The Amsterdam, Netherlands-based firm announced this week its lead candidate ATIR101 received Regenerative Medicine Advanced Therapy (RMAT) designation from the US Food and Drug Administration (FDA), a fast-track development pathway for cell therapies created through the 21st Century Cures Act last year.
Kiadis spokesman Karl Hård told this publication the firm is exploring various options to expand capacity in order to treat more patients, both in Europe and the US.
The product is made by obtaining donor lymphocytes to provide protection against relapse and infection, with those lymphocytes that may attack the patient and cause graft versus host disease selectively killed.
“We do this by activating those patient specific lymphocytes by mixing the donor graft with patient materials, which causes patient specific lymphocytes to become activated,” he said. “In those activated lymphocytes a proprietary photosensitive compound, TH9402, that we add will accumulate, in other lymphocytes this compound is pumped out.”
When exposed to green light TH9402 is activated killing the patient specific GVHD causing lymphocytes, he continued.
“The remaining lymphocytes that can still protect against relapse and infection are then frozen into liquid nitrogen, sent to the transplant clinic and infused into the patient. The whole process takes 5 days, of which 4 days in an incubator, and does not involve genetic engineering.”
Currently Kiadis uses German contract manufacturing organisation (CMO) Blutspendendienst for the manufacture, while critical release assays performed in-house.
As every production of ATIR101 is patient-specific, Hård said the production challenges lie in the logistics rather than the scale-up.
“The patient specific manufacturing process does not require scale up in the classical sense of increased batch size or volume, and the current batch size per patient is adequate,” he said.
“The main challenge is establishing a robust logistics and track-and-trace system, with patient specific batch release and associated Quality systems. This challenge is new to pharma, but we can of course learn a lot from experience in other industries (e.g., fedex or amazon).”
A similar challenge was recently raised following the approval of Novartis’ Kymriah (tisagenlecleucel) late last month. The product was the first FDA approved chimeric antigen receptor (CAR) T-cell therapy and – according to logistics firm Trakcel – require a far more complex and time-critical supply chain.
“CAR-T is an autologous therapy, as personalised as therapies get – the patient is part of the supply chain because a CAR-T therapy is produced from the patient’s own cells,” CEO Ravi Nalliah recently told Biopharma-Reporter.
“It is critical that the cellular material produced from one patient is only used to treat that patient. This requires a higher level of tracking than other cold-chain products that are not patient-specific.”