Amylyx Pharmaceuticals (AMLX) Study Result summary

Overview and Disease Background

• Wolfram Syndrome is a rare, progressive, fatal monogenic disorder caused by WFS1 mutations, leading to multi-organ dysfunction, early mortality, and no approved therapies.

• The disease manifests as juvenile-onset diabetes, vision and hearing loss, ataxia, neurodegeneration, and diabetes insipidus, with median death at age 30.

• Wolfram Syndrome is a prototypical ER stress disorder; AMX0035/AMX35 targets ER stress and mitochondrial dysfunction to slow neurodegeneration.

• Preclinical studies showed AMX0035/AMX35 improved WFS1 protein expression, insulin secretion, cell viability, and delayed diabetes progression in models.

Study Design and Patient Population

• HELIOS is an open-label, single-arm Phase 2 trial with 12 participants aged 17–39, all receiving AMX0035/AMX35 for up to 96 weeks.

• Primary endpoint: change in C-peptide AUC during MMTT at 24 weeks, assessing pancreatic beta cell function.

• Secondary endpoints: hemoglobin A1C, time in target glucose range, and best-corrected visual acuity.

• Eleven participants met full genetic criteria and were included in the per-protocol analysis; one was analyzed separately.

• Median participant age was 25 years, with a median of 5 years since diagnosis; 83% were female.

Efficacy and Clinical Outcomes

• C-peptide response improved at 24, 36, and 48 weeks, indicating enhanced beta cell function, contrary to expected decline.

• Hemoglobin A1C levels improved or stabilized in most participants, reflecting better glycemic control.

• Time in target glucose range increased or remained stable for the majority, sustained across all measured weeks.

• Visual acuity showed stabilization or improvement in most participants, with some moving from legally blind to legally sighted.

• 100% of participants met responder criteria for both clinician and patient global impressions of change at all measured time points.