This week’s announcement from Boehringer Ingelheim that it is acquiring, after entry into clinical trials, the key asset of FX125L from Funxional Therapeutics, may perhaps change the language of pharmaceutical discovery. FX125L is a first-in-class new anti-inflammatory, with potential in asthma, COPD and rheumatoid arthritis, working via the hitherto unrecognised somatostatin 2 (sstr2) pathway. Funxional got there by doing ‘what it says on the tin’ — functional screening.
In recent times much of pharmaceutical discovery has focussed rigidly on a reductionist approach that starts with genomically identified targets and proceeds linearly therefrom; yet, this is a story that couldn’t have happened that way, and relied instead on observed Function, not molecular biology. At long last, may we now use the F-word again in polite company without fear of riposte?
In the long distant past, pharmaceutical companies like Janssen turned out new drugs by the bucket load, based on careful analysis of animal behaviour to predict CNS activity: phenotypic screening was commonplace. It is relatively unpopular nowadays, despite a recent (2011) analysis published in Nature Reviews Drug Discovery indicating it has produced more FDA-approved drugs between 1999 and 2008 than target based drug discovery. Adherents of the latter approach point out the need to deconvolute functional effects lacking a mechanistic basis, and the difficulty in so-doing.
But as David Grainger, the man behind the Funxional story writes, Funxional’s screening uncovered a new inflammatory mechanism that we didn’t know we didn’t know, and optimised a new anti-inflammatory drug to work via this mechanism. Such things are likely to keep Systems Biologists awake at night. It’s a story of good old fashioned drug discovery, albeit one for the modern era: started in academe, built around a small team, backed by significant venture investment, and sold for a price significant enough that the major pharma purchaser wished to keep it quiet!
From the commercial perspective, that’s another thing that Funxional Therapeutics did. Work.