Voyager Therapeutics, Inc., a clinical-stage gene therapy company developing life-changing treatments for severe neurological diseases, has announced the selection of VY-HTT01, a clinical candidate for the treatment of Huntington’s disease. 

Huntington's disease is a fatal, inherited neurodegenerative disease that results in the progressive decline of motor and cognitive functions caused by an expansion mutation in the huntingtin, or HTT, gene.  VY-HTT01 is composed of an adeno-associated virus (AAV) capsid and proprietary transgene that harnesses the RNA interference pathway to selectively knock down the production of HTT messenger RNA (mRNA).  Direct delivery of VY-HTT01 to the brain with a one-time administration could potentially slow or halt the progression of this uniformly fatal disease.  Preclinical pharmacology and toxicology studies are now underway with VY-HTT01 to support filing of an investigational new drug (IND) application in 2018.

“We systematically and thoroughly optimized the AAV capsid and transgene before selecting VY-HTT01 as the lead clinical candidate for Huntington’s disease with scientists at Sanofi Genzyme, as part of our research alliance,” said Dinah Sah, Ph.D., chief scientific officer at Voyager.  “In preclinical models, a single administration of VY-HTT01 was well-tolerated and resulted in robust and widespread knockdown of HTT messenger RNA in disease-relevant regions of the non-human primate central nervous system.  The extent of HTT mRNA suppression (greater than 50%) and high precision and efficiency of primary microRNA processing in these preclinical studies supported the selection of VY-HTT01 as our lead clinical candidate.  Pre-IND safety studies are now underway in order to advance VY-HTT01 to Phase 1 clinical trials.  In addition, as part of our candidate selection process, we carried out extensive optimization of the vector genome resulting in a configuration that provided excellent yield and genome integrity for manufacturing scale-up of VY-HTT01 using Voyager’s baculovirus AAV manufacturing process in insect-derived cells.”

“CHDI Foundation is delighted to be collaborating with Voyager, a leader in developing gene therapy programs for severe neurological diseases,” said Robi Blumenstein, president of CHDI Management, Inc.  “The selection of VY-HTT01 as their lead clinical candidate is a significant milestone that brings us an important step closer to a clinical trial of a therapeutic for Huntington’s disease.”