Voyager Therapeutics has chosen a lead development candidate for its superoxide dismutase 1 (SOD1)-mutated amyotrophic lateral sclerosis (ALS) gene therapy programme.
ALS is a progressive neurodegenerative disease which sees motor neurons atrophy and die, leading to loss of the ability to speak, move, eat and, ultimately even breathe.
Voyager expects to file an investigational new drug (IND) application with the US Food and Drug Administration for the candidate in mid-2025.
The company’s SOD1-ALS lead candidate brings together a potent siRNA construct to reduce the expression of SOD1 with an IV-delivered, blood-brain barrier-penetrant TRACER capsid.
In a study on non-human primate, the candidate showed 73% reduction of SOD1 in cervical spinal cord motor neurons after a single intravenous dose in cynomolgus macaques.
It also showed strong knockdown of SOD1 across all levels of the spinal cord and motor cortex.
Additionally, the candidate indicated an ability to transduce neurons as well as astrocytes, two cell types that are believed to have an important role in ALS.
Voyager hopes to present further data on the candidate at an upcoming scientific conference.
In a data shared earlier at the 2022 American Society of Gene and Cell Therapy (ASGCT) annual meeting, another Voyager SOD1-ALS preclinical candidate raised survival by a median of 152 days in a G93A mouse model, with survival in some animals going beyond 430 days.
Voyager CEO Alfred W. Sandrock said: “Our SOD1-ALS program is one of several TRACER-powered gene therapy programmes we expect to see advance to IND in 2025.
“We believe our development candidate could represent a significant advancement in the treatment of SOD1-mutated ALS by offering the potential for durable SOD1 knockdown with a single IV administration.
“SOD1 is a validated target, and we plan to utilise established cerebrospinal fluid and plasma biomarkers in early clinical studies to efficiently achieve potential proof of concept.”