Adicet Bio has received FDA clearance to amend its investigational new drug (IND) application for ADI-001, allowing the inclusion of patients with idiopathic inflammatory myopathy (IIM) and stiff person syndrome (SPS) in its ongoing Phase 1 clinical trial (NCT06375993). ADI-001 is an investigational allogeneic chimeric antigen receptor (CAR)-engineered gamma delta T-cell therapy. This expansion builds upon Adicet's existing focus on autoimmune diseases, with the trial now encompassing six autoimmune indications.
Trial Expansion and Design
Originally, the Phase 1 trial was designed to evaluate ADI-001 in patients with lupus nephritis (LN). Subsequent amendments broadened the scope to include systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and antineutrophil cytoplasmic autoantibody-associated vasculitis (AAV). The trial will now feature distinct arms for LN/SLE, SSc, AAV, and IIM/SPS. Adicet specifies that IIM subtypes such as dermatomyositis, anti-synthetase syndrome, immune-mediated necrotizing myopathy, polymyositis, and overlap myositis will be eligible for participation. Treatment in the IIM and SPS arm is slated to commence in the first quarter of 2025.
Rationale and Biomarker Data
The decision to expand the trial is supported by clinical biomarker data from the Phase 1 GLEAN clinical trial (NCT04735471), which evaluated ADI-001 in B-cell malignancies. These data indicated ADI-001's potential efficacy in autoimmune diseases. Lymph node biopsies from treated patients showed a mean exposure of 236,701 CAR T-cells per million across all dose levels. Furthermore, CAR T-cells constituted 27% to 64% of total cellular material, as measured by ddPCR in evaluable biopsies from patients treated at the 1x109 dose level. Complete depletion of CD19+ B-cells, along with ADI-001 tissue trafficking and activation, was observed in lymphoid tissue analysis.
Executive Commentary
"The FDA’s acceptance of our IND amendment to evaluate ADI-001 in patients with IIM and SPS builds on our recent momentum in autoimmune diseases, expanding our efforts to 6 autoimmune indications as we aim to bring our differentiated gamma delta T-cell therapy candidates to more patients in need of new treatment options,” said Chen Schor, the president and chief executive officer at Adicet Bio, in a statement. “Following our recent announcement highlighting clinical biomarker data which demonstrated robust B-cell depletion and preferential trafficking to tissues and organs, we believe in ADI-001’s best-in-class potential for the treatment of autoimmune diseases, and we look forward to initiating patient enrollment in IIM and SPS in the first quarter of 2025 in our ongoing phase 1 clinical program.”
Competitive Landscape
Adicet is not the first company to receive FDA IND clearance for a CAR-engineered T-cell therapy in SPS. Kyverna Therapeutics' KYV-101, a CD19-directed CAR T-cell therapy, received clearance for a trial in SPS in June 2024. Kyverna also announced initial data on KYV-101's use in an SPS patient, showing improved walking speed after treatment.
