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VITAE PHARMACEUTICALS, INC filed this Form S-1 on 08/12/2014
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        VTP-38443 was administered via oral and intravenous routes in rats and cynomolgus monkeys to assess its pharmacokinetics. VTP-38443 was well absorbed in both species with approximately 50% bioavailability, and it exhibited a half-life which we believe is consistent with once-a-day dosing in humans.

Development Plans

        VTP-38443 is currently in preclinical development and we have successfully completed dose ranging toxicology studies. We anticipate completing the necessary preclinical studies and filing an IND in the first quarter of 2016, with Phase 1 clinical trials commencing thereafter. We expect that the single and multiple ascending dose Phase 1 clinical trials will be performed in healthy volunteers, and, in addition to assessing safety, tolerability, and pharmacokinetics, gene induction markers of RCT and inflammation will be analyzed.

VTP-38543 Targeted for Liver X Receptor Beta (LXRb) for Atopic Dermatitis

    Overview

        We have discovered and are developing VTP-38543, an LXRb selective agonist, as a topical agent for the treatment of atopic dermatitis. Atopic dermatitis is a common inflammatory skin disease in children that also affects a large number of adults. It is characterized by a loss of barrier function of the skin, as well as skin inflammation. Other diseases that have some of the same characteristics include contact or allergic dermatitis and psoriasis. The two most commonly used classes of topical therapies for atopic dermatitis are glucocorticoids and calcineurin inhibitors. Though effective, they both have been shown to have serious side effects in some patients. We believe there is a significant opportunity to develop a new therapy that is equally effective but has a better safety and tolerability profile.

        Activation of LXR in skin keratinocytes, the most common cell type in the outermost layer of "normal" skin, plays an important role in maintaining skin function. LXR activity is critical for maintaining the impermeable barrier of skin by stimulating the differentiation of keratinocytes into corneocytes, the major cell type in the protective outer layer of the skin, and stimulating the secretion of lipid rich bodies, called lamellar bodies, which "glue" the corneocytes into becoming the impermeable outer barrier of skin. LXR activation also has an anti-inflammatory effect in skin. We believe LXR agonists' ability to both improve skin inflammation and improve the barrier function of the skin is unique.

        In cell based assays, VTP-38543 has been shown to increase LXRb activity and increase markers of lipid synthesis and secretion of lipids from cells. Lipids is a general term for multiple types of fats. It has also shown decreases in the production of pro-inflammatory proteins from a human macrophage cell line. VTP-38543 decreases skin inflammation in a live mouse model of skin inflammation. It also increases the production of proteins in the skin that are involved in lipid synthesis and secretion that are critical for maintenance of barrier function. Early formulation work has been performed, and several formulations have been identified that provide acceptable skin penetration with appropriate efficacy. We expect to file an IND for VTP-38543 in the second half of 2015.

    Barrier Function and Inflammation in Atopic Dermatitis

        The most abundant cells in the epidermis are keratinocytes, shown in Figure 19 below. These cells differentiate to form the corneocytes, and also generate the lipids that, along with the corneocytes, make up the outermost layer of the epidermis, which is called the stratum corneum. The stratum corneum forms an impermeable protective barrier that prevents loss of water and blocks invasion by pathogens. Accumulating evidence from human genetic studies suggests that primary defects in the epidermal structure, particularly formation of the stratum corneum, play a pivotal role in driving the pathogenesis of atopic dermatitis. For example, filaggrin is an important structural protein in the stratum corneum. According to a 2009 study published in the Journal of Investigative Dermatology, up to 55% of Europeans with atopic dermatitis have mutations in the filaggrin gene. Other mutations have been identified in barrier

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