Supplementary Figure S5 from Nonclinical Development of Next-generation Site-specific HER2-targeting Antibody–drug Conjugate (ARX788) for Breast Cancer Treatment

Abstract

<p>Supplementary Figure S5 illustrates anti-drug antibody (ADA) titers in serum samples from the ARX788 repeat-dose cynomolgus toxicity study. Serum samples were collected pre-dose before the first and fourth ARX788 doses and during the 8-week recovery period. Samples were screened in validated methods for presence of ADA, putative positive samples were confirmed in competition assays, and confirmed positive samples were titrated to determine titer levels which were reported as the reciprocal of the dilution. The titers (at all time points) for animals with at least one confirmed positive ADA sample are shown. Significant treatment-induced ADA responses were observed in Animal 2004 with a very high ADA titer of 320000, while Animals 4505, 4003, and 4506 exhibited ADA titers of 6400, 3200, and 640, respectively. All other animals showed either transient ADA responses or ADA titer levels {less than or equal to}16. In concordance with the ADA titers, animal 2004 showed lower serum concentrations on Day 43 (by ~2-fold) and Day 64 (by ~20-fold or BLQ) when compared to other animals in the group. PK results from animals 4505, 4003, and 4506 were limited because the animals in the group did not receive 3rd and 4th doses because of adverse effects. However, the available sparse exposure results from these animals showed lower serum concentrations by 10 to >100-fold when compared to other animals in the group between Day 36 to Day 120.</p>