Uses multi-omics to identify a biomarker which could be predictive of '546 response in the clinic
Differentiated '546 development and patient enrichment strategy driven by Exscientia's precision medicine platform
Research highlights the relationship between Exscientia's high adenosine biomarker and prediction of checkpoint inhibitor response
Recently initiated Phase 1/2 clinical trial, IGNITE-AI, will evaluate biomarker signature and assess '546 in combination with a checkpoint inhibitor in solid tumours
Exscientia plc (Nasdaq: EXAI) today highlighted new data to identify patients that are more likely to respond to its A2A receptor antagonist, EXS-21546 (‘546) as well as the relationship to potential impact of adenosine on PD-1 inhibitor response. The research identified a novel patient selection multi-gene transcript signature, the adenosine burden score (ABS), that will be confirmed in the Company's Phase 1/2 study, IGNITE-AI. The data are being presented at the ESMO Immuno-Oncology Annual Congress, being held December 7-9 in Geneva, Switzerland.
In this study, researchers leveraged Exscientia's translational oncology platform with transcriptomics, to develop and begin pre-clinical biological confirmation of the ABS, a measure of adenosine burden. Data was also presented showing ABS outperformed other published adenosine signatures in specificity and sensitivity for detecting adenosine-rich microenvironments.
Additionally, the research identified an inverse relationship between ABS and another published signature that has been shown to be predictive of anti-PD-1 therapy success, the Tumour Inflammation Score (TIS). This suggests that reduction of adenosine burden through A2AR antagonism with ‘546 could result in the restoration of checkpoint inhibitor response. The combination therapy approach will be validated in the IGNITE-AI Phase 1/2 clinical trial, combining ‘546 with a checkpoint inhibitor in solid tumours.
“We believe that the signature identified by thoroughly assessing adenosine activity in primary patient samples through our functional precision medicine platform provides us with a guided way to enrich for patients that may respond to ‘546 therapy,” said Gregory Vladimer, VP of Translational Research at Exscientia. “Adenosine in the tumour microenvironment is immuno-suppressive and only patients with high adenosine will benefit from A2A receptor antagonist therapy. That is why we want to design our clinical programmes to specifically identify those patients and potentially improve the probability of response.”
Poster Presentation Details:
Title: Enriching for response: Patient selection criteria for A2AR inhibition by EXS-21546 through ex vivo modelling in primary patient material
Abstract Number: 23P
Session Title: Biomarker development
Date/Time: Thursday, December 08 / 12:30 PM – 13:15 PM CET
The poster is available on Exscientia's website.
EXS-21546 is a highly selective A2A receptor antagonist co-invented and developed through a collaboration between Exscientia and Evotec SE (Frankfurt Stock Exchange: EVT, MDAX/TecDAX, ISIN: DE0005664809; Nasdaq: EVO). In June 2022, Exscientia reported topline data from a healthy volunteer study which confirmed Exscientia’s target product profile design, including potency, high receptor selectivity and expected low brain exposure with no CNS adverse events reported. Exscientia recently initiated a Phase 1/2 clinical trial of ‘546 in combination with a checkpoint inhibitor in patients with relapsed or refractory renal cell carcinoma (RCC) and non-small cell lung cancer (NSCLC) who previously received treatment with an immune checkpoint inhibitor.
Exscientia is an AI-driven pharmatech 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.
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