NSI-189 / Palisade Bio - LARVOL DELTA

Serum metabolite profiles of thyroid autoimmunity patients in early pregnancy. (PubMed, PeerJ) - "We further identified 15 characteristic metabolites (6-Methylquinoline, D-erythrose 4-phosphate, 4-Hydroxyisoleucine, phosphatidylcholine (PC)(16:2e/16:0), N3,N4-Dimethyl-L-arginine, N-desmethyltramadol, 3-Methoxybenzaldehyde, sphingomyelin (SM)(d14:3/28:2), gamma-Glutamylleucine, NSI-189, 3-(1-cyano-1,2-dihydroisoquinolin-2-yl)-3-oxopropyl propionate, lysophosphatidylinositol (LPI) 16:0, cis-Aconitic acid, polyamide (PA)(18:1/18:2) and fatty acyl esters of hydroxy fatty acid (FAHFA)(17:0/18:0)) using least absolute shrinkage and selection operator (LASSO) regression...Thyroid autoantibodies were found to be associated with 14 metabolites identified using LASSO, with the exception of PA (18:1/18:2). Our findings provide new evidence supporting the early screening of serum metabolites and their potential for predicting adverse pregnancy outcomes in women with TAI."

Journal • Endocrine Disorders • Hematological Disorders

Discovery of Novel Diphenyl Acrylonitrile Derivatives That Promote Adult Rats' Hippocampal Neurogenesis. (PubMed, Int J Mol Sci) - "Most of the compounds could stimulate proliferation of progenitors, but just a few chemicals possessing a specific structural profile, exemplified by diphenyl acrylonitrile 29b, 32a, and 32b, showed better activity than the clinical drug NSI-189 in promoting newborn cells differentiation into mature neurons. The most potent diphenyl acrylonitrile 32b had an excellent brain AUC to plasma AUC ratio (B/P = 1.6), suggesting its potential for further development as a new lead."

Journal • Preclinical

Mitochondrial dysfunction following repeated administration of alprazolam causes attenuation of hippocampus-dependent memory consolidation in mice. (PubMed, Aging (Albany NY)) - "The frequently repeated administration of alprazolam (Alp), a highly effective benzodiazepine sedative-hypnotic agent, in anxiety, insomnia, and other diseases is closely related to many negative adverse reactions that are mainly manifested as memory impairment. Furthermore, in vivo behavioral experiments including IntelliCage System (ICS) and nover object recognition (NOR), hippocampal neuronal pathological changes with HE staining, and the expression levels of brain-deprived neuron factor (BDNF) with immunohistochemistry showed a significant decrease in memory consolidation in mice with repeated administration of Alp, which could be rescued by the co-administration of the mitochondrial protector NSI-189. To the best of our knowledge, this is the first study to identify a link between repeated administration of Alp and mitochondrial dysfunction and that mitochondrial impairment directly causes the attenuation of memory consolidation in mice."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Insomnia • Metabolic Disorders • Mood Disorders • Psychiatry • Sleep Disorder • BDNF

Enhancement of Mitochondrial Function by the Neurogenic Molecule NSI-189 Accompanies Reversal of Peripheral Neuropathy and Memory Impairment in a Rat Model of Type 2 Diabetes. (PubMed, J Diabetes Res) - "Efficacy of NSI-189 against dysfunction of the CNS and PNS function in type 2 diabetic rats was accompanied by improvement of mitochondrial function. NSI-189 exhibited actions at different levels of mitochondrial regulation in central and peripheral tissues."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Diabetes • Diabetic Neuropathy • Metabolic Disorders • Pain • Type 2 Diabetes Mellitus

Palisade Bio, Inc. Announces Sale of Seneca Asset NSI-189 for the Treatment of Central Nervous System Disorders (GlobeNewswire) - “Palisade Bio, Inc…announces today that an early exercise option has led to the acquisition of the Seneca asset NSI-189, a neurogenic compound which was part of Seneca Biopharma’s product portfolio at the time of the merger to form Palisade Bio and which is part of the Contingent Value Rights issued to the pre-merger Seneca shareholders. Prior to the merger (in December 2020) Seneca had exclusively out-licensed the NSI-189 program with a 3-year exercise option. Under the terms of the agreement to acquire NSI-189, the purchaser will pay an upfront cash payment of approximately $400,000 with up to an additional $4.5 million contingent on certain clinical development milestones or a subsequent license or sale of the asset by the purchaser within a certain period.”

M&A • Alzheimer's Disease • CNS Disorders • Depression • Major Depressive Disorder • Pain • Peripheral Neuropathic Pain

A phase 2, double-blind, placebo-controlled study of NSI-189 phosphate, a neurogenic compound, among outpatients with major depressive disorder. (PubMed, Mol Psychiatry) - "Both doses were well tolerated. These findings replicate those of phase 1b study, and warrant further exploration of the antidepressant and pro-cognitive effects of NSI-189."

Clinical • Journal • P2 data • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders

NSI-189 phosphate, a novel neurogenic compound, selectively benefits moderately depressed patients: A post-hoc analysis of a phase 2 study of major depressive disorder. (PubMed, Ann Clin Psychiatry) - "These results suggest that NSI-189 is effective as a safe adjunctive therapy, with most compelling antidepressant and procognitive benefits noted in patients with moderate depression."

Clinical • Journal • P2 data • Retrospective data • CNS Disorders • Depression • Mood Disorders

Seneca Biopharma reports 2020 first quarter results (PRNewswire) - "Seneca Biopharma, Inc....today reported its financial results for the quarter ended March 31, 2020....During the First Quarter of 2020, the Company achieved the following business milestones: Continued progress on the Company's out-licensing effort to partner NSI-566 and NSI-189 programs, while seeking to in-license or acquire novel therapeutics that could benefit from its development experience."

Licensing / partnership • CNS Disorders • Depression

A Phase 1B, randomized, double blind, placebo controlled, multiple-dose escalation study of NSI-189 phosphate, a neurogenic compound, in depressed patients. (PubMed) - Mol Psychiatry - No abstract available

Journal • Biosimilar

Amelioration of Both Central and Peripheral Neuropathy in Mouse Models of Type 1 and Type 2 Diabetes by the Neurogenic Molecule NSI-189. (PubMed, Diabetes) - "NSI-189 also halted progression of established peripheral and central neuropathy. NSI-189, which is currently in clinical trials against major depressive disorder, offers the opportunity for development of a single therapeutic agent against multiple indices of central and peripheral neuropathy."

Journal • Preclinical

Effects of the Neurogenic Molecule Nsi-189 on Indices of Cognition in an APP/Tau Mouse Model of Alzheimer’s Disease (AAIC 2019) - "Daily treatment with NSI-189 significantly reversed learning and memory deficits that were established in the TAPP mouse model of AD."

Preclinical