Orum Therapeutics, specializing in tumor-directed targeted protein degraders (TPDs), said on Tuesday that it completed the first patient dose with ORM-5029 in a U.S. 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) technology, which is designed to leverage antibody drug conjugates (ADCs) to precisely deliver and target intracellular proteins for degradation leading to cancer cell death.
Orum’s GSPT1 degrader conjugate platform is designed to deliver potent and differentiated TPDs for cancer treatment by combining novel small molecule degraders with the precise cellular delivery mechanism of antibodies.
The company 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 like ORM-5029.
"This clinical trial is the world's first patient drug administration with a technology that combines strong efficacy TPD and ADC," CEO Lee Sung-joo said. "We plan to challenge various blood and solid cancers, starting with breast cancer and expect higher safety by delivering decomposition agents through antibodies."
Lee added, that while existing ADCs inhibit DNA or microtubules, ORM-5029 presents a new mechanism of apoptosis.
The phase 1 trial is a 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.
“ORM-5029 combines the strengths of targeted protein degraders and ADCs while overcoming the limitations of each modality,” said Orum Therapeutics Chief Medical Officer Olaf Christensen. “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, “While 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 still need new therapeutic options.”