By Fineline Cube Suzhou-based Ascentage Pharma (HKG: 6855) has announced the submission of a clinical filing with the Center for Drug Evaluation (CDE) to initiate a randomized, double-blind, placebo-controlled Phase Ib/II clinical study. The study will assess the safety, pharmacokinetics, pharmacodynamics, and preliminary clinical efficacy of its Bcl-2 inhibitor, lisaftoclax (APG-2575), in patients with mild to moderate systemic lupus erythematosus (SLE).
Bcl-2 Overexpression and SLE Pathogenesis
The overexpression of the anti-apoptotic protein Bcl-2 has been identified as a key factor in the pathogenesis of SLE. Elevated levels of Bcl-2 in the lymphocytes of SLE patients provide survival advantages to T cells, B cells, plasmacytoid dendritic cells (pDC), and other inflammatory cells. This overexpression also confers resistance to commonly used glucocorticoid drugs, complicating the treatment of the disease.
Mechanism of Action and Preclinical Efficacy
Preclinical studies have demonstrated that APG-2575 can competitively bind to the Bcl-2 protein, disrupt the Bcl-2/Bim complex, and release Bim, thereby triggering a downstream apoptosis signal cascade reaction. This mechanism effectively induces apoptosis in hyperplastic T cells and B cells in SLE models. In SLE mouse models, APG-2575 has shown significant efficacy as a monotherapy and has exhibited strong synergistic effects when combined with hormone drugs.-Fineline Info & Tech