BOSTON & DAEJEON, South Korea– Orum Therapeutics, a private biotechnology company pioneering the development of tumor-directed targeted protein degraders (TPDs), today announced that the first patient has been dosed with ORM-5029 in a Phase 1 clinical trial for patients with HER2-expressing advanced solid tumors. ORM-5029 is one of two lead programs from the company’s GSPT1 platform leveraging the Dual-Precision Targeted Protein Degradation (TPD²) approach, which is designed to leverage antibody drug conjugates (ADCs) to precisely deliver and target intracellular proteins for degradation leading to cancer cell death.
“The initiation of this clinical trial represents a series of firsts for Orum—it’s our first drug candidate from our GSPT1 degrader conjugate platform to enter the clinic, and ORM-5029 is a first-in-class molecule that represents a novel approach to precision targeted protein degraders,” said Sung Joo Lee, Ph.D., CEO of Orum Therapeutics. “In addition to ORM-5029, we are harnessing the power of various protein degraders with the precision of antibodies with the potential to improve the treatment of cancer for more patients.”
The Phase 1 trial (ClinicalTrials.gov Identifier: NCT05511844) is an open label, multicenter, dose escalation and expansion study of ORM-5029 in patients with HER2-expressing advanced solid tumors who are not eligible for standard of care therapy. The study is designed to evaluate the safety, pharmacokinetics, and preliminary anti-tumor activity of ORM-5029 administered intravenously.
“ORM-5029 combines the strengths of targeted protein degraders and ADCs while overcoming the limitations of each modality,” said Olaf Christensen, M.D., Chief Medical Officer of Orum Therapeutics. “Using a GSPT1-degrading payload conjugated to a HER2-detecting antibody is a first-in-class approach for ADCs, differentiating ORM-5029 from ADCs with cytotoxic payloads.”
Dr. Christensen added, “Although important progress has been made for the treatment of HER2-expressing cancers, patients with tumors that are refractory or becoming resistant to approved treatment approaches will need new therapeutic options. The Phase 1 trial will help us to understand the potential clinical impact of ORM-5029 on HER2-expressing advanced tumors.”
Orum’s GSPT1 degrader conjugate platform is designed to deliver potent and differentiated TPDs by combining novel small molecule degraders with the precise cellular delivery mechanism of antibodies. For ORM-5029, Orum developed a proprietary class of GSPT1 degrader molecules, paired them with a HER2-targeting antibody pertuzumab, and screened numerous candidate conjugates to identify a molecule with the desired therapeutic profile. Preclinical data presented at AACR 2022 demonstrate robust potency in vitro and in vivo in low-HER2 settings and dose-dependent efficacy of ORM-5029 compared to either small molecule GSPT1 degraders or standard-of-care ADCs.
