Accro Bioscience (Suzhou) Limited (Accropeutics), a clinical-stage biotech company focused on molecular mechanisms of regulated cell death and related pathogenesis in human diseases, announced positive results from their phase 2 clinical trial of AC-201, an oral, selective TYK2/JAK1 Inhibitor, in moderate-to-severe plaque psoriasis. Primary and key secondary endpoints including Psoriasis Area and Severity Index (PASI)-75, PASI-90(=75% and 90% reduction in PASI) and static Physician’s Global Assessment (sPGA)-0/1 (score of 0 ‘clear’ or 1 ‘almost clear’) were achieved following 12 weeks of treatment in all 3 dosing groups of AC-201.
This multicenter, randomized, double-blind, placebo-controlled trial randomized (1:1:1:1) 145 Chinese patients with moderate to severe plaque psoriasis to receive AC-201 25mg BID, 50mg BID or 100mg QD versus placebo. The primary endpoint was PASI-75 at Week 12.
At week 12, PASI-75 response rates were 8.1% for placebo (PBO), 31.4% for 25mg BID (P=0.012 vs. PBO), 74.3% for 50mg BID (P<0.001 vs. PBO), and 59.5% for 100mg QD (P<0.001 vs. PBO). The PASI-90 response rate was 2.7% for placebo, 20% for 25mg BID (P=0.02 vs. PBO), 48.6% for 50mg BID (P<0.001 vs. PBO), and 24.3% for 100mg QD (P=0.007 vs. PBO). The percent of patients achieved sPGA-0/1 were 5.4% for placebo, 71.4% for 50mg BID (P<0.001 vs. PBO), 59.5% for 100mg QD (P<0.001 vs. PBO), and 31.4% for 25mg BID (P=0.004 vs. PBO).
Treatment with AC-201 was well tolerated. There was no serious adverse event (SAE) or AE leading to permanent discontinuation in the study. Majority of treatment emergent adverse events (TEAEs) were mild or moderate in severity. The most common TEAEs reported were upper respiratory tract infection and hypertriglyceridemia.
Dr. Xiaohu Zhang, co-founder and CEO of Accropeutics, said, ""We are excited to see the positive results from the phase II study of AC-201, and we will accelerate its clinical development to benefit patients with psoriasis and other autoimmune diseases.”
AC-201 is a novel, highly selective and potent oral small-molecule inhibitor of TYK2/JAK1 that binds to the pseudo kinase domain (JH2) of TYK2/JAK1, without having any effects on the JAK2/JAK2 signalling pathway. It is currently being developed to treat immune mediated inflammatory diseases such as psoriasis and systemic lupus erythematosus. AC-201 has successfully completed long-term nonclinical in vivo toxicology testing, including reproductive toxicity. Phase 1 studies of AC-201 in healthy volunteers conducted in Australia and China demonstrated an excellent safety and tolerability profile, supporting advancement into phase 2. These studies showed dose proportional PK, no significant drug accumulation upon multiple dosing, and absence of clinically relevant food effect. Low to middle doses of AC-201 were effective in inhibiting disease causing pro-inflammatory cytokines, consistent with AC-201’s mechanism of action.
Accropeutics is a clinical-stage biotech company with core focus on the molecular mechanisms of regulated cell death and related pathogenesis in human diseases.
