Exscientia plc announced two abstracts to be presented at the upcoming European Society for Medical Oncology (ESMO) Congress 2023 from October 20-24, 2023 in Madrid, Spain. This data underlines how Exscientia can bring together AI design and novel translational research capabilities to create better quality drug candidates. This also allows to system identify those patient populations who have the most potential benefit well before start clinical trials.

'539 is a novel, potent, selective and reversible LSD1 inhibitor under preclinical investigation as a monotherapy or in combination with standard of care for oncology and haematology indications including acute myeloid leukaemia (AML) and small cell lung cancer (SCLC). Leveraging primary human material and Exscientia's proprietary precision medicine platform, the Company confirmed '539's general efficacy, demonstrating that '539 induces AML cell differentiation marker expression when used on primary AML patient tissue ex vivo. Combination data with first line AML and targeted therapies will be presented.

Characterisation of EXS73565, a potent and selective MALT1 inhibitor with low drug-drug interaction risk and potential in lymphoma. Exscientia utilised generative design, machine learning and molecular dynamics approaches to precision-design '565, a potent and selective allosteric MALT1 inhibitor with a differentiated profile exhibiting low drug-drug interaction and hyperbilirubinemia risk. Preclinically, '565 exposure resulted in limited inhibition of UGT1A1, an enzyme involved in bilirubin metabolicism.

This approach has the potential to offer safety benefits compared to other clinical stage MALT1 inhibitors which carry a high UGT1A1 inhibition and hyperbilirubin toxicity risk. Significant tumour growth inhibition was observed for '565 in vivo in activated B-cell diffuse large B-cell lymphoma (ABC-DLBCL) xenograft models. Significant synergistic effects were observed for combination '565 and the BTK inhibitor ibrutinib in a xenograft model with low sensitivity to either single agent.

Overall, the profile of '565 offers the potential for clinical exploration of MALT1 inhibition as a monotherapy and/or in combination with other targeted agents in haematological malignancies.