Biotechnology and Translational Medicine

The process of translating a basic scientific discovery into a novel therapeutic that improves public health is immensely gratifying. A particularly exciting time in the translation process is the early clinical testing to assess—for the first time—whether a novel molecule is efficacious in humans. This “proof-of-concept” (POC) stage of translation has a high risk of failure and must be carefully tested, but a positive POC is scientifically—and often financially—rewarding. This is particularly true for small biotech companies where a positive POC is a “value inflection point,” leading to enhanced market valuation or strategic partnerships or even acquisition. Howmuch of the industry-sponsored POC science is done by small biotech companies? It is hard to say. There are over 3,500 industry-sponsored, open, interventional phase II studies currently listed at clinicaltrials.gov without any way of knowing which are definitive POC trials. However, if we examine the 86 New Molecular Entity and New Therapeutic Biological product approvals by the US Food and Drug Administration (FDA) over the past 2 years (2014–2015),1,2 we see that a significant percent of the POC science done for these recently approved molecules was conducted by small companies. For 26 of the 86 approvals, the approval was granted to a small company, and for another nine approvals the POC science was conducted by a small company, although the eventual approval was attributed to a large company. For example, the POC science for lesinurad, a URAT1 inhibitor for the treatment of gout (whose approval was granted to AstraZeneca) was conducted by Ardea Bioscience prior to the AstraZeneca acquisition3; the POC science for blinatumomab, a bispecific anti-CD3/anti-CD19 for the treatment of acute lymphoblastic lymphoma (ALL) (whose approval was granted to Amgen) was done byMicromet prior to the Amgen acquisition4; and idelalisib, a PI3K inhibitor for