Atara Biotherapeutics, Inc. announced preclinical data on ATA3431, a next-generation allogeneic CD20/CD19-dual targeted chimeric antigen receptor (CAR) EBV T-cell therapy candidate. Findings support ATA3431 advancement into clinical testing, initially focused on the treatment of B-cell malignancies. The data will be presented in a poster presentation at the 65thAmerican Society of Hematology (ASH) Annual Meeting taking place December 9-12, 2023, in San Diego.

ATA3431 is an allogeneic, bispecific CAR directed against CD20 and CD19, built on Atara?s EBV T-cell platform that does not require T-cell receptor (TCR) or human leukocyte antigen (HLA) gene editing. The design consists of a tandem CD20-CD19 design, with binders oriented to optimize potency. ATA3431 also incorporates the clinically validated 1XX costimulatory domain that enhances stemness and modulates exhaustion to extend functional persistence.

Compared to an autologous CD20/CD19 CAR-T benchmark, the ATA3431 preclinical data demonstrate potent antitumor activity, long-term persistence, and superior tumor growth inhibition. Data highlights include: In functional evaluation, ATA3431 showed stable CAR expression with a predominantly CD8+ T-cell distribution. The 1XX signaling domain and optimized manufacturing process that enriches for a less differentiated phenotype yielded a high central memory population compared with autologous CD20/CD19 bispecific CAR-T cells, achieving consistent killing of CD20+ and/or CD19+ tumor cells following repeated in vitro challenges; ATA3431 demonstrated minimal alloreactivity against HLA mismatched targets due to the inherent ability of EBV T cells to recognize defined viral antigens.

The cells also showed HLA-independent activity against CD20+/CD19+ targets in vitro; ATA3431 mediated highly potent tumor growth inhibition in a lymphoma animal model that correlates with long-term persistence without additional exogenous cytokine support; ATA3431 showed superior in vivo anti-tumor efficacy, survival, and functional persistence, in both CD19 high- and low-expressing lymphoma models, compared to autologous benchmark CAR-T cells with no observed treatment-related toxicities. This demonstrates ATA3431?s potential to overcome antigen escape, which is hypothesized to be a major cause of treatment resistance or disease relapse with current CD19-targeted CAR-T treatment. Separately, an academic study presented long-term follow-up data on heavily pre-treated patients infused with an earlier generation off-the-shelf CD19 targeted EBV CAR T-cell construct in B-cell lymphoma and acute lymphoblastic leukemia.

Encouraging overall survival of up to three years was observed in 12 patients with relapsed/refractory B-cell malignancies after hematopoietic cell transplant (HCT) treated with 3rd party donor derived allogeneic EBV CD19 CAR T.