Innovent Announces the China NMPA Approval of TYVYT® (sintilimab injection) in Combination with BYVASDA® (bevacizumab biosimilar injection) as First-Line Therapy for People with Hepatocellular Carcino

Innovent Biologics, Inc., a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of cancer, metabolic, autoimmune and other major diseases today announced that the National Medical Products Administration (NMPA) of China has approved the supplemental New Drug Application (sNDA) for TYVYT® (sintilimab injection) in combination with BYVASDA® (bevacizumab biosimilar injection) as a first-line treatment for people with advanced or unresectable hepatocellular carcinoma (HCC). This is the first regulatory approval of a PD-1 inhibitor-based combination therapy for the first-line treatment for HCC.

This is also the fourth NMPA-approved indication of TYVYT® (sintilimab injection) as well as the fourth NMPA-approved indication of BYVASDA® (bevacizumab biosimilar injection). TYVYT® (sintilimab injection) was approved in China for the treatment of relapsed or refractory classical Hodgkin's lymphoma in December 2018, the first-line treatment of nonsquamous non-small cell lung cancer (NSCLC) in February 2021, and the first-line treatment of squamous NSCLC in June 2021. BYVASDA® (bevacizumab biosimilar injection) was previously approved for advanced non-small cell lung cancer, metastatic colorectal cancer, and adult recurrent glioblastoma.

This new approval was based on the results of a randomized, open-label Phase 3 clinical trial (ORIENT-32) of TYVYT® (sintilimab injection) in combination with BYVASDA® (bevacizumab biosimilar injection) as first-line therapy for unresectable 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 overall survival (OS) and progression-free survival (PFS) as assessed by Independent Radiographic Review Committee (IRRC) compared to sorafenib, meeting the pre-defined efficacy criteria. Safety analyses revealed no new safety signals. The ORIENT-32 results were published in The Lancet Oncology on June 15, 2021.

Professor Fan Jia from Zhongshan Hospital of Fudan University stated," In China, liver cancer is the second most common cause of cancer-related death and ranks fourth in terms of incidence with a five-year survival rate of only 10 percent. Response of hepatocellular carcinoma to chemotherapy and targeted therapy is undesirable, while immunotherapy has emerged as breakthrough treatment for hepatocellular carcinoma. The ORIENT-32 has demonstrated that sintilimab plus bevacizumab can extend the overall survival and progression-free survival in this patient population and bring significant clinical benefits. The approval will provide a new option for the first-line treatment of these patients with few systemic options, and also contribute to the 'Healthy China 2030'."

Dr. Yongjun Liu, President of Innovent, stated: "Liver cancer is the third leading cause of cancer death globally, and China accounts for over 50 percent of all new cases and deaths worldwide. The disease is a serious threat to the life and health of Chinese people and a heavy burden on society and families, with hepatocellular carcinoma accounting for 85 to 90 percent of all liver cancer. We are very pleased that TYVYT® (sintilimab injection) plus BYVASDA® (bevacizumab biosimilar injection) – two drugs recognized by the China national innovation drug development project – is the first approved PD-1 inhibitor-based combination therapy for the first-line treatment of people with hepatocellular carcinoma. Innovent is proud to continue delivering on our mission of developing high-quality biopharmaceuticals that are affordable to ordinary people, while also contributing to the 'Healthy China 2030' Plan for cancer prevention and treatment."

About the ORIENT-32 Trial

ORIENT-32 is a Phase 3 randomized, open-label, multi-center study conducted in China to evaluate the efficacy and safety of TYVYT® (sintilimab injection) in combination with BYVASDA® (bevacizumab biosimilar injection) compared to sorafenib for the first-line treatment of patients with advanced hepatocellular carcinoma (ClinicalTrials.gov, NCT03794440). The primary endpoints of the trial were overall survival (OS) and progression-free survival (PFS) as assessed by Independent Radiographic Review Committee (IRRC) based on RECIST v1.1.

