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).
AdvertisementJean Lachowicz, Ph.D., CSO at Angiochem, said, "While our current data has focused on demonstrating the potential of Angiochem's technology in oncology, its applicability extends beyond oncology to include neurodegenerative diseases as well." The clinical study titled 'ANG4043, a Novel Brain-penetrant Peptide-mAb Conjugate, is Efficacious against HER2-positive Intracranial Tumors in Mice' is published in Molecular Cancer Therapeutics.
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