Six Data Presentations at the European Hematology Association's 19th Congress

Natick, Massachusetts (Press Release) - Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clin­i­cal-stage pharma­ceu­tical com­pany, today announced initial Phase 1 data from patients with multiple myeloma treated with Karyopharm's lead selective inhibitor of nuclear export (SINE), Selinexor (KPT-330), in com­bi­na­tion with "low-dose" (20 mg twice weekly) dexa­meth­a­sone. Among eight patients, the best responses were one stringent com­plete response (sCR), three partial responses (PRs), two minor responses (MRs), one pro­gressive disease and one non-evaluable. Accordingly, the clin­i­cal benefit response rate (sCR+PR+MR) is 75% and the over­all response rate (sCR+PR) is 50%. These new results will be reported at the 19th Con­gress of the European Hematology Association (EHA) in a poster presentation on Saturday, June 14th from 5:45 - 7:00 PM CEST (Abstract #5580).

As part of Karyopharm's Phase 1 clin­i­cal trial of Selinexor in patients with ad­vanced hema­to­logical malig­nan­cies, patients with multiple myeloma were treated with either single-agent Selinexor or Selinexor in com­bi­na­tion with low-dose dexa­meth­a­sone. Eight patients with multiple myeloma, whose disease was re­lapsed and/or refractory to all avail­able classes of approved ther­a­pies and progressing on study entry, were treated with 45 mg/m2 of oral Selinexor and 20 mg of dexa­meth­a­sone, each dosed twice weekly. Patients had received a median of 5.5 prior lines of ther­apy. All had received prior ther­apy with a pro­te­a­some inhibitor and an immuno­modu­la­tory agent, while seven of the eight patients also received stem cell trans­plan­ta­tions. Five of the six responding patients remain on study as of June 5, 2014, the data cut-off date. An addi­tional 12 patients with multiple myeloma may be dosed with Selinexor in com­bi­na­tion with dexa­meth­a­sone in this arm of Karyopharm's ongoing phase 1 hematology study.

Adverse events in patients receiving single-agent Selinexor were generally low-grade, con­sis­tent with events observed in patients with other hema­to­logical malig­nan­cies and re­spon­sive­ to standard sup­port­ive care. Compared with Selinexor given alone, fewer adverse events in patients receiving Selinexor in com­bi­na­tion with dexa­meth­a­sone were reported, con­sis­tent with dexa­meth­a­sone's reduction in Selinexor's main side effects of nausea, anorexia, and fatigue.

"We have observed patients with multiple myeloma receiving durable responses on Selinexor single-agent ther­apy. We are particularly excited to see that Selinexor with low-dose dexa­meth­a­sone shows marked ac­tiv­i­ty with rapid M-protein reductions and good tolerability, even in patients with disease refractory to poma­lido­mide and/or car­filz­o­mib," stated Dr. Sharon Shacham, Karyopharm's Founder, Pres­i­dent and CSO. "While we have seen safety and efficacy data to date with Selinexor as a single-agent ther­apy, we also be­lieve that Selinexor may have strong synergistic poten­tial with both existing and novel ther­a­pies."

In addi­tion to the myeloma data, three presentations on Selinexor in acute myeloid leukemia (AML) will be given at EHA:

• An oral presentation on Sunday, June 15th from 11:15 - 11:30 AM CEST will focus on the activity of single-agent Selinexor in patients with heavily pretreated AML in the ongoing phase 1 study (Abstract #5591).
• Preclinical data from the combination of Selinexor with the FLT3 inhibitor quizartinib will be reported in a poster presented on Saturday, June 14th from 5:45 - 7:00 PM CEST (Abstract #5575).
• Preclinical data from the Ohio State University providing evidence that Selinexor restores topoiso­mer­ase IIα (Topo IIα) to the nucleus and sensitizes resistant AML blasts to Topo IIα inhibitors including adriamycin will be reported in a poster presented on Saturday, June 14th from 5:45 - 7:00 PM CEST (Abstract #5296).

