On 19 Sept 2021, Akeso, Inc. (9926.HK, “the Company”) announces that Akeso’s CSO, Dr. Baiyong Li, presented the mechanism study results of the world’s only IgG1 isotype anti-PD-1 monoclonal antibody Penpulimab (trade name: 安尼可®) at the oral presentation session at the European Society for Medical Oncology Congress of 2021 (ESMO 2021) on 18 September 2021.
Presentation title: Penpulimab, an IgG1 anti-PD-1 antibody with Fc-engineering to eliminate effector functions and with unique epitope and binding properties
Oral presentation number: 2O
Speaker: Dr. Baiyong Li, Co-founder and CSO, Akeso
Currently most anti-PD-1 antibodies are IgG4 isotype, which has strong effects like antibody dependent cellular phagocytosis (ADCP) and relatively lower stability compared with IgG1, therefore better efficacy and safety profile could be acquired by applying and engineering IgG1 isotype.
This mechanism study of IgG1 isotype PD-1 antibody drug Penpulimab demonstrated that, compared with IgG4 isotype PD-1 antibody, as a humanized IgG1 isotype PD-1 antibody modified at the Fc region, Penpulimab exhibited no binding to FcγRIa, FcγRIIa_H131, FcγRIIb, FcγRIIIa_V158, FcγRIIIa_F158 or C1q. Thus, avoids antibody dependent cell-mediated cytotoxicity (ADCC), antibody dependent cellular phagocytosis (ADCP), and complement-dependent cytotoxicity (CDC) to minimize lymphocyte loss, and to avoid antibody dependent cytokine release (ADCR) such as IL-8 and IL-6, which are related to immune-related adverse events (IRAEs) and poor prognosis in immunotherapy.
In addition, different from most PD-1 antibody on the market, Penpulimab binds to human PD-1 N-glycosylation site at N58, which may enhance PD-1/PD-L1 interaction. Thus, Penpulimab showed a slower PD-1 binding off-rate compared to nivolumab (2.43E-04/s) and pembrolizumab (2.80E-04/s). Moreover, Penpulimab stimulated IL-2 and IFN-γ secretion in mix lymphocyte reaction, indicating strong T cell activation.
Study results show that the differentiation from IgG4 isotype PD-1 antibody may contribute to better clinical efficacy and safety profile of IgG1 isotype Penpulimab.
Information about 安尼可® (Penpulimab Antibody Injection)
安尼可® (Penpulimab antibody injection) is a new PD-1 monoclonal antibody with IgG1 subtype and Fc segment modification, which is structurally stable and less prone to aggregation. Antibody-dependent cell-mediated cytotoxicity (ADCC), acoustic doppler current profiler (ADCP) and complement dependent cytotoxicity (CDC) is avoided entirely, and antibody-drug conjugate reaction (ADCR) is lessened. Crystal structure analysis reveals a unique PD-1 binding epitope with a slower dissociation rate from PD-1 for durable blockade of PD-1/PD-L1 binding. This differentiation from other PD-1 products on the market may lead to a better efficacy and safety profile for the Penpulimab antibody.
Information about Akeso, Inc.
Akeso, Inc. is a biopharmaceutical company dedicated to the research, development, manufacturing and commercialization of new innovative antibody drugs that are affordable to patients worldwide. Since the Company’s establishment, the Company has established an end-to-end comprehensive drug development platform (ACE Platform) and system, encompassing fully integrated drug discovery and development functions, including target validation, antibody drug discovery and development, CMC production process development, and GMP compliant scale production. The Company has also successfully developed a bi-specific antibody drug development technology (Tetrabody technology). The Company currently has a pipeline of over 20 innovative drugs for the treatment of major diseases like tumors, autoimmune diseases, inflammation and metabolism diseases, 13 of which have entered clinical stage, including two first-in-class bi-specific antibody drugs (PD-1/CTLA-4 and PD-1/VEGF). In Aug 2021, the Company’s first in-house innovatively researched and developed differentiated PD-1 monoclonal antibody Penpulimab monoclonal antibody injection (安尼可®) was approved to the market. The Company’s vision is to become a global leading biopharmaceutical company through research and development (‘‘R&D’’) of high efficacy and breakthrough new drugs that are first-in-class and best-in-class therapies.
