Product information and disease description Product description Product information Pharmacology

Pharmacodynamics

5 evidence topics · 1 source

Human retinal pigment epithelial cells in vitro: VEGF-A neutralization and VEGF-C suppression

“Transduction of human retinal pigment epithelial cells in vitro by 4D-150 resulted in dose-dependent transgene expression and corresponding reductions in VEGF-A and VEGF-C.” (opens the source at this quote in a new tab)
“The 4D-150 plasmid cassette significantly reduced endothelial cell proliferation compared to the CAG-GFP plasmid and shock controls (1-way ANOVA, P < 0.01), whereas CAG-AFLB alone did not” (opens the source at this quote in a new tab)

Nonhuman primates: intraocular aflibercept and microRNA expression

“Mean 4D-150 aflibercept transgene product levels were nearly 8-fold higher in the retina/choroid (mean ±SD = 22,518 ± 24,981 ng aflibercept/g of tissue) compared to the aqueous humor (2,919 ± 2,366 ng aflibercept/mL).” (opens the source at this quote in a new tab)
“In addition, VEGF-C miRNA expression was detected (up to 91,910 copies per input RNA) from RNA isolated throughout the retina, including the superior, nasal, central, temporal, and inferior regions.” (opens the source at this quote in a new tab)

Nonhuman primates: aqueous aflibercept concentrations by dose and construct

“Analysis of free aflibercept protein concentration in aqueous humor samples collected 21 days after dosing showed a dose response between the highest dose (1 × 1012 vg/eye) and the 2 lower doses (3 × 1011 and 1 × 1011 vg/eye) of 4D-150” (opens the source at this quote in a new tab)
“Interestingly, IVT administration of 4D-150 to NHPs resulted in significantly higher levels of aflibercept protein in aqueous humor samples compared to an equivalent dose of the single-transgene construct (R100.CAG-AFLB), suggesting that the VEGF-C RNAi transgene or its position within the transgene cassette promotes aflibercept expression.” (opens the source at this quote in a new tab)

Nonhuman primate laser-induced choroidal neovascularization model

“At 2 weeks post laser administration, a significant reduction in the incidence of grade IV CNV lesions was observed at all tested doses of 4D-150 compared to vehicle (Fisher's Exact Prob test, P < 0.005 for all comparisons).” (opens the source at this quote in a new tab)
“The CNV complex area was significantly smaller in the 4D-150–treated groups compared to the vehicle group (52%–62% reduction; 2-way ANOVA followed by Tukey-Kramer Honestly Significant Difference (HSD), P < 0.005 for all comparisons; Fig. 7C).” (opens the source at this quote in a new tab)
“The lowest tested dose of 4D-150 (1 × 1011 vg/eye) conferred equivalent protection against CNV compared to the highest dose (1 × 1012 vg/eye).” (opens the source at this quote in a new tab)

Duration of transgene expression in nonhuman primates

“Transgene expression was detected as early as week 1 and increased markedly by week 3. Expression increased further between weeks 3 and 8 and was stably maintained until the final assessment 6 months after administration.” (opens the source at this quote in a new tab)

Aqueous aflibercept concentrations and VEGF suppression measured in participants

No evidence found.