repinatrabit (JNT-517) / Otsuka - LARVOL DELTA

A Trial to Examine if Repinatrabit is Processed Differently in Adults With Reduced Liver or Kidney Function Compared to Adults With Normal Liver and Kidney Function (clinicaltrials.gov) - P1 | N=32 | Recruiting | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Metabolic Disorders • Phenylketonuria • Rare Diseases • Renal Disease

A Trial to Examine the Interaction of Repinatrabit With Ethinyl Estradiol/Norethindrone, Metformin,Carbamazepine, Rosuvastatin, and Methotrexate When Administered Together (clinicaltrials.gov) - P1 | N=48 | Recruiting | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. | Trial completion date: Jun 2026 ➔ Nov 2026 | Trial primary completion date: Jun 2026 ➔ Nov 2026

Trial completion date • Trial primary completion date

A Trial to Examine if Repinatrabit is Processed Differently in Adults With Reduced Liver or Kidney Function Compared to Adults With Normal Liver and Kidney Function (clinicaltrials.gov) - P1 | N=32 | Not yet recruiting | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

New P1 trial • Metabolic Disorders • Phenylketonuria • Rare Diseases • Renal Disease

First-in-Human, Multiple Part Clinical Study of JNT-517 in Healthy Participants and in Participants With Phenylketonuria (clinicaltrials.gov) - P1/2 | N=163 | Completed | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. | N=111 ➔ 163

Enrollment change • First-in-human • Metabolic Disorders • Phenylketonuria • Rare Diseases

A Phase 2 Study of JNT-517 in Adolescent Participants With Phenylketonuria (clinicaltrials.gov) - P2 | N=14 | Completed | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. | Recruiting ➔ Completed | N=10 ➔ 14

Enrollment change • Trial completion • Metabolic Disorders • Phenylketonuria • Rare Diseases

How [14C]-JNT-517 is Absorbed, Broken Down, and Removed From the Body After a Single Oral Dose in Healthy Male Participants (clinicaltrials.gov) - P1 | N=8 | Completed | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

New P1 trial

First-in-Human, Multiple Part Clinical Study of JNT-517 in Healthy Participants and in Participants With Phenylketonuria (clinicaltrials.gov) - P1/2 | N=111 | Completed | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. | Active, not recruiting ➔ Completed | Trial completion date: Dec 2025 ➔ Jul 2025

First-in-human • Trial completion • Trial completion date • Metabolic Disorders • Phenylketonuria • Rare Diseases

A Long-Term Study of JNT-517 in Participants With Phenylketonuria (clinicaltrials.gov) - P3 | N=240 | Recruiting | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. | N=45 ➔ 240

Enrollment change • Metabolic Disorders • Phenylketonuria • Rare Diseases

A Phase 2 Study of JNT-517 in Adolescent Participants With Phenylketonuria (clinicaltrials.gov) - P2 | N=10 | Recruiting | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. | Trial completion date: Feb 2026 ➔ May 2026 | Trial primary completion date: Dec 2025 ➔ May 2026

Trial completion date • Trial primary completion date • Metabolic Disorders • Phenylketonuria • Rare Diseases

A Study to Evaluate the Long-Term Safety and Efficacy of JNT-517 in Participants With Phenylketonuria (clinicaltrials.gov) - P3 | N=45 | Recruiting | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Metabolic Disorders • Phenylketonuria • Rare Diseases

A Trial to Examine the Interaction of Repinatrabit With Ethinyl Estradiol/Norethindrone, Metformin,Carbamazepine, Rosuvastatin, and Methotrexate When Administered Together (clinicaltrials.gov) - P1 | N=48 | Recruiting | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open

A Study to Evaluate the Safety and Efficacy of JNT-517 in Participants With Phenylketonuria (PKU) (clinicaltrials.gov) - P3 | N=120 | Recruiting | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. | Trial completion date: Dec 2027 ➔ Apr 2028 | Trial primary completion date: Nov 2027 ➔ Mar 2028

Trial completion date • Trial primary completion date • Metabolic Disorders • Phenylketonuria • Rare Diseases

A Trial to Examine the Interaction of Repinatrabit With Ethinyl Estradiol/Norethindrone, Metformin,Carbamazepine, Rosuvastatin, and Methotrexate When Administered Together (clinicaltrials.gov) - P1 | N=48 | Not yet recruiting | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

New P1 trial

Clinical Efficacy and Safety Data in Adolescents Treated with Repinatrabit for Phenylketonuria (ACMG 2026) - P2, P3 | No abstract available

Clinical • Metabolic Disorders • Phenylketonuria • Rare Diseases

JNT517-301: A Phase 3 Study of JNT-517 in Participants with Phenylketonuria (clinicaltrialsregister.eu) - P2/3 | N=38 | Recruiting | Sponsor: Otsuka Pharmaceutical Development & Commercialization Inc.

