May 05, 2020
SHANGHAI, China – May 5, 2020 – 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 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.
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).
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 currently ongoing evaluating eltanexor in myelodysplastic syndrome, colorectal cancer and castrate-resistant prostate cancer.
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.
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 currently being evaluated in a Phase 1 clinical study in advanced solid tumors and non-Hodgkin’s lymphoma.
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 currently 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 currently 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 currently 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.
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 currently 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.