Allogeneic RPE cell suspension manufactured at scale demonstrating preclinical safety and efficacy led to IND approval
Cell replacement therapy is a promising therapeutic option for dry age-related macular degeneration (AMD). In this study, we outline our design for scalable manufacture with appropriate quality gates and present in vivo data for establishing preclinical safety and efficacy of an induced pluripotent stem cell (iPSC)-derived retinal pigment epithelium (RPE) product, thus laying the foundation for Phase 1/2a trial approval in India (ClinicalTrials.gov ID: NCT06394232; date of registration: 23<sup>rd</sup> September 2024). Escalating doses of RPE cell suspension in immunocompromised animals demonstrated absence of tumor formation up to 9 months post-injection. Good Laboratory Practices (GLP) toxicology and tolerability studies in rabbits and non-human primates (NHP) respectively showed no major adverse events. RPE transplanted into immune suppressed RCS rats showed integration, neuroprotection and rescue of visual function. In addition, we provide a detailed description of the modifications in GMP manufacturing protocol to create a final product with a unique composition and Chemistry, Manufacturing and Controls (CMC) studies performed during product development.
Authors
- Harshini Surendran
- Rajarshi Pal (ORCID: https://orcid.org/0000-0001-6334-4562)
- Jonathan Stoddard (ORCID: https://orcid.org/0000-0002-5180-1428)
- Renee C. Ryals (ORCID: https://orcid.org/0000-0002-7182-7238)
- Zengping Liu (ORCID: https://orcid.org/0000-0002-2578-293X)
- Lalitha Soundararajan
- Xinyi Su (ORCID: https://orcid.org/0000-0002-1480-6713)
- Lingam Gopal (ORCID: https://orcid.org/0000-0001-9130-5712)
- Niharika Patlolla (ORCID: https://orcid.org/0000-0002-5704-4640)
- Sebastian Arrizabalaga
- Rajani Battu
Institutions
- Agency for Science, Technology and Research (SG)
- Oregon Health & Science University (US)
- National University of Singapore (SG)
- Centre for Cellular and Molecular Biology (IN)
- Singapore National Eye Center (SG)
- University of Trans-Disciplinary Health Sciences and Technology (IN)
- Singapore Eye Research Institute (SG)
- National University Hospital (SG)
- Vasan Eye Care Hospital (IN)
- Institute of Molecular and Cell Biology (SG)
Publication Details
- Journal
- npj Regenerative Medicine
- Published
- 2025-04-19
- DOI
- https://doi.org/10.1038/s41536-025-00407-0
- Citations
- 8
- Primary Topic
- Retinal Development and Disorders
- Type
- article
- Field-Weighted Citation Impact
- 6.45
Funders
- Department of Biotechnology, Ministry of Science and Technology, India
- National Institutes of Health
- Institute of Molecular and Cell Biology
- Biotechnology Industry Research Assistance Council