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Data presented at SSIEM 2024 Annual Symposium Twice-daily oral treatment with JNT-517 at 150mg dose delivered highly statistically significant mean blood phenylalanine reduction of 60% versus baseline in individuals with PKU JNT-517 was safe and well tolerated with no serious adverse events observed JNT-517 has been granted Orphan Drug Designation by the U.S. FDA for the treatment of PKU, as well as Orphan Designation by the European Commission and eligibility Sept. 04, 2024 -- Jnana Therapeutics, a clinical-stage biotechnology company leveraging its next-generation chemoproteomics platform to discover medicines for challenging-to-drug targets, today released results from the second-dose cohort of 150mg BID (twice daily) from its Phase 1/2 clinical trial of JNT-517 in adults with phenylketonuria (PKU). Both the 75mg and 150mg cohorts delivered clinically meaningful, statistically significant effects, and these results were presented at the Society for the Study of Inborn Errors of Metabolism (SSIEM) 2024 Annual Symposium in Porto, Portugal. JNT-517, a small molecule inhibitor of the phenylalanine (Phe) transporter SLC6A19, is being evaluated as a potential first-in-class oral treatment for PKU across all ages and genotypes. “Treatment with JNT-517 in individuals with PKU, regardless of disease severity, demonstrated rapid, clinically meaningful reductions in plasma Phe, the registrational endpoint for PKU, and was well tolerated with a favorable safety profile,” said George Vratsanos, M.D., Chief Medical Officer and Head of R&D at Jnana Therapeutics. “We are grateful to the study participants and highly encouraged by these results, which are prompting us to move quickly toward a registrational study.” JNT-517 is being studied in a randomized, double-blind, placebo-controlled trial in individuals with mild to severe, or classical, PKU. Following a 28-day screening period, study participants were randomized to 150mg BID of JNT-517 or placebo in the recently completed second-dose cohort. Importantly, all qualifying study participants were randomized without a run-in period to test for response to JNT-517. The 150mg BID cohort data presented at SSIEM were based on 18 participants, 11 dosed with JNT-517 and 7 dosed with placebo over 28 days, and demonstrated the following results: The 150mg BID dose of JNT-517 led to a statistically significant (p=<0.0001 vs. placebo) mean blood Phe reduction from baseline of 60% on average across days 14, 21, and 28 and a 58% reduction from baseline to day 28. This compares favorably to the previously studied 75mg BID dose, which led to a mean blood Phe reduction of 44% on average across days 14, 21, and 28 and a 51% reduction from baseline to day 28. Going forward, Jnana intends to use a measure of Phe reduction across multiple timepoints as it believes this is a more representative measure of drug effect. A rapid onset of effect was observed with statistically significant blood Phe reduction achieved within seven days after commencing dosing, which was sustained through the full 28 days of dosing. Mean (across days 14, 21, and 28) plasma Phe levels A robust response was observed across all participants irrespective of baseline blood Phe levels and prior PKU treatment. A mean baseline blood Phe of 920 μM and PAH genotypes indicated a majority of subjects had classical (severe) disease. Eight of 11 participants had previously tried sapropterin, and 1 out of 8 was deemed a responder to sapropterin. Seven of 11 participants had previously tried pegvaliase, and 0 out of 7 were deemed a responder to pegvaliase. JNT-517 was well tolerated with no serious adverse events, no clinically significant changes in laboratory parameters, and no clinically significant changes in plasma amino acids other than Phe observed, all consistent with the safety profile demonstrated in the 75mg BID cohort and Phase 1a healthy volunteer study. “These clinical results indicate that JNT-517 can drive a robust reduction in plasma Phe in individuals with high baseline Phe levels who have failed or had an inadequate response to the currently approved therapies,” said Nicola Longo, M.D., study investigator and Professor and Vice-Chair of Human Genetics at the University of California Los Angeles (UCLA) David Geffen School of Medicine. “JNT-517 has the potential to be a major new treatment option for PKU, particularly for those individuals with the most severe disease who currently lack effective treatment options.” On the basis of these positive results and recently granted regulatory designations from the FDA, the European Commission and EMA, Jnana plans to engage in discussions with U.S. and European regulators in the second half of 2024 with the goal of advancing JNT-517 directly into a pivotal Phase 3 study in early 2025. Jnana’s JNT-517 recently received Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) for the treatment of PKU, Orphan Designation from the European Commission, and eligibility to the European Medicines Agency (EMA) PRIME scheme for the treatment of hyperphenylalaninemia, which collectively reinforce JNT-517 as a potential new medicine for PKU, a disease that lacks adequate therapies and where 60% of individuals with PKU are not currently on any therapy. JNT-517 was granted Rare Pediatric Disease Designation by the FDA in September 2022 for the treatment of PKU. The Phase 1/2 clinical program includes a randomized, double-blind, placebo-controlled trial evaluating the safety, tolerability, pharmacokinetics, and effect on blood and urinary Phe of JNT-517 dosed over a four-week period in individuals diagnosed with PKU. The study dosed its first participant with PKU in August 2023 and is enrolling 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). JNT-517 is a selective small molecule inhibitor of the Phe 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. JNT-517 has received Rare Pediatric Disease Designation and Orphan Drug Designation from the FDA for the treatment of PKU, as well as Orphan Designation from the European Commission and has been granted eligibility to the EMA PRIME scheme for the treatment of hyperphenylalaninemia. 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 (hyperphenylalaninemia). 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. 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 and immune-mediated diseases. 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. Recently, Jnana announced that it has entered into an agreement to be acquired by Otsuka Pharmaceutical Co., Ltd., which is expected to close in the third quarter of 2024. For more information, please visit www.jnanatx.com and follow us on Twitter/X and LinkedIn. 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