VGM-R02b Glutaric Acidemia Type I (GA-1), IND submitted

Received FDA RPDD & ODD

Disease Biology

Due to glutaryl-CoA dehydrogenase (GCDH) deficiency, lysine, hydroxylysine and tryptophan cannot be correctly catalyzed, resulting in the accumulation of glutaric acid. Glutaric acid accumulation in the CNS is toxic and results in neurodegeneration.
Signs and Symptoms

Without proper treatment, acute encephalopathy crisis occurs in 87% of patients before 2 years old, with symptoms like macrocephaly, striatal dysfunction, hypotonia and even death.

Epidemiology/Prevalence

Global: ~1/100,000
China: >1/200,000

Available Care/Treatments

Lysine-free diet and carnitine supplementation.
Emergency treatment for acute encephalopathy crisis.

Vitalgen Strategy

Gene replacement by rAAV9 delivery of a functional glutaryl-CoA dehydrogenase (GCDH) transgene via intracerebroventricular (ICV) injection

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VGM-R02 in vivo PoC

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VGM-R02 Summaries

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Demonstrated dose dependent rescuing of GCDH KO mice under metabolic stress in a GA-1 mouse model
Clean safety profile in pre-clinical tox studies
CMC development of Ph1 clinical batch completed
In an IIT, VGM-R02 is well-tolerated as demonstrated >12 months after treatment of a pediatric GA-1 patient, with lowering of relevant biomarkers observed