NV354
preclinicaldrug program · high · Thu Jan 01 2026 00:00:00 GMT+0000 (Coordinated Universal Time)
Treat mitochondrial complex I-related neurodegeneration and primary mitochondrial disease by bypassing mitochondrial dysfunction and supporting energy metabolism.
Orally bioavailable succinate prodrug with brain uptake, studied in animal models including Ndufs4 knockout mice for Leigh syndrome, rotenone-induced Parkinson disease model, and fluoroacetate intoxication model.
Preclinical publication in 2026 showing effects in mitochondrial complex I deficiency models.
NV354 prevented brain stem lesion development, attenuated neuronal loss and glial activation, reduced ROS levels, delayed ataxia scores, improved body weight development, and partially alleviated motor symptoms/metabolic decompensation in a rotenone model. In fluoroacetate intoxication, it alleviated brain complex I-linked oxidative phosphorylation impairment but did not counteract cardiac toxicity at the tested dose.
KL1333
phase 2drug program · high · Wed Jan 01 2025 00:00:00 GMT+0000 (Coordinated Universal Time)
Treat primary mitochondrial disease by improving fatigue, functional strength, endurance, and energy metabolism.
Oral small molecule intended to normalize the NAD+:NADH ratio critical for ATP production; evaluated in Phase 1a/1b SAD/MAD studies and an ongoing Phase 2 pivotal efficacy study referenced as informed by earlier trial results.
Ongoing Phase 2 pivotal efficacy study; prior Phase 1a/1b and drug-drug interaction studies completed or registered.
Phase 1a/1b results reported KL1333 was safe and well tolerated, with dose-dependent gastrointestinal side effects, and supported potential efficacy based on improvements in fatigue and functional strength/endurance.
PROMIS Fatigue Mitochondrial Disease Short Form
exploratorybiomarker · medium · Wed Jan 01 2025 00:00:00 GMT+0000 (Coordinated Universal Time)
Create a primary mitochondrial disease-specific patient-reported outcome measure for fatigue assessment in clinical trials.
Qualitative concept elicitation interviews and cognitive interviews in adults with genetically confirmed primary mitochondrial disease, mapping fatigue concepts to PROMIS Fatigue item bank items.
Nine-item PROMIS Fatigue Mitochondrial Disease Short Form developed with demonstrated content validity; future longitudinal psychometric studies planned.
The study identified tiredness, muscle weakness/fatigue, exhaustion, lack of energy, and mental fatigue as frequent fatigue characteristics, and produced a nine-item short form judged relevant and understandable by participants.
NeuroSTAT
phase 2drug program · medium
Reduce secondary brain injury after traumatic brain injury by targeting mitochondrial permeability transition.
Cyclosporine formulation evaluated as a neuroprotective therapy in traumatic brain injury, including the Phase Ib/IIa Copenhagen Head Injury Ciclosporin trial.
Phase Ib/IIa clinical evidence reported positive effects on injury biomarker levels in severe traumatic brain injury patients.
NeuroSTAT displayed positive effects on injury biomarker levels in patients with severe traumatic brain injury enrolled in the Copenhagen Head Injury Ciclosporin trial.
