background

Our exceptional product engine is built on two interconnected components directed to frontier cancer targets: we have established deep expertise in cancer biology that guides and enables our precision medicine framework, and we deploy sophisticated drug discovery skills and methods for the design and optimization of small molecule drug candidates for such targets.

Our cancer biology platform focuses on largely undrugged tumor-intrinsic and immune system proteins playing key roles in preeminent signal transduction pathways. We specialize in atypical drug binding sites and mechanisms of action, including allosteric regulation and protein-protein interaction in protein complexes. To understand these regulatory mechanisms and produce high-throughput assays that enable drug discovery targeting these protein dynamics, we apply state-of-the-art biochemistry, enzymology, cell biology and a wide variety of biophysical and computational methods. We also invest extensively in chemical biology, genetics on the cellular and whole-organism level, and biomarker discovery to identify tumors that are dependent on the target of interest and can be recognized by a diagnostic test. Our experienced team of biologists and pharmacologists deploy this platform to validate frontier cancer targets, define sites on a target that could be drugged, and guide us toward precision medicines for cancer patients.

Our discovery of new drug candidates is enabled by advanced chemical synthesis and medicinal chemistry methods that give us broad chemical access to frontier cancer targets. We draw on a diverse set of chemical compound libraries, small chemical fragments, and natural products and natural product-like compounds to identify and elaborate ligands that are optimized to modulate the target of interest potently and specifically. In some cases, these ligands may be traditional Ro5 compounds. In other cases, particularly for bRo5 targets, we use powerful modular chemistry to assemble simple chemical “building blocks” into more complex and elaborate chemical structures that have best-in-class properties as drug candidates; this proprietary technology, named RevBlocks™, is used to synthesize, modify and improve many complex compounds that would be very challenging or even impossible to produce without this approach.

Our medicinal chemistry is guided by rational drug design supported by biophysical assays, including X-ray crystallography. These methods help define target protein structures and dynamics at the atomic level in order to facilitate design of optimal ligands. We also deploy Reveal™, our deep computational platform that incorporates computationally intensive molecular dynamics, virtual screening and proprietary small molecule informatics to help guide design and synthesis of compounds. Reveal™ is a knowledge-driven informatics system designed to expose advantageous structural and functional properties of scaffolds and ligands that can be leveraged on behalf of small molecule drug candidates that engage these targets therapeutically.