Intravitreal RTH258 (brolucizumab) demonstrates no effect on pregnancy, parturition, embryofetal or postnatal development in cynomolgus monkeys.

RTH258 (brolucizumab) is a humanized single chain antibody fragment, the smallest functional unit of an antibody designed to target vascular endothelial growth factor in angiogenic retinal disease. To further understand the safe use of RTH258, this study assessed the potential impact of intravitreal RTH258 on pre- and postnatal development in the offspring of cynomolgus monkeys following administration to the mother. Three groups of 16 pregnant females were included: a low dose group (RTH258 3 mg/50 µl [60 mg/ml]), a high dose group (RTH258 6 mg/50 µl [120 mg/ml]), and a control group.

International consortium for innovation and quality: An industry perspective on the nonclinical and early clinical development of intravitreal drugs.

The eye, which is under constant exposure to environmental pathogens, has evolved various anatomic and immunological barriers critical to the protection of tissues lacking regenerative capacity, and the maintenance of a clear optic pathway essential to vision. By bypassing the ocular barriers, intravitreal (IVT) injection has become the mainstay for the delivery of drugs to treat conditions that affect the back of the eye. Both small molecules and biotherapeutics have been successfully administered intravitreally, and several drugs have been approved for the treatment of (wet) age-related macular degeneration and diabetic macular edema.

Synthesis and SAR of heteroaryl-phenyl-substituted pyrazole derivatives as highly selective and potent canine COX-2 inhibitors.

The discovery of heteroaryl-phenyl-substituted pyrazole derivatives as canine selective COX-2 inhibitors is described. Structure-activity relationship (SAR) studies of this class of compounds led to the identification of compound 1 which demonstrated a canine whole blood COX-2 inhibitory IC50 of 12 nM and selectivity ratio of COX-1/COX-2 greater than 4000-fold.