Inhibition of Annexin A2 for the Treatment and Prevention of Retinopathies

Summary

• Annexin A2 (A2) is a calcium-regulated, phospholipid-binding protein that is a key component of the fibrinolytic system
• Dr. Hajjar, a pediatric hematologist-oncologist and prolific researcher, has demonstrated that A2 plays a central role in the development of ocular vascular proliferative disorders
• Dr. Hajjar has collaborated with the Tri-Institutional Therapeutics Discovery Institute (Tri-I TDI) to develop a series of novel anti-A2 antibodies that have delivered promising initial results
• The team is looking for collaborators with expertise in preclinical models of retinopathies to further validate the anti-A2 antibodies and prioritize indications for clinical development 

Technical Overview

• A2-deficient mice have impaired angiogenesis and are protected in two models of diabetic retinopathy (DR) (oxygen-induced retinopathy and Akita diabetic mice) and one of proliferative vitreoretinopathy (PVR) (dispasemodel)
• Dr. Hajjar is thus exploring A2 inhibition to inhibit retinal neovascularization and proliferation of retinal pigmented epithelial (RPE) cells that are implicated in the pathogenesis of such retinopathies
• In collaboration with the Tri-I TDI, the team developed two lead anti-A2 antibodies, 02L21 and 36H22, for further testing
• The team has generated preliminary data in the oxygen-induced retinopathy (OIR) model and is looking to expand to other animal models of retinopathies to further characterize the antibodies and nominate a candidate for further development

Market Opportunity

• Diabetic Retinopathy (DR) is the most common cause of moderate and severe vision loss in working-age adults
• It is estimated that by 2045, >160 M diabetes will have DR
• Proliferative Vitreoretinopathy (PVR) is the most common cause for failure of rhegmatogenousretinal detachment repair, and occurs in about 8–10% of patients receiving the surgery
• PVR can be treated with surgery to reattach the detached retina, but the visual outcomes of the surgery is very poor

Partnering Opportunity

Weill Cornell Medicine is seeking an industrial partner with deep domain expertise and a strong presence in retinopathy to drive further characterization and optimization of the annexin A2 antibodies

Figure 1: The annexin A2 system promotes retinal neoangiogenesisin the oxygen-induced retinopathy (OIR) model. Left: Representative retinal images showing total retinal area and regions of vaso-obliteration and neovascularization in P17 oxygen-treated Anxa2+/+andAnxa2-/-mice. Right: Anxa2-/-mice have significantly less neovascularization than Anxa2+/+mice. *Huang et al. Blood. 2011.