Newton, MA and Petah Tikva, Israel (Press Release) – Karyo­pharm Thera­peutics Inc. (Nasdaq:KPTI), an on­col­ogy-focused pharma­ceu­tical com­pany, and Promedico, a member of the Neopharm Group, today announced their entry into an ex­clu­sive distribution agree­ment for the com­mer­cial­iza­tion of XPOVIO® (seli­nexor), Karyo­pharm’s lead SINE com­pound, in Israel and the Palestinian Authority.

Under the terms of the agree­ment, Karyo­pharm will re­ceive cer­tain prespecified pay­ments and is eli­gible to re­ceive addi­tional pay­ments if prespecified regu­la­tory and commercial mile­stones are achieved by Promedico, a fully-owned Neopharm LTD com­pany. Karyo­pharm is also eli­gible to re­ceive double-digit royalties on future net sales of XPOVIO in the covered territory. In ex­change, Promedico will re­ceive ex­clu­sive rights to com­mer­cial­ize XPOVIO in the covered territory and is responsible for all regu­la­tory filings and obli­ga­tions required for registering XPOVIO. Karyo­pharm has retained ex­clu­sive pro­duc­tion rights and will supply finished prod­uct for commercial use in the covered territory.

“The addi­tion of XPOVIO fits our port­folio of inno­va­tive on­col­ogy prod­ucts designed to treat dis­eases with sig­nif­i­cant unmet need,” said Avishay Zlotnik, Chief Executive Officer of Promedico Ltd. “We share Karyo­pharm’s com­mitment to cancer patients and believe our deep ex­per­tise as one of the largest health­care distributor groups in Israeli will allow us to effectively bring XPOVIO to the Israeli mar­ket.”

“Neopharm com­pa­nies have a proven track record of suc­cess­fully com­mer­cial­iz­ing new thera­peutics in Israel, making them an ideal partner to further ex­pand the global reach of XPOVIO,” said Sharon Shacham, PhD, MBA, Founder, Pres­i­dent and Chief Scientific Officer of Karyo­pharm. “We look for­ward to work­ing with their world-class team to bring XPOVIO to cancer patients in need of novel ther­a­pies.”

About XPOVIO® (seli­nexor)

XPOVIO is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) com­pound. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein exportin 1 (XPO1, also called CRM1). XPOVIO blocks the nuclear export of tumor sup­pressor, growth regu­la­tory and anti-inflammatory proteins, leading to accumulation of these proteins in the nucleus and enhancing their anti-cancer activity in the cell. The forced nuclear retention of these proteins can coun­ter­act a mul­ti­tude of the oncogenic path­ways that, unchecked, allow cancer cells with severe DNA damage to con­tinue to grow and divide in an unrestrained fashion. In addi­tion to re­ceiv­ing ac­cel­er­ated U.S. Food and Drug Admin­istra­tion (FDA) approval of XPOVIO in July 2019 in com­bi­na­tion with dexa­meth­a­sone for the treat­ment of adult patients with re­lapsed re­frac­tory multiple myeloma (RRMM) who have re­ceived at least four prior ther­a­pies and whose dis­ease is re­frac­tory to at least two pro­te­a­some in­hib­i­tors, at least two immuno­modu­la­tory agents, and an anti-CD38 mono­clonal anti­body, Karyo­pharm has also sub­mitted a Marketing Authori­za­tion Application (MAA) to the European Medicines Agency (EMA) with a request for con­di­tional approval of selinexor. A New Drug Application was recently sub­mitted to the FDA seek­ing ac­cel­er­ated approval for selinexor as a new treat­ment for patients with re­lapsed or re­frac­tory diffuse large B-cell lym­phoma (DLBCL). Selinexor has re­ceived Fast Track and Orphan desig­na­tion from the FDA for the patient pop­u­la­tion eval­u­ated in the SADAL study. 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 liposarcoma (SEAL) and 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.

