OXFORD, England–(BUSINESS WIRE)–Exscientia plc (Nasdaq: EXAI) today announced clinical trial application (CTA) approval of IGNITE-AI, enabling site activation in its first European country. IGNITE-AI is a Phase 1/2 trial studying EXS-21546 (‘546), Exscientia’s A2A receptor antagonist in combination with anti-PD-1 therapy in patients with immunotherapy relapsed or refractory renal cell carcinoma (RCC) and non-small cell lung cancer (NSCLC). The study will evaluate safety, efficacy, pharmacokinetics and pharmacodynamics in up to 110 patients. Exscientia intends to expand to additional tumour types, including breast cancer, in future trials after assessment of ‘546 activity and validation of its selection biomarkers.
“High adenosine levels in the tumour microenvironment have the potential to suppress immune function, which can inhibit the efficacy of checkpoint inhibitors,” said Dr. Michael Krams, Chief Quantitative Medicine Officer of Exscientia. “We have designed this trial not only to learn about ‘546, but also to enhance our confidence in our patient enrichment strategy. We place a strong emphasis on biomarker qualification, because our goal is to identify the right patients for the right treatment.”
Exscientia used simulation guided clinical trial design to determine the operating characteristics of the two stages of the trial. The first stage will apply a continuous reassessment model to use accruing data from the dose escalation phase to establish the maximum tolerated dose (MTD) of Exscientia’s A2A receptor antagonist. Once the MTD is identified with sufficient confidence, the study will advance to the second stage, where the MTD is applied to an expansion cohort. The goal of the expansion phase is to create evidence of efficacy of ‘546 in combination with a PD-1 inhibitor as well as further enhance confidence in Exscientia’s biomarker signature.
At a medical meeting in December, Exscientia will present data on its novel multi-gene signature for identifying high adenosine patient populations, referred to as the adenosine burden score (ABS). IGNITE-AI is designed to prospectively evaluate the ABS in comparison to patient responses in order to validate its use in patient selection. Once statistical confidence in the ABS has been reached, the Company plans to apply the biomarker signature to directly enrich the patient population in clinical development.
“We are proud to move forward with this industry-leading trial and the first patient study for Exscientia. Exscientia is a precision medicine company, and this trial exemplifies how we are extending our AI-driven, adaptive learning approach that we use in discovery now into development,” said Professor Andrew Hopkins, D.Phil., founder and Chief Executive Officer of Exscientia. “We believe that our precision medicine platform can help us select the right patients, which could allow us to translate the scientific potential for A2A receptor antagonists into clinical results.”
About the Phase 1/2 IGNITE-AI trial
The IGNITE-AI Phase 1/2 trial is a multicentre, open-label, two-stage clinical trial to evaluate safety, pharmacokinetics, pharmacodynamics and efficacy of EXS-21546 in combination with PD-1 inhibition. The Company intends to enrol patients with relapsed or refractory RCC or NSCLC who previously received treatment with an immune checkpoint inhibitor. By evaluating patients that have progressed after checkpoint inhibition therapy, the trial is designed to test whether A2A receptor antagonism will restore the ability of the immune system to respond to checkpoint inhibitors.
The dose escalation portion of the trial will enrol a maximum of 30 patients across up to seven dose levels, depending on how many dose levels are needed to define the maximum tolerated dose (MTD). The dose expansion phase of the trial will commence upon identification of the MTD and will enrol up to 80 patients. The primary efficacy endpoint of the expansion phase is objective response rate (ORR).
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). The molecule was identified in 9 months after testing 163 compounds and is one of the first AI designed drugs in the industry to enter the clinic. 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 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.
Exscientia is headquartered in Oxford (England, U.K.), with offices in Vienna (Austria), Dundee (Scotland, U.K.), Boston (Mass., U.S.), Miami (Fla., U.S.), Cambridge (England, U.K.), and Osaka (Japan).
Exscientia Forward-Looking Statements
This press release contains forward-looking statements as that term is defined in the Private Securities Litigation Reform Act of 1995, including with respect to the progress of discovery and development of candidate molecules, and the timing and progress of, and data reported from, clinical trials of Exscientia’s product candidate EXS-21546. Any statement describing Exscientia’s goals, plans, expectations, or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to a number of risks, uncertainties and assumptions, including those related to: the impact that the COVID-19 pandemic could have on the Company’s business, including the scope, progress and expansion of Exscientia’s product development efforts; the initiation, scope and progress of Exscientia’s and its partners’ planned and ongoing pre-clinical studies and clinical trials and ramifications for the cost thereof; clinical, scientific, regulatory and technical developments; the process of discovering, developing and commercialising product candidates that are safe and effective for use as human therapeutics; and the endeavour of building a business around such product candidates. In light of these risks and uncertainties, and other risks and uncertainties that are described in the Risk Factors section and other sections of Exscientia’s Annual Report on Form 20-F, filed with the Securities and Exchange Commission (SEC) on March 23, 2022 (File No. 001-40850), and other filings that Exscientia makes with the SEC from time to time (which are available at https://www.sec.gov/), the events and circumstances discussed in such forward-looking statements may not occur, and Exscientia’s actual results could differ materially and adversely from those anticipated or implied thereby. Although Exscientia’s forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by the Company. As a result, you are cautioned not to rely on these forward-looking statements.