With seven molecules in clinical development, another three preclinical compounds approaching the clinic, and a half-dozen discovery programs divided equally between virology and bacteriology, AiCuris is seeking the keys to thwarting viral replication. The start-up has drug candidates targeting herpes simplex virus, human cytomegalovirus and hepatitis C.

Only 10% of compounds that enter Phase I trials survive to FDA approval, and that has a lot to do with the inadequacy of early-stage research in cell lines. They are poor predictors of what will happen in animal models, much less in patients. The problem stems in part from the fact that cells, once removed from an organism and maintained artificially in a laboratory environment, change their behavior and phenotype in equally artificial ways, which in turn warp their response to drug candidates. HemoShear LLC's technology simulates a cell's natural environment by introducing hemodynamic blood flow and the accompanying shear stresses. Its first system focuses on blood vessels.

As much as anti-hepatitis C drug telaprevir is leading the way, it has also defined what is going to be needed in a best-in-class molecule, according to the founders of Avila Therapeutics Inc. Avila's platform technology creates highly selective drugs that bond covalently to receptors, effectively silencing them and overcoming resistance mechanisms for the day or two the targets live. The Waltham, MA, biotech is the only company currently focused on covalent drugs, the company believes.