ExpressGraft™ Genetically Enhanced Skin Tissues:
ExpressGraft Skin Substitutes for Non-healing Ulcers
Stratatech is developing a suite of next-generation, genetically enhanced tissues that produce elevated levels of natural wound healing and anti-microbial factors. Delivered this way, these therapeutic proteins are available where and as needed, at no incremental cost. This strategy creates a targeted, biological mechanism through which to protect and modulate the local wound microenvironment, fight infection, and accelerate healing.
Similar to StrataGraft, these tissues will be viable, full-thickness skin substitute products that will be applied topically and resorbed during the wound healing process. The sole difference is that the parent NIKS® cell line will be genetically modified to over-produce beneficial naturally occurring proteins.
The lead product in this class expresses elevated levels of cathelicidin, an innate host defense peptide known to play an active role in wound healing and having broad anti-microbial properties. In research models, these tissues produced 140-fold greater levels of cathelicidin protein in vitro versus unmodified control tissues, and in vivo showed a 100-1,000 fold reduction of a clinical isolate of the multidrug-resistant nosocomial strain, Acinetobacter baumannii. Research data published in Molecular Therapy elicited independent commentary by German surgeons hailing this capability as a “paradigm shift in the management of skin pathologies”.
The second product in this class expresses VEGF, a pro-angiogenic growth factor that plays a central role in controlling angiogenesis and enhancing blood supply. Because many chronic wounds are associated with insufficient tissue oxygenation, boosting local levels of VEGF may favorably enhance the frequency and rate of wound healing. Results to date are promising, supporting further preclinical development. A number of additional ExpressGraft products have also achieved discovery proof-of-concept, demonstrating the versatility and potency of this platform.
Clinical development for these ExpressGraft products will focus on large, underserved markets in chronic, non-healing ulcers, including diabetic foot ulcers, venous leg ulcers and sclerotic digital ulcers. The incidence of severe non-healing cases totals in the hundreds of thousands of patients annually, with the most severe cases leading to the amputation of tens of thousands of digits and limbs. The current market is primarily served by two skin substitutes, but neither of these products is genetically enhanced and both are contraindicated in infected ulcers and have suboptimal physical integrity and other properties.
In mid-2015, the FDA approved an Investigational New Drug Application authorizing Stratatech to begin a Phase I/II clinical study of ExpressGraft anti-infective tissue in patients with diabetic foot ulcers. The NIH Recombinant DNA Advisory Committee had previously reviewed and unanimously endorsed its clinical progression.
ExpressGraft Non-Viable Temporary Skin Substitute
In certain markets such as military theatres, there is a need to achieve temporary wound closure to stabilize a patient and reduce the risk of infection until relocation to a properly equipped trauma center becomes feasible. Fresh or frozen tissues would be impractical in this environment, but a freeze-dried tissue might be.
Under a program funded by the Department of Defense, Stratatech has been able to demonstrate research proof-of-concept confirming its ExpressGraft antimicrobial tissue can be freeze dried. As expected, the cells in the tissues were no longer viable post-processing, but the tissues retained their structural integrity and antimicrobial properties. Further development of this product, called EpiReady, will be dependent upon military or other third party support.
ExpressGraft Antineoplastic Skin Substitute
Skin substitutes have traditionally been used as tools to achieve wound closure, with a straightforward goal of healing wounds. The ability to create genetically modified tissues opens the door to entirely new therapeutic concepts. Stratatech is pursuing discovery proof-of-concept with one such tissue, a treatment for skin cancer.
The National Cancer Institute projects that more than 1 million cases of skin cancer are expected to be diagnosed in the US in 2008, including more than 62,000 new cases of melanoma. Although surgical excision of the primary tumor is curative for the majority of squamous and basal cell skin cancers, tumor recurrence near the site of a primary tumor remains a predominant cause of treatment failure. Accordingly, there is a need for novel strategies to eradicate residual tumors after resection of the primary tumor.
Stratatech has developed a genetically modified tissue that expresses high levels of Interleukin-12 (IL-12), a human cytokine proven to have potent antitumor properties. The product concept is that this tissue would be applied to a surgical resection site to achieve closure. The IL-12 would be expressed for a limited period within the wound microenvironment, eliminating any residual tumor cells. Local expression would be expected to mitigate or eliminate the toxic side effects commonly associated with systemic administration of this anticancer agent. Research on this program is ongoing.