ANT045: A novel format, antibody fragment drug-conjugate (FDC) product for challenging cMET-expressing solid tumors

Antibody Fragment Drug Conjugates (FDCs), a new product class tailored for solid tumors promise many advantages over conventional ADCs including rapid tumor penetration and faster and safer systemic clearance. However, these formats have been technologically-challenging to apply in oncology. Our novel approach enables high-Drug:Antibody Ratios (DARs) whilst retaining effective binding and other favourable biophysical properties. To achieve this, single-chain Fvs and other recombinant antibody formats must be considered in context with complex linker-payload chemical moieties. In some cases, antibody surface charge needs to be manipulated to achieve high DARs. This platform technology has led to our lead product, ANT-045 is a cMET-targeted FDC addressing a wide range of solid tumors. ANT-045 demonstrates superior tumor cure efficacy in cMET high, moderate and low CDX and PDX gastric cancer xenograft models and better tolerability compared to the leading competitor ADCs, notably telisotuzumab vedotin. In a non-GLP, non-human primate study, ANT-045 was well tolerated with a predicted half-life in humans of around 12-14 hours supporting a viable clinical dosing strategy with a wide therapeutic window. Insights into how FDCs behave in vivo through quantitative uptake studies and toxicological parameters will be shared and how these have informed our follow-up products.