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VITAE PHARMACEUTICALS, INC filed this Form S-1 on 08/12/2014
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ABCA1 mRNA in Human Skin Fibroblasts


Figure 15: VTP-38443 is a potent inducer of ABCA1 mRNA expression in a human fibroblast cell line.

        LXR activation has been shown in preclinical studies to suppress inflammatory proteins in multiple human cell types, including macrophages. IL-6 is a key inflammatory protein and is expressed in human macrophages. As shown in Figure 16 below, VTP-38443 reduced IL-6 secretion from the human derived, activated, THP-1 macrophage cell line in a concentration dependent manner.

Inhibition of IL-6 Secretion in THP-1 Macrophages


Figure 16: VTP-38443 significantly decreased secretion of IL-6 in activated THP-1 macrophages.

        One of the key issues with prior LXR agonists is their inability to clearly separate the induction of ABCA1 from the induction of plasma and liver TGs, driven primarily by LXRa. To test the hypothesis that a potent LXRb-selective partial agonist, such as our VTP-38443, in a reporter assay would show improved separation between these two effects, we looked at the ability of VTP-38443 to induce ABCA1 and TG levels upon oral administration to cynomolgus monkeys.

        Cynomolgus monkeys were dosed with VTP-38443 orally at 0.01 and 0.03 mg/kg, or mpk, per day for 14 days. As shown in Figure 17 below, VTP-38443 increased the expression of ABCA1 and ABCG1, markers of RCT, in monkey blood at both doses tested and did not have significant triglyceride elevations in plasma at either dose. Including data from these and other experiments, we have determined that there