eiletoclax (ZE50-0134) / Eilean Therap - LARVOL DELTA

A Phase 1b Study of Lonitoclax + Azacitidine in Acute Myeloid Leukemia Patients (clinicaltrials.gov) - P1 | N=66 | Not yet recruiting | Sponsor: Lomond Therapeutics Holdings, Inc.

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

A novel: Plasma apoptosis assay to demonstrate CLL cell target engagement in first-in-human study of a highly selective oral bcl-2 inhibitor lonitoclax (ZE50-0134) (ASH 2025) - "To date, clinical trials with the first generation Bcl-2 inhibitor, venetoclax, have shown single agent or combination activity in a variety of B-cell malignancies (chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), select Non-Hodgkin's lymphoma subtypes, multiple myeloma) and myeloid diseases (acute myeloid leukemia)...Lonitoclax has demonstrated monotherapy activity in pre-clinical models, as well as synergistic activity when combined with azacytidine, FLT3 and menin inhibitors in AML xenograft models...Pharmacokinetic AUC 0-inf was increased (3.5-fold) with food but minimally influenced by itraconazole (+3%) or PPI administration (-27%)...Lonitoclax demonstrates favorable PK and safety profiles when administered orally as a single dose of up to 800 mg, with dose-proportional increases in systemic exposure, food but not DDI or PPI effect, target engagement using the novel PAA, and no treatment-related adverse events. By using the PAA to..."

First-in-human • P1 data • Acute Myelogenous Leukemia • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Leukemia • Lymphoma • Multiple Myeloma • Small Lymphocytic Lymphoma • ANXA5 • CASP3 • CD8 • CYP3A4 • FLT3

A Novel Selective BCL2 Inhibitor with Limited Immune Suppression and Improved Safety Compared to Venetoclax (ASH 2023) - "An in vivo murine study examining the pharmacology of ZE50-0134 or venetoclax given with ketoconazole, a strong CYP3A inhibitor, was performed demonstrating a 0.84-fold decrease in AUC with ZE50-0134 vs. a 1.52-fold increase in AUC with venetoclax suggesting less Cyp3A influence on ZE50-0134...In AML, venetoclax is typically not effective as monotherapy and if often used in combination with azacytidine...The pharmacology of this agent makes it an ideal therapeutic to optimize tumor BCL2 dependence and avoid untoward toxicity that occurs through continuous BCL2 targeting. This data supports the further clinical development of ZE50-0134 in both B cell malignancies and AML."

Clinical • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Neutropenia • Oncology • Thrombocytopenia • BCL2L1 • CD8

A Double-Blind, Placebo-Controlled, First-in-Human Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ZE50 0134 in Healthy Volunteers (ANZCTR) - P1 | N=96 | Completed | Sponsor: Lomond Therapeutics AU Pty Ltd | Recruiting ➔ Completed

First-in-human • Trial completion • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology

Clinical Study Aiming to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of a Single Administration of ZE50-0134 at 5 Dose Levels in Healthy Volunteers (clinicaltrials.gov) - P1 | N=104 | Completed | Sponsor: Eilean Therapeutics | Recruiting ➔ Completed | Trial completion date: Jan 2025 ➔ Jul 2025 | Trial primary completion date: Jan 2025 ➔ Jul 2025

First-in-human • Trial completion • Trial completion date • Trial primary completion date

ZE50-0134-0002: A Phase 1 Study of ZE50-0134 in Relapsed and Refractory Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, and Select Low-grad Lymphomas (clinicaltrials.gov) - P1 | N=66 | Recruiting | Sponsor: Eilean Therapeutics | Not yet recruiting ➔ Recruiting | Initiation date: Jan 2025 ➔ Apr 2025

Enrollment open • Trial initiation date • Chronic Lymphocytic Leukemia • Hematological Malignancies • Indolent Lymphoma • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

Clinical Study Aiming to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of a Single Administration of ZE50-0134 at 5 Dose Levels in Healthy Volunteers (clinicaltrials.gov) - P1 | N=88 | Recruiting | Sponsor: Eilean Therapeutics

New P1 trial

A Double-Blind, Placebo-Controlled, First-in-Human Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ZE50 0134 in Healthy Volunteers (ANZCTR) - P1 | N=88 | Recruiting | Sponsor: Eilean Therapeutics AU Pty Ltd (A subsidiary of Eilean Therapeutics LLC) | N=40 ➔ 88 | Initiation date: May 2024

Enrollment change • Trial initiation date • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology

A Phase 1 Study of ZE50-0134 in Relapsed and Refractory Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, and Select Low-grad Lymphomas (clinicaltrials.gov) - P1 | N=66 | Not yet recruiting | Sponsor: Eilean Therapeutics

New P1 trial • Chronic Lymphocytic Leukemia • Hematological Malignancies • Indolent Lymphoma • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma • CASP3

A Double-Blind, Placebo-Controlled, First-in-Human Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ZE50 0134 in Healthy Volunteers (ANZCTR) - P1 | N=40 | Recruiting | Sponsor: Eilean Therapeutics AU Pty Ltd (A subsidiary of Eilean Therapeutics LLC) | Not yet recruiting ➔ Recruiting

Enrollment open • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology

A Double-Blind, Placebo-Controlled, First-in-Human Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ZE50 0134 in Healthy Volunteers (ANZCTR) - P1 | N=40 | Not yet recruiting | Sponsor: Eilean Therapeutics AU Pty Ltd (A subsidiary of Eilean Therapeutics LLC)

New P1 trial • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology

EILEAN THERAPEUTICS INITIATES FIRST IN HUMAN TRIAL WITH EILETOCLAX, A SELECTIVE BCL2 INHIBITOR WITH LIMITED IMMUNE SUPPRESSION AND IMPROVED SAFETY COMPARED TO VENETOCLAX AND VENETOCLAX-LIKE MOLECULES (PRNewswire) - "Eilean Therapeutics LLC...announced the clearance from the Human Research Ethics Committee in Australia to begin human dosing in the Phase 1 clinical program of eiletoclax, a highly potent and selective BCL2 inhibitor. 'The first in human dosing of eiletoclax in Australia represents another important milestone for Eilean Therapeutics, as we progress, with an accelerated development of our portfolio of best-in-class agents targeting hematological malignancies'..."

New P1 trial • Hematological Malignancies