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Karyopharm Therapeutics Inc. Closes $20 Million Series A Financing to Advance Pipeline of Novel Nuclear Transport Modulators for Cancer, Inflammation and Other Disorders

Karyopharm Therapeutics Inc. Closes $20 Million Series A Financing to Advance Pipeline of Novel Nuclear Transport Modulators for Cancer, Inflammation and Other DisordersNewton, Mass. – November 3, 2010

Karyopharm Therapeutics Inc., a leader in the new field of nuclear transport modulators, has completed a $20M Series A financing. The nuclear transport machinery plays an integral role in the regulation of many molecules involved in a broad spectrum of human and animal disease. Karyopharm is focused on the discovery and development of novel selective inhibitors of nuclear export (SINE) for the treatment of cancer, autoimmune diseases and HIV. These SINEs act by forcing the nuclear localization of major tumor suppressor and growth regulatory proteins, causing selective death of cancer cells, while sparing normal cells. The Karyopharm platform, utilizing rapid chemical optimization with integrated computational/in silico rational drug design, has yielded multiple novel active small molecule SINEs, which have shown activity in animal models of cancer.

The Series A financing, which follows approximately $1M in Angel investments, will be used to expand Karyopharm’s research and development platform and to drive its first drug candidates into the clinic. Sharon Shacham, PhD, MBA, Karyopharm’s CSO and Acting President, remarked, “With this financing, we are able to move decisively to select a clinical candidate for our first indication in cancer. We believe that SINEs represent a completely new and highly effective approach to the treatment of cancers and other diseases with major unmet need. Preclinical studies of our advanced SINEs have shown impressive single agent activity and synergy in combination with specific anti-cancer drugs while exhibiting good tolerability in animal models.”

By inhibiting the nuclear export of tumor suppressor proteins, Karyopharm’s drug candidates force the activation of the cell’s own key regulatory pathways including those activated those activated by p53, p27, pRB, BRACA1/2, FoxO, and the inhibitor of NF-kB (i.e., IkB). According to Karyopharm Co-Founder, Ronald A. DePinho, M.D., “The targeting of single molecules have provided marginal advances in cancer. By blocking the export of multiple tumor suppressor proteins, this strategic point of intervention can impact on multiple pathways which 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.”

Following the Series A investment, Drs. Mansoor Raza Mirza, Ronald DePinho, and Michael Kauffman will comprise the Board of Directors. Dr. Mirza, M.D. is Chief Oncologist at the Department of Oncology, Rigshospitalet – the Copenhagen University Hospital, Denmark. Dr. DePinho is the Director of the Belfer Institute for Applied Cancer Science and Professor of Medicine and Genetics at the Dana-Farber Cancer Institute and Harvard Medical School. Dr. Giulio Draetta, M.D., Ph.D., a leader in cancer drug development, is Deputy Director of the Belfer Institute and Chief Research Business Officer at the Dana-Farber Cancer Institute. Dr. Draetta will chair the Scientific Advisory Board.

About Karyopharm Therapeutics Inc.
Karyopharm is a privately held oncology company headquartered in Newton, Massachusetts. The Company was founded in 2009 by Drs. Sharon Shacham, Michael Kauffman, Ronald DePinho, and Giulio Draetta. Karyopharm’s founding team and scientific advisory board have demonstrated entrepreneurial success in developing project ideas to productive clinical outcomes. The company is focused on the development of modulators of nuclear transport as novel therapies for cancer, inflammatory and other diseases. With the recent determination of the 3-dimensional structure of the nuclear pore complex, the mechanisms of nuclear transport have become more apparent. Many key tumor suppressor and growth regulatory proteins are exported from the nucleus by the major export protein CRM1. Using its proprietary computational chemistry platform, Karyopharm has rapidly discovered and optimized a series of selective inhibitors of nuclear export (SINE) targeting the CRM1 protein. Additional programs focused on other aspects of nuclear export, as well as nuclear import, have been initiated.

Cautionary Note Regarding Forward-Looking Statements
This press release, and information contained on Karyopharm’s website, contains forward-looking statements that involve substantial risks and uncertainties, including statements regarding Karyopharm’s strategies and future plans, prospects and results, are forward-looking statements. The words “anticipate,” “believe,” “expect,” “intend,” “may,” “plan,” and other similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Karyopharm may not actually achieve the plans or expectations disclosed in its forward-looking statements, and you should not place undue reliance on its forward-looking statements.

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