Allogeneic CAR-iNK Therapy to be Evaluated in B-Cell Malignancies

The FDA has granted investigational new drug (IND) clearance to Century Therapeutics’ chimeric antigen receptor (CAR) induced pluripotent stem cell (iPSC)-derived natural killer (NK) cell therapy CNTY-101 being investigated for the treatment of B-cell malignancies.

Century will now proceed with its phase 1ELiPSE-1 clinical study (NCT05336409) which plans to assess the safety, tolerability, pharmacokinetics and preliminary efficacy of CNTY-101 in around 75 participants with relapsed or refractory CD19 positive B-cell malignancies. Participants will receive cyclophosphamide (300 mg/m2) and fludarabine (30mg/m2) conditioning chemotherapy for 3 days. The trial will evaluate 2 schedules, a single-dose escalation and subcutaneous IL-2 and a 3-dose schedule per cycle of CNTY-101. Pending FDA clearance, patients that experience a clinical benefit may be able to receive additional cycles of treatment.

“This IND clearance is a significant milestone for Century as we execute on our vision to merge two disruptive platforms, precision gene editing and the powerful potential of iPSCs, to potentially move the allogeneic cell therapy field forward, and continue on our path to becoming a leader in the space,” Lalo Flores, chief executive officer, Century Therapeutics, said in a statement. “We believe that CNTY-101, our first and wholly owned product candidate, will be the most technically advanced and differentiated CD19-targeted cell product when it enters the clinic, which is anticipated to occur later this year. We look forward to assessing the potential of Allo-Evasion™ to prevent immunological rejection and enhance persistence of multiple dosing of CNTY-101 regimens with the aim to increase the proportion of patients that achieve durable responses.”

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CNTY-101 is an allogeneic CAR-iNK cell therapy that utilizes 4 technologies to boost its safety and efficacy. The therapy has a CD19 CAR for tumor targeting, IL-15 support for enhanced persistence, Century’s Allo-Evasion technology to prevent host rejection and also enhance persistence, and a safety switch to eliminate the therapy in the body if necessary. These modifications are present in the clonal iPSC master cell bank that CNTY-101 is manufactured from.

The company’s Allo-Evasion technology allows engineered products to evade identification by the host immune system, enabling repeated dosing without rejection and increased persistence of the cells during the treatment period. Century believes the technology will allow cell therapy products to yeilddeeper and more durable responses. Allo-Evasion uses 3 gene edits to accomplish the stealthing, knocking out beta-2-microglobulin, Class II Major Histocompatibility Complex Transactivator, and knocking in the HLA-E gene.

“CNTY-101 is the first allogeneic cell product candidate with six genetic modifications incorporated using sequential rounds of CRISPR-mediated homologous recombination and repair that has received IND clearance by the FDA,” Luis Borges, chief scientific officer, Century Therapeutics, added to the statement. “We believe CNTY-101 will demonstrate the power of Century’s iPSC technology and cell engineering technology platforms. This accomplishment is a testament to the expertise and dedication of our team as we continue to make progress developing our pipeline of iPSC-derived NK and T cell product candidates.”

REFERENCE

Century Therapeutics receives study may proceed notification from FDA for CNTY-101, the first allogeneic cell therapy product candidate engineered to overcome three major pathways of host vs graft rejection. News release. Century Therapeutics. August 25, 2022. https://finance.yahoo.com/news/century-therapeutics-receives-study-may-113000642.html