Eucure Biopharma, as a biopharmaceutical company dedicated to the development of tumor and immune antibody drugs with independent intellectual property rights, announced encouraging anti-tumor activity as demonstrated in the dose escalation phase of the Phase I clinical study of CTLA-4 antibody (YH001) in combination with Junshi Biosciences' anti-PD-1 monoclonal antibody Toripalimab Injection (Brand Name: TuoYi ?) in Australia.
A 64-year-old male subject with gastroesophageal junction tumor with liver/lung metastases, Subject Number 10104, who progressed after prior third-line chemotherapy, was enrolled in the 0.3 mg/kg dose group of YH001 in this study on September 17, 2020.
The subject received one-cycle (21 days/cycle) YH001 monotherapy, followed by combination therapy with Toripalimab 240 mg. As of March 1, 2021, the subject had received 7 cycles (21 weeks) of study drug. The first imaging assessment at Week 8 post-treatment indicated stable disease (SD), with a 12.7% reduction from baseline in the total diameter of all target lesions. The second imaging assessment at Week 15 post-treatment indicated a partial response (PR), with a 60.9% reduction from baseline in the total diameter of all target lesions. During the study, no dose-limiting toxicity (DLT) events were observed, study drug-related adverse events were only Grade 1 fatigue, and no Grade 2 or above adverse events occurred. The clinical study YH001002 is intended to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of CTLA-4 (YH001) in combination with toripalimab in patients with solid tumors.
YH001, a monoclonal antibody targeting CTLA-4, can enhance the removal of regulatory T cells (Treg cells) in the tumor microenvironment by improving the immune response against tumor cells in order to treat multiple tumors. Enhancing patients' immune responses to tumors by blocking inhibitory signals of human anti-tumor responses is considered the most promising tumor immunotherapy at present. Guided by this theory, CTLA-4 and PD-1 are considered as two significant checkpoints of the immune system, as well as cornerstone targets for tumor immunotherapy as they initiate anti-tumor immune attacks by affecting different types of T cells, respectively. As the first approved tumor immunotherapy antibody drug, Ipilimumab targeting CTLA-4 demonstrated good efficacy in the treatment of advanced metastatic melanoma and other tumors, and showed strong potential in combination with the PD-1 antibody. However, the clinical toxicity of Ipilimumab has been always the biggest worry limiting its clinical manifestation, and also prompted the scientific community to reexamine and investigate the mechanism of action of CTLA-4. YH001 is a recombinant humanized anti-CTLA-4 IgG1 monoclonal antibody injection developed by Eucure (Beijing) Biopharma Co., Ltd. Preclinical data demonstrated that binding and ADCC activity of YH001 were higher than that of Ipilimumab under the same conditions; YH001 also can block the binding of CTLA-4 to CD80/CD86, so YH001 is predicted to have a good anti-tumor effect.
In response, Dr. Yuelei Shen, the President of Biocytogen and CEO of Eucure Biopharma, commented, "We are very pleased to see a partial response of target tumor lesions in this clinical study, which is going fast and smoothly in Australia. We will accelerate the development to initiate trials in combination with PD-1 monoclonal antibody drug in China as soon as possible in order to provide effective innovative products for Chinese patients. Our three independently developed products have advanced to the clinical phase and the first patient has been screened in Australia successively since May 2020. The first patient screening was completed and the first administration was received in the Phase I clinical study of YH001 (CTLA4) in combination with PD-1 in Australia in May 2020; the first patient screening was completed and the first administration was received in the second clinical trial of YH002 (OX40) in Australia in June 2020. In July 2020, the first patient screening was completed and the first administration was received for YH003, an important cornerstone of the tumor immunotherapy. The Phase I clinical studies of these three products have been moved smoothly and have escalated to the effective dose. This also marks a successful transition of Biocytogen/Eucure Biopharma from a preclinical company to an innovative drug company in the clinical phase."
