Aclaris Therapeutics (ACRS) Earnings Call Presentation

ATI-2138 Pharmacology and Preclinical Data - ATI-2138 is a highly potent dual inhibitor of ITK and JAK3, with IC50 values of 0.2 nM for ITK and 0.5 nM for JAK3 [6] - ATI-2138 is 44.4 times more potent than ritlecitinib in inhibiting anti-CD3 induced IFNγ production (ITK) and 5.4 times more potent for inhibiting JAK3 dependent IL-2 induced IFNγ production in human whole blood [14] - ATI-2138 is 15 to 38 times more potent than CPI-818 in inhibiting the ITK enzyme activity [18] Phase 2a Clinical Trial - Safety and Efficacy - ATI-2138 was generally well-tolerated in the Phase 2a trial, with no serious adverse events (SAEs) or treatment-emergent adverse events (TEAEs) reported [28] - In the Phase 2a trial, the mean improvement in EASI score at 12 weeks was 61%, and the median improvement was 77% [30] - Excluding an outlier, the mean improvement in EASI score at 12 weeks was 77%, and the median improvement was 82% [37] - At week 12, 63% of patients experienced a ≥4-point improvement in worst itch in the past 24 hours (PP-NRS) [43] Phase 2a Clinical Trial - Pharmacodynamic Assessments - Phase 2a results showed approximately 90% inhibition of both IL2 and IFNγ mRNA observed 1 hour post-dose (~peak) across the 12 weeks of dosing in ITK-TCR Assay [48] - Near complete ATI-2138 ITK target occupancy observed one hour post-dose (~peak) across the 12 weeks of dosing [52] - Phase 2a results showed approximately 80% inhibition of JAK3-induced IFNγ observed 1 hour post dose (~peak) [58] Future Development Plans - Aclaris intends to further develop ATI-2138 in alopecia areata and is exploring other indications relevant to the mechanism of action [78] - Preclinical work is ongoing for next-generation ITK inhibitors, with Aclaris expecting to provide the basis for new INDs starting in 2026 [78]