This is a two-part study that will evaluate the safety and efficacy of APG777 in participants with moderate-to-severe Atopic Dermatitis (AD). Part A (Proof-of-concept) and Part B (Dose-regimen Finding) will evaluate the safety and efficacy of various induction and maintenance dose regimens of APG777 compared to placebo. The study duration for any individual participant will be up to 106 weeks which includes: screening, induction, maintenance, and post-treatment follow-up periods. Participants randomized in Part A are not permitted to participate in Part B.

Inclusion Criteria:

• Have a diagnosis of AD that has been present for >=1 year prior to the Screening visit
• Moderate-to-severe AD at Screening and Baseline visits
• History of inadequate response to treatment with topical medications, or medical determination that topical therapies are inadvisable
• Applied a stable dose of non-medicated over-the-counter emollient/moisturizer of their choice on their skin for >=14 days prior to Baseline visit and agrees to continue using the same moisturizer throughout the study except the day of the study visits.
• Have completed itch questionnaires in the electronic diary for >=4 of 7 days prior to Baseline visit

Exclusion Criteria:

• Participation in a prior study with APG777.
• 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

Note: Other protocol defined inclusion/exclusion criteria may apply.

The Sponsor's study staff will also be blinded in the study.