BIO 2014: Antisense and Disruptive Technologies for Drug Discovery


Xconomy San Diego — 

Editor’s note: The BIO 2014 convention begins today in San Diego. Stanley Crooke is among the speakers at a breakout session Wednesday titled Blazing New Trails in Disruptive Innovation: Stem Cells, RNA and Epigenetics-Based Therapeutics. —BVB

For the past 25 years I, with my colleagues at Isis Pharmaceuticals, have persevered in the creation and validation of a genuinely disruptive drug discovery platform, antisense technology. To advance from a blank canvas to a mature technology, now proven by the marketing approval of mipomersen (Kynamro) and encouraging clinical data from a number of Isis’ later-stage drugs, has required two decades of innovation and commitment to the science and patients—and, yes, money.

For all the time, effort, and capital, you might well ask, “Was it worth it?” or even, “Why pursue a disruptive technology for drug discovery?”

Part of the answer is obvious: the well-documented decline in the productivity of our industry’s drug discovery processes. A couple years ago, Sanford Bernstein’s Jack Scannell and colleagues showed that from roughly 1950 to 2010, the number of new drugs per billion dollars of R&D spending has declined from more than 30 to less than one. This trend manifests in increasing prices charged for new drugs, as well as industry’s greater reliance on a few blockbusters for profits. Successive pharmaceutical mergers to resolve this bottleneck through increased scale have had no effect in improving this lop-sided ratio.

The major cause for this productivity decline, however, is our industry’s failure to successfully invest in disruptive innovation through more efficient research technologies, prolonging reliance on the century-old platform of small molecule drug discovery. That this approach continues to generate drug candidates is both a blessing—because there is some ROI—and a curse, because the predictability of getting some products to market reduces the incentive to make high-cost, high-risk, high-reward research investments.

Meanwhile, there has been a quiet revolution in the “redefinition” of diseases. This realization was critical in my decision to pursue antisense technology; i.e., designing pharmaceuticals that will functionally “silence” a gene mutation; or activate a gene to compensate for an underlying genetic defect.

Unlike classic medical definitions, which rely primarily on the symptoms observed in the later stages of disease progression, modern definitions of disease now focus on the molecular and pathological factors that cause or maintain disease—not the symptoms or outcomes. Importantly, molecular pathological definitions are actionable, and bring focus to causes of disease. This relatively new definition has resulted in a … Next Page »

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