Jnana Therapeutics Reports Positive Topline Results from Phase 1a Clinical Study of JNT-517, a Potential First-in-Class Oral Treatment for PKU
JNT-517 demonstrated proof of mechanism and was safe and well tolerated in healthy volunteers
Results support advancement to Phase 1b study in individuals with PKU; study now open for enrollment
BOSTON, May 31, 2023 – Jnana Therapeutics, a clinical-stage biotechnology company leveraging its next-generation chemoproteomics platform to discover medicines for challenging-to-drug targets, today announced positive topline results from the Phase 1a clinical trial of JNT-517 in healthy volunteers. Data from the study indicate that JNT-517 was safe and well tolerated with no serious adverse events and demonstrate compelling proof of mechanism.
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 phenylketonuria (PKU). SLC6A19 is responsible for kidney reabsorption of Phe back into the bloodstream, and the inhibition of SLC6A19 offers a novel approach for the treatment of PKU by facilitating urinary excretion of excess Phe. In the study, 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.
“We are encouraged by the positive results from the Phase 1a portion of our first-in-human trial of JNT-517. These initial data are consistent with human genetics and preclinical data and confirm that JNT-517 inhibits SLC6A19 and results in the increased excretion of Phe at doses that are safe and well tolerated,” said Joanne Kotz, Ph.D., co-founder and CEO of Jnana Therapeutics. “Jnana’s RAPID platform enabled the identification of JNT-517, a first-in-class inhibitor acting at a cryptic allosteric site, validating RAPID’s ability to successfully identify leads for difficult-to-drug targets.”
Jnana’s ongoing Phase 1 program of JNT-517 was initiated in Australia in the fourth quarter of 2022. The Phase 1a enrolled 64 healthy adults in a randomized, double-blind, placebo-controlled study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of JNT-517. JNT-517 was safe and well tolerated at all dose levels studied; the study also demonstrated comparability of suspension and tablet formulations. The company plans to present the full results and analyses at a future scientific meeting.
“Demonstration of clinical proof of mechanism represents a major milestone for JNT-517. We look forward to partnering with the PKU community as we proceed into the Phase 1b portion of the trial in individuals with PKU, bringing us a step closer to potentially providing a first-in-class oral therapy for the treatment of PKU,” said John Throup, Ph.D., Senior Vice President & Head of Development at Jnana Therapeutics.
The Phase 1b is a randomized, double-blind, placebo-controlled study and is expected to begin dosing in the third quarter. It is enrolling participants with PKU at clinical sites in the United States and Australia. For more information about the study, please see clinicaltrials.gov (NCT05781399).
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, 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 U.S. Food and Drug Administration granted JNT-517 Rare Pediatric Disease Designation in late 2022.
About Jnana Therapeutics
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, please visit www.jnanatx.com and follow us on Twitter and LinkedIn.