Jaguar Gene Therapy Announces Target Genes for Initial Pipeline Programs in Severe Genetic Diseases

  • JAG101 is designed to address the root cause of Type 1 galactosemia by delivering the functional GALT gene to reduce multiple toxic metabolites
  • JAG201 is designed to address mutation or deletion of the SHANK3 gene, a leading autism candidate gene, by delivering SHANK3 gene replacement therapy
  • JAG301 is designed to produce functional beta cells in the pancreas and restore insulin secretion in Type 1 diabetes through transdifferentiation using the PAX4 gene

LAKE FOREST, Ill., Dec. 14, 2021 – Jaguar Gene Therapy, a company accelerating breakthroughs in gene therapy for sizeable patient populations suffering from severe genetic diseases, today announced additional details, including target genes, for its initial preclinical pipeline programs: JAG101 for Type 1 galactosemia; JAG201 for a genetic cause of autism spectrum disorder (ASD) and Phelan-McDermid syndrome and other severe neurodevelopmental disorders with a SHANK3 mutation or deletion; and JAG301 for Type 1 diabetes.

“We are excited to share more details around our initial pipeline programs, which aim to address the root cause of a range of severe genetic diseases in sizeable patient populations,” said Joe Nolan, CEO of Jaguar Gene Therapy. “The promising preclinical proof-of-concept data that has been generated in academic settings coupled with the significant unmet medical need, inspired us to pursue the development of potentially transformative therapies for patients and families suffering with devastating diseases, including Type 1 galactosemia, a genetic form of ASD, Phelan-McDermid syndrome and other severe neurodevelopmental disorders with a SHANK3 mutation or deletion, and Type 1 diabetes.”

JAG101 for Type 1 Galactosemia

Type 1 galactosemia is a severe genetic disease caused by mutations in the GALT gene, leading to a severe deficiency of the GALT enzyme that breaks down galactose, a simple sugar found in dairy and other foods including breast milk. The toxic buildup of galactose and other metabolites, including GAL-1p and galactitol, that result from GALT enzyme deficiency is life-threatening in newborns and leads to lifelong neurological, speech and behavioral complications, as well as primary ovarian insufficiency in girls and women. Newborn screening is in place in all 50 states of the United States due to the life-threatening consequences of the buildup of multiple toxic metabolites that results from GALT enzyme deficiency. No treatments are currently approved for galactosemia, and there is significant unmet medical need. The current standard of care – a galactose-restricted diet – is insufficient because the body naturally produces galactose, causing chronic exposure to multiple toxic metabolites that results in patients experiencing lifelong complications.

Jaguar is advancing JAG101, an investigational gene therapy currently in preclinical development that aims to deliver a gene replacement solution to address the root cause of Type 1 galactosemia by delivering the functional GALT gene via the AAV9 vector. Gene therapy offers to potentially reduce multiple toxic metabolites, bringing them closer to a normal level. The treatment is intended for younger patients, where there is urgency to potentially prevent lifelong complications. Jaguar has research agreements in place for the program with Emory University and the University of Utah, where encouraging preclinical proof-of-concept data was produced.

JAG201 for a Genetic Cause of Autism Spectrum Disorder and Phelan-McDermid Syndrome and Other Severe Neurodevelopmental Disorders with a SHANK3 Mutation or Deletion

Individuals can be diagnosed with ASD, Phelan-McDermid syndrome and/or other severe neurodevelopmental disorders if a mutation or deletion in the SHANK3 gene is present. Disorders that result from a SHANK3 mutation or deletion are associated with prefrontal lobe dysfunction, autism, moderate to severe intellectual disability, absent or severely delayed speech, and neurodevelopmental behavioral abnormalities among other characteristics. SHANK3 is a leading candidate gene thought to cause ASD. In the United States, approximately 30,000 individuals living with ASD have a SHANK3 mutation or deletion. Currently, there is no treatment available for disorders that result from a SHANK3 mutation or deletion. 

Jaguar is advancing JAG201, an investigational gene therapy currently in preclinical development that aims to deliver appropriate SHANK3 genetic function via the AAV9 vector to treat the root cause of the disease and rescue behavioral abnormalities​. The program is exclusively licensed from Broad Institute of MIT and Harvard, where encouraging preclinical proof-of-concept data was produced.

JAG301 for Type 1 Diabetes

Type 1 diabetes is an autoimmune disease that destroys beta cells, which are specialized cells in the pancreas that produce insulin. A lack of insulin results in the inability of cells to use glucose for energy and unregulated glucose levels in the blood, which can lead to long-term complications, including frequent hospitalizations, blindness, heart disease, stroke, kidney disease and nerve damage. No cure is available today, and treatment is based on diet, insulin injections and continuous glucose monitoring. In the United States, approximately 1.5 million individuals are living with Type 1 diabetes.

Jaguar Gene Therapy is advancing JAG301, an investigational AAV-based gene therapy currently in preclinical development that works to address the root cause of the disease by producing functional beta cells using the PAX4 gene to convert alpha cells to beta cells, a process called transdifferentiation. Jaguar has exclusively licensed the program from Tulane University, where encouraging preclinical proof-of-concept data was produced. Additionally, Jaguar has a research agreement in place with Tulane.

“The gene of interest targets for each of our programs were carefully selected based on promising scientific data from world-renowned academic institutions, giving us confidence that it’s possible to safely and effectively treat rare disease populations as well as larger disease states,” said Suku Nagendran, M.D., President of R&D at Jaguar. “There is significant unmet medical need across all our initial pipeline programs, and the combination of our cutting-edge science and unparalleled CMC (Chemistry, Manufacturing and Controls) capabilities positions us to deliver for the patients and families waiting for treatment options.”

The company will leverage its internal CMC expertise, its process sciences lab in Cary, North Carolina, and, once fully converted, its recently announced state-of-the-art gene therapy commercial manufacturing facility in Durham, North Carolina, in addition to existing contract development manufacturing organization (CDMO) partners to support all programs. Jaguar plans to use the latest technologies and purification techniques to increase product yields while reducing product impurities. The team’s experience in developing a scalable and commercially viable manufacturing process at the outset has guided the company’s approach to invest early and often in manufacturing and quality. In doing so, Jaguar aims to be on the leading edge of producing the purest and most efficacious gene therapy products in the world.

About Jaguar Gene Therapy

Jaguar Gene Therapy, LLC is dedicated to accelerating breakthroughs in gene therapy for patients suffering from severe genetic diseases including those that impact sizeable patient populations. The company is made up of a proven and growing team of experts with unparalleled CMC (Chemistry, Manufacturing and Controls), regulatory, clinical and commercial acumen who have first-hand experience in bringing novel gene therapy treatments to patients and their families. Committed to patient safety and product purity, Jaguar is rapidly advancing an initial pipeline of three programs targeting: 1) Type 1 galactosemia; 2) a genetic cause of autism spectrum disorder and Phelan-McDermid syndrome and other severe neurodevelopmental disorders with a SHANK3 mutation or deletion; and 3) Type 1 diabetes. The company continues to evaluate opportunities to expand its pipeline using the strength of the team and close relationships with numerous academic institutions. For more information, please visit www.jaguargenetherapy.com and follow Jaguar Gene Therapy on LinkedIn.


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