On October 26, 2022 Exscientia plc (Nasdaq: EXAI) reported that new data aimed at enriching for patients that are more likely to respond to its precision-designed CDK7 inhibitor, GTAEXS-617 (‘617) (Press release, Exscientia, OCT 26, 2022, View Source [SID1234622430]). The research confirmed a CDK7-specific pharmacodynamic (PD) biomarker, while revealing potential novel PD markers, and identified an initial novel patient selection gene expression signature that will, in part, be evaluated in its planned Phase 1/2 study. The data are being presented at the 34th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) (ENA 2022) Symposium on Molecular Targets and Cancer Therapeutics, being held October 26-28, 2022, in Barcelona, Spain.
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In this study, researchers leveraged Exscientia’s translational oncology platform, combining AI-based primary cancer tissue profiling with transcriptomics, to understand how cells from diverse patient populations respond to therapy with ‘617. Results demonstrated differential sensitivity in some patient samples, enabling Exscientia to correlate response with individual patient genomic and phenomic profiles. These correlations can then be used to identify which patients are most likely to respond to ‘617 therapy and can be incorporated into upcoming clinical trials.
In addition, the data showed that ‘617 induced less cell death on immune cells than select CDK4/6 and other investigational CDK7 inhibitors, potentially indicating a differentiated clinical safety profile. ‘617 is currently in IND-enabling studies as a potential treatment for transcriptionally addicted cancers.
"We’re excited to highlight new data supporting the power of our translational platform to rapidly assess the activity of new targeted therapies that could lead to improved clinical outcomes for patients," said Gregory Vladimer, VP of Translational Research at Exscientia. "By leveraging our functional precision medicine platform coupled with single cell transcriptomics and AI modeling in primary disease tissue, we believe we are uniquely positioned to enrich studies for patient groups more likely to respond, or not respond, to a therapy, therefore meaningfully improving cancer treatment outcomes for patients."
Poster Presentation Details:
Title: Defining activity and patient selection of a novel CDK7 inhibitor, GTAEXS-617, through AI-supported primary cancer tissue profiling
Poster Session Title: Preclinical Models
Abstract Number: #124
Date/Time: Wednesday, October 26 / 12:00 PM – 8:00 PM CET
GTAEXS-617 is a novel CDK7 inhibitor that has been designed by Exscientia in collaboration with GT Apeiron for high potency, selectivity, bioavailability and safety. CDK7 inhibition combines cell cycle disruption with transcription inhibition, making it an attractive target to overcome common resistance pathways in CDK4/6 inhibition.
Exscientia anticipates submitting a Clinical Trial Application (CTA) by the end of 2022 and initiating a Phase 1/2 clinical trial in multiple solid tumour indications, including ovarian cancer, in the first half of 2023.
The poster is available on Exscientia’s website.