Exscientia to Present New Preclinical Data for AI-designed LSD1 and MALT1 Inhibitors at ESMO 2023

Published a year ago via Business Wire

— Demonstrated preclinical efficacy of LSD1 inhibitor in primary AML samples —

— Initial data supporting combination potential of LSD1 inhibitor with AML standard of care therapies —

— Tumour growth inhibition through MALT1 in monotherapy and combination while lowering bilirubin toxicity risk —

Exscientia plc (Nasdaq: EXAI) today 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.

“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 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

About Exscientia

Exscientia is an AI-driven precision medicine company committed to discovering, designing and developing the best possible drugs in the fastest and most effective manner. Exscientia developed the first-ever functional precision oncology platform to successfully guide treatment selection and improve patient outcomes in a prospective interventional clinical study, as well as to progress AI-designed small molecules into the clinical setting. Our internal pipeline is focused on leveraging our precision medicine platform in oncology, while our partnered pipeline broadens our approach to other therapeutic areas. By pioneering a new approach to medicine creation, we believe the best ideas of science can rapidly become the best medicines for patients.

Forward-Looking Statements

This press release contains certain forward-looking statements within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995, including statements with regard to Exscientia’s expectations regarding its Board of Directors. Words such as “anticipates,” "believes," “expects,” "intends," "projects," "anticipates," and "future" or similar expressions are intended to identify forward-looking statements. These forward-looking statements are subject to the uncertainties inherent in predicting future results and conditions and no assurance can be given that the drug discovery and precision medicine platforms discussed above will be successful in optimising drug candidates for specific patient populations. The success of Exscientia’s platforms is subject to numerous factors, many of which are beyond the control of Exscientia, including, without limitation, the ability of Exscientia to design clinical trials that are cleared by the FDA and of healthcare providers to collect viable patient tissue samples. Exscientia undertakes no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as may be required by law.

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