Laboratory toxicities were graded according to the Common Terminology Criteria for Adverse Events (Version 4) on a scale from grade 1 (mild) to 5 (death).

All study samples (tezepelumab and placebo) were tested using an electrochemiluminescence (ECL) based immunoassay to detect and confirm the presence of antibodies capable of binding to tezepelumab. Samples identified as positive in the immunoassay were tested in a receptor-binding ECL-based assay to detect neutralizing or inhibitory effects toward tezepelumab.

The number of participants with positive anti-tezepelumab binding antibodies / neutralizing antibodies at any time post-baseline with a negative or no result at baseline is reported.

Participants underwent allergen inhalation challenge on study days 42 and 84 to induce airway bronchoconstriction. FEV1 was measured prior to the challenge and between 0 to 2 hours post challenge to assess early asthmatic response (EAR).

The maximum percent decrease in FEV1 from pre-allergen challenge is the percent change in FEV1 representing the largest percentage decrease (or minimum percentage increase) from pre-allergen challenge FEV1 during early (0-2 hour) asthmatic response time frame.

Participants underwent allergen inhalation challenge on study days 42 and 84 to induce airway bronchoconstriction. FEV1 was measured prior to the challenge and between 0 to 2 hours post challenge to assess early asthmatic response (EAR).

The percent change in FEV1 from pre-allergen challenge was calculated to each time point between 0 to 2 hours post challenge. The area under the curve for the percent change at each time point was calculated using the linear trapezoidal rule, then time adjusted by dividing by the length of time over which the AUC was calculated.

Participants underwent allergen inhalation challenge on study days 42 and 84 to induce airway bronchoconstriction. FEV1 was measured prior to the challenge and between 0 to 2 hours post challenge to assess early asthmatic response (EAR).

The minimum FEV1 post onset of the allergen challenge for EAR is defined as the smallest value of FEV1 measured during 0 to 2 hours post allergen challenge.

Participants underwent allergen inhalation challenge on study days 42 and 84 to induce airway bronchoconstriction. FEV1 was measured prior to the challenge and between 0 to 2 hours post challenge to assess early asthmatic response (EAR).

The area under the curve for the FEV1 between 0 to 2 hours post allergen challenge was calculated using the linear trapezoidal rule, then time adjusted by dividing by the length of time over which the AUC was calculated.

Participants underwent allergen inhalation challenge on study days 42 and 84 to induce airway bronchoconstriction. FEV1 was measured prior to the challenge and between 3 to 7 hours post challenge to assess late asthmatic response (LAR).

The minimum FEV1 post allergen challenge for LAR is defined as the smallest value of FEV1 measured during 3 to 7 hours post allergen challenge.

Participants underwent allergen inhalation challenge on study days 42 and 84 to induce airway bronchoconstriction. FEV1 was measured prior to the challenge and between 3 to 7 hours post allergen challenge to assess late asthmatic response (LAR).

The area under the curve for the FEV1 between 3 to 7 hours post allergen challenge was calculated using the linear trapezoidal rule, then time adjusted by dividing by the length of time over which the AUC was calculated.

The PK parameter Cmax was estimated based on the serum concentrations of tezepelumab using noncompartmental methods. The concentration of tezepelumab in human serum was measured using a validated ELISA. The lower limit of quantification of the assay was 10 ng/mL.

The PK parameter Tmax was estimated based on the serum concentrations of tezepelumab using noncompartmental methods. The concentration of tezepelumab in human serum was measured using a validated ELISA. The lower limit of quantification of the assay was 10 ng/mL.

The PK parameter Cmin was estimated based on the serum concentrations of tezepelumab using noncompartmental methods. The concentration of tezepelumab in human serum was measured using a validated ELISA. The lower limit of quantification of the assay was 10 ng/mL.

The PK parameter AUCtau was estimated based on the serum concentrations of tezepelumab using noncompartmental methods.

The dosing interval (tau) was 28 days. The concentration of tezepelumab in human serum was measured using a validated ELISA. The lower limit of quantification of the assay was 10 ng/mL.

Accumulation ratio (AR) based on AUCtau was calculated as AUCtau after last dose / AUCtau after first dose.

Accumulation ratio based on Cmax calculated as Cmax after last dose / Cmax after first dose.

The PK parameter AUCinf was estimated based on the serum concentrations of tezepelumab using noncompartmental methods. The concentration of tezepelumab in human serum was measured using a validated ELISA. The lower limit of quantification of the assay was 10 ng/mL.

The PK parameter t1/2,z was estimated based on the serum concentrations of tezepelumab using noncompartmental methods. The concentration of tezepelumab in human serum was measured using a validated ELISA. The lower limit of quantification of the assay was 10 ng/mL.

Total of all reporting groups

Participants received 700 mg tezepelumab administered by intravenous infusion on study days 1, 29, and 57.

Participants underwent allergen inhalation challenge on study days 42 and 84 to induce airway bronchoconstriction. FEV1 was measured prior to the challenge and between 3 to 7 hours post challenge to assess late asthmatic response (LAR).

