Year/Course: 2020-2021, Easter 2021

Inventors: Dr. Steve Walsh, Dr. Jessica Iegre & Professor David Spring, Chemistry
Mentor: Dr. Cathy Boucher

There is a clear need for better and kinder treatments for cancer patients, with improved safety and lower rates of side effects, and one route to this involves the use of antibody-drug conjugates (ADCs). Currently there are 9 FDA-approved ADC treatments, with most being approved since 2017.

ADCs comprise an antibody to target specific cancer cells, a drug compound that is toxic to cells and a linker molecule to join them together. This gives better safety because the antibody specifically targets the cancer cells rather than allowing the drug to act throughout the body, and also better efficacy because it allows the use of more toxic drug compounds. However, ADCs have been slow to come to market due to their cost and problems with tolerability in the body and stability (low stability can result in the drug being released prematurely). Existing ADCs have also had problems with batch-to-batch consistency because they tend to produce mixtures of molecules with the drugs attached at different locations on the antibodies.

The inventors have developed a novel linker molecule which has several advantages over other linker technologies. Their linker can be used with existing antibodies, making the ADCs cheaper and easier to manufacture. It also allows fine control of drug loading, ensuring that all the ADC molecules in a batch are identical to each other. They have conducted in vitro studies of the effectiveness against cancer cells and the safety for other cells, and are starting to carry out in vivo studies this year.

The i-Team will need to investigate the market need for ADC-based cancer treatments, by talking to relevant experts and clinicians. Questions include identifying the therapeutic areas with the greatest need for new treatment, and understanding what proof points would be needed for a drug or antibody developer to be willing to adopt the new linker technology.