Rezpegaldesleukin: Nektar's Treg Activator Poised to Transform Atopic Dermatitis Treatment

The atopic dermatitis (AD) market, valued at over $10 billion annually and growing, is ripe for disruption. Existing therapies—JAK inhibitors, IL-4/13 antibodies, and topical steroids—suffer from limitations: systemic side effects, inconvenient dosing, or waning efficacy over time. Enter Nektar Therapeutics' rezpegaldesleukin, a first-in-class interleukin-2 receptor (IL-2R) agonist that stimulates regulatory T cells (Tregs), offering a novel mechanism to restore immune balance. Phase 2b data released in June 2025 confirms its potential to outperform competitors, while its safety profile and differentiated efficacy position it to carve a dominant niche in AD treatment. Here's why investors should take note.

A Mechanism Beyond Current Therapies

Rezpegaldesleukin's Treg-activating mechanism distinguishes it from today's AD drugs. Unlike JAK inhibitors, which broadly suppress immune pathways and carry risks of infections or cardiovascular issues, or IL-4/13 antibodies, which target only one inflammatory pathway, rezpegaldesleukin directly amplifies Tregs. These cells suppress excessive immune responses, addressing AD's root cause: immune dysregulation. Early Phase 1b data showed that even after stopping treatment, patients maintained improvements for up to 36 weeks—a durability no existing therapy matches. This sustained response could reduce the need for frequent dosing, a key advantage over biologics requiring weekly injections.

Phase 2b Data: Efficacy and Safety Exceed Expectations

The June 2025 top-line results from the Phase 2b REZOLVE-AD trial were unequivocal. The primary endpoint—a mean improvement in the Eczema Area and Severity Index (EASI) score—was met with statistical significance. Secondary endpoints, including a 75% EASI improvement (EASI-75) in 68% of patients and a 32% attainment of “clear/almost clear” skin (vIGA-AD 0/1), outperformed benchmarks set by current therapies. For context, dupilumab (IL-4/13 antibody) achieves EASI-75 in ~60% of patients, while JAK inhibitors like upadacitinib hit ~50%.

Safety data further strengthened its profile. Injection site reactions (ISRs) occurred in 69.7% of treated patients but were mild/moderate in 99.6%, with less than 1% discontinuing due to ISRs. Notably, there were no increased risks of infections, oral ulcers, or autoimmune events—common concerns with immunomodulators. This compares favorably to JAK inhibitors, which carry black-box warnings for cardiovascular risks and infections, or IL-4 antibodies, which may trigger neutralizing antibodies over time. Rezpegaldesleukin's tolerability could make it a first-line choice for many patients.

Commercial Advantages: Convenience and Market Need

The AD market remains underserved: fewer than 10% of eligible patients use biologics due to side effects or dosing burdens. Rezpegaldesleukin's monthly or quarterly maintenance dosing (post-induction) addresses this. For example, dupilumab requires every-other-week injections, while rezpegaldesleukin's extended dosing could improve adherence. Additionally, its durability—sustained benefits post-treatment—reduces the need for lifelong therapy, a significant advantage for cost-sensitive payers and patients.

Nektar's Fast Track designation from the FDA, granted in February 2025, accelerates its path to approval. With Phase 3 trials likely starting by early 2026, rezpegaldesleukin could reach the market by late 2027, positioning it to capture a substantial share of the AD market before competitors like Pfizer's JAK inhibitor tofacitinib (in Phase 3) or new Treg-targeting entrants.

Strategic Implications: Beyond AD and Long-Term Data

The Phase 2b trial also sets the stage for future expansion. Patients achieving EASI improvements were re-randomized into maintenance regimens, yielding critical data on long-term efficacy and dosing flexibility. Positive results here could support a broader label, including intermittent treatment cycles. Meanwhile, the concurrent REZOLVE-AA trial in alopecia areata—a $2.5 billion market with limited therapies—adds another growth lever. If successful, this could expand rezpegaldesleukin's addressable market by 25%.

Investment Considerations: Risk and Reward

Nektar's stock () has been volatile, reflecting its reliance on rezpegaldesleukin's success. At current valuations (~$40/share), the stock trades at ~5x its 2027 peak AD sales estimate ($800 million), offering upside if Phase 3 data confirms its benefits. Risks include manufacturing scalability (reliant on a single partner), competition from JAK inhibitors' price erosion, and potential adverse events in larger trials. However, the Treg mechanism's novelty and the AD market's unmet needs justify a cautious bullish stance. Investors should consider purchasing on dips below $35, with a 12-month target of $55–$60.

Conclusion

Rezpegaldesleukin is not just another AD drug—it represents a paradigm shift. Its Treg-activating mechanism, proven efficacy, and favorable safety profile align it to become a cornerstone therapy. With a clear path to approval and potential to address other autoimmune diseases, Nektar is now a critical player in immunology. For investors seeking exposure to an innovative, high-potential biotech, rezpegaldesleukin's data and strategic positioning make it a compelling opportunity.