Cambridge, Mass. — Zag Bio has advanced its lead Type 1 diabetes program, ZAG-101, into clinical development with the launch of a first-in-human Phase 1b/2a trial.
The LANTERN study will evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of ZAG-101 and explore whether the investigational therapy can preserve insulin-producing beta-cell function in people with Type 1 diabetes.
“Advancing ZAG-101 into the clinic marks Zag’s transition to a clinical stage company,” said Jason Cole, Chief Executive Officer of Zag Bio. “We are beginning in Type 1 diabetes, where there remains a significant unmet need for safe, durable therapies that can address the underlying autoimmune process and help patients maintain natural insulin production.”
ZAG-101 is a bifunctional antibody designed to deliver an insulin-derived antigen directly to antigen-presenting cells in the thymus.
The therapy is intended to harness the thymus’ natural role in establishing immune tolerance by generating long-lived, antigen-specific regulatory T cells while reducing autoreactive conventional T cells. The regulatory T cells are then designed to migrate to the pancreas and suppress the autoimmune response that damages insulin-producing beta cells.
Type 1 diabetes is a chronic autoimmune disease in which the immune system attacks and destroys beta cells in the pancreas. Although insulin delivery systems and glucose-monitoring technologies have improved disease management, they do not address the autoimmune process underlying the disease.
In preclinical studies, Zag Bio said ZAG-101 generated antigen-specific regulatory T cells and increased the ratio of regulatory to conventional T cells in the thymus. The therapy also demonstrated activity in disease-relevant models.
“People living with Type 1 diabetes face the daily burden of managing a lifelong disease, and there remains a significant need for therapies that address the underlying autoimmunity,” said Jan Hillson, MD, Chief Medical Officer of Zag Bio.
The Phase 1b/2a LANTERN trial will initially enroll adults with Stage 3 Type 1 diabetes and evaluate single and multiple ascending doses of ZAG-101. The company plans to test both intravenous and subcutaneous administration.
Researchers will assess safety, tolerability and pharmacology as well as metabolic and immune-related endpoints. Those measures will include C-peptide, an indicator of the body’s own insulin production and beta-cell function, along with tests of regulatory and effector T-cell responses.
Following the initial adult study, Zag Bio plans to expand development into adolescents with Stage 3 Type 1 diabetes and eventually investigate the therapy in earlier stages of the disease, when preserving beta-cell function may have a greater impact.
The clinical program will initially enroll patients in Australia and Europe.
