compared to the effects of the vehicle. These results demonstrate that topically applied SNAs are potentially capable of reducing gene expression in the skin of psoriasis patients, and we believe that these results demonstrate the potential therapeutic application of our gene regulatory SNA platform. While the results of the clinical trial did not show antipsoriatic efficacy, we believe antipsoriatic efficacy was not to be expected based on the length of treatment in this clinical trial. The results of a clinical trial with etanercept, a systemic TNF inhibitor, indicate that four weeks of therapy is required before antipsoriatic efficacy can be observed.
A gel containing AST-005 reduced the target TNF mRNA expression in the lesional psoriatic skin of patients in a dose dependent manner after topical application in a Phase 1 clinical trial. The knockdown achieved by the high strength of gel was statistically significant compared to the vehicle treated skin. * p < 0.05
On December 2, 2016, we entered into the Purdue Collaboration for further development of AST-005 in mild to moderate psoriasis and in other indications. Together with Purdue, we will pursue continued development of AST-005 in psoriasis and potentially in other indications. Pursuant to the Purdue Collaboration, Purdue is conducting a Phase 1b clinical trial in psoriasis patients in Germany to evaluate the effect of higher concentrations of AST-005 gel on TNF mRNA and downstream mRNA expression. Patient dosing is complete and no serious adverse events have been reported. We expect to have the topline results of the clinical trial in early 2018.
XCUR17—a topically applied anti-IL-17RA SNA
XCUR17, our second therapeutic candidate, targets the mRNA that encodes IL-17RA, a protein that is considered essential in the initiation and maintenance of psoriasis. Although the availability of inhibitors of TNF revolutionized the systemic treatment of severe psoriasis, studies of disease pathogenesis have shifted attention to the IL-17 pathway, in which IL-17RA is a key driver of psoriasis. IL-17 binding to IL-17RA on keratinocytes stimulates and perpetuates the inflammation cascade of psoriasis. IL-17RA-mediated inflammation can be inhibited by disrupting the protein’s function. Brodalumab, an anti-IL-17RA monoclonal antibody, was approved by the FDA as an effective treatment for chronic moderate to severe plaque psoriasis. Our strategy is to reduce the levels of IL-17RA in the skin by topically applying XCUR17. In preclinical studies, XCUR17 showed inhibition of IL-17RA expression in the keratinocytes of the skin. We filed a CTA for a Phase 1 clinical trial of XCUR17 in patients with psoriasis in Germany in the third quarter of 2017. Our CTA was approved in February 2018 and we expect the first