Purpose: Thyroid Eye Disease (TED) is an autoimmune disease that leads to inflammation and tissue damage to the orbital tissues around the eye. Previous clinical studies have demonstrated that antagonistic IGF-1R (Insulin Like Growth Factor 1 Receptor) antibodies significantly reduced the orbital inflammation and clinical symptoms in TED patients. However, substantial unmet medical needs still exist. We describe the preclinical and nonclinical primate studies of BCG009, a second-generation IGF-1R antagonist antibody with improved activities.
Methods: Fully human transgenic RenMab mice were immunized with recombinant IGF-1R extracellular domain to generate the parental clone that later became BCG009. Affinity measurement with surface plasmon resonance (SPR) and a battery of in vitro assays were performed to examine BCG009's ability to inhibit IGF- 1R-mediated functions such as signal transduction in IGF-1R-positive cells and the release of hyaluronic acid (HA) in human ocular choroidal fibroblasts (HOCFs) from TED patients upon IGF-1
stimulation. Pharmacokinetics (PK), bioavailability, and safety evaluation in nonhuman primates (NHP) were also performed.
Results: The BCG009 demonstrated robust in vitro inhibitory effect on IGF-1/IGF-1R axis in our in vitro assays, including potently blocking HA release from cultured patient samples. BCG009 demonstrated an extended PK profile as well as high solubility suitable for high concentration formulation. Nonclinical results will be presented.
Conclusions: BCG009, a fully human anti-IGF-1R antagonist, demonstrated a series of robust preclinical and nonclinical properties with a potential of a best-in-class therapeutics for TED.
