The primary purpose of this study is to evaluate the safety, tolerability, and pharmacokinetic (PK) parameters of the combination of APG777 + APG990 in adults with moderate-to-severe atopic dermatitis (AD), in comparison to dupilumab. The duration of the study will be approximately 82 weeks for each participant and will consist of a Screening Period (up to 6 weeks), Treatment Period (Baseline-Week 24), and Follow-up Period (Week 28-Week 76).

Participants will be randomized to APG777 + APG990 or dupilumab in a 1:1 ratio. Randomization will be stratified on Day 1 according to Baseline disease severity and geographic region.

Inclusion Criteria

• Have a diagnosis of AD that has been present for ≥ 1 year prior to the Screening visit and as determined by the Investigator through participant interview and/or review of the medical history.
• Moderate-to-severe AD at Screening and Baseline (Day 1) visits, defined as: a) Eczema Area and Severity Index (EASI) score of ≥ 16, b) vIGA-AD score of ≥ 3, and c) AD affecting ≥10% of body surface area (BSA).
• History of inadequate response to treatment with topical medications
• Women of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Baseline (Day 1) visit.

Exclusion Criteria

• Participation in a prior study with APG777 or APG990.
• Prior treatment with protocol-specified monoclonal antibodies (mAbs).
• Has used any AD-related topical medications within 7 days prior to Baseline visit.
• Has used systemic treatments (other than biologics) and/or phototherapies and/or laser therapy that could affect AD within 4 weeks prior to Baseline visit
• History of known hypersensitivity to any of the ingredients in APG777, APG990, or dupilumab.
• Presence of dermatologic conditions and/or comorbidities that might confound the diagnosis of AD and/or might interfere with study assessments

Note: Additional protocol defined Inclusion/Exclusion criteria apply