IMPORTANT SAFETY INFORMATION

Thrombocytopenia

XPOVIO can cause thrombo­cyto­penia, leading to poten­tially fatal hemorrhage. Thrombocytopenia was reported as an adverse reac­tion in 74% of patients, and severe (Grade 3-4) thrombo­cyto­penia occurred in 61% of patients treated with XPOVIO. The median time to onset of the first event was 22 days. Bleeding occurred in 23% of patients with thrombo­cyto­penia, clin­i­cally sig­nif­i­cant bleeding occurred in 5% of patients with thrombo­cyto­penia and fatal hemorrhage occurred in <1% of patients.

Monitor platelet counts at base­line, during treat­ment, and as clin­i­cally in­di­cated. Monitor more fre­quently during the first two months of treat­ment. Institute platelet transfusion and/or other treat­ments as clin­i­cally in­di­cated. Monitor patients for signs and symp­toms of bleeding and eval­u­ate promptly. Interrupt and/or reduce dose, or perma­nently dis­con­tinue based on severity of adverse reac­tion.

Neutropenia

XPOVIO can cause neu­tro­penia, poten­tially in­creas­ing the risk of in­fec­tion. Neutropenia was reported as an adverse reac­tion in 34% of patients, and severe (Grade 3-4) neu­tro­penia occurred in 21% of patients treated with XPOVIO. The median time to onset of the first event was 25 days. Febrile neu­tro­penia was reported in 3% of patients.

Obtain neu­tro­phil counts at base­line, during treat­ment, and as clin­i­cally in­di­cated. Monitor more fre­quently during the first two months of treat­ment. Monitor patients for signs and symp­toms of con­com­i­tant in­fec­tion and eval­u­ate promptly. Consider sup­port­ive measures in­clud­ing antimicrobials for signs of in­fec­tion and use of growth factors (e.g., G-CSF). Interrupt and/or reduce dose, or perma­nently dis­con­tinue based on severity of adverse reac­tion.

Gastrointestinal Toxicity

Gastrointestinal toxicities occurred in patients treated with XPOVIO.

Nausea / Vomiting

Nausea was reported as an adverse reac­tion in 72% of patients, and Grade 3 nausea occurred in 9% of patients treated with XPOVIO. The median time to onset of the first nausea event was 3 days.

Vomiting was reported in 41% of patients, and Grade 3 vomiting occurred in 4% of patients treated with XPOVIO. The median time to onset of the first vomiting event was 5 days.

Provide pro­phy­lactic 5-HT3 antagonists and/or other anti-nausea agents, prior to and during treat­ment with XPOVIO. Manage nausea / vomiting by dose inter­rup­tion, re­duc­tion, and/or dis­con­tinu­a­tion. Admin­ister in­tra­venous fluids and replace electrolytes to prevent dehydration in patients at risk. Use addi­tional anti-nausea med­i­ca­tions as clin­i­cally in­di­cated.

Diarrhea

Diarrhea was reported as an adverse reac­tion in 44% of patients, and Grade 3 diarrhea occurred in 6% of patients treated with XPOVIO. The median time to onset of diarrhea was 15 days.

Manage diarrhea by dose modifications and/or standard anti-diarrheal agents; admin­ister in­tra­venous fluids to prevent dehydration in patients at risk.

Anorexia / Weight Loss

Anorexia was reported as an adverse reac­tion in 53% of patients, and Grade 3 anorexia occurred in 5% of patients treated with XPOVIO. The median time to onset of anorexia was 8 days.

Weight loss was reported as an adverse reac­tion in 47% of patients, and Grade 3 weight loss occurred in 1% of patients treated with XPOVIO. The median time to onset of weight loss was 15 days.

Monitor patient weight at base­line, during treat­ment, and as clin­i­cally in­di­cated. Monitor more fre­quently during the first two months of treat­ment. Manage anorexia and weight loss with dose modifications, appetite stimulants, and nutritional sup­port.

Hyponatremia

XPOVIO can cause hyponatremia; 39% of patients treated with XPOVIO ex­peri­enced hyponatremia, 22% of patients ex­peri­enced Grade 3 or 4 hyponatremia. The median time to onset of the first event was 8 days.