New P2/3 trial • Metabolic Disorders • Phenylketonuria • Rare Diseases

Design of a Randomized, Double-Blind, Placebo-Controlled, Phase 3, Efficacy and Safety Trial of Repinatrabit in Adults with Phenylketonuria (ACMG 2026) - P3 | "Participants with a history of pegvaliase treatment must have at least a 4-week washout before screening... This Phase 3, randomized, placebo-controlled, 52-week trial will provide pivotal efficacy and safety data on the use of repinatrabit in adults with PKU. Enrollment criteria will enable the recruitment of a population with a broad range of disease severity and treatment history. Sponsored by Otsuka Pharmaceutical Development and Commercialization, Inc."

Clinical • P3 data • Metabolic Disorders • Phenylketonuria • Rare Diseases • SLC6A19

A Study to Evaluate the Safety and Efficacy of JNT-517 in Participants With Phenylketonuria (PKU) (clinicaltrials.gov) - P3 | N=120 | Recruiting | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. | Trial primary completion date: Nov 2026 ➔ Nov 2027

Trial primary completion date • Metabolic Disorders • Phenylketonuria • Rare Diseases

A Study to Evaluate the Safety and Efficacy of JNT-517 in Participants With Phenylketonuria (PKU) (clinicaltrials.gov) - P3 | N=120 | Recruiting | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Metabolic Disorders • Phenylketonuria • Rare Diseases

First in human clinical study of a novel drug JNT-517 to assess its safety and tolerability in healthy volunteers (ANZCTR) - P1 | N=91 | Completed | Sponsor: CTI Clinical Trial and Consulting Services Australia Pty Ltd. | Recruiting ➔ Completed

Trial completion • Metabolic Disorders • Phenylketonuria • Rare Diseases

Safety, Tolerability and Proof-Of-Mechanism in Healthy Volunteers for JNT-517, a First-In-Class SLC6A19 Inhibitor for the Treatment of Phenylketonuria (SSIEM 2023) - "JNT-517 is a safe and well-tolerated novel SLC6A19 inhibitor, which effectively increases the excretion of neutral amino acids including Phe in urine and warrants investigation as a potential therapeutic candidate for PKU."

Clinical • Metabolic Disorders • Phenylketonuria • Rare Diseases • SLC6A19

Engineering and immobilization of imine reductase enable chemoenzymatic synthesis of SLC6A19 inhibitor JNT-517. (PubMed, Bioresour Technol) - "This biocatalytic system was successfully integrated into the chemoenzymatic synthesis of SLC6A19 inhibitor JNT-517, where the enzymatically produced (R)-N-cyclopropylpiperidin-3-amine was efficiently converted to JNT-517 in three chemical steps, demonstrating promising potential for industrial-scale applications. Protein engineering and enzyme immobilization technology endow IRED with superior catalytic performance, stability, and reusability, thereby enabling sustainable bioprocessing for industrial applications."

Journal • SLC6A19

First-in-Human, Multiple Part Clinical Study of JNT-517 in Healthy Participants and in Participants With Phenylketonuria (clinicaltrials.gov) - P1/2 | N=135 | Active, not recruiting | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. | Trial completion date: Jul 2025 ➔ Dec 2025 | Trial primary completion date: Jun 2025 ➔ Sep 2025

Trial completion date • Trial primary completion date • Metabolic Disorders • Phenylketonuria • Rare Diseases

A Phase 2 Study of JNT-517 in Adolescent Participants With Phenylketonuria (clinicaltrials.gov) - P2 | N=10 | Recruiting | Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Metabolic Disorders • Phenylketonuria • Rare Diseases

GSC002874, a highly potent inhibitor of SLC6A19, for treatment of phenylketonuria (ENDO 2025) - "For the classic PKU cohort accounting for over 60 percent of cases, the only approved drug is pegvaliase; however, it is associated with inconvenient dosing and side effects...In an PAH pR408W PKU mouse model with its mouse SLC6A19 replaced by human orthologue, GSC002874 significant decreased phenylalanine level in plasma at lower dosage that of JNT-517...GSC002874 also displayed good safety window in 14-day toxicology study in rats. GSC002874 is under active IND-enabling studies and expected to enter clinic in early 2026."

Genetic Disorders • Metabolic Disorders • Phenylketonuria • Rare Diseases • SLC6A19

GSC002874, a highly potent inhibitor of SLC6A19, for treatment of phenylketonuria (ENDO 2025) - "For the classic PKU cohort accounting for over 60 percent of cases, the only approved drug is pegvaliase; however, it is associated with inconvenient dosing and side effects...In an PAH pR408W PKU mouse model with its mouse SLC6A19 replaced by human orthologue, GSC002874 significant decreased phenylalanine level in plasma at lower dosage that of JNT-517...GSC002874 also displayed good safety window in 14-day toxicology study in rats. GSC002874 is under active IND-enabling studies and expected to enter clinic in early 2026."

Genetic Disorders • Metabolic Disorders • Phenylketonuria • Rare Diseases • SLC6A19