A Dose Ranging Placebo-Controlled Double-Blind Study to Evaluate the Safety and Efficacy of Tezepelumab in Atopic Dermatitis

All subjects will receive a SC dose of either investigational product or placebo as the first
dose on day 1.

Subjects who are determined to be non-responders in Part A will receive tezepelumab SC Q2W
following completion of all week 16 study activities. Nonresponders are defined as those
subjects who have not achieved at least a 50% improvement in EASI at week 16 compared to
baseline (day 1).

Safety follow-up is 12 weeks after the EOT visit (14 weeks after the final dose of
investigational product).

Inclusion Criteria:

- Subject has provided informed consent prior to initiation of any study specific
activities/procedures.

- Age greater than or equal to 18 to less than or equal to 75 years at screening.

- Clinical diagnosis of chronic AD (also known as atopic eczema) for at least 2 years
prior to screening and has confirmed AD (Hanifin and Rajka criteria for AD (Hanifin
and Rajka, 1980).

- AD that affects greater than or equal to' 10% body surface area as assessed by EASI at
screening and on day 1.

- An IGA score of greater than or equal to 3 at screening and on day 1.

- An EASI score of greater than or equal to 16 at screening and on day 1.

- Subject discontinued treatment with TCS, topical calcineurin inhibitors (TCI),
prescription moisturizers, or moisturizers containing additives such as ceramide,
hyaluronic acid, urea, or filaggrin for at least the 7 days immediately prior to the
first dose of investigational product.

- Documented recent history (within 12 months before the screening visit) of inadequate
response totreatment with topical TCS or subjects for whom topical treatments are
otherwise medically inadvisable (ie, because of important side effects or safety
risks).

- Inadequate response is defined as failure to achieve and maintain remission or a low
disease activity state (comparable to IGA 0 = clear to IGA 2 = mild) despite treatment
with a daily regimen of TCS of medium or higher potency (with or without TCI as
appropriate).

Exclusion Criteria:

- Active dermatologic conditions, which might confound the diagnosis of AD or would
interfere with the assessment of treatment, such as scabies, seborrheic dermatitis,
cutaneous lymphoma, ichthyosis, psoriasis, allergic contact dermatitis, or irritant
contact dermatitis.

- History of a clinically significant infection within 28 days prior to day 1 that, in
the opinion of the investigator or medical monitor, might compromise the safety of the
subject in the study, interfere with evaluation of the investigational product, or
reduce the subject's ability to participate in the study. Clinically significant
infections are defined as either of the following: 1) a systemic infection; or 2) a
serious skin infection requiring parenteral antibiotic, antiviral, or antifungal
medication.

- Diagnosis of a helminth parasitic infection within 6 months prior to screening that
had not been treated with or had failed to respond to standard of care therapy.

- Documented medical history of chronic alcohol or drug abuse within 12 months prior to
screening.

- History of anaphylaxis following any biologic therapy.

- Evidence of active liver disease at screening, including jaundice or aspartate
aminotransferase (AST), alanine aminotransferase (ALT), or alkaline phosphatase
greater than twice the upper limit of normal (ULN).

- Diagnosis and/or treatment of tuberculosis within the 12 months prior to screening.

- Positive hepatitis B surface antigen or hepatitis C antibody serology. Subjects with a
history of hepatitis B vaccination without a history of hepatitis B are allowed to
enroll in the study.

- Positive human immunodeficiency virus (HIV) test at screening or the subject is taking
antiretroviral medications, as determined by medical history, prior medications,
and/or the subject's verbal report.

- Other Medical Conditions>

- History of malignancy, except for basal cell carcinoma or in situ carcinoma of the
cervix treated with apparent success with curative therapy ≥ 12 months prior to
screening or other malignancies treated with apparent success with curative therapy ≥
5 years prior to screening.

- History or evidence of severe depression, schizophrenia, previous suicide attempts, or
suicidal ideation.