A total of 571 patients were enrolled and randomly assigned 2:1 to receive either TYVYT® (sintilimab injection) plus BYVASDA® (bevacizumab biosimilar injection) or sorafenib until disease progression or unacceptable toxicity. The combination therapy showed significant improvements in OS and PFS compared to sorafenib, and safety was consistent with previously reported safety profiles of each drug. The full results of ORIENT-32 were published in The Lancet Oncology on June 15, 2021.

About Hepatocellular Carcinoma
Primary liver cancer（PLC）is a common malignancy of the digestive system worldwide, among which about half of all new cases and deaths occur in China. The main pathological types of liver cancer are hepatocellular carcinoma (HCC), which accounts 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 Sintilimab

Sintilimab, marketed as TYVYT® (sintilimab injection) in China, is an innovative PD-1 inhibitor with global quality standards jointly developed by Innovent and Eli Lilly and Company. Sintilimab is an 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 of sintilimab to evaluate its safety and efficacy in a wide variety of cancer indications, including more than 10 registrational or pivotal clinical trials.

In China, sintilimab has been approved for four indications, including:

• The treatment of relapsed or refractory classic Hodgkin's lymphoma after two lines or later of systemic chemotherapy

• In combination with pemetrexed and platinum chemotherapy, for the first-line treatment of nonsquamous non-small cell lung cancer

• In combination with gemcitabine and platinum chemotherapy, for the first-line treatment of squamous non-small cell lung cancer

• In combination with BYVASDA® (bevacizumab biosimilar injection) for the first-line treatment of hepatocellular carcinoma

Additionally, Innovent currently has a regulatory submission under review in China for sintilimab for the second-line treatment of squamous non-small cell lung cancer.

Innovent also has two clinical studies of sintilimab that have met their primary endpoints:

• In combination with cisplatin plus paclitaxel or cisplatin plus 5-fluorouracil for the first-line treatment of esophageal squamous cell carcinoma

• The second-line treatment of esophageal squamous cell carcinoma

In May 2021, the U.S. FDA accepted for review the Biologics License Application (BLA) for sintilimab in combination with pemetrexed and platinum chemotherapy for the first-line treatment of nonsquamous non-small cell lung cancer.

Sintilimab was included in China's National Reimbursement Drug List (NRDL) in 2019 as the first PD-1 inhibitor and the only PD-1 included in the list in that year.

About BYVASDA® (bevacizumab biosimilar injection)

BYVASDA®, also known as 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-A selectively with high affinity and blocks its binding to VEGF-2 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 its launch, bevacizumab 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 in these tumor types have been well recognized worldwide.

In China, BYVASDA® (bevacizumab biosimilar injection) is approved for indications including advanced non-small cell lung cancer, metastatic colorectal cancer, adult recurrent glioblastoma, and advanced or unresectable hepatocellular carcinoma.

About Innovent

Inspired by the spirit of "Start with Integrity, Succeed through Action," Innovent's mission is to develop, manufacture 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, autoimmune, metabolic 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 24 valuable assets in the fields of cancer, metabolic, autoimmune disease and other major therapeutic areas, with 5 products – TYVYT® (sintilimab injection), BYVASDA® (bevacizumab biosimilar injection), SULINNO® (adalimumab biosimilar injection), HALPRYZA® (rituximab biosimilar injection) and Pemazyre® (pemigatinib oral inhibitor) – officially approved for marketing, sintilimab's Biologics License Application (BLA) acceptance in the U.S., 6 assets in Phase 3 or pivotal clinical trials, and an additional 14 molecules in clinical studies.

Innovent has built an international team with advanced talent in high-end biological drug development and commercialization, including many global experts. The company has also entered into strategic collaborations with Eli Lilly and Company, Adimab, Incyte, MD Anderson Cancer Center, Hanmi and other international partners. Innovent strives to work with many collaborators to help advance China's biopharmaceutical industry, improve drug availability and enhance the quality of the patients' lives.