RepliCel Life Sciences Inc. announced that it's clinical advisory team has completed the primary design of the next-phase clinical study of its skin rejuvenation product, RCS-01, to be conducted as part of its First-In-Japan early commercialization strategy. After extensive clinical advisory participation, the RCS-01 the study synopsis has now been delivered to RepliCel's Tokyo-based CRO (clinical research organization) and regulatory teams who have commenced preparation of all the necessary Japanese-language documentation to launch the clinical study. These teams have been tasked with creation of the full clinical protocol, investigator's brochure, and the necessary documentation for clinical site participation, IRB (institutional research board) approvals, and clearances from the MHLW (Ministry of Health, Labour and Welfare) and its oversight committees.

At the request of the MHLW, Japan's PMDA (Pharmaceutical and Medical Devices Agency (PMDA) is now working with RepliCel's contract manufacturer to schedule dates for an audit to be conducted for the purposes of certifying the facility for the manufacture and importation of RCS-01 for use in the proposed clinical study. RepliCel's RCS-01 has been the subject of a successful phase 1 study in Germany. The next-phase clinical research studies in Japan will be conducted under that country's Act for Safety of Regenerative Medicine (ASRM) and, upon successfully meeting its endpoints, could lead to a commercial launch of the product in Japan.

RCS-01 is a patient-specific cell therapy in development to regenerate the extracellular tissue matrix under aging or sun-damaged skin characterized by fine wrinkles and loss collagen structure. RepliCel was one of the first foreign regenerative medicine companies to have a Japanese partnership (signed in 2013). In 2015, RepliCel was one of the first foreign regenerative medicine companies to initiate a consultation process, under the new regulations for regenerative medicine products, with Japan's PMDA.

In 2016, RepliCel's licensee, Shiseido Company, was one of the first companies to fund and manufacture a product for use in a clinical research study under the newly legislated ASRM. Now RepliCel is on-track to be one of the first foreign regenerative medicine companies based outside of Asia to directly engage in a clinical study of a cell therapy product under the ASRM regulatory pathway to commercialization. RepliCel will also be one of the first such companies to apply for certification of a manufacturing facility outside of Asia for the production of a cell therapy product to be imported for use in a clinical study governed by the ASRM regulations.

RepliCel is currently preparing for the clinical testing and commercialization of three more technologies in Japan. These include two cell therapies - one for skin rejuvenation and one for tendon regeneration - and a next-generation dermal injector (DermaPrecise™) for aesthetic treatments involving a wide variety of injectable substances including cells, PRP, muscle paralysis toxins, fillers, enzymes, drugs, and other biologics. RepliCel's cell therapy technology is the subject of active, ongoing partnership discussions in Japan and has already been the subject of two successfully completed consultations with Japan's PMDA while planning for clinical research studies under Japan's ASRM has commenced.

Manufacturing of the clinical product will be performed by a Japanese-owned contract manufacturer preparing now for PMDA-certification under Japan's MHLW applicable guidelines. Conduct of the clinical research studies will be managed by an independent clinical research organization. RCS-01 is an autologous cell-based regenerative medicine product comprised of cells highly-expressive of type 1 collagen and other tissue-building protein.

The product is developed, manufactured, and injected to regenerate the extracellular matrix under aging and/or sun-damaged skin characterized by fine wrinkles and loss of collagen structure. A randomized, double-blind, placebo-controlled, single-centre, phase I clinical study evaluated RCS-01 produced statistically and clinically significant positive data revealing a nearly two-fold increase in gene expression of collagen-related biomarkers in the skin, after a single injection of RCS-01. The study observed the impact of the injection on ten different biomarkers that, in peer-reviewed medical literature, are highly correlated with skin aging and chronically sun-damaged skin.

Notably, gene expression markers, such as tissue inhibitor of metalloproteinases (TIMP), showed significant changes expected to correlate with increased collagen fibers. Increased collagen production, and reduced collagen degradation, is associated with fewer wrinkles and the repair of sun-damaged skin. The publication presents data, showing for the first time, that injections of NBDS-derived autologous cells into the human skin dermis layer alters the transcriptional expression profile of genes, which are involved in ECM homeostasis.

Specifically, that in comparison to placebo treated skin areas, injection of NBDS-derived fibroblasts promoted the expression of the genes TGFbeta1, CTGF, COL1A1, COL1A2, COL3A1 and lumican. These genes encode for proteins which are important for ECM homeostasis, thought to be of pathogenetic relevance for skin aging. In aged skin, levels of type 1 and type 3 collagen precursors and crosslinks are reduced.

The observation that injection of NBDS-derived cells is associated with an increased transcriptional expression of these genes indicates the possibility that cell therapy treatment with RCS-01 might ameliorate the clinical and aesthetic signs of skin aging, such as wrinkles. This assumption is in line with observations that increased expression of collagen type 1 and type 3 is a prerequisite for wrinkle reduction caused by retinol.