Allogene Therapeutics’ ALLO-329 Snags FDA Fast Track Designations for 3 Rheumatology Indications

Allogene Therapeutics’ ALLO-329, an investigational allogeneic chimeric antigen receptor T-cell (CAR-T) therapy, has been granted fast track designation from the FDA for active refractory moderate-to-severe systemic lupus erythematous (SLE); active severe/refractory idiopathic inflammatory myopathy (IIM), specifically including dermatomyositis, immune mediated necrotizing myopathy, and antisynthetase syndrome; and active refractory diffuse systemic sclerosis (SSc).¹

Allogene Therapeutics is currently set to evaluate ALLO-329 for these 3 indications in a phase 1 basket study referred to as RESOLUTION (NCT identifier pending).² The trial will also include patients with lupus nephritis. Allogene received clearance of an investigational new drug (IND) application from the FDA for RESOLUTION in January 2025, and expects that the trial will begin in the middle of this year.^1,2 Notably, the study will include 2 lymphodepletion arms: one in which patients will receive cyclophosphamide alone for lymphodepletion and the other in which no lymphodepletion regimen will be used.

"Receiving these designations for ALLO-329 underscores the versatility and transformative promise of this next-generation allogeneic CAR T investigational product in redefining the autoimmune treatment landscape," Zachary Roberts, MD, PhD, the executive vice president of research and development and the chief medical officer at Allogene.¹ "Leveraging our extensive expertise, we've developed this off-the-shelf CAR T specifically for autoimmune diseases, prioritizing both scalability and the reduction or elimination of lymphodepletion – a key barrier in this patient population."

Allogene stated that it anticipates proof-of-concept in RESOLUTION will be achieved by the end of 2025. Notably, ALLO-329 targets both CD19+ B-cells and CD70+ activated T-cells, with the intention of eliminating dysfunctional cells of both types.² Furthermore, the CAR-T product utilizes the company’s Dagger technology, which is intended to reduce or eliminate the need for lymphodepletion by making the CAR-T more resistant to rejection by the patient’s immune system.

“A year ago, we unveiled the concept of ALLO-329, an allogeneic CAR-T product specifically designed to address the unique challenges faced by patients with autoimmune diseases,” David Chang, MD, PhD, the president, CEO, and cofounder of Allogene, said in a statement at the time of the IND clearance.² “[W]ith the FDA’s clearance of our IND, that vision has become a reality, achieved at an extraordinary pace thanks to Allogene’s unparalleled expertise in research, manufacturing, and clinical development. Demonstrating the power of an allogeneic CAR-T to reset the immune system, combined with the ability of our Dagger technology to reduce or eliminate lymphodepletion, could represent a transformative step forward. Successful proof-of-concept in this basket study has the potential to not only validate our best-in-class approach but also paves the way for expanding into a broad range of autoimmune indications beyond rheumatology.”

ALLO-329 is not the first cell therapy to have received fast track designation from the FDA for SLE and IIM indications so far this year. In February 2025, Adicet Bio’s ADI-100, its investigational allogeneic CAR-engineered gamma delta T-cell therapy being evaluated for the treatment of various autoimmune diseases, received FDA fast track designation for refractory systemic lupus erythematosus (SLE) with extrarenal involvement.³ The product had previously received fast track designation from the FDA for relapsed/refractory class III or class IV lupus nephritis (LN).^3,4 In addition, in January 2025 RESTEM’s Restem-L, an investigational umbilical cord outer lining stem cells (ULSCs) product, was granted fast track designation by the FDA for IIM (also known as polymyositis and dermatomyositis, PM/DM).⁵ Restem-L had previously received orphan drug designation from the FDA for PM/DM in December 2024.⁶

REFERENCES
1. Allogene Granted Three U.S. FDA Fast Track Designations (FTD) for ALLO-329, a Next-Generation Dual-Targeted CD19/CD70 Allogeneic CAR T, for the Treatment of Lupus, Myositis and Scleroderma. News release. Allogene Therapeutics, Inc. April 7, 2025. Accessed April 7, 2025. https://ir.allogene.com/news-releases/news-release-details/allogene-granted-three-us-fda-fast-track-designations-ftd-allo
2.Allogene Therapeutics secures U.S. FDA IND clearance for ALLO-329, advancing its next-generation allogeneic CAR T into autoimmune diseases. News release. Allogene Therapeutics, Inc. January 28, 2025. Accessed April 7, 2025. https://ir.allogene.com/news-releases/news-release-details/allogene-therapeutics-secures-us-fda-ind-clearance-allo-329
3.Adicet Bio. Adicet Bio Receives FDA Fast Track Designation for ADI-001 for the Treatment of Refractory Systemic Lupus Erythematosus (SLE) with Extrarenal Involvement. February 5, 2025. Accessed April 7, 2025. https://investor.adicetbio.com/news-releases/news-release-details/adicet-bio-receives-fda-fast-track-designation-adi-001-treatment
4.Adicet Bio. Adicet Bio Receives FDA Fast Track Designation for ADI-001 in Lupus Nephritis. June 5, 2024. Accessed April 7, 2025. https://investor.adicetbio.com/news-releases/news-release-details/adicet-bio-receives-fda-fast-track-designation-adi-001-lupus
5. RESTEM receives FDA fast track designation for restem-l for idiopathic inflammatory myopathy. News release. RESTEM. January 7, 2024. Accessed April 7, 2025. https://www.globenewswire.com/news-release/2025/01/07/3005317/0/en/RESTEM-Receives-FDA-Fast-Track-Designation-for-Restem-L-for-Idiopathic-Inflammatory-Myopathy.html
6. RESTEM receives FDA orphan drug designation for its ULSC program for the treatment of polymyositis and dermatomyositis. News release. RESTEM. December 3, 2024. Accessed April 7, 2025. https://www.globenewswire.com/news-release/2024/12/03/2990556/0/en/RESTEM-Receives-FDA-Orphan-Drug-Designation-for-its-ULSC-Program-for-the-Treatment-of-Polymyositis-and-Dermatomyositis.html#:~:text=CORONA%2C%20Calif.%2C%20Dec