SBIR-STTR Award

This Phase I SBIR proposal targets the development of recombinant human MG rhMG a novel tissue repair protein as a topical therapeutic candidate to facilitate healing of chronic wounds Wound care represents a challenging problem to the public health as no effective treatments for chronic non healing wounds are available MG is an essential component of the cell membrane repair machinery that protects against tissue injuries Research and development efforts at TRIM edicine a university spin off biotechnology company have established that rhMG protein has great potential in facilitation of wound healing and reduction of scar formation targeting multiple cellular processes The chemistry manufacture and control CMC process for scale up production of rhMG has been developed Preliminary toxicological studies in rodent and dog models support the safety for rhMG in topical and intravenous applications There is extensive evidence to support the efficacy for rhMG in treatment of cutaneous wounds in rodent and rabbit models Based on these studies TRIM edicine initiated a pre IND meeting with the FDA and obtained guidance from the Agency for developing rhMG as a topical agent to facilitate healing of chronic wounds The goal of this SBIR project is to conduct the required pre clinical studies testing the safety and efficacy of rhMG as a topical therapy toward evaluating this agent in human subjects with wound healing problems Studies proposed in this application will involve joint development efforts between TRIM edicine and Wound Care Center at The Ohio State University Specifically we propose to produce sufficient rhMG proteins to support the IND enabling topical formulation for rhMG with adequate shelf life and activity Aim and then test the lead prototype formulation in a porcine model of chronic ischemic wounds to evaluate the safety and efficacy of rhMG as a topical therapy Aim Fulfillment of these studies is pivotal for our future development effort with testing rhMG in human clinical trials to facilitate healing of chronic wounds NARRATIVE Development of a therapeutic approach to facilitate healing of chronic wound represents an important area of biomedical and clinical research The lead molecule for this application is MG a novel tissue repair gene Fulfillment of the studies proposed here will aid the pre clinical and clinical development of this molecule a potential viable option for treating non healing wounds We have clearly defined the measurable goals that we plan to achieve in this grant proposal

This proposal builds upon the advances from the SBIR-Phase I program (R43GM123887), targeting the development of recombinant human MG53 (rhMG53), a novel tissue repair protein, as a topical therapeutic agent to facilitate healing of chronic wounds. Wound care represents a challenging problem to the public health, as no effective treatments for chronic non-healing wounds are available. MG53 is an essential component of cell membrane repair that protects against tissue injuries. Research and development efforts at TRIM-edicine, Inc. have established that rhMG53 protein has great potential in facilitation of wound healing and reduction of scar formation. From the SBIR-Phase I program we obtained proof-of-concept data that support our translational and commercialization effort toward developing rhMG53 as a protein therapeutic to treat chronic wounds. We developed the protocol for scale-up production of rhMG53 and the analytical methods for quantification and quality control of rhMG53. We obtained promising data to support the efficacy for rhMG53 in treatment of cutaneous wounds in multiple animal models. We also conducted non-GLP toxicological studies in rodent and dog models and found that rhMG53 as a topical cream did not cause irritation to the skin. No-observed-adverse-effect-level with intravenous administration is >40 mg/kg in rats, supporting the safety of rhMG53 to treat chronic wounds. In this SBIR-Phase II application, we outlined a milestone-driven research plan with deliverable matrixes to reach the goal of filling an Investigational New Drug (IND) application with the FDA to initiate the human clinical trials. Our understanding of MG53’s biological role in tissue repair-regeneration support the multi-cellular function of MG53 in promoting the healing process, as well as in mitigation of scarring associated with dermal injuries. We envision that rhMG53 has advantage over the current paradigms to treat human chronic wounds.

Public Health Relevance Statement:
NARRATIVE Development of a therapeutic approach to facilitate healing of chronic wound represents an important area of biomedical and clinical research. The lead molecule for this application is MG53, a novel tissue repair gene. Fulfillment of the studies proposed here will aid the development of this molecule, a potential viable option for treating non-healing wounds.

NIH Spending Category:
Biotechnology; Injury (total) Accidents/Adverse Effects; Regenerative Medicine

Project Terms:
Ablation; Affect; aging population; analytical method; Animal Model; Area; Biological; Biomedical Research; Biotechnology; Blood Circulation; Canis familiaris; Caring; Cell membrane; Cell physiology; Cellular Structures; Chemistry; Chronic; chronic wound; Cicatrix; Clinical Protocols; Clinical Research; Clinical Trials; Collaborations; commercialization; Contracts; Cream; Critical Care; Cutaneous; Cyclic GMP; Data; Development; Diabetes Mellitus; Disease; Dose; Drug Controls; Drug Kinetics; effective therapy; Ensure; Evaluation; Family suidae; Formulation; Functional disorder; gene repair; Genes; Goals; healing; Health Care Costs; Heart; Human; human subject; Incidence; Injury; injury and repair; Intravenous; intravenous administration; Investigational Drugs; Investigational New Drug Application; irritation; Laboratories; Lead; Longevity; Medical center; meetings; Modeling; Mus; Muscle; National Institute of General Medical Sciences; Natural regeneration; No-Observed-Adverse-Effect Level; non-healing wounds; novel; Obesity; Ohio; operation; Organ; Pathology; Patients; Pharmaceutical Preparations; Pharmacodynamics; Phase; phase 1 study; Physiological; Physiology; Placebos; preclinical study; Process; Production; programs; Protein Family; Proteins; Protocols documentation; prototype; Public Health; Quality Control; Rattus; Recombinants; repaired; Research; research and development; Research Contracts; Rivers; Rodent; Role; Safety; scale up; Skin; Skin injury; skin irritation; Small Business Innovation Research Grant; Testing; Therapeutic; Therapeutic Agents; therapeutic protein; Tissue membrane; tissue regeneration; tissue repair; Tissues; Topical agent; Topical application; Toxicology; Transgenic Mice; Trauma; TRIM Family; TRIM Gene; Ulcer; United States; United States Food and Drug Administration; Universities; wound; wound healing