The percent change in FEV1 from pre-challenge was calculated to each time point between 3 to 7 hours post challenge. The area under the curve for the percent change at each time point was calculated using the linear trapezoidal rule, then time adjusted by dividing by the length of time over which the AUC was calculated.

Participants who received at least 1 dose of study drug and with available AUC data on each day.

A serious adverse event is defined as an adverse event that meets at least 1 of the following serious criteria:

• fatal,
• life-threatening,
• requires in-patient hospitalization or prolongation of existing hospitalization,
• results in persistent or significant disability/incapacity,
• congenital anomaly/birth defect, and/or
• other medically important serious event. The severity of each adverse event was graded by the Investigator as mild, moderate, severe, life-threatening, or fatal according to the Common Terminology Criteria for Adverse Events (Version 4).

Participants who received at least 1 dose of study drug.

Laboratory toxicities were graded according to the Common Terminology Criteria for Adverse Events (Version 4) on a scale from grade 1 (mild) to 5 (death).

Participants who received at least 1 dose of study drug.

All study samples (tezepelumab and placebo) were tested using an electrochemiluminescence (ECL) based immunoassay to detect and confirm the presence of antibodies capable of binding to tezepelumab. Samples identified as positive in the immunoassay were tested in a receptor-binding ECL-based assay to detect neutralizing or inhibitory effects toward tezepelumab.

The number of participants with positive anti-tezepelumab binding antibodies / neutralizing antibodies at any time post-baseline with a negative or no result at baseline is reported.

Participants who received at least 1 dose of study drug.

Participants underwent allergen inhalation challenge on study days 42 and 84 to induce airway bronchoconstriction. FEV1 was measured prior to the challenge and between 0 to 2 hours post challenge to assess early asthmatic response (EAR).

The maximum percent decrease in FEV1 from pre-allergen challenge is the percent change in FEV1 representing the largest percentage decrease (or minimum percentage increase) from pre-allergen challenge FEV1 during early (0-2 hour) asthmatic response time frame.

Participants who received at least 1 dose of study drug with available data on each day.

Participants underwent allergen inhalation challenge on study days 42 and 84 to induce airway bronchoconstriction. FEV1 was measured prior to the challenge and between 0 to 2 hours post challenge to assess early asthmatic response (EAR).

The percent change in FEV1 from pre-allergen challenge was calculated to each time point between 0 to 2 hours post challenge. The area under the curve for the percent change at each time point was calculated using the linear trapezoidal rule, then time adjusted by dividing by the length of time over which the AUC was calculated.

Participants who received at least 1 dose of study drug and with available AUC data on each day.

Participants underwent allergen inhalation challenge on study days 42 and 84 to induce airway bronchoconstriction. FEV1 was measured prior to the challenge and between 0 to 2 hours post challenge to assess early asthmatic response (EAR).

The minimum FEV1 post onset of the allergen challenge for EAR is defined as the smallest value of FEV1 measured during 0 to 2 hours post allergen challenge.

Participants who received at least 1 dose of study drug with available data on each day.

Participants underwent allergen inhalation challenge on study days 42 and 84 to induce airway bronchoconstriction. FEV1 was measured prior to the challenge and between 0 to 2 hours post challenge to assess early asthmatic response (EAR).

The area under the curve for the FEV1 between 0 to 2 hours post allergen challenge was calculated using the linear trapezoidal rule, then time adjusted by dividing by the length of time over which the AUC was calculated.

Participants who received at least 1 dose of study drug and with available AUC data on each day.

Participants underwent allergen inhalation challenge on study days 42 and 84 to induce airway bronchoconstriction. FEV1 was measured prior to the challenge and between 3 to 7 hours post challenge to assess late asthmatic response (LAR).

The minimum FEV1 post allergen challenge for LAR is defined as the smallest value of FEV1 measured during 3 to 7 hours post allergen challenge.

Participants who received at least 1 dose of study drug with available data on each day.

Participants underwent allergen inhalation challenge on study days 42 and 84 to induce airway bronchoconstriction. FEV1 was measured prior to the challenge and between 3 to 7 hours post allergen challenge to assess late asthmatic response (LAR).

The area under the curve for the FEV1 between 3 to 7 hours post allergen challenge was calculated using the linear trapezoidal rule, then time adjusted by dividing by the length of time over which the AUC was calculated.

Participants who received at least 1 dose of study drug and with available AUC data on each day.

The PK parameter Cmax was estimated based on the serum concentrations of tezepelumab using noncompartmental methods. The concentration of tezepelumab in human serum was measured using a validated ELISA. The lower limit of quantification of the assay was 10 ng/mL.

The pharmacokinetic (PK) parameter analysis set includes participants for whom pharmacokinetic parameter estimates could be derived after first dose and after last dose.

The PK parameter Tmax was estimated based on the serum concentrations of tezepelumab using noncompartmental methods. The concentration of tezepelumab in human serum was measured using a validated ELISA. The lower limit of quantification of the assay was 10 ng/mL.

The PK parameter analysis set includes participants for whom pharmacokinetic parameter estimates could be derived after first dose and after last dose.

