JNT-517 demonstrated sustained, dose-dependent pharmacodynamic effects and was safe and well tolerated in healthy volunteers

Phase 1b study is ongoing in individuals with PKU

BOSTON, August 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 that additional data from its Phase 1a clinical trial of JNT-517 in healthy volunteers were presented at the Society for the Study of Inborn Errors of Metabolism (SSIEM) Annual Symposium 2023. JNT-517 is a first-in-class, oral, allosteric inhibitor of the phenylalanine (Phe) transporter SLC6A19 that Jnana is developing for the treatment of phenylketonuria (PKU). The data were presented by Cary O. Harding, M.D., study investigator and Professor of Molecular and Medical Genetics at Oregon Health and Science University School of Medicine.

The Phase 1a study enrolled 64 healthy adults in a randomized, double-blind, placebo-controlled trial to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of JNT-517 across single (SAD) and multiple (MAD) ascending dose cohorts.

The data presented at SSIEM demonstrated: 

  • Dose-dependent increases in 24-hour urinary excretion of SLC6A19 amino acid substrates were observed in SAD doses of 25mg, 50mg, 100mg, and 170mg and MAD doses of 25mg BID and 75mg BID. 
  • JNT-517-driven aminoaciduria was sustained over 14 days across MAD cohorts with a greater than 10-fold increase in total Phe excretion in the 75mg BID dose at day 14.  Elevations in urinary excretion of amino acids remained consistent throughout the 14-day dosing interval.
  • As expected in healthy volunteers, no clinically significant changes in plasma amino acid levels were observed following JNT-517 dosing. The ongoing Phase 1b study will assess the impact of JNT-517 on plasma Phe levels in individuals with PKU. 
  • Treatment with JNT-517 was safe and well tolerated at all dose levels studied, with no serious adverse events. 

“The compelling proof of mechanism data for JNT-517 confirms that blockade of SLC6A19 can dramatically increase excretion of Phe,” said Dr. Harding. “This may offer a new oral treatment approach for individuals with PKU across all ages and genotypes, especially those with classical PKU for whom new therapeutic options are urgently needed.” 

“Based on these positive data, we continue to rapidly advance JNT-517. We recently dosed the first participant in our Phase 1b study in individuals with PKU and look forward to announcing topline data in the first half of 2024,” said George Vratsanos, M.D., Chief Medical Officer and Head of R&D at Jnana Therapeutics. “Further, these findings support the potential evaluation of JNT-517 in additional metabolic disorders characterized by high neutral amino acids and demonstrate clear clinical validation of our RAPID platform’s ability to identify novel binders for therapeutically important targets.”

Phase 1b Clinical Trial Ongoing

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 dosed over a four-week period in individuals diagnosed with PKU. The study dosed its first participant in August 2023 and expects to enroll 28 individuals aged 18 to 65 at clinical sites in the United States and Australia. For more information about the study, please see clinicaltrials.gov (NCT05781399).

About JNT-517

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 PKU

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.

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/X and LinkedIn.

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