• Oral Selinexor Achieves 25.4% Overall Response Rate and Median Duration of Response of 4.4 Months in Patients with Penta-Refractory Myeloma
• Company Plans to Submit a New Drug Application to the FDA in the Second Half of 2018
• Selinexor Continues to Demonstrate a Predictable and Manageable Tolerability Profile
• Management to Host Conference Call Tomorrow, May 1, 2018 at 8:00 a.m. ET

{{image}}Newton, MA (Press Release) – Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clin­i­cal-stage pharma­ceutical com­pany, today reported pos­i­tive top-line results from the Phase 2b STORM study eval­u­ating the Company’s lead, oral Selective Inhibitor of Nuclear Export (SINE) com­­pound selinexor in heavily pre­treated patients with refractory multiple myeloma. Regarding the STORM study’s pri­mary objective, oral selinexor achieved a 25.4% over­all response rate (ORR), which in­cluded two com­plete responses (CRs) and 29 partial (PRs) or very good partial responses (VGPRs) in these patients with penta-refractory myeloma. The median duration of response (DOR), a key sec­ond­ary objective, was 4.4 months. All responses were con­firmed by an Independent Review Committee (IRC). Selinexor was recently granted Fast-Track desig­na­tion by the U.S. Food and Drug Admin­istra­tion (FDA) for this indi­ca­tion.

The data reported today are from Part 2 of the inter­na­tional, multi-center, single-arm Phase 2b STORM (Selinexor Treatment of Refractory Myeloma) study, which enrolled 122 heavily pre­treated patients with penta-refractory myeloma. Each patient received 80mg oral selinexor twice weekly in com­bi­na­tion with low-dose dexa­metha­sone (20mg twice weekly). In this study, penta-refractory is defined as patients who have pre­vi­ously received at least one alkylating agent, gluco­corticoids, two immuno­modu­la­tory drugs (IMiDs) (Revlimid® (lena­lido­mide) and Pomalyst® (poma­lido­mide)), two pro­te­a­some inhibitors (PIs) (Velcade® (bor­tez­o­mib) and Kyprolis® (car­filz­o­mib)), and Darzalex® (dara­tu­mu­mab), an anti-CD38 mono­clonal anti­body, and whose disease is refractory to gluco­corticoids, at least one PI, at least one IMiD, and Darzalex, and whose disease has progressed fol­low­ing their most recent ther­apy.

Oral selinexor dem­onstrated a predictable and man­ageable tolerability profile, with safety results that were con­sis­tent with those pre­vi­ously reported from Part 1 of this study (Vogl et al., J Clin Oncol, 2018) and from other selinexor studies. As antici­pated, the most common adverse events (AEs) were nausea, vomiting, fatigue and reduced appetite and were primarily low grade and man­ageable with standard sup­port­ive care and/or dose modification. The most common hema­to­logic AEs were Grade ≥3 cytopenias and were gen­er­ally not asso­ci­ated with clin­i­cal sequelae. Karyopharm plans to submit detailed STORM study results for presentation at an upcoming medical on­col­ogy meeting.

Paul G. Richardson, MD, Director of Clinical Research, Jerome Lipper Multiple Myeloma Center at the Dana-Farber Cancer Institute, said, “Despite numerous ad­vances in myeloma treat­ment, cur­rently avail­able ther­a­pies are insufficient to address the in­creas­ing number of patients with highly resistant, penta-refractory myeloma, where the disease has ultimately be­come non-responsive to approved ther­apy. There is, there­fore, a real urgency for new ther­a­pies with novel mech­a­nisms of action for these patients, who have a critical unmet medical need. Selinexor’s targeted inhibition of nuclear export could poten­tially expand the armamentarium of treat­ment options sig­nif­i­cantly in this im­por­tant pop­u­la­tion for which no other estab­lish­ed treat­ment is readily avail­able.”

“The 25.4% response rate and 4.4 month duration of response observed in the STORM study are highly compelling,” stated Sundar Jagannath, MD, Director of the Multiple Myeloma Program and Pro­fessor of Medicine (Hematology and Medical Oncology) at Tisch Cancer Institute at Mount Sinai School of Medicine. “For an orally admin­istered ther­apy, these new data underscore selinexor’s poten­tial to be an exciting new treat­ment option for these dif­fi­cult-to-treat patients who have exhausted approved ther­a­pies.”

