Abstract

Development of an Allogeneic iPSC-derived Cell Therapy Product

Ross Macdonald, Chief Executive Officer, Cynata Therapeutics Ltd

From the first description of reprogramming methods able to generate pluripotent cells from adult somatic tissues in the middle of the last decade, the science and clinical potential of induced pluripotent stem cells – iPSCs – has taken many important steps forward.   The use of iPSCs in modelling and investigating human diseases, as well as for screening drugs, has already been enormously enlightening.  But it is perhaps their use in the development of therapeutic products where the greatest opportunity for iPSCs arises.  Notably iPSCs share many properties with embryonic stem cells (ESCs) but because iPSCs are not derived from embryos they are not associated with the substantial ethical controversies that have overshadowed ESC research and which will most certainly influence commercial development of ESC-derived therapeutic products.  iPSCs are now being used to develop a broad range of cell therapy products, including myocardial tissue for potential use to effect recovery post-myocardial infarction, retinal pigmented epithelium for potential use in age-related macular degeneration and mesenchymal stem cells (MSCs) for a broad range of disease targets.  The latter cell type is the most advanced, with Cynata Therapeutics Ltd, an Australian biotechnology company, completing in 2018 a Phase 1 clinical trial in acute steroid resistant graft-versus-host disease (GvHD) with a unique allogeneic iPSC-derived MSC cell therapy product.  This clinical trial, the first in the world using an allogeneic iPSC derived product, demonstrated very encouraging safety and efficacy, paving the way for a Phase 2 trial in this and further indications.  The trial confirms a viable and clinically relevant process for large scale manufacture of a highly consistent cell therapy product without the challenges presented by requiring multiple donors and massive expansion of the finished product.  Data from the Cynata trial in GvHD and the pathway to trial approval and beyond will be discussed.