Induced pluripotent stem (iPS) cells are a type of stem cell that can be generated directly from adult cells. They were first developed in 2006 by Shinya Yamanaka and his team. iPS cells are engineered by reprogramming adult cells, such as skin cells, to revert to a pluripotent state, meaning they have the ability to differentiate into any cell type in the body. This reprogramming is typically achieved by introducing a combination of specific genes or gene factors into the adult cells, which resets their developmental clock.
iPSCs, also called iPS cells, hold immense potential for regenerative medicine, disease modeling, and drug discovery, because they offer a non-controversial and patient-specific source of stem cells. Unlike embryonic stem cells, which are derived from embryos and raise ethical concerns, iPS cells can be generated from a patient’s own cells, reducing the risk of rejection by the immune system when used in regenerative medicine.
Despite their enormous promise though, no iPSC-derived cellular therapeutic has yet to receive regulatory approval in any jurisdiction worldwide. With this said, there are now over 60 different companies who are trying to change this reality.
Companies Undertaking Clinical Trials with iPSC-Derived Cellular Therapeutics
At the forefront of this mission is Cynata Therapeutics Ltd. (ASX: CYP). Cynata is a clinical-stage regenerative medicine company specializing in stem cell therapeutics that has a proprietary technology for manufacturing induced pluripotent stem cell (iPSC) derived mesenchymal stem cells (MSCs). Headquartered in Australia, Cynata has completed a Phase 1 clinical trial focusing on the application of CYP-001, an iPSC-derived mesenchymal stem cell (MSC), for the treatment of graft-versus-host disease (GVHD). That trial, conducted in 2018, achieved success in 16 patients with GVHD resistant to steroids.
In August 2023, Cynata was granted regulatory approval from the regulatory authorities in the Netherlands for a Phase 1 trial of CYP-001 in kidney transplant patients. Additionally, the company is testing CYP-001 in patients with High-Risk acute Graft versus Host Disease (HR-aGvHD) in a Phase 2 trial with sites in the U.S. and Australia. In December 2023, Cynata received approval to launch a Phase 2 trial of CYP-001 in Turkey as well.
In other impressive news, Cynata is testing another of its iPSC-derived cell therapeutic, CYP 004, in a Phase 3 clinical trial with 440 enrolled patients. If that wasn’t enough, it is also pursuing an Phase 1 clinical trial for its iPSC-derived product, CYP-006TK, for the treatment of diabetic foot ulcers (DFU). Promising initial 10 week follow-up data has already been released for the first 16 patients enrolled in the Phase 1 DFU trial, with a “median percentage reduction in wound surface area of 87.6% in the active CYP-006TK group, compared to 51.1% in the control group.”
Of course, FUJIFILM has a 10.01% ownership stake in Cynata Therapeutics, so it deserves indirect credit for progressing iPSC-derived therapeutics in human trials as well.
Another company that is progressing iPSC-derived cellular therapeutics into clinical trials is Fate Therapeutics. First, Fate is conducting a Phase I trial (NCT03841110) to evaluate its product candidate, FT500, as monotherapy and in combination with immune checkpoint inhibitors in patients who are experiencing advanced solid tumors.
Second, Fate is clinically testing FT825 (ONO-8250), an iPSC-derived CAR T-cell product candidate that incorporates a novel HER2-targeted antigen binding domain that arms it to address the unique challenges presented by solid tumors. The company’s Phase 1 study of FT825 / ONO-8250 is being conducted under a strategic collaboration with Ono Pharmaceutical Co., Ltd. In January 2023, Fate announced it was initiating a Phase 1 clinical trial of FT825 in patients with HER2-expressing advanced solid tumors.
In Japan, the Japanese company Healios K.K., in collaboration with Sumitomo Dainippon Pharma, has been pursuing for a clinical trial using allogeneic iPSC-derived retinal cells to treat age-related macular degeneration (AMD).
Additionally, Century Therapeutics, which acquired Clade Therapeutics in April 2024, recently launched its CALiPSO-1 Study. It is a clinical trial of CNTY-101—its allogeneic iPSC-derived NK cell therapy that was engineered using Allo-Evasion™ edits—that is being evaluated in participants with moderate to severe systemic lupus erythematosus.
Organizations Undertaking Clinical Trials with iPSC-Derived Cellular Therapeutics
Of course, there are also many other entities who are progressing iPSC-derived cellular therapeutics into clinical trials. These noncommercial entities include:
University Medical Center Goettingen
- Safety and Efficacy of Induced Pluripotent Stem Cell-derived Engineered Human Myocardium as Biological Ventricular Assist Tissue in Terminal Heart Failure (NCT04396899)
Osaka University
- Clinical Trial of Human (Allogeneic) iPS Cell-derived Cardiomyocytes Sheet for Ischemic Cardiomyopathy (NCT04696328)
Nanjing University Medical School
- The Study of Human Epicardial Injection With Allogenic Induced Pluripotent Stem Cell-derived Cardiomyocytes in Ischemic Heart Failure (Journal of Cardiology)
Masonic Cancer Center
- Study of FT516 Safety and Feasibility for the Treatment of Coronavirus Disease 2019 (COVID-19) in Hospitalized Patients With Hypoxia (NCT04363346)
Kyoto University Hospital
- Kyoto Trial to Evaluate the Safety and Efficacy of iPSC-derived dopaminergic progenitors in the treatment of Parkinson’s Disease (CiRA)
- Clinical research for the transfer of autologous iPS cell-derived platelets to a thrombocytopenia patient (CiRA)
Kyoto University
- Practical evaluation of PET studies with [18F]-GE180, [18F]-FDOPA and [18F]-FLT for a future clinical trial of iPSC-based cell therapy in Parkinson’s disease (UMIN-CTR – UMIN000030084)
Keio University
- Regenerative medicine using iPS cell-derived neural progenitor cells for subacute spinal cord injury (Keio)
Kobe City Eye Hospital
- Allogeneic iPS cell-derived retinal sheet transplantation for retinitis pigmentosa (Kobe)
- A Study of transplantation of allogenic induced pluripotent stem cell (iPSC) derived retinal pigment epithelium (RPE) cell suspension in subjects with neovascular age related macular degeneration (UMIN-CTR – UMIN000026003)
NIH Clinical Center
- A Phase I/IIa Trial for Autologous Transplantation of Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium for Geographic Atrophy Associated With Age-Related Macular Degeneration (NCT04339764)
Tehran University of Medical Science
- A Clinical Trial to Evaluate the Effects of Autologous induced Pluripotent Stem Cell-Derived Natural Killer Cells in Personalized Treatment of Patients with Advanced Metastatic Breast Cancer (IRCT20200429047241N1)
Would you like to see a list of all known companies worldwide who are in various stages of developing iPSC-derived cellular therapeutics, including preclinical development? If so, you can view that here.
To learn more about this promising market, view the “Global Induced Pluripotent Stem Cell (iPSC) Industry Report – Market Size, Trends, and Forecasts, 2024.”
