Innovent and Eli Lilly and Company Announced Final Clinical Results and Biomarker Analysis of Phase Ib Study of TYVYT® (Sintilimab Injection) Plus Bevacizumab Biosimilar Injection for Advanced Hepatocellular Carcinoma at ASCO GI Annual Meeting 2022

SAN FRANCISCO and SUZHOU, China, Jan. 21, 2022 /PRNewswire/ -- Innovent Biologics, Inc. ("Innovent", HKEX: 01801), 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 jointly announced with Eli Lilly and Company ("Lilly", NYSE: LLY) the final clinical outcome and biomarker analysis of the open label, phase Ib study (NCT04072679) of sintilimab plus bevacizumab biosimilar injection for advanced hepatocellular carcinoma at the 2022 ASCO Gastrointestinal Cancers Symposium (Abstract# 455).

The study, which was conducted in China, evaluated the treatment of sintilimab plus bevacizumab biosimilar injection for patients with local advanced or metastatic HCC with or without previous systemic treatment or systemic treatment failure. The Phase Ib study included dose escalation and dose expansion stages. In the dose escalation stage, patients were randomly assigned to receive sintilimab 200mg plus bevacizumab biosimilar 7.5 mg/kg (low-dose group) or 15 mg/kg (high-dose group). In the dose expansion stage safety and efficacy were assessed for each dose group. A total of fifty patients were enrolled in final analysis, with 29 patients administered bevacizumab biosimilar 7.5 mg/kg and 21 patients 15 mg/kg. The safety profile was consistent with that observed in previously reported studies of sintilimab and bevacizumab biosimilar, without new or unexpected safety signals. The most common treatment-related adverse events (TRAE) were as hypertension (32%), proteinuria (26%) and fever (26%). The incidence of grade ≥ 3 adverse events in the high-dose group was 28.6%, while 13.8% in  the low-dose group.

The overall response rate (ORR) was 34% (17/50) and ORRs for the low-dose and high-dose groups were 31% and 38%, respectively. The disease control rate (DCR) was 78% (39/50). Median progression-free survival (PFS) was 10.5 months (95%CI, 8.4-12.7) and  median overall survival (OS) was 20.2 months (95%CI, 16.1 -24.3). Further biomarker analysis showed that patients with a high level of CD137 ≥ 31.8 pg/mL have longer PFS (mPFS:14.2 vs. 4.1months, p=0.001) and OS (mOS: NR vs.15.6months, p=0.023). In addition, the Tumor immune Microenvironment（TiME）analysis demonstrated that the high density of M1 macrophages (CD68+, CD163-) in stroma was related to higher efficacy (p=0.033), longer PFS (p=0. 024) and OS (p =0.046).

Professor Zhou Aiping from the Cancer Hospital of the Chinese Academy of Medical Sciences stated: "This study not only showed the safety and efficacy data for sintilimab in combination with different doses of bevacizumab, but also identified biomarkers that could predict the efficacy of the combined treatment regimen for hepatocellular carcinoma, which lays the groundwork for more individualized treatment."

Dr. Zhou Hui, Senior Vice President of Innovent Biologics, stated: "Sintilimab plus bevacizumab biosimilar was approved for advanced hepatocellular carcinoma by National Medical Products Administration (NMPA) and successfully included in the National Reimbursement Drug List (NRDL) in 2021. This study showed the clinical data of sintilimab in combination with two different doses of bevacizumab biosimilar, potentially offering more treatment options for physicians. Meanwhile, the exploration of biomarkers for predicting hepatocellular carcinoma immunotherapy will contribute to better treatment options and represent a step towards precise and individualized treatment."

Dr. Li WANG , Senior Vice President of Lilly China and Head of Lilly China Drug Development and Medical Affairs commented that: "Lilly and Innovent are committed to bringing  innovative oncology medicines with global quality to serve patients in China.  The clinical outcome and biomarker analysis result in this phase Ib study of sintilimab plus bevacizumab biosimilar injection for advanced hepatocellular carcinoma provides more solid basis for individualized and precise treatment.  The advancement of HCC treatment may contribute to the government's goal of increasing the overall 5-year cancer survival rate by 15% by 2030, and also supports accelerating the implementation of the 'Health China 2030' initiative. In the future, we will continue to strengthen cooperation with Innovent to endeavor to bring additional treatment options to patients."

