AAV enrollment into CAR T-cell trial pushed to 2nd half of 2025
Adicet trial tests ADI-001 in patients with autoimmune conditions
Adicet Bio has pushed to the second half of 2025 the expected timing for enrolling patients with ANCA-associated vasculitis (AAV) in an ongoing Phase 1 clinical trial testing ADI-001, an experimental CAR T-cell therapy for a number of autoimmune diseases.
The company had said it expected enrollment to start by the end of last year for the most common form of lupus, known as systemic lupus erythematosus (SLE), systemic sclerosis, and AAV, but the Phase 1 trial (NCT06375993) remains open only to adults with lupus nephritis, a common complication of lupus.
The U.S. Food and Drug Administration cleared the company to expand clinical testing of ADI-001 beyond lupus nephritis to include three other autoimmune diseases. Preliminary data for the additional indications are expected by the second half of 2025, Adicet said.
Last year “was a momentous year for Adicet as we amplified our efforts in autoimmune diseases,” Chen Schor, Adicet’s president and CEO, said in a company press release. “As we look ahead to 2025, we believe we are well positioned to build on this momentum to advance our product candidates.”
An autoimmune disease, AAV is caused by self-reactive antibodies that guide an immune attack against the cells lining the small blood vessels in tissues across the body, causing inflammation and damage. Antibodies, including self-reactive ones, are produced by a type of immune cell called B-cells.
Collecting T-cells to target B-cells
ADI-001 involves collecting a patient’s immune T-cells and modifying them in the lab before returning them to the patient by infusion. The T-cells are modified to produce a chimeric antigen receptor (CAR) that binds to CD20, a protein found on B-cells.
Most of the T-cells present in ADI-001 are a subtype of T-cells called gamma delta T-cells, which exist in many body tissues. Once CAR T-cells bind to CD20, they are activated to kill B-cells, which is expected to lower the production of self-reactive antibodies and ease symptoms.
The therapy is also being evaluated as a potential treatment for B-cell cancers, with early clinical data showing that ADI-001 was present in patients’ lymph nodes after infusion into the bloodstream. Lymph nodes are a type of secondary lymphoid tissue where T-cells and B-cells are activated to initiate an immune response. Ten days after infusion, ADI-001 resulted in a complete depletion of B-cells in certain tissues, called secondary lymphoid tissues, such as the lymph nodes and spleen.
“The successful expansion of our Phase 1 trial of ADI-001 into six autoimmune indications, building upon clinical biomarker data demonstrating ADI-001’s robust tissue trafficking and complete [B-cell] depletion in secondary lymphoid tissue, further reinforces ADI-001’s potential as an off-the-shelf treatment option,” Schor said.
The Phase 1 trial will test ADI-001 in people with lupus nephritis and systemic lupus erythematosus, systemic sclerosis, AAV, idiopathic inflammatory myopathy and stiff-person syndrome.
After screening, all patients receive chemotherapy with fludarabine and cyclophosphamide to deplete their T-cells and make room for the modified ones, which are then infused back as a single dose into the bloodstream.
ADI-001 is first given as a single infusion to find the safest dose level. Once a dose is considered safe, more patients are treated at that dose level to confirm its safety profile. The confirmed dose is used to establish the recommended dose for future Phase 2 clinical testing.
The trial’s main goal is to assess how safe and well tolerated ADI-001 is over 28 days, which is the dose-limiting toxicity window, and throughout two years. Secondary goals include looking at how ADI-001 behaves in the body, its effect on the production of self-reactive antibodies, and changes in disease activity scores for each autoimmune disease.
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