NNI-362 / NeuroNascent - LARVOL DELTA

First-in-human study of neuron regenerative therapy NNI-362 to evaluate the safety, pharmacokinetics, and pharmacodynamics in healthy aged population. (PubMed, Alzheimers Res Ther) - P1 | "These findings suggest in older subjects, oral NNI-362 appeared safe, well tolerated and reduced plasma p-tau181. Phase 2 studies of NNI-362 are warranted for Alzheimer's disease and age-related degenerative disorders."

Biomarker • Clinical • Journal • P1 data • PK/PD data • Alzheimer's Disease • CNS Disorders • p-tau181

Neuronascent Announces Progress for Lead Candidate NNI-362: Publication of Phase 1a Clinical Trial Results... (GlobeNewswire) - "The article...demonstrated the agent to be well tolerated and able to reduce the plasma pTau181 over pre-treatment levels (i.e., pharmacodynamics)....'Neuronascent discovered NNI-362 through a novel screening program aimed at identifying small molecules that easily enter the human brain and promote nascent, adult-born neurons to replace those lost in aging and disease.'....These clinical results along with further completed safety and manufacturing, also supported by the NIA, further support entering Phase 2 trials of NNI-362 in AD."

New P2 trial • P1 data • Alzheimer's Disease

Neuronascent Announces NIA Grant Award for NNI-362 to Reach Phase 2 Clinical Trials for Mild to Moderate Alzheimer’s Disease (GlobeNewswire) - "Neuronascent Inc...today announced that the National Institute of Aging (NIA), has awarded a U01 grant to Neuronascent, with the CEO, Dr. Judith Kelleher-Andersson being the principal investigator. The grant...will allow for the longer-term assessment of Neuronascent’s investigational drug, in a proof-of-concept clinical trial....This grant award should allow the further long-term safety testing and further GMP manufacture of NNI-362 required before running a critical trial to assess whether NNI-362 will indeed address the next stage of AD disease progression by halting and potentially reversing disease back to a time when the patient had greater memory and executive function."

Financing • Alzheimer's Disease • CNS Disorders • Parkinson's Disease

Clinical stage Alzheimer’s therapy, NNI-362 promotes TH+ neurons associated with a reversal of motor deficits in AAV-alpha synuclein model, leaving alpha synuclein unchanged (AAIC 2023) - "Oral NNI-362 may be a cause-agnostic therapeutic - promoting region-specific new neurons, TH + neuronal protection, and behavioral improvement when induced by dopaminergic deficit, including neurogenesis deficit. After AAV-alpha-synuclein induction of 2 weeks, and then followed by chronic NNI-362 treatment, both behavior and neuron numbers were no different than AAV-GFP control levels in this clinically-relevant experimental model of PD."

Clinical • Alzheimer's Disease • CNS Disorders • Movement Disorders • Parkinson's Disease

Neuronascent to Present New Parkinson’s Model Data at AAIC 2023 for the Alzheimer’s Disease Investigational Therapy, NNI-362 (GlobeNewswire) - "Neuronascent Inc., today announced its abstract...has been accepted for a poster presentation at the Alzheimer’s Association International Conference (AAIC) to be held in Amsterdam, Holland, on July 19, 2023....Neuronascent’s lead neuron regenerative therapy, NNI-362 has demonstrated the ability to promote new neurons in human cell culture and in aging and degenerative models, especially in the very active region of new neuron growth, the hippocampus. This region of the brain, which is involved in learning and memory, is not the only region where new adult-born neurons are found in normal aged and diseased human brains."

Preclinical • CNS Disorders • Parkinson's Disease

Phase1a, Dose-escalation Study of NNI-362 in Healthy Aged Volunteers (clinicaltrials.gov) - P1 | N=56 | Completed | Sponsor: Neuronascent, Inc. | Unknown status ➔ Completed

Trial completion • Alzheimer's Disease • CNS Disorders

REDUCTION OF PLASMA P-TAU181 FROM A PHASE1A RANDOMIZED TRIAL OF NNI-362 IN A HEALTHY AGED POPULATION CONSISTENT WITH AMELIORATION OF TAU HYPERPHOSPHORYLATION IN HUMAN DIFFERENTIATED NEURON CULTURES. (CTAD 2022) - "These findings suggest that even in a small number of healthy older subjects, oral NNI-362 appeared safe and well-tolerated, and reduced plasma p-tau181 levels - a blood-based biomarker of AD pathology. Further study, including a Phase 2 trial of NNI-362, are warranted in individuals with neurodegenerative tauopathies including AD."

P1 data • Alzheimer's Disease • CNS Disorders

Neuronascent Releases Further Positive Results of NNI-362 in A Randomized Phase 1a Trial for Alzheimer’s Disease (GlobeNewswire) - “…A Phase 1 study of Neuronascent’s NNI-362, completed in 2021, demonstrated NNI-362 to have a favorable safety profile, and in March 2022, showed a significant reduction of an Alzheimer’s disease pathological biomarker. This indicates an initial step toward demonstrating NNI-362’s potential to affect disease progression.”

