Guest blog post by Victoria English, Editor, MedNous, Evernow Publishing Ltd
It is often said that cell and gene therapies are a ‘process’ rather than typical drugs. This is based on the fact that their success depends on the quality of their starting materials and how they are manufactured. This could be an autologous chimeric antigen receptor (CAR) T cell-based gene therapy, or any one of the many allogeneic products in clinical development. Manufacturing is the key strategic issue for developers of these therapies, according to speakers at the On Helix annual meeting in Cambridge, UK on 7 July.
For more traditional drug molecules, the manufacturing step is one element in a larger development plan. In the case of cell and gene therapy products, the manufacturing step is the development plan – at least initially. This has consequences for how companies solicit funding and plan for the future, the panellists noted.
“Investors are looking for a detailed CMC strategy before a Series A funding,” said Angela Osborne, founder and chief executive of the consultancy eXmoor pharma concepts Ltd.
The manufacturing step differs depending on whether the prospective therapy is autologous, or based on cells or tissues from a patient, or allogeneic where cells are taken from different individuals of the same species and prepared for the patient.
The autologous approach is illustrated by Kymriah, the pioneering CAR T cell therapy for acute lymphoblastic leukaemia which was approved by the US Food and Drug Administration in 2017. Kymriah is made by extracting white blood cells from a patient, shipping them to a manufacturing site for reprogramming and then returning the cells to the patient. By comparison, the allogeneic approach relies on a single source of cells to treat many patients and is often described as an ‘off-the-shelf’ approach.
Thus far, most of the approved allogeneic therapies are cord blood products for stem cell transplantation procedures. But other products are in development. For example, BlueRock Therapeutics LP is using induced pluripotent stem cells (iPSCs) as source material for a stem cell therapy for Parkinson’s disease. This candidate product started a Phase 1 study in January.
“The field is going allogeneic,” said Kerstin Papenfuss, associate director of therapeutics at Deep Science Ventures. At the meeting, panellists said there are currently two main sources for the new allogeneic cell therapies: cells from healthy donors and iPSCs. The iPS cell approach has generated a lot of interest, but it is still a young industry.
“Can you create cells that have the correct phenotype?” asked Dr Papenfuss. This is just one of many questions still to be answered.
Beside Drs Papenfuss and Osborne, the panel included the IP lawyer Adrian Toutoungi; Laurent Jespers, chief scientific officer at Xap Therapeutics; Julie Wood from Thermo Fisher Scientific and Stephen Howe from GlaxoSmithKline Plc.