PureTech Health gets US$11.4m to advance LYT-300

PureTech Health plc has been awarded up to $11.4 million from the US government to advance LYT-300 (oral allopregnanolone) for the treatment of Fragile X-associated Tremor Ataxia Syndrome. (FXTAS). The funds will support a Phase II study of LYT-300-

Developed using PureTech’s Glyph^TM technology platform, LYT-300 is an oral prodrug of endogenous allopregnanolone that is designed to overcome its poor oral bioavailability. PureTech completed a Phase 1 clinical trial of LYT-300 in 2022, which demonstrated oral bioavailability, tolerability and ?-aminobutyric-acid type A (GABA_A) receptor target engagement in healthy volunteers. Allopregnanolone is a positive allosteric modulator (PAM) of GABA_A receptors and has been shown to regulate mood and other neurological conditions. Unlike benzodiazepines, allopregnanolone can provide both transient and longer-term normalization of overactive neural circuits because it also acts at GABA receptors outside of synapses.

FXTAS, which was discovered by Dr. Randi Hagerman and her colleagues at the University of California, Davis, is a devastating neurological condition that is closely related to, but distinct from, Fragile X syndrome (FXS). Both conditions are the result of repeated elements in the Fragile X Messenger Ribonucleoprotein Gene 1 (FMR1) gene. While FXS is associated with intellectual disability and autism, FXTAS leads to neurodegeneration in otherwise normally developed, aging individuals who carry a premutation of the FMR1 gene. 

An exploratory, open-label trial of six men with FXTAS, evaluated IV-administration of allopregnanolone across multiple neuropsychological and emotional tests. In addition to being well-tolerated, allopregnanolone showed signals of pharmacologic benefit across multiple neurological endpoints, including the Behavioral Dyscontrol Scale, which measures executive, cognitive and motor function, and demonstrated improvement compared to baseline (p=0.009).[1] IV administration is not feasible in most indications, especially for a chronic therapy, and there remains a need for treatments that can address this debilitating condition. PureTech plans to evaluate LYT-300 in a placebo-controlled trial to demonstrate the safety, tolerability and efficacy of the drug in people with FXTAS.