The main objective of this study is to assess the safety and tolerability of AMG 691 as single doses (healthy participants only) and multiple doses in healthy participants and participants with mild-to-moderate asthma.

Inclusion Part A and B

• Participants must be capable of giving informed consent and have provided informed consent.
• Participants must be 18 to 65, inclusive at time of signing of informed consent.
• Participants must have a Body Mass Index between 18.0 to 30 kg/m^2 and total body weight ≥ 40 kg at screening.
• Participants must be overtly healthy as determined by the investigator based on medical evaluation and study screening procedures.
• Female participants must be of non-childbearing potential.

Inclusion Part C

• Participants must be capable of giving informed consent and have provided informed consent.
• Participants must be 18 to 70, inclusive at time of signing of informed consent.
• Body mass index between 18.0 to 35 kg/m^2 and total body weight ≥ 40 kg at screening.
• Participants must have documentation of physician diagnosed asthma for ≥ 12 months prior to screening.
• Participants must have documented bronchodilator responsiveness of forced expiratory volume in 1 second (FEV1) ≥ 10% in the 10 years before screening or at the screening visit.
• Participants must have a pre-bronchodilator percent predicted FEV1 ≥ 50% at screening visit and Day -1. For participants on high-dose ICS, participants must have a percent-predicted FEV1 ≥ 70% at screening visit and on day -1.
• Participants must have peripheral blood eosinophils ≥ 200 cells/μl at screening visit and Day -1.
• Participants must have a fractional exhaled nitric oxide (FeNO) ≥ 25 ppb at screening visit and Day -1.
• Participant must not use inhaled corticosteroids (ICS) or must be treated with low-dose, medium-dose, or high-dose ICS and on a stable dose for a minimum of 12 weeks prior to screening.

Exclusion (applicable to all study parts)

• History of malignancy (except for in situ cervical cancer or surgically excised non-melanoma skin cancer occurring more than 5 years prior to randomization).
• History of anaphylaxis or hypersensitivity to biologic therapy or sensitivity to mammalian derived products.
• History of immunodeficiency or history of severe infection within the last 3 years requiring IV antibiotics.
• History of tuberculosis (TB), TB symptoms, or positive interferon gamma release assay.
• History of untreated or unresolved helminthic infection within 24 weeks of day 1.
• Positive human immunodeficiency virus (HIV) antibodies, hepatitis B core antigen, hepatitis B core antibody, or hepatitis C virus (HCV) ribonucleic acid (RNA).
• Male participants unwilling to follow contraceptive requirements.

Additional Exclusion for Part C only

• Female of childbearing potential not willing to use 2 methods of contraception with one being a highly effective method of contraception.
• History of pulmonary disease that may interfere with interpretation of study results.
• History of upper respiratory infection within 6 weeks of screening.
• Asthma Control Questionnaire (ACQ-6) > 3.
• Asthma symptoms or exacerbations requiring 2 or more systemic corticosteroid bursts (≥10 mg/day prednisone or equivalent for ≥ 3 days each) in the previous 12 months.
• More than one hospitalization or emergency department visit in the last year.
• History of life-threatening asthma exacerbation after the 12 years age requiring admission to intensive care unit.

De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.

Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.

Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.