Cell communication occurs through two main mechanisms. One involves cell contact through surface molecules and the other is through the secretion of soluble mediators mainly growth factors, peptides and cytokines. These soluble mediators are strong modifiers of cell responses and have important roles in immune-mediated processes and control cell growth, proliferation and differentiation. They are therefore potentially important therapeutic agents. However, when used as therapeutics they have many limitations because they have short half-lives and many cells in the body can respond as they express the relevant receptors; this leads to strong unwanted side effects. Stealthyx technology resolves all these limitations by increasing half-life and only target, delivery, and release to sites of disease. The technology is based on the production of a fusion protein between the precursor region of transforming growth factor (TGF) β that forms a shell-like structure around the therapeutic agent and is linked via a metalloproteinase cleavable site. Metalloproteinases are increased in most pathological processes including tissue destruction and remodelling in arthritis, autoimmune conditions, inflammation, cancer and tissue repair and regeneration. Stealthyx technology enables specific delivery and release at sites of disease reducing side effects and allowing lower doses of the active drug.
- First description of the technology and its efficacy at treatment of a rheumatoid arthritis model (2003). This work established that the extended half-life of the therapeutic agent was longer than pegylation; showed that our fusion protein containing a matrix metalloproteinase cleavage site was cleaved by synovial fluids from patients with rheumatoid arthritis and osteoarthritis and by cerebral spinal fluid of patients with multiple sclerosis and meningitis but not by their serum indicating that drug release is possible at sites of disease in vivo;
- Developed an aggrecanase-specific cleavage site (2007).
- Showed proof of principle that the platform delivery technology can be used for cytokines, small peptides and drugs that cross membranes using peptide translocating domains. (2012-2015).
- Demonstrated drug delivery was at sites of disease in vivo, was dose dependent and the presence of a cleavage site was essential for therapeutic efficacy (2014).
- Established, by measuring biomarkers, that our delivery technology has much lower systemic side effects (2014).
In 2016 we signed a research collaboration agreement with GSK to develop a LAP fused compound for potential use in autoimmunity and transplantation
Proof of principle with cytokines and short immunomodulatory peptides has been demonstrated in models of arthritis, peritonitis, cancer, multiple sclerosis, atherosclerosis and graft versus host disease. Additional potential applications include viral infections, regenerative medicine, delivery of antibody fragments and other anti-cytokine therapeutics. The delivery of siRNA and small synthetic drugs is also feasible.