• Single ascending doses of VTP-43742 safe and generally well-tolerated, demonstrated once-daily pharmacokinetics
  • Robust ex vivo biomarker response, suppressing pro-inflammatory IL-17A by more than 90 percent

FORT WASHINGTON, PA, USA I September 8, 2015 I Vitae Pharmaceuticals, Inc. (VTAE), a clinical-stage biotechnology company, today announced positive top-line results from its Phase 1 single ascending dose clinical study of VTP-43742 in autoimmune disorders. VTP-43742 is Vitae’s first-in-class, wholly owned RORγt inhibitor being developed for the treatment of a range of autoimmune disorders, potentially including psoriasis, psoriatic arthritis, rheumatoid arthritis, multiple sclerosis and irritable bowel disease (IBD), as well as numerous orphan diseases.


In this double-blind, randomized, placebo-controlled study that evaluated the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) profile of single oral doses of VTP-43742 in 53 healthy human volunteers, VTP-43742 was safe and generally well tolerated at all dose levels across a 60-fold dose range. No serious adverse events were reported and there were no drug-related clinical laboratory or electrocardiogram (ECG) abnormalities.

VTP-43742 was also evaluated in an ex vivo assay for its ability to inhibit the production of pro-inflammatory cytokine IL-17A in blood obtained from study subjects. Subjects receiving VTP-43742 showed a dose-dependent suppression of RORγt dependent IL-17A production by more than 90 percent, with the effect largely sustained over the full 24-hour measurement period.

In animal studies, steady inhibition of RORγt was necessary to achieve full therapeutic efficacy, indicating the importance of a relatively long plasma half-life. The plasma half-life of VTP-43742 was observed to be approximately 30 hours in this clinical trial, supporting the potential for effective once-a-day dosing in humans.

“VTP-43742’s robust and sustained lowering of IL-17A production observed in the ex vivo blood assay, paired with its favorable safety, tolerability and PK profile, demonstrate that this first-in-class drug candidate has the potential to safely and effectively treat a range of autoimmune conditions,” said Dr. Richard Gregg, Chief Scientific Officer of Vitae. “We are extremely encouraged by the PK and PD data, and look forward to reporting additional clinical results, including top-line proof-of-concept data in psoriasis patients, by the end of the year.”

Vitae is currently conducting a Phase 1 multiple ascending dose clinical trial of VTP-43742, which was initiated in August 2015. This trial includes both healthy human volunteers and patients with moderate to severe psoriasis. The Company plans to begin dosing psoriatic patients in the second half of 2015, with top-line clinical efficacy results expected by the end of 2015.

About Autoimmune Disorders

Autoimmune disorders, where a patient’s own immune system attacks normal tissue, make up a large number of human disorders. Increased activity of a class of lymphocytes called Th17 cells, and the subsequent excess production of pro-inflammatory cytokines, including IL-17, by those cells are critical parts of the pathophysiology of many human autoimmune disorders. RORγt is a nuclear hormone receptor that is essential for the formation and function of Th17 cells. Vitae believes inhibition of excess RORγt activity in immune cells will be beneficial for the treatment of multiple autoimmune disorders, potentially including psoriasis, psoriatic arthritis, rheumatoid arthritis, multiple sclerosis and / or IBD, as well as numerous orphan diseases.

About VTP-43742

VTP-43742 is Vitae’s first-in-class, wholly owned product candidate for the potential treatment of a variety of autoimmune disorders and orphan diseases. In preclinical studies, VTP-43742 inhibited the activity of RORγt and has demonstrated potent inhibition of multiple Th17 cell-dependent pro-inflammatory cytokines, including IL-17. It is highly selective versus other ROR isotypes, and has a plasma half following single oral dosing that is consistent with a once a day dosing schedule. VTP-43742 has demonstrated superior efficacy in an animal model of multiple sclerosis in direct comparison to an IL-17A monoclonal antibody. Vitae initiated Phase 1 testing with VTP-43742 in June of 2015 with this Phase 1 single ascending dose clinical trial in healthy human volunteers. A Phase 1 multiple ascending dose clinical trial in healthy human volunteers was initiated in August 2015.

About Vitae Pharmaceuticals

Vitae Pharmaceuticals is a clinical-stage biotechnology company focused on discovering and developing first-in-class, small molecule drugs for difficult-to-drug disease targets that can potentially address significant unmet medical needs, including programs in autoimmune disorders, atopic dermatitis, Alzheimer’s disease and diabetes. This robust and growing portfolio of novel product candidates is generated internally by Contour(R), Vitae’s proprietary structure-based drug discovery platform.

SOURCE: Vitae Pharmaceuticals