Manufacturing and analytical development for JLK-247 gene therapy

The National Institute of Neurological Disorders and Stroke awarded Phoenix Nest Inc. $1,492,329 on July 14, 2026, under the Extramural Research Programs in the Neurosciences and Neurological Disorders program (CFDA 93.853) to manufacture and develop analytical methods for JLK-247 gene therapy for Mucopolysaccharidosis Type IIIC (Sanfilippo Disease Type C).

Phoenix Nest Inc., a woman-owned small business, will produce a 500-liter cGMP lot of the JLK-247 gene therapy vector to support a Phase I clinical trial treating MPS IIIC patients. The manufacturing and analytical development work addresses an unmet medical need; MPS IIIC is a lysosomal storage disease caused by HGSNAT enzyme deficiency that results in heparan sulfate accumulation, progressive neurological deterioration beginning around age 3.5 years, and loss of verbal communication before age 15. Currently no treatments exist for MPS IIIC beyond supportive care. Gene therapy represents a promising approach to provide long-term therapeutic benefit. Phoenix Nest received FDA guidance supporting transition of the program to clinical intervention and requires the manufactured product to meet critical quality attributes of purity, potency, and sterility for clinical dosing.

Performance occurs in Brooklyn, New York, with work concluding by June 30, 2028.

Abstract

Lysosomal storage diseases (LSD) are rare and are an inherited metabolic disorder caused by defects in the cellular catabolic system. Mucopolysaccharidosis type iiic (MPS iiic or sanfilippo disease type C) is one such LSD that is caused by deficiency of the enzyme heparan sulfate acetyl COA: -glucosaminide N- acetyltransferase, (HGSNAT) essential for degradation of heparan sulfate, a repeating carbohydrate generally found attached to proteoglycans. This disease causes accumulation of heparan sulfate resulting in progressive and severe neurological deterioration early in life with little somatic features. The symptoms in patients with MPS iiic may present at an average age of 3.5 years of age with psychomotor developmental delays and behavioral problems. Before the age of 15 years verbal communication is often lost in patients with MPS iiic. Most lose the ability to walk between the 20 and 30 years of age. The condition is fatal by an average age of 34 years (range, 25-48). Enzyme replacement therapies are not an option since the protein is localized and bound to lysosomal membrane. There are currently no treatments available for MPS iiic. Individuals affected by MPS iiic are managed with supportive care, consultation with medical professionals from multiple disciplines, physical therapy, and pharmacological interventions to alleviate symptoms. Gene therapy represents a reasonable and promising approach to provide a meaningful and long-term therapeutic benefit for this population soon. We had a positive interaction with the FDA and received guidance for moving our program into the clinics. In preparation for the interventional study we need to manufacture a 500 L cgmp lot of JLK-247 gene therapy vector to treat MPS iiic patients. The product used for dosing clinical patients on a phase I trial is required to meet the critical quality attributes of being pure, potent and sterile. The product undergoes stringent testing to demonstrate its suitability for human dosing. The analytical testing itself needs to be developed and qualified prior to the release of material for dosing. Such standards require a well-regulated environment and the manufacturing is routinely performed by certified contract development and manufacturing organization (CDMO). Most of the work proposed in this application will be executed by contracted service providers as a fee for service. Producing sufficient JLK-247 by scaling up the manufacturing will put US a step closer to treating the patients suffering from this terrible disease.