About NCT04072679 study

NCT04072679 study is a Phase 1b study assessing the safety, tolerability and anti-tumor activity of sintilimab in combination with bevacizumab biosimilar in subjects with local advanced or metastatic HCC with or without previous systemic treatment or systemic treatment failure in China. The study has two stages, the first is a dose escalation stage and the second is a dose expansion stage. In the dose escalation stage, subjects will receive either 7.5 mg/kg (low-dose group) or 15 mg/kg (high-dose group) of bevacizumab biosimilar (IBI305) in combination with a fixed dose of 200 mg of sintilimab, respectively, and then entered into the dose expansion stage.

About Hepatocellular Carcinoma

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 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 worldwide, 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 and included in the National Reimbursement Drug List (NRDL) 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 non-squamous 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 bevacizumab biosimilar for the first-line treatment of unresectable or advanced hepatocellular carcinoma.
• Additionally, sintilimab currently has three regulatory submissions accepted for review in NMPA, including:
• In combination with cisplatin plus paclitaxel or cisplatin plus 5-fluorouracil for the first-line treatment of esophageal squamous cell carcinoma;
• In combination with chemotherapy for the first-line treatment of unresectable, locally advanced, recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma;
• In combination with bevacizumab biosimilar and chemotherapy for EGFR-mutated non-squamous NSCLC following EGFR-TKI treatment.

Additionally, two clinical studies of sintilimab have met their primary endpoints:

• Phase 2 study as second-line treatment of esophageal squamous cell carcinoma;
• Phase 3 study as second-line treatment for squamous NSCLC with disease progression following platinum-based chemotherapy.

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 non-squamous non-small cell lung cancer.

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 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 26 valuable assets in the fields of cancer, metabolic, autoimmune disease and other major therapeutic areas, with 6 products approved for marketing in China – TYVYT® (sintilimab injection), BYVASDA® (bevacizumab biosimilar injection), SULINNO® (adalimumab biosimilar injection), HALPRYZA® (rituximab biosimilar injection) , Pemazyre® (pemigatinib oral inhibitor) and olverembatinib (BCR ABL TKI), a Biologics License Application (BLA) for sintilimab accepted for review in the U.S., 5 assets in Phase 3 or pivotal clinical trials, and an additional 15 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. For more information, please visit: www.innoventbio.com. and www.linkedin.com/company/innovent-biologics/.

About Eli Lilly and Company

Lilly is a global healthcare leader that unites caring with discovery to create medicines to make life better for people around the world. We were founded more than a century ago by a man committed to creating high-quality medicines that meet real needs, and today we remain true to that mission in all our work. Across the globe, Lilly employees work to discover and bring life-changing medicines to those who need them, improve the understanding and management of disease, and give back to communities through philanthropy and volunteerism. To learn more about Lilly, please visit us at www.lilly.com and http://newsroom.lilly.com/social-channels.

About Eli Lilly and Company's strategic cooperation with Innovent Biologics

Lilly entered into a strategy collaboration with Innovent focused on biological medicine in March 2015 – a groundbreaking partnership between a Chinese pharmaceutical company and a multinational pharmaceutical company. Under the agreement, Lilly and Innovent will co-develop and commercialize oncology medicines, including Tyvyt® (sintilimab injection) in China. In October 2015, the two companies announced the extension of their existing collaboration to include co-development of three additional oncology antibodies targeting oncology indications. In August 2019, Innovent further entered a licensing agreement with Lilly to develop and commercialize a potentially global best-in-class diabetes medicine in China. Its collaboration with Lilly indicates that Innovent has established a comprehensive level of cooperation between China's innovative pharmaceuticals sector and the international pharmaceuticals sector in fields such as R&D, CMC, clinical development and commercialization.

Note:

TYVYT® (sintilimab injection) is not an approved product in the United States.
BYVASDA® (bevacizumab biosimilar injection), SULINNO®, and HALPRYZA® (rituximab biosimilar injection) are not approved products in the United States.

TYVYT® (sintilimab injection, Innovent)
BYVASDA® (bevacizumab biosimilar injection, Innovent)
HALPRYZA® (rituximab biosimilar injection, Innovent)
SULINNO® (adalimumab biosimilar injection, Innovent)
Pemazyre® (pemigatinib oral inhibitor, Incyte Corporation). Pemazyre® was discovered by Incyte Corporation and licensed to Innovent for development and commercialization in Mainland China, Hong Kong, Macau and Taiwan.

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SOURCE Innovent Biologics