lomonitinib (ZE46-0134) / Eilean Therap - LARVOL DELTA

A healthy volunteer study with lomonitinib predicts pharmacokinetics and pharmacodynamics in a relapsed refractory AML study (ASH 2025) - P1 | "Multiple in vivo studies with both xenograft and syngeneic immune competent murine models demonstrated that lomonitinib has superior efficacy to gilteritinib in ITD and gatekeeper mutation-dependent disease. The safety profile of lomonitinib enables rapid FLT3 engagement by using a loading dose (5-fold higher than the maintenance dose) which is not possible with other long half-life FLT3 inhibitors with less favorable therapeutic indices. Application of healthy volunteer studies with agents having a broad therapeutic index such as lomonitinib offer the opportunity to enter a subsequent AML patient clinical trial at a clinically effective dose identified from pre-clinical models."

Clinical • PK/PD data • Acute Myelogenous Leukemia • FLT3 • IRAK4

CTN-03208-1: Study of Single and Multiple Ascending Doses of ZE46-0134 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=112 | Completed | Sponsor: Lomond Therapeutics Holdings, Inc. | Active, not recruiting ➔ Completed

First-in-human • Trial completion • Acute Myelogenous Leukemia

A Phase 1, Open-Label, Dose Escalation and Dose Expansion, Multicenter Clinical Trial to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of Lomonitinib (ZE46-0134) in Adults with FLT3-Mutated Relapsed or Refractory Acute Myeloid Leukemia (ASH 2024) - P1/2 | "In vitro studies with FLT3-mutated cell lines demonstrated potent inhibition and differential decrease of FLT3 protein expression as compared to gilteritinib. Pharmacodynamic biomarkers of potential interest that will be assessed include changes in phosphorylation of FLT3/STAT5/MAPK, and cytokine profile. Next-generation sequencing will identify the genomic features of responding, non-responding, and relapse patients."

Clinical • IO biomarker • P1 data • PK/PD data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • BCL2 • FLT3 • IRAK4 • STAT5

A Randomized Placebo-Controlled Phase 1 Trial in Healthy Volunteers Investigating the Safety, Pharmacokinetics and Pharmacodynamics of a Novel FLT3/IRAK4 Inhibitor, Lomonitinib (ZE46-0134) (ASH 2024) - P1 | "In vitro studies with FLT3-ITD cell lines demonstrated potent inhibition and differential decrease of FLT3 protein expression compared to gilteritinib...The exposure of lomonitinib was minimally affected by the PPI and no significant influence on PK was observed with itraconazole...The safety profile of lomonitinib enables rapid FLT3 engagement by using a loading dose (5-fold higher than the maintenance dose) which is not possible with other long half-life FLT3 inhibitors with less favorable therapeutic indices. A phase 1B study in R/R AML with mutated FLT3 is underway in Australia as well as in the US in collaboration with The Leukemia & Lymphoma Society Beat AML"

Clinical • IO biomarker • P1 data • PK/PD data • Hematological Malignancies • Leukemia • Oncology • BCL2 • FLT3 • IRAK4

A Randomised, Double-Blind, Placebo-Controlled, First-in-Human Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Ascending Doses of ZE46 0134 in Healthy Volunteers (ANZCTR) - P1 | N=104 | Completed | Sponsor: Lomond Therapeutics AU Pty Ltd | Recruiting ➔ Completed

First-in-human • Trial completion • Oncology

CTN-03208-1: Study of Single and Multiple Ascending Doses of ZE46-0134 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=112 | Active, not recruiting | Sponsor: Eilean Therapeutics | N=64 ➔ 112 | Recruiting ➔ Active, not recruiting | Trial completion date: Nov 2024 ➔ Oct 2025 | Trial primary completion date: Oct 2024 ➔ Jun 2025

