Innovent Biologics, Inc., a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of oncology, metabolic, autoimmune and other major diseases, today announced the results of a Phase 3, open label, randomized study in China. The ORIENT-32 trial evaluating TYVYT? (sintilimab injection) in combination with BYVASDA? (bevacizumab biosimilar injection, or IBI305) as a first-line treatment in advanced hepatocellular carcinoma (HCC) met the predefined primary endpoints of progression-free survival (PFS) and overall survival (OS) in an interim analysis. This is the first Phase 3 clinical trial using PD-1 inhibitor-based combination therapy that has met the primary endpoint in the first-line treatment of advanced HCC.

Based on the interim analysis conducted by the Independent Data Monitoring Committee (IDMC), TYVYT? (sintilimab injection) in combination with BYVASDA? (bevacizumab biosimilar injection) demonstrated a statistically significant improvement in PFS and OS compared with sorafenib. The safety profile of TYVYT? (sintilimab injection) and BYVASDA? (bevacizumab biosimilar injection) in this trial was consistent with previously reported studies, and no new safety signals were identified. These data will be presented at an upcoming medical conference. Based on the IDMC recommendation, Innovent will review these results with the Drug Evaluation Center (CDE) of the National Medical Products Administration (NMPA) in China.

The principal investigator of the ORIENT-32 study, Professor Fan Jia from Zhongshan Hospital of Fudan University, stated: "In China, HCC is the fourth most common malignancy with the second highest mortality rate. More than half of new and fatal cases of HCC in the world occur in China every year. At present, sorafenib, lenvatinib and chemotherapy are the main treatments for HCC in the first-line treatment setting in China, with very limited efficacy. About 85% of HCC patients in China have the history of HBV infection, which is a quite different feature from HCC in the European and American countries. Therefore, continued clinical research in treating HCC is of great importance in China. The ORIENT-32 study confirmed that TYVYT? (sintilimab injection), in combination with BYVASDA? (bevacizumab biosimilar injection), can prolong PFS and OS in the first-line treatment of HCC. Despite the COVID-19 pandemic, all study investigators worked to overcome many challenges to continue this trial with the goal of bringing new hope to HCC patients."

Dr. Hui Zhou, Vice President and Head of Oncology Strategy and Medical Sciences of Innovent stated: "TYVYT? is the only anti-PD-1 monoclonal antibody included in the New Catalogue of the National Reimbursement Drug List in China. It was officially approved by the NMPA on December 24, 2018 for the treatment of relapsed or refractory classic Hodgkin's lymphoma after two lines or later of systemic chemotherapy. BYVASDA? (bevacizumab biosimilar injection) was officially approved by the NMPA for patients with advanced non-small cell lung cancer and metastatic colorectal cancer in China. The results of the ORIENT-32 study demonstrate the potential of TYVYT? in combination with BYVASDA? to treat patients with advanced HCC in the first-line setting. We hope this clinical trial can potentially provide a more effective treatment option for clinicians and HCC patients. We would like to express our sincere gratitude to all the patients and investigators who participated in the ORIENT-32 study. Outstanding contributions were made through the joint efforts of investigators and the study team, despite the challenges and impact from the COVID-19 pandemic.

About ORIENT-32 Trial

ORIENT-32 is a Phase 3 randomized, open-label, multi-center study to evaluate the efficacy and safety of TYVYT? (sintilimab injection) in combination with BYVASDA? (bevacizumab biosimilar injection) compared to sorafenib in the first-line treatment of patients with advanced hepatocellular carcinoma (ClinicalTrials.gov, NCT 03794440). The primary endpoints are progression-free survival (PFS) and overall survival (OS) assessed by Independent Radiographic Review Committee (IRRC) based on RECIST v1.1.

Enrolled patients were randomly assigned 2:1 to receive TYVYT? (sintilimab injection) combination with BYVASDA? (bevacizumab biosimilar injection) or sorafenib, until disease progression, unacceptable toxicity, withdrawal of consent, death, or other reasons stated in the protocol, whichever occurs first.

About Hepatocellular Carcinoma (HCC)

Primary liver cancer (PLC) is a common malignancy of the digestive system worldwide, among which about half new cases and deaths occur in China. The main pathological types of liver cancer are hepatocellular carcinoma (HCC), accounting for 85 to 90 percent, and a small number of cases of intrahepatic cholangiocarcinoma (ICC) and HCC-ICC mixed liver cancer. In China, HCC is primarily caused by hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection.

