ANG4043, a Brain-penetrant Peptide-monoclonal Antibody Conjugate, Effective in Treating HER2-positive Intracranial Tumors

Mice study by Angiochem has revealed that ANG4043, a peptide-monoclonal antibody (mAb) conjugate, entered the brain at therapeutic concentrations, resulting in significantly prolonged survival in mice. Angiochem is a biotechnology company creating and developing drugs that cross the blood-brain barrier (BBB).

mAb is directed against HER2, which is the protein targeted by Herceptin. As mAb is conjugated to Angiopep-2, it is recognized by the LRP1 receptor and takes advantage of a receptor-mediated transcytosis mechanism to cross the BBB. Angiochem researchers found that ANG4043 binds LRP1 receptors while retaining the pharmacological properties of the native anti-HER2 mAb, including high affinity HER2 binding and anti-proliferative activity in HER2-expressing cells. ANG4043 achieves therapeutic brain concentrations in healthy mice and in mice bearing HER2+ intracranial tumors. Treatment with ANG4043 (15 mg/kg IV, twice-weekly) increased median survival time by 78% (80 days compared to 45 days for control).