First Patient Dosed in Trial for Adicet's T-Cell Therapy ADI-100 in Autoimmune Disease
Adicet is also presenting biomarker data at ACR Convergance from a trial evaluating ADI-001 in B-cell malignancies that may indicate its potential to treat autoimmune diseases.
The first patient, who has lupus nephritis (LN), has been dosed in Adicet Bio’s phase 1 clinical trial (NCT06375993) evaluating ADI-100, its investigational allogeneic chimeric antigen receptor (CAR)-engineered gamma delta T-cell therapy, for the treatment of autoimmune diseases.1
In addition to patients with LN, the trial will also include patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc), antineutrophil cytoplasmic autoantibody associated vasculitis (AAV), idiopathic inflammatory myopathy (IIM), and stiff person syndrome (SPS). Adicet stated that it expects to begin enrolling patients with SLE, SSc, IIM, and SPS in the first half of next year. On the other hand, enrollment of patients with AAV is expected to begin in the second half of next year. Adicet additionally noted that it plans to announce initial data from patients with LN in the first half of 2025.
Also this month, at the 2024 American College of Rheumatology (ACR) Convergence, held November 14 to 19 in Washington, DC, Adicet is presenting biomarker data from 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, 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, which Adicet pointed out exceeds previously reported levels for patients treated with autologous alpha-beta CAR-T therapies. 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. The activation profile for CAR T-cells in tissues was characterized as “robust” with regard to granzyme B levels in situ.
“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,” Francesco Galimi, MD, PhD, the senior vice president and chief medical officer of Adicet Bio, said in a statement.2 “We are proud to share data and analyses, including clinical biomarker data, at ACR that support the potential of ADI-001 in autoimmune diseases. After activating clinical trial sites for LN and receiving investigational new drug application (IND) clearances to pursue additional autoimmune indications, we are committed to advancing ADI-001 in a basket study across 6 autoimmune indications. This strategy highlights our focus on addressing the significant unmet medical needs of patients who urgently require innovative and effective new treatment options.”
Although the phase 1 trial in autoimmune disease was originally only cleared for patients with LN, later IND amendments added eligibility for patients with SLE, SSc, AAV, IIM, and SPS.3 The protocol for the trial will divide patients into an arm for LN and SLE, an arm for SSc, an arm for IIM and SPS, and an arm for AAV.1 ADI-001 will be administered as a single dose. The primary end point of the study will cover safety an tolerability and the secondary end points will cover cellular kinetics, pharmacodynamics, changes in autoantibody titers, and disease activity scores relevant to patients’ diseases.
“Dosing the first LN patient in our phase 1 trial of ADI-001 marks an important step forward in our mission of improving the lives of patients affected by autoimmune diseases, particularly LN,” Galimi said in a separate statement regarding the first patient’s dosing.1 “With clinical biomarker data from our study in nonHodgkin’s lymphoma demonstrating robust tissue trafficking and complete CD19+ B-cell depletion in peripheral blood and secondary lymphoid tissue, ADI-001 has the potential to be a transformative off-the-shelf treatment option for several autoimmune diseases. Additionally, the FDA’s Fast Track Designation to ADI-001 in relapsed/refractory class III or class IV LN and the clearance of our investigational IND amendment application of ADI-001 for the treatment of SPS and IIM further serves to emphasize the broad and urgent unmet need for approved therapies to address autoimmune diseases.”
