Therapeutic applications of induced pluripotent stem cells (iPSCs) have surged in recent years. Since the creation of human iPSCs in 2007, it took only seven years for the first iPSC-derived cell product to be transplanted into a human patient in 2014. From 2014 to present, additional trials and physician-led studies employing human iPSC-derived cell types have been initiated across multiple geographies worldwide.
More promising yet, there are a burgeoning number of iPSC trials on the horizon.
Landmark Years in iPSC Therapeutics
2014 was a landmark year because it saw the first cellular therapy involving the transplant of iPSCs into humans initiated at the RIKEN Center in Kobe, Japan. Led by Dr. Masayo Takahashi, it investigated the safety of iPSC-derived cell sheets in patients with macular degeneration.
By 2016, Cynata Therapeutics received approval to launch the world’s first formal clinical trial of an allogeneic iPSC-derived cell product (CYP-001) for the treatment of GvHD. CYP-001 is a iPSC-derived mesenchymal stem cell (MSC) product.
In this historic trial, CYP-001 met all of its clinical endpoints and produced positive safety and efficacy data for the treatment of steroid-resistant acute GvHD. Thus, Cynata is forging forward with CYP-001 in later stage trials and pursuing new indications.
Specifically, Cynata plans to advance its iPSC-derived MSCs into Phase 2 trials for complications associated with COVID-19, as well as GvHD and critical limb ischemia (CLI). It is also undertaking an impressive Phase 3 trial that will utilize Cynata’s iPSC-derived mesenchymal stem cell (MSC) product, CYP-004, in 440 patients with osteoarthritis (OA).
Not surprisingly, the Japanese behemoth FUJIFILM has been involved with the co-development and commercialization of CYP-001 through its 9% ownership stake in Cynata Therapeutics. Headquartered in Tokyo, Fujifilm is one of the largest players in regenerative medicine field and has invested significantly into stem cells through their acquisition of Cellular Dynamics International (CDI). Additionally, Fujifilm has invested in Japan Tissue Engineering Co. Ltd. (J-Tec), giving it a broad base in regenerative medicine across multiple therapeutic areas.
The Japanese company Healios K.K. is also preparing, in collaboration with Sumitomo Dainippon Pharma, for a clinical trial using allogeneic iPSC-derived retinal cells to treat age-related macular degeneration (AMD).
Mass Production and Differentiation of iPSCs
Riding the momentum within the CAR-T field, Fate Therapeutics Inc is developing FT819, its off-the-shelf iPSC-derived CAR-T cell product candidate.
FT819 is the world’s first CAR-T therapy derived from a clonal master iPSC line and is engineered with several novel features designed to improve the safety and efficacy of CAR T-cell therapy. Notably, the use of a clonal master iPSC line as the starting cell source could enable CAR-T cells to be mass produced and delivered off-the-shelf at an industrial scale.
TreeFrog Therapeutics, headquartered in Pessac, France, has developed C-Stem™, a high-throughput cell encapsulation technology allowing for the mass-production and differentiation of iPSCs in industrial bioreactors. This C-Stem™ technology platform could provide a scalable solution to improve the quality of iPSC-derived therapeutics and slash treatment costs.
Companies with earlier-stage iPSC derived cell therapeutics under development include Bluerock Therapeutics (acquired by Bayer in 2019), Century Therapeutics, Aspen Neuroscience, Semma Therapeutics, ImStem, and Platelet BioGenesis.
Physician-Led iPSC Studies in Japan
Finally, numerous physician-led studies using iPSCs are underway in Japan, a leading country for basic and applied iPSC applications. These trials are exploring potential iPSC-based treatments for macular degeneration, ischemic cardiomyopathy, Parkinson’s disease, solid tumors, spinal cord injury (SCI) and platelet production.