An adverse event (AE) is any untoward medical occurrence, which does not necessarily have to have a causal relationship with study treatment. An SAE is defined as any AE occurring at any dose that results in any of the following outcomes: death; life-threatening; hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; important medical events. TEAEs are defined as those AEs that started or worsened in severity after the initiation of study drug administration.

Safety Population: all participants who received ≥1 dose of study drug, grouped according to actual study drug taken.

Study baseline is defined as the Day -1 assessment.

Safety Population: all participants who received ≥1 dose of study drug, grouped according to actual study drug taken.

Study baseline is defined as the Day -1 assessment.

Safety Population: all participants who received ≥1 dose of study drug, grouped according to actual study drug taken.

Study baseline is defined as the Day -1 assessment.

Safety Population: all participants who received ≥1 dose of study drug, grouped according to actual study drug taken.

Study baseline is defined as the Day -1 assessment.

Safety Population: all participants who received ≥1 dose of study drug, grouped according to actual study drug taken.

Study baseline is defined as the Day -1 assessment.

Safety Population: all participants who received ≥1 dose of study drug, grouped according to actual study drug taken.

Study baseline is defined as the Day -1 assessment.

Safety Population: all participants who received ≥1 dose of study drug, grouped according to actual study drug taken.

Study baseline is defined as the Day -1 assessment.

Safety Population: all participants who received ≥1 dose of study drug, grouped according to actual study drug taken.

Study baseline is defined as the Day -1 assessment.

Safety Population: all participants who received ≥1 dose of study drug, grouped according to actual study drug taken.

Time-matched baseline is defined as the corresponding assessment on Day 2 of the placebo cycle.

Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment). To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose are presented as the second row of data.

Pharmacodynamic (PD) Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment.

Time-matched baseline is defined as the corresponding assessment on Day 2 of the placebo cycle.

Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment). To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose are presented as the second row of data.

PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment.

Supine systolic blood pressure (SSBP):

≥ 180 mmHg and increase (↑) from baseline (BL) ≥ 30 mmHg; ≤ 90 mmHg and decrease (↓) from BL ≥ 30 mmHg.

Supine Diastolic Blood Pressure (SDBP):

≥ 105 mmHg and ↑ from BL ≥ 20 mmHg; ≤ 50 mmHg and ↓ from BL ≥ 20 mmHg.

Supine pulse rate (SPR):

≥ 110 beats per minute (bpm) and ↑ from BL ≥ 20 bpm; ≤ 50 bpm and ↓ from BL ≥ 20 bpm.

Standing systolic blood pressure (StSBP):

≥ 180 mmHg and increase (↑) from baseline (BL) ≥ 30 mmHg; ≤ 90 mmHg and decrease (↓) from BL ≥ 30 mmHg.

Standing Diastolic Blood Pressure (StDBP):

≥ 105 mmHg and ↑ from BL ≥ 20 mmHg; ≤ 50 mmHg and ↓ from BL ≥ 20 mmHg.

Standing pulse rate (StPR):

≥ 110 beats per minute (bpm) and ↑ from BL ≥ 20 bpm; ≤ 50 bpm and ↓ from BL ≥ 20 bpm.

PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment

Systolic blood pressure (SBP): Decrease of > 20 mmHg from supine to standing Diastolic blood pressure (DBP): Decrease of > 10 mmHg from supine to standing Pulse rate (PR): Increase of > 20 bpm from supine to standing.

PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment

Safety Population: all participants who received ≥1 dose of study drug, grouped according to actual study drug taken.

Safety Population: all participants who received ≥1 dose of study drug, grouped according to actual study drug taken.

Safety Population: all participants who received ≥1 dose of study drug, grouped according to actual study drug taken.

Safety Population: all participants who received ≥1 dose of study drug, grouped according to actual study drug taken.

Safety Population: all participants who received ≥1 dose of study drug, grouped according to actual study drug taken.

Study baseline is defined as the Day -1 assessment.

PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.

Time-matched baseline for each timepoint is defined as the corresponding assessment during the placebo cycle.

Baseline is designated per protocol as Day 1 or 3 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 1 or 3 of each IW-1973 dose at given time point are presented as the second row of data.

PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.

Study baseline is defined as the Day -1 assessment.

PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.

Time-matched baseline for each timepoint is defined as the corresponding assessment during the placebo cycle.

Baseline is designated per protocol as Day 1 or 3 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 1 or 3 of each IW-1973 dose at given time point are presented as the second row of data.

PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.

Study baseline is defined as the Day -1 assessment.

PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.

Time-matched baseline for each timepoint is defined as the corresponding assessment during the placebo cycle.

Baseline is designated per protocol as Day 1 or 3 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 1 or 3 of each IW-1973 dose at given time point are presented as the second row of data.

PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.

An orthostatic measurement is obtained by subtracting the supine measurement from the standing measurement.

PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.

An orthostatic measurement is obtained by subtracting the supine measurement from the standing measurement.

PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.

An orthostatic measurement is obtained by subtracting the supine measurement from the standing measurement.

PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.

Four-hour average is the average of ABPM assessments over 4 hours intervals from the time of dosing. Time-matched baseline is the 4 hours average during the placebo cycle (Day 2).

Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data.

PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.

Thirty-minute average is the average of ABPM assessments over 30 minutes intervals from the time of dosing. Time-matched baseline is the 30 minutes average during the placebo cycle (Day 2).

Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data.

PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.

Daytime average is the average of ABPM assessments over 12 hours from the time of dosing. Time-matched baseline is the daytime average during the placebo cycle (Day 2).

Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data.

PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.

Four-hour average is the average of ABPM assessments over 4 hours intervals from the time of dosing. Time-matched baseline is the 4 hours average during the placebo cycle (Day 2).

Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data.

PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.

Thirty-minute average is the average of ABPM assessments over 30 minutes intervals from the time of dosing. Time-matched baseline is the 30 minutes average during the placebo cycle (Day 2).

Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data.

PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.

Daytime average is the average of ABPM assessments over 12 hours from the time of dosing. Time-matched baseline is the daytime average during the placebo cycle (Day 2).

Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment). To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose are presented as the second row of data.

PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.

Four-hour average is the average of ABPM assessments over 4 hours intervals from the time of dosing. Time-matched baseline is the 4 hours average during the placebo cycle (Day 2).

Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data.

PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.

Thirty-minute average is the average of ABPM assessments over 30 minutes intervals from the time of dosing. Time-matched baseline is the 30 minutes average during the placebo cycle (Day 2).

Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data.

PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.

Daytime average is the average of ABPM assessments over 12 hours from the time of dosing. Time-matched baseline is the daytime average during the placebo cycle (Day 2).

Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment). To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose are presented as the second row of data.

PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.

Four-hour average is the average of ABPM assessments over 4 hours intervals from the time of dosing. Time-matched baseline is the 4 hours average during the placebo cycle (Day 2).

Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data.

PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.

Thirty-minute average is the average of ABPM assessments over 30 minutes intervals from the time of dosing. Time-matched baseline is the 30 minutes average during the placebo cycle (Day 2).

Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose at given time point are presented as the second row of data.

PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.

Daytime average is the average of ABPM assessments over 12 hours from the time of dosing. Time-matched baseline is the daytime average during the placebo cycle (Day 2).

Baseline is designated per protocol as Day 2 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment). To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 2 of each IW-1973 dose are presented as the second row of data.

PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.

PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment.

PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment.

PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment.

Study baseline is defined as the Day -1 assessment.

Endothelial function was assessed by RHI value determined using the noninvasive EndoPAT™ (Itamar Medical; Caesarea, Israel) device. RHI is a validated measure of endothelial function, with a higher RHI indicating better endothelial function compared to a lower value. The full EndoPAT 2000 user manual (software version 3.7.x) recommends using RHI values >1.67 as a cutoff for normal endothelial function, with values ≤1.67 indicating endothelial dysfunction.

PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.

Time-matched baseline for each timepoint is defined as the corresponding assessment during the placebo cycle.

Endothelial function was assessed by RHI value determined using the noninvasive EndoPAT™ (Itamar Medical; Caesarea, Israel) device. RHI is a validated measure of endothelial function, with a higher RHI indicating better endothelial function compared to a lower value. The full EndoPAT 2000 user manual (software version 3.7.x) recommends using RHI values >1.67 as a cutoff for normal endothelial function, with values ≤1.67 indicating endothelial dysfunction.

Baseline is designated per protocol as Day 3 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 3 of each IW-1973 dose at given time point are presented as the second row of data.

PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.

Endothelial function was assessed by RHI value determined using the noninvasive EndoPAT™ (Itamar Medical; Caesarea, Israel) device. RHI is a validated measure of endothelial function, with a higher RHI indicating better endothelial function compared to a lower value. The full EndoPAT 2000 user manual (software version 3.7.x) recommends using RHI values >1.67 as a cutoff for normal endothelial function, with values ≤1.67 indicating endothelial dysfunction.

PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment.

Time-matched baseline is defined as the corresponding assessment on Day 1 of the placebo cycle.

Platelet function assessment used the PFA-100® instrument to evaluate collagen/epinephrine time to aggregation.

Baseline is designated per protocol as Day 1 of the placebo cycle (Days 1-3; i.e., the first cycle of treatment) at given time point. To present 'change from time-matched baseline' endpoints, the values for time-matched baseline are presented as the first row of data, and the changes at Day 1 of each IW-1973 dose at given time point are presented as the second row of data.

PD Population: all participants who received ≥1 dose of study drug and had ≥1 postdose PD assessment with an assessment at given time point.