EMA Grants Orphan Drug Designation to OXC-101 for Acute Myeloid Leukemia

The European Medicines Agency (EMA) has granted orphan drug designation (ODD) to OXC-101 (formerly karonudib [TH588], for the treatment of acute myeloid leukemia (AML).¹

OXC-101is a first-in-class mitotic MTH1 inhibitor with a dual mechanism of action that exploits a key vulnerability in cancer cells. By inducing additional oxidative stress and preventing repair of DNA damage, OXC-101 enhances the cytotoxic burden on leukemia cells, ultimately impairing their survival.

The FDA previously granted orphan drug designation to OXC-101 for the treatment of AML.

OXC-101 is currently being investigated in patients with advanced hematologic malignancies in the phase 1/2 MAATEO study (NCT04077307), which includes an expansion trial enrolling patients with relapsed or recurrent AML to evaluate the agent in combination with idarubicin.^1,2

In preclinical studies, OXC-101 has demonstrated the ability to significantly reduce tumor growth and extend survival in AML models.¹ Data have also supported the potential use of OXC-101 as part of various standard combinations with chemotherapy.

MAATEO Study Overview

This ongoing trial is designed to evaluate the safety, tolerability, and preliminary efficacy of OXC-101 in patients 18 to 75 years of age with relapsed/refractory or progressive advanced hematologic malignancies who had received standard-of-care therapies and had no suitable options available.² The first four cohorts include patients with AML, acute lymphoblastic leukemia, diffuse large B-cell lymphoma, Burkitt lymphoma, multiple myeloma or high-risk myelodysplastic syndrome (MDS), according to the WHO 2016 criteria. A fifth expansion cohort is enrolling patients with relapsed/refractory or progressive AML or MDS.

All patients are required to have measurable disease, a life expectancy of at least 8 weeks, an ECOG performance status of 0 to 2, normal left ventricular ejection fraction, and normal hepatic and renal function.

Investigators are excluding patients who experienced a clinically significant cardiovascular event such as myocardial infarction, unstable angina, angioplasty, bypass surgery, stroke, or TIA, within 6 months of study enrollment. Other key exclusion criteria comprise congestive heart failure of NYHA class II or higher; a history of arrhythmias or arrhythmias discovered during screening; a diagnosis of acute promyelocytic leukemia (AML M3); or uncontrolled, ongoing systemic or localized infection.

During the dose-escalation portion of the study, oral OXC-101 is being given once every other day. In dose expansion, the agent is given on the same schedule in combination with idarubicin on days 1 to 3 of each cycle.

Safety and tolerability are serving as the study’s primary end point. Secondary end points include efficacy measures per ELN/IWG response criteria.

References

1. EMA approves ODD for OXC-101 in AML. News Release. Oxcia. August 26, 2025. Accessed August 29, 2025. https://news.cision.com/oxcia-ab–publ-/r/ema-approves-odd-for-oxc-101-in-aml,c4210875
2. A study in leukemia patients with karonudib (MAATEO). ClinicalTrials.gov. Updated June 12, 2024. Accessed August 29, 2025. https://clinicaltrials.gov/study/NCT04077307