Complete final pre-clinical development of humanized anti-CD160 monoclonal antibody against ocular neoangiogenesis – MAB-VISION

Pathological ocular neoangiogenesis is a major cause of blindness and low vision in the world. In particular, haemorrhages associated with neovascularisations are primary causes of severe vision loss in retinal diseases such as the wet form of age-related macular degeneration (AMD). The seven majors prevalence of wet AMD accounts for more than 1.7 million people (300,000 patients in France) with about 200,000 new cases of wet AMD diagnosed each year. Wet AMD is diagnosed in people over the age of 50 in industrial countries. The prevalence segmentation is as follows: 0.3% before 70 years old, 1% between 70 and 80 years old and 4% after 80 years old. Today, only a small portion of the diseased population is treated, the reasons being most probably the cost, and the fact that all the patients are not correctly diagnosed. It is anticipated that the global population eligible to treatment will grow dramatically to nearly 3 million by 2020.

Over the recent years, the care of wet AMDs has been revolutionized by the use of biological antiangiogenic agents that target a protein called vascular endothelial growth factor (VEGF), an important element in angiogenesis. Lucentis (antibody Fab fragment), which is the current gold standard treatment, demonstrated its ability to slow down the rate of progression of vision loss from wet AMD. In addition, only one-third of patients treated by Lucentis present some improvement in vision. Furthermore, 15-20% of wet AMD forms are not responder to Lucentis treatments. In such cases, wet AMD non receptive patients have no alternative treatments available. It is worth mentioning that, in order to obtain a stable result with Lucentis, many patients may be treated with up to 24 Lucentis intravitreal injections during 2 years; such high frequency and long lasting treatment increases the risk of deleterious events and undesirable side effects, inducing conjunctival hemorrhage, pain in the eye, increased intraocular pressure, iris inflammation or uveitis and blurred vision, which evidently leads to compliance issue. Therefore, alternative treatments to such gold standard, conferring long-lasting antiangiogenic efficacy, no resistance nor side effects phenomena, by targeting distinct neo-angiogenic pathways, are needed.
Besides, current AMD treatment represents a high economic burden for health systems. Indeed, Lucentis currently represents 90% of the wet AMD market, with a pricing around 1200 € per injection, approximately representing 15k€ a year per patient, during two years. Therefore, novel molecules targeting AMD market are likely to promote competition in a field where the current monopoly seems to burden public health system costs.

The MAB-Vision project proposes to develop a new antibody-based strategy for AMD treatment, as for Lucentis, with a VEGF-independent mode of action through a new target exclusively expressed on neovessels CD160), to offer a new solution with better and more durable activity (in particular towards patients not responding to anti-VEGF treatments).

The consortium, which has been selected for the good complementarities of competencies of the partners, is composed by 1 industrial and 3 academics. MABLife, a SME company, will bring in its expertise in antibodies design, production and characterisation. INSERM (UMR1043) and CHU PURPAN will bring their expertise in vivo and in vitro experiments on corneal, retinal and choroidal neaoangiogenesis with anti-CD160 monoclonal antibody, while GENOPOLE will bring their expertise in mAB cGMP production (CMC). It is worth mentioning that CHU PURPAN will also add significant value in the programme through its expertise and experience in the daily treatment of AMD patients. The strong expertises of the four teams constitute a convincing evidence that the goals proposed in this application for an ANR grant will be achieved.