Kidney Week

Abstract: INFO11-FR

A Phase 1 Study of ADI-001, an Allogeneic CD20-Targeted γδ CAR T cell Therapy, in Adults with Autoimmune Disease

Session Information

• Informational Posters - 2
  October 25, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• No subcategory defined

Authors

• Hsu, Ben L., Adicet Bio, Inc., Redwood City, California, United States

Ben L. Hsu, MD, PhD

• Ye, Yining, Adicet Bio, Inc., Redwood City, California, United States

Yining Ye, PhD

• Moreno, Monica, Adicet Bio, Inc., Redwood City, California, United States

Monica Moreno, PhD

• Vosganian, Gregory, Adicet Bio, Inc., Redwood City, California, United States

Gregory Vosganian, MD

• Costanzo, Simona, Adicet Bio, Inc., Redwood City, California, United States

Simona Costanzo, PhD

• Galimi, Francesco, Adicet Bio, Inc., Redwood City, California, United States

Francesco Galimi, MD, PhD

• Boin, Francesco, Cedars-Sinai Medical Center, Los Angeles, California, United States

Francesco Boin, MD

• Al-Rabadi, Laith, University of Utah Health, Salt Lake City, Utah, United States

Laith Al-Rabadi, MD

• Koumpouras, Fotios, Yale University School of Medicine, New Haven, Connecticut, United States

Fotios Koumpouras, MD

Description

Chimeric antigen receptor (CAR) T therapy is emerging as a highly promising treatment approach for autoimmune diseases (AID), including those with renal involvement¹. B-cell targeting CAR-T have achieved drug-free remissions in patients with AID, possibly from deeper B cell depletion compared to antibody therapies.

ADI-001 is an allogeneic CD20-targeted Vδ1 γδ CAR T cell product derived from healthy donor peripheral blood mononuclear cells (PBMC) which have been genetically engineered ex vivo to express a 2^nd generation anti-CD20 CAR. Given that Vδ1 γδ T cells preferentially home to tissues, ADI-001 may result in deep B-cell depletion in lymph nodes and organs affected by AID. ADI-001 has been administered to nearly 40 patients with B-cell malignancies in an ongoing trial.

We are conducting a phase 1, open label study evaluating the safety and efficacy of ADI-001 in subjects with lupus nephritis (LN), systemic lupus erythematosus (SLE) with extrarenal involvement, systemic sclerosis (SSc), and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) (NCT06375993). This basket study will enroll up to 140 subjects as follows:
Part 1 - 3+3 dose-finding study² to establish the maximum tolerated dose (MTD)/maximum administered dose (MAD) in 3 cohorts of up to 20 subjects each: i) LN or extrarenal SLE, ii) SSc, iii) AAV
Part 2 - dose expansion cohorts of up to 20 subjects each at the MTD/MAD: LN, extrarenal SLE, SSc and AAV

Key eligibility criteria:
LN: active Class III or IV LN (coexistent class V permitted) documented by renal biopsy in the past 6 months; inadequate response to ≥ 2 standard immunosuppressants for LN; urine protein-creatinine ratio >1.0
SSc: progressive cutaneous or interstitial lung disease, despite treatment with ≥ 1 immunosuppressant
AAV: granulomatosis with polyangiitis or microscopic polyangiitis; ≥ 1 major sign or symptom per the Birmingham Vasculitis Activity Score (BVAS)³, or ≥ 3 minor items, or at least 2 renal items (proteinuria,hematuria); relapse/refractory to ≥ 1 standard immunosuppressant

This is the first study of an allogeneic Vδ1 γδ CAR T cell product in autoimmune disease.

References: 1. Müller F, et al. N Engl J Med, 2024; 2.Storer BE, Biometrics, 1989; 3. Mukhtyar C, et al. Ann Rheum Dis, 2009

Funding

• Adicet Bio, Inc.