Jnana Therapeutics Reveals Positive Phase 1/2 Data for JNT-517 in Phenylketonuria, Paving Way for 2025 Pivotal Study

Jnana Therapeutics, a clinical-stage biotechnology company, has unveiled promising results from its Phase 1/2 clinical trial of JNT-517, a novel oral therapy for phenylketonuria (PKU). The trial's second-dose cohort, involving a twice-daily 150mg dose, showcased significant efficacy and safety, marking a substantial advancement in PKU treatment. These findings were shared at the Society for the Study of Inborn Errors of Metabolism (SSIEM) 2024 Annual Symposium in Porto, Portugal.

JNT-517 operates as a small molecule inhibitor targeting the phenylalanine (Phe) transporter SLC6A19. This mechanism is being explored as a potential first-in-class oral treatment for PKU, a genetic metabolic disorder characterized by the inability to break down Phe, an amino acid found in protein-containing foods. Elevated Phe levels can lead to severe neurological impairments if untreated. The innovative approach of JNT-517 involves inhibiting SLC6A19 to prevent kidney reabsorption of Phe, facilitating its excretion and reducing toxic blood levels.

The Phase 1/2 trial evaluated JNT-517 in adults with varying severities of PKU. The 150mg twice-daily dose cohort involved 18 participants randomized to receive either the drug or a placebo over 28 days. Results indicated a highly significant mean reduction in blood Phe levels by 60% from baseline, sustained across multiple time points up to day 28. This compares favorably with a previous 75mg dose cohort, which achieved a mean reduction of 44%.

Study participants demonstrated rapid responses, with significant reductions in blood Phe within seven days of commencing treatment. Importantly, these effects were consistent regardless of participants' baseline Phe levels or prior treatments. Many participants had previously tried other PKU therapies like sapropterin and pegvaliase, with limited success. JNT-517's robust efficacy in this population highlights its potential as a superior treatment option.

Safety data from the trial were equally encouraging. JNT-517 was well tolerated, with no serious adverse events reported. Laboratory parameters and plasma amino acid levels, aside from Phe, remained stable, reinforcing the drug's favorable safety profile seen in earlier studies.

Dr. George Vratsanos, Chief Medical Officer at Jnana Therapeutics, emphasized the significance of these findings, expressing gratitude towards the study participants and highlighting the company's commitment to advancing JNT-517 towards a registrational study. The compelling data and recent regulatory designations, including Orphan Drug Designation from the U.S. FDA and Orphan Designation from the European Commission, underscore JNT-517's potential to address the unmet needs in PKU treatment.

Study investigator Dr. Nicola Longo from UCLA highlighted JNT-517's potential as a major new treatment option, particularly for individuals with severe PKU who lack effective therapies. The promising results have spurred Jnana to engage with regulatory bodies in the U.S. and Europe, aiming to initiate a pivotal Phase 3 study in early 2025.

Jnana's clinical program includes a randomized, double-blind, placebo-controlled trial assessing JNT-517's safety, tolerability, pharmacokinetics, and impact on blood and urinary Phe over four weeks in PKU patients. The first participant was dosed in August 2023, with enrollment ongoing in the U.S. and Australia.

Jnana Therapeutics leverages its RAPID chemoproteomics platform to discover drugs for challenging targets. The Boston-based company, supported by prominent investors, is focused on developing innovative therapies for rare and immune-mediated diseases. JNT-517, targeting an allosteric site on SLC6A19, represents a novel approach to treating PKU, a condition with significant unmet medical needs.

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