Development of novel biologic inhibitors of Semaphorin3A for the treatment of retinal vascular diseases.


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Challenge: Diabetic retinopathy and age-related macular degeneration are the leading causes of blindness in working age and elderly populations. While anti-VEGFs revolutionized treatment of retinal vasculopathies, currently available drugs can cause neuronal degeneration. Besides, over 40% of patients respond poorly to these treatments, leaving patients with no alternative, ultimately leading them to blindness. There is thus a clear need for novel therapeutics in this area.

Solution: Over the past decade, the team has been elucidating novel pathways that cause retinal vasculopathies. More importantly they identified a neuron-derived protein called Semaphorin3A (SEMA3A) as a central mediator of diabetic retinopathy. After providing robust proof of concept for the neutralization of SEMA3A in retinal vascular diseases, they developed a first generation of biologic inhibitors that target SEMA3A and VEGF. Beyond preventing vascular permeability, the lead compound also enhances reparative vascular regeneration in the ischemic retina, making it the first drug in development with such properties. In the current project, the team aims to pursue the development and optimization of novel biologic inhibitors of SEMA3A for ocular applications, as well as determining their ocular pharmacokinetic and safety profiles in animal models.

Expected achievements/Impact: The proposed work will bring a novel first-in-class drug for one of the most prevalent causes of blindness to the doorstep of an IND filling. Based on the fact that over a third of patients with diabetic retinal disease poorly respond to current standards of care, rationale and proof of concept suggest that SEMA3A-traps will fill a currently unmet clinical need. Moreover, any maturation of the project and further developments of the technologies will create value for SemaThera, whose objective is to become a major player in the field of ophthalmology in a near future.

Principal Investigator
Mike Sapieha
Hôpital Maisonneuve-Rosemont
Véronique Bougie
Ongoing Project
$ 1 959 871 / 2.5 years
Supported by CQDM through:
And by co-funding partners
– SemaThera
– SENJU Pharmaceutical
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