EXS21546 / Evotec, Recursion Pharma - LARVOL DELTA

Study to Assess EXS21546 in Combination in Patients With Advanced Solid Tumours (clinicaltrials.gov) - P1b/2a | N=6 | Terminated | Sponsor: Exscientia AI Limited | N=110 ➔ 6 | Trial completion date: Mar 2026 ➔ Oct 2023 | Recruiting ➔ Terminated | Trial primary completion date: Sep 2025 ➔ Sep 2023; Emerging data demonstrates challenge for EXS21546 to reach suitable therapeutic index.

Combination therapy • Enrollment change • Metastases • Trial completion date • Trial primary completion date • Trial termination • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Exscientia Details Pipeline Prioritisation Strategy (Businesswire) - "In addition to a validated patient selection strategy, the Company believes a prolonged, high level of target coverage is necessary for therapeutic effect, which has been supported by recently announced peer data. Based on modelling of the clinical and preclinical data, it will be challenging for ‘546 to reach a suitable therapeutic index. The Phase 1/2 trial will be wound down and internal research around the target will be discontinued. Exscientia believes in the A2A mechanism and its value for a potential partner with an existing immunotherapy pipeline. Exscientia will evaluate potential partnerships for its next-generation compounds and precision medicine capabilities."

Clinical • Licensing / partnership • Oncology

Exscientia Business Update for First Quarter 2023 (Businesswire) - "In May 2023, the first patient was dosed in the Phase 1/2 IGNITE clinical trial of EXS21546 (‘546), Exscientia's A2AR antagonist, for the treatment of relapsed/refractory renal cell carcinoma (RCC) and non-small cell lung cancer (NSCLC)."

Trial status • Genito-urinary Cancer • Kidney Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Data from first-in-human study of EXS21546, an A2A receptor antagonist, now progressing into phase 1 in RCC/NSCLC (AACR 2023) - P1 | "Safety and tolerability of our A2AR antagonist EXS21546 were confirmed in a HV study, allowing selection of a starting dose for the ongoing IGNITE Phase 1/2 study. IGNITE trial design was based on extensive simulations to enable the most efficient continuous reassessment method settings, and will allow further verification of the patient enrichment biomarker strategy."

IO biomarker • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • ADORA2A • CD8

Identification of transcript adenosine fingerprint to enrich for A2AR and PD-1 inhibition responders (AACR 2023) - P1 | "This paradigm is gaining importance during the early clinical lifecycle of a new potential drug to improve patient-centric trial designs, drive clinical success and eventually increase approval rates - enlarging the therapeutic arsenal available for oncology patients.To optimize the chance of success with our A2AR-selective antagonist, EXS-21546 (546; NCT04727138, discovered in collaboration with Evotec), we have identified an adenosine-induced immunosuppression biomarker signature (adenosine burden score or ABS) for clinical trial patient selection that also correlates with checkpoint inhibitor (CI) response prediction in ex vivo primary models.Here we present transcriptional and functional data mapping adenosine burden at the single cell level, and investigate subsequent modulation through antagonism of A2AR with 546, combination effects with CI, to prioritize patients for 546+CI therapy. By leveraging disease-relevant primary human tissues together with matched..."

IO biomarker • Oncology

Data Presented at AACR 2023 Highlights Exscientia’s Clinical and Preclinical Development (Businesswire) - "Exscientia plc...announced four presentations at the American Association for Cancer Research (AACR) Annual Meeting 2023....Abstract Number: #CT114:...Phase 1 objectives were achieved in a healthy volunteer study...allowing selection of a starting dose for the ongoing IGNITE Phase 1/2 study ​​in combination with a PD-1 inhibitor in patients with relapsed/refractory renal cell carcinoma (RCC) and non-small cell lung cancer (NSCLC)....The poster highlights the IGNITE trial design, which is based on extensive simulations to enable the most efficient continuous reassessment method settings to predict and most accurately evaluate the anti-tumoural effect of ‘546 in combination with checkpoint inhibition as well as any dose limiting toxicity...The first patient is expected to be enrolled in the first half of 2023."

Trial status • Genito-urinary Cancer • Kidney Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Thoracic Cancer

Data Presented at AACR 2023 Highlights Exscientia’s Clinical and Preclinical Development (Businesswire) - "Exscientia plc...announced four presentations at the American Association for Cancer Research (AACR) Annual Meeting 2023....Abstract Number: #2151:...In this poster, Exscientia reveals its internally and preclinically developed adenosine burden score (ABS; first revealed at the end of 2022) is based on B-cell biology and that EXS21546 (‘546), Exscientia’s selective clinical stage A2AR antagonist, reverts effects of adenosine analogues ex vivo in patient tissue samples and other complex models...Analysis of public human and mouse data confirms an enrichment of ABS-high samples are among those less likely to respond to checkpoint inhibition."

