Highlights from the oral presentation include:
- For the first time, 4DMT described the design of 4D-150: a dual transgene, intravitreal gene therapy inhibiting four distinct VEGF family members for the treatment of wet AMD and DME. The combination of transgenes independently encoding for VEGF-C RNAi and for aflibercept provides a multi-mechanistic approach to inhibiting angiogenesis.
- In the NHP laser-induced CNV model, a single intravitreal injection of 4D-150 resulted in 100% suppression of CNV lesions 4-weeks after laser administration, the primary endpoint of the study, including at the lowest dose tested of 1E11 vg/eye; no uveitis or retinal abnormalities were reported at this 1E11 vg/eye dose level.
- In an acute biodistribution study of 4D-150 in NHP, a single intravitreal injection resulted in both high levels of ocular aflibercept expression and VEGF-C miRNA expression within the retina at 4 weeks, with no evidence of uveitis or retinal abnormalities observed.
- A single intravitreal injection of a 4D-150 prototype at two dose-levels (1E11 & 1E12 vg/eye) resulted in sustained, durable ocular anti-VEGF expression through 12 months in the NHP laser-induced CNV model.
