EP0042 / Ellipses Pharma - LARVOL DELTA

EP0042, a Dual FLT3 and Aurora Kinase Inhibitor: Final Results of Dose Escalation and Optimization Cohorts from a Phase I/IIa Study in Patients with Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML), Chronic Myelomonocytic Leukemia (CMML) or Myelodysplastic Syndrome (MDS) (ASH 2024) - "The median number of prior treatments was 2 (range 1-6).13 pts received a prior FLT3 inhibitor (midostaurin, gilteritinib, sorafenib), with 10 receiving ≥2 inhibitors. The 100 mg BID dose schedule has been selected for further evaluation based on tolerability, safety, PK and evidence of efficacy. A further module will assess the combination of EP0042 with venetoclax and azacitidine - preliminary data will be presented at the conference."

Clinical • P1/2 data • Acute Myelogenous Leukemia • Ataxia • Chronic Myelomonocytic Leukemia • CNS Disorders • Constipation • Dental Disorders • Fatigue • Febrile Neutropenia • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Leukemia • Movement Disorders • Myelodysplastic Syndrome • Neutropenia • Oncology • Pulmonary Disease • Stomatitis • Thrombocytopenia

EP0042, a Dual FLT3 and Aurora Kinase Inhibitor: Results from an Ongoing Phase I/IIa Dose-Finding/Dose Optimization Study in Patients with Relapsed/Refractory Acute Myeloid Leukemia (ASH 2023) - "12 patients received a prior FLT3 inhibitor including midostaurin, gilteritinib or sorafenib and 8/12 patients received ≥2 prior FLT3 inhibitors. Dose optimisation cohorts are continuing to identify the RP2D. Further cohorts are planned for evaluation of EP0042 in combination with standard of care therapies."

Clinical • P1/2 data • Acute Myelogenous Leukemia • Ataxia • Chronic Myelomonocytic Leukemia • CNS Disorders • Constipation • Fatigue • Febrile Neutropenia • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Leukemia • Movement Disorders • Myelodysplastic Syndrome • Neutropenia • Oncology • Pulmonary Disease • FLT3

EP0042-101: Study to Evaluate the Safety and Tolerability of EP0042 (clinicaltrials.gov) - P1/2 | N=70 | Recruiting | Sponsor: Ellipses Pharma | Trial completion date: Dec 2025 ➔ Dec 2026

Trial completion date • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Ellipses Pharma publishes data from phase 1/2 clinical trial of EP0042 (European Pharmaceutical Manufacturer) - P1/2a | N=70 | NCT04581512 | Sponsor: Ellipses Pharma | "The data was presented at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition, in San Diego, California via poster 1500: EP0042, a dual FLT3 and Aurora kinase inhibitor: final results of dose escalation and optimisation cohorts from a phase 1/2a study in patients with R/R AML, CMML or MDS...Preliminary data from an ongoing cohort of patients receiving EP0042 + venetoclax indicate that the combination has a manageable safety profile and promising initial evidence of activity in patients with R/R AML +/- TP53 mutations with/without prior treatment with venetoclax."

P1 data • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Myelodysplastic Syndrome

EP0042-101: Study to Evaluate the Safety and Tolerability of EP0042 (clinicaltrials.gov) - P1/2 | N=70 | Recruiting | Sponsor: Ellipses Pharma | N=50 ➔ 70

Combination therapy • Enrollment change • Metastases • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

EP0042-101: Study to Evaluate the Safety and Tolerability of EP0042 (clinicaltrials.gov) - P1/2 | N=50 | Recruiting | Sponsor: Ellipses Pharma | Trial completion date: Dec 2023 ➔ Dec 2025 | Trial primary completion date: Sep 2023 ➔ Oct 2025

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

EP0042, a Dual FLT3 and Aurora Kinase Inhibitor: Preliminary Results of an Ongoing Phase I/IIa First in Human Study in Patients with Relapsed/Refractory Acute Myeloid Leukemia (ASH 2022) - "EP0042 has resulted in inhibition of tumor growth in FLT3-ITD and FLT3-ITD-TKD human tumor xenograft models and in quizartinib-resistant primary AML samples (Moore A et al...5 pts received a prior FLT3 inhibitor including midostaurin, gilteritinib or sorafenib...The dose escalation is continuing at intermittent and continuous dosing to establish the MTD and optimal RP2D dose for further evaluation. Once a RP2D is confirmed, a single arm dose expansion is planned in FLT3 mutated and wild type R/R AML, and the combination of EP0042 with other agents will be explored."

