Preclinical Development of CTX120, an Allogeneic CAR-T Cell Targeting Bcma

Autologous CAR-T cells targeting BCMA have induced robust and durable responses in patients with relapsed/refractory multiple myeloma. However, autologous cell therapies face several challenges which will likely limit the number of patients that will have access to these therapies. These limitations include manufacturing failure rates, wait time and supply constraints in addition to other factors such as reimbursement. Allogeneic CAR-T cells can potentially overcome these access challenges, and may have several other advantages over autologous therapies. Allogeneic CAR-T cells are derived from robust healthy donor T cells through a batch manufacturing process, which may result in a highly consistent product with greater potency and enable better safety management. Here we show further development and preclinical data for CTX120, an allogeneic "off the shelf" CAR-T cell targeting BCMA. CTX120 is produced using the CRISPR/Cas9 system to eliminate TCR and MHC class I, coupled with specific insertion of the CAR at the TRAC locus. CTX120 shows consistent and high percent CAR expression from this controlled insertion and exhibits target-specific cytotoxicity and cytokine secretion in response to BCMA positive cell lines. CTX120 CAR-T cells retain their cytotoxic capacity over multiple in vitro re-challenges, demonstrating durable potency and lack of exhaustion. In mouse models of multiple myeloma, CTX120 showed typical CAR-T persistence and eliminated tumors completely, resulting in long-term survival as compared to untreated animals. These data support the ongoing development of CTX120 for treatment of patients with multiple myeloma and further demonstrate the potential for our CRISPR/Cas9 engineered allogeneic CAR-T platform to generate potent CAR-T cells targeting different tumor antigens. Disclosures Dar: CRISPR Therapeutics: Employment, Equity Ownership. Henderson: CRISPR Therapeutics: Employment, Equity Ownership. Padalia: CRISPR Therapeutics: Employment, Equity Ownership. Porras: CRISPR Therapeutics: Employment, Equity Ownership. Mu: CRISPR Therapeutics: Employment, Equity Ownership. Kyungah: CRISPR Therapeutics: Employment, Equity Ownership. Police: CRISPR Therapeutics: Employment, Equity Ownership. Kalaitzidis: CRISPR Therapeutics: Employment, Equity Ownership. Terrett: CRISPR Therapeutics: Employment, Equity Ownership. Sagert: CRISPR Therapeutics: Employment, Equity Ownership.