A Dose Titration Study to Assess the Effects of SAR407899 in Patients With MVA and/or Persistent Stable Angina Despite Angiographically Successful PCI

The total duration of study per subject is:

- up to 9 weeks for patients with previous coronary artery angiography or coronary computed
tomography angiography (CCTA) within 24 months prior to screening with up to 4 weeks
screening period, 3 weeks titration phase, 1 week maintenance period, and 1 week follow-up
after the last investigational medicinal product administration.

or

- up to 11 weeks for patients with previous coronary artery angiography or CCTA between 24
months and 5 years prior to screening, who need CCTA during screening period with up to 6
weeks screening period, 3 weeks titration phase, 1 week maintenance period, and 1 week
follow-up after the last investigational medicinal product administration.

Inclusion criteria:

- Male or female patient not at childbearing potential ≥18 year-old or legal age of
majority.

- Female patient if she has undergone sterilization at least 3 months earlier or is
post-menopausal.

- Post-menopausal status is defined by having no menses for 12 months without an
alternative medical cause.

- In females not treated with hormonal replacement therapy (HRT), menopausal status is
confirmed by a high follicle stimulating hormone (FSH) level greater than 40 IU/L.

- In females on HRT and whose menopausal status is in doubt (ie, in women aged less than
45 years), a highly effective contraception methods will be required. Contraception
should be used during the whole study and for at least seven days corresponding to
time needed to eliminate study treatment.

- Symptomatic stable angina pectoris (typical or atypical symptoms with an average of at
least bi-weekly episodes over the past month).

- Patients with non-obstructive (<50% stenosis) coronary arteries or intermediate
stenosis (between 50 and 70%) should have fractional flow reserve (FFR) >0.80 or
instantaneous wave-free ratio (iFR) >0.89 on angiogram, documented within the previous
24 months*. In patients with stenting, a minimum diameter stenosis of <10% is
required.

or Coronary computed tomography angiography (CCTA) with finding of non-obstructive coronary
arteries within the past 24 months* in patients without previous percutaneous coronary
intervention (PCI).

*Note: in cases of clinically suspected progression of atherosclerosis as per the
Investigator, a more contemporary (i.e., 6 months) evidence should be provided.

or CCTA performed during screening period, with finding of non-obstructive coronary
arteries, in patients diagnosed with microvascular angina (MVA) and stable angina without
previous PCI who did not have a coronary angiogram or CCTA in the previous 24 months but
between 24 months to 5 years.

- Baseline global coronary flow reserve (CFR) (measured during the study) assessed by
13N-ammonia or 82Rubidium positron emission tomography (PET) scan <2.0.

Exclusion criteria:

- Any use of nitrates (except short-acting nitrates) and/or dipyridamole and/or
phosphodiesterase type 5 (PDE 5) inhibitors within one week prior to baseline PET scan
or anticipated to be used during the study.

- Esophageal dysmotility or esophagitis.

- Patients with acute coronary syndrome (ACS) (myocardial infarction [MI] and/or
unstable angina) in previous 3 months.

- Unsuccessful or incomplete coronary revascularization with residual obstructive
stenosis or coronary artery disease (CAD) progression in native vessels as documented
on invasive coronary angiography (≥50% stenosis) within 24 months of enrollment.

- Percutaneous coronary intervention performed at the time of an ACS (MI or unstable
angina) in the previous 12 months.

- Recent PCI within the past 3 months.

- Patients with history of coronary artery bypass grafting (CABG).

- Recent (≤3 months) major surgery (ie, valvular surgery, surgery for congenital heart
disease), stroke, transient ischemic attack [TIA], sustained ventricular arrhythmia,
clinically significant structural heart disease (moderate-severe valvular disease,
hypertrophic cardiomyopathy, congenital heart disease, pulmonary hypertension).

- Regional local flow abnormal perfusion defects at baseline PET scan*.

*Note: if contemporary evidence with invasive coronary angiography or coronary
computed tomography angiography (CCTA) demonstrates non-obstructive coronary arteries
or if the regional local flow abnormal perfusion defect on PET scan is consistent with
previous studies then patient qualifies for the study.

- Patients with cardiac conduction abnormalities (second or third degree
atrioventricular [AV] block, sick sinus syndrome, symptomatic bradycardia, sinus node
disease) except in patients fitted with a functioning pacemaker.

- History or known carotid stenosis:

- Carotid stenosis (>50%) or

- History of carotid stenosis in patients with previous symptoms.

- Contraindication or known hypersensitivity to adenosine or regadenoson.

- Contraindication to aminophylline.

- Contraindication to vasodilator stress PET scan and/or CCTA if CCTA needed during
screening.

- Inability to discontinue treatment with methylxanthines treatment within 24 hours
prior to PET scan.

- Patient unable to read, understand and fill a questionnaire without any help (eg,
partially visually impaired or blind).

- Systolic blood pressure (SBP) <110 mmHg at baseline.

- Presence at baseline of symptomatic orthostatic hypotension (SBP decrease of 20 mmHg
or more at Minute 3 or Minute 5 between seated and standing position), or asymptomatic
orthostatic hypotension with a decrease in SBP equal or greater than 30 mmHg at Minute
3 or Minute 5 when changing from the seated to the standing position.

- Renal impairment with estimated glomerular filtration rate (eGFR) <50 mL/min/1.73 m2
at screening and baseline.

- Drug-induced liver injury related criteria:

- Underlying hepatobiliary disease.

- Alanine Aminotransferase (ALT) >3 times the upper limit of normal (ULN).

The above information is not intended to contain all considerations relevant to a patient's
potential participation in a clinical trial.