Stratatech is a regenerative medicine business focused on skin regeneration therapies for severe burns and other rare diseases, as well as chronic non-healing ulcers; it was founded in 2000 to commercialize an extraordinary discovery made at the University of Wisconsin-Madison. The discovery of NIKS® cells – a human keratinocyte cell line that produces living tissue nearly identical to native human skin – has the potential to revolutionize wound care.
Keratinocytes are the cells that make up approximately 90 percent of the epidermis, the outer layer of human skin. NIKS keratinocytes are a consistent source of pathogen-free, non-tumor-producing, long-lived adult progenitor cells. These cells faithfully reproduce normal skin tissue architecture and barrier function when cultured appropriately.
Technically and strategically, this discovery has profound implications. Traditional allogeneic skin substitutes utilize donated primary keratinocytes that must be periodically replenished and requalified at significant cost. Moreover, this may impact product consistency, performance and safety.
The NIKS progenitor cell line avoids these issues, providing a consistent, well-characterized technology platform. Importantly, having a clonal cell source enables Stratatech to create genetically enhanced, skin regeneration products that heretofore have been impossible.
StrataGraft® Regenerative Skin Tissue
The flagship product, StrataGraft tissue, is entering Phase III clinical development as a treatment for severe burns. It was designed to mimic natural human skin, with both dermal and fully differentiated epidermal layers. Unlike first generation cell based products, this resorbable tissue is easily sutured or stapled and remains intact in the wound bed, providing critical barrier functionality during the natural skin regeneration and repair process.
A proof-of-concept clinical trial in patients with deep partial thickness burns was completed in October 2014. Of 28 evaluable per-protocol patients, 27 (96%) achieved complete wound closure by Day 90 with a single application of StrataGraft tissue. Moreover, no StrataGraft DNA was detectable at Day 90, confirming the patients had regenerated their own skin. The outcome of one patient is shown below. This is the first therapeutic product to achieve a clinical outcome comparable or superior to autografting!
There is an urgent need for new treatment options for burns. Currently, patients with severe 2nd and 3rd degree burns must endure painful skin transplants called autografts, and frequently are treated with cadaver skin as a temporary wound covering prior to autograft procedures. StrataGraft tissue is the first therapy that has shown the potential to avoid painful skin transplants and regenerate the patients' own skin.
ExpressGraft™ Genetically Enhanced Regenerative Tissue
The business 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.
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. 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 growing prevalence of antibiotic-resistant “superbugs” and the concomitant dearth of new antibiotic drugs has created a dramatic need for new therapeutic strategies and more effective use of existing technologies. Combining the utility of our full thickness skin tissue with a natural ability to fight bacterial and viral infections makes this a highly compelling technical and commercial strategy. Clinical development of this product will focus initially on non-healing, diabetic foot ulcers. A Phase I/II clinical trial is anticipated to start in 2015. The NIH Recombinant DNA Advisory Committee has already endorsed its clinical progression.
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. Clinical development of this product will focus on large, underserved markets in chronic, non-healing ulcers, including diabetic foot ulcers and venous leg ulcers.
A number of additional ExpressGraft products have also achieved discovery proof-of-concept, demonstrating the versatility and potency of this platform. While some of these are targeted towards wound healing, others open the door to entirely new product concepts. For example, by creating custom tissues that express Interleukin-12, a natural potent anticancer protein, it may be possible to create a product that surgeons could apply after debulking a solid skin tumor. The locally concentrated IL-12 expressed by this tissue would be available to destroy any residual tumor cells missed during the surgery, thus reducing the probability or rate of recurrence.