Breast cancer has exceeded lung cancer as the most diagnosed cancer and the fifth cause of cancer deaths worldwide in 2020. ER+/HER2- patients are the major population and endocrine therapy in combo with CDK4/6 inhibitors is the standard treatment for this population with advanced or metastatic disease. However, the overall response rate is less than 50%, indicating a huge unmet medical need in this area.

Molecular dysregulation of KAT6A, including amplification and fusion, has been reported in many cancers. In breast cancer, KAT6A is amplified as part of 8p11 amplicon in about 10-15% of the population and functions as an epigenetic modulator of expression level of estrogen receptor (ER). Therefore, targeting KAT6A will be a promising therapy for ER+/HER2- breast cancer patients. As KAT6A regulates ER expression at transcription level, it has the potential to overcome resistance to endocrine therapies due to mutation or ligand-independent constitutive activation of ER.

In January 2024, lnsilico announced the exclusive licensing agreement of
$12 million upfront with Menarini Group, granting the global rights to develop and commercialize ISM5043, the novel, small molecule KAT6 inhibitor designed using Insilico's Al platform. The total deal size is over $500 million, followed by royalties up to double digits.

In preclinical studies, the molecule has demonstrated potent inhibition in multiple COX and POX models with good efficacy and safety.