New clinical development of RGTA based Matrix therapy technology in regenerative medicine

ABSTRACT

Background: Matrix therapy is a newly coined name emphasizing the importance of the extracellular matrix in regenerative medicine. Heparan sulfates (HS) are key elements of the extracellular matrix (ECM) scaffold which store and protect most growth factors/ cytokines controlling the cell migration and differentiation required for healing processes. We have engineered biodegradable nanopolymers (alpha 1-6 polyglucose carboxymethyl sulfate) mimicking (RGTA) to replace destroyed HS in the damaged ECM scaffolding and to protect cytokines produced by healthy neighboring cells, thereby restoring the ECM microenvironment and tissue homeostasis and, if needed, provide a homing niche for cell therapy. This matrix therapy approach has considerably improved the quality of healing in various animal tissue injury models including skin, cornea, digestive mucosa, muscle lung and brain tissues showing tissue protection with reduction or absence of fibrosis resulting in a regeneration process. Due to the ubiquity of HS, numerous clinical developments have been identified and over 200 000 patients have been treated in the last 10 years for skin and corneal wounds with dedicated products based on this technology. Material(s) and Method(s) RGTA OTR4120 and 4132 have been designed to optimize binding and protection of several chemokines and growth factors, are produced in GMP facilities and fulfill all preclinical requirements for quality, safety and pharmacological data for human clinical trials. Result(s) In this short presentation we shall describe some preclinical data supporting brain ischemia protection, lung fibrosis and skin scar reduction, as well as clinical data on going trials aiming at reducing stroke sequala (safety phase 1/2*), pilot study on 13 patients with Covid (showing safety and efficacy on reduction of fibrosis, time to recovery from dyspnoea and fatigue* *). Skin scar reduction studies and submitted RCT proposal. Conclusion(s) Matrix therapy using the RGTA strategy has taken time before optimizing molecules and dosages but is now mature for a wide variety of developments and treatments. In all the cases safety was assessed and efficacy needed to be supported by RCT which are now in progress.