SHANGHAI, China and PHILADELPHIA, U.S. — April 24, 2020 — Antengene announced today that it has dosed the first patient in a registration trial in China with ATG-010 (selinexor)，an oral Selective Inhibitor of Nuclear Export (SINE) compound cooperatively developed for the treatment of relapsed or refractory diffuse large B-cell lymphoma (RR DLBCL). This trial aims to evaluate the efficacy and safety of ATG-010 in the treatment of patients with relapsed or refractory diffuse large B-cell lymphoma (RR DLBCL) who have received at least 2 but no more than 5 previous systemic regimens.
As one of the most common lymphomas in adults, DLBCL is an aggressive tumor with high heterogeneity in terms of clinical manifestation and prognosis. Part of patients can be cured, but 40% remain refractory or relapsed. The standard treatment of relapsing or refractory DLBCL is high dose chemotherapy and stem cell transplantation. Patients that have failed second-line treatment or are not candidates for transplantation suffer terrible prognosis, therefore an effective treatment for them is urgently needed.
ATG-010 is oral Selective Inhibitor of Nuclear Export (SINE) compound that could specifically blocks nuclear export protein 1 (XPO1). In many tumor types, inhibition of XPO1 may restore the activity of multiple tumor suppressor proteins and reduces the synthesis of oncogenic proteins, thereby inducing tumor cells apoptosis. ATG-010 has shown encouraging clinical efficacy and is well-tolerated according to the results of SADAL study of ATG-010 for the treatment of relapsed or refractory DLBCL. Based on data from SADAL study, the FDA has accepted the supplemental New Drug Application (sNDA) seeking accelerated approval of ATG-010 for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma, who have received at least two prior therapies, and has assigned a user fee goal date of June 23, 2020 under the Prescription Drug User-Fee Act (PDUFA).
“A well-tolerated oral drug with new mechanism of action has become an urgent demand for patients with DLBCL who are not curable with currently available drugs, especially the elderly and those with multiple comorbidities.” Dr. Jay Mei, Founder and CEO of Antengene said, “ATG-010 is a first-in-class oral drug launched after continuous exploration on tumor pathogenesis. We hope this trial could provide new evidence and ideas for the treatment of the targeted patients while prolonging their survival and improving their prognosis.”
ATG-010 (selinexor) is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound. ATG-010 functions by selectively binding to and inhibiting the nuclear export protein exportin 1 (XPO1, also called CRM1). ATG-010 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. The US Food and Drug Administration (FDA) has granted in July 2019 accelerated approval to the oral therapy selinexor (Xpovio®) in combination with low-dose dexamethasone for the treatment of adults with relapsed/refractory multiple myeloma (RRMM) who are out of treatment options. Furthermore, a European Marketing Authorization Application has been submitted to the European Medicines Agency. ATG-010 has been granted both Fast Track and Orphan Drug designations by FDA to conduct clinical studies on patients with relapsed or refractory diffuse large B-cell lymphoma who have previously received at least 2-lines treatments. In addition, on February 19, 2020, FDA has included in its accelerated approval a new indication marketing application for the use of ATG-010 in the treatment of patients with relapsed or refractory diffuse large B-cell lymphoma. ATG-010 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 bortezomib and low-dose dexamethasone (BOSTON), as a potential backbone therapy in combination with approved therapies (STOMP), in liposarcoma (SEAL), in recurrent gliomas (KING) and in endometrial cancer (SIENDO). In China, ATG-010 is conducting a registered clinical trial in relapsed refractory multiple myeloma (MARCH), 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).
Antengene is a China-and-U.S. based biopharmaceutical company focusing on drug discovery, clinical development and the commercialization of innovative therapeutics to meet unmet medical needs. Antengene aims to provide the most advanced and first-in-class anti-cancer drugs and other treatments for patients in China, 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 in Antengene. In January 2020, former Celgene chairman and CEO Mark J. Alles joined Antengene Board of Directors and former Celgene China GM John Chin joined the company as Chief Business Officer.
At present, Antengene’s pipeline includes six clinical stage products:
ATG-010 (selinexor) is the first oral selective inhibitor of nuclear export compound with novel mechanisms in the world. On July 3, 2019, the U.S. FDA approved ATG-010 in combination with low-dose dexamethasone for the treatment of adult patients with relapsed refractory multiple myeloma. Currently, the registered 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 and the stage of registered clinical trials for various other hematologic malignancies and solid tumors. In addition, preclinical studies have shown that inhibitors of nuclear protein export can effectively treat a wide range of tumors carrying KRAS mutation, and related clinical studies have been conducted recently; 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, including in combination with anti-PD-1 antibody; 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), gastric carcinoma (GC), triple-negative breast cancer (TNBC) 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.
*SADAL is an open label, Phase 2b study initiated by Antengene’s partner Karyopharm Therapeutics Inc. (Nasdaq: KPTI) to evaluate the clinical efficacy of selinexor（KPT-330） in patients with relapsed refractory DLBCL who have received at least two prior multi-agent therapies.