cysteamine-pantetheine disulfide (TTI-0102) / VA San Diego Healthcare System, Thiogenesis Therap - LARVOL DELTA

Pilot Study of TTI-0102 in Cystinosis (clinicaltrials.gov) - P2 | N=6 | Not yet recruiting | Sponsor: Thiogenesis Therapeutics, Inc.

New P2 trial • Rare Diseases • Renal Disease

Mitochondrial DNA A3243G variant-associated MELAS: Recent advances in clinical trials, therapeutic interventions, and disease-modifying strategies. (PubMed, Intractable Rare Dis Res) - P3 | "Key advances include: i) regulatory approval of high-dose taurine supplementation (9-12 g/day), which achieved complete prevention of stroke-like episodes in 60% of participants in a phase III trial; ii) phase IIb data (company-reported) indicating that sonlicromanol (KH176) showed signals of improvement in cognition, mood, and fatigue, supporting progression to a phase III registrational trial (KHENERFIN, NCT06451757); iii) ongoing trials of zagociguat and TTI-0102 targeting vascular dysfunction and oxidative stress; iv) KL1333, a novel NAD+ modulator, in phase II evaluation (FALCON trial); and v) promising preclinical gene-based approaches-including mitochondria-targeted TALENs, DdCBE base editors, and mitoARCUS nucleases-demonstrating heteroplasmy shifting in patient-derived cells and animal models, though direct clinical applicability to m.3243A>G MELAS requires further investigation. The therapeutic landscape for MELAS is evolving from symptomatic care..."

Journal • Review • Cardiovascular • CNS Disorders • Fatigue • Gene Therapies • Metabolic Disorders

A Dose-ranging Study of TTI-0102 in Adults and Children With Leigh Syndrome Spectrum (LSS) (clinicaltrials.gov) - P2 | N=18 | Not yet recruiting | Sponsor: Thiogenesis Therapeutics, Inc. | Trial completion date: Sep 2026 ➔ Sep 2027 | Trial primary completion date: Sep 2026 ➔ Jun 2027

Trial completion date • Trial primary completion date • Metabolic Disorders

A Study to Assess TTI-0102 vs Placebo in MELAS Patients (clinicaltrials.gov) - P2 | N=9 | Completed | Sponsor: Thiogenesis Therapeutics, Inc. | Recruiting ➔ Completed | Trial completion date: Jun 2026 ➔ Jan 2026 | Trial primary completion date: Apr 2026 ➔ Jan 2026

Trial completion • Trial completion date • Trial primary completion date • Cardiovascular • CNS Disorders • Metabolic Disorders • TMB

Thiogenesis Therapeutics…reported that the U.S. FDA has granted Rare Pediatric Disease (RPD) designation to its lead candidate TTI-0102 for the treatment of Leigh syndrome, a serious mitochondrial disorder primarily affecting children. (StockTitan.net) - "Thiogenesis also noted that, since obtaining prior FDA IND clearance, it has refined the planned Phase 2 trial of TTI-0102 for the Leigh syndrome spectrum by integrating pharmacokinetic insights from its MELAS clinical program, and is completing final start-up activities before initiating the Phase 2 study."

FDA event • New P2 trial • Genetic Disorders

Thiogenesis Receives Confirmatory Guidance on IMPD for Pediatric MASH Phase 2a Clinical Trial in Europe and Core Patent Granted in EU (The Globe and Mail) - "Thiogenesis Therapeutics, Inc...announced that the Committee for Medicinal Products for Human Use ('CHMP') of the European Medicines Agency ('EMA') has provided scientific advice supporting the company's submission of an Investigational Medicinal Product Dossier ('IMPD') for a Phase 2a clinical trial in pediatric patients with metabolic dysfunction-associated steatohepatitis...In parallel with the clinical advancement of TTI-0102, Thiogenesis has recently been granted a European Union patent for its asymmetric disulfide prodrugs of cysteamine, titled 'Compositions for Controlled Release of Cysteamine and Systemic Treatment of Cysteamine Sensitive Disorders - PCT Pub No. WO2017161318.' This intellectual property establishes the company's competitive position in both mitochondrial and metabolic disease indications until 2038."

CHMP • New P2a trial • Patent • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

A Dose-ranging Study of TTI-0102 in Adults and Children With Leigh Syndrome Spectrum (LSS) (clinicaltrials.gov) - P2 | N=18 | Not yet recruiting | Sponsor: Thiogenesis Therapeutics, Inc.

