Selinexor Marketing Authori­za­tion Appli­ca­tion to be Reviewed Under Accelerated Assessment

Newton, MA (Press Release) – Karyo­pharm Thera­peutics Inc. (Nasdaq:KPTI), a clin­i­cal-stage pharma­ceu­tical com­pany, to­day an­nounced that it has sub­mitted a Mar­ket­ing Authori­za­tion Appli­ca­tion (MAA) to the Euro­pean Medicines Agency (EMA) for selinexor, the Com­pany’s first-in-class, oral Sel­ective Inhibitor of Nuclear Export (SINE) com­pound, re­quest­ing con­di­tional ap­prov­al for the treat­ment of patients with re­lapsed or re­frac­tory mul­ti­ple myeloma (MM) who have re­ceived at least three prior lines of ther­apy and whose dis­ease is re­frac­tory to at least one pro­te­a­some in­hib­i­tor (PI), one immuno­modu­la­tory agent (IMiD), and one anti-CD38 mono­clonal anti­body (mAb), and to their most recent treat­ment regi­men (penta-refractory MM). Karyo­pharm also an­nounced that the selinexor MAA has been granted ac­cel­er­ated assess­ment by the EMA’s Com­mit­tee for Medicinal Products for Human Use (CHMP).

“The MAA sub­mission for selinexor is an im­por­tant mile­stone for Karyo­pharm and the CHMP’s granting of ac­cel­er­ated assess­ment fur­ther underscores the urgent need to im­prove out­comes for patients with highly re­frac­tory mul­ti­ple myeloma,” said Sharon Shacham, PhD, MBA, Founder, Pres­i­dent and Chief Scientific Officer of Karyo­pharm. “The results from the pivotal Phase 2b STORM study provide compelling evi­dence that selinexor in com­bi­na­tion with low-dose dexa­meth­a­sone has the poten­tial to be an ef­fec­tive new treat­ment op­tion for patients with this dif­fi­cult to treat dis­ease. With the filing of the MAA and an ac­cel­er­ated assess­ment desig­na­tion from the EMA, we hope to make oral selinexor avail­able as quickly as possible to patients throughout Europe.”

An ac­cel­er­ated assess­ment is granted to prod­ucts deemed by the CHMP to be of major interest for pub­lic health and rep­re­sent thera­peutic inno­va­tion. Accelerated assess­ments can reduce the active review time of an MAA from the standard 210 days down to 150 days once it has been val­i­dated by the EMA. Selinexor has also pre­vi­ously re­ceived orphan desig­na­tion in mul­ti­ple myeloma from the EMA.

A New Drug Appli­ca­tion (NDA) seek­ing ac­cel­er­ated ap­prov­al for oral selinexor with low dose dexa­meth­a­sone as a treat­ment for patients with penta-refractory mul­ti­ple myeloma is under Priority Review by the U.S. Food and Drug Admin­istra­tion (FDA) with an action date of April 6, 2019, under the Pre­scrip­tion Drug User-Fee Act (PDUFA).

About Selinexor

Selinexor 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. In 2018, Karyo­pharm reported pos­i­tive data from the Phase 2b STORM study eval­u­ating selinexor in com­bi­na­tion with low-dose dexa­meth­a­sone in patients with penta-refractory mul­ti­ple myeloma. Selinexor has been granted Orphan Drug Desig­na­tion in mul­ti­ple myeloma and Fast Track desig­na­tion for the patient pop­u­la­tion eval­u­ated in the STORM study. Karyo­pharm’s New Drug Appli­ca­tion (NDA) has been ac­cepted for filing and granted Priority Review by the FDA, and oral selinexor is cur­rently under review by the FDA as a possible new treat­ment for patients with penta-refractory mul­ti­ple myeloma. The Com­pany has also sub­mitted a Mar­ket­ing Authori­za­tion Appli­ca­tion (MAA) to the Euro­pean Medicines Agency (EMA) with a re­quest for con­di­tional ap­prov­al and was granted ac­cel­er­ated assess­ment. Selinexor is also being eval­u­ated in several other mid-and later-phase clin­i­cal trials across mul­ti­ple cancer indi­ca­tions, in­­clud­ing in mul­ti­ple myeloma in a pivotal, ran­dom­ized Phase 3 study in com­bi­na­tion with Velcade® (bor­tez­o­mib) and low-dose dexa­meth­a­sone (BOSTON), as a poten­tial back­bone ther­apy in com­bi­na­tion with approved ther­a­pies (STOMP), in diffuse large B-cell lym­phoma (SADAL), liposarcoma (SEAL), and an in­ves­ti­ga­tor-sponsored study in endometrial cancer (SIENDO), among others. Additional Phase 1, Phase 2 and Phase 3 stud­ies are on­go­ing or cur­rently planned, in­­clud­ing mul­ti­ple stud­ies in com­bi­na­tion with approved ther­a­pies in a variety of tumor types to fur­ther in­form Karyo­pharm's clin­i­cal devel­op­ment priorities for selinexor. Additional 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 and related 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 and com­bi­na­tion ac­­tiv­ity against a variety of human cancers, SINE com­pounds have also shown bio­logical ac­­tiv­ity in models of neu­ro­de­gen­er­a­tion, inflammation, auto­immune dis­ease, cer­tain viruses and wound-healing. Karyo­pharm, which was founded by Dr. Sharon Shacham, cur­rently has several inves­ti­ga­tional pro­grams in clin­i­cal or pre­clin­i­cal devel­op­ment. 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 our ex­pec­ta­tions relating to sub­missions and to the review and poten­tial ap­prov­al of selinexor by regu­la­tory author­i­ties, in­­clud­ing the antic­i­pated timing of such sub­missions and actions, and the poten­tial avail­ability of ac­cel­er­ated ap­prov­al path­ways, the thera­peutic poten­tial of and poten­tial clin­i­cal devel­op­ment plans for Karyo­pharm's drug can­di­dates, especially selinexor, and the plans for com­mer­cial­iza­tion. Such state­ments are subject to nu­mer­ous im­por­tant factors, risks and un­cer­tain­ties, many of which are beyond Karyo­pharm’s con­trol, that may cause actual events or results to differ ma­teri­ally from Karyo­pharm's current ex­pec­ta­tions. For example, there can be no guar­an­tee that regulators will agree that selinexor qualifies for ac­cel­er­ated ap­prov­al in the U.S. or con­di­tional ap­prov­al in the E.U. as a result of the data from the STORM study in patients with penta-refractory myeloma or the SADAL study in patients with re­lapsed or re­frac­tory DLBCL or that any of Karyo­pharm's drug can­di­dates, in­­clud­ing selinexor, will suc­cess­fully com­plete nec­es­sary 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, in­­clud­ing with respect to the need for addi­tional clin­i­cal stud­ies; 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, 2018, which was filed with the Se­cu­ri­ties and Ex­change Com­mis­sion (SEC) on No­vem­ber 8, 2018, 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, except as re­quired by law, Karyo­pharm expressly disclaims any obli­ga­tion to up­date any for­ward-looking state­ments, whether as a result of new in­for­ma­tion, future events or other­wise.

Velcade® is a registered trademark of Takeda Pharma­ceu­tical Com­pany Limited

Source: Karyo­pharm Thera­peutics.