ALBRIOZA Commercial Launch

Potential of AMX0035 in Wolfram syndrome Wolfram syndrome Ultra-rare disease, affecting ~5,000 people in U.S.,¹ with an estimated prevalence of 1 in 500,000 people worldwide. 2 Causes multi-system failure resulting in blindness, deafness, diabetes, ataxia, neurodegeneration, and typically death by early adulthood. Characterized as a prototypical disease of ER stress. Dysfunction of the WFS1 gene causes the accumulation of unfolded/misfolded proteins in the ER (referred to as ER stress); terminal ER stress and cell death in pancreatic B-cells and neuronal cells thought to be the mechanism of Wolfram syndrome development.³ Effect of AMX0035 in Preclinical Studies³ Improved WFS1 protein expression and increased insulin secretion in ẞ cells with the WFS1 variant (Figure) Inhibited cell death in ẞ cells with the WFS1 variant (Figure), ameliorated organelle dysfunction, mitophagy, ER stress JCI insIGHT Delayed onset of the diabetic phenotype in Wolfram syndrome mouse model KO, Ctrl: Baseline 500 800- 1000- 400- 2000- ## 800- 800- 0000 600- 300- 600- 1500- 600- 400- 200- KO, P+T: Baseline WT: Baseline KO, Ctrl: 1 month KO, P+T: 1 month WT: 1 month 400- 400- 1000- 100 **** 200- *** 200- 200- 500- 0- 20mM 2mM 2mM 20mM Ctrl P+T 0 2mM 20mM 2mM 0 30 20mM Ctrl P+T Ctrl P+T 1. U.S. Department of Health and Human Services. (n.d.). Wolfram syndrome. Genetic and Rare Diseases Information Center. Retrieved April 28, 2023, from https://rarediseases.info.nih.gov/diseases/7898/wolfram-syndrome. 2. U.S. National Library of Medicine. (n.d.). Wolfram syndrome. MedlinePlus. Retrieved April 28, 2023, from https://medlineplus.gov/genetics/condition/wolfram-syndrome/. 3. Morikawa et al. Front. Endocrinol., 25 March 2022, Sec. Diabetes: Molecular Mechanisms, Volume 13 - 2022, https://doi.org/10.3389/fendo.2022.849204 4. Kitamura RA, et al. JCI Insight. 2022;7(18):e156549. AMYLYX 31 60 min 90 120

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