Allogene grabs fast track tag for allogeneic CAR-T in lupus, myositis and scleroderma

Allogene Therapeutics announced that its investigational dual-targeted CD19/CD70 allogeneic CAR-T therapy has received three fast track designations from the U.S. FDA for the treatment of adult patients with autoimmune diseases.

ALLO-329 has been fast tracked for active refractory moderate-to-severe systemic lupus erythematous (SLE); active severe/refractory idiopathic inflammatory myopathy (IIM), specifically dermatomyositis, immune mediated necrotizing myopathy and anti-synthetase syndrome; and active refractory diffuse systemic sclerosis (SSc).

ALLO-329 utilizes CRISPR-based site-specific integration for dual CAR expression. This approach targets both CD19+ B cells and CD70+ T cells, which play a role in autoimmune disease pathogenesis. Additionally, ALLO-329 incorporates Allogene's clinically validated Dagger technology, designed to reduce or eliminate the need for lymphodepletion, a pre-treatment regimen that may be a significant barrier to CAR-T cell therapy adoption in autoimmune indications.

Allogene expects to initiate the phase 1 RESOLUTION basket trial in mid-2025. The trial is designed to evaluate the safety and preliminary efficacy of ALLO-329 in patients with SLE, IIM, and SSc. Proof-of-concept from the trial is expected by year-end 2025.

Allogene’s announcement comes amid a flurry of news — both good and bad — in what has quickly become a crowded autoimmune space. In early March, Atara cut its workforce and paused the study of its allogeneic CD19-targeted CAR-T therapy in systemic lupus erythematosus. Nkarta then revealed a restructuring and workforce reduction of 34% to extend its cash runway by more than one year to enable clinical milestones for its natural killer (NK) cell therapy in autoimmune diseases.

On the good news front, Cabaletta and Cellares announced that they had successfully delivered automated, concurrent manufacture of multiple batches of Cabaletta’s lead clinical candidate, a CD19-targeting CAR-T cell therapy for patients with autoimmune diseases, on a single Cellares Cell Shuttle platform.