Zai Lab’s ZL-1503 demonstrated at least 90% pSTAT6 inhibition through Week 12 in healthy volunteers, supporting further development of its dual-target atopic dermatitis therapy.
Written By: Anamika Koshri, PharmD
Reviewed By: Pharmacally Editorial Team
Zai Lab has reported first-in-human results for ZL-1503, an investigational bispecific antibody targeting interleukin-13 (IL-13) and interleukin-31 receptor alpha (IL-31Rα), two pathways implicated in atopic dermatitis (AD). In healthy volunteers, a single intravenous dose of 200 mg or higher produced at least 90% inhibition of phosphorylated STAT6 (pSTAT6), a marker of IL-13 pathway activity, through Week 12. The antibody also demonstrated a serum half-life of approximately 40 to 50 days. These findings support further investigation of less frequent dosing, although clinical efficacy and the proposed maintenance interval remain unestablished. The data were presented at the ACAAI 2026 Annual Scientific Meeting.
Dual Targeting of Inflammation and Itch
Atopic dermatitis involves interconnected inflammatory and pruritogenic pathways. IL-13 contributes to type 2 inflammation, while IL-31 signalling through IL-31Rα is associated with itch and the itch-scratch cycle. ZL-1503 is designed to inhibit both pathways through a single bispecific antibody.
Preclinical studies in non-human primates demonstrated inhibition of IL-13-mediated pSTAT6 signalling and IL-31-induced scratching. Following a single intravenous dose, both responses were completely inhibited for at least 76 days in all three animals, with selected pharmacodynamic effects persisting beyond 115 days. These findings provided the rationale for evaluating the molecule’s prolonged activity in humans.
Phase 1/1b Study and Subcutaneous Development
The first-in-human findings come from the single-ascending-dose (SAD) component of a randomized, double-blind, placebo-controlled Phase 1/1b study (NCT07235384). The analysis included 48 healthy volunteers receiving intravenous doses ranging from 50 to 1,000 mg or placebo.
The study’s second component evaluates multiple ascending doses in adults with moderate-to-severe atopic dermatitis, with initial patient data expected in the first half of 2027.
Zai Lab is also advancing a separate Phase 1 intravenous-to-subcutaneous (IV-to-SC) bioavailability bridging study (NCT07658482). The company completed enrollment in this study in October 2026. Evaluating both administration routes is an important development step towards determining whether prolonged systemic exposure can be translated into a practical subcutaneous maintenance regimen. However, SC bioavailability and the suitability of a 12-week dosing interval remain to be established.
Extended Exposure and Sustained Biomarker Suppression
Pharmacokinetics: ZL-1503 demonstrated a serum half-life of approximately 40 to 50 days, with systemic exposure increasing proportionally with dose. Zai Lab attributes this extended exposure to its half-life-extension antibody engineering and describes the half-life as nearly twice that of several approved anti-IL-13 and anti-IL-31 biologics. The company has not identified the specific comparators or disclosed sufficient detail to establish the contribution of individual engineering modifications.
Pharmacodynamics: A single dose of 200 mg or higher produced at least 90% inhibition of pSTAT6 through Week 12. Reductions were also reported in TARC, CCL26 and IgE, biomarkers associated with type 2 inflammatory activity. However, quantitative reductions and detailed time-course results for these additional markers were not disclosed.
Safety and immunogenicity: Zai Lab described ZL-1503 as well tolerated across evaluated doses. No serious adverse events, dose-limiting toxicities or treatment-emergent adverse events leading to study drug interruption were reported. Most adverse events were mild and associated with study procedures or intercurrent illnesses. No anti-drug antibodies were detected at the data cut-off. Detailed adverse-event rates by dose group were not provided.
Potential Dosing Differentiation in a Competitive Market
Zai Lab is targeting maintenance administration once every 12 weeks, although this remains a development objective.
The competitive landscape includes several approved biologics targeting overlapping pathways. Lebrikizumab and tralokinumab selectively inhibit IL-13, while dupilumab blocks IL-4Rα-mediated IL-4 and IL-13 signalling. Tralokinumab offers every-two-week maintenance dosing, with every-four-week administration considered for patients achieving clear or almost clear skin after 16 weeks. Lebrikizumab offers every-eight-week maintenance dosing for eligible patients following initial treatment. Nemolizumab targets IL-31Rα and is approved in the United States for moderate-to-severe atopic dermatitis.
ZL-1503’s potential differentiation lies in combining IL-13 and IL-31Rα inhibition with extended systemic exposure. If its proposed 12-week interval can be achieved without compromising disease control, it could offer a less frequent dosing option. However, this advantage will depend on successful subcutaneous development and confirmation of sustained clinical response.
Clinical Interpretation
The first-in-human findings establish prolonged pharmacological activity but do not demonstrate therapeutic benefit in atopic dermatitis. Importantly, the reported human pharmacodynamic evidence primarily establishes sustained IL-13 pathway inhibition through pSTAT6 suppression. Although ZL-1503 is designed to block IL-31Rα signalling, the available disclosure does not provide a direct human pharmacodynamic assessment quantifying the duration of IL-31Rα pathway inhibition. The durability of its dual-target activity in humans therefore remains incompletely characterized.
The 40–50-day half-life provides a rationale for investigating less frequent administration, but intravenous exposure alone cannot establish the feasibility of a 12-week subcutaneous regimen. The separate bridging study and forthcoming patient data will be important in evaluating this proposition.
Ultimately, ZL-1503’s differentiation will depend on whether its extended exposure and dual-target mechanism translate into sustained improvements in skin disease and itch, alongside a practical maintenance schedule. These clinical benefits remain to be demonstrated.
References
Zai Lab Presents Positive First-in-Human Data for ZL-1503, a Novel IL-13/IL-31Rα Bispecific, Demonstrating Rapid and Sustained Inhibition of Key Atopic Dermatitis Biomarkers and Extended Serum Half-Life Supporting Less Frequent Dosing, Zai Lab, 13 November 2026
A Phase 1/1b Study to Evaluate Safety, Tolerability and Pharmacokinetics of ZL-1503 in Healthy Volunteers and Participants with Moderate to Severe Atopic Dermatitis, ClinicalTrials.gov ID NCT07235384
A Phase 1 Study to Evaluate Pharmacokinetics, Safety and Tolerability of ZL-1503 in Healthy Volunteers, ClinicalTrials.gov ID NCT07658482
About the Writer
Anamika Koshti (LinkedIn) is a PharmD professional and healthcare writer with interests in clinical research, pharmacovigilance, and evidence-based medicine. She has authored peer-reviewed publications on Alzheimer’s disease and PCOS, presented research at national conferences, and gained hands-on experience in medical content development and clinical data interpretation. She is committed to translating complex medical research into accurate, accessible content for healthcare professionals and patients.