Monitor sodium level at base­line, during treat­ment, and as clin­i­cally in­di­cated. Monitor more fre­quently during the first two months of treat­ment. Correct sodium levels for concurrent hyperglycemia (serum glucose >150 mg/dL) and high serum paraprotein levels. Treat hyponatremia per clin­i­cal guidelines (intravenous saline and/or salt tablets), in­clud­ing dietary review. Interrupt and/or reduce dose, or perma­nently dis­con­tinue based on severity of adverse reac­tion.

Infections

In patients re­ceiv­ing XPOVIO, 52% of patients ex­peri­enced any grade of in­fec­tion. Upper res­pira­tory tract in­fec­tion of any grade occurred in 21%, pneu­monia in 13%, and sepsis in 6% of patients. Grade ≥3 in­fec­tions were reported in 25% of patients, and deaths resulting from an in­fec­tion occurred in 4% of patients. The most commonly reported Grade ≥3 in­fec­tions were pneu­monia in 9% of patients, followed by sepsis in 6%. The median time to onset was 54 days for pneu­monia and 42 days for sepsis. Most in­fec­tions were not asso­ci­ated with neu­tro­penia and were caused by non-opportunistic organisms.

Neurological Toxicity

Neurological toxicities occurred in patients treated with XPOVIO.

Neurological adverse reac­tions in­clud­ing dizzi­ness, syncope, depressed level of consciousness, and mental status changes (including delirium and confusional state) occurred in 30% of patients, and severe events (Grade 3-4) occurred in 9% of patients treated with XPOVIO. Median time to the first event was 15 days.

Optimize hydration status, hemoglobin level, and con­com­i­tant med­i­ca­tions to avoid exacerbating dizzi­ness or mental status changes.

Embryo-Fetal Toxicity

Based on data from animal studies and its mech­a­nism of action, XPOVIO can cause fetal harm when admin­istered to a pregnant woman. Selinexor admin­istra­tion to pregnant animals during or­gano­gen­e­sis resulted in structural ab­nor­mal­i­ties and alterations to growth at exposures below those occurring clin­i­cally at the rec­om­mended dose.

Advise pregnant women of the poten­tial risk to a fetus. Advise females of reproductive poten­tial and males with a female partner of reproductive poten­tial to use effective con­tra­cep­tion during treat­ment with XPOVIO and for 1 week after the last dose.

ADVERSE REACTIONS

The most common adverse reac­tions (incidence ≥20%) are thrombo­cyto­penia, fatigue, nausea, anemia, de­creased appetite, de­creased weight, diarrhea, vomiting, hyponatremia, neu­tro­penia, leu­ko­penia, con­sti­pa­tion, dyspnea, and upper res­pira­tory tract in­fec­tion.

The treat­ment dis­con­tinu­a­tion rate due to adverse reac­tions was 27%; 53% of patients had a re­duc­tion in the XPOVIO dose, and 65.3% had the dose of XPOVIO interrupted. The most fre­quent adverse reac­tions requiring perma­nent dis­con­tinu­a­tion in 4% or greater of patients who re­ceived XPOVIO in­cluded fatigue, nausea, and thrombo­cyto­penia. The rate of fatal adverse reac­tions was 8.9%.

Please see XPOVIO Full Prescribing Information avail­able at www.XPOVIO.com.

About Karyo­pharm Thera­peutics

Karyopharm Thera­peutics Inc. (Nasdaq: KPTI) is an on­col­ogy-focused pharma­ceu­tical com­pany dedicated to the discovery, devel­op­ment, and com­mer­cial­iza­tion of novel first-in-class drugs directed against nuclear export and related targets for the treat­ment of cancer and other major dis­eases. Karyo­pharm's Selective Inhibitor of Nuclear Export (SINE) com­pounds function by binding with and inhibiting the nuclear export protein XPO1 (or CRM1). Karyo­pharm’s lead com­pound, XPOVIO® (seli­nexor), re­ceived ac­cel­er­ated approval from the U.S. Food and Drug Admin­istra­tion (FDA) in July 2019 in com­bi­na­tion with dexa­meth­a­sone as a treat­ment for patients with heavily pre­treated multiple myeloma. A Marketing Authori­za­tion Application for selinexor is also cur­rently under review by the European Medicines Agency. Karyo­pharm recently sub­mitted a New Drug Application to the FDA seek­ing ac­cel­er­ated approval for XPOVIO in patients with diffuse large B-Cell lym­phoma. 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 has several inves­ti­ga­tional pro­grams in clin­i­cal or pre­clin­i­cal devel­op­ment. For more in­for­ma­tion, please visit www.karyopharm.com.

