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Biological Chemistry

Merck, Harvard sign hefty drug pact

Cancer compounds from chemist Matthew Shair’s lab bring in $20 million

by Lisa M. Jarvis
March 24, 2016 | APPEARED IN VOLUME 94, ISSUE 13

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Credit: Stephanie Mitchell/Harvard Staff Photographer
Shair
Credit: Stephanie Mitchell/Harvard Staff Photographer
Shair

Representing the largest license fee ever for a technology developed at Harvard University, Merck & Co. will pay $20 million up front for preclinical compounds for leukemia developed in the labs of chemist Matthew Shair.

Merck gains small molecules that block enzymes controlling the transcription of gene expression that goes awry in acute myeloid leukemia (AML). The compounds are the culmination of several years of research in Shair’s lab, which works at the intersection of chemistry and biology.

That interdisciplinary approach allows the Shair lab to synthesize complex natural products to probe the fundamental drivers of disease. His team recently unraveled how cortistatin A, a natural product isolated from sea sponges, stops AML cells from growing. Shair found that the compound potently and selectively blocks CDK8 and CDK19, protein kinases that tune the transcription of certain genes. The researchers then designed easier-to-make derivatives of cortistatin A, the synthesis of which requires dozens of steps.

The project licensed to Merck could easily have been spun off into a start-up. Indeed, many of Shair’s Harvard colleagues have formed biotech firms that have attracted significant backing.

“We thought hard about this, and given the stage of the project, we thought it was best to hand it off to a company with deeper resources and the experts in place to move quickly into human clinical trials,” Shair says.

Merck frequently dips into academic institutions for early-stage research. In 2007, for example, the drugmaker agreed to fund six labs at Harvard to speed up research in oncology and central nervous system disorders; a year later, it signed a substantial pact to work with immunologist Laurie Glimcher on osteoporosis therapies.

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