The multicentre, open-label, dose escalation, and expansion trial will analyse ORM-5029 in HER2-expressing advanced solid tumour patients who are not eligible to receive standard-of-care treatment.
It will evaluate the safety, pharmacokinetics, and initial anti-tumour activity of ORM-5029 given as intravenous doses.
Through antibody targeting, ORM-5029 offers catalytic GSPT1 protein degraders to HER2-expressing tumour cells.
It is one of two lead programmes using Orum ’s GSPT1 platform that utilises the Dual-Precision Targeted Protein Degradation (TPD²) approach.
This method uses antibody drug conjugates (ADCs) to accurately deliver and act on intracellular proteins for degradation causing the death of cancer cells.
For ORM-5029, the company developed a class of GSPT1 degrader molecules and combined them with pertuzumab, a HER2-targeting antibody. It then analysed various candidate conjugates to detect a molecule with the preferred therapeutic profile.
In preclinical research, ORM-5029 showed strong potency in vitro and in vivo in low-HER2 settings, as well as dose-dependent efficacy as against small molecule GSPT1 degraders or standard-of-care ADCs.
Orum Therapeutics CEO Sung Joo Lee said: “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.
“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.”