Company Plans to Complete Submission During the Second Half of 2018

Newtown, MA (Press Release) – Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clin­i­cal-stage pharma­ceu­tical com­pany, today announced that the Company has ini­ti­ated a rolling sub­mission of a New Drug Application (NDA) to the U.S. Food and Drug Admin­istra­tion (FDA) seeking accelerated approval for selinexor, its novel, oral SINE com­­pound, as a new treat­ment for patients with penta-refractory multiple myeloma. Patients with penta-refractory myeloma have pre­vi­ously received the two pro­te­a­some inhibitors (PIs), Velcade® (bor­tez­o­mib) and Kyprolis® (car­filz­o­mib), the two immuno­modu­la­tory drugs (IMiDs), Revlimid® (lena­lido­mide) and Pomalyst® (poma­lido­mide), and the anti-CD38 mono­clonal anti­body Darzalex® (dara­tu­mu­mab), and their disease is refractory to at least one PI, at least one IMiD, Darzalex and their most recent ther­apy. The Company ex­pec­ts to com­plete the NDA sub­mission during the second half of 2018. Selinexor has received both Orphan Drug and Fast Track desig­na­tions from the FDA for this indi­ca­tion.

“We believe that selinexor has the poten­tial to address the critical unmet need for patients with highly resistant, penta-refractory myeloma, where the disease is no longer re­spon­sive­ to standard approved ther­a­pies,” said Sharon Shacham, PhD, MBA, Founder, Pres­i­dent and Chief Scientific Officer of Karyopharm. “The commencement of this rolling sub­mission for the oral selinexor NDA marks the first-ever appli­ca­tion for regu­la­tory approval of an Exportin 1 (XPO1) inhibitor and rep­re­sents a major mile­stone for the Company. We are proud of the pos­i­tive Phase 2b STORM study results under­lying this appli­ca­tion and we will work expeditiously to com­plete the sub­mission this year.”

Pending mar­ket­ing approval by the FDA, Karyopharm plans to com­mer­cial­ize selinexor in the U.S. The Company also plans to submit a Marketing Authorization Application to the European Medicines Agency in early 2019 with a request for con­di­tional approval.

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. To date, over 2,500 patients have been treated with selinexor. In April 2018, Karyopharm reported pos­i­tive top-line 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 has ini­ti­ated a rolling sub­mission for a New Drug Application (NDA) to the U.S. Food and Drug Admin­istra­tion (FDA), with a request for accelerated approval for oral selinexor as a new treat­ment for patients with penta-refractory multiple myeloma and ex­pec­ts the sub­mission to be com­plete during the second half of 2018. The Company also plans to submit a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) in early 2019 with a request for con­di­tional approval. 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.

Further Information About Potential Accelerated Approval for Selinexor in Multiple Myeloma

The FDA instituted its Accelerated Approval Program to allow for expedited approval of drugs that treat serious con­di­tions and that fill an unmet medical need based on a surrogate end­point or an intermediate clin­i­cal end­point thought to predict clin­i­cal benefit, like over­all response rate (ORR). Accelerated approval is avail­able only for drugs that provide a meaningful thera­peutic benefit over existing treat­ments at the time of con­sid­er­a­tion of the appli­ca­tion for accelerated approval, which the FDA has reiterated in its feedback to the Company. Particularly in disease areas with multiple avail­able and poten­tial new ther­a­pies, such as multiple myeloma, accelerated approval carries a high regu­la­tory threshold. Consistent with its general guidance, the FDA has noted to the Company its pref­er­ence for ran­domized studies geared to­ward full approval, which the Company has under­taken with the ongoing pivotal, Phase 3 BOSTON study, and has reminded the Company that accelerated approval requires patients to have exhausted all avail­able approved ther­a­pies. FDA’s Fast Track desig­na­tion is avail­able to thera­peutics treating an unmet medical need in a serious con­di­tion; the Company has received Fast Track desig­na­tion from the FDA specifically for the pop­u­la­tion treated in the STORM trial. In light of this recognition that the STORM patient pop­u­la­tion rep­re­sents an unmet medical need and the pos­i­tive top-line data reported in April 2018, the Company believes that the STORM study should sup­port its request to the FDA for accelerated approval.

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 the sub­missions to regu­la­tory author­i­ties, in­­clud­ing the antic­i­pated timing of such sub­missions, 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 that may cause actual events or results to differ ma­teri­ally from Karyopharm's current ex­pec­ta­tions. For example, there can be no guar­an­tee that any of Karyopharm's drug can­di­dates, in­­clud­ing selinexor, will suc­cess­fully com­plete nec­es­sary clin­i­cal devel­op­ment phases, that devel­op­ment of any of Karyopharm's drug can­di­dates will con­tinue or that any feedback from regu­la­tory author­i­ties will ultimately lead to the approval of selinexor or any of Karyopharm’s other drug can­di­dates. 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 March 31, 2018, which was filed with the Se­cu­ri­ties and Exchange Com­mis­sion (SEC) on May 10, 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.
Revlimid® and Pomalyst® are registered trademarks of Celgene Corpo­ra­tion
Kyprolis® is a registered trademark of Onyx Pharma­ceu­ticals, Inc.
Darzalex® is a registered trademark of Janssen Biotech, Inc.

Source: Karyopharm Therapeutics Inc.