Tissue Engineering Technology: GAM Technology
Gene Activated Matrix Technology Platform | Excellarate
Gene Activated Matrix Technology Platform
Gene Activated Matrix (GAM) Technology
Cardium’s proprietary Gene Activated Matrix™ technology platform is designed to provide a therapeutic level of protein synthesis at a specific site in the body and can be used in soft tissue such as skin, ligament, tendons and cartilage, as well as in hard tissue such as bone. The technology is distinctive in that it is immobilized gene delivery that allows for gene uptake restricted to the application site. The Gene Activated Matrix comprises any biocompatible matrix containing a gene or DNA vector encoding for a growth factor or any therapeutic protein. The technology allows for a broad spectrum of formulations and the use of any biocompatible matrix, natural or synthetic, which would include, but not be limited to, collagen, de-mineralized bone, allograft and other synthetic graft materials.
Company studies have shown that proliferative cells migrate into the Gene Activated Matrix and then take up the immobilized gene resulting in localized and sustained production of small but physiologically active quantities of growth factor proteins or other therapeutic proteins based on the protein-producing DNA of choice. Compared with protein therapy, which may be limited due to the inherently short half-life of proteins, the Company believes that the localized and sustained production of therapeutically significant concentrations of DNA-driven proteins at the delivery site can significantly enhance the stimulation of localized therapeutic processes such as tissue repair.
Excellarate
Excellarate™ is a collagen-based topical gel employing the Company’s Gene Activated Matrix™ technology to locally stimulate the release of platelet-derived growth factor-B protein (PDGF-B), an important key in the human body’s wound healing process. Sustained, localized micro-release of PDGF-B by a patient’s own cells directly at the wound site is believed to stimulate angiogenesis and granulation tissue formation through the recruitment and proliferation of cells such as monocytes, fibroblasts and endothelial cells. These cell types are critical for the effective stimulation of a variety of wound healing processes.
The Excellarate™ product candidate is initially being developed to facilitate wound closure in non-healing diabetic foot ulcers. The Excellarate product candidate is designed to provide physicians and patients with a potentially simpler, easy-to-use treatment regimen compared to most diabetic wound healing agents or devices in use that require repeated administrations over a long term (weeks to months). Cardium plans to re-formulate Excellarate as an easy-to-use single syringe that is pre-mixed and ready to be applied to patients’ wounds. The reformulation will allow Excellarate to be maintained in a physician’s office using a standard refrigerator (at 2-8°C) and is expected to have a shelf life of 15-18 months.
The multi-center Matrix Phase 2b clinical trial for patients with chronic non-healing diabetic foot ulcers evaluated patients treated with the Excellarate product candidate (combination of Ad5PDGF-B and 2.6% collagen) or 2.6% collagen alone compared to patients who received only the protocol specified standard of care. Nearly half of patients (48%) receiving a one-time Excellarate treatment had complete wound closure by 12 weeks, compared to a 31% wound closure rate for standard of care. Among combined one and two dose groups of Excellarate approximately 41% of patients achieved complete closure by 12 weeks. In addition to overall wound closures by 12 weeks, the Phase 2b study also evaluated wound closure rates and trajectories following product administration in order to assess the timing and extent of bioactivity. The data revealed that patients receiving Excellarate exhibited early and rapid wound healing responses as evidenced by substantial reductions in wound radius over the first several weeks following product administration, which responses were both greater and faster than those observed among patients that had received standard of care. For example, a 108% relative improvement (decrease in ulcer radius) compared to standard of care was observed over the first week following administration of Excellarate, and a 50% relative improvement was observed as an average over the first four weeks.
Phase 2b Matrix Study Excellarate Patient Photos
Before Treatment
After Treatment
Patient #1: This patient is a 60-year old male with a non-healing diabetic foot ulcer that had been unsuccessfully treated for five years before enrolling in the Excellarate Matrix Phase 2b clinical study.
Before Treatment
After Treatment
Patient #2: This patient is a 62 year old male with a non-healing diabetic foot ulcer that had been unsuccessfully treated for 12 weeks before enrolling in the Excellarate Matrix Phase 2b clinical study.
PHASE 1/2 EXCELLARATE CLINICAL STUDY
Excellarate has been studied in a Phase 1/2 clinical trial that evaluated safety and included a preliminary assessment of healing. The positive findings of this open label multi-center Phase 1/2 Excellarate clinical study were published in the November-December 2009 issue of Wound Repair and Regeneration, a peer-reviewed journal of the Wound Healing Society. The principal findings of the study concluded that Excellarate appeared to be both safe and well tolerated and that complete wound closure was observed at 14 weeks in 10 of the 15 patients (67%), seven of whom had received only a single application of the Excellarate product candidate. In addition, Excellarate appeared to be associated with early rapid healing responses (around half of the patients achieved a 50-99% reduction in wound size by week 2).