Prior/Concomitant Therapy:

- Subjects who are unwilling to abstain from the use of TCS, TCI, prescription
moisturizers, or moisturizers containing additives such as ceramide, hyaluronic acid,
urea, or filaggrin from screening through week 16 (applies only to Part A subjects)

- Subjects who have had side effects of topical medications including intolerance to
treatment, hypersensitivity reactions, significant skin atrophy, or systemic effects
as assessed by the investigator or by the subject's treating physician (applies only
to Part B subjects)

- More than or equal to 30% of the total lesional surface is located on areas of thin
skin that cannot be safely treated with medium or higher potency TCS (eg, face, neck,
intertriginous areas, areas of skin atrophy) (applies only to Part B subjects)

- Receipt of any approved biologic agent (eg, dupilumab) within 4 months prior to
screening

- Have used immunosuppressive/immunomodulating drugs (eg, systemic corticosteroids,
cyclosporine, mycophenolate-mofetil, interferon (IFN)-gamma, Janus kinase inhibitors,
azathioprine, methotrexate) within 4 weeks prior to screening, or any condition that,
in the opinion of the investigator, is likely to require such treatment(s) during the
first 4 weeks of study treatment.

- Have had phototherapy for AD in the 2 months prior to day 1, and subjects unwilling to
avoid phototherapy during the first 16 weeks of the study

- If on allergen-specific immunotherapy, subjects must be on a maintenance dose and
schedule for ≥ 28 days prior to screening. Allergen-specific immunotherapy is defined
as SC immunotherapy to aeroallergens and/o venom (Hymenoptera) as well as sublingual
immunotherapy to aeroallergens

- Vaccination with a live or attenuated vaccine within 28 days prior to day 1. Receipt
of inactive/killed vaccinations (eg, inactive influenza) is allowed, provided the
vaccinations are not administered within 7 days before or after any study visit. Note
that receipt of the Th2 cytokine inhibitor suplatast within 15 days prior to screening
is allowed.

- Major surgery within 8 weeks prior to screening or planned inpatient surgery or
hospitalization during the study period

- Currently receiving treatment in another investigational device or drug study, or less
than 6 months since ending treatment on another investigational device or drug
study(ies). Other investigational procedures while participating in this study are
excluded.

Other Exclusions:

- Female subject is pregnant or breastfeeding or planning to become pregnant or
breastfeed during treatment and for an additional 14 weeks after the last dose of
investigational product. (Females of childbearing potential should only be enrolled in
the study after a negative highly sensitive serum pregnancy test).

- Female subjects of childbearing potential who are sexually active with unsterilized
male partners unwilling to use 1 highly effective method of contraception during
treatment and for an additional 14 weeks after the last dose of investigational
product. Cessation of contraception after this point must be discussed with a
responsible physician. Females of childbearing potential are defined as those who are
not surgically sterile (ie, had bilateral tubal ligation, bilateral oophorectomy, or
complete hysterectomy) or postmenopausal (defined as 12 months with no menses without
an alternative medical cause). A highly effective method of contraception is defined
as one that resulted in a low failure rate (ie, < 1% per year) when used consistently
and correctly. Refer to Appendix 5 for additional contraceptive information.

- Male subjects with a female partner of childbearing potential who are unwilling to
practice sexual abstinence (refrain from heterosexual intercourse) or use
contraception during treatment and for an additional 14 weeks after the last dose of
investigational product. Refer to Appendix 5 for additional contraceptive information.

- Male subjects with a pregnant partner who are unwilling to practice abstinence or use
a condom during treatment and for an additional 14 weeks after the last dose of
investigational product.

- Male subjects unwilling to abstain from donating sperm during treatment and for an
additional 14 weeks after the last dose of investigational product.

- Subject has known sensitivity to any of the products or components to be administered
during dosing.

- History or evidence of any other clinically significant disorder, condition or disease
(with the exception of those outlined above) that, in the opinion of the investigator
or Amgen physician, if consulted, would pose a risk to subject safety or interfere
with the study evaluation, procedures, or completion.