REC-3565 / Recursion Pharma - LARVOL DELTA

Dose Determining Study of EXS73565 in Participants With Relapsed or Refractory B-Cell Malignancies (clinicaltrials.gov) - P1 | N=50 | Recruiting | Sponsor: Exscientia AI Limited

New P1 trial • Hematological Malignancies • Oncology

Recursion Reports First Quarter 2025 Financial Results and Provides Business Update (GlobeNewswire) - "Upcoming milestones: REC-3565 (MALT1): Early Phase 1 safety and PK monotherapy data expected in 2H26; REV102 (ENPP1): Phase 1 initiation expected in 2H26."

New P1 trial • P1 data • Hematological Malignancies

Recursion Announces First Patient Dosed in Phase 1 Clinical Study of REC-3565, a Selective MALT1 Inhibitor for Relapsed or Refractory B-cell Lymphomas (GlobeNewswire) - "Recursion...today announced that the first patient has been dosed in the Phase 1 EXCELERIZE clinical study evaluating REC-3565 for the treatment of relapsed or refractory B-cell lymphomas."

Trial status • B Cell Lymphoma

Recursion Announces Two Key Investigational Oncology Drugs Advancing to Clinical Trials, Targeting High Unmet Needs in Hematologic Malignancies, Small-Cell Lung Cancer, & More (GlobeNewswire) - "Recursion...announced today that the UK Medicines and Healthcare Products Regulatory Agency (MHRA) has cleared a clinical trial application (CTA) for a Phase 1 clinical trial of REC-3565, a potential best-in-class MALT1 inhibitor for B-cell malignancies. For REC-3565, the total addressable population could include a range of hematological indications, with approximately 41,000 relapsed and/or refractory (R/R) patients with chronic lymphocytic leukemia (CLL) and B-cell lymphomas in the US+EU5 annually....The first patient is expected to be dosed in the Phase 1 EXCELERIZE clinical trial in Q1 2025. The trial will evaluate the safety/tolerability of REC-3565 and provide a recommendation for dosing in later combination studies with standard of care agents for B-cell malignancies."

New P1 trial • B Cell Lymphoma • Chronic Lymphocytic Leukemia

Combining next-generation BTK and MALT1 inhibitors to enhance efficacy and therapeutic utility in B-cell malignancies (EORTC-NCI-AACR 2024) - "We assess the potential of the next generation BTKi, zanubrutinib, combined with the MALT1i, EXS73565 ('565), to provide deeper, more durable tumour responses.Material and '565, a highly selective MALT1i clinical candidate with low UGT1A1 inhibition risk, and zanubrutinib, a selective BTKi approved for multiple B-cell malignancies but not diffuse large B-cell lymphoma (DLBCL), were used in this study. Combining '565 and zanubrutinib in models of B-cell malignancies provided deeper, more durable efficacy than either agent alone, including in ABC-DLBCL where BTKi are not currently approved. The selective profile of '565 and zanubrutinib may maximise the therapeutic index of MALT1 and BTK inhibition in combination, providing scope for enhanced efficacy for patients with B-cell malignancies."

Clinical • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • MALT1 • UGT1A1

Demonstrated combination potential for MALT1 and BTK inhibitors in models of B-cell malignancies (Businesswire) - "EXS73565 (‘565) is a potent, selective allosteric MALT1 inhibitor designed to have an improved safety profile, with clinical studies expected to start in early 2025. Combining MALT1 inhibitors, such as ‘565, with BTK inhibitors has the potential to provide enhanced efficacy in B-cell malignancies, by greater inhibition of pathogenic nuclear factor-kappa B (NF-kB) signalling and addressing BTK-resistance mechanisms. Exscientia researchers combined ‘565 with the BTK inhibitor zanubrutinib and observed deeper, more durable efficacy responses in xenograft models of B-cell malignancies, with long-lasting tumour eradication seen for activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL)."

New trial • Preclinical • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology

Exscientia Business Update for First Quarter 2024 (Businesswire) - "Based on patient unmet need, supporting preclinical data and the unique precision designed properties of Exscientia’s MALT1 inhibitor, EXS73565 (‘565), the Company is preparing to submit an IND or CTA in the second half of 2024 to study ‘565 in a Phase 1/2 clinical trial in B-cell malignancies, including CLL, which Exscientia expects to launch in early 2025....EXS4318 (‘4318), a potential first-in-class PKC-theta inhibitor designed by Exscientia and in-licensed by Bristol Myers Squibb, has shown positive early results in its Phase 1 study and has the potential to be a first-in-class immunology drug...Exscientia retains rights to receive milestone payments and potential royalties for ‘4318."

IND • Licensing / partnership • New P1/2 trial • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

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

Characterisation of EXS73565: A potent and selective MALT1 inhibitor with low drug-drug interaction risk and potential in lymphoma (ESMO 2023) - "In vivo efficacy of '565 was assessed in mouse xenograft models, alone and in combination with the BTK inhibitor ibrutinib. Conclusions We describe the characterisation of EXS73565, an allosteric inhibitor of MALT1 which is currently in IND/CTA-enabling studies. Importantly, we show that '565 exhibits a low drug-drug interaction and hyperbilirubinemia risk, offering the prospect of fully exploring the potential of MALT1 inhibition as a monotherapy and/or in combination with other targeted agents."

Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • IL10 • MALT1

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

Exscientia Announces Expansion of its Precision Oncology Pipeline (Businesswire) - "EXS73565 ('565) is a mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) protease inhibitor with potential applications in haematology....In vivo studies of '565 have shown anti-tumour activity in mouse models and favourable pharmacokinetics both as monotherapy and in combination with ibrutinib. Toxicology studies have shown that ‘565 has an acceptable therapeutic index, with the ability to maintain high levels of potency, selectivity and safety benchmarks while avoiding meaningful inhibition of UGT1A1, which can lead to hyperbilirubinemia. 'With three existing clinical programmes already in the pipeline, we feel very confident we will meet our goal of four clinical stage compounds in 2024...'"

Preclinical • Oncology

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