This is a study to evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, and clinical activity of orally administered KT-621 in adult male and female patients with moderate to severe atopic dermatitis (AD).

Inclusion Criteria:

• Participants aged 18 to 55 years (inclusive) at the time of screening
• Participants must be willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other procedures
• Participants must have had chronic atopic dermatitis (AD) for at least 1 year before Screening.
• Moderate to very severe eczema as determined by Eczema Area and Severity Index (EASI) score of at least 16 at the baseline visit.
• A validated Investigator Global Assessment (vIGA) score of at least 3 at the baseline visit, indicating moderate to severe AD.
• At least 10% body surface area (BSA) of AD involvement at the baseline visit.
• Weekly average Peak Pruritus Numeric Rating Scale (NRS) of at least 4 at the baseline visit.
• Documented history within 6 months prior to baseline visit of either inadequate response or contraindication to topical medications for AD.
• Application of stable dose of moisturizer at least twice daily for at least 7 consecutive days immediately prior to the baseline visit.

Exclusion Criteria:

• Participants who have a clinically relevant history of respiratory, gastrointestinal (GI), renal, hepatic, hematological, lymphatic, endocrinological, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, ophthalmological, or connective tissue diseases or disorders.
• Participants who have any surgical or medical procedure planned during participation in the study.
• Participants with a history of alcohol or substance abuse within the previous 2 years.
• Participants who have any known factor, condition, or disease that might interfere with treatment compliance, study conduct or interpretation of the results.
• Participants whose results from clinical laboratory safety tests are outside the local reference range at Screening.
• Participants who have been dosed with any investigational drug or device in a clinical study within 8 weeks or 5 half-lives (whichever is longer) of KT-621 administration.
• Participants with a history of lack of response to any medication targeting interleukin (IL)-4, IL-13, and/or janus kinase (JAK)- signal transducer and activator of transcription (STAT) pathways (e.g. dupilumab, tralokinumab, upadacitinib, abrocitinib) at approved doses after at least 16 weeks of therapy.
• Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study.
• Female participants of childbearing potential with a positive or undetermined pregnancy result at the Screening and baseline visits.
• Participants with a known sensitivity to any of the components of KT-621.
• Participants who are a member of the investigational team or his/her immediate family.