Evaluation of a Novel Connexin-Based Peptide for the Treatment of Diabetic Wounds - Project Summary
An estimated 347 million people worldwide have diabetes, including over 29.1 million Americans. A
major cause of morbidity and hospitalization in patients with diabetes is diabetic foot ulceration (DFU), which
can result in infection, amputation, prolonged hospitalization, and costly treatments. Diabetes treatments cost
the American healthcare system ~$245 billion annually, representing 20% of the total healthcare expenditure;
and DFU treatment consumes ~50% of these costs. Chronic diabetic wounds remain stalled in the initial
inflammatory phase of wound healing and remain unresponsive to conventional treatments. Current treatment
approaches tend to have limited to marginal efficacy and high cost. A large unmet need exists for safe, cost-
effective therapeutics that are easily applied in the home care or clinical setting and conform to practice of
medicine in DFU care without reducing efficacy.
FirstString Research, Inc., a clinical stage biopharmaceutical company, is advancing the development
of novel bioengineered peptides based on the C-terminus of connexin proteins; a protein with important roles in
the wound healing process. Our lead peptide, aCT1 (25 amino acids) based on connexin43, has demonstrated
a unique capability of switching the body's healing response from excessive inflammation and scarring to a
healthy regenerative stage. With the assistance of SBIR/STTR grants and significant private funding,
FirstString has developed aCT1 in a topical product called Granexin® gel (Granexin); obtained IND approval;
and demonstrated its mechanism of action, safety, and efficacy in a Phase 1 (N=48) and three Phase 2 clinical
trials (N=276). Tissue injuries treated with Granexin show clinically and statistically significant faster healing,
reduced inflammation, and improved mechanical properties without treatment related adverse events.
FirstString has received Phase IIb SBIR funding to continue clinical development and evaluate the
efficacy and safety of Granexin in a larger clinical trial currently underway. During the End of Phase 2 meeting,
the FDA requested a 9-month repeat dose pig study as an integral part of Granexin's NDA (New Drug
Approval) review process, in line with FDA's Guidance for Industry in the development and approval for chronic
wound therapeutics. The Specific Aim of this CRP SB1 project is to conduct a standard 39-week repeat
dose GLP dermal toxicity study of Granexin® gel in the Göttingen mini-pig followed by a 14-day
recovery. Subaim 1 involves the assessment of the safety of repeat topical dosing of Granexin at low (100
µM), medium (200 µM), and high (500 µM) concentrations, with appropriate controls, on skin wounds that will
be rewounded every 15 days. Subaim 2 will involve the toxicokinetic analysis of aCT1 peptide and assessment
of systemic exposure. This study is similar to our previously conducted 92-day repeat dose toxicity study in
pigs. Successful completion of this aim will fill in a necessary gap in obtaining NDA approval for Granexin from
the FDA and support the eventual market launch of Granexin for the treatment of DFUs.
