REC-617 / Recursion Pharma - LARVOL DELTA

CDK7 inhibition as a synthetic lethal strategy in Rb-deficient ER+/HER2- breast cancer and sarcoma cells resistant to CDK4/6 inhibitors (AACR 2025) - "This study aims to evaluate the efficacy of REC-617 in both ER+/HER2-breast cancer and STS cell lines, especially within Rb-deficient contexts, as a therapeutic strategy for overcoming resistance and broadening targeted treatment options. CDK4/6i-resistant cell lines were generated by progressively exposing MCF7 breast cancer cells to increasing concentrations of palbociclib (1.2-4.8 μmol/L), ribociclib (1.2-4.8 μmol/L), and abemaciclib (0.5 and 1 μmol/L). These findings demonstrate that CDK7 inhibition via REC-617 offers a potent synthetic lethal approach in Rb-deficient, CDK4/6i-resistant ER+/HER2-breast cancer and soft tissue sarcomas. Reduced Rb expression may be predictive of the level of response to REC-617, thus providing a targeted treatment option for overcoming resistance in both cancer types and addressing a critical need in resistant ER+/HER2-breast cancers and soft tissue sarcomas."

Synthetic lethality • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • CCNB1 • CDC25C • CDK1 • CDK2 • ER • GNRP • HER-2 • RB1 • TP53BP1

Recursion Reports Interim Phase 1 Clinical Data for REC-617 Monotherapy, a Potential Best-in-Class CDK7 Inhibitor, With Encouraging Patient Response and Favorable Tolerability (GlobeNewswire) - P1/2 | N=170 | ELUCIDATE (NCT05985655) | Sponsor: Exscientia AI Limited | "These results were presented today after market close at an AACR Special Conference in Cancer Research....As of the November 15, 2024 data cutoff, preliminary findings include 18 patients with advanced solid tumors who were response evaluable in the monotherapy dose-escalation phase....REC-617 was generally well-tolerated across all dose levels, with no discontinuations due to adverse events (AEs)....A confirmed durable partial response (PR) by RECIST on REC-617 monotherapy was achieved in a patient with metastatic, platinum-resistant ovarian cancer....Combination studies are expected to initiate for ELUCIDATE in H1, 2025.....Four additional patients achieved durable (up to 6 months of treatment) response of stable disease (SD) as best response across multiple dose levels....Three CRC patients (6L-7L) and one NSCLC patient (4L)."

P1 data • Trial status • Colorectal Cancer • Non Small Cell Lung Cancer • Ovarian Cancer

Exscientia Business Update for Second Quarter and First Half 2024 (Businesswire) - "Exscientia expects to transition to the dose expansion phase of ELUCIDATE in the second half of this year or early next year, starting with the evaluation of ‘617 in HR+/HER2- breast cancer in combination with a selective estrogen receptor degrader (SERD); EXS74539 (‘539), Exscientia’s highly differentiated, brain penetrant LSD1 inhibitor, continues to advance towards the clinic, with an IND expected to be submitted later this year. The Company expects to initiate a Phase 1/2 clinical trial in early 2025."

IND • New P1/2 trial • Trial status • Breast Cancer • Hematological Malignancies • Oncology • Solid Tumor

Exscientia Acquires Full Rights to Potential Best-in-Class CDK7 Inhibitor Ahead of Phase 1 Dose Escalation Data Readout (Businesswire) - "Exscientia plc...today announced it has reached an agreement to acquire GT Apeiron’s share of its oral CDK7 inhibitor programme, gaining full control of GTAEXS617 (‘617) and all related intellectual property. The monotherapy dose escalation phase of ELUCIDATE is designed to assess the safety, pharmacokinetics and pharmacodynamics of '617 in advanced solid tumours. Recruitment for the trial is progressing well with monotherapy dose escalation data on track to readout in the second half of 2024. In late 2024/early 2025, the study will transition to a combination dose escalation phase. The first tumour type to be explored in this portion of the study is expected to be HR+/HER2- breast cancer patients that have progressed on CDK4/6 inhibitors, assessing ‘617 in combination with a selective estrogen receptor degrader (SERD)."

Licensing / partnership • P1/2 data • Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

Exscientia Business Update for First Quarter 2024 (Businesswire) - "Patient enrolment for the dose escalation phase of the Company’s adaptive Phase 1/2 ELUCIDATE trial evaluating ‘617, a potential best-in-class CDK7 inhibitor for the treatment of advanced solid tumours, is ongoing. Exscientia anticipates moving into a combination phase of the trial in the second half of 2024. The Company expects to announce topline pharmacokinetics and safety data from the dose escalation phase of the trial in the second half of 2024. EXS74539 (‘539), Exscientia’s highly differentiated LSD1 inhibitor, is advancing through IND/CTA-enabling studies. The Company anticipates submitting an IND or CTA in the third quarter of 2024, with the goal to initiate a Phase 1/2 clinical trial in AML patients by the end of 2024."