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia

Dose Escalation and Expansion Study to Evaluate the Safety, PK, PD and Efficacy of ZE46-0134 in Adults With FLT3 Mutated Relapsed or Refractory Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=60 | Recruiting | Sponsor: Eilean Therapeutics | Not yet recruiting ➔ Recruiting | Trial primary completion date: Sep 2025 ➔ Jan 2026

Enrollment open • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Lomond Therapeutics Completes Second and Third Closings and adds Two New Investors (PRNewswire) - "Lomond Therapeutics Holdings, Inc...announced the addition of two new investors, Yosemite Capital and QIA Investments, coincident with a second and third closing, respectively, and the raising of an additional $20 million private placement financing....This transaction provides the additional resources necessary to advance our potentially best-in-class or first-in-class programs, lomonitinib, lonitoclax and our menin inhibitor, through clinical development."

Financing • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Lymphoma

The Leukemia & Lymphoma Society (LLS) Data at ASH Provides Glimpse into the Future of Blood Cancer Treatment (PRNewswire) - "The Leukemia & Lymphoma Society (LLS) will present new data from its Beat AML Master Clinical Trial and Pediatric Acute Leukemia (PedAL) Master Clinical Trial at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition....Additional data indicate that IDH inhibitors as single agent or in combination with low-intensity therapies may be a viable treatment option for older adults with acute leukemias....Beat AML also recently opened its first clinical subtrial to investigate the safety and efficacy of lomonitinib (ZE46-0134) in patients with FLT3-mutated relapsed or refractory AML in partnership with Eilean Therapeutics."

Diagnostic • P1/2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Oncology

LOMOND THERAPEUTICS ANNOUNCES UPCOMING PRESENTATION AT THE ASH ANNUAL MEETING (PRNewswire) - "Lomond Therapeutics...announced an abstract related to the company's Lomonitinib, a highly potent and selective pan-FLT3/IRAK4 inhibitor that targets clinically relevant FLT3 mutations and putative escape pathways, has been accepted for a poster presentation at the upcoming American Society of Hematology (ASH) Annual Meeting, which will be held from December 7-10, 2024 in San Diego."

P1 data • Oncology

INTERIM ANALYSIS OF A RANDOMIZED PHASE 1 TRIAL IN HEALTHY VOLUNTEERS INVESTIGATING THE SAFETY, PHARMACOKINETICS AND PHARMACODYNAMICS OF A NOVEL FLT3/IRAK4 INHIBITOR, LOMONITINIB (ZE46-0134) (EHA 2024) - "In vitro studies with FLT3-specific cell lines demonstrate potent inhibition and differential decreaseof FLT3 protein expression as compared to gilteritinib. Lomonitinib demonstrates favorable PK and safety profiles when administered orally as single dose, with dose-proportional increases in systemic exposure, target engagement, and no treatment-related adverse events. Inaddition, lomonitinib was well tolerated with no treatment-related safety signals in the first MAD cohortthereby enabling a rapid FLT3 engagement strategy by using a loading dose that is not possible with otherFLT3 inhibitors. A phase 1B study in R/R AML with mutated FLT3 has been initiated."

Clinical • IO biomarker • P1 data • PK/PD data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • BCL2 • FLT3 • IRAK4

A Randomised, Double-Blind, Placebo-Controlled, First-in-Human Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Ascending Doses of ZE46 0134 in Healthy Volunteers (ANZCTR) - P1 | N=80 | Recruiting | Sponsor: Eilean Therapeutics | N=40 ➔ 80

Enrollment change • Oncology

Eilean Therapeutics Joins The Leukemia & Lymphoma Society's Groundbreaking Beat AML Master Clinical Trial (PRNewswire) - "Eilean Therapeutics AU Pty Ltd...has joined The Leukemia & Lymphoma Society (LLS) in the groundbreaking collaborative Beat AML Master Clinical Trial. Eilean's investigational agent, lomonitinib (ZE46-0134) has been selected for a new trial arm for patients with FLT3 mutated relapsed/refractory (R/R) acute myeloid leukemia (AML)."

