First process ready for clinical testing
Valbonne, France, February 21, 2018, 5.45pm CET
TxCell SA (FR0010127662 – TXCL), a developer of cellular immunotherapies based on regulatory T cells (Tregs) for inflammation, autoimmunity and transplantation, today announces details of its CAR-Treg manufacturing process presented at the CAR-TCR Summit Europe, held in London, UK, on February 20-22, 2018. Dr. Pierre Heimendinger, VP Pharmaceutical Development, TxCell, will deliver an oral presentation describing how TxCell has succeeded in developing the industry’s very first CAR Treg Good Manufacturing Practice (GMP) process ready for clinical testing.
TxCell selected a population of Treg cells with the CD4+ CD25+ CD45RA+ phenotype (CD45RA+ Tregs). TxCell’s CD45RA+ Tregs display both strong anti-inflammatory activity and stability. This starting Treg subset is rare, accounting for less than 5% of CD4+ T lymphocytes. TxCell’s process enables the manufacturing of clinical doses of CD45RA+ based CAR-Tregs in under two weeks, ready for post-production quality control. Key achievements to be highlighted during Dr. Heimendinger’s presentation include a demonstration of the stability of the TxCell Treg phenotype after both expansion of the CAR Treg cells and thawing of the final drug product.
TxCell has conducted several full-scale pilot batches using clinical-grade raw and ancillary materials, as well as equipment to be used by the contract manufacturing organization (CMO) for GMP production. Key findings from these pilot batches are:
- Cells extracted from leukapheresis keep their Treg identity after cell transduction with a CAR and cell expansion throughout the process. This is achieved with limited donor to donor variability.
- A high cell purity of the selected CD45RA+ Treg subset is achieved at the end of the expansion phase.
- Expression of the Foxp3 intracellular cell marker remains constant throughout the process. Foxp3 expression is known to be related to the suppressive capacity of Treg cells.
- Importantly, the drug product could be both frozen and thawed with no change in phenotype and function.
“Completing TxCell’s first CAR-Treg manufacturing process is a major step towards the clinical phase in CAR-Treg development,” said Francois Meyer, Chairman and Head of Research of TxCell. “To the best of our knowledge, this is the very first CAR-Treg GMP process in the industry. The production lead-time, not including quality control, is already under two weeks, in line with general CAR T standards and with reasonable associated costs. The CAR TCR Summit gives us the opportunity to share our Quality by Design methodology with the industry.”
Transfer of TxCell’s CAR-Treg GMP process to a CMO has started in early February. TxCell expects to disclose the name of the CMO in the coming weeks, and to file its first CTA and/or IND late in Q4 2018. TxCell maintains its goal of being the first company to ever start clinical development with a CAR-Treg program.
TxCell is also releasing today an animated video explaining its process and CAR-Treg approach: https://vimeo.com/256395803. Details of the TxCell overall process can also be seen on the Company’s website.
TxCell used the Quality by Design (QbD) approach to achieve its GMP manufacturing process. Critical steps included Treg cell subset isolation, CAR transduction, CAR-Treg activation, CAR Treg expansion and freezing and thawing. These steps were studied and optimized by using Design of Experiment (DoE). For every step, all commercially-available solutions were screened to select the best for TxCell’s requirements. Statistical plans were then used to determine optimal values for each process parameter identified as critical or key.
- Title: CAR-Treg cells for clinical use.
- Speaker: Dr. Pierre Heimendinger, VP Pharmaceutical Development of TxCell.
- Event: CAR-TCR Summit Europe, February 20-22, 2018, London, United Kingdom.
- Presentation date & time: February 22, 2018, 2.30 pm GMT.