Preclinical • Oncology

Exscientia Business and Financial Update for the Full Year 2022 (Businesswire) - "Exscientia anticipates enrolling the first patient in a Phase 1/2 trial for its CDK7 inhibitor, GTAEXS617 (‘617), in the first half of 2023; Four posters will be presented at AACR from April 14-19, 2023, highlighting data from the ‘546 and ‘539 programmes as well as data from the Company's precision medicine platform leveraged for biomarker and target discovery."

Clinical data • Trial status • Oncology • Solid Tumor

Exscientia to Present Data Highlighting Pipeline and Precision Medicine Platform at AACR (Businesswire) - "Exscientia plc...announced that four abstracts have been accepted for poster presentation at the upcoming American Association for Cancer Research (AACR) Annual Meeting 2023, being held April 14-19, 2023, at the Orange County Convention Center in Orlando, FL. These abstracts highlight the components of Exscientia's approach to precision discovery, design and personalised medicine as well as planned innovation in the clinic....Preclinical data has shown that ‘539 has potent anti-proliferative activity in in vitro models of small cell lung cancer (SCLC), with anti-tumour activity observed in selected SCLC xenograft tumour-bearing mice."

Preclinical • Trial status • Genito-urinary Cancer • Kidney Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Small Cell Lung Cancer • Solid Tumor

Enriching for response: patient selection criteria for A2AR inhibition by EXS-21546 through ex vivo modelling in primary patient material (ESMO-IO 2022) - P1 | "Conclusions Combining deep learning of single cell functional and multi-omics profiling data of disease relevant primary model systems, we model the association of the immune response potential to A2AR antagonism in cancer to define a biomarker signature with the potential to identify patients likely to benefit from A2AR antagonism. This could be implemented in future studies of our clinical candidate '546 to deliver the right drug at the right time to the right patients."

IO biomarker • Preclinical • Oncology

Enriching for adenosine antagonist patient responses through deep learning (AACR 2022) - P1 | "Combining single cell transcriptomic and functional response data, we demonstrate preclinical mechanistic studies of A2AR antagonism on infiltrating immune cells, with the ultimate aim of discovering predictive algorithms to enrich patients more likely respond to adenosine pathway inhibitors. Patient selection gene signatures are functionally validated using a high content imaging platform with proven translational capabilities (Kornauth et al, Cancer Disc., 2021), demonstrating the association of anti-cancer immune activity with inhibition of adenosine signaling by EXS21546. Signatures and patient selection algorithms are cross-validated with publicly available data. Gathering multiple layers of data from primary tumor tissues, we reveal and map the association of immune response potential to A2AR inhibition in cancer.Patient stratification gene signatures identified have the aim to be implemented in future studies of our candidate A2ARi EXS21546, to deliver the..."

Clinical • Oncology • ADORA2A • ENTPD1

Exscientia Presents Novel Immuno-Oncology Biomarker for EXS-21546 at the ESMO I-O Annual Congress (Businesswire) - "Exscientia plc...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 data are being presented at the ESMO Immuno-Oncology Annual Congress, being held December 7-9 in Geneva, Switzerland....'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."

Biomarker • Preclinical • Oncology • Solid Tumor

Exscientia Receives First CTA Approval to Initiate IGNITE-AI, a Phase 1/2 Trial of EXS-21546 in Patients with Advanced Solid Tumours (Businesswire) - "Study will enrol up to 110 patients in immunotherapy relapsed/refractory RCC and NSCLC...CTA for GTAEXS-617, Exscientia's CDK7 inhibitor, on track to be submitted in December 2022....Exscientia plc...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)....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....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)."

Clinical data • New P1/2 trial • Genito-urinary Cancer • Kidney Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Exscientia Business and Financial Update for the Third Quarter 2022 (Businesswire) - "Exscientia announced novel patient stratification methods and biomarker data supporting development of GTAEXS-617 ('617) at the 34th EORTC-NCI-AACR (ENA) Annual Symposium...CTA submission expected by year-end 2022...Anticipate Phase 1/2 study to begin in the first half of 2023 in multiple solid tumour indications, including ovarian cancer; The Company remains on track to initiate 'IGNITE-AI,' a Phase 1b/2 study of its A2A programme EXS-21546 ('546) by year-end 2022...Planned clinical study to look at combination therapies, including checkpoint inhibitors...Additional data on patient selection modelling to be presented at a medical meeting by year-end 2022"

New P1/2 trial • P1/2 data • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor

