Karyopharm Therapeutics (KPTI) Announces Publication of Selinexor Phase 1 Data in XPO1 Inhibition

September 28, 2016 7:31 AM EDT

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Karyopharm Therapeutics Inc. (Nasdaq: KPTI) announced that preclinical and Phase 1 clinical data describing XPO1 inhibition with selinexor (KPT-330), the Company’s lead, oral Selective Inhibitor of Nuclear Export / SINE™ compound, in ovarian cancer models and in patients, were published online in Clinical Cancer Research. The paper, entitled “Inhibition of the Nuclear Export Receptor XPO1 as a Therapeutic Target for Platinum Resistant Ovarian Cancer,” discusses scientific results supporting selinexor’s potential as a new therapeutic strategy for platinum resistant ovarian cancer.

Published data have shown that XPO1 mRNA overexpression is correlated with decreased survival and platinum resistance in human ovarian cancer. Inhibition of XPO1 with Karyopharm’s SINE compounds decreased cell viability and synergistically restored platinum sensitivity in preclinical models. In addition, selinexor treatment, alone and in combination with cisplatin, markedly decreased tumor growth and prolonged survival in a platinum-resistant ovarian cancer in vivo model. These results were further confirmed in a Phase 1 clinical trial, which evaluated single agent oral selinexor in patients with late-stage, recurrent, and heavily pre-treated, platinum resistant ovarian cancer. In this study, selinexor had manageable toxicity and tumor growth was halted in three of five evaluable patients, including one patient with a confirmed partial response. These results lead to the Phase 2 clinical study “SIGN” (Selinexor in Gynecologic Malignancies), with results to be released in an oral presentation at the European Society of Medical Oncology (ESMO) 2016 annual meeting in Copenhagen.

“Ovarian cancer mortality rates are high, with chemoresistance representing the major cause of treatment failure. These data are encouraging, not only because they demonstrate that inhibition of XPO1 with selinexor significantly increased tumor killing regardless of platinum sensitivity, but also because selinexor can be given safely in this late-stage, heavily pretreated and platinum-resistant disease setting,” said John A. Martignetti, MD, PhD, Associate Professor, The Mount Sinai Hospital, and co-lead author of the paper.

Sharon Shacham, PhD, MBA, President and Chief Scientific Officer of Karyopharm commented, “These findings are important because they provide insights into the potential value of XPO1 as a therapeutic target in ovarian cancer. We look forward to expanding on our growing body of selinexor clinical data in early October when we report results from the Phase 2 SIGN study in patients with gynecological malignancies, including ovarian cancer, at the ESMO Meeting.”

About Selinexor

Selinexor (KPT-330) is a first-in-class, oral Selective Inhibitor of Nuclear Export / SINE™ compound. Selinexor functions by binding with and inhibiting the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor suppressor proteins in the cell nucleus. This reinitiates and amplifies their tumor suppressor function and is believed to lead to the selective induction of apoptosis in cancer cells, while largely sparing normal cells. To date, over 1,700 patients have been treated with selinexor, which is currently being evaluated in several mid- and later-phase clinical trials across multiple cancer indications, including multiple myeloma in combination with low-dose dexamethasone (STORM) and backbone therapies (STOMP), acute myeloid leukemia (SOPRA), diffuse large B-cell lymphoma (SADAL), and liposarcoma (SEAL), among others. Karyopharm plans to initiate a pivotal randomized Phase 3 study of selinexor in combination with bortezomib (Velcade®) and low-dose dexamethasone (BOSTON) in patients with multiple myeloma in early 2017. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with one or more approved therapies in a variety of tumor types to further inform the Company's clinical development priorities for selinexor. The latest clinical trial information for selinexor is available at www.clinicaltrials.gov.

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