Enhanced HER2-Targeted Therapy: The Preclinical Profile of MP0274, a Novel Apoptosis-Inducing DARPin

A novel HER2-targeted molecule, MP0274, has been developed to enhance treatment outcomes for cancers that are HER2 positive. This molecule is distinct due to its dual binding capacity to HER2 and human serum albumin, which extends its half-life. In vitro studies have shown that MP0274 can induce apoptosis and inhibit cell proliferation in HER2-expressing cells, and it effectively suppresses HER2/HER3 signaling pathways.

To evaluate MP0274's potential for clinical use, its efficacy was tested in patient-derived xenograft (PDX) models of breast and gastric cancers, where it demonstrated superior antitumor activity compared to standard treatments. MP0274 was also found to effectively localize to HER2-expressing tumors within a short timeframe, as evidenced by whole-body SPECT/CT imaging using an Indium-111 labeled version of the molecule.

Pharmacokinetic analysis in cynomolgus monkeys indicated that MP0274 has a long half-life, exceeding five days at higher doses and showing target-mediated clearance saturation. The molecule was well tolerated in all conducted studies.

These findings indicate that MP0274, with its unique mechanism of action promoting apoptosis, shows promise in preclinical models, with rapid tumor targeting and a prolonged presence in the body. The molecule is currently undergoing further toxicology studies, and preparations are being made for a phase I clinical trial to assess its safety and efficacy in humans.