With proprietary glycan engineering technology at its core, CHO Pharma (CHO) has brought the world’s first homogenous antibody drug, CHO-H01, to begin the first-in-human clinical trial. The new generation of carbohydrate-modified antibody drugs that target the complicated structure of the specific antigens on cancer cells can precisely modulate cellular cytotoxicity. It is further regarded to have a significant impact in leading the next wave of research and development in new drugs since the introduction of monoclonal antibodies. Licensing the core technology from the prestigious research team of Academia Sinica led by Chi-Huey Wong that has unequivocally captured the leading position in glycoscience, CHO quickly established itself as the international leader in the field of carbohydrate-related drug development.
By employing its patented carbohydrate synthesis technologies (one-pot synthesis and enzymatic synthesis) and the modular synthesis technology, CHO can quickly synthesize over 20,000 types of N-glycan structures of human glycoproteins using only 30 different modular structures. The technology has become the most effective method for studying the function of glycoprotein molecules and producing glycan arrays. With this technology as the basis, CHO has further developed a carbohydrate homogenization technology for antibody drugs. The technology uses different enzyme actions to remove the complex and diverse glycan structures on the Fc (Fragment, crystallizable) regions responsible for binding to immune cells. The remaining single N-Acetyl glucosamine structure (mono-GlcNAc) can be modified into a homogenous antibody by attaching a single defined glycan, which further allows for determination of the optimal glycosylation pattern for different antibodies.
Through the process of glycoengineering, CHO has discovered a unique glycan pattern that significantly boosts the antibody-dependent cell-mediated cytotoxicity (ADCC) in immune cells, improving the treatment effect of antibodies against cancers, influenza, and autoimmune diseases. Moreover, through homogenization, not only are the antibody effects enhanced and side effects reduced, but the manufacturing and quality control of antibodies are also simplified.
CHO has utilized this technology to transform three types of antibody drugs on the market into the first homogenized glycan bio-betters in the world. Among them, the homogeneous antibody drug, CHO-H01, based on the monoclonal antibody Rituxan, is aimed at follicular lymphoma as the initial indication. It has gained approval from the US FDA to start phase 1 clinical trial at the University of Rochester Medical Center and has the potential to become the first carbohydrate-homogenized biobetter product in the world. Meanwhile, the company has two new biological drugs that target carbohydrate surface antigens under the pre-clinical development.
Breakthrough in Homogeneous Antibody Development and a New Generation of Glycoarray Technology
Lastly, CHO has used the modular synthesis approach to develop a new generation of glycoarrays. Using this method, the density of glycans on the glycoarrays is enhanced, eliminating the uneven glycan distribution seen on traditional glycoarrays. In collaboration with the US National Institute of Health (NIH) and the Scripps Research Institute, the newly developed glycoarrays can precisely analyze the glycan antigen structure of some highly potent broadly neutralizing HIV antibodies previously not detectable using traditional arrays. The glycoarrays were further used to discover specific types of glycans that can interact with HIV antibodies. This new technology will greatly contribute to the development of AIDS vaccines in the future. With such cutting-edge research achievements, CHO has successfully secured its world-leading position in developing glycan-based pharmaceuticals.
(Editing by Research Center for Biotechnology and Medicine Policy)