Financial Officer Jim Frates said the company ended Q4 with $317 million in cash and marketable securities, compared with $344 million at the end of Q3. He said this capital provides an anticipated runway into 2028 to fund operations through expected milestones, including the LUCIDITY top-line readout in Q3 2026, potential FDA approval, and a potential 2027 commercial launch.
For Q4, Frates reported total operating expenses of $36.6 million, down 8% from the same period in 2024. R&D expenses were $21.2 million versus $22.9 million in Q4 2024, with the decrease primarily due to lower spending on AMX0035 in ALS and PSP, offset by increased avexitide development spending. SG&A expenses were $15.4 million versus $17.1 million in Q4 2024, driven primarily by lower consulting and professional services. Non-cash stock-based compensation was $6.4 million for the quarter, compared with $6.8 million a year earlier.
Frates also noted a $4 million milestone payment to Gubra tied to the selection and handover of AMX0318, which the company expects to reflect in R&D expense in its Q1 2026 income statement.
About Amylyx Pharmaceuticals (NASDAQ:AMLX)
Amylyx Pharmaceuticals, Inc is a biopharmaceutical company dedicated to developing treatments for rare and debilitating neurological diseases. Founded in 2013 and headquartered in Cambridge, Massachusetts, the company focuses on leveraging novel approaches to target cellular pathways implicated in neurodegeneration. Amylyx’s research platform centers on small-molecule therapies designed to protect neurons and support cellular health in patients with conditions that currently have limited or no disease-modifying treatment options.
The company’s lead product, AMX0035, is marketed under the trade name Relyvrio following U.S.
Featured Stories
- Five stocks we like better than Amylyx Pharmaceuticals
- The gold chart Wall Street is terrified of…
- America’s 1776 happening again
- Buy this Gold Stock Before May 2026
- I’m 70 With $1.5M: Would Converting $120K a Year to a Roth Be Smart or a Costly Mistake? (Ask An Advisor)
- ALERT: Drop these 5 stocks before the market opens tomorrow!
