Cutaneous Gel Delivering an Intriguing MOA Therapeutic to Treat DFU

PROJECT SUMMARY Diabetes mellitus is a chronic metabolic disorder that has reached epidemic proportions globally. One of the most important complications of diabetes is the major risk of the development of diabetic foot ulcers (DFUs) in approximately a quarter of diabetic patients at some point in their lives. DFUs are extremely debilitating and difficult to treat. Current clinical DFU management modalities are limited in efficacy with a large proportion of DFUs not responding to treatment and progressing further, leading to staggeringly high mortality rates of 16.7% at 12 months and 50% at 5 years – mortality rates that are comparable to those of colon cancer. Consequently, 85% of all lower extremity amputations (LEA) in diabetic patients are a direct result of these DFUs. DFUs cause tremendous financial burden on individual patients to the tune of ~$9K annually, and on the entire healthcare system to the tune of $9 – 13B annually to manage these DFUs, in addition to the cost for management of diabetes in just the USA alone. Thus, there is a dire need for more effective treatments for DFU. Lynntech, Inc. in collaboration with Texas Tech University Health Science Center and in consultation with the University of Miami Miller School of Medicine proposes to develop a cutaneous gel to controllably deliver a small molecule therapeutic with an intriguing mechanism of action in order to effectively address the impaired healing in DFU. Controlled delivery of this therapeutic has the potential to improve wound healing outcomes and significantly reduce mean time to DFU closure, mitigate the adverse risks associated with other interventions, reduce the necessity for LEA, significantly reduce mortality and enable considerable cost savings to DFU patients. In order to obtain proof-of-concept for this innovative new approach to address DFU, our specific aims will be to (1) prepare, characterize and select to a preferred cutaneous gel formulation for controlled delivery of the therapeutic, (2) further elucidate the intriguing mechanism of action whereby this gel formulation can potentially improve the healing of DFU and (3) evaluate the potential of the gel formulation to improve wound healing outcomes in an appropriate in vivo diabetic murine model. The successful completion of these aims is expected to bolster the evidence for the potential clinical utility of this new approach to treat DFU. This will set the stage for a comprehensive IND enabling SBIR Phase II thrust that will focus on providing a solid estimate of in vivo biocompatibility, safety, and efficacy in accepted diabetic animal models of wound healing. The SBIR Phase III effort will focus on human clinical trials, FDA regulatory clearance, CMS reimbursement codes approval and commercialization of this innovative new product for treatment of DFU. The overall impact could therefore be to sustain an effective new paradigm in the clinical management of DFU. This product could provide significant clinical benefits to the millions of patients afflicted with DFU, including improved wound healing outcomes, reduced risk of LEA and mortality and lowered treatment costs.