Orum Therapeutics recently announced that the first patient has been dosed in a phase 1 clinical trial evaluating ORM-1153, the company’s investigational CD123-GSPT1 DAC, in patients with relapsed or refractory Acute Myeloid Leukemia (AML) and other CD123-expressing hematologic malignancies.

ORM-1153 combines Orum’s internally developed CD123-targeting antibody with a proprietary GSPT1 degrader payload. The antibody was engineered for efficient internalisation into target cells and reduced Fc-gamma receptor interactions, with a linker designed for plasma stability. Preclinical studies demonstrated activity across primary AML patient samples and models with TP53 mutations, providing a rationale for evaluating ORM-1153 in patients with difficult-to-treat disease.

Olaf Christensen, MD, Chief Medical Officer, Orum Therapeutics, said, “We have built a substantial preclinical data package for ORM-1153, and our task now is to establish how those findings translate clinically. The preparation of our team and the support of our clinical site partners enabled us to move efficiently from IND clearance through site activation to dosing. The study will allow us to assess whether the improvements in payload delivery observed preclinically translate into a favorable balance of activity and tolerability in patients.”

The first-in-human phase 1 study is an open-label, dose-escalation trial designed to identify the optimal biological dose and evaluate the safety and tolerability of ORM-1153. The study will also characterise its pharmacokinetic and pharmacodynamic profile and assess preliminary antileukemic activity. Approximately, 42 patients are expected to be enrolled at multiple clinical sites initially in the US, potentially followed by sites in other regions.

Andrew Sochacki, MD, Associate Director—Hematology, START Midwest, said, “Patients with relapsed or refractory AML, particularly those with high-risk molecular features, continue to have poor outcomes and need additional treatment options. Targeted delivery of a GSPT1 degrader offers a different approach to treating these cancers. This phase 1 study will provide important initial information about ORM-1153’s safety, pharmacology, and potential activity in patients.”