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Nov 3, 2010

Karyopharm Completes $20M Series A Financing to Develop Nuclear Export-Blocking Drugs

  • Karyopharm Therapeutics raised $20 million in a Series A financing round to support the development of a first clinical oncology candidate and expand its R&D platform. Established in 2009, Karyopharm is using a technology platform that combines computational and in silico rational drug design with chemical optimization to identify and develop small molecule drugs that inhibit the transport of key proteins out of the cell nucleus. Initially focused on anticancer indications, these SINE (selective inhibitors of nuclear export) molecules act by forcing the nuclear localization of major tumor suppressor and growth regulatory proteins, causing selective death of cancer cells, the firm claims.

    Karyopharm says its initial anticancer target, Crm1, is the main exporter of key tumor suppressor proteins, and has been shown to correlate with poor prognosis in cervical, ovarian, and liver cancers, as well as osteosarcoma and gliomas.

    The firm’s genomic analyses have identified genetic alterations in Crm1 in specific cancers, a feature that is being exploited to design and develop Crm1 inhibitors. Karyotype says preclinical studies with the most advanced SINE candidates have already found the molecules exhibit both single agent activity and synergy in combination with specific anticancer drugs.

    “The targeting of single molecules has provided marginal advances in cancer,” comments co-founder Ronald A. DePinho, M.D. “By blocking the export of multiple tumor suppressor proteins, this strategic point of intervention can impact on multiple pathways that cooperate to maintain tumors. As normal cells want to keep these proteins in the nucleus, these SINEs should also exhibit an excellent safety profile in patients.”

    Karyotype hopes that using this same approach of inhibiting the export or indeed import of specific nuclear proteins could ultimately lead to new drugs targeting a range of other diseases, including autoimmune disorders and viral infections such as HIV.

    In June the firm announced a deal with discovery services firm O2h, under which the latter is providing relevant expertise to accelerate Karyopharm's small molecule program toward the selection of a development candidate. O2h is a discovery services company co-located in Cambridge, U.K. and Ahmedabad, India. The Indian operations provide a chemistry expertise while the U.K. office provides project-management support.


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