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

Eilean Therapeutics Announces FDA Clearance of Investigational New Drug (IND) Application for Lomonitinib for the Treatment of Acute Myeloid Leukemia (AML) (PRNewswire) - "Eilean Therapeutics LLC, is pleased to announce that the U.S. Food and Drug Administration (FDA) has cleared the IND for lomonitinib (ZE46-0134), allowing the company to proceed with a Phase 1 clinical trial in FLT3 mutated relapsed/refractory (R/R) AML. While the Phase 1 study has already initiated in Australia, clearance from the FDA will allow the trial to be initiated in the US. Lomonitinib is a highly potent and selective pan-FLT3/IRAK4 inhibitor that targets clinically relevant FLT3 mutations and putative escape pathways."

IND • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Study of Single and Multiple Ascending Doses of ZE46-0134 in Healthy Volunteers (clinicaltrials.gov) - P1 | N=64 | Recruiting | Sponsor: Eilean Therapeutics

New P1 trial • Acute Myelogenous Leukemia

Dose Escalation and Expansion Study to Evaluate the Safety, PK, PD and Efficacy of ZE46-0134 in Adults With FLT3 Mutated Relapsed or Refractory Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=60 | Not yet recruiting | Sponsor: Eilean Therapeutics

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

EILEAN THERAPEUTICS RECEIVES CLEARANCE TO INITIATE R/R AML TRIAL WITH LOMONITINIB, A SELECTIVE PAN-FLT3/IRAK4 INHIBITOR (PRNewswire) - "Eilean Therapeutics LLC...is pleased to announce the clearance from the Human Research Ethics Committee in Australia for lomonitinib (ZE46-0134) allowing the company to proceed with a Phase I clinical trial in relapsed/refractory (R/R) AML....Eilean Therapeutics is planning to initiate the study in Q2 2024 across multiple investigative sites in Australia."

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

EILEAN THERAPEUTICS COMPLETES SINGLE DOSE STUDIES AND INITIATES MULTIPLE DOSING OF HEALTHY VOLUNTEERS WITH LOMONITINIB, A SELECTIVE PAN-FLT3/IRAK4 INHIBITOR (PRNewswire) - "Eilean Therapeutics LLC...announced the completion of a single ascending dose Phase 1 clinical study of lomonitinib and initiation of a multiple ascending dose Phase 1 program. Lomonitinib is a highly potent and selective pan-FLT3/ IRAK4 inhibitor that targets clinically relevant FLT3 mutations (ITD, TKD) including the gatekeeper mutation as well as putative escape pathways. The initial phase 1 program demonstrated excellent safety of lomonitinib with no reportable adverse events at exposures that resulted in robust target engagement."

Trial status • Oncology

A Randomised, Double-Blind, Placebo-Controlled, First-in-Human Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Ascending Doses of ZE46 0134 in Healthy Volunteers (ANZCTR) - P1 | N=44 | Recruiting | Sponsor: Eilean Therapeutics | Not yet recruiting ➔ Recruiting

Enrollment open • Trial initiation date • Oncology

A Randomised, Double-Blind, Placebo-Controlled, First-in-Human Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Ascending Doses of ZE46 0134 in Healthy Volunteers (ANZCTR) - P1 | N=44 | Not yet recruiting | Sponsor: Eilean Therapeutics

New P1 trial • Oncology

EILEAN THERAPEUTICS DOSES FIRST PATIENT WITH ZE46-0134, A SELECTIVE FLT3wt-SPARING, PAN FLT3mut INHIBITOR (PRNewswire) - "Eilean Therapeutics LLC...announced the initiation of human dosing in the Phase 1 clinical program of ZE46-0134, a highly potent and selective pan-FLT3 inhibitor that targets clinically relevant FLT3 mutations including the FLT3 gatekeeper mutation, while sparing the wild type form of the protein."

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