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VITAE PHARMACEUTICALS, INC filed this Form S-1 on 08/12/2014
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        The goal of the RORgt program is to develop an orally active agent. VTP-43742 was administered via oral and intravenous routes in rats and dogs to assess its pharmacokinetics, and the oral bioavailability in dogs was 66% and half-life was 15 hours; exhibiting good oral bioavailability and long plasma half-life. Based on additional preclinical studies, we believe VTP-43742 should be well absorbed in humans, and we believe it may offer a first-in-class therapy for patients suffering from autoimmune disease. We predict that VTP-43742 will have a plasma half-life of approximately 24 hours in humans.

    Development Plans

        We plan to file an investigational new drug application, or IND, with the FDA for VTP-43742 in the first half of 2015, and expect to begin Phase 1 clinical trials thereafter. The initial Phase 1 clinical trial is expected to be a single ascending dose trial in healthy human volunteers. The clinical trial will be designed to demonstrate that VTP-43742 is well tolerated by the trial subjects and that it does not cause clinically significant changes in clinical laboratory tests or vital signs. This clinical trial will also access the pharmacokinetics properties of the product candidate. We plan to begin a two week, Phase 1, multiple ascending dose clinical trial in the second half of 2015. This clinical trial will be performed in patients with psoriasis, in which we will analyze the safety, tolerability and pharmacokinetics of two weeks of once-a-day dosing of VTP-43742. This clinical trial is expected to provide proof-of-concept against an autoimmune disease since two weeks is generally a sufficient time period to test for improvements in the skin lesions of psoriasis patients. In addition to demonstrating clinical improvement in the skin lesions of psoriatic patients, skin biopsies will be performed to assess inflammation as well as treatment related changes in Th17, IL-17, and other effector cytokines.

VTP-38443 Targeting Liver X Receptor Beta (LXRb) for Acute Coronary Syndrome (ACS)

    Overview

        We discovered and are developing VTP-38443, an orally active LXRb selective agonist which is wholly owned by us, for the treatment of acute coronary syndrome, or ACS. ACS includes unstable angina and myocardial infarction, referred to herein as a MI or heart attack. Patients who have an ACS event have a 10-20% chance of having a significant cardiovascular event within six months of the original event. ACS patients have atherosclerotic plaques which contain lipid rich foam cells, inflammatory cell infiltrates, a thin cap of the atherosclerotic plaque prone to rupture, and a surface to the plaque that is prone to form blood clots. Current therapies include antiplatelet, anti-blood clotting and cholesterol lowering agents. LXRs are involved in cholesterol homeostasis and regulate removal of cholesterol from cells, or RCT, via ABCA1, which is a cellular transporter that moves cholesterol out of cells and onto HDL. We believe that an LXR agonist would be useful in treating ACS patients because it both augments RCT, which removes cholesterol from the plaque, and inhibits the production of pro-inflammatory proteins. Both of these mechanisms make the plaque less inflamed and less lipid rich, resulting in the plaque surface being less prone to formation of blood clots.

        In preclinical studies, VTP-38443 has been shown to be active in both rodent and human cell assays in inducing proteins that are involved in RCT and suppressing proteins involved in inflammation. In a mouse model that mimics the processes of ACS, VTP-38443 decreased cholesterol in the atherosclerotic vessels and simultaneously decreased inflammation in the vessels. In dose ranging toxicology studies, the safety margins between efficacious systemic exposures and toxic exposures were identified. VTP-38443 is progressing into preclinical development.

    Reverse Cholesterol Transport (RCT) in ACS

        ACS patients have a high rate of recurrent cardiovascular events. Statin treatment lowers cholesterol levels and has been demonstrated to reduce the number of subsequent cardiovascular events. While statin treatment has clinical benefit, protection is not complete. We believe treatment with agents that remove cholesterol from atherosclerotic plaques to induce direct plaque regression and stabilization may result in additional reduction in events. One approach is to directly target the active removal of cholesterol from

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