Zai Lab (ZLAB) Study update summary

Trial design and rationale

• ZL-1503 is a half-life-extended bispecific targeting IL-13 and IL-31Ra to address inflammation and itch in atopic dermatitis.

• Randomized, double-blind, placebo-controlled Phase 1/1b: Part A evaluated single ascending doses in healthy volunteers; Part B enrolls moderate-to-severe AD patients.

• ACAAI 2026 results included 48 healthy volunteers across 50, 200, 600 and 1,000 mg dose groups and placebo; data cutoff was Aug. 27, 2026.

Safety and pharmacokinetics

• Well tolerated across evaluated doses, with no SAEs, dose-limiting toxicities or TEAEs leading to treatment interruption; most TEAEs were mild and related to procedures or intercurrent illnesses.

• TEAEs occurred in 41.7%-50.0% of active-dose groups versus 75.0% with placebo; no Grade ≥3 TEAEs occurred in active groups.

• Single IV doses of 50-1,000 mg showed dose-proportional Cmax and AUC; exposure was similar in China and New Zealand cohorts at 600 and 1,000 mg.

• Mean terminal half-life was 40-50 days across 50-1,000 mg doses; no detectable anti-drug antibodies were reported as of the data cutoff.

Pharmacodynamic findings

• Single doses of 200-1,000 mg produced ≥90% inhibition of IL-13-stimulated pSTAT6 through Week 12.

• TARC declined across dose levels, with maximum inhibition comparable to single-dose dupilumab 300 mg in a separate Phase 1 study.

• CCL26 reductions of 20%-30% across active-dose groups and progressive IgE reductions at higher doses supported downstream type 2 pathway modulation.

• In nonhuman primates, a single dose suppressed itch for 112 days; magnitude and duration increased with dose, with a reported PK/PD correlation.