• Antengene Rights Include All Human Oncology Indications for Selinexor, Eltanexor and KPT-9274, and Non-Oncology Human Indications for Verdinexor
• Karyopharm to Receive $12 Million (USD) Upfront; Total Deal Valued at up to $162 Million with Karyo­pharm Eligible to Receive up to $150 Million (USD) in Future Milestones, Plus Royalties

Newton, MA and Shanghai, China (Press Release) – Karyo­pharm Thera­peutics Inc. (Nasdaq:KPTI) (Karyopharm) and Antengene Corpo­ra­tion (Antengene), to­day an­nounced their entry into an ex­clu­sive license agree­ment for the de­vel­op­ment and com­mer­cial­iza­tion of four of Karyo­pharm’s novel, oral drug can­di­dates, in­clud­ing selinexor, Karyo­pharm’s lead SINE com­pound, eltanexor, Karyo­pharm’s sec­ond-generation SINE com­pound, verdinexor, Karyo­pharm’s lead com­pound in de­vel­op­ment for viral and other non-oncology in­di­ca­tions, and KPT-9274, Karyo­pharm’s dual in­hib­i­tor of PAK4 and NAMPT. The agree­ment in­cludes the de­vel­op­ment and com­mer­cial­iza­tion of selinexor and eltanexor for the diag­nosis, treat­ment and/or prevention of all human on­col­ogy in­di­ca­tions in China and Macau. The agree­ment also in­cludes the de­vel­op­ment and com­mer­cial­iza­tion of KPT-9274 in all human on­col­ogy in­di­ca­tions and verdinexor in human non-oncology in­di­ca­tions in mainland China, Macau, Taiwan, Hong Kong, South Korea, and the ASEAN countries.

Under the terms of the agree­ment, Karyo­pharm will re­ceive a one-time up­front pay­ment of $12 million (USD) from Antengene. Karyo­pharm is eli­gible to re­ceive up to an addi­tional $150 million (USD) if cer­tain future prespecified de­vel­op­ment, regu­la­tory and com­mer­cial mile­stones are achieved by Antengene. Karyo­pharm is also eli­gible to re­ceive tiered double-digit royalties based on future net sales of selinexor and eltanexor in China and Macau, and tiered single- to double-digit royalties based on future net sales of verdinexor and KPT-9274 in the relevant territories. In ex­change, Antengene will re­ceive ex­clu­sive rights to de­vel­op, manu­fac­ture and com­mer­cialize the com­pounds in the agreed to territories, at its own cost and expense. Antengene will also have the ability to par­tic­i­pate in any global clin­i­cal study of selinexor, eltanexor, verdinexor or KPT-9274, and will bear the cost and expense for patients en­rolled in clin­i­cal studies in the agreed to territories.

“This agree­ment with Karyo­pharm brings to our pipe­line four promising, clin­i­cal-stage prod­uct can­di­dates with broad applicability across multiple dis­ease areas, with a par­tic­u­lar focus in on­col­ogy, with the poten­tial to help patients in a number of Asian territories. To com­ple­ment the ongoing clin­i­cal de­vel­op­ment efforts by Karyo­pharm, Antengene may ini­ti­ate addi­tional clin­i­cal trials in dis­eases with high in­ci­dence in Greater China and other Asian regions,” said Jay Mei, MD, PhD, Chairman and Chief Executive Officer of Antengene. “At Antengene, we are driven by a higher pur­pose and our goal is to be­come a mar­ket leader in devel­op­ing inno­va­tive ther­a­pies that address unmet med­i­cal needs in the Asia Pacific region. We are delighted to part­ner with Karyo­pharm, a pioneering on­col­ogy com­pany with a strong track record in the re­search and de­vel­op­ment of novel, targeted com­pounds, and we believe this trans­action underscores our strong focus on and com­mitment to health­care inno­va­tion.”

“Antengene is ded­i­cated to devel­op­ing novel, cutting-edge ther­a­pies and has strong clin­i­cal and regu­la­tory ex­per­tise and capabilities in China and the other licensed Asian regions,” said Michael G. Kauffman, MD, PhD, Chief Executive Officer of Karyo­pharm. “This stra­te­gic alliance adds to the impressive consortium of global Karyo­pharm part­ners who are actively ad­vanc­ing our novel oral drug can­di­dates in these im­por­tant mar­kets, while allow­ing us to focus our in­ternal resources on executing our late-phase selinexor trials and pursue regu­la­tory ap­prov­al in the United States and the European Union. In par­tic­u­lar, this col­lab­o­ration for addi­tional territories in Asia com­ple­ments our existing part­ner­ship with Ono Pharma­ceu­tical for selinexor and eltanexor in Japan, Taiwan, South Korea, Hong Kong and the ASEAN countries.”

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), 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 2,400 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 plans to submit a New Drug Appli­ca­tion (NDA) to the U.S. Food and Drug Admin­istra­tion (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. 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) and as a poten­tial back­bone ther­apy in com­bi­na­tion with approved ther­a­pies (STOMP), and 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 cur­rent 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. Additional clin­i­cal trial in­for­ma­tion for selinexor is avail­able at www.clinicaltrials.gov.

