How Nektar's Rezpegaldesleukin Could Redefine Treatment for Autoimmune Disorders

In part 2 of his conversation with Dermatology Times, Jonathan Zalevsky, PhD, Chief Research and Development Officer at Nektar Therapeutics, shares his long-term vision for rezpegaldesleukin (REZPEG) and its expanding role across autoimmune and inflammatory diseases. Following promising results in dermatologic conditions such as atopic dermatitis (AD) and alopecia areata, Nektar is strategically positioning rezpegaldesleukin as a first-in-class T regulatory (Treg) cell agonist therapy with potential far beyond dermatology.

Rezpegaldesleukin's initial clinical successes stem from its unique mechanism of activating and expanding Tregs, a cell population critical for immune homeostasis and suppression of unwanted inflammation. Zalevsky underscored the novelty of this approach, contrasting it with the more common strategy of blocking inflammatory pathways, as seen with JAK inhibitors or cytokine antagonists. As a cellular agonist, rezpegaldesleukin aims to restore the body’s natural immune balance.

“For many years, many decades, we've been trying to figure out how to target and really create drugs that could access the cell population, because this is the body's natural mechanism of fixing unwanted inflammation [and] autoimmunity,” he said.

Beyond alopecia and AD, rezpegaldesleukin has shown efficacy in early studies of lupus and psoriasis, and Zalevsky highlighted vitiligo as another high-priority dermatologic target. Outside of dermatology, rezpegaldesleukin is entering a new frontier through a partnership with TrialNet, part of the National Institutes of Health’s NIDDK division, to study rezpegaldesleukin in new-onset type 1 diabetes. This investigator-led study will evaluate the drug’s potential to slow beta cell loss and possibly even prevent disease progression.

Despite Nektar’s status as a small biotech company, its near-term focus remains on dermatologic conditions, with ongoing studies in AD (Phase 2b maintenance and follow-up) and the pivotal REZOLVE-AA trial in severe alopecia areata. Should the December topline readout from REZOLVE-AA demonstrate clear efficacy, Zalevsky envisions initiating a registrational Phase 3 program. Endpoints like SALT20 in the US and SALT10 in Europe will guide regulatory strategy, with rezpegaldesleukin positioned to potentially become the first approved biologic in alopecia areata.

“We want to thank all of the patients and physicians and other people that have helped us along the way to demonstrate these indications and we look forward to all that continued partnership working together in the coming years,” Zalevksy concluded.