SAN FRANCISCO, July 21, 2026
Nektar Therapeutics has announced the initiation of its global Phase 3 ZENITH AD clinical development program, advancing rezpegaldesleukin (REZPEG), a first-in-class regulatory T-cell (T-reg) biologic, for the treatment of moderate-to-severe atopic dermatitis (AD). The registrational program begins with the launch of ZENITH AD-1 and ZENITH AD-2, while a third pivotal trial, ZENITH AD-3, is scheduled to commence in September 2026. Together, the three randomized, placebo-controlled studies are expected to enroll 1,530 patients aged 12 years and older across North America, Europe, and the Asia-Pacific region. The Phase 3 program follows encouraging results from a 393-patient Phase 2b study, which demonstrated clinically meaningful efficacy, durable disease control, and a favorable safety profile, including a five-fold increase in EASI-100 responses between Weeks 16 and 52 during maintenance therapy. Initial topline Phase 3 data are anticipated in mid-2028, with a Biologics License Application (BLA) planned for 2029, marking a major milestone in the development of next-generation immunology therapies.
Global Phase 3 Trials Target Long-Term Disease Control
The ZENITH AD program has been designed as a comprehensive global registrational effort consisting of three pivotal Phase 3 trials evaluating rezpegaldesleukin in patients with moderate-to-severe atopic dermatitis. ZENITH AD-1 and ZENITH AD-2 will enroll patients who are biologic and JAK inhibitor treatment-naïve, while ZENITH AD-3 will focus on patients previously treated with systemic biologics or JAK inhibitors. Each study includes a 24-week induction period followed by a 28-week maintenance phase, allowing investigators to assess the durability of treatment response through monthly and quarterly dosing schedules. The primary endpoint will evaluate Investigator’s Global Assessment (IGA) 0/1 responses, with EASI-75, EASI-90, itch reduction, patient-reported outcomes, and asthma control serving as important secondary efficacy measures. The broad trial design aims to generate robust evidence supporting regulatory submissions in both the United States and Europe while addressing the unmet need for durable therapies capable of maintaining long-term disease remission.
First-in-Class T-Reg Biologic Offers Novel Immunology Approach
Unlike currently approved therapies that primarily suppress inflammatory pathways, rezpegaldesleukin is designed to restore immune balance by selectively stimulating the interleukin-2 receptor complex to expand regulatory T cells (T-regs). This unique mechanism addresses the underlying immune dysfunction responsible for autoimmune and chronic inflammatory diseases rather than simply controlling symptoms. In the completed Phase 2b study, the investigational biologic demonstrated rapid onset of EASI-75 responses, durable improvements in skin disease severity, meaningful itch reduction, and improved asthma control among patients with coexisting asthma. These encouraging findings supported advancement into Phase 3 development following successful End-of-Phase 2 discussions with the U.S. Food and Drug Administration (FDA) and scientific advice from the European Medicines Agency (EMA). The company believes REZPEG has the potential to redefine treatment by delivering deep and sustained disease control while also expanding into additional autoimmune indications.
Advertisement
Broad Autoimmune Pipeline Continues to Expand
Beyond atopic dermatitis, rezpegaldesleukin is also being developed for alopecia areata and Type 1 diabetes, highlighting its broad immunology potential. The therapy previously received FDA Fast Track Designation for both moderate-to-severe atopic dermatitis and severe alopecia areata, reinforcing regulatory recognition of its potential to address significant unmet medical needs. Nektar plans to initiate a registrational Phase 3 trial in alopecia areata during early 2027, while ongoing Phase 2 evaluation in Type 1 diabetes continues to explore the biologic’s disease-modifying capabilities. As the ZENITH AD program progresses, the company aims to establish rezpegaldesleukin as a first-in-class regulatory T-cell therapy capable of transforming the treatment landscape across multiple autoimmune diseases through immune restoration rather than immune suppression.
Source: Nektar Therapeutics Press release
