Innovent Announces First Patient Dosed in Phase III ORIENT-31 Trial of Tyvyt® (Sintilimab) and IBI305 Combined with Chemotherapy for EGFR-TKI–Resistant, EGFR-Mutant Non-Squamous NSCLC

Suzhou, July 25, 2019 /PRNewswire/ -- Innovent Biologics (HKEX stock code: 01801), a biopharmaceutical company dedicated to the research and development, manufacturing, and commercialization of innovative drugs for the treatment of major diseases such as cancer and autoimmune diseases, announced today that Tyvyt, an innovative oncology drug co-developed with Eli Lilly and Company^®(Recombinant Fully Human Anti-PD-1 Monoclonal Antibody, English Brand Name: Tyvyt^®, chemical generic name: sintilimab injection) and recombinant humanized anti-VEGF monoclonal antibody injection (development code: IBI305) in combination with chemotherapy for the treatment of EGFR-mutated non-squamous non-small cell lung cancer that has failed epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy (ORIENT-31) completed the first patient dosing.

The ORIENT-31 study is a clinical trial conducted in China to evaluateSintilimab andA Randomized, Double-Blind, Multicenter Phase III Clinical Study to Evaluate the Efficacy and Safety of IBI305 in Combination with Chemotherapy in Patients with EGFR-Mutated Locally Advanced or Metastatic Non-Squamous Non-Small Cell Lung Cancer Who Have Failed EGFR-TKI Therapy, with a Planned Enrollment of 480 Patients.

Professor Lu Shun, Director of the Department of Medical Oncology at Shanghai Chest Hospital, pointed out: "Lung cancer is the most common malignant tumor in China, with both the highest incidence and mortality rates. In 2018, there were approximately 2.09 million new cases of lung cancer worldwide, including over 770,000 new cases in China. Non-small cell lung cancer (NSCLC) accounts for about 80% to 85% of all cases, and approximately 70% of NSCLC patients are diagnosed with locally advanced or metastatic disease that is not suitable for surgical resection. For advanced NSCLC patients with EGFR mutations, tyrosine kinase inhibitors (TKIs) are recommended as first-line treatment."），However, there is an urgent clinical need for new treatment options following disease progression on TKI therapy. Immune checkpoint inhibitors and anti-angiogenic agents have brought new hope to this field. Through the ORIENT-31 study, we aim to validate the therapeutic value of sintilimab and IBI305 in combination with chemotherapy in this patient population.”

Dr. Zhou Hui, Vice President of the Medical Science and Strategic Oncology Department at Innovent Biologics, stated“China bears a substantial burden of lung cancer, accounting for nearly 40% of new lung cancer cases globally. Treatment options and efficacy remain highly limited for EGFR-positive non-small cell lung cancer (NSCLC) after failure of EGFR-TKI therapy, representing a significant unmet clinical need. Through the ORIENT-31 study, we aim to provide more effective cancer treatment options for patients, thereby benefiting more patients and their families.”

About Tyvyt^®(Sintilimab Injection)

Tyvyt®^®(Sintilimab Injection) is an innovative biologic of international quality jointly developed by Innovent Biologics and Eli Lilly and Company in China. Innovent Biologics is currently conducting clinical research on Sintilimab Injection in the United States. Tyvyt^®(Sintilimab Injection) is a human immunoglobulin G4 (IgG4) monoclonal antibody that specifically binds to the PD-1 molecule on the surface of T cells, thereby blocking the PD-1/Programmed Cell Death-Ligand 1 (PD-L1) pathway that leads to tumor immune tolerance, reactivating the anti-tumor activity of lymphocytes, and thus achieving the purpose of treating tumors. Tyvyt^®(Sintilimab Injection) is a Chinese innovative PD-1 inhibitor of international quality. Its marketing application has been officially approved by the National Medical Products Administration (NMPA). The first approved indication is for relapsed/refractory classical Hodgkin lymphoma, and it has been included in the 2019 edition of the Chinese Society of Clinical Oncology (CSCO) Guidelines for the Diagnosis and Treatment of Lymphoma. Currently, more than twenty clinical studies (including eight registrational clinical trials) are underway to investigate the antitumor effects of sintilimab in other solid tumors.

