Study to Assess the Safety and Tolerability of Multiple Ascending Doses of REGN1033 (SAR391786)

Inclusion Criteria:

Eligible subjects are males and females aged 60 years and older with no significant health
issues or clinically significant abnormal laboratory values.

A subject must meet the following criteria to be eligible for inclusion in the study:

1. Sexually active males willing to use contraceptives during the study and through 4
months after the study.

2. Female subjects not of child bearing potential (surgically sterile or postmenopausal
for longer than 1 year)

3. Body mass index (BMI) between 18.5 and 32 kg/m2 inclusive

4. Willing to maintain current diet and exercise routine for the duration of the study

5. Willing and able to return for all clinic visits and complete all study-related
procedures

6. Able to read and understand, and willing to sign the ICF

Exclusion Criteria:

1. Significant concomitant illness such as, but not limited to cardiac, renal,
rheumatologic, gastrointestinal, hematological, skeletal/muscular, neurologic,
psychiatric, endocrine, metabolic or immunological disease.

2. Evidence of malnutrition

3. Cachexia of any cause

4. Evidence or history of muscle diseases or weakness with the exception of age related
muscle loss

5. Limb amputation

6. Immobilization, surgical procedure, fracture, or trauma to the upper or lower limb
within 6 months

7. History or evidence of heart diseases including but not limited to coronary heart
disease with/without history of myocardial infarction, chronic or acute heart failure
(New York Heart Association [NYHA] stage 2-4), cardiac arrhythmia with clinical
symptoms, valvular heart disease, and cardiac hypertrophy of clinical significance

8. Women of childbearing potential (not surgically sterile or amenorrheic for at least
12 months if postmenopausal)

9. Uncontrolled diabetes defined as HbA1C > 7.5 at screening; if taking oral
hypoglycemic drugs, have to be on stable doses of medication for more than 3 months.
Diabetics using insulin are excluded

10. Asthmatic subjects with current or recurring symptoms within 1 year.

11. History of, COPD, chronic kidney disease, cancer except primary basal-cell skin
cancer that has been adequately treated

12. Neurological injury (eg, stroke) within 1 year

13. Abnormal or uncontrolled blood pressure at screening visit defined as diastolic BP
>95 and/or systolic BP >160 mm Hg; if taking hypertensive medication, have to be on
stable doses of medication for more than 3 months

14. Hepatic transaminases (ALT and or AST) > 2X ULN

15. Reduced renal function as defined by eGFR<60 mL/min

16. Current smokers or previous smokers who stopped smoking within 6 months

17. Current or recent history (within 1 year of screen) of alcohol or drug abuse

18. History of hypersensitivity response to any biologics

19. History of hypersensitivity to doxycycline or other tetracycline antibiotics

20. Current or recent participation in any clinical trial (within 30 days of small
molecular drugs or within 3 months of biologics)

21. Exposure within 3 months to approved biological drugs. (The name of the drug and
duration of previous exposure will be recorded). Vaccines are allowed.

22. Sexually active men* who are unwilling to practice adequate contraception during the
study