Directed evolution has revolutionized several areas of biology, including the discovery of protein therapeutics within the pharmaceutical industry. The production of monoclonal antibodies was slow, artsy, and unreliable in the 1990s. Transport of key pieces of the mammalian genetic repertoire out of mice and into more tractable platforms, such as yeast, enabled the process to be rendered algorithmic, fast and highly predictable. Utilization of the genetic algorithm (repeated cycles of the gene modification, selection, and amplification cycle) in these newer platforms has commoditized the production of fully humanized monoclonal antibodies against almost any target and in the process, has radically changed the attitude of pharmaceutical scientists toward previously intractable classes of targets. This new outlook has also produced a pronounced uptick in revenues along the way.
At DiCE we are combining the best features of directed biological evolution with a number of mature chemistry technologies, including DNA-encoded libraries and mix-and-split combinatorial chemistry. The result is a uniquely powerful approach. With it, we can use libraries in a complexity range of 109-1010 to access hits to historically difficult targets. In addition, we have developed a path forward allowing robust hit-to-lead expansions on the scale of tens of millions of compounds, across many discrete structural families, and are able to subsequently profile them for affinity and selectivity on bulk scale at that stage. Finally, we have optimized methods to screen entire families of these potent, selective molecules in proprietary assays that empirically select members of these families with appropriate logD and in vitro metabolic stability properties.