AMX0035, developed by Amylyx, is a combination of two compounds — sodium phenylbutyrate (PB) and tauroursodeoxycholic acid (TUDCA) — that work together to minimize cellular mechanisms linked to cell death in amyotrophic lateral sclerosis (ALS). 

The first patient has already been dosed in a Phase 2 clinical trial assessing AMX0035’s safety, tolerability, and effectiveness in treating ALS. 

How AMX0035 works

AMX0035 is designed to reduce nerve cell death by blocking key cellular death pathways that originate in cellular compartments called the mitochondria and endoplasmic reticulum.

Mithocondrial and endoplasmic reticulum stress are key mediators of both nerve cell death and neuroinflammatory processes. Mitochondria are the energy production centers of the cell, and the endoplasmic reticulum can be thought of as the “quality control centers.” Both are in constant communication and are vital for cell survival. When one of the two compartments fails to function properly, the resulting stress can kill the cell or lead to inflammation. Brain cells are particularly sensitive to this stress, which has been implicated in the development of neurodegenerative diseases such as ALS.

AMX0035 was designed to target both the mitochondria and endoplasmic reticulum simultaneously by blocking stress and creating a balance between them.

AMX0035 in clinical trials

Both elements of AMX0035, sodium phenylbutyrate and tauroursodeoxycholic acid, have been used clinically and were shown to be safe. They also showed preliminary signs of effectiveness in laboratory and animal studies.

A preclinical study has shown that AMX0035 limited cell death and neurotoxic inflammation in different ALS models.

A Phase 2 clinical trial (NCT03127514) called CENTAUR has completed recruiting 132 ALS participants to assess the safety and effectiveness of AMX0035. During the randomized, double-blind, placebo-controlled trial, patients will receive either AMX0035 or a placebo twice daily for 24 weeks. Primary objectives include the measure of decline in function according to the ALS functional rating scale, the incidence of adverse events, and the number of participants in each group who are able to remain on treatment until planned discontinuation. Secondary objectives include changes in muscle strength, blood and imaging-based biomarkers, slow vital capacity, a measure of lung function, survival, need for tracheostomy, and hospitalizations during the study. The trial is expected to be completed in December 2019.

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