ATI-1777, a Topical Jak1/3 Inhibitor, May Benefit Atopic Dermatitis without Systemic Drug Exposure: Results from Preclinical Development and Phase 2a Randomized Control Study ATI-1777-AD-201

• Published in: JID innovations 2024-03, Vol.4 (2), p.100251, Article 100251
• Main Authors: Changelian, Paul, Xu, Canxin, Mnich, Steve, Hope, Heidi, Kostecki, Kourtney, Hirsch, Jeff, Loh, Chin-Yi, Anderson, David, Blinn, James, Hockerman, Susan, Dick, Evan, Smith, Walter, Monahan, Joseph, Raoof, Tooraj, Forman, Seth, Burt, David, Barnes, Brad, Gordon, David, Walker, Neal, Sudzina, John, Tucker, Stephen, Jacobsen, Jon
• Format: Article
• Language: English
• Subjects: Hematopoiesis; Metabolism; Original; Porcine model; Screening; Skin
• ISSN: 2667-0267; 2667-0267
• DOI: 10.1016/j.xjidi.2023.100251

Atopic dermatitis, a chronic, pruritic skin disease, affects 10–30% of children and up to 14% of adults in developed countries. ATI-1777, a potent and selective Jak1/3 inhibitor, was designed with multiple sites of metabolism to deliver local efficacy in the skin and limit systemic exposure. In preclinical studies, ATI-1777 selectively inhibited Jak1/3 with limited systemic exposure and without any adverse effects. The primary goal of this study was to assess the preliminary clinical efficacy of ATI-1777 topical solution in adults with moderate or severe atopic dermatitis. ATI-1777-AD-201, a phase 2a, first-in-human, randomized, double-blind, vehicle-controlled, parallel-group study, evaluated the efficacy, safety, tolerability, and pharmacokinetics of ATI-1777 topical solution in 48 participants with atopic dermatitis over 4 weeks. The primary endpoint was a reduction of a modified Eczema Area and Severity Index score from baseline. Reduction was significantly greater in the ATI-1777–treated group on day 28 than in vehicle-treated group (percentage reduction from baseline = 74.45% [standard error = 6.455] and 41.43% [standard error = 6.189], respectively [P < .001]). Average plasma concentrations of ATI-1777 were