Press Release

Mar 09, 2020

Clinical trial of Antengene’s ATG-008 in combination with Junshi Biosciences' Toripalimab for treatment of advanced solid tumors and hepatocellular carcinoma officially initiated

- ATG-008 is a new generation mTORC1 / 2 dual-targeted inhibitor

- This trial is an open-label, incremental and expanded study to evaluate the safety, tolerability and pharmacokinetics

- ATG-008 is highly valuable for developing the combination therapy in patients with advanced solid tumors and hepatocellular carcinoma

Shanghai, China -- March 9, 2020 -- Antengene and Junshi Biosciences (1877.HK) jointly announced the start of a new clinical trial of ATG-008 in combination with Toripalimab, an anti-PD-1 monoclonal antibody, for the treatment of advanced solid tumors and hepatocellular carcinoma (HCC), after approval by Ethics Committee (EC) from West China Hospital of Sichuan University. The trial is an open-label, dose-escalation and expansion study designed to assess the safety, tolerance, and pharmacokinetics of this combination therapy for patients with advanced solid tumors and hepatocellular carcinoma, and to provide the basis for the design and administration of the next phase of clinical trials.

According to data released by the National Cancer Center in 2019, in recent years, the morbidity and mortality of cancer is increasing in China, and deaths caused by malignant tumors account for 23.91% of all-cause deaths, furthermore, the leading 8 deaths from tumors were all attributed to solid tumors. Hepatocellular carcinoma accounts for 85%-90% of liver cancer, being the second largest cause of tumor death in China. Due to its high invasion and limited treatment options, the median survival time of patients with advanced hepatocellular carcinoma is only about 1 year, and the 5-year survival rate is 10.1%. Therefore, safer and more effective novel treatments are urgently needed for patients with advanced solid tumors and hepatocellular carcinoma in China.

ATG-008 is the first innovative drug of Antengene approved to enter clinical trial in the Asian-Pacific region, and the first drug in development of the same kind to enter clinical trial of advanced liver cancer. Six clinical studies of ATG-008 have been completed in the United States and Europe. At present, Antengene is conducting international multi-center clinical trial of ATG-008 for the treatment of advanced liver cancer in mainland China, Taiwan, and South Korea, and has obtained the support from “National Science & Technology Pillar Program during the thirteenth Five-year Plan Period ”. Available data indicate that ATG-008 has demonstrated encouraging anti-tumor signals in multiple tumor types including liver cancer.

Toripalimab Injection (trade name: Tuoyi) is the first domestic anti-PD-1 monoclonal antibody approved in China, which was independently developed by Junshi Biosciences, Antengene’s strategic partner. It was approved on December 17, 2018 for the treatment of unresectable locally advanced or metastatic melanoma after failure of standard systemic treatment. In addition, more than 30 clinical trials involving 14 types of tumor have been performed by Junshi Biosciences in several countries including China and the United States, in which Toripalimab demonstrated favorable antitumor effects.

In April 2019, Antengene and Junshi Biosciences reached a strategic cooperation to jointly carry out the clinical study of ATG-008 in combination with Toripalimab in the field of oncology. The immune targeted therapy for advanced solid tumors and hepatocellular carcinoma is worth expecting.

Dr. Jay Mei, founder, chairman and CEO of Antengene said: “It has always been Antengene’s responsibility and mission to bring innovative therapies to patients in China and Asia-Pacific. Faced with the unmet clinical needs of a vast number of liver cancer patients, Antengene is continuously advancing international multi-center clinical trial of ATG-008 both as monotherapy and combined therapy. In this cooperation with Junshi Biosciences, we are full of confidence, and hope to discover more possibilities of tumor immunotherapy drugs combined with targeted drugs in the field of oncology by exploring the potential of ATG-008 in combination with Toripalimab.”

About ATG-008

ATG-008 is a new generation of dual target inhibitors of mTOR kinase, which is currently in Phase 2 clinical trial and has not been marketed in any country or region. mTOR is in the key position of tumor signaling pathway, and mTOR inhibitors are widely used in tumor targeted therapy.2017 Albert Lasker Basic Medical Research Award was granted to Michael N. Hall, who discovered the nutrient-activated TOR proteins and their central role in the metabolic control of cell growth.

About Tuoyi (toripalimab)

In December 2018, Junshi Biosciences' anti-PD-1 therapy Tuoyi (toripalimab) was conditionally granted marketing approval for second line treatment of unresectable local progression or metastatic melanoma by the National Medical Products Administration of China (NMPA). In the pivotal clinical trial, patients were observed with the ORR of 17.3% and the DCR of 57.5%, and the one-year overall survival rate is 69.3%. The company has conducted or has been ready to conduct 11 Phase II/Phase III pivotal clinical trials of the monotherapy or in combination with standard therapy for advanced melanoma, advanced esophageal cancer, adjuvant treatment of advanced hepatocellular carcinoma, non-small cell lung cancer, advanced nasopharyngeal cancer and urothelial carcinoma. Phase Ia clinical trial in the United States has been completed and Phase Ib is on-going. The Company is expanding its cooperation with more third parties to further explore the various efficacy and safety of toripalimab in combination therapy.

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. For more information, please visit www.antengene.com.

About Junshi Biosciences

Established in 2012, Junshi Biosciences is committed to developing first-in-class and best-in-class drugs through original innovation and becoming a pioneer in the area of translational medicine to provide patients with treatment options that work better and cost less. On December 24, 2018, Junshi Biosciences was listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code: 1877.HK.

The Company has established a diversified R&D pipeline comprising 20 drug candidates with therapeutic areas covering anti-tumor, metabolic diseases, autoimmune diseases, and neurologic diseases. Product types include monoclonal antibodies, fusion proteins, ADCs, and small molecule drugs. With a 33,000L fermentation capacity of biopharmaceutical production established in Shanghai and Wujiang by the end of 2019, we will satisfy the needs for commercialization and provide our partners and patients with a global supply chain network. For more information, please visit www.junshipharma.com