Exscientia Reports Topline Data From EXS-21546 Phase 1a Study Demonstrating Targeted A2A Receptor Signaling Inhibition in Healthy Volunteers (Businesswire) - P1a | N=64 | NCT04727138 | Sponsor: Exscientia Limited | "Topline data from this healthy volunteer study confirmed Exscientia’s target product profile design, including potency, high receptor selectivity and expected low brain exposure with no CNS adverse events reported, supporting advancement of EXS-21546 to a Phase 1b/2 study in patients with solid tumours exhibiting high adenosine signatures....The study showed that observed human PK for EXS-21546 was in line with what had been designed for and predicted in preclinical modeling, supporting a twice-daily (BID) dose for continuous A2A receptor inhibition over a dosing interval...Based on these results, Exscientia expects to initiate a Phase 1b/2 study of EXS-21546 in patients with high adenosine signature solid tumours in the second half of 2022. The Phase 1b/2 study is being designed to evaluate higher doses of EXS-21546. The Company expects to share additional data from this Phase 1a study at future medical meetings."

New P1/2 trial • P1 data • Oncology

Exscientia Business Update for First Quarter 2022 (Businesswire) - "Co-owned programmes: GTAEXS-617 CTA submission expected by year-end 2022, progress in generating data in additional tumour types to inform planned Phase I clinical trial in cancer patients. CTA and IND-enabling studies are ongoing, including pre-clinical studies to explore potential dosing regimens for planned clinical trials; Wholly and majority owned programmes: EXS-21546 top-line data for Phase 1 healthy volunteer study on track for the first half of 2022. Anticipate commencing Phase 1b/2 study in patients with high adenosine signature cancers in the second half of 2022."

New P1 trial • New P1/2 trial • P1 data • Oncology

3-part Study to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of EXS21546 (clinicaltrials.gov) - P1 | N=64 | Completed | Sponsor: Exscientia Limited | Recruiting ➔ Completed

Trial completion • Oncology

3-part Study to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of EXS21546 (clinicaltrials.gov) - P1 | N=84 | Recruiting | Sponsor: Exscientia Limited | Trial completion date: Dec 2021 ➔ Apr 2022 | Trial primary completion date: Dec 2021 ➔ Apr 2022

Trial completion date • Trial primary completion date • Oncology

Exscientia to Highlight Precision Medicine Platform and Pipeline Data at the American Association of Cancer Research Annual Meeting 2022 (Businesswire) - "These encouraging data suggest that stratification of patient gene signatures could be implemented in future studies of EXS-21546 to identify patients that may respond optimally to A2aR targeted therapies....GTAEXS-617, currently in IND-enabling studies as a potential treatment for transcriptionally addicted cancers, including ovarian and breast cancer. Preclinical data show that ‘617 has potent anti-proliferative activity in in vitro models of high-grade serous ovarian cancer (HGSOC) and triple negative breast cancer (TNBC)....These encouraging data support further research of patient-focused drug development using human disease relevant models and deep learning to better understand the target landscape for ovarian cancer and the potential for the development of novel therapeutic approaches."

Preclinical • Breast Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer

3-part Study to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of EXS21546 (clinicaltrials.gov) - P1; N=84; Recruiting; Sponsor: Exscientia Limited; Trial completion date: Sep 2021 ➔ Dec 2021; Trial primary completion date: Sep 2021 ➔ Dec 2021

Clinical • Trial completion date • Trial primary completion date • Oncology

[VIRTUAL] EXS21546, a non-CNS penetrant A2AR-selective antagonist for anti-cancer immunotherapy (AACR 2021) - "Together, these data indicate the potential for EXS21546 may have a role in cancer therapy. EXS21546 has completed pre-IND studies in preparation for initiation of first-in-human clinical studies."

Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CD8

Evotec And Exscientia Announce Start of Human Clinical Trials of Novel Immuno-Oncology Drug (Yahoo Finance) - “Evotec…announced the most advanced asset arising from their joint venture with Exscientia has entered human clinical trials. The A2a receptor antagonist, which is in development for adult patients with advanced solid tumours, was co-invented and developed between Exscientia and Evotec, including application of Exscientia's next generation 3-D evolutionary AI-design platform, Centaur Chemist(R). The drug candidate has potential for best-in-class characteristics, with high selectivity for the target receptor, bringing together potential benefits of reduced systemic side effects as well as minimal brain exposure to avoid potential undesired centrally-mediated side effects.”

Trial status • Oncology

3-part Study to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of EXS21546 (clinicaltrials.gov) - P1; N=84; Recruiting; Sponsor: Exscientia Limited

Clinical • New P1 trial • Oncology