Biomarker • P1 data • Alzheimer's Disease • CNS Disorders

A Phase 1a, Randomized, Placebo-controlled, Single and Multiple Dose, Dose-Escalation Study to Evaluate the Safety and Tolerability of Novel Regenerative Therapeutic NNI-362 (CTAD 2021) - "Stable use of all FDA-approved medications, including aducanumab, will be permitted. Oral NNI-362 is safe and well tolerated at oral doses up to 240 mg. A maximum tolerated dose was not achieved in a healthy aged population. The lipid formulation of NNI-362 at 120 and 240 mg revealed an increased Cmax and AUClast but no increase in AEs."

Clinical • Late-breaking abstract • Alzheimer's Disease • CNS Disorders

Neuronascent Releases Positive Topline Phase 1a Safety Results of NNI-362 for Alzheimer's Disease (PRNewswire) - P1, N=56; NCT04074837; Sponsor: Neuronascent, Inc.; “Neuronascent Inc…announced the completion of its Phase 1a trial of NNI-362 for Alzheimer's disease. This placebo-controlled, randomized trial was fully supported by a grant from the National Institute on Aging (NIA), part of the National Institutes of Health. The primary goal of this trial was to assess the safety and tolerability of oral NNI-362 in a healthy aged population of subjects 50-72 years of age. In topline results, oral liquid-formulated NNI-362 administration in single and multiple ascending doses never reached a Maximum Tolerated Dose (MTD). NNI-362, administered from 10 to 240 milligrams orally, once daily, showed no serious adverse events and no dose-dependent adverse events. This Phase 1a trial enrolled 56 subjects who were randomized to receive placebo or NNI-362.”

P1 data • Trial completion • Alzheimer's Disease • CNS Disorders

[VIRTUAL] Pioneering Neuron Regeneration Therapeutics to Fill the Void in Treatment Options for AD (CNSS 2021) - "Synopsis Exploring the unique mechanism of action of NNI-362, selectively stimulating the conversion of human brain neural progenitor cells to mature functioning neurons Allowing the function to guide the target, assessing the journey from phenotypic screening of regenerative targets to the clinic Safety profile in aged humans (SAD) Plasma biomarkers can be used post-Phase 1a to guide the future POC trial Evaluating brain adult-born neurons numbers in future trials based on preclinical data in aged and Down syndrome-modeled animals"

Alzheimer's Disease • CNS Disorders

Neuronascent Announces Publication of Pre-clinical Results of Alzheimer’s Disease Clinical Candidate, NNI-362 in SCR&T Journal (GlobeNewswire) - "Neuronascent Inc....today announced the publication of results of their novel pharmacotherapy: NNI-362 to allosterically stimulate neural regeneration in human cultures and in vivo models of aging and disease....'The innovative therapy developed by Neuronascent (NNI-362) shows promising results in animal models of aging and disease as it moves forward toward proof-of-concept clinical trials'. Neuronascent expects that NNI-362 will provide benefit for any number of age-related disorders beyond just Alzheimer’s; that is, those disorders that occur due to lack or loss of adult-born neurons in cognitive and motor regions of the brain."

Preclinical • Alzheimer's Disease • CNS Disorders

Novel pharmacotherapy: NNI-362, an allosteric p70S6 kinase stimulator, reverses cognitive and neural regenerative deficits in models of aging and disease. (PubMed, Stem Cell Res Ther) - "NNI-362 promoted the associative reversal of age- and disease-related cognitive deficits in aged mice and Down syndrome-modeled mice. This oral, allosteric modulator may ultimately be beneficial for age-related neurodegenerative disorders involving hippocampal-dependent cognitive impairment, specifically AD, by promoting endogenous hippocampal regeneration."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Developmental Disorders • Genetic Disorders

[VIRTUAL] Neuron Regenerative Therapy, NNI-362, Aiming to Reverse Deficits in Alzheimer’s and Down Syndrome (AAIC 2020) - No abstract available

Alzheimer's Disease • CNS Disorders • Developmental Disorders • Genetic Disorders

Phase1a, Dose-escalation Study of NNI-362 in Healthy Aged Volunteers (clinicaltrials.gov) - P1; N=56; Recruiting; Sponsor: Neuronascent, Inc.; Trial completion date: Apr 2020 ➔ Dec 2020; Trial primary completion date: Mar 2020 ➔ Oct 2020

Clinical • Trial completion date • Trial primary completion date

Phase1a, Dose-escalation Study of NNI-362 in Healthy Aged Volunteers (clinicaltrials.gov) - P1; N=56; Recruiting; Sponsor: Neuronascent, Inc.

Clinical • New P1 trial