8-K: Nektar's Rezpegaldesleukin Shows Strong Asthma Benefit in AD Trial

Nektar Therapeutics announced new Phase 2b data for rezpegaldesleukin, demonstrating statistically significant and clinically meaningful improvements in asthma control for atopic dermatitis patients.

Summary

• Nektar Therapeutics presented new data from its ongoing Phase 2b REZOLVE-AD (atopic dermatitis) clinical trial at the ACAAI 2025 Annual Scientific Meeting on November 8, 2025.
• The trial enrolled 393 patients with moderate-to-severe atopic dermatitis, including 99 patients with a history of asthma.
• A pre-planned analysis showed that two rezpegaldesleukin dose arms (24 µg/kg q2w and 24 µg/kg q4w) achieved statistical significance (p<0.05) in reducing mean ACQ-5 scores at week 16 compared to placebo in patients with a history of asthma.
• Patients in the placebo arm reported an overall worsening of mean ACQ-5 scores.
• In patients with a baseline ACQ-5 score of 0.5 or higher (N=53), at least half experienced clinically significant improvement (0.5 point reduction) across all treatment arms, versus 13% in the placebo arm.
• For 25 patients with uncontrolled asthma at baseline (≥1.5 ACQ-5 score), all three active doses showed meaningful improvement, with all dose arms achieving statistical significance (p<0.05) compared to placebo.
• Placebo-adjusted reductions in mean ACQ-5 scores for uncontrolled asthma patients ranged from 1.0 to 1.4.
• Data from 42 placebo patients who crossed over to high-dose rezpegaldesleukin (24 µg/kg q2w) at week 16 showed strong responses at week 24: EASI-75 response rate of 60% (n=30), vIGA-AD 0/1 response rate of 33% (n=30), EASI-90 response rate of 37% (n=30), and Itch NRS response rate of 50% (n=28) in patients with baseline score ≥4.
• Safety data were generally consistent with previously reported profiles.

Sentiment

Score: 8

Explanation: The clinical trial results for rezpegaldesleukin are highly positive, demonstrating statistically significant and clinically meaningful improvements in both atopic dermatitis and comorbid asthma symptoms. The differentiation from other biologics and the support for Phase 3 advancement indicate strong potential for the drug. While it's still in Phase 2b, the consistent positive data and Fast Track designations are very encouraging.

Positives

• Statistically significant and clinically meaningful improvements in mean ACQ-5 scores were observed at week 16 versus placebo in atopic dermatitis patients with a history of asthma.
• Two dose arms (24 µg/kg q2w and 24 µg/kg q4w) achieved statistical significance (p<0.05) in reducing ACQ-5 scores.
• Improvements were more pronounced in patients with partly controlled or uncontrolled asthma, with up to 75% of patients in the 24 µg/kg q2w arm with uncontrolled asthma showing clinically significant improvement.
• Crossover data from placebo patients receiving high-dose rezpegaldesleukin demonstrated strong efficacy at week 24 across key atopic dermatitis endpoints, including EASI-75 (60%), EASI-90 (37%), vIGA-AD 0/1 (33%), and Itch NRS (50%).
• The data supports advancing the 24 µg/kg q2w dose regimen with a 24-week induction period into Phase 3 studies.
• Rezpegaldesleukin's Treg mechanism shows broad potential across multiple T-cell mediated inflammatory diseases and offers a unique, differentiated treatment for atopic dermatitis.
• Rezpegaldesleukin previously received FDA Fast Track designation for moderate-to-severe atopic dermatitis (February 2025) and severe alopecia areata (July 2025).

Risks

• Statements regarding therapeutic potential and future development plans are based on preclinical and clinical findings and observations and are subject to change.
• Rezpegaldesleukin is an investigational agent, and continued research and development is subject to substantial risks, including negative safety and efficacy findings in future clinical studies.
• The drug candidate is in clinical development, and the risk of failure is high and can occur at any stage prior to regulatory approval.
• Data reported from ongoing clinical trials are interim data only, and final results may change based on continuing observations.
• The timing of clinical trials and data availability may be delayed or unsuccessful due to regulatory delays, slow patient enrollment, manufacturing challenges, changing standards of care, evolving regulatory requirements, clinical trial design, clinical outcomes, or competitive factors.
• A Fast Track designation does not increase the likelihood of receiving marketing approval in the United States.
• Patents may not issue from patent applications, issued patents may not be enforceable, or additional intellectual property licenses from third parties may be required.

