Allogene's Dual-Acting CAR T Candidate ALLO-329 Gets FDA Green Light for Autoimmune Disease Trial

Allogene Therapeutics announced yesterday that the FDA has cleared its IND application for a to begin a clinical trial of ALLO-329 across several autoimmune diseases, including lupus, idiopathic inflammatory myopathies and systemic sclerosis.

ALLO-329 is an investigational, allogeneic CRISPR-edited CD19/CD70 dual CAR T-cell therapy candidate, and the first CAR T-cell therapy designed to target both CD19+ B cells and CD70+ activated T cells.

Targeting of B cells has been demonstrated to induce durable, treatment-free remissions in patients with certain autoimmune diseases, while CD70 is expressed in activated T cells, which have been implicated in immune responses, including in autoimmunity. Simultaneous elimination of CD70+ T cells is anticipated to increase the therapeutic benefit of ALLO-329 and expand the list of addressable indications.

The RESOLUTION trial

The Phase 1 RESOLUTION trial is planned to start in mid-2025, with a year-end 2025 proof-of-concept target to demonstrate safety and efficacy of ALLO-329 in patients with systemic lupus erythematosus, including lupus nephritis, idiopathic inflammatory myopathies, and systemic sclerosis.

The trial design includes two distinct lymphodepletion arms: one using a dose of cyclophosphamide alone which is used by rheumatologists, and another that eliminates lymphodepletion entirely.

According to a press release published yesterday, ALLO-329 is designed to be a best-in-class, off-the-shelf dual-targeting system (depleting CD19+ B cells and CD70+ T cells) with enhanced therapeutic benefit by resetting the autoimmune system. This dual-targeting approach is combined with the ability of Allogene’s Dagger^® technology to overcome rejection, thereby reducing or eliminating lymphodepletion.

In December, Allogene presented pre-clinical data for ALLO-329 demonstrating that it induces deep, transient depletion of CD19+ B Cells and CD70+ T cells, and reduction in IgG and IgM without lymphodepletion in humanised murine models of lupus.

We will continue to update you on ALLO-329 and the RESOLUTION trial as new details emerge.

For a complete overview of current gene editing clinical trials, check out CRISPR Medicine News' Clinical Trials Database.

When this article was originally published on 29th Janaury 2025, it was incorrectly stated that ALLO-329 is an investigational, allogeneic TALEN-edited CD19/CD70 dual CAR T-cell therapy candidate. ALLO-329 is an investigational, allogeneic CRISPR-edited CD19/CD70 dual CAR T-cell therapy candidate. The text was amended to correct this error after publication.