Accropeutics has announced positive results from a Phase 2 clinical trial evaluating AC-201, its oral selective TYK2/JAK1 inhibitor, for the treatment of moderate-to-severe plaque psoriasis. The study met its primary endpoint and key secondary endpoints across all three dosing regimens, demonstrating significant clinical improvement compared to placebo.
The multicenter, randomized, double-blind, placebo-controlled trial enrolled 145 Chinese patients with moderate-to-severe plaque psoriasis. Participants were randomized in equal groups to receive AC-201 at doses of 25mg twice daily, 50mg twice daily, 100mg once daily, or placebo for 12 weeks.
Significant Efficacy Across Multiple Endpoints
The trial's primary endpoint was the proportion of patients achieving at least 75% improvement in the Psoriasis Area and Severity Index (PASI-75) at week 12. Results showed dose-dependent responses with PASI-75 rates of 31.4% for the 25mg twice-daily group (p=0.012 vs. placebo), 74.3% for the 50mg twice-daily group (p<0.001), and 59.5% for the 100mg once-daily group (p<0.001), compared to just 8.1% for placebo.
Secondary endpoints also demonstrated significant improvements. PASI-90 response rates (representing 90% or greater improvement) were 20% for the 25mg twice-daily group, 48.6% for the 50mg twice-daily group, and 24.3% for the 100mg once-daily group, versus 2.7% for placebo. All p-values were statistically significant compared to placebo.
Additionally, the static Physician's Global Assessment (sPGA) scores of 0 or 1 ("clear" or "almost clear") were achieved by 31.4% of patients in the 25mg twice-daily group, 71.4% in the 50mg twice-daily group, and 59.5% in the 100mg once-daily group, compared to 5.4% in the placebo group.
Favorable Safety and Tolerability Profile
AC-201 was generally well-tolerated across all dose levels. No serious adverse events (SAEs) or adverse events leading to permanent discontinuation were reported during the study. The majority of treatment-emergent adverse events (TEAEs) were mild to moderate in severity, with upper respiratory tract infection and hypertriglyceridemia being the most commonly reported.
This safety profile is particularly noteworthy in the context of JAK inhibitors, a class that has faced regulatory scrutiny due to safety concerns with some members of the class.
Mechanism of Action
AC-201 is a novel, highly selective oral small-molecule inhibitor that targets the pseudo kinase domain (JH2) of TYK2/JAK1, without affecting the JAK2/JAK2 signaling pathway. This selective inhibition is designed to block pro-inflammatory cytokine signaling involved in psoriasis pathogenesis while potentially avoiding some of the safety concerns associated with broader JAK inhibition.
The drug has previously completed long-term nonclinical toxicology testing, including reproductive toxicity studies. Phase 1 studies in healthy volunteers conducted in Australia and China demonstrated favorable pharmacokinetics with dose-proportional exposure, no significant drug accumulation upon multiple dosing, and no clinically relevant food effects.
Market Context and Future Development
"We are excited to see the positive results from the Phase 2 study of AC-201, and we will accelerate its clinical development to benefit patients with psoriasis and other autoimmune diseases," said Dr. Xiaohu Zhang, co-founder and CEO of Accropeutics.
Psoriasis affects approximately 125 million people worldwide, with moderate-to-severe cases representing a significant portion requiring systemic therapy. While injectable biologics have transformed treatment options, there remains high demand for effective oral therapies that offer convenience without compromising efficacy.
The efficacy and safety findings from this Phase 2 trial support advancing AC-201 into Phase 3 development for plaque psoriasis. Accropeutics is also exploring the potential of AC-201 in other immune-mediated inflammatory diseases, including systemic lupus erythematosus.
About Accropeutics
Accropeutics, formally known as Accro Bioscience (Suzhou) Limited, is a clinical-stage biotech company focused on molecular mechanisms of regulated cell death and related pathogenesis in human diseases. The company has developed a portfolio of innovative drug candidates at various stages of development.
In addition to AC-201, the company's pipeline includes AC-003, a RIPK1 inhibitor that has completed Phase 1 trials in China and the United States and received Orphan Drug Designation from the FDA for acute graft-versus-host disease (aGVHD). Another candidate, AC-101, is a RIPK2 inhibitor currently in Phase 1b trials for ulcerative colitis.
Accropeutics holds global rights to these assets with 24 patents issued across major markets including China, Japan, Korea, the United States, and the European Union.
