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Biotech Targets “Undruggable” Cancer Gene

DNA illustration

(National Heart, Lung, and Blood Institute, NIH)

9 November 2015. A biotechnology company says it plans to focus its technology platform on a cancer-causing gene previously considered beyond the direct reach of today’s cancer drugs. Warp Drive Bio, in Cambridge, Massachusetts told an American Association of Cancer Research meeting in Boston on Saturday the company plans to target the Ras oncogene, a gene that turns normal function cells into a wide range of tumor cells.

Mutations in Ras oncogenes produce proteins that send signals encouraging cell proliferation and inhibit normal cell death resulting in the formation and growth of tumors. These mutations are associated with about 30 percent of human cancers including, non-small cell lung, colorectal, pancreatic, bladder, kidney, thyroid, melanoma, and liver tumors, as well as blood-related cancers.

At the AACR meeting on Saturday, Warp Drive Bio’s president and chief scientist Greg Verdine said disease targets inside cells based on human proteins are difficult to address, with some 80 percent of these proteins considered “undruggable,” or beyond the direct reach of today’s therapeutics. Most biologics cannot penetrate cells, while small molecules, or low molecular weight compounds, that can penetrate cells are limited to about 10 percent of proteins with certain surface properties required for binding with small molecules.

Warp Drive Bio claims its technology platform, called Small Molecule-Assisted Receptor Targeting or Smart, creates therapies that combine a mechanism similar to small molecules that penetrates cells, with biologic cancer drugs that act on the cancer-causing proteins. The Smart platform creates a receptor on the surface of the target protein that makes it possible for the biologic therapy to penetrate the surface and block the protein’s activity. Warp Drive Bio plans to develop several therapeutics that apply the Smart platform to proteins from Ras genes in various states, including their mutated forms.

The Smart technology is based on biochemical research by Verdine and colleagues at Harvard University on synthetic biologics that address processes underlying growth and proliferation of human cancer cells, control of gene expression, and preservation of genomic integrity. Verdine’s lab studies epigenetics, external influences on genetic activity, resulting in changes to DNA that repress activities of genes for transcribing their codes into proteins.

Verdine founded Warp Drive Bio in 2012 with Harvard University geneticist George Church and protein biochemist James Wells at University of California in San Francisco. As reported in Science & Enterprise, the company is a joint project of the French pharmaceutical company Sanofi and venture capital firm Third Rock Ventures. Sanofi and Third Rock invested $50 million cash and took a $75 million equity stake in Warp Drive Bio. Sanofi has access rights to Warp Drive’s products and an option to acquire the company if certain milestones are met.

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