of psoriatic phenotype in mouse models of the disease. A biomarker is a substance whose measurement is indicative of a disease state.
Finally, we performed studies which demonstrate that our SNAs cause minimal off-target changes in gene expression in human skin cells and in mouse tissue. Such experiments demonstrated that SNA treatment leads to fewer genetic misregulations as compared to linear oligonucleotides against the same target delivered with a commercially available lipid encapsulation-based oligonucleotide delivery system. A misregulated gene is expressed at an inappropriately high or low level.
Phase 1 clinical development for AST-005
We conducted a Phase 1 clinical trial to assess the safety, antipsoriatic efficacy and pharmacodynamic effect of AST-005 in 15 mild to moderate psoriasis patients in Germany. The primary endpoint of the clinical trial was the change in psoriatic infiltrate thickness compared to the start of the study, which is a method of measuring antipsoriatic effects. Secondary endpoints included evaluation of antipsoriatic efficacy by a clinical score, safety and tolerability assessments, and target mRNA reduction. The clinical trial design allowed for intrapatient comparisons of AST-005 to a placebo and a currently approved therapeutic. A mask containing five holes, or test fields, was placed on the patients’ psoriatic lesions, enabling the application of different agents within one lesion. The test fields were treated with one of three strengths of a gel containing AST-005, a matched control gel without AST-005 and an approved therapeutic administered 10 times over a 12-day treatment period. Safety assessments included a complete physical examination with special focus on the skin, vital signs, and laboratory assessments. At the end of the clinical trial, full biopsy punches were taken of the AST-005 gel and vehicle gel treated areas for measurement of TNF mRNA expression.
The Phase 1 clinical trial design utilized a mask that allowed for the evaluation of multiple strengths of AST-005, a placebo, and a currently approved therapeutic within one psoriatic lesion.
We believe our clinical trial design is consistent with other topical studies that have been accepted by the FDA, and the European Medicines Agency, or the EMA.
The results of the clinical trial showed no adverse events related to treatment with AST-005. In addition, AST-005 application reduced the expression of TNF mRNA in a dose dependent manner in the psoriatic skin of the patients. The TNF mRNA reduction elicited by the highest strength of AST-005 gel was statistically significant when