About TuoYi ? (Toripalimab Injection)
Toripalimab Injection (TuoYi ?) was the first domestic monoclonal antibody drug targeting PD-1 approved for marketing in China, and received the support as a National Science and Technology Major Project. The first approved indication for TuoYi is the treatment of patients with unresectable or metastatic melanoma who have failed in prior systemic therapy, and TuoYi is recommended in Guidelines of Chinese Society of Clinical Oncology (CSCO) - Melanoma (2019, 2020). In December 2020, TuoYi ? passed the negotiation procedure for national health insurance successfully and was included in the new version of National Reimbursement Drug List. In February 2021, TuoYi? was approved by NMPA for the treatment of patients with recurrent/metastatic nasopharyngeal cancer who have failed in prior second-line or above systemic therapies. An application for NDA approval of toripalimab for a new indication of treatment of patients with locally advanced or metastatic urothelial carcinoma who have failed in or intolerable to systemic therapy was accepted by NMPA in May 2020, and was included in the priority review procedure by the NMPA in July 2020. In September 2020, Toripalimab received Breakthrough Therapy Designation for the treatment of nasopharyngeal carcinoma from FDA. An application for NDA approval for a new indication of toripalimab in combination with chemotherapy for advanced recurrent and metastatic nasopharyngeal cancer without prior first-line systemic therapy was accepted by NMPA in February 2021. Toripalimab has received 1 Breakthrough Therapy Designation, 1 Fast Track Designation, and 3 Orphan Drug Designations from FDA in the treatment of mucosal melanoma, nasopharyngeal carcinoma, and soft tissue sarcoma by now. Over 30 clinical studies has been conducted worldwide since toripalimab was clinically developed at the beginning of 2016 to actively explore the efficacy and safety of TuoYi in indications such as melanoma, nasopharyngeal cancer, urothelial cancer, lung cancer, gastric cancer, esophageal cancer, liver cancer, bile duct cancer, breast cancer, renal cancer, etc. Collaboration with domestic and foreign first-in-class innovative pharmaceutical companies in combination therapies is also ongoing, and more patients in China and other countries are expected to receive the most advanced tumor immunotherapy in the world.
Biocytogen is an international biotechnology company that develops new drugs based on innovative technology. Biocytogen is committed to becoming the birthplace of global new drugs with the mission of focusing on technological innovation, continuous new drug production, and safeguarding of human health. Biocytogen has established a unique new drug development system covering the whole drug development process by organically integrating the single-cell antibody discovery technology platform, efficient gene editing model development platform, large-scale animal model supply platform, and rapid animal in vivo and in vitro drug efficacy evaluation platform with powerful clinical development capabilities based on the fully human antibody RenMab? , RenLite?, and RenNano? mice independently developed by Biocytogen with completely independent intellectual property rights. Therefore, Biocytogen successfully transformed into Biotech, and will focus more on development of innovative antibody drugs in the future. As implementation of the large-scale antibody drug development - "Project Integrum", Biocytogen will work with global partners to jointly accelerate the new drug development. Biocytogen is headquartered in Beijing, with branches in Haimen (Jiangsu), Boston, Shanghai. Eucure Biopharma, a wholly-owned subsidiary of Biocytogen, focuses on clinical development.
About Junshi Biosciences
Founded in December 2012, Junshi Biosciences (1877.HK, 688180.SH) is an innovation-driven biopharmaceutical company dedicated to the discovery, development and commercialization of innovative therapies. Junshi Biosciences has abundant product pipelines under investigation, including 28 innovative drugs and 2 biosimilars, and covering five major therapeutic areas of malignant tumors, autoimmune system disorders, chronic metabolic disorders, nervous system disorders, and infectious diseases. Based on the core platform technology of protein engineering, Junshi Biosciences stands at the frontier of R&D of macromolecular drugs. Junshi Biosciences is the first PRC company to obtain the NDA approval from the NMPA for anti-PD-1 monoclonal antibody, and also the first PRC company to receive IND approvals from the NMPA for anti-PCSK9 monoclonal antibody. Junshi Biosciences is the first company around the world to obtain the IND approvals from both NMPA and FDA for the anti-BTLA blocking antibody for tumor treatment, which are under Phase I clinical studies conducted in China and the United States. Junshi Biosciences also worked with domestic scientific research institutions to combat the COVID-19 epidemic in 2020. The jointly developed JS016 has entered clinical trials as the first monoclonal neutralizing antibody against COVID-19 in China, and has received emergency use authorization in the United States and Italy, thereby contributing to disease prevention and control in China and the world with local innovation. Junshi Biosciences currently owns nearly 2,000 employees worldwide, located in San Francisco and Maryland, the United States, and Shanghai, Suzhou, Beijing and Guangzhou, China.