About TYVYT? (Sintilimab Injection)

TYVYT? (sintilimab injection) is an innovative drug with global quality standards jointly developed by Innovent and Lilly in China. TYVYT? has been granted marketing approval by the NMPA for the treatment of relapsed or refractory classic Hodgkin's lymphoma after two lines or later of systemic chemotherapy and was included in the 2019 Guidelines of Chinese Society of Clinical Oncology for Lymphoid Malignancies. TYVYT? is the only PD-1 inhibitor that has been included in the new Catalogue of the NRDL in November 2019.

In April 2020, the NMPA accepted the supplemental new drug application for TYVYT? in combination with ALIMTA? (pemetrexed) and platinum chemotherapy as first-line therapy in nonsquamous non-small cell lung cancer (NSCLC). In May 2020, TYVYT? combined with GEMZAR? (gemcitabine for injection) and platinum chemotherapy met the predefined primary endpoint in the Phase 3 ORIENT-12 study as first-line therapy in patients with locally advanced or metastatic squamous NSCLC. TYVYT? monotherapy met the primary endpoint in the ORIENT-2 study as second-line therapy in patients with advanced or metastatic esophageal squamous cell carcinoma as well. In August 2020, the NMPA accepted the sNDA for TYVYT? in combination with GEMZAR? (gemcitabine for injection) and platinum chemotherapy as first-line therapy in patients with locally advanced or metastatic squamous NSCLC.

TYVYT is a type of immunoglobulin G4 monoclonal antibody, which binds to PD-1 molecules on the surface of T-cells, blocks the PD-1/ PD-Ligand 1 (PD-L1) pathway and reactivates T-cells to kill cancer cells. Innovent is currently conducting more than 20 clinical studies with TYVYT? to evaluate its safety and efficacy in a wide variety of cancer indications globally, including more than 10 registrational or pivotal clinical trials.

About BYVASDA? (Bevacizumab Biosimilar Injection)

BYVASDA? (IBI305) is a bevacizumab biosimilar and a recombinant humanized anti-VEGF monoclonal antibody drug. Vascular endothelial growth factor (VEGF) is an important factor in angiogenesis that is highly expressed by the endothelial cells in most human tumors. An anti-VEGF antibody binds VEGF selectively with high affinity and blocks its binding to VEGF receptors on the surface of vascular endothelial cells, thereby inhibiting signaling pathways such as PI3K-Akt/PKB and Ras-Raf-MEK-ERK. BYVASDA? produces anti-tumor effects by inhibiting the growth, proliferation and migration of vascular endothelial cells, blocking angiogenesis, reducing vascular permeability, blocking blood supply to tumor tissues, inhibiting the proliferation and metastasis of tumor cells and inducing apoptosis in tumor cells. Since the launch of bevacizumab, it has been approved for the treatment of patients with multiple malignant tumors globally, including non-small cell lung cancer, metastatic colorectal cancer, glioblastoma, renal cell carcinoma, cervical cancer, and epithelial ovarian, fallopian tube, or primary peritoneal cancer. The efficacy and safety of bevacizumab have been well recognized worldwide.

About Innovent

Inspired by the spirit of "Start with Integrity, Succeed through Action," Innovent's mission is to develop and commercialize high quality biopharmaceutical products that are affordable to ordinary people. Established in 2011, Innovent is committed to developing, manufacturing and commercializing high quality innovative medicines for the treatment of cancer, metabolic, autoimmune and other major diseases. On October 31, 2018, Innovent was listed on the Main Board of the Stock Exchange of Hong Kong, S.A.R., China Limited with the stock code: 01801.HK.

Since its inception, Innovent has developed a fully integrated multi-functional platform which includes R&D, CMC (Chemistry, Manufacturing, and Controls), clinical development and commercialization capabilities. Leveraging the platform, the company has built a robust pipeline of 23 valuable assets in the fields of cancer, metabolic, autoimmune diseases and other major therapeutic areas, with three products, TYVYT? (sintilimab injection), BYVASDA? (bevacizumab biosimilar injection) and SULINNO? (adalimumab biosimilar injection), officially approved for marketing in China, one asset under NDA review with priority review status, four assets in Phase 3 or pivotal clinical trials, and additional 15 molecules in or close to entering clinical trials. TYVYT? (sintilimab injection) is the only PD-1 inhibitor included in the NRDL, since 2019.

Innovent has built an international team with expertise in cutting-edge biological drug development and commercialization. The company has also entered into strategic collaborations with Eli Lilly and Company, Adimab, Incyte, Alector, MD Anderson Cancer Center, Hanmi and other international partners.