On December 8, 2025 Orum Therapeutics ("Orum" or the "Company") (KRX: 475830), a public biotechnology company pioneering the field of degrader-antibody conjugates (DACs), reported the presentation of preclinical data for ORM-1153 at the 67th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, taking place December 6 to 9, 2025, in Orlando, Florida. ORM-1153 is a novel CD123-targeting DAC designed to deliver Orum’s proprietary GSPT1-degrading payload selectively into cancer cells to achieve targeted protein degradation and antitumor activity in acute myeloid leukemia (AML) and other CD123-positive hematological malignancies.
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"These data highlight ORM-1153 as a differentiated therapeutic candidate designed to address the need for more effective and better-tolerated treatments for acute myeloid leukemia," said Sung Joo (SJ) Lee, Ph.D., Founder and CEO of Orum Therapeutics. "AML remains one of the most challenging hematologic cancers to treat, with frequent relapse and limited options, particularly for patients with TP53-mutant disease. These data demonstrate the potential of ORM-1153 to achieve potent antitumor activity with a differentiated safety profile, addressing long-standing limitations of current AML therapies and further validating the versatility of our targeted protein degrader approach."
The preclinical data presented at ASH (Free ASH Whitepaper) show that ORM-1153 drives efficient, CD123-dependent internalization and degradation of GSPT1, resulting in strong and durable antitumor activity in AML models, including TP53-mutant disease. In comparative studies, ORM-1153 demonstrated approximately 1,000-fold higher potency than the unconjugated degrader payload and produced dose-dependent tumor regression in a disseminated AML xenograft model, with complete and durable responses at the highest dose level.
Importantly, ORM-1153 maintained a favorable tolerability profile and showed minimal effects on normal hematopoietic progenitors in colony-forming assays, suggesting potential for a differentiated therapeutic window compared with current standard-of-care. Together, these findings support ORM-1153 as a promising candidate for the treatment of AML and other CD123-positive hematologic malignancies.
About Orum’s TPD² Approach
Orum’s unique Dual-Precision Targeted Protein Degradation (TPD²) approach builds novel targeted protein degraders combined with the precise cell delivery mechanisms of antibodies to generate innovative, first-in-class, cell-selective TPDs for the treatment of cancer and other serious diseases. Orum has developed new targeted protein degrader payloads to specifically degrade an intracellular target protein within cancer cells via the E3 ubiquitin ligase pathway. Conjugated to antibodies, the payloads are designed to be delivered specifically to target cells and precisely degrade the intracellular target protein of interest.
(Press release, Orum Therapeutics, DEC 8, 2025, View Source [SID1234661268])