Jnana Therapeutics Announces Dosing of First Participant in Phase 1b Clinical Trial in Individuals With PKU

Jnana Therapeutics recently announced the first participant has been dosed in its Phase 1b clinical trial of JNT-517 in individuals with phenylketonuria (PKU). JNT-517 is a small molecule inhibitor of the phenylalanine (Phe) transporter SLC6A19 and is in development as a potential first-in-class oral treatment for PKU.

“Dosing the first individual with PKU with JNT-517 is an important next step toward potentially improving the quality of life and health for people living with PKU,” said George Vratsanos, MD, CMO, and Head of R&D for Jnana Therapeutics. “I’m thrilled to have joined Jnana at this critical point in the PKU program’s progression.”

The Phase 1b study is a randomized, double-blind, placebo-controlled trial evaluating the safety, tolerability, pharmacokinetics, and effect on plasma and urinary Phe of JNT-517 over a four-week period in individuals with PKU. The study expects to enroll 28 participants aged 18 to 65 diagnosed with PKU at clinical sites in the US and Australia. For more information about the study, please see clinicaltrials.gov (NCT05781399).

“New treatments are needed that address all genotypes, especially the classical, or severe, form of PKU. JNT-517 offers a promising new approach, with the potential to reduce elevated plasma Phe levels across all levels of disease severity, and has demonstrated positive results with compelling proof of mechanism in a Phase 1a study,” said John Throup, PhD, Senior Vice President & Head of Development at Jnana Therapeutics. “I’d like to thank the PKU community and clinical investigators for their partnership in initiating this study.”

Jnana recently reported topline data from the Phase 1a portion of the study in 64 healthy individuals showing that JNT-517 resulted in dose-dependent increases in urinary Phe​ across single and multiple ascending dose cohorts, consistent with increased urinary Phe excretion in individuals with loss-of-function mutations in SLC6A19. JNT-517 was also safe and well tolerated at all dose levels studied.

On behalf of the company, Cary O. Harding, MD, Professor of Molecular and Medical Genetics at Oregon Health & Science University School of Medicine, will deliver an oral presentation on August 31 titled Safety, Tolerability and Proof of Mechanism in Healthy Volunteers for JNT-517, a First-in-Class SLC6A19 Inhibitor for the Treatment of Phenylketonuria (Abstract 564) at the Society for the Study of Inborn Errors of Metabolism (SSIEM) Annual Symposium 2023, which takes place from August 29 – September 1 in Jerusalem, Israel.

PKU is a rare inherited metabolic disorder caused by a deficiency of the enzyme phenylalanine hydroxylase (PAH). This enzyme is required for the breakdown of phenylalanine (Phe), an amino acid found in all protein-containing foods. When PAH is deficient or defective, Phe accumulates to abnormally high levels in the blood. If left untreated, toxic levels of Phe in the blood can result in progressive and severe neurological impairment and neuropsychological complications. The SLC transporter SLC6A19 is responsible for kidney reabsorption of Phe back into the bloodstream, and the inhibition of SLC6A19 offers a novel, oral approach for the treatment of PKU by facilitating urinary excretion of excess Phe.

JNT-517 is a selective small molecule inhibitor of the phenylalanine transporter SLC6A19 that has the potential to be a first-in-class oral therapy used to treat any person with PKU, regardless of age or genotype. JNT-517 acts at a novel, cryptic allosteric site to block kidney reabsorption of Phe and offers a promising new approach to reduce blood Phe levels. The US FDA granted JNT-517 Rare Pediatric Disease Designation in late 2022.

Jnana Therapeutics is a clinical-stage biotechnology company leveraging its next-generation RAPID chemoproteomics platform to discover medicines for highly validated, challenging-to-drug targets to treat diseases with high unmet needs. Jnana is focused on developing first- and best-in-class therapies to treat a wide range of diseases, including rare diseases, immune-mediated diseases, and cancer. Jnana’s wholly owned lead program, JNT-517, which targets an allosteric site on the phenylalanine transporter SLC6A19, is a potential first-in-class oral approach for the treatment of PKU, a rare genetic metabolic disease. Located in Boston, Jnana brings together scientific leaders in small molecule drug discovery and development, a highly experienced management team, and the backing of leading life science investors Bain Capital Life Sciences, RA Capital Management, Polaris Partners, Versant Ventures, Avalon Ventures, Pfizer Ventures, and AbbVie Ventures. For more information, visit www.jnanatx.com.