Jaguar Gene Therapy to Launch First Pediatric Trial for Genetic Autism and Phelan-McDermid Syndrome

Jaguar Gene Therapy, a Lake Forest-based clinical-stage biotechnology company, has received the go-ahead from the U.S. Food and Drug Administration (FDA) to proceed with the dosing of pediatric patients in its Phase I clinical trial for JAG201. The trial will target a genetic form of autism spectrum disorder (ASD) characterized by SHANK3 mutations or deletions, as well as Phelan-McDermid syndrome. The company plans to begin dosing pediatric patients in the first quarter of 2025, with plans to expand the trial to adult patients thereafter.

Joe Nolan, CEO of Jaguar Gene Therapy, expressed his satisfaction with the FDA's decision, emphasizing the potential benefits of early intervention with the gene therapy. Nolan highlighted the company's preclinical data, which suggests that early administration of JAG201 could yield significant benefits. He also expressed hope that early success in pediatric patients could pave the way for broader applications of the therapy.

Dr. Alexander Kolevzon, Professor of Psychiatry and Pediatrics at the Icahn School of Medicine at Mount Sinai, echoed Nolan's sentiments. Kolevzon emphasized that addressing the underlying deficits caused by SHANK3 deficiencies during early development could offer greater potential benefits. He also noted the high unmet need among people living with Phelan-McDermid syndrome and anticipated a large number of eligible patients for the clinical trial.

JAG201 operates by delivering a functional SHANK3 minigene using an adeno-associated virus serotype 9 (AAV9) vector. The therapy targets neurons in the central nervous system and is administered via a one-time unilateral intracerebroventricular (ICV) injection. This method aims to transduce haploinsufficient neurons, restore proper SHANK3 levels, and ensure durable synaptic function. Proper synaptic function is crucial for learning, memory, and the maintenance of cognitive, communicative, social, and motor skills. The JAG201 program is licensed exclusively from the Broad Institute of MIT and Harvard.

The FDA has granted JAG201 Rare Pediatric Disease designation, which is reserved for products that treat serious and life-threatening rare pediatric diseases. This designation allows companies to receive a priority review voucher for a subsequent marketing application for a different product if the initially designated product is approved.

JAG201 has also received Fast Track designation from the FDA due to its potential to address the high unmet medical needs of patients with ASD and Phelan-McDermid syndrome, both of which involve SHANK3 mutations or deletions. The Fast Track status facilitates enhanced communication and collaboration between the FDA and drug developers, potentially speeding up the delivery of treatments to patients.

SHANK3 haploinsufficiency leads to synaptic dysfunction, disrupting communication between nerve cells. This condition reduces several key receptors and signaling proteins at excitatory synapses, impairing synaptic formation and function. Adequate synapse function is essential for all neuronal processing, including higher cognitive functions and learning.

Phelan-McDermid syndrome, also known as 22q13.3 deletion syndrome, is a rare genetic disorder with an estimated prevalence of 1 in 10,000. Genetic studies suggest that SHANK3 mutations may be present in approximately 0.5% to 0.69% of patients with ASD, translating to about 46,000 individuals in the U.S., including 10,000 pediatric patients. Among ASD patients with moderate to profound intellectual disabilities, the prevalence of SHANK3 mutations increases to 2.12%.

Jaguar Gene Therapy is dedicated to accelerating breakthroughs in gene therapy for severe genetic diseases affecting sizeable patient populations. The company's lead program focuses on neurodevelopmental disorders caused by SHANK3 haploinsufficiency. Jaguar also has pipeline programs targeting Type 1 galactosemia and Type 1 diabetes. The company’s leading investors include Deerfield Management Company, ARCH Venture Partners, and Eli Lilly and Company.