Atara Biotherapeutics Shares Preclinical Data on ATA3219 CAR T Therapy at ISCT 2024

Atara Biotherapeutics, Inc., a leader in T-cell immunotherapy, has released promising preclinical data for its allogeneic, anti-CD19 chimeric antigen receptor (CAR) T-cell therapy candidate, ATA3219. This therapy is aimed at treating B-cell-driven autoimmune diseases such as systemic lupus erythematosus (SLE) and multiple sclerosis (MS). The findings will be showcased at the International Society for Cell & Gene Therapy (ISCT) 2024 Annual Meeting in Vancouver, Canada.

ATA3219's Composition and Mechanism
ATA3219 uses allogeneic CD19-directed CAR Epstein-Barr virus (EBV) T cells, designed to be readily available off-the-shelf. The therapy involves clinically validated technologies, including a modified CD3ζ signaling domain (1XX), which ensures sustained effector function while managing activation and inflammation. The cells maintain a less differentiated phenotype for robust expansion and persistence, and their endogenous T-cell receptor remains unaltered, enhancing survival signals for T cells.

Preclinical Findings
Dr. Cokey Nguyen, Atara's Executive Vice President and Chief Scientific & Technical Officer, highlighted the therapy's potential benefits over existing autologous CD19 CAR T treatments. ATA3219 shows robust B-cell depletion in SLE and MS patient-derived immune cells while producing lower levels of pro-inflammatory cytokines. This feature suggests reduced toxicity and improved tolerability, making it a promising candidate for further clinical evaluation.

The preclinical data reveal that ATA3219 has potent CD19 antigen-specific cytotoxic activity both in vitro and in vivo. Key comparisons to autologous benchmark CD19 CAR T cells include:
- A more robust central memory cell population due to the 1XX co-stimulatory domain and optimized manufacturing.
- Complete B-cell depletion against SLE and MS patient peripheral blood mononuclear cells, with similar potency.
- Lower secretion of pro-inflammatory cytokines such as IFN-γ, TNF-α, and IL-6, along with Th2 cytokines IL-4 and IL-5, while maintaining effective B-cell depletion.

These findings support the advancement of ATA3219 into clinical trials for B-cell-driven autoimmune diseases.

Clinical Evaluation Plans
ATA3219 is currently undergoing a Phase 1 trial (NCT06256484) for relapsed/refractory B-cell non-Hodgkin’s lymphoma (NHL), with initial clinical data expected by the fourth quarter of 2024. Additionally, a multi-center, Phase 1, open-label, single-arm, dose-escalation study will evaluate ATA3219 for lupus nephritis (LN) with lymphodepletion and severe SLE without lymphodepletion. Initial data for LN and severe SLE are anticipated in the first and second halves of 2025, respectively.

Future Directions and ATA3219's Potential
ATA3219 represents a next-generation approach to CAR T therapy, leveraging the natural biology of unedited T cells with allogeneic therapy benefits. Atara's EBV T-cell platform has treated over 600 patients, demonstrating low alloreactivity and functional persistence. Unlike gene-edited therapies that deactivate T-cell receptor (TCR) functions, Atara’s approach maintains the native EBV TCR expression, reducing graft-vs-host disease risk while promoting in vivo persistence.

Atara Biotherapeutics continues to harness cutting-edge science for developing off-the-shelf cell therapies aimed at difficult-to-treat cancers and autoimmune conditions. The company's versatile T-cell platform, which does not require T-cell receptor or HLA gene editing, supports a diverse portfolio targeting EBV-related diseases and next-generation AlloCAR-Ts for hematological malignancies and B-cell-driven autoimmune diseases.

In summary, ATA3219 shows significant promise in offering a potent and potentially less toxic treatment option for B-cell-driven autoimmune diseases. The ongoing and upcoming clinical trials will further elucidate its efficacy and safety, paving the way for potentially transformative therapies for patients with these challenging conditions.

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