Topical application of XCUR17 in a prototype gel to healthy human skin ex vivo results in a dose-dependent decrease in IL-17RA mRNA expression. * p < 0.05; *** p< 0.001 vs the controls
Planned Phase 1 clinical development for XCUR17
We filed a CTA to conduct 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 patient in our Phase 1 clinical trial to be dosed in early 2018. We expect this clinical trial to be completed in mid-2018. The primary endpoints of the clinical trial will be safety and tolerability, and the secondary endpoints will include the measurement of IL-17RA mRNA and protein levels from lesional skin biopsies, lesional skin histology and other assessments of mRNA targets in the psoriasis network.
The clinical trial design allows for intrapatient comparisons of XCUR17 to a placebo and a currently approved therapeutic. A mask containing 5 holes will be placed on the patient’s skin, enabling the application of three different strengths of a gel containing XCUR17 as well as a placebo and a currently approved therapeutic within one psoriatic lesion. The drug will be applied daily for 26 days in up to 25 patients. Over the course of the clinical trial, the safety and tolerability of XCUR17 will be monitored. In addition, the severity of psoriasis in the treated areas will be assessed. At the end of the clinical trial, biopsy samples from XCUR17- and vehicle-treated areas will be taken and interrogated for IL-17RA and downstream mRNA modulation to demonstrate that XCUR17 engages the target of interest and has an effect on inflammation in the skin. We believe our clinical trial design is consistent with the clinical trial design for other topically applied therapeutic candidates that have been accepted by the FDA and EMA.
Additional gene regulation programs
We believe that additional gene regulation programs are enabled by the successful results of our Phase 1 clinical trial with AST-005 and the results from preclinical testing of XCUR17. We are also evaluating the use of AST-005 in other indications where anti-TNF therapeutics have been successful and where we believe we have a strategic advantage. In addition, we believe that the initial clinical results of our Phase 1 clinical trial of AST-005 may have important implications for the application of our proprietary SNA technology across a broad range of organs and diseases. First, there were no adverse events related to treatment with AST-005 in the Phase 1 clinical trial and we also observed initial pharmacodynamic activity in the Phase 1 clinical trial. We believe that there are other skin diseases for which we can design therapeutically relevant SNAs. Other targets of interest include IL-17RA, which