Value Proposition
· Comprehensive Targeting: Engineered antagonist proteins combine elements of both VEGF receptor (VEGFR)-1 and VEGFR-2 to target all human VEGF ligands and sequester 2 ligand homodimers simultaneously.
· Superior Inhibition: Comprehensive ligand blockade inhibits neovascularization more effectively than existing VEGF-A only therapies.
· Addresses Treatment Resistance: Targets additional ligands (e.g., VEGF-C) to improve outcomes in patients who are non-responders or who develop resistance to current anti-VEGF treatments.
· Demonstrated Efficacy: Dramatically reduces ocular neovascularization in mouse models, including scenarios where current standard-of-care anti-VEGF therapies are ineffective.
· Novel Mechanism: New receptor decoy architecture represents a significant advancement in VEGF pathway inhibition.
· Expands Treatment Paradigm: Provides therapeutic option for patients who do not benefit from current anti-VEGF therapies, expanding treatment possibilities beyond current clinical options.
Unmet Need
· Retinal and choroidal neovascular diseases are the most common causes of vision loss worldwide. This includes neovascular age-related macular degeneration (NVAMD), which had a global prevalence of 196 million cases in 2020 and is projected to reach 288 million by 2040, as the population ages.
· Anti-VEGF-A therapies have emerged as a powerful strategy to treat ocular neovascular diseases; however, up to 50% of patients do not respond or experience reduced effectiveness over time.
· The resistance to current anti-VEGF therapies highlights the need for innovative approaches that can comprehensively target all VEGF ligands.
· The inability of existing therapies to effectively manage neovascularization in a significant subset of patients reveals a critical gap in treatment options
· Failure to control ocular neovascularization can lead to progressive vision loss and diminished quality of life. Therefore, there is an urgent need for new therapeutic solutions that can reliably inhibit the pathological growth of blood vessels in the eye.
Technology Description
· The technology features an innovative class of antagonist proteins designed to target all human VEGF ligands and bind multiple ligands simultaneously. This approach enhances treatment efficacy in combating ocular neovascularization.
· The antagonist proteins work by blocking VEGF interactions with its receptors on endothelial cells. This interruption of the signaling pathway reduces the proliferation, migration, and survival of cells responsible for angiogenesis, thereby preventing the development of unwanted and leaky blood vessels.
Stage of Development
· Preclinical Stage
Data Availability
· Data available upon request.
Publication
· Sargunas, P. R., Ariail, E., Lima E Silva, R., Patil, A., Zhang, M., Shen, J., Lopes, B. S., Oh, Y., McCue, A. C., Ramasubramanian, R., Stephenson, A. C., Popel, A. S., Campochiaro, P. A., & Spangler, J. B. (2025). Bispecific receptor decoy proteins block ocular neovascularization via simultaneous blockade of vascular endothelial growth factor A and C. Molecular therapy : the journal of the American Society of Gene Therapy, 33(7), 3128–3146. https://doi.org/10.1016/j.ymthe.2025.03.027
