Adicet Bio, Inc. (Nasdaq: ACET) announced clinical biomarker data for its allogeneic gamma delta CAR T-cell therapy, ADI-001, at the ACR Convergence 2024, highlighting its potential in treating various autoimmune diseases. The data demonstrated robust tissue homing and complete CD19+ B cell depletion in secondary lymphoid tissue, with CAR T-cell activation levels ranging from 27% to 64% at the 1E9 dose.
The Phase 1 GLEAN trial data, featured in an oral session at the conference, showed that ADI-001 achieved significant CAR T-cell activation and tissue exposure in lymph node biopsies. This level of activation exceeds those previously reported for autologous alpha-beta CAR T-cell therapies. The study also revealed a robust activation profile of CAR T-cells detected in tissues, based on in situ levels of granzyme B.
Key Biomarker Findings
The clinical biomarker data for ADI-001 indicates significant therapeutic potential in autoimmune diseases. A key finding was the CAR T-cell activation levels of 27-64% in lymph node biopsies at the 1E9 dose, notably higher than previous autologous alpha-beta CAR T therapies. Complete depletion of CD19+ B cells in lymphoid tissue was also observed, a promising result given that current anti-CD20 antibody treatments often fail to achieve this level of depletion.
Francesco Galimi, M.D., Ph.D., Chief Medical Officer, stated, "We believe the key to advancing care for autoimmune patients is to develop a therapeutic candidate that demonstrates robust tissue homing, complete CD19+ B cell depletion in tissue, and superior drug exposure in secondary lymphoid tissue with a positive safety profile."
Clinical Development and Trial Design
Adicet is currently pursuing ADI-001 in a basket study across six autoimmune indications, including lupus nephritis (LN), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), idiopathic inflammatory myopathy (IIM), stiff person syndrome (SPS), and anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). The company has received investigational new drug application (IND) clearances to pursue these additional autoimmune indications.
The Phase 1 study has four separate arms, enrolling LN and SLE patients into one arm, SSc patients into a second arm, IIM and SPS patients in a third arm, and AAV patients into a fourth arm. Enrolled patients will receive a single dose of ADI-001. The primary objectives of the study are to evaluate the safety and tolerability of ADI-001. Secondary objectives include measuring cellular kinetics, pharmacodynamics, changes in autoantibody titers, and appropriate disease activity scores in each indication.
Implications for Autoimmune Disease Treatment
These data are particularly meaningful for treating autoimmune conditions because they demonstrate both robust tissue penetration and complete B cell depletion in target areas. The basket trial approach across six different autoimmune indications suggests broad therapeutic potential. The results support ADI-001’s potential for achieving complete B-cell depletion in peripheral blood and within tissues, which could offer a significant advantage over existing treatments.
ADI-001 has been granted Fast Track Designation by the FDA for the potential treatment of relapsed/refractory class III or class IV lupus nephritis (LN).
