Pharma small molecule discovery has continued its longtime inexorable decline noted some time ago in this paper. There is little doubt that the bang for the buck is now a desperate wheeze, as the number of drugs obtained per billion dollars spent on drug development has dropped 80 to 100 fold since the glory days of the 1980s. Yes, everyone knows that and, yes, we all seem to know the causes and are flopping around in learned helplessness, but what this interesting paper noted was: maybe we don’t know the causes.
The paper argues that for whatever reason (denial?) the true problems can be broken down into four main issues: 1) having eyes only for blockbusters (the “better than the Beatles” phenomenon), 2) the FDA/bad apples spoling the barrel (“cautious regulator”), 3) having too much money to be incentivized to work smarter (“throw money at it”) and 4) our love of the quantitive and technical over elegance and creativity (“research brute force bias”). Basically, the right side of our brain did us in. The implications of this diagnosis are obvious, heal thyself. These are all fixable problems, but they require drug developers to take a hard look at themselves and recognize their bad habits. And perhaps, if things get bad enough, they'll be motivated to do so. This paper is fascinating and, while it may have missed some other key themes, clearly hits the nail on the head of a major problem in the industry.
Today, most have fled to biologics, phenotype screens, and fragments. But what if the traditional targeted, drug-like compound could be intelligently enabled to overcome the “better than the Beatles” and “brute force” problems? Genecentrix tools are designed to do just that by using creativity and elegance in the form of integrated tissue specificity analysis.