On December 6, 2022 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 (Press release, Exscientia, DEC 6, 2022, View Source [SID1234624870]). 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 (Free ESMO Whitepaper) Immuno-Oncology Annual Congress, being held December 7-9 in Geneva, Switzerland.
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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.
About EXS-21546
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.