Harmonic Discovery

Market position

Harmonic Discovery positions itself among computational drug discovery companies applying machine learning to small-molecule design, with a focus area that includes protein kinases.

Rather than optimizing compounds for selectivity against a single protein, Harmonic Discovery designs molecules with an intended polypharmacology profile, explicitly dialing out anti-targets associated with toxicity while dialing in secondary targets intended to enhance efficacy, mitigate toxicities and suppress resistance pathways. The company states this work is grounded in peer-reviewed science and industry experience.

Technology

The platform is a generative chemistry system that identifies modifications to molecules in order to remove interactions with specified anti-targets and add interactions with beneficial secondary targets. It integrates multiple layers of protein information, from sequence-level point mutations to 3D conformational states to gene expression changes. Associated research work described by the company includes a model integrating multiple bioactivity data types to improve compound-kinase bioactivity prediction, an investigation of the conformational landscape of AlphaFold2-predicted protein kinase structures, and the use of Direct Preference Optimization to align generative molecular language models with medicinal chemist preferences.