Calico Life Sciences has received breakthrough therapy designation from the FDA for fosigotifator to treat vanishing white matter (VWM) disease, a rare, inherited neurological disorder.
Fosigotifator is an investigational, orally-active, brain penetrant, eIF2B activator. By targeting a translation initiation factor, it reduces enzymatic activity that leads to the chronic activation of the integrated stress response (ISR). In VWM disease, this chronic activation causes degeneration of white matter – the tissue responsible for transmitting signals between different brain regions.
Calico tested fosigotifator in preclinical disease models with VWM variations. The drug decreased the ISR in the brain and spinal cord, improved coordination, reduced movement problems, and extended lifespan. The company is now beginning a phase 1b/2 trial to evaluate safety and efficacy in adult, pediatric and infant patients. It will be the first time that an eIF2B is administered to people with VWM disease.