NPT520-34 / EVER Pharma - LARVOL DELTA

EFFECTS OF NPT520-34 ON MITOCHONDRIAL DYSFUNCTION AND INFLAMMATORY PATHWAYS RELEVANT TO NEURODEGENERATIVE DISEASES (ADPD 2024) - "NPT520-34 also decreased superoxide production induced by rotenone or LPS, but not by piericidin A, imiquimod, or Pam3. NPT520-34 shows a selective ability to inhibit ROS production and NLRP3 inflammasome activation induced by Complex I inhibitors. These results suggest that NPT520-34 is neither a direct inflammasome inhibitor nor a simple antioxidant, but rather acts to maintain mitochondrial function by a direct action on Complex I. These beneficial actions on mitochondrial function may account for the robust actions of NPT520-34 in animal models of neurodegenerative diseases."

CNS Disorders • Metabolic Disorders • Movement Disorders • Parkinson's Disease • IL1B • NLRP3 • TNFA

CLINICAL AND PRECLINICAL EVALUATIONS OF NPT520-34, AN ORALLY ADMINISTERED SMALL MOLECULE UNDER DEVELOPMENT AS A DISEASE-MODIFYING THERAPEUTIC FOR NEURODEGENERATIVE DISORDERS (ADPD 2023) - P1 | "The combination of robust effects in animal models of neurodegenerative disease and the promising safety and pharmacokinetic results from initial clinical evaluations in healthy volunteers support the continued development of NPT520 -34 in PD and ALS."

Preclinical • Amyotrophic Lateral Sclerosis • CNS Disorders • Developmental Disorders • Immunology • Inflammation • Metabolic Disorders • Movement Disorders • Parkinson's Disease

NPT520-34 SELECTIVELY BLOCKS NLRP3 INFLAMMASOME ACTIVATION INDUCED BY COMPLEX I INHIBITORS OVER TYPICAL CANONICAL OR NONCANONICAL INFLAMMASOME STIMULI (ADPD 2023) - "Established inflammasome activators and Complex I inhibitors were applied to cel ls after pretreatment with NPT520 -34, inflammasome or K+ channel inhibitors, or the Complex I -bypassing quinone idebenone. Because the action of NPT520 -34 was selective for Complex I inhibition -induced NLRP3 inflammasome activation, we propose that NPT520 -34 likely does not block IL -1β secretion by directly inhibiting inflammasome component proteins. Instead, it may act indirectly by binding to Complex I to prevent recruitment and activation of the NLRP3 inflammasome at the mitochondrial membrane and/or the association of Kv1.3 with Complex I."

CNS Disorders • Metabolic Disorders • Movement Disorders • Parkinson's Disease • NLRP3

The clinical stage small molecule NPT520-34 improves disease-relevant endpoints in a preclinical transgenic mouse model of amyotrophic lateral sclerosis (Neuroscience 2022) - P1 | "A successful disease-modifying therapeutic will rectify multiple pathogenic mechanisms underlying progressive and complex neurological diseases. Taken altogether, our in vivo evaluations of NPT520-34 in transgenic mouse models have provided support for further clinical development of NPT520-34 as a disease-modifying therapeutic for Parkinson’s disease (NCT03954600) and amyotrophic lateral sclerosis (ALS) (granted FDA ODD status)."

Preclinical • Amyotrophic Lateral Sclerosis • CNS Disorders • Parkinson's Disease

NPT520-34 improves neuropathology and motor deficits in a transgenic mouse model of Parkinson's disease. (PubMed, Brain) - "These findings further suggest that NPT520-34 may have two complementary actions: (1) to increase the clearance of neurotoxic protein aggregates and (2) to directly attenuate inflammation. NPT520-34 treatment may thereby address two of the predominate underlying pathophysiological aspects of neurodegenerative disorders such as Parkinson's disease."

Journal • Preclinical • CNS Disorders • Immunology • Inflammation • Movement Disorders • Parkinson's Disease

[VIRTUAL] A PHASE 1 STUDY IN HEALTHY VOLUNTEERS WITH NPT520-34, A NOVEL THERAPEUTIC CANDIDATE FOR THE TREATMENT OF NEURODEGENERATIVE DISORDERS (AAT-ADPD 2020) - "Additional findings from this study will be presented. Conclusions The findingd from this clinical trial enable and support the continued development of NPT520-34 as a therapeutic candidate for the treatment of neurodegenerative disorders."

Clinical • P1 data

Neuropore completes phase 1 clinical trial in healthy volunteers with NPT520-34, a therapeutic candidate aimed at treating Parkinson’s disease and amyotrophic lateral sclerosis (Businesswire) - "Neuropore Therapies...announced today that it has successfully completed the Phase 1 clinical trial in healthy volunteers with NPT520-34....NPT520-34 proved to be safe and tolerable at all doses tested, including those believed to be therapeutically relevant....Our team is currently evaluating the optimal study design and patient population for the next study."

Trial completion

Neuropore’s potential ALS oral treatment found to be safe and well-tolerated in healthy volunteers, phase 1 trial shows (ALS News Today) - P1, N=49; NCT03954600; Sponsor: Neuropore Therapies; “‘NPT520-34 proved to be safe and tolerable at all doses tested, including those believed to be therapeutically relevant…The results of this study support moving forward to a safety study in patients. Our team is currently evaluating the optimal study design and patient population for the next study’… ”

P1 data

A Study to Assess the Safety, Tolerability and PK of NPT520-34 in Healthy Subjects (clinicaltrials.gov) - P1; N=49; Completed; Sponsor: Neuropore Therapies Inc.; Recruiting ➔ Completed

Clinical • Trial completion

Neuropore receives orphan drug designation for NPT520-34 for the treatment of amyotrophic lateral sclerosis (Businesswire) - “Neuropore Therapies, Inc. announced today that it has received orphan drug designation for NPT520-34 for the treatment of amyotrophic lateral sclerosis or ALS….In addition, Neuropore reports the successful completion of the initial, single dose, safety and the food effect studies of NPT520-34 in healthy volunteers.”

Orphan drug • Trial status

Newly added product (Businesswire) - P1, Parkinson's Disease, ALS

Pipeline update