RORγt inhibitors as potential back-ups for the phase II candidate VTP-43742 from Vitae Pharmaceuticals: patent evaluation of WO2016061160 and US20160122345. (2nd January 2017)

• Record Type: Journal Article
• Authors: Gege, Christian
• Is Part Of: Expert opinion on therapeutic patents. Volume 27:Number 1(2017:Jan.)
• Page Start: 1
• Page End: 8
• Publication Date: 2017-01-02
• Subjects: Retinoid-related orphan receptor gamma t -- RORγt -- RORc2 -- VTP-43742 -- VTP-45489 -- back-up compound; Drugs -- Patents -- Periodicals; 615.10272
• DOI: 10.1080/13543776.2017.1262350
• Languages: English
• ISSNs: 1354-3776

Abstract

ABSTRACT: Retinoic acid receptor-related orphan nuclear receptor gamma t (RORγt or RORc2) is a key transcription factor for the differentiation of naïve proinflammatory CD4 + T cells and the production of T helper-17 (TH 17) cells. Inhibiting RORγt activity is thought to be beneficial in targeting a variety of inflammatory and autoimmune disorders. Recently Vitae Pharmaceuticals (to be acquired by Allergan) reported positive top-line results from a Phase 2a clinical trial of RORγt inhibitorVTP-43742 in psoriatic patients. The compound was reported to demonstrate a clear signal of efficacy over a short four-week period and no drug-related cardiac abnormalities were observed; however, in the 700 mg dose group reversible transaminase elevations were observed in four patients, which prompted the company to cancel testingVTP-43742 at a initially planned third, higher dose. In Vitae Pharmaceuticals latest patent applications, WO2016061160 and US20160122345, potential dihydropyrrolopyridine back-up compounds of clinical candidateVTP-43742 (covered in WO2015116904) are disclosed. In light of the recently announced RORγt back-up moleculeVTP-45489, the improvements of the new compounds are discussed and their potential impact is elucidated.