On May 5, 2020 Antengene Corporation (Antengene) reported 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 (Press release, Antengene, MAY 5, 2020, View Source [SID1234557059]). 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.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
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 (Free ASCO Whitepaper) 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).
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 currently 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 currently being evaluated in a Phase 1 clinical study in advanced solid tumors and non-Hodgkin’s lymphoma.