World Lupus Day 2025: Cell Therapy Continues its March of Progress

Over the past few years interest has ramped up across industry and academia in bringing advanced cell therapy modalities such as chimeric antigen receptor T-cell (CAR-T) therapy to the field of autoimmune disease, with many directing their initial efforts at systemic lupus erythematosus (SLE) and lupus nephritis (LN). Thus far, late 2024 and early 2025 have not been any exception to the trend, as in the past few months alone a number of companies have hit milestones or otherwise made progress in their cell therapy programs for lupus.

For World Lupus Day, observed annually on May 10 by the patient and clinician communities, CGTLive® is taking a look back at some of the major news stories in this field that have taken place during recent months. Click the "READ MORE" buttons for more details and information about each item.

Fate Therapeutics’ iPSC-derived CAR-T FT819 Nabs FDA RMAT Designation for Lupus

April 14, 2025 — Fate Therapeutics’ FT819, an investigational allogeneic induced pluripotent stem cell (iPSC)-derived CAR-T therapy, has garnered regenerative medicine advanced therapy (RMAT) designation from the FDA for active moderate to severe SLE, including LN.

FT819, the development of which is supported by a California Institute of Regenerative Medicine grant that provides $7.9 million in funding, is currently being evaluated in a multicenter phase 1 clinical trial (NCT06308978) for the aforementioned SLE indications. Notably, patients in the study are receiving FT819 after a conditioning regimen that consists of either bendamustine alone or cyclophosphamide alone. Dose expansion in up to 10 patients is currently underway at a dose of 360 million cells and a dose of 900 million cells is being assessed in dose escalation. Initial clinical safety and activity data from the trial informed the FDA’s decision to provide the RMAT designation. Fate expends that additional data from the study will be announced at medical conferences this year.

“RMAT designation recognizes the unique therapeutic potential of our off-the-shelf CAR T-cell therapy to address the unmet need of a wide range of lupus patients,” Bob Valamehr, PhD, MBA, the president and chief executive officer of Fate Therapeutics, said in a statement. “We believe our current development strategy for FT819, which is designed to provide CAR T-cell therapy on-demand in a cost-effective manner and alleviate patient burden associated with intense conditioning chemotherapy and extended hospitalization, may enable treatment in the community setting and access to patients in underserved areas. With this designation, we look forward to working closely with the FDA as we seek to accelerate development of FT819 to bring this unique treatment to patients across the continuum of care.”

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

April 7, 2025 — Allogene Therapeutics’ ALLO-329, an investigational allogeneic CAR-T therapy, has been granted fast track designation from the FDA for active refractory moderate-to-severe 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).

Allogene Therapeutics is currently set to evaluate ALLO-329 for these 3 indications in a phase 1 basket study referred to as RESOLUTION. 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. 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. "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."

Adicet's T-Cell Therapy ADI-100 Fast Tracked by FDA for Refractory Systemic Lupus Erythematosus

February 6, 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, has received FDA fast track designation for refractory SLE with extrarenal involvement.

Notably, the product previously received fast track designation from the FDA for relapsed/refractory class III or class IV LN.

The therapy, which targets the CD20 antigen, is currently being evaluated in a phase 1 clinical trial (NCT06375993) for patients with SLE, SSc, antineutrophil cytoplasmic autoantibody associated vasculitis (AAV), IIM, and stiff person syndrome (SPS). ADI-001 is also being evaluated in the phase 1 GLEAN clinical trial (NCT04735471) for B-cell malignancies. In GLEAN, the CAR-T showed robust exposure and was able to bring about complete depletion of CD19+ B-cells in the peripheral blood and in secondary lymphoid tissue.

SC291 CAR T-Cell Therapy Fast Tracked for Relapsed/Refractory SLE

December 4, 2024 — Sana Biotechnology’s investigational CAR T-cell therapy, known as SC291, has been granted fast track designation by the FDA for the treatment of relapsed or refractory SLE, including both LN and extrarenal lupus.

Dhaval Patel, MD, PhD, the chief scientific officer of Sana, said in a statement that the company was pleased to receive the designation, noting that it “highlights the need for new treatment options for patients with relapsed/refractory SLE."

The therapy is a CD19-directed, hypoimmune (HIP)-modified allogeneic CAR-T agent, designed as an off-the-shelf treatment. "As a HIP-modified allogeneic CAR T therapy with a scaled manufacturing process that produces hundreds of patient doses per manufacturing run, SC291 has the potential to serve as a universal off-the-shelf therapy that can address this large unmet need. We look forward to sharing initial data from the ongoing GLEAM trial," Patel said.

Cabaletta Bio’s CAR-T CABA-201 Effects Clinical Responses in Autoimmune Diseases

November 27, 2024 — Cabaletta Bio’s CABA-201, an investigational CD19-directed CAR-T therapy intended to treat various indications, has effected responses or possible emerging responses in some patients treated in the phase 1/2 RESET-SLE clinical trial (NCT06121297) for SLE and LN, the phase 1/2 RESET-Myositis clinical trial (NCT06154252) for active IIM, and the phase 1/2 RESET-SSc clinical trial (NCT06328777) in SSc. These data were presented at the 2024 American College of Rheumatology (ACR) Convergence, held November 14 to 19 in Washington, DC.

Cabaletta reported that in RESET-Myositis, a patient with immune-mediated necrotizing myopathy (IMNM) who has 6 months of follow-up showed a sustained and improved clinical response without flares, and was off of immunosuppressants. Another patient with IMNM and 1 month of follow-up showed a total improvement score in line with the aforementioned patient and was also off immunosuppressants at 1 month posttreatment. A patient with dermatomyositis achieved a major total improvement score response and was off immunosuppressants at 1 month posttreatment. This patient also showed an improvement to normal in muscle strength and improved from 25 to 9 on the Cutaneous Dermatomyositis Disease Area and Severity Index – Activity.

In RESET-SLE, 3 patients with nonrenal SLE had no clinical symptoms on the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) 2000 at their latest follow-up. The first patient in this group to have been treated also finished tapering off of prednisone. A patient with LN improved from 22 to 8 on SLEDAI from baseline to 4 months of follow-up. The patient’s proteinuria also approached normal levels, constituting an improvement of greater than 90%. This patient, who is off immunosuppressants, is in the process of tapering off prednisone.