Press Release

Mar 12, 2020

Phase 2 clinical trial of ATG-010 as targeted therapy for advanced non-small-cell lung cancer initiated in China

Shanghai, China and Philadelphia, U.S. -- March 12, 2020 -- Antengene announced the launch of a clinical trial of ATG-010 in patients with KRAS-mutant advanced Chinese non-small-cell lung cancer (NSCLC). This study is an open-label, multi-center, umbrella phase 2 clinical trial, conducted by Professor Yilong Wu, the principal investigator, from Guangdong Provincial People's Hospital.This trail aims to evaluate the efficacy of ATG-010 for the treatment of KRAS-mutant advanced NSCLC.

NSCLC is the most common type of lung cancer in the clinic, accounting for about 85% of the total number of lung cancers. The current treatment options for NSCLC include surgery, chemoradiotherapy, immunotherapy and targeted therapy. However, surgery and chemoradiotherapy have little effect on advanced NSCLC, immunotherapy cannot cure all patients with NSCLC and targeted therapy still needs further exploration. In patients with advanced NSCLC, 15%-25% of them have KRAS (Kirsten rat sarcoma viral oncogene homolog) mutation,and there are currently no effective drugs available for this target. Therefore, NSCLC patients urgently need therapeutic regimens targeting KRAS mutation.

ATG-010 is an oral Selective Inhibitor of Nuclear Export (SINE) compound, which can specifically block the nuclear export protein exportin 1 (XPO1), leading to accumulation and activation of tumor suppressor protein and other growth regulatory proteins in the nucleus, as well as downregulation of multiple oncogenic proteins in the cell, and induce tumor cell apoptosis. STORM study demonstrated that ATG-010 combined with low-dose dexamethasone has significant effect in treating relapsed refractory multiple myeloma, with an ORR of 26.2%. This indication have been given accelerated approval from the US Food and Drug Administration (FDA) in July 3,2019. In addition, on February 19, 2020, the FDA accepted supplemental New Drug Application (sNDA) seeking accelerated approval for selinexor as a treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (RR DLBCL) who have received at least two prior therapies, and announced a PDUFA date of June 23, 2020. The European Marketing Authorization Application (MAA) of selinexor has been submitted to the European Medicines Agency (EMA). Antengene expects to submit its New Drug Application (NDA) in China this year.

According to preclinical trials, ATG-010 has extensive antitumor activities, enabling a broad application potential in the field of solid tumors and hematological tumors. Previous studies confirmed that SINE drugs have antitumor activities against NSCLC cell lines, and nuclear transport is the only functional pathway that can produce synthetic lethal effect with KRAS-driven tumors alone. Based on the preclinical results of ATG-010 in KRAS-mutant NSCLC, clinical trial of ATG-010 for the treatment of patients with KRAS-mutant NSCLC is ongoing.

“The mortality rate of advanced NSCLC is high, and it has a poor prognosis. Existing treatments are difficult to meet the clinical needs of patients. ATG-010 has extensive antitumor activities, and produce favorable synergistic effects when combined with a variety of chemotherapies and targeted drugs.” said Dr. Jay Mei, the founder, chairman and CEO of Antengene, “I hope that through in-depth cooperation, the investigators of the trial and Antengeners will provide an innovative and potent therapeutic regimen for advanced NSCLC patients.”

About ATG-010

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. ATG-010 combined with low-dose dexamethasone in the treatment of relapsed refractory multiple myeloma after lenalidomide, pomalidomide, bortezomib, carfilzomib, and daratumumab no longer work, This therapy has been given accelerated approval by the U.S. FDA in July 2019, 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).

About Antengene

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. In 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 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 will be conducted within the year; 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.