Julia is a Senior Scientist at Promega Corporation. Her group specialises in the development of bioassays for immuno-oncology applications, with a special focus on cell therapies and the use of primary human cells. She received her PhD in Biomedical Sciences with a focus in immunology from the University of California, San Francisco and completed postdoctoral training in cell biology and parasitology at the University of Wisconsin Madison.

Frances is a team leader in the Assays, Profiling and Pharmacology group within Biologics Engineering at AstraZeneca. She has over 20 years industrial experience in developing and running assays for biologics drug discovery across therapeutic areas. These include biochemical and cell-based assays to thoroughly characterise lead IgG for affinity, epitope, species cross reactivity, functional activity and mechanism of action. She is also highly experienced in leading strategy of multi-discipline teams to delivery high quality antibody therapeutics.

Antibody Drug Conjugates (ADCs) are combinations of the unique targeting ability of monoclonal antibodies and powerful cytotoxic drugs, which results in antibody-directed killing of cancer cells.

The functional assessment of ADCs during early drug discovery traditionally relies on proliferation assays. Whilst these assays are reliable and robust they can lengthen drug discovery timelines as they typically take 5 to 7 days to complete a single assay depending on the growth rate of the overexpressing target or tumour cells. To address this bottleneck, we are establishing a high throughput ADC assay platform using two different methods. Firstly, assessing a range of assay readouts that measure early markers of cell death, such as caspase 3/7 activity. Secondly, evaluating assays that measure a direct effect which is specific to the cytotoxic drug's mechanism of action. For example, a measure of DNA damaging agents such as topoisomerase inhibitors can be measured by induction of histone pH2AX phosphorylation.

This suite of assays offers advantages over proliferation assays as they are independent of cell growth rate, making them suitable for a wide range of cell lines, and can significantly reduce incubation times by up to 67%. Our work not only presents the lead isolation of an ADC but also showcases the development of an early cell death assay platform, promising faster identification of lead antibodies.

Antibody Fragment Drug Conjugates (FDCs), a new product class tailored for solid tumours, promise many advantages over ADCs including rapid tumour penetration and faster systemic clearance. However, these 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. Our lead product, ANT-045 is a cMET-targeted FDC addressing a wide range of solid tumours. We will show that ANT-045 demonstrates superior tumour cure efficacy and tolerability compared to the leading competitor ADC telisotuzumab vedotin in multiple models in vivo with supporting quantitative biodistribution, imaging, biophysical stability and toxicology data. In a dose-range finding, non-GLP non-human primate study, ANT-045 was well tolerated demonstrating no signs of the usual dose-limited adverse effects seen with ADCs (neutropenia, thrombocytopenia) with a predicted half-life in human of around 12 hours supporting a viable clinical dosing strategy with a wide therapeutic window. 

Chris is the UK Science lead for Immunology & Immunotoxicology at Labcorp with a special focus on in vitro alternatives and NAMs.  Chris studied Biomedical science at the Leeds Becket University and has worked at Labcorp (aka Covance) for the past 17 years.  Chris spent his early years there in clinical pathology laboratories group building the Human cell-based assays In vitro Immunology capabilities. In 2017 the Immunology & Immunotoxicology group was formed, Chris continued as a senior scientist and later in his current role as UK science lead, responsible for science and strategy for the groups in Harrogate & Huntingdon.

He regularly presents data at scientific meetings in the form of posters/ presentations on NAMs and has been a regular attender of ACT, EUROTOX as well as SOT more recently. 

Automation of cell-based screening assays provides multiple benefits for identifying superior Biologic molecules, such as increasing screening throughput, improving reproducibility and enhancing precision and accuracy of the results obtained. In collaboration with Sanofi, Arctoris developed a cell-based screening assay on the Ulysses™ platform. This screen was optimised to identify active non-purified biologics, further increasing the scope and speed of samples that can be tested. This presentation will cover the key steps of this assay development; from initial optimisation of assay parameters and expanding capabilities for screening non-purified biologics, to developing the fully end to end automated workflow.