Adicet's T-Cell Therapy ADI-100 Snags Clearance for Evaluation in Idiopathic Inflammatory Myopathy and Stiff Person Syndrome
Originally, the phase 1 clinical trial was only cleared for the recruitment of patients with lupus nephritis, but IND amendments have added more eligible indications.
Chen Schor, the president and chief executive officer of Adicet Bio
Adicet Bio’s ADI-100, an investigational allogeneic chimeric antigen receptor (CAR)-engineered gamma delta T-cell therapy currently being evaluated in a phase 1 clinical trial (NCT06375993) for lupus nephritis (LN), has received clearance from the FDA of an amendment to its investigational new drug (IND) application, allowing for the recruitment of patients with idiopathic inflammatory myopathy (IIM) and stiff person syndrome (SPS) into the trial.1
Originally, the phase 1 clinical trial was only cleared for the recruitment of patients with lupus nephritis (LN). Although, a prior IND amendment allowed for the recruitment of patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and antineutrophil cytoplasmic autoantibody associated vasculitis (AAV). Adicet noted that the trial will divide patients into an arm for LN and SLE, an arm for SSc, an arm for AAV, and an arm for IIM and SPS. The company stated that patients with IIM subtypes dermatomyositis, anti-synthetase syndrome, immune-mediated necrotizing myopathy, polymyositis, and overlap myositis will be eligible for participation. The treatment of patients in the IIM and SPS arm is expected to commence in the first quarter of next year.
“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,” Chen Schor, the president and chief executive officer at Adicet Bio, said in a statement.1 “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.”
In September 2024, Adicet reported biomarker data collected in the phase 1 GLEAN clinical trial (NCT04735471), which is evaluating ADI-001 for the treatment of B-cell malignancies, that may indicate it’s potential to treat autoimmune diseases.2 In lymph node biopsies from patients treated in the study, a mean exposure of 236,701 CAR T-cells per million across all dose levels was observed. Furthermore, CAR T-cells comprised 27% to 64% of total cellular material as measured by ddPCR in evaluable biopsies from patients treated at the 1x109 dose level. It was also noted that complete depletion of CD19+ B-cells alongside ADI-001 tissue trafficking and activation was observed upon analysis of lymphoid tissue.
“These results clearly support the potential of ADI-001 and Adicet’s off-the-shelf gamma delta CAR T-cell platform, by demonstrating robust trafficking and complete B-cell depletion in tissue, while providing superior exposure of ADI-001 in secondary lymphoid tissue compared to published third-party data reported for alpha-beta CAR T therapies,” Blake Aftab, PhD, the chief scientific officer of Adicet Bio, said in a September 2024 statement.2 “Together, the totality of our findings provide multiple levels of evidence highlighting the significant advantages of our approach and present a compelling opportunity for ADI-001 to extend B-cell targeting into tissues, as we look to address a range of autoimmune diseases in the clinic.”
Notably, Adicet is not the first company to receive an FDA IND clearance for a CAR-engineered T-cell therapy in SPS.3 In June 2024, Kyverna Therapeutics’ KYV-101, an investigational CD19-directed CAR T-cell therapy was cleared by the FDA for a trial in SPS. The clearance came just after Kyverna announced the first data of KYV-101’s use in a patient with SPS earlier in the month. The patient, a 59-year-old woman whose first symptoms of SPS appeared in 2014, was treated with a single dose of 1x108 CAR T-cells on Day 0 of the study, after having undergone a lymphodepletion regimen with fludarabine and cyclophosphamide. It was noted that the patient’s walking speed increased to 0.83 m/s on Day 20, up more than 100% from 0.37 m/s at Day 1, on the 5.5-m walking test, which was conducted with the patient using a wheeled walker.
