Advancing Diabetic Foot Ulcer Treatment with Provasliex, a Controlled PDGF Release Hydrogel for Promoting Vascularization and Managing Overactive Inflammation

Summary GelSana is developing the Provasliex GelTM, a zwitterionic hydrogel that delivers controlled release of platelet derived growth factor (PDGF) to address the need for better treatments for impaired wound healing associated with diabetes. There are approximately 37 million people in the U.S. with diabetes and nearly 25% of patients will suffer from diabetic foot ulcers (DFU) and lower leg ulcerations in their lifetime. Lower limb amputations associated with impaired wound healing and lower leg ulceration are the primary reason for hospitalization of patients with diabetes leading to 154,000 lower limb amputations per year in the U.S. The current standard of care approach for treatment of diabetic wounds are to use standard gauze and antibacterial solutions to reduce infection, but these approaches do not address underlying issues associated with inflammation of the wound. Becaplermin (Regranex) is a topical gel that provides PDGF to the wound bed that has been shown to be safe and can improve diabetic wound healing. Unfortunately, Regranex is limited clinically, as dressings must be changed frequently, often 2x per day, as biologics like PDGF degrade fairly rapidly in the wound healing environment and therefore must be consistently supplied to have a therapeutic impact. There is significant potential for controlled release of PDGF over time to significantly improve the rate of wound healing and reduce the frequency of dressing changes for patients. To address this need, GelSana has developed a zwitterionic hydrogel that repels protein adsorption, prevents the foreign body response, reduces inflammation by modulating macrophage state, and supports controlled release of PDGF. The Provasliex Gel (zwitterionic hydrogel + PDGF) will have a multifactorial impact on wound healing as the hydrogel alone reduces inflammation in the wound bed, protects PDGF from degradation, and enables consistent controlled release to promote wound healing. Prior to this Phase I submission, GelSana has demonstrated controlled release of PDGF across several days, that the zwitterionic hydrogel alone reduces healing time of wounds in a diabetic mouse model, and that the hydrogel limits activation of an inflammatory macrophage phenotype. The goal of this project will be to demonstrate feasibility towards improved wound healing with Provasliex Gel in mouse and pig models of diabetic wound healing compared to Regranex. Commercialization of Provasliex Gel would significantly improve patient morbidity outcomes through accelerated wound healing and would substantially improve patient quality of life by reducing the frequency of painful dressing changes.