Shanghai, China (Press Release) – Anten­gene Corpo­ra­tion (Antengene) to­day an­nounced a broadened part­ner­ship and territory ex­pan­sion agree­ment with Karyo­pharm Thera­peutics Inc. (NASDAQ: KPTI) (Karyopharm) for de­vel­op­ment and com­mer­cial­iza­tion of four oral novel drugs and drug can­di­dates to sup­port its mission of treating patients beyond borders. This agree­ment broadens Anten­gene's rights in the Asia Pacific region for XPOVIO® (seli­nexor, aka ATG-010), the first-in-class sel­ective in­hib­i­tor of nuclear export (SINE); eltanexor (ATG-016), a sec­ond-generation SINE com­pound; verdinexor (ATG-527), a lead com­pound in de­vel­op­ment for anti-viral and other non-oncology in­di­ca­tions; and KPT-9274 (ATG-019), a dual in­hib­i­tor of PAK4 and NAMPT.

In May 2018, Anten­gene and Karyo­pharm entered into a stra­te­gic col­lab­o­ration for the de­vel­op­ment, manu­fac­tur­ing and com­mer­cial­iza­tion of XPOVIO® and eltanexor for all human on­col­ogy in­di­ca­tions in mainland China and Macau; and 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 mar­kets.

As part of the ex­panded territory, Anten­gene has re­ceived extended rights to de­vel­op, manu­fac­ture and com­mer­cialize XPOVIO® and eltanexor in Australia, New Zealand, South Korea, Taiwan, Hong Kong, and the entire ASEAN mar­kets; KPT-9274 and verdinexor rights have also been extended to Australia and New Zealand.

This ex­panded col­lab­o­ration broadens Anten­gene's port­folio and geographic footprint to addi­tional Asian mar­kets. In July 2019, the U.S. FDA approved XPOVIO® in com­bi­na­tion with low-dose dexa­meth­a­sone for the treat­ment of adult patients with re­lapsed / re­frac­tory multiple myeloma (RRMM). The data from the recently released phase 3 BOSTON trial com­par­ing SVd to Vd in 2nd and later lines in RRMM patients, has been selected as a late-breaking abstract for oral pre­sen­ta­tion at the upcoming virtual ASCO conference later this month.

Antengene is presently ex­panding its com­mer­cial op­er­a­tions to sup­port the launch of XPOVIO® in mainland China and other APAC mar­kets; and conducting clin­i­cal trials with XPOVIO® in RRMM, diffuse large B-cell lym­phoma (DLBCL) and T-cell lym­phomas in China. Anten­gene has also an­nounced the ongoing recruitment of patients with ad­vanced solid tumor and non-Hodgkin's lym­phoma in a clin­i­cal trial with ATG-019 (KPT-9274). In addi­tion, clin­i­cal trials of ATG-016 (eltanexor) and ATG-527 (verdinexor) will be ini­ti­ated in these mar­kets in 2020.

"Upon the achieve­ment of sig­nif­i­cant regu­la­tory and clin­i­cal mile­stones in mainland China and other mar­kets in Asia, Anten­gene is now ex­panding to addi­tional Asia Pacific mar­kets with clin­i­cal de­vel­op­ment and com­mer­cial­iza­tion. We are pleased to have ex­panded our col­lab­o­ration and part­ner­ship with Karyo­pharm in devel­op­ing these novel drugs for patients in Asia Pacific," said Jay Mei, MD, PhD, Chairman and Chief Executive Officer of Anten­gene. "This critical geographic ex­pan­sion is a step in our de­vel­op­ment and com­mer­cial­iza­tion strat­e­gy, and we are build­ing a world-class com­mer­cial team while continuing to add clin­i­cal and com­mer­cial-stage first-in-class novel drugs to address unmet med­i­cal needs and to fur­ther ex­pand our strong pipe­line. This is a fur­ther testament to our mission of treating patients beyond borders."

"We are delighted to have the oppor­tu­ni­ty to ex­pand our very prod­uctive, efficient and results-driven col­lab­o­ration with Anten­gene which began two years ago," said Michael G. Kauffman, MD, PhD, Chief Executive Officer of Karyo­pharm. "The exemplary part­ner­ship be­tween the two com­pa­nies enables Karyo­pharm to fulfill its mission to de­vel­op and de­liver novel drug can­di­dates to patients around the world."

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. Karyo­pharm re­ceived 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 supple­mental New Drug Appli­ca­tion was ac­cepted by the FDA seek­ing ac­cel­er­ated ap­prov­al for selinexor as a new treat­ment for patients with re­lapsed or re­frac­tory diffuse large B-cell lym­phoma (DLBCL), and selinexor has re­ceived Fast Track and Orphan desig­na­tion and Priority Review from the FDA with a scheduled PDUFA date of June 23, 2020 for this patient pop­u­la­tion. 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), for which Karyo­pharm an­nounced pos­i­tive top-line results in March 2020. Additional, ongoing trials for selinexor in­clude as a poten­tial back­bone ther­apy in com­bi­na­tion with approved myeloma ther­a­pies (STOMP), in liposarcoma (SEAL) and 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 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.

