Abstract 909: Antibody fragment drug-conjugates (FDCs)-application of ANT-043 and ANT-045 in solid tumors

Abstract

Abstract Despite the recent resurgence, Antibody Drug Conjugates (ADCs) are failing to address challenging cancer indications due to 3 critical limitations: Low potency, ineffective solid-tumour penetration and poor tolerability. The industry is well-served by approaches where full-length Immunoglobulins are designed to carry defined numbers of payloads. However, antibody fragments (e.g. single-chain Fvs-scFvs), which have many advantages including rapid tumour penetration, faster clearance, inexpensive manufacture, have been technologically challenging to apply in oncology. Our novel approach enables scFvs to have a high Drug:Antibody loading ratio (DAR) whilst retaining effective binding and other favourable biophysical properties, leading to a new product class tailored for solid tumours. Antikor has two ‘first-in-class' FDC products in development for solid tumours: anti-HER2 FDC (ANT-043) a follow-up product against a second target (ANT-045) which will be disclosed during this presentation. ANT-043 has demonstrated excellent tumour ablation effects in breast, ovarian and gastric cancer xenograft models and superior tolerability compared to an ADC. Quantitative payload tumour uptake by mass spectrometry and fluorescent immuno-histological studies demonstrate superior solid tumour penetration across the entire tumour and diffusion from blood vessels and rapid kinetic uptake. In collaboration with our partners, Essex Biotechnology, ANT-043 is moving into IND-enabling studies for clinical development. Our new flagship product, ANT-045, which emerged from our proprietary FDC ‘discovery engine', is progressing well and new data will illustrate how ANT-045 could have a broader patient benefit in gastro-intestinal cancers. Like ANT-043, ANT-045 has potent in vitro cell-kill properties, excellent stability and drug-like features and illustrates how linker-payload design is critical for the tailoring properties of this emerging format of ADC. This presentation will focus on ANT-045's remarkable development and show that this FDC demonstrates superior efficacy and tolerability compared to an ADC when equated on an equi-mass, equi-molar and equi-payload basis. ANT-045 could be used to switch ‘immunologically-cold' tumour ‘hot' to benefit from checkpoint inhibitor therapy and data will be presented to support this concept. Citation Format: Mahendra P. Deonarain, Gokhan Yahioglu, Ioanna Stamati, Bryan Edwards, Soraya Diez-Posada, Anja Pomowski, Ashleigh Stewart, Isabel Perez-Castro, Laura Bouche, Triin Jurgenson, Monika Maciuszek, Sam Ness, Malcolm Ngiam, Quinn Xue. Antibody fragment drug-conjugates (FDCs)-application of ANT-043 and ANT-045 in solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 909.