Karyopharm Therapeutics Initiates Phase 2 Study of Selinexor

Karyopharm Therapeutics Inc. KPTI, a clinical-stage pharmaceutical company focused on the discovery and development of novel first-in-class drugs directed against nuclear transport targets for the treatment of cancer and other major diseases, today announced the initiation of a Phase 2 trial of its novel, oral Selective Inhibitor of Nuclear Export (SINE) compound Selinexor (KPT-330) in patients with glioblastoma following treatment with radiation and temozolomide. The study, referred to as the KING study, is being run by Drs. Morten Mau-Sørensen at the Rigshospitalet in Copenhagen, Denmark, Andrew Lassman at Columbia University, New York, and Patrick Wen, Dana Farber Cancer Institute, Boston, Massachusetts. Eligible patients have disease that has recurred after prior treatment with radiation therapy and temozolomide and may undergo surgery as required. The primary goal of the study is to determine the anti-tumor activity of single agent Selinexor in up to 30 patients with relapsed glioblastoma (grade 4 glioma), as well as to document brain penetration of Selinexor and determine tolerability in this population. Full description of the study is available at www.clinicaltrials.gov (NCT01986348). Selinexor is a covalent inhibitor of the nuclear export protein XPO1 that forces the accumulation and activation of multiple tumor suppressor proteins in the nucleus. This leads to induction of apoptosis in neoplastic cells, while largely sparing normal cells. Preclinical results have shown that Selinexor kills glioblastoma neurospheres in culture, crosses the blood brain barrier of animals and has activity against glioblastoma xenografts and primagrafts with various genetic lesions. Dr. Mau-Sørensen stated, "We are very pleased to initiate this multi-center study of oral Selinexor in patients with recurrent glioblastoma. This is a very difficult-to-treat patient population with limited options. Because Selinexor works by a completely novel mechanism, crosses the blood brain barrier and has shown activity in preclinical models of glioblastoma, we look forward to the results of this study." "This study recognizes our commitment to the treatment of patients with recurrent brain tumors, and we hope will set a foundation for the combination of Selinexor with other treatment modalities in the future," commented Dr. Sharon Shacham, founder, President and CSO of Karyopharm. "In addition, this study could provide a basis for the evaluation of other types of central nervous system tumors, as well as patients with brain metastases associated with non-brain cancers." About Selinexor Selinexor (KPT-330) is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound. Selinexor functions by binding with the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor suppressor proteins in the cell nucleus, which subsequently reinitiates and amplifies their tumor suppressor function. This is believed to lead to the selective induction of apoptosis in cancer cells, while largely sparing normal cells. Over 300 patients have been treated with Selinexor in Phase 1 and Phase 2 trials in advanced hematologic malignancies and solid tumors. Additional Phase 1 and Phase 2 studies are ongoing or currently planned and three registration-directed clinical trials in hematological indications are expected to begin enrollment during 2014. The latest clinical trial information for Selinexor is available at www.clinicaltrials.gov.