Zai Lab’s Long-Acting Atopic Dermatitis Bispecific Points to Every-12-Week Dosin

Zai Lab’s ZL-1503, a long-acting bispecific antibody targeting interleukin (IL)-13 and the IL-31 receptor alpha (IL-31Rα), produced near-complete and sustained inhibition of a key atopic dermatitis (AD) signaling biomarker after a single dose in healthy volunteers, according to first-in-human data presented at the American College of Allergy, Asthma & Immunology (ACAAI) 2026 Annual Scientific Meeting.¹ The antibody also showed a serum half-life of approximately 40 to 50 days, supporting the company’s goal of maintenance dosing once every 12 weeks.¹

“These first-in-human findings reinforce the potential of ZL-1503 as a differentiated, first-in-class treatment option for patients with atopic dermatitis,” said Rafael G. Amado, MD, president and head of global research and development at Zai Lab.¹

How is ZL-1503 designed?

ZL-1503 was discovered internally at Zai Lab and is designed to block two cytokines that drive AD.¹ IL-13 promotes type 2 inflammation and tissue remodeling, while IL-31 drives itch and amplifies local immune responses, and together they perpetuate the itch-scratch-inflammation cycle.¹ The antibody also incorporates serum half-life extension technology to prolong systemic exposure.¹

Both pathways are already validated by approved antibodies. FDA approved Eli Lilly’s Ebglyss (lebrikizumab), an IL-13 inhibitor, in September 2024, with maintenance dosing of one 250-mg injection every four weeks.² In December 2024, FDA approved Galderma’s Nemluvio (nemolizumab), the first approved monoclonal antibody that exclusively targets IL-31Rα.³ ZL-1503’s half-life is nearly twice as long as that of several approved anti-IL-13 and anti-IL-31 biologics, according to Zai Lab.¹

Developers are increasingly combining AD targets in a single molecule. BioPharm International® has reported on Aclaris Therapeutics’ TSLP/IL-4Rα bispecific ATI-052, and on AbbVie’s agreement to acquire Apogee Therapeutics, gaining the half-life-extended IL-13 antibody zumilokibart, in a deal valued at $10.9 billion.

What did the phase 1 data show?

The randomized, double-blind, placebo-controlled phase 1/1b trial (NCT07235384) evaluated single ascending doses of 50 mg to 1,000 mg of ZL-1503 or placebo in 48 healthy volunteers.¹ At Week 12, doses of 200 mg to 1,000 mg achieved at least 90% inhibition of IL-13-stimulated phosphorylated STAT6 (pSTAT6), an AD-related signaling biomarker.¹ Treatment also reduced circulating type 2 inflammatory biomarkers associated with AD, including TARC, CCL26, and IgE.¹

ZL-1503 showed dose-proportional exposure, and as of the data cutoff, no anti-drug antibodies were detected.¹ The antibody was well tolerated at all dose levels, with no dose-limiting toxicities, serious adverse events, or treatment-emergent adverse events leading to study drug interruption.¹ Most treatment-emergent adverse events were mild and associated with study procedures or intercurrent illnesses.¹

The phase 1 data build on preclinical results presented earlier this year, in which ZL-1503 provided rapid itch relief and significantly reduced inflammation in animal models of atopic disease.¹ Because the study enrolled healthy volunteers, it did not assess clinical efficacy.¹

Why does subcutaneous dosing matter?

Single doses in the study reached up to 1,000 mg, and Zai Lab is also developing a subcutaneous formulation.¹ The company has completed enrollment in an intravenous-to-subcutaneous bioavailability bridging study, with initial data expected in 2027.¹

Delivering high-dose antibodies under the skin, ideally at home, remains a formulation challenge. In a BioPharm International video interview, Chris Worrall, PhD, vice president of US business development at Nanoform, said high-concentration formulations that enable at-home administration could be “potentially game-changing.”

What happens next?

Zai Lab has initiated the next phases of the study, which are evaluating the pharmacokinetics, safety, and initial efficacy of repeated doses of ZL-1503 in patients with moderate-to-severe AD.¹ Data from the Part B cohort, evaluating multiple ascending doses in patients, are expected in the first half of 2027.¹ “By combining two clinically validated mechanisms in a single, half-life-extended bispecific, ZL-1503 has the potential to control inflammation, deliver rapid and durable itch relief, and enable less frequent dosing,” Amado said.¹

References

1. 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. News release. Zai Lab; November 13, 2026. Accessed November 13, 2026.
2. Halsey G. Lilly announces FDA approval for lebrikizumab-lbkz for moderate to severe atopic dermatitis. Patient Care Online. Published September 16, 2024. Accessed November 13, 2026.
3. Jennings S. FDA approves nemolizumab for treatment of moderate to severe atopic dermatitis. Patient Care Online. Published December 16, 2024. Accessed November 13, 2026.