Karyopharma Offers Data on Oncology Pipeline at EORTC-NCI-AACR Annual Meeting

Karyopharm Therapeutics Inc.

, a clinical-stage pharmaceutical company, today announced the presentation of data describing its oncology product candidates at the 26^th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Barcelona, Spain held November 18 to 21, 2014. Data for its lead product candidate, Selinexor (KPT-330), a first-in-class, oral Selective Inhibitor of Nuclear Export / SINE™ compound, described its synergistic anti-tumor activity in combination with DNA damage-inducing treatments such as anthracyclines or radiation in a non-small cell lung cancer (NSCLC) mouse model. In addition, a description of a newly developed pharmacodynamic assay designed to evaluate direct Selinexor binding to XPO1 in patients was presented. Finally, data describing the identification of novel mechanism PAK4 allosteric modulators (PAMs) and their ability to inhibit tumor cell growth and induce apoptosis were presented. "Presentations on Karyopharm's oncology pipeline at the EORTC-NCI-AACR Annual Meeting included data highlighting key Selinexor advantages, such as synergistic activity in combination with DNA damaging agents and the development of a new pharmcodynamic assay, as well as promising data on our earlier-stage PAK4 program," said Sharon Shacham, PhD, MBA, President and Chief Scientific Officer of Karyopharm. "Selinexor's synergy with DNA damaging agents, such as anthracyclines and radiation in solid and hematological cancers, provide the rationale for future combination clinical studies." In a poster entitled "Selective Inhibitors of Nuclear Export (SINE™) Block the Expression of DNA Damage Repair Proteins and Sensitize Cancer Cells to DNA Damage Inducing Agents," data demonstrated that Selinexor inhibited the DNA repair mechanisms in solid and hematological cancer cell lines and therefore, preventing the cancer cell recovery following treatment with agents that cause DNA damage, leading to increased cancer cell death. These results suggest that such a combination treatment has the potential to result in improved clinical outcomes compared to each agent alone: * Selinexor treatment following exposure to DNA damaging agents such as doxorubicin and idarubicin inhibited the repair mechanism of DNA damage caused by these agents and resulted in synergistic Acute Myeloid Leukemia (AML) cell killing as measured by induction of PARP and Caspase 3 cleavage. * In vivo, low dose Selinexor (5 mg/kg) and radiation (3 Gy) decreased xenograft tumor size of non-small cell lung cancer (A549 cell line) by 12% and 30% relative to vehicle, respectively. In contrast, combination of Selinexor and radiation resulted in an 86% tumor decrease. In a poster presentation entitled "Quantification of Exportin-1 (XPO1) Occupancy by Selective Inhibitor of Nuclear Export / SINE™ Compounds," data demonstrated the development of a new pharmacodynamic assay that evaluate direct binding of SINE to XPO1 by measuring XPO1 occupancy. This assay can be used to correlate Selinexor dose, XPO1 binding and anti-tumor activity. In a poster entitled "Identification of Novel Small Molecules as Selective PAK4 Allosteric Modulators (PAMs) by Stable Isotope Labeling of Amino acids in Cells (SILAC)", results of preclinical developmental studies with Karyopharm's lead PAK4 allosteric modulators (PAMs) demonstrated anti-tumor activity both in vitro and in vivo. These novel orally bioavailable small molecules showed efficacy in both solid and hematological tumor xenograft models in mice with minimal toxicity.