EXS74539 / Recursion Pharma - LARVOL DELTA

Recursion Announces Two Key Investigational Oncology Drugs Advancing to Clinical Trials, Targeting High Unmet Needs...Small-Cell Lung Cancer, & More (GlobeNewswire) - "Recursion also announced that the U.S. Food and Drug Administration (FDA) has cleared an investigational new drug (IND) application for a Phase 1/2 clinical trial of REC-4539, a potential best-in-class LSD1 inhibitor for small-cell lung cancer (SCLC) and other potential indications. For REC-4539, the total addressable population in the US+EU5 for extensive stage SCLC is approximately 45,000 patients annually....The first patient is expected to be dosed in the Phase 1/2 ENLYGHT clinical trial in H1 2025. The trial willevaluate REC-4539 as monotherapy and in combination with durvalumab in patients with SCLC."

IND • New P1/2 trial • Small Cell Lung Cancer • Solid Tumor

In Vivo Pharmacokinetics, Pharmacodynamics and Anti-tumour Efficacy of EXS74539: A Novel, Reversible LSD1 Inhibitor for Acute Myeloid Leukaemia (EORTC-NCI-AACR 2024) - "We describe in vitro and in vivo concentration-dependent gene expression correlations associated with LSD1 sensitivity and detailed characterisation of PK/PD and anti-tumour activity of '539 in a AML xenograft model. These data, combined with '539's reversible mechanism-of-action and anticipated suitable human half-life, may provide an opportunity to better adapt drug regimens for maximal target engagement while managing on-target dose-limiting thrombocytopenia."

PK/PD data • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Data highlights efficacy of ‘539 in a preclinical AML model, with limited impact on platelet levels (Businesswire) - "539 is a novel, potent, selective and reversible LSD1 inhibitor, with a highly differentiated profile and designed to be brain penetrant, expected to enter the clinic in early 2025. The poster highlights that by combining ex vivo perturbation of primary human acute myeloid lymphoma (AML) samples with ‘539 and omics profiling, 12 potential pharmacodynamic (PD) biomarker gene candidates were identified that correlate with LSD1 inhibitor activity. Upregulation of the identified biomarker gene candidates was confirmed in an in vivo AML xenograft model post ‘539 treatment. Treatment of the in vivo model with the reversible inhibitor ‘539 resulted in limited platelet level effects, highlighting how ‘539 was designed to maximise target engagement while limiting thrombocytopenia."

New trial • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

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 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

Exscientia Initiates Clinical Study to Further Evaluate Functional Precision Medicine Platform in Cancer Patients (Businesswire) - "Exscientia plc...announced the initiation of EXCYTE-2, an observational clinical study in acute myeloid leukaemia (AML) to investigate the relationship between ex vivo drug response (EVDR) measured in primary blood or bone marrow samples using the company’s deep learning, single-cell precision medicine platform and actual patient clinical response....In addition, the study allows for the evaluation of activity of EXS74539 (‘539), Exscientia’s LSD1 inhibitor, in a large clinically annotated sample set."

Trial status • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Solid Tumor

Determining anti-cancer efficacy of a reversible LSD1 inhibitor, EXS74539, in primary AML tissues with limited thrombocytopenic effects (ESMO 2023) - "Conclusions Our preclinical data demonstrated ex vivo efficacy of '539 against AML blast cells and supported the combinatorial potential of '539 with first line clinical AML treatment strategies. Leveraging the reversibility of '539 allowed the design of adapted drug regimens, to preserve the safety profile of this inhibitor on non-transformed healthy cells."

Clinical • Acute Myelogenous Leukemia • Oncology

Exscientia to Present New Preclinical Data for AI-designed LSD1 and MALT1 Inhibitors at ESMO 2023 (Businesswire) - "Exscientia plc...announced two abstracts to be presented at the upcoming European Society for Medical Oncology (ESMO) Congress 2023 from October 20-24, 2023 in Madrid, Spain....Leveraging primary human material and Exscientia’s proprietary precision medicine platform, the Company confirmed ‘539’s general efficacy, demonstrating that ‘539 induces AML cell differentiation marker expression when used on primary AML patient tissue ex vivo. Combination data with first line AML and targeted therapies will be presented....Significant tumour growth inhibition was observed for ‘565 in vivo in activated B-cell diffuse large B-cell lymphoma (ABC-DLBCL) xenograft models. Significant synergistic effects were observed for combination ‘565 and the BTK inhibitor ibrutinib in a xenograft model with low sensitivity to either single agent."

Preclinical • Acute Myelogenous Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Exscientia Details Pipeline Prioritisation Strategy (Businesswire) - "Prioritising CDK7 and LSD1 advancement...EXS74539 (LSD1): The Company will further prioritise the advancement of its LSD1 inhibitor into the clinic; IND submission expected in the first quarter of 2024...The Company intends to initiate a Phase 1 healthy volunteer trial in the first half of 2024 that could support more efficient development of ‘539 in multiple indications and in combination with other therapies; LSD1-related data from Exscientia's precision medicine technology will be presented at ESMO in October, including data in primary AML tissues....EXS73565 (MALT1): Exscientia’s MALT1 inhibitor is progressing through IND/CTA enabling studies and the Company expects to be able to provide further updates in the first half of 2024....Data will be presented at ESMO in late October highlighting '565's precision design and its potential for low drug-drug interaction."

IND • New P1 trial • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Characterizing antitumor responses to EXS-74539, a novel, reversible LSD1 inhibitor with potential in small-cell lung cancer (AACR 2023) - "The reversible LSD1 inhibitor, EXS-74539, is a potent inhibitor of SCLC cell line proliferation and shows in vivo efficacy. Characterizing SCLC cell line sensitivity in vitro and in vivo identified gene signatures that may have use as markers of sensitivity, which we are currently characterizing and validating in human SCLC patient samples.Rudin et al., Nat Rev Cancer, 2019"

Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor • ASCL1 • KDM1A • NEUROD1 • NEUROD1 • POU2F3 • YAP1

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: #6290:...In vitro sensitivity analysis of small cell lung cancer (SCLC) cell line models to ‘539 alone was shown to not sufficiently predict in vivo response; researchers believe that predicting in vivo tumour response to ‘539 is critical to ensuring optimal use of the compound. Combining transcriptional and functional responses in vitro, however, may overcome this."

Preclinical • Lung Cancer • Oncology • Small Cell Lung 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 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

Exscientia Announces Expansion of its Precision Oncology Pipeline (Businesswire) - "Exscientia plc...announced two new wholly-owned precision oncology development candidates, EXS74539 (‘539), an LSD1 inhibitor, and EXS73565 ('565), a MALT1 protease inhibitor....IND-enabling studies are underway and the Company expects to provide an update on clinical development plans leveraging Exscientia's personalised medicine platform in the second half of 2023....Additionally, in vivo studies of '539 have shown favourable activity in small cell lung cancer (SCLC) xenograft models, with dose dependent inhibition of tumour growth. Studies have also shown a favourable absorption, distribution, metabolism, and excretion (ADME) profile, with a shorter predicted human half-life than some LSD1 inhibitors currently in clinical trials....Exscientia will present data on the discovery and development of '539 at an upcoming scientific conference in the first half of 2023."

New molecule • Preclinical • Lung Cancer • Oncology • Small Cell Lung Cancer