PROJECT SUMMARY/ABSTRACT Acute spinal cord injury (SCI) is a traumatic event that results in the loss of normal motor, sensory, and autonomic function in over 17,000 individuals in the US every year. Currently, there are no FDA approved therapies to treat acute SCI which causes almost all cases to become chronic and last a lifetime. The annual economic loss due to SCI in the US is approximately $8.0B, and lifetime costs per patient can exceed $5.0M depending on the level on the injury. VersaPeutics is a small business that is developing VERSAMAB-101, a novel monoclonal antibody therapy for acute SCI. A commercial scale manufacturing process for the antibody has been developed, and the preclinical safety studies done so far have indicated that the antibody is well tolerated in rodents and non-human primates. The goal of this project is to continue the preclinical development of VERSAMAB-101 through two studies requested by the FDA. (1) A possible method of delivering the antibody to the site of injury is via one of the implanted intrathecal infusion devices that are currently approved for delivering pain medications (aka “pain pumps”). In order for one of these devices to be useful in the clinic, VERSAMAB-101 must be stable inside the device for the duration that it will be in use. VersaPeutics will conduct a study to determine the stability of VERSAMAB-101 while inside an intrathecal infusion device during a simulated clinical administration. To our knowledge, no study on the stability of any antibody in any intrathecal infusion device has ever been made public. VersaPeutics will publish the results of this study in a scientific journal for the benefit of the public and scientific community. (2) Prior to any first-in-human studies, the FDA and international guidance state that monoclonal antibody binding to human tissue should be tested in order to help determine any sites of unintended or unpredicted binding. These studies are known as tissue cross-reactivity (TCR) studies and are typically done using good laboratory practices (GLP). We will perform a GLP TCR study for VERSAMAB-101 and examine antibody binding to the FDA recommended set of tissues from 37 different human organs collected from 3 unrelated individuals. The results of this study will be included in any future requests to the FDA or other regulatory agencies for permission to use VERSAMAB-101 in clinical trials. (Future Phase II Project) The future Phase II portion of this project will continue the preclinical development of VERSAMAB-101 through other studies that are necessary to complete prior to filing an Investigational New Drug application with the FDA.