AX-0422

AX-0422 is an orally bioavailable small molecule inhibitor of the mitochondrial caseinolytic protease P (ClpP), currently under development by Axeleos Therapeutics. ClpP is a key mitochondrial matrix protease responsible for maintaining mitochondrial protein homeostasis (proteostasis) by degrading misfolded or damaged proteins. In certain cancers, particularly acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), cells exhibit a heightened dependency on mitochondrial function and proteostasis. By inhibiting ClpP, AX-0422 induces mitochondrial stress, impairs oxidative phosphorylation, and triggers apoptosis in malignant cells while demonstrating a favorable safety profile in preclinical models. The drug is being investigated in Phase 1 clinical trials for patients with relapsed or refractory hematologic malignancies.