New Bioconjugation Technology may help Better Control the Location of Payload Conjugation to an Antibody

A novel, proprietary site-selective bioconjugation technology, called AJICAP™ allows developers of therapeutic Antibody-drug Conjugates (ADCs) to better control both the location of payload conjugation to an antibody along with fine tuning the quantity of payload attached.

Data describing the technology, developed by Ajinomoto’s Research and Development organization in Kawasaki, Japan, was presented during the World ADC Summit held in San Diego, held November 11 – 13, 2018.

Conventional antibody-drug conjugates which are currently commercially available are produced as heterogeneous mixtures containing a stochastic distribution of payloads decorating the antibody molecules. The controlling of the Drug-to-Antibody Ratio (DAR) in the development of next generation ADCs is believed to assist in increasing the therapeutic window of these targeted biologics. Scientists believe that this will result in an overall better clinical efficacy and less toxicity.

The presented data, obtained via internal research as well as partnerships with biopharmaceutical companies, shows that deployment of the AJICAP technology in preparation of ADCs demonstrated enhancement of the therapeutic window by achieving a site-specific DAR of 2 with native antibodies when compared to stochastic ADCs which contain a mixture of DAR species.

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The data also showed a wide drug-linker compatibility and reactive group compatibility including thiol and azide functionalities. In addition, the Ajinomoto Bio-Pharma team demonstrated that the technology could be scaled to produce gram quantities of ADCs for pre-clinical testing.

Scale-up
One of the most challenges aspects in the development of antibody-drug conjugates is the scale up process, which, like most biologics, is carried out at a milligram scale. However, a consistent result in the manufacturing on small scale manufacturing does not necessarily mean that the same outcome can be realized at larger scales. This variation is, in part, caused by changes in equipment and raw materials.

“The AJICAP technology utilizes a proprietary affinity peptide to direct controlled conjugation to the antibody in a relatively straight-forward synthetic process. This is technology that can easily be transferred to the manufacturing floor since it shows high productivity and short conjugation reaction times, which all lead to an ease of manufacture,” said Brian Mendelsohn, Ph.D., Director of ADC Process Development and Tech Transfer at Aji Bio-Pharma, a company that provides ADC process development, analytical, drug substance and drug product manufacturing services from its recently constructed facility in San Diego, CA.

“We have demonstrated with model ADCs and utilizing client provided materials that the technology is effective and scalable,” he added.

Site-specific technology
“This is the next step in Ajinomoto Bio-Pharma’s service offering to our clients. The AJICAP platform developed by our colleagues in Japan provides our clients access to site-specific conjugation technology that can be coupled with our process development and manufacturing services in San Diego, CA. We look forward to introducing the technology to our client base interested in ADCs and other products requiring bioconjugation,” Jason Brady, Ph.D., Sr. Director Business Development, Aji Bio-Pharma, noted.

“The demonstration of feasibility of the first generation AJICAP technology has been successful. We are now working to improve the platform in order to broaden the scope of capabilities including additional conjugation sites on the antibody. We look forward to presenting updates at future meetings,” concluded Tatsuya Okuzumi, Ph.D., Associate General Manager of R&D Planning at Ajinomoto.

New facility
Earlier this month, Ajinomoto Bio-Pharma opened the company’s first production suite designed to develop, manufacture, test, and release novel targeted agents, including Antibody-drug Conjugates (ADCs). The company also announced the signing of their first major contract providing manufacturing services for ADCs.

Although the terms of the deal are confidential, the scope of the project includes technology transfer, analytical method implementation, process validation, and GMP Drug Product manufacture in preparation for commercial launch of one the key therapeutic drugs of one of Ajinomoto Bio-Pharma clients.

“This a clear sign that our investment which addresses the high containment manufacturing needs of our clients will positively impact our growing business. There is limited capacity in the marketplace and customers are eager to secure availability in a state-of-the-art facility managed by a company with an outstanding quality track record,” Brady concluded.