In China, Anten­gene is conducting reg­is­tra­tion clin­i­cal trials in re­lapsed re­frac­tory multiple myeloma (MARCH) and in diffuse large B-cell lym­phoma (SEARCH), and has ini­ti­ated the clin­i­cal trial for the treat­ment of periph­eral T-cells lym­phoma and NK / T-cell lym­phoma (TOUCH).

About Eltanexor

Eltanexor (ATG-016) 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 (ATG-527) 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 (ATG-019) 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 Anten­gene

Antengene is a bio­pharma­ceu­tical com­pany with integrated drug discovery, clin­i­cal de­vel­op­ment, manu­fac­tur­ing and com­mer­cial­iza­tion anchored in Asia Pacific region with global layout, aiming to provide the most ad­vanced and first-in-class anti-cancer drugs and other treat­ments for patients in China, the rest of Asia and around the world. In April 2017, Celgene (now officially acquired by Bristol-Myers Squibb, and be­come the world's top ten pharma­ceu­tical com­pany after the merge), a global leading inno­va­tive bio­pharma­ceu­tical com­pany became a long-term stra­te­gic part­ner and obtained an equity position as an in­vestor in Anten­gene. Over the past 3 years, Anten­gene has obtained 7 IND ap­prov­als with 6 first-in-class drugs in more than 10 ongoing cross-regional clin­i­cal trials in Asia Pacific regions, and has built a prod­uct pipe­line of 12 clin­i­cal and pre-clinical stage pro­grams. The vision of Anten­gene, "Treating Patients Beyond Borders", is to meet the unmet med­i­cal needs of patients in Asia Pacific regions and around the world through re­search & de­vel­op­ment and com­mer­cial­iza­tion of first-in-class drugs.

ATG-010 (seli­nexor) is the first oral sel­ective in­hib­i­tor of nuclear export com­pound with novel mech­a­nisms in the world. In July 2019, the U.S. FDA approved selinexor in com­bi­na­tion with low-dose dexa­meth­a­sone for the treat­ment of adult patients with re­lapsed re­frac­tory multiple myeloma. Currently, the reg­is­tra­tional clin­i­cal trials of ATG-010 in re­lapsed re­frac­tory multiple myeloma (RRMM) and diffuse large B-cell lym­phoma (DLBCL) is ongoing in China. The com­pound is also in late clin­i­cal de­vel­op­ment for var­i­ous other hema­to­logic malig­nan­cies and solid tumors. In addi­tion, pre­clin­i­cal studies have shown that in­hib­i­tors of nuclear pro­tein export can effectively treat KRAS mutant tumor, and related clin­i­cal studies is cur­rent being conducted; ATG-008 is a sec­ond-generation dual mTORC1/2 in­hib­i­tor and is in a multi-regional clin­i­cal trial for treat­ment of ad­vanced liver cancer, lung cancer, and several other tumors; ATG-016 is a sec­ond-generation oral sel­ective in­hib­i­tor of nuclear export pro­tein, and is cur­rent being studied in myelo­dys­plastic syn­drome (MDS) as well as in several clin­i­cal trials of solid tumors, in­clud­ing colorectal cancer (CRC) and prostate cancer (PrC) ; ATG-019 is the first-in-class PAK4/NAMPT dual-target in­hib­i­tors, and is cur­rent been studied in a number of clin­i­cal trials in­clud­ing non-Hodgkin's lym­phoma (NHL), colorectal cancer, lung cancer, and mel­anoma. In addi­tion, pre­clin­i­cal studies have dem­onstrated that ATG-019 in com­bi­na­tion with anti-PD-1 anti­bodies can effectively im­prove the anti-tumor ac­­tiv­ity and is effective in patients who acquire resistance to anti-PD-1 ther­apy. Related clin­i­cal trial is about to ini­ti­ate; ATG-527 is an inno­va­tive prod­uct under de­vel­op­ment for antiviral and treat­ment of auto­immune dis­eases, and has been in clin­i­cal trials conducted in Epstein-Barr virus (EBV), res­pira­tory syncytial virus (RSV) in­fec­tion, cytomegalovirus (CMV) in­fec­tion and Systemic lupus erythematosus (SLE) and other related dis­eases; ATG-017 is a potent and sel­ective small mol­e­cule extracellular signal–regulated kinases 1 and 2 (ERK1/2) in­hib­i­tor, in clin­i­cal de­vel­op­ment for the treat­ment of var­i­ous solid tumors, non-Hodgkin's lym­phoma, acute myelocytic leukemia (AML) and multiple myeloma. In addi­tion, the drug discovery team of Anten­gene focuses on the early pre­clin­i­cal de­vel­op­ment of multiple inno­va­tive target drugs in the fields of small mol­e­cule, mono­clonal and bi-specific anti­bodies. For more in­for­ma­tion, please visit www.antengene.com.

About Karyo­pharm

Karyopharm Thera­peutics Inc. (Nasdaq: KPTI) is an inno­va­tion driven 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 cur­rent under review by the European Medicines Agency. A supple­mental New Drug Appli­ca­tion was ac­cepted by the FDA seek­ing ac­cel­er­ated ap­prov­al for selinexor as a new treat­ment for adult patients with re­lapsed or re­frac­tory diffuse large B-cell lym­phoma (DLBCL). 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.

Source: Anten­gene.