OPN-9840

OPN-9840 is an orally active, non-covalent, small molecule pan-inhibitor of the transcriptional enhanced associate domain (TEAD) family of transcription factors. It is being developed by Opna Bio for the treatment of cancers driven by dysregulated Hippo pathway signaling, particularly malignant mesothelioma with neurofibromatosis 2 (NF2) mutations. TEAD proteins are key effectors in the Hippo pathway and regulate genes involved in cell proliferation and survival; their aberrant activation promotes tumor growth and therapy resistance. OPN-9840 binds to the palmitate-binding pocket of TEAD proteins, inhibiting their function and thereby suppressing pro-growth and anti-apoptotic gene expression. Preclinical studies have shown that OPN-9840 demonstrates dose-dependent antitumor activity as a single agent in NF2-mutant malignant mesothelioma models without significant toxicity or weight loss in animals. The drug is currently at the IND-enabling stage prior to clinical trials[1][2][3][4][7].