Drugs which inhibit VEGF and its receptors are already the standard of care for a number of diseases including wAMD and DME and is a mainstay of cancer therapy. VEGF is alternatively spliced into two classes of protein: pro-angiogenic VEGF-Axxxa isoforms which are responsible for disease progression, and anti-angiogenic VEGF-Axxxb isoforms which mitigate these effects through competitive binding.
Current therapies, however, target all isoforms of VEGF, are associated with limited efficacy, resistance, off-target effects and toxicity. Modulation of VEGF splicing using our novel compounds aims to reduces pathological VEGF, angiogenesis and disease progression without inhibiting non-pathological, protective forms of VEGF, and so has the potential to offer safer, more efficacious therapies.
Wet Age-Related Macular Degeneration (wAMD) is a neovascular disease of the retina, which means blood vessel growth is upregulated in the back of the eye, in a process largely driven by VEGF. In wAMD, the growth of new vasculature through from the choroid ruptures Bruch’s membrane and causes disruption to the usually uniform layer of photoreceptive cells responsible for vision.
By exploiting the alternative splicing of vascular endothelial growth factor (VEGF) we aim to use our cutting edge technology to introduce an Eye Drop to treat wet AMD and DME. This has the potential to become the patients treatment of choice in an area of high medical unmet need. Our novel small molecule inhibitors have the ability to alter VEGF splicing in a number of indications in addition to our lead ophthalmology programme.
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