Press Release

Jan 25, 2020

News Express! The Clinical Trial of ATG-010 for Peripheral T-cell Lymphoma and NK/T-cell Lymphoma Has Been Approved

Antengene announced today that NMPA has approved the clinical trial application of ATG-010 for relapsed or refractory peripheral T and NK/T-cell lymphoma on January 13, 2020. This is a single-arm, open-label, multi-center phase Ib clinical trial to evaluate the safety and preliminary efficacy of ATG-010 in combination with chemotherapy followed by sequential ATG-010 single-agent maintenance therapy in patients with relapsed or refractory peripheral T and NK/T-cell lymphoma.

Peripheral T-cell lymphoma and NK/T-cell lymphoma are lymphoid malignancies derived from T-cell and NK-cell lines, with significant regional differences in distribution and incidence. Peripheral T-cell lymphoma accounts for 10-15% of all non-Hodgkin's lymphomas in Europe and the United States, while NK/T-cell lymphoma is more common in East Asia, accounting for approximately 25% of T-cell lymphoma, and about 25~30% in China. As a group of highly heterogeneous and highly invasive diseases, there is no standard therapeutic regimen for peripheral T-cell lymphoma and NK/T-cell lymphoma, and with poor prognosis.

As an oral selective inhibitor of nuclear export, ATG-010 induces the apoptosis of both solid and hematological tumor cells by causing the nuclear storage and activation of tumor suppressor proteins and other growth-regulating proteins, and by down-regulating the intracytoplasmic levels of various oncogenic proteins. The results of preclinical studies show that ATG-010 has extensive anti-tumor activities, and has synergistic effects when combined with a variety of chemotherapeutic and targeted drugs. On July 3 2019, FDA approved the combination of ATG-010 and dexamethasone for the treatment of patients with relapsed and refractory multiple myeloma. Besides, in phase I studies and small-sample phase II studies conducted in the United States, Denmark, Canada, and Singapore, ATG-010 has demonstrated favorable preliminary efficacy against peripheral T-cell lymphoma and NK/T-cell lymphoma, and further exploration is required.

Regarding the successful clinical trial approval of ATG-010, Dr. Jay Mei, the founder and chairman of Antengene said, “There is still no standard therapeutic regimen for relapsed or refractory peripheral T and NK/T-cell lymphoma, and the prognosis is poor. In previous clinical studies, ATG-010 has demonstrated extensive anti-tumor effects and preliminary efficacy against such lymphomas, which is expected to provide a new therapy with novel mechanisms for these patients. We hope that with international cooperation and the efforts of all the colleagues, patients from China and the Asia-Pacific region will be able to share the research and development achievements of global innovative drugs as soon as possible.”

About ATG-010

ATG-010 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. In addition to receiving accelerated FDA approval of ATG-010 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 ATG-010. ATG-010 is also being studied in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). 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 Velcade (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), among others.

About Antengene

Antengene is a China-and-U.S. based biopharmaceutical company focusing ondrug discovery, clinical development and the commercialization of innovative therapeutics to meet unmet medical needs.

In April 2017, Celgene(now part of BMS), 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 joins Antengene Board of Directors and former Celgene China GM John Chin joins the company as Chief Business Officer.

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. Antengene's pipeline includes six clinical stage products:

ATG-010(selinexor), in combination with the corticosteroid dexamethasone, has been approved by the U.S. Food and Drug Administration, and is currently in registration study in China for the treatment of patients with relapsed or refractory multiple myeloma, and for patients with diffuse large B-cell lymphoma. The drug is also in late clinical development for various other hematologic malignancies and solid tumors. ATG-008, a second-generation dual mTORC1/2 inhibitor, is in a multi-regional clinicaltrial for treatment of hepatocellular carcinoma as well as clinical studies inmultiple other solid tumors. Two other Phase 1 and Phase 2 clinical stagedrugs, ATG-016 and ATG-019, are being studied in multiple cancer types, including colorectal, prostate, NHL, MDS and other solid and hematological malignancies. ATG-527 is being explored for multipleanti-viral indications, including Epstein-Barr virus (EBV) 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 multiple solid tumors, NHL and AML. The drug discovery team of Antengene focuses on the development of first-in-class novel molecules with six projects in pre-clinical development, including small molecule, monoclonal and bi-specific antibodies.