CGMP Compliant Closed Cell Culture System for Reproducible De-differentiation of human somatic cells into iPSCs Abstract The advancement of iPSC-based personalized cell therapies is currently hindered by the challenges in the biomanufacturing of therapeutic cells. Despite approaches that have made the derivation, growth and differentiation of iPSCs more efficient, there remains significant variability in reprogramming efficacy, genomic integrity and developmental potential of iPSCs derived from patient tissue samples. These variabilities include lot-dependent or technician-dependent differentiation efficiency, bacterial or fungal contamination risks, CO2 or O2 concentration level stresses during cell maintenance, high costs or cross- contamination risks with centralized biomanufacturing facility and requirement of cGMP criteria or regulatory compliance. The difference of iPSCs derived from the same sample in their in-vitro growth characteristics and their inability to re-differentiate into the desired tissue type will cause serious problems in therapy. The further advance of iPSC-based personalized medicine is currently limited by the difficulty to generate iPSCs for large populations and at an affordable cost. Therefore Biopico Systems Inc will solve such challenges by developing an automated cGMP Compliant Closed Cell Culture System for reproducible de-differentiation of human somatic cells into iPSCs. To commercialize Biopico's “CellsMX” system, optimization of closed media exchange system and integration of customized mRNA/ media formulation front-end for reprogramming will be performed in this Phase II research. The CellsMX system will provide quality assurance to the customers for mass production under cGMP guidelines, as operating license are issued to biological entities along with how cells are produced, tested, and released for therapeutic use. Further, even, if a large number of patients need iPSC-based personalized cell therapies, under CellsMX closed system, patient cells are not cross-contaminated and the system can be deployed at the point of care avoiding high costs and risks associated with the transportation, logistics, tracking, and recording. While patient-specific iPSC strategy's reduction of immunologic stimulus will drive the initial market segment for the CellsMX system, Biopico will develop a suite of products for several of such therapeutic culture processes.

Narrative The stem cells can address diseases such as cancer or damaged or dysfunctional organs using tissues or cell therapies. The enormous transplant waiting lists results in many people die awaiting transplants. Further, to provide stem cells as a viable source of replacement cells to treat diseases, the manufacturing costs are presently not affordable keeping public expectations unrealistic. Biopico's CellsMX reprogramming platform can address these issues to generate large number of iPSC and supply cells for stem cell banking or stem cell therapy applications.