Fate touts potential to make 15,000 cell therapy doses per cGMP run

The shift in focus from autologous to allogeneic cell therapies stands to eliminate the logistical issues associated with approved CAR-Ts Kymriah and Yescarta by ending the need to work with a patient’s own cells. However, the reliance of allogeneic products on donor cells comes with its own problems.

Maximum capacity is tied to the availability of donor cells and the quality of starting materials is variable. To make allogeneic cell therapies of consistent quality at large scale, companies may need to find a new starting material.

Fate sees induced pluripotent stem cells (iPSCs) as the answer to the problem.  Human iPSCs can be engineered and expanded, giving Fate a potentially renewable source of material for its off-the-shelf cell therapies.

Having opened a ‘/GMP compliant manufacturing facility in San Diego last year, Fate is putting that idea to the test. FT538, Fate’s fourth off-the-shelf, iPSC-derived natural killer cell therapy, recently came through a manufacturing run at the San Diego site in support of an early-phase clinical trial in blood cancer patients.

Fate CEO Scott Wolchko talked investors through the process on a recent quarterly results conference call. Wolchko’s team made a clonal iPSC cell line by reprogramming and engineering cells taken from a healthy donor, giving the company a renewable starting material for the production of FT538.

The first small-scale manufacturing campaign yielded 300 billion FT538 cells that Fate filled into more than 300 units of cryopreserved infusion-ready drug product. That gives an incomplete picture of the potential capacity, though.

“Since we rightsized our fill/finish activities to successfully produce drug product for dose escalation only, the campaign was not designed to maximize drug product yield​,” said Wolchko.

Fate used the small-scale run to calculate the yield it could achieve from a cGMP campaign, coming out with a prediction that it could make trillions of cells capable of filling 15,000 unit doses.

The calculation suggests Fate’s iPSC-based approach may support the production of cell therapies at scale. Allogene, through its alliance with Notch Therapeutics, and other cell therapy developers are trying to achieve the same outcome using iPSCs and other approaches.

So far, none of the biotechs have generated clinical data to show the cell therapies have the required safety and efficacy but work toward that goal is advancing apace. Fate secured clearance to start a clinical trial of the first iPSC-derived CAR-T cell therapy last month and has multiple other prospects already in the clinic.