Selinexor has been granted Orphan Drug Desig­na­tion in multiple myeloma and Fast Track desig­na­tion for the patient pop­u­la­tion eval­u­ated in the STORM study. Karyopharm plans to submit a New Drug Application (NDA) to the FDA during the second half of 2018, with a request for accelerated approval for oral selinexor as a new treat­ment for patients with penta-refractory multiple myeloma. 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. In parallel, Karyopharm is also conducting the pivotal, ran­domized Phase 3 BOSTON study eval­u­ating selinexor in com­bi­na­tion with the pro­te­a­some inhibitor Velcade and dexa­metha­sone (SVd) for the treat­ment of patients with multiple myeloma who have had one to three prior lines of ther­apy. The Company is ex­pec­ting to com­plete enrollment in the BOSTON study by the end of 2018, with top-line data antic­i­pated in 2019. Assuming a pos­i­tive out­come, Karyopharm plans to use the results from the BOSTON study to sup­port an appli­ca­tion for full approval in the U.S.

“We are extremely grateful to, and thank, the patients, their families and the investigators for their im­por­tant con­tri­bu­tions to the STORM study,” said Sharon Shacham, PhD, Founder, Pres­i­dent and Chief Scientific Officer of Karyopharm. “Penta-refractory myeloma is an area of true unmet medical need as these patients have con­tinued to progress despite receiving avail­able ther­a­pies. We are fully committed to bringing this new, orally admin­istered poten­tial treat­ment option to patients who have no other ther­apy options of proven benefit. To our knowledge, oral selinexor is the most ad­vanced agent being in­ves­ti­gated in patients with penta-refractory myeloma and we look for­ward to submitting our NDA to the FDA during the second half of this year, with a sub­mission to the EMA to follow.”

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 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 recently 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 pivotal, Phase 3 BOSTON study, and has reminded the Company that accelerated approval requires patients to have exhausted approved ther­a­pies. The Company recently received Fast Track desig­na­tion from the FDA, which is avail­able to thera­peutics treating an unmet medical need in a serious con­di­tion. In light of this recognition that the STORM patient pop­u­la­tion rep­re­sents an unmet medical need and the pos­i­tive top-line data reported today, the Company believes that the STORM study should sup­port its request to the FDA for accelerated approval.

Conference Call Information

Karyopharm will host a conference call tomorrow, Tuesday, May 1, 2018, at 8:00 a.m. Eastern Time, to discuss the top-line Phase 2b STORM clin­i­cal data. The call will feature recog­nized myeloma experts Drs. Sundar Jagannath and Paul Richardson, along with members of the Karyopharm exec­u­tive leadership team. To access the conference call, please dial (855) 437-4406 or (484) 756-4292 (international) at least five min­utes prior to the start time and refer to conference ID: 9869309. The call will also be webcast live on the Company’s website, http://www.karyopharm.com. An audio recording of the call will be avail­able under “Events & Presentations” in the “Investors” section of Karyopharm's website approx­i­mately two hours after the event.

About Selinexor

Selinexor (KPT-330) 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), thus leading to the accumulation of tumor sup­pressor proteins in the cell nucleus. This reinitiates and amplifies the tumor sup­pressor functions of these proteins and is believed to lead to the selective induction of apop­tosis in cancer cells, while largely sparing nor­mal cells. To date, over 2,400 patients have been treated with selinexor, and it is cur­rently being eval­u­ated in several 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), in com­bi­na­tion with low-dose dexa­meth­a­sone (STORM) and back­bone ther­a­pies (STOMP), and in diffuse large B-cell lym­phoma (SADAL) and lipo­sarcoma (SEAL), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or cur­rently planned, in­­clud­ing multiple studies in com­bi­na­tion with one or more approved ther­a­pies in a variety of tumor types to further inform Karyopharm's clin­i­cal devel­op­ment priorities for selinexor. Karyopharm’s composition of matter patent protection for selinexor is ex­pec­ted to remain in effect through at least 2032 prior to any appli­­cable extensions (e.g., Hatch-Waxman Act, also known as the Drug Price Competition and Patent Term Restoration Act). 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 the thera­peutic poten­tial of and poten­tial clin­i­cal develop­ment plans for Karyopharm's drug can­di­dates, especially selinexor. 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 Annual Report on Form 10-K for the year ended December 31, 2017, which was filed with the Se­cu­ri­ties and Exchange Com­mis­sion (SEC) on March 15, 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.