104599Improved Linkers for Antibody Fragment Drug ConjugatesClosedCollaborative R&DInnovate UK"Antikor is developing a novel and disruptive platform for oncology drug delivery called **Fragment Drug Conjugates (FDC)**. Here, cytotoxic payloads are specifically delivered to solid tumours. Our platform differentiates from other similar Antibody Drug Conjugates (ADC) approaches in that our format can penetrate tumours faster and more effectively, deliver more payload and clear from normal tissues quicker, leading to better products for increased patient survival and quality of life. The current generation of linkers used to connect the payload to the antibody were designed for large antibodies. This project will develop shorter linkers that do not hinder antibody binding but can maintain FDC solubility and other beneficial features. This project will innovate around the design and chemical synthesis of novel linkers containing hydrophilic sugar units and short polyethylene glycol chains using three clinically-established cytotoxic payloads. These linker-payloads will be synthesised to laboratory scale (tens of milligrams) and then be used to make model FDCs to test in a range of biophysical (binding, aggregation and stability) and biological (cell-kill potency and plasma clearance) assays to identify novel, next-generation linkers that better-match our FDC technology. These linkers will be innovative by having novel structures and features that enhance FDCs, leading to improved future products for solid cancers."