Orum Therapeutics Announces U.S. FDA Clearance of IND for ORM-1153, a First-in-Class CD123-GSPT1 Degrader-Antibody Conjugate
核心洞察
The U.S. FDA has cleared Orum Therapeutics (搜索)' Investigational New Drug (IND) application for ORM-1153, a CD123 (搜索)-GSPT1 (搜索) degrader-antibody conjugate (DAC).
Orum plans to initiate a first-in-human Phase 1 study in patients with relapsed or refractory acute myeloid leukemia (搜索) (AML) and other hematologic malignancies by the end of 2026.
Preclinical data presented at AACR 2026 showed broad activity across AML models, including primary patient samples and TP53-relevant models, with low-dose in vivo activity and favorable tolerability.
Orum Therapeutics (搜索) (KRX: 475830), a biotechnology company pioneering the field of degrader-antibody conjugates (DACs), announced that the U.S. Food and Drug Administration (FDA) has cleared the Company's Investigational New Drug (IND) application for ORM-1153, a CD123 (搜索)-GSPT1 (搜索) DAC. Orum plans to initiate a first-in-human Phase 1 study of ORM-1153 in patients with relapsed or refractory acute myeloid leukemia (搜索) (AML) and other hematologic malignancies by the end of 2026.
"FDA clearance of the IND for ORM-1153 is an important milestone for Orum, bringing another first-in-class DAC into the clinic and extending our approach into CD123 (搜索)-expressing hematologic malignancies," said Olaf Christensen, M.D., Chief Medical Officer of Orum Therapeutics (搜索). "By combining cell-selective delivery with targeted protein degradation in a single molecule, we believe ORM-1153 has the potential to improve treatment efficacy and tolerability for patients with severe hematologic malignancies."
Mechanism of Action and Preclinical Evidence
ORM-1153 uses Orum's TPD²® (Dual-Precision Targeted Protein Degradation) approach to deliver a GSPT1 (搜索) degrader payload to CD123 (搜索)-expressing cells, enabling targeted degradation of GSPT1. The TPD² approach builds novel targeted protein degraders combined with the precise cell delivery mechanisms of antibodies to generate first-in-class, cell-selective targeted protein degraders for the treatment of cancer and other serious diseases.
Orum has developed new targeted protein degrader payloads designed to specifically degrade an intracellular target protein within cancer cells via the E3 ubiquitin ligase pathway. Conjugated to antibodies, these payloads are designed to be delivered specifically to target cells and precisely degrade the intracellular target protein of interest.
In preclinical studies presented at the American Association for Cancer Research (AACR) Annual Meeting 2026, ORM-1153 demonstrated broad activity across AML models, including activity in primary AML patient samples and TP53-relevant models, as well as low-dose in vivo activity and favorable repeat-dose tolerability.
Phase 1 Study Design
The first-in-human Phase 1 study will assess the safety and tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of ORM-1153 in patients with relapsed or refractory AML and other hematologic malignancies. The multicenter study is expected to enroll approximately 42 patients initially at U.S. clinical sites, with potential expansion to other regions.
Company Outlook
Orum is advancing its GSPT1 (搜索)-directed TPD² programs and developing novel degrader payloads to expand the potential of targeted protein degradation. The Company's novel targeted protein degrader payloads are designed to selectively degrade key intracellular proteins, offering a highly targeted approach to treating difficult-to-treat diseases. Orum is located in Daejeon, South Korea, and Lexington, MA, US.
Orum will host a conference call on Monday, August 24, at 7:00 a.m. KST (Sunday, August 23, at 6:00 p.m. EDT) to discuss the ORM-1153 IND clearance and provide a high-level overview of the Phase 1 clinical study.