Partnership Benefits

Centered about its unparalleled proficiency in computational drug design, Locus has implemented a suite of cutting-edge preclinical discovery capabilities that can reduce the time and cost of advancing an IND candidate. Locus is making available these significant proprietary assets to help select partners to accelerate or realize their drug discovery objectives. Locus' computational suite of tools can be applied selectively to solve specific chemistry or protein structural challenges; alternatively, approaches can be fully bundled with Locus' internal chemistry, biology and protein crystallography expertise to deliver novel, potent, synthetically tractable and regulatory viable preclinical candidates.

For example, the Locus computational platform can provide partners with any or all of the following benefits:

• Accurate and novel computed protein structures and binding sites suitable for drug design
• Structural validation of experimental structure-activity relationships (SAR) even in the absence of co-crystal structures
• Ability to synthetically advance chemical series that have met a ‘dead-end'
• Introduce patentable features into public domain chemical structures or series

An area of strong expertise at Locus is the design of protein kinase inhibitors. Protein kinases are attractive drug targets because they act as control switches for many biochemical pathways that become dysregulated by molecular and signaling events in disease states. While kinases are of particular interest as targets for drug development, there are more than 500 structurally related members of the class and a safe drug often requires high selectivity for the intended kinase target. The challenge is exacerbated by the lack of structural information for most members of the class and the fact that all kinases share a common high-affinity ATP pocket that is the binding site of most small molecule leads. Locus has demonstrated cutting-edge approaches to solving these problems by successfully identifying non-ATP binding sites, designing IND leads to these sites, and producing high quality protein models that are suitable for the design of new chemotypes that bind to the target with high selectivity. Using these tools Locus has successfully advanced to IND status two orally active drug candidates, a p38 kinase candidate, and a kinase inhibitor for cancer.