Pharmacokinetic Results: Systemic exposure was low as indicated by plasma drug levels that were below the limits of quantification (1ng/ml) in all subjects at day 28. • Consistent with low systemic exposure, no significant changes in circulating T, B and NK cells were observed at day 28. To assess skin penetration, punch biopsies were obtained at baseline and day 28 which demonstrated topical ATI-502 absorption consistent with pre-clinical skin models. • Mean of 5650 nanograms/gram at day 28 (range 3130 - 8170 ng/g).
Pharmacodynamic / RNA Sequencing Results: 2 patients had marked elevation of the interferon gamma and cytotoxic T-cell gene expression signatures at baseline: one received active drug and one received vehicle. At day 28, the patient on active drug demonstrated a positive change in the 2 biomarkers, while the patient on vehicle did not demonstrate a positive change in the 2 biomarkers. 2 patients had low elevation of the interferon gamma and cytotoxic T-cell gene expression signatures at baseline: one received active drug, one received vehicle. At day 28 both patients showed a partial positive change in the 2 biomarkers. 2 patients had no elevation of the interferon gamma and cytotoxic T-cell gene expression signatures at baseline: both patients received active drug. At day 28, neither patient showed any material change in the 2 biomarkers. Safety No serious adverse events (SAEs) were reported during the 28-day dosing period. One subject receiving AT
Key Results Summary: This data is the first indication that ATI-502 is absorbed through human skin in the clinical setting and engages the target. The results also demonstrate the pharmacodynamic effect of modulating the appropriate genes associated with the interferon gamma pathway and cytotoxic T-lymphocytes, which are 2 of 3 biomarker components of the Alopecia Areata Disease Activity Index (ALADIN) score. Our hypothesis is this response can be predicted by a patient’s baseline genetic signature. “This is the first time we have demonstrated that Topical ATI-502 is positively impacting the genetic signature implicated in alopecia areata,” said Stuart Shanler, M.D., Chief Scientific Officer of Aclaris Therapeutics, Inc.
