Repositioning Candidate Details
| Candidate ID: | R1558 |
| Source ID: | DB15303 |
| Source Type: | investigational |
| Compound Type: | biotech |
| Compound Name: | Faricimab |
| Synonyms: | Faricimab |
| Molecular Formula: | -- |
| SMILES: | -- |
| DrugBank Description: | Retinal vascular diseases (RVDs) such as diabetic macular edema (DME), age-related macular degeneration (AMD), and retinal vein occlusion (RVO) are typically caused by retinal ischemia and subsequent neovascularization (NV). Vascular endothelial growth factor A (VEGF-A) is a well-known mediator of retinal NV, and many currently approved RVD therapies such as and solely target VEGF-A. However, another set of factors, the Tie/Ang axis, comprising the transmembrane Tie-2 receptor and its soluble ligands Ang-1 and Ang-2, has been shown to play critical roles in mediating VEGF-A-induced NV. Faricimab is an IgG<sub>1</sub>-derived bispecific antibody capable of simultaneously binding to and depleting VEGF-A and Ang-2, which has been developed to improve therapeutic efficacy, especially in patients that respond poorly to anti-VEGF-A monotherapy. Faricimab is under investigation in clinical trial NCT03823287 (A Study to Evaluate the Efficacy and Safety of Faricimab in Participants With Neovascular Age-Related Macular Degeneration (TENAYA)). |
| CAS Number: | 1607793-29-2 |
| Molecular Weight: | |
| DrugBank Indication: | -- |
| DrugBank Pharmacology: | -- |
| DrugBank MoA: | The retina is largely avascular to facilitate effective photoreceptor function; rather, the retina is fed by both retinal and choroidal capillary networks, pathologies of which result in retinal and choroidal vascular diseases such as diabetic macular edema (DME), age-related macular degeneration (AMD), and retinal vein occlusion (RVO). One of the underlying causes of retinal vascular diseases (RVDs) is retinal neovascularization (NV), the aberrant growth of new vasculature, usually due to sustained retinal ischemia and mediated primarily by vascular endothelial growth factor A (VEGF-A). VEGF-A is a VEGF family member, which also includes VEGF-B, -C, and -D, whose members signal through the VEGF receptors (VEGFRs) VEGFR-1, -2, and -3 to mediate endothelial and lymphatic growth. Extensive work in animal models of RVD has demonstrated that VEGF-A is necessary but not sufficient in many cases to mediate NV, suggesting that additional factors may be required in deep retinal capillary beds. One such factor has been identified as the angiopoietins Ang-1 and Ang-2 and their cellular receptor Tie-2; Ang-1 is a full Tie-2 agonist whose binding results in Tie-2 phosphorylation and downstream signalling, whereas Ang-2 is a Tie-2 partial agonist/antagonist that inhibits Tie-2 phosphorylation. Ang-1 generally has a protective effect, making endothelial cells less responsive to VEGF-A, while Ang-2 increases VEGF-A-dependent NV and stimulates pericyte apoptosis and breakdown of both the blood-brain and blood-retinal barriers; Ang-2 is upregulated in retinal vascular development and retinal ischemia. Faricimab is a bispecific antibody (bsAb) based on human IgG<sub>1</sub> comprising two different heavy and two different light chains capable of simultaneously binding to both VEGF-A and Ang-2 produced using the "CrossMab" platform. Faricimab binds VEGF-A and Ang-2 with binding affinities (K<sub>D</sub>) of approximately 3 and 22 nM, respectively; importantly, faricimab does not detectably bind Ang-1. Also, the faricimab Fc region has been modified to reduce binding to FcγR and FcRn receptors. The former virtually eliminates immune-mediated functions such as antibody- and complement-dependent cytotoxicity and antibody-dependent phagocytosis, whereas the latter increases faricimab systemic clearance by reducing FcRn-mediated IgG recycling. Thus, faricimab works by depleting both VEGF-A and Ang-2 to prevent retinal NV in the privileged ophthalmic environment. |
| Targets: | Vascular endothelial growth factor A antagonist; Angiopoietin-2 antagonist |
| Inclusion Criteria: | Therapeutic strategy associated |
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