ActoBio Therapeutics and Intrexon T1D Partners have been granted allowance by the U.S. Food and Drug Administration (FDA) for their Investigational New Drug (IND) application to initiate a Phase Ib/IIa study for the treatment of early onset type 1 diabetes (T1D) with AG019, a disease-modifying approach to induce immune tolerance in T1D. Currently no disease-modifying treatment for T1D is available, and standard of care is primarily based on exogenous insulin and diet regulation in combination with lifestyle modification.
AG019 is an oral capsule formulation composed of engineered L. lactis delivering the autoantigen human proinsulin and tolerance-enhancing cytokine IL-10. AG019 is designed to reduce T1D pathology by re-establishing immunological tolerance to islet antigens via the production of regulatory T-cells. Preclinical tests in new-onset diabetes animal models demonstrated stable reversion to normoglycemia after treatment with AG019 (L. lactis expressing IL-10 and human proinsulin) in approximately 60% of mice. The most effective treatment effects were seen for AG019 in combination with short-term treatment with an anti-CD3 monoclonal antibody with a maximum level of diabetic reversion of 89% when treatment started at early diabetes. AG019 also preserved residual β-cell function, halted insulitis progression and increased the frequency of regulatory T cells.
"With ActoBio's AG019, I see for the first time the prospect of a disease-modifying treatment for type 1 diabetes patients, mostly children and young adults. The preclinical tests of AG019 showed a significant diabetes remission rate when treatment started at early stage. It could be a real game changer in disease management, which currently exists in life-long insulin dependence and adapted lifestyle. Together with my patients, my team is looking forward to participate in clinical studies to further develop this application," said Prof. Chantal Mathieu, head of the Diabetes division of R&D at the Leuven University and head of Clinical and Experimental Endocrinology University Hospital Leuven Belgium.