ADC Reviews

Future Development Prospects of Antibody Drug Conjugates

ADC Development

Due to the advantages of clear targets, mature technology and good selectivity, the research of antibody-drug conjugates is expected to continue to become a research hotspot in the field of anti-cancer in the next few years. To keep up with the pace of new drug research and development in the world, powerful pharmaceutical companies must join the trend of ADC research and development. Of course, this field has high technical requirements and a relatively narrow space for intellectual property rights. Moreover, companies such as Seattle Genetics have been operating in this field for decades, and it is difficult to occupy a place without certain technical support. The fundamental reason why international pharmaceutical giants choose to buy mature technologies or patents such as Seattle Genetics and ImmunoGen. The principle of ADC research and development is very clear, but technology and experience are very important, especially the design of connectors is almost an art. The opportunity to enter this huge market must be skillful.

Despite decades of R&D history, ADCs still have huge room for improvement. In fact, multiple studies have shown that the proportion of ADC compounds delivering effector molecules to target cells is much less than 1%, and an optimistic estimate is only 1.5%. Many people are disappointed by this figure. Even so, the targeting of drug delivery is still much higher than the traditional systemic drug delivery mode, and the incidence of adverse reactions is significantly lower than that of traditional drugs. Conversely, it leaves more room for us to design a new generation of antibody-drug conjugates. Because it has been clinically proven that the current ADC drugs have brought unprecedented efficacy to patients, the new generation of ADC drugs may be even better.

How to enter the huge market of ADC in the future should comprehensively consider various factors including financial strength, technical experience and research team of each company. For those companies with independent intellectual property rights in the field of monoclonal antibodies, the acquisition of mature effector molecules and linkers can jump into the forefront of ADC research. Having unique effector molecules is also another ideal entry point into ADC research. Of course, more space will be gained with the distinctive new joints. Mersana Therapeutics, for example, devised a new joint concept called the Fleximer. The water-soluble linker uses biodegradable polyvalent polysaccharide derivatives, so that dozens of drug molecules can be connected to each antibody junction. And because the polysaccharide has good water solubility, it avoids the self-precipitation of antibodies and other pharmacokinetic defects caused by linking too many drugs. Thereby, the confusion caused by insufficient number or activity of effector molecules can be solved. Of course, the clinical performance of the Fleximer joint remains to be further verified.

As with the development of novel linkers, any other technique that can effectively improve ADC characteristics is an entry point into this field. For example, the connection position and coupling method of effector molecule and antibody are also critical to the stability of ADC. The introduction of specific amino acid residues at specific positions for conjugation is also another entry point. Ambrx Pharmaceuticals has a presence in this space. In addition to improving antibody stability, it also plays a key role in ADC uniformity and mass production. Ambrx, SutroBiopharma, Genentech and Pfizer are all leading the way in this area.

Finally, successful ADC drug design is not only about optimizing each ADC component, but also the manner and details of how each part is connected, including adaptor linkers and isolation regions between antibodies or effector molecules.