IND • New P1/2 trial • P1/2 data • Trial status • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Solid Tumor

Exscientia Business and Financial Update for the Full Year 2023 (Businesswire) - "Recent advancements in the Company’s pipeline, collaborations and operations, as well as financial results for the fourth quarter and full year 2023, are summarised below. Exscientia will host a conference call Thursday, March 21 at 12:30 p.m. GMT / 8:30 a.m. EDT...Patient enrolment is continuing to progress for the dose escalation phase of ELUCIDATE, the adaptive Phase 1/2 trial studying ‘617...Company expects to announce a transition from the dose escalation to dose expansion phase in the second half of 2024; EXS74539 (‘539), a highly differentiated LSD1 inhibitor, is continuing through IND/CTA enabling studies, and the Company anticipates initiating a Phase 1 clinical trial in cancer patients in 2024...EXS73565 (‘565), the Company’s differentiated MALT1 inhibitor, precision designed with selectivity over UGT1A1, is also advancing through IND/CTA-enabling studies. The Company expects to provide further updates in 1H 2024."

New P1 trial • Preclinical • Trial status • Hematological Malignancies • Oncology • Solid Tumor

ELUCIDATE: Study to Assess GTAEXS617 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=170 | Recruiting | Sponsor: Exscientia AI Limited

Metastases • New P1/2 trial • Breast Cancer • Colorectal Adenocarcinoma • Gastrointestinal Cancer • Head and Neck Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • CD4 • CDK6 • HER-2

First Patient Enrolled in Phase 1/2 “ELUCIDATE” Trial Assessing GTAEXS617 in Advanced Solid Tumours (Businesswire) - "Exscientia plc...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."

Trial status • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Gynecologic Cancers • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor • Thoracic Cancer

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 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

Defining activity and patient selection of a novel CDK7 inhibitor, GTAEXS-617, through AI-supported primary cancer tissue profiling (AACR-NCI-EORTC 2022) - "Primary cancer samples from various indications had a broad differential sensitivity to '617, with specific sensitivity in high grade ovarian cancer versus low grade. Ex vivo cancer cell sensitivity differences in various ovarian cancer grades, as identified by correlation of phenotypic response to differential single cell transcriptomics after '617 perturbation, indicates a potential stratification point that could be used for patient enrichment in clinical trials. Further, '617 displayed less cytotoxic effects on the immune compartment than other CDK7 and CDK4/6 inhibitors."

Clinical • Breast Cancer • Hematological Malignancies • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Ovarian Cancer • Solid Tumor • HER-2

Exscientia Presents Novel Patient Stratification and Biomarker Data for GTAEXS-617 at the 34th EORTC-NCI-AACR Annual Symposium (Businesswire) - "Exscientia plc...today highlighted new data aimed at enriching for patients that are more likely to respond to its precision-designed CDK7 inhibitor, GTAEXS-617 (‘617)....The data are being presented at the 34th EORTC-NCI-AACR (ENA 2022) Symposium on Molecular Targets and Cancer Therapeutics, being held October 26-28, 2022, in Barcelona, Spain....Results demonstrated differential sensitivity in some patient samples, enabling Exscientia to correlate response with individual patient genomic and phenomic profiles....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....Initiating a Phase 1/2 clinical trial in multiple solid tumour indications, including ovarian cancer, in the first half of 2023."

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

Exscientia Presents Novel Patient Stratification and Biomarker Data for GTAEXS-617 at the 34th EORTC-NCI-AACR Annual Symposium (Businesswire) - "Exscientia plc...highlighted new data aimed at enriching for patients that are more likely to respond to its precision-designed CDK7 inhibitor, GTAEXS-617 (‘617)...The data are being presented at the 34th EORTC-NCI-AACR (ENA 2022) Symposium on Molecular Targets and Cancer Therapeutics, being held October 26-28, 2022...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....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."

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

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

AI-driven discovery and profiling of GTAEXS-617, a selective and highly potent inhibitor of CDK7 (AACR 2022) - "In summary, Excientia’s AI platform enabled rapid and highly efficient discovery of ‘617, an orally bioavailable CDK7 inhibitor, demonstrating potent anti-tumour activity in vivo and preferential activity against primary human tumour cells vs non-transformed immune cells. These data support the advancement of ‘617 towards clinical development."

Breast Cancer • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor • Triple Negative Breast Cancer • CDK7

Exscientia Business Update for Fourth Quarter and Full Year 2021 (Businesswire) - "Entered into IND-enabling studies for GTAEXS-617, a CDK7 inhibitor co-owned with GT Apeiron; IND/CTA submission expected by year-end 2022; additional translational data in several tumour types to be presented at the April 2022 American Association of Cancer Research (AACR) Annual Meeting and throughout 2022."

IND • Preclinical • Oncology • Solid Tumor

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