About IBI305 (Bevacizumab Biosimilar)

IBI305 is a biosimilar to bevacizumab injection, also known as recombinant humanized anti-VEGF monoclonal antibody injection. VEGF is a critical factor in angiogenesis and is pathologically overexpressed in the endothelial cells of most human tumors. Anti-VEGF antibodies can selectively bind to VEGF with high affinity. By blocking the interaction between VEGF and its receptors on the surface of vascular endothelial cells, these antibodies inhibit the transmission of signaling pathways such as PI3K-Akt/PKB and Ras-Raf-MEK-ERK. This inhibition suppresses the growth, proliferation, and migration of vascular endothelial cells as well as neovascularization, reduces vascular permeability, blocks blood supply to tumor tissues, inhibits tumor cell proliferation and metastasis, and induces tumor cell apoptosis, thereby achieving antitumor therapeutic effects. On January 29, 2019, the National Medical Products Administration (NMPA) accepted the New Drug Application (NDA) for IBI305 and included it in the priority review program.

About the ORIENT-31 Study

The ORIENT-31 study is a randomized, double-blind, multicenter, Phase III clinical trial conducted in China to evaluate the efficacy and safety of sintilimab plus IBI305 in combination with chemotherapy in patients with EGFR-mutated locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) who have progressed after treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Participants will be randomized in a 1:1:1 ratio to receive sintilimab plus IBI305 combined with chemotherapy, sintilimab plus chemotherapy, or chemotherapy alone. The study plans to enroll 480 patients. The primary endpoint is progression-free survival (PFS).

About Combination Therapy

Anti-angiogenic inhibitors combined with immune checkpoint inhibitors can produce synergistic anti-tumor effects. Anti-VEGF therapy promotes the maturation of antigen-presenting cells (APCs) and the activation of cytotoxic T lymphocytes (CTLs), downregulates myeloid-derived suppressor cells (MDSCs) and regulatory T cell populations (Tregs) to modulate the tumor immune microenvironment, and enhances T-cell infiltration through normalization of tumor vasculature. Such combination therapy directly facilitates tumor clearance.

About Innovent Bio

“Rooted in Trust, Realized through Action.” Innovent Bio’s vision and mission are to develop high-quality biologics that are affordable for the general public. Founded in 2011, Innovent Bio is dedicated to the development, manufacturing, and commercialization of innovative medicines for the treatment of major diseases such as cancer. On October 31, 2018, Innovent Biologics was listed on the Main Board of The Stock Exchange of Hong Kong Limited, with stock code: 01801.

Currently, the company has established a high-quality technical platform covering the entire lifecycle of innovative biological drug development, including R&D, pharmaceutical development and industrialization, clinical research, and marketing. It has built a product pipeline comprising 20 new drug candidates in development, spanning four major therapeutic areas: oncology, fundus diseases, autoimmune diseases, and metabolic disorders. Among these, 14 candidates have entered clinical trials, with 4 in Phase III clinical studies. Marketing applications for three monoclonal antibody products have been accepted by the National Medical Products Administration (NMPA), two of which have been included in the priority review program. One product (Sintilimab Injection, brand name: Tyvyt)^®) approved for marketing by the National Medical Products Administration, with the first approved indication being relapsed/refractory classical Hodgkin lymphoma.

Innovent Bio has assembled a world-class team of experts in the development and industrialization of high-end biologics, including numerous overseas-returning specialists, and has established strategic collaborations with international pharmaceutical companies such as Eli Lilly and Company, Adimab, Incyte, and Hanmi Pharmaceutical. Innovent Bio is committed to working together with all stakeholders to advance the development of China’s biopharmaceutical industry, thereby improving medication accessibility for the public and fulfilling people’s aspirations for better health and well-being. For more details, please visit the company website:www.innoventbio.com。

About Eli Lilly and Company

Eli Lilly and Company is a global leading pharmaceutical company dedicated to improving human health through innovation. Founded over a century ago, the company’s founder was committed to producing high-quality medicines to meet tangible medical needs. Today, we remain steadfast in this mission and guide our work by it. Worldwide, our employees strive to discover and develop medicines that can transform lives and deliver them to patients who truly need them. Furthermore, we are committed to enhancing public understanding of diseases and improving disease management, while giving back to society through charitable initiatives and volunteer activities. For more information about Eli Lilly and Company, please visit:www.lilly.com。

Strategic Collaboration Between Innovent Bio and Eli Lilly

Innovent Bio (Innovent Biologics) and Eli Lilly and Company entered into a biopharmaceutical development collaboration in March 2015, which remains one of the largest partnerships to date between a Chinese biopharmaceutical company and a multinational pharmaceutical corporation. Under the terms of the agreement, Innovent Bio and Eli Lilly will jointly develop and commercialize at least three oncology therapeutic antibodies over the following decade. In October 2015, the two parties announced an expansion of their established drug development collaboration, adding three additional novel oncology therapeutic antibodies. These two collaborations with Eli Lilly mark the establishment of a comprehensive strategic partnership between Innovent Bio, as an innovative Chinese pharmaceutical enterprise, and a global pharmaceutical giant, encompassing new drug research and development, manufacturing quality, and marketing and sales.