On October 16, 2023 Exscientia plc (Nasdaq: EXAI) reported that two abstracts to be presented at the upcoming European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023 from October 20-24, 2023 in Madrid, Spain (Press release, Exscientia, OCT 16, 2023, View Source [SID1234636043]).
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"We are excited to share new preclinical data on our precision-designed LSD1 and MALT1 inhibitors, which we introduced to our oncology pipeline earlier this year," said Professor Andrew Hopkins FRS FMedSci, founder and Chief Executive Officer of Exscientia. "We believe these compounds bear strong potential for differentiation, patient benefit and value creation. This data underlines how Exscientia can bring together AI design and novel translational research capabilities to create better quality drug candidates. This also allows us to systematically identify those patient populations who have the most potential benefit well before we start clinical trials."
Both ESMO (Free ESMO Whitepaper) posters will be available on the Exscientia website from their time of presentation.
Poster Presentations
Title: Determining anti-cancer efficacy of a reversible LSD1 inhibitor, EXS74539, in primary AML tissues with limited thrombocytopenic effects
Session Title: Translational research (agnostic)
Abstract Number: 2289P
Date/Time: Saturday, October 21 / 12:00 PM – 1:00 PM CEST
‘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
Title: Characterisation of EXS73565, a potent and selective MALT1 inhibitor with low drug-drug interaction risk and potential in lymphoma
Session Title: Haematological malignancies
Abstract Number: 832P
Date/Time: Monday, October 23 / 12:00 PM – 1:00 PM CEST
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 metabolism. This approach has the potential to offer safety benefits compared to other clinical stage MALT1 inhibitors which carry a high UGT1A1 inhibition and hyperbilirubinemia 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