ANX007 is a clinical-stage investigational monoclonal antibody antigen-binding fragment (Fab) for the treatment of patients with complement-mediated neurodegenerative ophthalmic diseases. Formulated for IVT administration, ANX007 is designed to potently bind to C1q and inhibit activation of all downstream components of the classical complement cascade, including C3 and C5, but to not interfere with the normal function of C3 and C5 as part of other complement pathways.

We have completed a Phase 1b clinical trial of ANX007 in patients with glaucoma who were treated with multiple doses (n=17) of intravitreal ANX007. ANX007 was well-tolerated at all dose levels. At the two higher dose levels, a single intravitreal injection of ANX007 achieved complete suppression of the C1q target for at least four weeks, as measured in ocular fluid from aqueous humor taps. These results were consistent with preclinical models.

Based on these promising top-line results, our preclinical data to date, and our knowledge of C1q biology in this setting, we plan to advance ANX007 into later-stage clinical trials for glaucoma or geographic atrophy (GA). The classical complement pathway is implicated in GA by human genetics, and C1q appears to play a potential dual role in GA. C1q accumulates on photoreceptor cell synapses with normal age or disease and may lead to aberrant synapse removal and neuronal loss in disease. C1q also accumulates in the retina below photoreceptor cells on extracellular deposits called drusen, and may contribute to the localized tissue damage unique to the specialized compartment of the outer retina in GA. C1q is produced locally in the eye by infiltrating immune cells and, in contrast to other complement factors, may be more amenable to local inhibition by intravitreal administration of ANX007. In a preclinical model of photoreceptor cell loss, C1q inhibition was shown to be protective against cell loss and functional decline, and in a pharmacokinetic analysis, ANX007 achieved complete C1q suppression for at least four weeks following intravitreal administration.