Future Outlook

Nektar Therapeutics plans to advance rezpegaldesleukin 24 µg/kg q2w with a 24-week treatment induction period into Phase 3 studies for atopic dermatitis. The company expects to report data from the long-term maintenance portion of the REZOLVE-AD study (52 weeks of treatment) in Q1 2026 and top-line Phase 2b data for rezpegaldesleukin in alopecia areata in December 2025. Rezpegaldesleukin is being developed as a self-administered injection for various autoimmune and inflammatory diseases.

Management Comments

• Dr. Jonathan Corren, Associate Clinical Professor of Medicine and Pediatrics at UCLA, stated that the results with rezpegaldesleukin in patients with atopic dermatitis and comorbid asthma demonstrate that promotion of Treg activity may also have benefits to the lower airways, an observation which warrants further investigation.
• Jonathan Zalevsky, Ph.D., Chief Research and Development Officer of Nektar, commented that the observations of improvement in asthma control in REZOLVE-AD support the broad potential of rezpegaldesleukin's Treg mechanism across multiple T-cell mediated inflammatory diseases.
• Dr. Zalevsky also noted that the data demonstrate rezpegaldesleukin could offer a unique and differentiated innovative treatment for atopic dermatitis, particularly as these findings have not been observed with other biologic mechanisms recently approved or in advanced development.

Industry Context

Rezpegaldesleukin, as a first-in-class IL-2 pathway agonist and regulatory T-cell (Treg) biologic, represents a potentially differentiated approach in the treatment of atopic dermatitis and comorbid asthma. The observed improvements in asthma control, which are noted as not having been seen with other recently approved or advanced biologic mechanisms, suggest a unique therapeutic profile. This could position Nektar favorably in the competitive landscape of inflammatory disease treatments, especially given the significant unmet need for therapies addressing comorbidities like asthma in atopic dermatitis patients.

Comparison to Industry Standards

• The data for rezpegaldesleukin demonstrate a unique and differentiated innovative treatment for atopic dermatitis, particularly as these findings regarding asthma control have not been observed with other biologic mechanisms recently approved or in advanced development.
• The promotion of Treg activity by rezpegaldesleukin may offer benefits to the lower airways, which is a novel observation compared to existing treatments for atopic dermatitis.

Stakeholder Impact

• Shareholders: Positive clinical data for a key pipeline asset could lead to increased investor confidence and potential share price appreciation, contingent on future trial success and market conditions.
• Patients: The data suggests rezpegaldesleukin could offer a unique and effective treatment option for moderate-to-severe atopic dermatitis, particularly those with comorbid asthma, potentially improving quality of life.
• Employees: Continued positive clinical development supports the company's strategic direction and job security.
• Regulatory Authorities: The positive data and Fast Track designations may facilitate future regulatory review processes.

Next Steps

• Advance the rezpegaldesleukin 24 µg/kg q2w dose regimen with a 24-week treatment induction period into Phase 3 studies.
• Report data from the long-term maintenance portion of the REZOLVE-AD study (52 weeks of treatment) in Q1 2026.
• Report top-line Phase 2b data for rezpegaldesleukin in alopecia areata in December 2025.

Key Dates

Recommendation

The new Phase 2b data for rezpegaldesleukin is highly encouraging, demonstrating statistically significant and clinically meaningful improvements in both atopic dermatitis and comorbid asthma. The drug's unique mechanism of action and differentiated profile, particularly in addressing asthma comorbidity, positions it favorably against existing and developing treatments. The strong efficacy observed in the crossover arm and the planned advancement to Phase 3 studies, coupled with prior Fast Track designations, de-risk the development pathway to some extent. While clinical development always carries risk, these results suggest a strong potential for future market success, making it an attractive investment for long-term growth.

Keywords

Nektar Therapeutics, Rezpegaldesleukin, NKTR-358, Atopic Dermatitis, Asthma, Phase 2b, REZOLVE-AD, Clinical Trial, Biotechnology, Immunology, Treg, IL-2 pathway agonist, ACAAI, FDA Fast Track