This is an interventional, randomized, parallel group, treatment, Phase IIb, double blind, 4-arm study to assess the effect of pegylated-recombinant-human interleukin-2 (rezpegaldesleukin) in adult participants with moderate to severe atopic dermatitis.

The estimated duration is 15-35 days for screening, an Induction Period of 16 weeks, a Maintenance Period from Week 16-Week 52, and a Posttreatment Follow-Up Period for an additional year up to approximately Week 104 for all patients. Patients with a response at Week 16 (end of induction therapy) will be re-randomized for the maintenance therapy period.

Inclusion Criteria:

• Adults (from at least 18 years of age) with AD as defined by the American Academy of Dermatology Consensus Criteria for 1 year or longer prior to screening.

• AD disease severity at screening and randomization:

  • EASI of 16 or higher
  • IGA of 3 or 4
  • BSA of 10% or more

• Documented history, within 6 months prior to the screening visit, of either inadequate response or inadvisability of topical treatments.

• Able to complete patient questionnaires.

• Able and willing to comply with requested study visits and procedures.

• Able and willing to provide written informed consent.

Exclusion Criteria:

• Prior use of systemic immune modulating therapies for AD (i.e., JAK inhibitors or biologics)
• Other skin conditions that would interfere with assessment of AD
• Treatment with a live (attenuated) immunization within 12 weeks prior to screening.
• Men and women (of reproductive potential) unwilling to use highly effective birth control and women who are pregnant or breastfeeding.
• Any malignancies or history of malignancies within 5 years prior to randomization (except for basal cell or squamous epithelial carcinomas of the skin that have been successfully treated with no evidence of metastatic disease for 3 years or cervical carcinoma in situ that has been successfully treated, with no evidence of recurrence within the 3 years prior to randomization).
• Known history of, or suspected, significant current immunosuppression, including history of invasive opportunistic infections despite infection resolution or otherwise recurrent infections of abnormal frequency or prolonged duration.
• Positive for human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) at screening.
• Severe concomitant illness that would in the Investigator's opinion inhibit the patient's participation in the study, including for example, but not limited to, hypertension, renal disease, neurological conditions, heart failure and pulmonary disease.
• Concurrent participation in any other investigational clinical study.