Clinical • P1/2 data • Acute Myelogenous Leukemia • Ataxia • Fatigue • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Leukemia • Movement Disorders • Neutropenia • Oncology • AURKB • FLT3 • STAT5

Ellipses Pharma: EP0042 Receives Orphan Drug Designation from the US Food and Drug Administration (Businesswire) - "Ellipses Pharma...announces that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to EP0042, a dual FLT-3 and Aurora kinase inhibitor, for the treatment of acute myeloid leukaemia (AML)....EP0042 is being developed as a new potential treatment to combat acquired resistance to FLT3 inhibitors in patients with AML."

Orphan drug • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Ellipses Pharma Announces FDA Approval of IND Application for EP0042 for Patients With Acute Myeloid Leukaemia (Businesswire) - "Ellipses Pharma...announces that the U.S. Food and Drug Administration (FDA) has cleared the company’s Investigational New Drug (IND) application for EP0042, a dual FLT-3 and Aurora kinase inhibitor....This approval will allow Ellipses to expand its ongoing first in human phase 1/2 clinical trial, which is currently undergoing its dose ranging phase."

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

Ellipses Pharma Presents Preliminary Data From the First in Human Phase-1/2 Trial of EP0042, a Dual FLT-3 and Aurora Kinase Inhibitor, at ASH (Businesswire) - P1/2 | N=63 | NCT04581512 | Sponsor:Ellipses Pharma | "Ellipses Pharma Limited...has presented preliminary data from the first in human phase 1/2 trial of EP0042, a dual FLT-3 an Aurora kinase inhibitor, in patients with acute myeloid leukaemia (AML) at the 64th American Society of Hematology (ASH) Annual Meeting in New Orleans, Louisiana...The preliminary data, from the ongoing dose ranging module of the trial, demonstrated that EP0042 had acceptable safety and tolerability with evidence of prolonged disease stabilisation in a number of heavily pre-treated patients.2 No dose-limiting toxicities were observed, and the emerging adverse event profile of EP0042 appears to be characterised by febrile neutropenia, fatigue diarrhoea, peripheral oedema, dizziness, and ataxia ."

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

Ellipses Pharma to Present Clinical Updates at Leading U.S. Breast and Blood Cancer Conferences (Businesswire) - "At ASH, Ellipses’ preliminary results of the dose escalation part of the Phase 1 / 2a first-in-human study of EP0042 in patients with acute myeloid leukaemia (AML) will be presented. EP0042 is a dual FLT3 and aurora kinase inhibitor. The trial is investigating the use of EP0042 as both a monotherapy and in combination with existing therapies."

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

ICR’s ‘resistance-busting’ drug advances into Phase I trial (PharmaTimes) - "The Institute of Cancer Research, London (ICR) has announced that its ‘resistance-busting’ drug EP0042 has entered a Phase I clinical trial in patients with cancers including acute myeloid leukaemia...Under the terms of the deal between ICR and Ellipses, the company retains full responsibility for the EP0042 development programme, including pre-clinical studies and reformulation of the drug product to obtain clinical trial authorisation....The Phase I trial will be conducted at study centres planned in the UK, the Netherlands and Australia. If successful, EP0042 could progress into larger trials and become a new potential treatment for AML and neuroblastoma..."

Licensing / partnership • New P1 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Neuroblastoma • Oncology

Study to Evaluate the Safety and Tolerability of EP0042 (clinicaltrials.gov) - P1/2; N=63; Recruiting; Sponsor: Ellipses Pharma; Not yet recruiting ➔ Recruiting

Clinical • Combination therapy • Enrollment open • Acute Myelogenous Leukemia • Chronic Myeloid Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Study to Evaluate the Safety and Tolerability of EP0042 (clinicaltrials.gov) - P1/2; N=63; Not yet recruiting; Sponsor: Ellipses Pharma

Clinical • Combination therapy • New P1/2 trial • Acute Myelogenous Leukemia • Chronic Myeloid Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

A research study looking at a new treatment for patients with advanced cancer, to investigate different doses of the experimental study drug, EP0042, in order to determine a dose, which is safe, well-tolerated and likely to be effective in treating AML (acute myeloid leukaemia). (clinicaltrialsregister.eu) - P1/2; N=63; Ongoing; Sponsor: Ellipses Pharma Limited

Clinical • Combination therapy • New P1/2 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology