After two years of operating under the radar, DiCE Molecules has stepped into the spotlight with $50 million in backing from Sanofi. Based on technology from the labs of Stanford University biochemist Pehr Harbury, DiCE is developing small molecules that disrupt protein-protein interactions—a job currently delegated to biologics.
Sanofi wants to tap DiCE’s ability to use “directed chemical evolution” to find natural-product-like molecules that can wedge into the sizable gaps between proteins. The partners will develop drug candidates against up to 12 targets selected by Sanofi.
Harbury’s technology builds on the concept of DNA-encoded libraries (DELs), which are created by applying traditional combinatorial chemistry techniques to chemical building blocks decorated with a specific piece of DNA. The resulting libraries are washed over a protein target, and the identity of the “hits” is determined by sequencing the DNA tags.
Although DNA is a useful bar code, Harbury wanted to use it in the way nature intended: as a recipe for making molecules. The biochemist embeds 20-base-pair-long regions carrying the instructions for chemical steps within a longer piece of DNA; that DNA is then put through a router that directs split-pool synthesis of small molecules.
A vast library is generated and, as with a DEL, is washed over a protein to see whether any molecules stick. But instead of simply sequencing the DNA to unveil the identity of the hits, DiCE amplifies and retranslates that winning DNA to facilitate another round of panning for hits. This process is repeated, sometimes three or four times. DiCE ends up with an enriched pool of hits with less “junk” and compounds with better pharmacological properties than a DEL delivers, says CEO J. Kevin Judice.
The technology behind DiCE incubated in Harbury’s labs for more than a decade. Judice and Phil Patten, the firm’s chief scientific officer, had stayed in touch with Harbury since the three were postdocs in Peter Schultz’s labs at the University of California, Berkeley. When Harbury was finally ready to commercialize his platform, Patten left his job at DuPont and convinced Judice, a veteran of three biotech firms, to sign on.
The company was formed in 2014 with the support of a group of angel investors. The five-year pact with Sanofi gives the biotech firm financial stability, a good set of targets to test-drive its technology against, and access to resources that could speed up its drug development efforts, Judice says.