Over 700,000 surgical hernia repairs are performed each year in the United States and despite recent advances, a significant rate of recurrence persists. The incorporation of biocompatible mesh to strengthen the abdominal fascia has largely replaced high-tension suturing techniques in hernia repair. Currently, the preferred biomaterials include durable synthetic mesh, which bears all the pitfalls of a permanent foreign body; or other collagen-based meshes, which are bioabsorbable but fail at an unacceptably high rate causing recurrent hernias. Surgeons are therefore left to choose either a foreign body or a weak repair. Our goal is to apply our site-specific delivery technology toward the improvement of current biomaterials, shortening the critical period between initial repair, and endogenous wound healing. Using phage display technology, we have isolated peptide sequences which selectively bind PDGF-BB and TGF- 3 and collagen-based surgical repair materials with sub-micromolar relative affinity as synthetic peptides. During our Phase I research program, we have linked these peptides to generate a bifunctional molecule, capable of localized retention of biologically active doses of growth factor on the surface of collagen-based mesh materials. The technology presented here provides a unique means of sustaining the retention and delivery of growth factors to a surgical site, without altering the structural composition of collagen-based resorbable hernia repair mesh. The proposed Phase II research plan will continue the commercialization of our leading PDGF-BB:collagen peptide as a coating for collagen-based repair mesh. The TGF- 3:collagen peptide will be put through a similar battery of tests and optimization efforts during a follow-up product development plan. First, we will employ our extensive experience in peptide chemistry and sequence optimization to devise an efficient pilot-scale peptide synthesis strategy capable of generating > 500 mg of peptide per batch. In parallel with these synthesis efforts, testing will begin on Affinergy's PDGF:collagen binding peptide using autologously harvested sources of growth factor, such as platelet rich plasma. Success in these efforts would remove any future need for a partner with proprietary rights to a recombinant growth factor. The PDGF-BB:collagen and peptide will then be subjected to the battery of biocompatibility testing required for regulatory approval. Peptide will also be examined for stability and function after simulated long-term storage and after exposure widely-used sterilization technique(s). Finally, a rodent model for soft tissue healing after mesh implantation will be used to establish both pharmacokinetics and wound healing rates using peptide-delivered PDGF-BB on collagen repair mesh. These data will provide the first evidence for in vivo efficacy of our peptide, and will be essential for regulatory submissions and partnership development. We feel that the proposed Phase II research plan accelerates the entrance of this product to market, refreshes our product pipeline and extends our core capabilities into critical areas for our continued growth as an innovative medical technology company.
Improving the rate of healing after surgical hernia repair would reduce pain, discomfort and follow-up care. The introduction of biologics into soft tissue healing represents a potential improvement, but due to a lack of clinically viable delivery mechanisms, these molecules remain under-utilized. This proposal aims to further the commercialization of a novel peptide linkage system for the local retention of growth factors on a collagen-based surgical repair mesh. We believe that this primary product concept has the potential to enhance healing after surgical hernia repair by adding growth factors to collagen meshes without altering their desireable properties. However, we also seek to extend our technology to the use of autologous growth factors from platelet rich plasma, to provide partnership flexibility, and accelerate our route to market. Because hernia repair is one of the most common surgical procedures world-wide, this product will provide substantially improved clinical outcomes. .