First Patient Enrolled in Phase 1/2 “ELUCIDATE” Trial Assessing GTAEXS617 in Advanced Solid Tumours
- Precision-designed potent and selective CDK7 inhibitor with potential for improved therapeutic index -
- Preclinically discovered non-invasive PD biomarker to be confirmed alongside clinical trial -
OXFORD, England--(BUSINESS WIRE)--Exscientia Ltd. (Nasdaq: EXAI) today announced that it has enrolled the first patient in its Phase 1/2 “ELUCIDATE” (GTAEXS617-001) study evaluating GTAEXS617 (‘617), Exscientia’s precision-designed CDK7 inhibitor, for the treatment of advanced solid tumours. The clinical trial will evaluate the safety, efficacy and pharmacokinetics of ‘617 across multiple ascending doses in patients with advanced solid tumours including head and neck cancer, colorectal cancer, pancreatic cancer, non-small cell lung cancer (NSCLC), HR+/HER2- breast carcinoma and ovarian cancer. ‘617 is a novel CDK7 inhibitor that has been designed by Exscientia in collaboration with GT Apeiron for high potency, selectivity, oral bioavailability and safety.
“We are excited to begin the clinical evaluation of another AI-designed molecule at Exscientia,” said Dr. Michael Krams, Chief Quantitative Medicine Officer at Exscientia. “‘617 was created to solve critical design challenges not met by traditional drug discovery methods with a focus on on-target potency, selectivity and safety. Combined with our unique ability to gather data from primary patient samples to predict response, we believe our ‘617 programme exemplifies the power of the various ways in which we create value through our precision medicine platform. We look forward to enrolling additional patients into the ELUCIDATE trial and anticipate that ‘617, if approved, could meaningfully improve treatment outcomes for patients.”
As in Exscientia's IGNITE trial evaluating its A2AR antagonist, EXS21546, the company used simulation guided clinical trial design to determine the operating characteristics of the two stages of the trial. The dose escalation (Phase 1) portion of the study will characterise the safety profile of ‘617 and establish the recommended Phase 2 dose (RP2D) both as monotherapy and in combination with selected standard of care regimens. The dose expansion (Phase 2) portion of the study will evaluate the preliminary anti-tumour activity of ‘617 as monotherapy and in combination with standard of care.
Exscientia previously highlighted novel ex vivo patient sample response data at the EORTC-NCI-AACR (ENA) Symposium in October 2022 identifying and confirming CDK7-specific pharmacodynamic biomarkers in cancer and immune cells and identifying high and low responder groups from patient samples across the indications tested ex vivo. Leveraging this translational data has the potential to eventually predict ‘617 treatment response among individual patients, therefore increasing the chances of treatment success. Alongside the evaluation of ‘617 in the ELUCIDATE trial programme, Exscientia and GT Apeiron will also generate data, including clinical endpoints, peripheral and tumour multi-omics, and correlate data and response to previously collected ex vivo results to further support the value of Exscientia's precision medicine platform.
About the Phase 1/2 ELUCIDATE trial
The ELUCIDATE trial is a multicentre, open-label, two-stage clinical trial to evaluate safety, pharmacokinetics, pharmacodynamics and efficacy of ‘617 administered orally as monotherapy and in combination with standard of care therapies. The company is enrolling patients with solid tumours who have advanced, recurrent or metastatic disease and have failed standard of care.
Both the monotherapy and combination therapy dose escalation portion of the trial will enrol patients across up to seven dose levels, depending on how many dose levels are needed to define the RP2D. The dose expansion phase of the trial will commence upon identification of the RP2D. The primary efficacy endpoint of the expansion phase is objective response rate (ORR).
CDK7 inhibition combines cell cycle disruption with transcription inhibition, making it an attractive target to overcome common resistance pathways in CDK4/6 inhibition, which only targets the cell cycle. ‘617 has the potential to overcome significant safety and efficacy limitations of existing treatments due to its differentiated reversibility and potentially reduced gastrointestinal (GI) toxicity.
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.
About GT Apeiron
GT Apeiron is redefining medical discovery, using artificial intelligence to streamline the drug development process—from target selection to clinical trials. With strategic locations in Shanghai and the San Francisco Bay Area, and significant partnerships in Europe, Apeiron integrates talent and cutting-edge technologies spanning multiple regions. We believe that by pushing the frontiers of biomedical innovation and engaging talent globally we can create breakthrough medicines for the highest unmet medical needs.
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 timing and progress of, and data reported from, clinical trials of ‘617 and Exscientia’s other product candidates; and any potential benefits to patients from ‘617, if approved. Any statement describing Exscientia’s goals, plans, expectations, 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 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 judgement 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.
Source: Exscientia plc