About Neopharm Group

Established in 1941, Neopharm is one of Israel's leading providers of inno­va­tive integrated solu­tions across the pharma­ceu­tical, medical and health­care mar­kets. Neopharm focuses on the sale and mar­ket­ing of novel ground­break­ing specialty and orphan med­i­ca­tions as well as home health­care services in Israel via part­ner­ships with the world's leading multinational bio-pharma com­pa­nies. Neopharm is the partner-of-choice and one-stop-shop for multinational bio-pharma com­pa­nies seek­ing to enter or ex­pand their business in the Israeli pharma­ceu­tical, medical and bio­technology mar­kets and is proud of its best-in-class plat­form, repu­ta­tion and track- record of success for launching and mar­ket­ing ground­break­ing novel ther­a­pies in Israel.

The incorporation of Orphan Technologies Ltd. and the acquisition of Neovii during the past decade transitioned us into a fully-integrated and rapidly-growing bio­pharma­ceu­tical com­pany, with global patient reach, that is pursuing its global patient-focused mission to de­vel­op and bring novel life-transforming biological ther­a­pies to patients around the world that suffer from complex, severe and rare dis­eases.

Neopharm group of com­pa­nies employs more than 900 employees, has an annual sales turnover in excess of US$450M and sales in 60 countries.

For more in­for­ma­tion, please visit http://www.promedico.co.il/en/

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 Karyo­pharm’s ex­pec­ta­tions relating to XPOVIO for the treat­ment of patients with heavily pre­treated multiple myeloma or re­lapsed or re­frac­tory diffuse large B-cell lym­phoma; com­mer­cial­iza­tion of XPOVIO or any of its drug can­di­dates and the commercial per­for­mance of XPOVIO; sub­missions to, and the review and poten­tial approval of selinexor by, regu­la­tory author­i­ties, in­clud­ing the antic­i­pated avail­a­bil­ity of data to sup­port such sub­missions, timing of such sub­missions and actions by regu­la­tory author­i­ties and the poten­tial avail­a­bil­ity of ac­cel­er­ated approval path­ways; and 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, 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 Karyo­pharm will suc­cess­fully com­mer­cial­ize XPOVIO; that regulators will agree that selinexor qualifies for con­di­tional approval in the E.U. as a result of data from the STORM study or con­firmatory approval in the U.S. or EU based on the BOSTON study in patients with re­lapsed or re­frac­tory multiple myeloma, or ac­cel­er­ated approval in the U.S. for patients with re­lapsed or re­frac­tory DLBCL as a result of data from the SADAL study, 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 the devel­op­ment or com­mer­cial­iza­tion of 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: adoption of XPOVIO in the commercial mar­ket­place, the timing and costs in­volve­d in com­mer­cial­iz­ing XPOVIO or any of Karyo­pharm’s drug can­di­dates that re­ceive regu­la­tory approval; the ability to retain regu­la­tory approval of XPOVIO or any of Karyo­pharm’s drug can­di­dates that re­ceive regu­la­tory approval; 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; the ability of Karyo­pharm or its third party col­lab­o­rators or successors in interest to fully per­form their re­spec­tive­ obli­ga­tions under the appli­cable agree­ment and the poten­tial future fi­nan­cial implications of such agree­ment; 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, 2019, which was filed with the Se­cu­ri­ties and Ex­change Com­mis­sion (SEC) on No­vem­ber 4, 2019, 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.