Clinical and pre­clin­i­cal data on Selinexor in patients with double hit diffuse large B-Cell lym­phoma (DLBCL) will be presented in a poster on Friday, June 13th from 5:45 - 7:00 PM CEST (Abstract #5378). New pre­clinical data in­clude in vitro evi­dence of XPO1 overexpression in DLBCL cells along with cyto­tox­icity in DLBCL cell lines of multiple subtypes, in­­clud­ing double hit DLBCL. Analyses of DLBCL cell lines show Selinexor can reduce cytoplasmic BCL2/BCL6 and c-MYC mRNAs, which likely con­trib­utes to Selinexor's activity in DLBCL. In the ongoing phase 1 study in patients with DLBCL treated with 3-80 mg/m2 of Selinexor, responses were observed across GCB, non-GCB, and double-hit subtypes, and were also independent of prior ther­a­pies.

An addi­tional poster presentation on Saturday, June 14th from 5:45 - 7:00 PM CEST will provide results of Phase 1 and Phase 2 clin­i­cal trials of related SINE drug can­di­date Verdinexor (KPT-335) in spontaneous canine cancers, particularly lym­phomas (Abstract #4791).

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. To date, over 300 patients have been treated with Selinexor in Phase 1 and Phase 2 clin­i­cal 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.

About Karyopharm Therapeutics

Karyopharm Therapeutics Inc. (Nasdaq:KPTI) is 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. SINE com­­pounds have shown biological activity in models of cancer, auto­immune disease, certain viruses, and wound-healing. Karyopharm was founded by Dr. Sharon Shacham and is located in Natick, Massachusetts. For more in­­for­ma­tion about Karyopharm, please visit www.karyopharm.com.

Forward-Looking Statements

This press release con­tains for­ward-looking state­ments within the meaning of The Private Se­cu­ri­ties Lit­i­ga­tion Reform Act of 1995. Such for­ward-looking state­ments in­clude those re­gard­ing the thera­peutic poten­tial of and poten­tial clin­i­cal devel­op­ment plans for Karyopharm's drug can­di­dates, in­­clud­ing the timing of initiation of certain trials and of the reporting of data from such trials. Such state­ments are subject to numerous im­por­tant factors, risks and un­cer­tain­ties that may cause actual events or results to differ ma­teri­ally from the com­pany's current ex­pec­ta­tions. For example, there can be no guar­an­tee that any of Karyopharm's SINE com­­pounds, in­­clud­ing Selinexor (KPT-330), or any other drug can­di­date that Karyopharm is devel­op­ing will suc­cess­fully com­plete nec­es­sary pre­clin­i­cal and clin­i­cal devel­op­ment phases or that devel­op­ment of any of Karyopharm's drug can­di­dates will con­tinue. Further, there can be no guar­an­tee that any pos­i­tive devel­op­ments in Karyopharm's drug can­di­date portfolio will result in stock price ap­pre­ci­a­tion. Management's ex­pec­ta­tions and, there­fore, any for­ward-looking state­ments in this press release could also be affected by risks and un­cer­tain­ties relating to a number of other factors, in­­clud­ing the fol­low­ing: Karyopharm's results of clin­i­cal trials and pre­clin­i­cal studies, in­­clud­ing sub­se­quent analysis of existing data and new data received from ongoing and future studies; the content and timing of de­ci­sions made by the U.S. Food and Drug Admin­istra­tion and other regu­la­tory author­i­ties, inves­ti­ga­tional review boards at clin­i­cal trial sites and publication review bodies; Karyopharm's ability to obtain and main­tain requisite regu­la­tory approvals and to enroll patients in its clin­i­cal trials; unplanned cash require­ments and ex­pen­di­tures; devel­op­ment of drug can­di­dates by Karyopharm's com­pet­i­tors for diseases in which Karyopharm is cur­rently devel­op­ing its drug can­di­dates; and Karyopharm's ability to obtain, main­tain and enforce patent and other intellectual property protection for any drug can­di­dates it is devel­op­ing. These and other risks are described under the caption "Risk Factors" in Karyopharm's Annual Report on Form 10-K for the year ended December 31, 2013, which is on file with the Se­cu­ri­ties and Exchange Com­mis­sion (SEC), and in other filings that Karyopharm may make with the SEC in the future. Any for­ward-looking state­ments con­tained in this press release speak only as of the date hereof, and Karyopharm expressly disclaims any obli­ga­tion to update any for­ward-looking state­ments, whether as a result of new in­­for­ma­tion, future events or other­wise.

Source: Karyopharm Therapeutics.