Harnessing FDC technology for metastatic colorectal cancer (mCRC)

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Antikor Biopharma is pioneering an innovative drug delivery platform called OptiLink, tailored for solid tumours. It is unique by utilising specially-engineered, small-format, tumour-specific antibodies with appropriately-designed linkers to specifically deliver potent cytotoxic payloads deep into tumours. Unlike its competitors, who use full-size antibody-drug conjugates (ADCs), Antikor's technology enables much smaller fragment-drug conjugates (FDCs) to be developed. These have many advantages: FDC products potentially have a higher therapeutic index for cancer therapy as they are more potent, can be dosed more aggressively because they clear from normal tissues more quickly and penetrate rapidly and deeply into tumours enabling faster and more effective tumour destruction.Through previous Innovate-UK support, Antikor expanded and refined its technology and discovered a strong pre-clinical FDC candidate (ANT-045) aimed at gastric cancer which is now entering formal IND-enabling studies with expectations for a regulatory filing in 18 months.Antikor is now expanding its pipeline to another difficult-to-treat solid tumour, colorectal cancer (CRC). Although gastrointestinal in nature, this has very different challenges to gastric. There are fewer well-characterised targets for CRC and this disease is notoriously insensitive or rapidly-develops resistance to microtubule inhibitor drugs. We have identified a suitable but emerging target for CRC, well- matched to our technology and we need to innovate and develop our expertise around DNA-damaging payloads. This discovery and early development project aims to discover a panel of antibody fragments (using our proprietary libraries optimised for FDCs) and to synthesize linker-payload derivatives that are compatible with our smaller, more penetrating format.We have already implemented the discovery strategy and have preliminary data on some promising candidates and we need to expand this to have a wider range to choose from. We also have preliminary chemistry data and this project builds on this to refine the synthesis and discover some potentially novel and patentable new linker-payloadsNew payloads will be conjugated to new antibody fragments to create novel and proprietary FDCs for CRC therapy. Using our established process, we will use our suite of biophysical analytical techniques and biological assays to fully-characterise candidate FDCs, aiming to generate early proof-of-concept in animal models. Success will be followed by further investment to develop leads in advanced models and ultimately fill Antikor's pipeline with a second innovate and much- needed product for solid tumour therapy.