The PK parameter Cmin was estimated based on the serum concentrations of tezepelumab using noncompartmental methods. The concentration of tezepelumab in human serum was measured using a validated ELISA. The lower limit of quantification of the assay was 10 ng/mL.

The PK parameter analysis set includes participants for whom pharmacokinetic parameter estimates could be derived after first dose and after last dose.

The PK parameter AUCtau was estimated based on the serum concentrations of tezepelumab using noncompartmental methods.

The dosing interval (tau) was 28 days. The concentration of tezepelumab in human serum was measured using a validated ELISA. The lower limit of quantification of the assay was 10 ng/mL.

The PK parameter analysis set includes participants for whom pharmacokinetic parameter estimates could be derived after first dose and after last dose.

Accumulation ratio (AR) based on AUCtau was calculated as AUCtau after last dose / AUCtau after first dose.

The PK parameter analysis set includes participants for whom pharmacokinetic parameter estimates could be derived after first dose and after last dose.

Accumulation ratio based on Cmax calculated as Cmax after last dose / Cmax after first dose.

The PK parameter analysis set includes participants for whom pharmacokinetic parameter estimates could be derived after first dose and after last dose.

The PK parameter AUCinf was estimated based on the serum concentrations of tezepelumab using noncompartmental methods. The concentration of tezepelumab in human serum was measured using a validated ELISA. The lower limit of quantification of the assay was 10 ng/mL.

The PK parameter analysis set includes participants for whom pharmacokinetic parameter estimates could be derived after last dose.

The PK parameter t1/2,z was estimated based on the serum concentrations of tezepelumab using noncompartmental methods. The concentration of tezepelumab in human serum was measured using a validated ELISA. The lower limit of quantification of the assay was 10 ng/mL.

The PK parameter analysis set includes participants for whom pharmacokinetic parameter estimates could be derived after last dose.

Participants received 700 mg tezepelumab administered by intravenous infusion on study days 1, 29, and 57.

Treatment difference in late asthmatic response at day 84 was evaluated using a repeated-measures ANCOVA that included study treatment and study visit as independent variables, treatment by study visit as an interaction term, and the corresponding baseline value (as measured 14 days before the first dose of a study drug) as a model covariate.

Model includes treatment, visit, treatment by visit interaction as fixed effects and day -14 value as covariate.

Treatment difference estimate (tezepelumab minus placebo) is mean estimate based on ANCOVA.

Treatment difference in early asthmatic response at day 84 was evaluated using a repeated-measures ANCOVA that included study treatment and study visit as independent variables, treatment by study visit as an interaction term, and the corresponding baseline value (as measured 14 days before the first dose of a study drug) as a model covariate.

Model includes treatment, visit, treatment by visit interaction as fixed effects and Day -14 value as covariate.

Treatment difference estimate (tezepelumab minus placebo) is mean estimate based on ANCOVA.

Treatment difference in early asthmatic response at day 84 was evaluated using a repeated-measures ANCOVA that included study treatment and study visit as independent variables, treatment by study visit as an interaction term, and the corresponding baseline value (as measured 14 days before the first dose of a study drug) as a model covariate.

Model includes treatment, visit, treatment by visit interaction as fixed effects and day -14 value as covariate.

Treatment difference estimate (tezepelumab minus placebo) is mean estimate based on ANCOVA.

Treatment difference in early asthmatic response at day 84 was evaluated using a repeated-measures ANCOVA that included study treatment and study visit as independent variables, treatment by study visit as an interaction term, and the corresponding baseline value (as measured 14 days before the first dose of a study drug) as a model covariate.

Model includes treatment, visit, treatment by visit interaction as fixed effects and Day -14 value as covariate.

Treatment difference estimate (tezepelumab minus placebo) is mean estimate based on ANCOVA.

Treatment difference in early asthmatic response at day 84 was evaluated using a repeated-measures ANCOVA that included study treatment and study visit as independent variables, treatment by study visit as an interaction term, and the corresponding baseline value (as measured 14 days before the first dose of a study drug) as a model covariate.

Model includes treatment, visit, treatment by visit interaction as fixed effects and day -14 value as covariate.

Treatment difference estimate (tezepelumab minus placebo) is mean estimate based on ANCOVA.

Treatment difference in late asthmatic response at day 84 was evaluated using a repeated-measures ANCOVA that included study treatment and study visit as independent variables, treatment by study visit as an interaction term, and the corresponding baseline value (as measured 14 days before the first dose of a study drug) as a model covariate.

Model includes treatment, visit, treatment by visit interaction as fixed effects and Day -14 value as covariate.

Treatment difference estimate (tezepelumab minus placebo) is mean estimate based on ANCOVA.

Treatment difference in late asthmatic response at day 84 was evaluated using a repeated-measures ANCOVA that included study treatment and study visit as independent variables, treatment by study visit as an interaction term, and the corresponding baseline value (as measured 14 days before the first dose of a study drug) as a model covariate.

Model includes treatment, visit, treatment by visit interaction as fixed effects and day -14 value as covariate.

Treatment difference estimate (tezepelumab minus placebo) is mean estimate based on ANCOVA.