Phase 1/2 Study to Evaluate KPT-8602 in Patients With Relapsed/Refractory Multiple Myeloma

Newton, MA (Press Release) – Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clin­i­cal-stage phar­ma­ceu­ti­cal com­pany, announced today the initiation of a Phase 1/2 study of oral KPT-8602, a novel, second gen­er­a­tion, small-molecule selective inhibitor of nuclear export (SINE^TM) protein XPO1, in patients with re­lapsed/​refractory multiple myeloma (MM). This first-in-human study is designed to eval­u­ate the safety, tolerability and activity of approx­i­mately eight dose levels of KPT-8602 in up to 116 patients in multiple centers in the United States and Canada. Karyopharm con­tinues to expand its leadership in SINE-based ther­a­pies and is committed to being the world leader in nuclear transport modulation.

“We are encouraged by the pre­clin­i­cal profile of KPT-8602 and data presented at the 2015 American Society of Hematology annual meeting, which dem­onstrate that the com­pound can be dosed daily over five days per week in animals,” said Sharon Shacham, PhD, Pres­i­dent and Chief Scientific Officer of Karyopharm. “This dosing schedule and tolerability profile, if translated to the clinic, has the poten­tial to yield a drug profile distinct from selinexor, Karyopharm’s first-in-class, oral SINE com­pound. More frequent dosing provides continuous XPO1 inhibition and the poten­tial for dif­fer­en­ti­ated tolerability, efficacy, and combinability with avail­able on­col­ogy treat­ments and targeted ther­a­pies. This first-in-human study rep­re­sents a key expansion of our clin­i­cal pipe­line and a new avenue for exploring and leveraging the mech­a­nism for XPO1 inhibition in hema­to­logic malig­nan­cies."

Data from several pre­clin­i­cal studies of KPT-8602 presented at the 2015 American Society of Hematology (ASH) annual meeting dem­onstrated that the com­pound had single-agent anti-MM activity. In addi­tion, KPT-8602 showed synergistic activity against MM when com­bined with bor­tez­o­mib, car­filz­o­mib, doxorubicin, mel­phalan, topotecan, or VP16 as shown in proliferation and/or apop­tosis assays on parental or drug-resistant cell lines, or patient derived MM samples. KPT-8602 was shown to have anti-MM activity in human tumor xenograft models as a single agent or in com­bi­na­tion with mel­phalan. Promising pre­clin­i­cal efficacy in­cluded apparent cures in dif­fi­cult murine models of AML and CLL. KPT-8602 rep­re­sents a novel chemical series with pharmacological properties distinct from selinexor with more reversible binding to XPO1, similar potency in cell-based assays and sub­stan­tially reduced brain penetration.

About KPT-8602

KPT-8602 is a second generation oral SINE^TM com­pound. KPT-8602 functions by binding to and inhibiting the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor sup­pressor proteins in the cell nucleus. KPT-8602 has dem­onstrated minimal brain penetration in animals, which has been asso­ci­ated with reduced toxicities in pre­clin­i­cal studies while main­taining potent anti-tumor effects.

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. Karyopharm's SINE™ com­pounds function by binding with and inhibiting the nuclear export protein XPO1 (or CRM1). In addi­tion to single-agent activity against a variety of human cancers, SINE™ com­pounds have also shown biological activity in models of inflammation, auto­immune disease, certain viruses and wound-healing. Karyopharm was founded by Dr. Sharon Shacham and is located in Newton, Massachusetts. For more in­for­ma­tion, 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), KPT-8602 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 Quarterly Report on Form 10-Q for the quarter ended September 30, 2015, which is on file with the Securities and Exchange Com­mis­sion (SEC) as of November 9, 2015, 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.