(RTTNews) - Nektar Therapeutics (NKTR) entered a quiet period beginning this month as it awaits the trial results for its lead drug candidate, Rezpegaldesleukin, in alopecia areata.
Rezpegaldesleukin, also known as Rezpeg, NKTR-358, or formerly LY3471851, is a pegylated recombinant human interleukin-2 (IL-2) therapeutic. This engineered biologic is a modified form of a naturally occurring protein that plays a key role in regulating immune system activity.
Administered via subcutaneous injection, Rezpegaldesleukin works by targeting the interleukin-2 receptor complex to stimulate the proliferation of powerful inhibitory immune cells known as regulatory T cells. By activating these cells, Rezpegaldesleukin may help restore immune system balance.
This mechanism is particularly relevant in autoimmune and inflammatory diseases such as alopecia areata, type 1 diabetes, and atopic dermatitis. In these conditions, a breakdown in the body's self-tolerance allows pathogenic T lymphocytes to mistakenly attack healthy tissues. So, by reinforcing regulatory T-cell function, Rezpegaldesleukin may help counteract this immune dysfunction and reduce disease activity.
REZOLVE-AA Phase 2b Study in Alopecia Areata
The company reported topline results from REZOLVE-AA, a global phase 2b study of Rezpegaldesleukin, which enrolled 92 patients with severe-to-very-severe alopecia areata, in December 2025.
Alopecia areata is an autoimmune disorder where the immune system attacks hair follicles, leading to patchy or complete hair loss.
The REZOLVE-AA study evaluated two dose regimens of Rezpegaldesleukin (24 µg/kg and 18 µg/kg) administered as a subcutaneous injection every two weeks against placebo, with the primary endpoint defined as the mean percentage reduction from baseline in Severity of Alopecia Tool (SALT) score at Week 36.
According to the study results, the primary endpoint narrowly missed statistical significance, with mean SALT score reductions of 28.2% for the 24 µg/kg group and 30.3% for the 18 µg/kg group, compared to 11.2% for the placebo.
However, further analysis revealed that of the 92 patients enrolled, four patients had major eligibility violations and should not have been randomized. After excluding these patients, the results strengthened notably: both Rezpegaldesleukin dose groups demonstrated a 30% mean reduction in SALT scores at Week 36, compared to 6% for placebo, achieving statistical significance.
After 36 weeks of treatment, patients who showed evidence of hair regrowth but had not yet achieved a SALT score improvement greater than 20% were eligible to continue therapy for an additional 16 weeks, extending through Week 52, within a blinded extension phase to further assess treatment benefit.
The company expects to report topline data from the blinded 16-week treatment extension period in the phase 2b REZOLVE-AA study of Rezpegaldesleukin in alopecia areata this month (April 2026). So, it entered a quiet period starting April 1, 2026, which will remain in effect until the public disclosure of these results.
Rezpegaldesleukin in Atopic Dermatitis
Rezpegaldesleukin is also being explored in moderate-to-severe atopic dermatitis.
The company expects to commence phase 3 studies for Rezpegaldesleukin in patients with moderate-to-severe atopic dermatitis this quarter.
In a phase 2b study in moderate-to-severe atopic dermatitis, including patients with comorbid asthma, dubbed REZOLVE-AD, Rezpegaldesleukin demonstrated statistically significant and clinically meaningful improvements in mean ACQ-5 scores at week 16 versus placebo in patients who had atopic dermatitis and a history of asthma.
The ACQ-5 (Asthma Control Questionnaire, 5-item version) is a 5-question survey that measures how well a person's asthma is controlled, including symptoms like wheezing, shortness of breath, and nighttime awakenings. Scores range from 0 (well controlled) to 6 (poorly controlled) (Source: Asthma Australia).
The study also demonstrated durable and new responses with Rezpegaldesleukin across key disease measurements at Week 52 with both monthly and quarterly dosing.
Rezpegaldesleukin in Type 1 Diabetes
Nektar has a collaboration agreement with TrialNet, an international clinical trial network at the forefront of diabetes research, to evaluate Rezpegaldesleukin in patients with new-onset stage 3 type 1 diabetes mellitus (T1D).
A phase 2 study of Rezpegaldesleukin in Stage 3 new onset type 1 diabetes, sponsored by TrialNet, is underway. Initial data from this trial is expected in 2027.
Financial Numbers
For the full year 2025, the company reported a net loss of $164.1 million, or $9.73 per share, compared with a net loss of $119.0 million, or $8.68 per share, for 2024.
Revenue for 2025 totaled $55.2 million, down from $98.4 million in the prior year.
Nektar's revenue has historically been generated through collaboration agreements, which include product sales revenue, royalties, license fees, and milestone or other contingent payments related to development and sales. However, following the sale of its Huntsville manufacturing facility in December 2024, the company no longer recognizes product sales or cost of goods sold under these arrangements.
As of December 31, 2025, the company held $245.8 million in cash and investments in marketable securities. The cash on hand excludes net proceeds of approximately $432 million from the secondary offering completed in February 2026 and $44 million from share sales under the at-the-market offering facility.
Conclusion
It is estimated that approximately 700,000 people in the U.S. have alopecia areata (AA), with about 300,000 individuals affected by moderate-to-severe disease.
Janus kinase (JAK) inhibitors, including Lilly's Olumiant (daily oral pill), Pfizer's Litfulo (once-daily oral medication), and Sun Pharma's Leqselvi (twice-daily oral medication), are promising treatment options for AA. However, all three carry black-box warnings due to the risk of serious adverse events, including infections, cardiovascular events, cancer, and death.
In this context, clinical trials to date have demonstrated that Nektar's Rezpegaldesleukin exhibits a favorable safety profile, with no evidence of increased risk for serious adverse events, including conjunctivitis, facial swelling or erythema, oral ulcers, myocardial infarction, pulmonary embolism, deep vein thrombosis, or malignancy. The most frequently reported treatment-emergent adverse events were local injection site reactions, which were generally mild to moderate in severity and self-resolving, underscoring the therapy's overall tolerability.
So, with a highly differentiated safety profile and proof-of-concept supporting its potential as a first-in-class biologic for alopecia areata, Rezpegaldesleukin positions Nektar Therapeutics at a critical juncture, making upcoming clinical updates and share performance worthy of close monitoring.
When we alerted readers to NKTR on June 11, 2025, it was trading at $11.25. The 52-week high of $78.81, recorded on April 1, 2026, reflects a gain of about 600% in ten months.
The views and opinions expressed herein are the views and opinions of the author and do not necessarily reflect those of Nasdaq, Inc.