New P2 trial • Metabolic Disorders

A Study to Assess TTI-0102 vs Placebo in MELAS Patients (clinicaltrials.gov) - P2 | N=12 | Recruiting | Sponsor: Thiogenesis Therapeutics, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • CNS Disorders • Metabolic Disorders

A Study to Assess TTI-0102 Vs Placebo in MELAS Patients (clinicaltrials.gov) - P2 | N=12 | Not yet recruiting | Sponsor: Thiogenesis Therapeutics, Inc. | Trial completion date: Oct 2025 ➔ Jun 2026 | Initiation date: Nov 2024 ➔ Mar 2025 | Trial primary completion date: Sep 2025 ➔ Apr 2026

Trial completion date • Trial initiation date • Trial primary completion date • Cardiovascular • CNS Disorders • Metabolic Disorders

A Study to Assess TTI-0102 vs Placebo in MELAS Patients (clinicaltrials.gov) - P2 | N=12 | Not yet recruiting | Sponsor: Thiogenesis Therapeutics, Inc.

New P2 trial • Cardiovascular • CNS Disorders • Metabolic Disorders

Study of Cysteamine-pantetheine Disulfide (TTI-0102) in Mild to Moderate COVID-19 (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: Thiogenesis Therapeutics, Inc. | N=60 ➔ 0 | Trial completion date: Sep 2025 ➔ Sep 2024 | Not yet recruiting ➔ Withdrawn | Trial primary completion date: Jun 2025 ➔ Sep 2024

Enrollment change • Trial completion date • Trial primary completion date • Trial withdrawal • Acute Respiratory Distress Syndrome • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases

Study of Cysteamine-pantetheine Disulfide (TTI-0102) in Mild to Moderate COVID-19 (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: Thiogenesis Therapeutics, Inc. | Trial completion date: Jun 2023 ➔ Sep 2025

Trial completion date • Acute Respiratory Distress Syndrome • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases

Study of Cysteamine-pantetheine Disulfide (TTI-0102) in Mild to Moderate COVID-19 (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: Thiogenesis Therapeutics, Inc. | Trial completion date: Dec 2022 ➔ Jun 2023 | Initiation date: Jun 2022 ➔ Sep 2022 | Trial primary completion date: Sep 2022 ➔ Mar 2023

Trial completion date • Trial initiation date • Trial primary completion date • Acute Respiratory Distress Syndrome • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases

Study of Cysteamine-pantetheine Disulfide (TTI-0102) in Mild to Moderate COVID-19 (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: Thiogenesis Therapeutics, Inc.

New P2 trial • Acute Respiratory Distress Syndrome • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases

TTI-0102 for Veterans With TBI (clinicaltrials.gov) - P1/2; N=0; Withdrawn; Sponsor: VA Office of Research and Development; N=42 ➔ 0; Trial completion date: Sep 2023 ➔ Oct 2021; Not yet recruiting ➔ Withdrawn; Trial primary completion date: Sep 2023 ➔ Oct 2021

Enrollment change • Trial completion date • Trial primary completion date • Trial withdrawal • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder • BDNF • CRP • IL6

TTI-0102 for Veterans With TBI (clinicaltrials.gov) - P1/2; N=42; Not yet recruiting; Sponsor: VA Office of Research and Development; Trial completion date: Jun 2022 ➔ Sep 2023; Trial primary completion date: Jun 2022 ➔ Sep 2023

Trial completion date • Trial primary completion date • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder • BDNF • CRP • IL6

TTI-0102 for Veterans With TBI (clinicaltrials.gov) - P1/2; N=42; Not yet recruiting; Sponsor: VA Office of Research and Development; Initiation date: Jan 2021 ➔ Apr 2021

Trial initiation date • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder • BDNF • CRP • IL6

TTI-0102 for Veterans With TBI (clinicaltrials.gov) - P1/2; N=42; Not yet recruiting; Sponsor: VA Office of Research and Development; Trial completion date: Dec 2021 ➔ Jun 2022; Initiation date: Jul 2020 ➔ Jan 2021; Trial primary completion date: Dec 2021 ➔ Jun 2022

Trial completion date • Trial initiation date • Trial primary completion date • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder • BDNF • CRP • IL6

TTI-0102 for Veterans With TBI (clinicaltrials.gov) - P1/2; N=42; Not yet recruiting; Sponsor: VA Office of Research and Development

New P1/2 trial