Abstract Details

Title A Placebo-Controlled Phase I Study of NVG-291 in Healthy Subjects, Targeting CNS Receptor Protein Tyrosine Phosphatase Sigma (PTPs)

Topic General Neurology

Presentation(s) S8 - General Neurology: Clinical Treatment and Practice (5:06 PM-5:18 PM)

Poster/Presentation
Number 009

Background Substantial data from animal models of CNS injury, e.g. spinal cord injury (SCI), multiple sclerosis (MS) and Alzheimer’s disease (AD), support that upregulation of chondroitin sulfate proteoglycans (CSPGs) is a fundamental response to CNS damage and inhibits endogenous repair mechanisms. The inhibitory effect of CSPGs is mediated through protein tyrosine phosphatase sigma receptor (PTPσ), the principal receptor for CSPGs in the CNS. NVG-291 is a peptide mimetic derived from the regulatory wedge domain of PTPσ and administered as a once-daily subcutaneous (SC) injection. In animal models, NVG-291 crossed the blood brain barrier, by virtue of its cell-penetrating tag, and improved functional outcomes by promoting remyelination, axonal regeneration, and neuroplasticity.

Objective There are no approved pharmacologic treatments that can restore function following damage to the CNS, whether due to trauma or disease. This randomized, triple-blind, placebo-controlled trial assesses the safety, tolerability, and pharmacokinetics (PK) of single (SAD) and multiple ascending doses (MAD) of NVG-291 in healthy subjects.

Design/Methods In Part 1 (SAD portion), 38 healthy adult volunteers have been randomly assigned into 6 cohorts of placebo or NVG-291 (doses ranging from 0.032 mg/kg to 0.864 mg/kg) SC. Doses tested are in the (human equivalent) range that showed efficacy in several animal models. In Part 2 (MAD portion), up to 18 subjects will be randomly assigned into 3 dose cohorts to receive NVG-291 or placebo once-daily for 14 days. Cerebrospinal fluid (CSF) is being collected for analysis of NVG-291 concentration and pharmacodynamic response.

Results NVG-291 has been safe and well-tolerated to date. Part 1 completed dosing in October 2021, and Part 2 is expected to complete dosing in March 2022. Safety, tolerability, PK and CSF results will be presented.

Conclusions The safety and tolerability of NVG-291 and plasma exposure to date support advancement to clinical trials in patients with SCI, MS, and AD, planned for 2022.

Authors/Disclosures
Daniel D. Mikol, MD, PhD PRESENTER	Dr. Mikol has received personal compensation for serving as an employee of NervGen. Dr. Mikol has received personal compensation for serving as an employee of Amgen. Dr. Mikol has received personal compensation in the range of $100,000-$499,999 for serving as an officer or member of the Board of Directors for NervGen. Dr. Mikol has stock in NervGen. Dr. Mikol has stock in Amgen. Dr. Mikol has received personal compensation in the range of $100,000-$499,999 for serving as a Employee with NervGen.
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