About Eltanexor

Eltanexor is a sec­ond generation oral SINE com­pound. Eltanexor 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. Eltanexor has dem­onstrated minimal brain penetration in animals, which has been asso­ci­ated with reduced toxicities in pre­clin­i­cal studies while main­taining potent anti-tumor effects. A Phase 1/2 clin­i­cal study is cur­rent ongoing eval­u­ating eltanexor in myelo­dys­plastic syn­drome, colorectal cancer and castrate-resistant prostate cancer.

About Verdinexor

Verdinexor (KPT-335) is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) com­pound being in­ves­ti­gated across a variety of non-oncology in­di­ca­tions in humans with an initial focus as a poten­tial broad-spectrum treat­ment for viral dis­eases. Verdinexor functions by binding to and in­hib­iting the nuclear export pro­tein XPO1 (also called CRM1), which is believed to be responsible for the movement of critical host cell and pathogen encoded cargoes across the nuclear membrane into the cytoplasm. Inhibition of this process with verdinexor results in accumulation of these cargoes in the nucleus, where they promote an anti-in­flam­ma­tory state and prevent key steps in pathogen rep­li­ca­tion from oc­curring. Prior pre­clin­i­cal re­search showed efficacy of verdinexor in several viral models, in­clud­ing HIV and promising pre-clinical data has also been observed in multiple addi­tional non-oncology in­di­ca­tions. In a pre­vi­ously conducted ran­dom­ized, double-blind, placebo-controlled, dose-escalating Phase 1 clin­i­cal trial in healthy human volunteers, verdinexor was found to be generally safe and well tolerated, with adverse events oc­curring in similar number and grade as placebo.

About KPT-9274

KPT-9274 is a first-in-class, orally bioavailable, small mol­e­cule immunometabolic modulator that works through non-competitive dual in­hib­ition of p21-activated kinase 4 (PAK4) and nicotinamide phosphoribosyltransferase (NAMPT). NAMPT and NAPRT (Nicotinate Phosphoribosyltransferas) are the two main path­ways for pro­duc­tion of the NAD (nicotinamide dinucleotide). About 15-30% of all solid tumors are deficient in NAPRT, making them reliant on NAMPT for NAD pro­duc­tion. Co-inhibition of PAK4 and NAMPT is believed to lead to synergistic anti-tumor effects through sup­pres­sion of ß-catenin by blocking PAK4, leading to both immune cell activation and in­hib­ition of tumor growth, blockade of DNA repair, cell cycle arrest, and energy depletion through NAMPT in­hib­ition, and ultimately apop­tosis. KPT-9274 may there­fore have both immune-activating and direct antitumor effects. Tumors deficient in NAPRT may be par­tic­u­larly sus­cep­tible to KPT-9274's actions. In contrast, nor­mal cells are less sensitive to in­hib­ition by KPT-9274 due in part to their rel­a­tive genomic stability and lower metabolic demands. KPT-9274 is cur­rent being eval­u­ated in a Phase 1 clin­i­cal study in ad­vanced solid tumors and non-Hodgkin’s lym­phoma.

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, cur­rent has several inves­ti­ga­tional pro­grams in clin­i­cal or pre­clin­i­cal de­vel­op­ment. For more in­for­ma­tion, please visit www.karyopharm.com.

About Antengene Corpo­ra­tion

Antengene Corpo­ra­tion is a clin­i­cal-stage bio­pharma­ceu­tical com­pany focused on devel­op­ing and com­mer­cializing inno­va­tive thera­peutics to meet unmet med­i­cal needs in Asia. Antengene aims to provide the most ad­vanced and first-in-class anti-cancer drug treat­ments for patients in China and rest of Asia. On April 13, 2017, Celgene Corpo­ra­tion, a global leading inno­va­tive bio­pharma­ceu­tical com­pany became a long-term stra­te­gic part­ner and obtained an equity position in Antengene. Antengene cur­rent has several inves­ti­ga­tional pro­grams at Phase 2/3 stage. Antengene’s lead pipe­line asset ATG-008, a dual mTORC1/2 in­hib­i­tor, is cur­rent in multi-regional clin­i­cal trials (MRCT) for the treat­ment of hepato­cellular carcinoma (HCC) patients in Asian countries/regions in­clud­ing mainland China, Taiwan, and South Korea. For more in­for­ma­tion, please visit www.antengene.com.

Karyopharm 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 poten­tial to re­ceive mile­stone and royalty pay­ments under the license agree­ment with Antengene, the success of Karyo­pharm’s arrangement with Antengene and the parties’ ability to work effectively to­geth­er, the timing of sub­missions to regu­la­tory author­i­ties and the poten­tial avail­a­bil­ity of ac­cel­er­ated ap­prov­al path­ways, and thera­peutic poten­tial of and poten­tial clin­i­cal de­vel­op­ment plans for Karyo­pharm's drug can­di­dates. 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 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 that any of Karyo­pharm's drug can­di­dates, in­clud­ing selinexor (KPT-330), eltanexor (KPT-8602), Karyo­pharm’s sec­ond-generation oral SINE com­pound, or KPT-9274, Karyo­pharm's first-in-class oral dual in­hib­i­tor of PAK4 and NAMPT, 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: the ability of Karyo­pharm or Antengene to fully per­form their re­spec­tive obli­ga­tions under the license agree­ment, 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 FDA 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 cur­rent 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

Source: Karyo­pharm.