A Phase 3 Study to Determine if RTB101 Prevents Clinically Symptomatic Respiratory Illness in the Elderly

Inclusion Criteria:

1. Written informed consent must be obtained before any assessment is performed.
2. Male and female subjects who, in the clinical judgement of the Investigator, arewithout unstable medical conditions defined as conditions that require acute medicalintervention or ongoing adjustments of concomitant medications (as determined bymedical history, current concomitant medications and laboratory test results atScreening, and physical examination, electrocardiogram (ECG) and vital signs atScreening and Baseline).
3. Subjects must be ≥65 years of age.
4. Subjects should require no or minimal assistance with self-care and activities ofdaily living. Subjects in assisted-living or long-term care residential facilitiesthat provide minimal assistance are eligible.
5. Females must be post-menopausal. Women are considered postmenopausal and not ofchildbearing potential if they have had:

• 12 months of natural (spontaneous) amenorrhea with an appropriate clinicalprofile (e.g., age appropriate, history of vasomotor symptoms) OR
• Surgical bilateral oophorectomy (with or without hysterectomy), totalhysterectomy or tubal ligation at least 6 weeks prior to Screening. In the caseof oophorectomy alone, only when the reproductive status of the woman has beenconfirmed by follow up hormone level assessment will she be considered not ofchildbearing potential.

6. Sexually active male subjects with a partner of child-bearing potential must bewilling to wear a condom while on study drug and for 1 week after stopping study drugand should not father a child in this period. A condom is required to be used also byvasectomized men with a partner of child-bearing potential to prevent delivery of thedrug via seminal fluid.
7. Subject must weigh at least 40 kg.
8. Subject must be able to communicate well with the Investigator, and to understand andcomply with the requirements of the study including completing a daily eDiary at home.

Exclusion Criteria:

1. Any subject who:

• Is a current smoker as assessed by medical history or a positive serum cotininetest (or positive urine cotinine test if serum cotinine testing is unavailable)at Screening. Stopped smoking ≤1 year prior to Screening.
• Is a previous smoker with a ≥10 pack year smoking history. Has a household memberwho currently smokes in the house

2. Subjects with a medical history of clinically significant lung diseases other thanasthma (e.g., chronic obstructive pulmonary disease (COPD), emphysema, interstitialpulmonary fibrosis (IPF), bronchiectasis, etc.).
3. Subjects with a Mini Mental Status Examination (MMSE) score <24 at Screening.
4. Subjects with current evidence of a serious and/or unstable medical disorder includingcardiovascular, respiratory, gastrointestinal, renal (including subjects with anestimated glomerular filtration rate (eGFR) as estimated by the modified diet in renaldisease (MDRD) GFR equation that is ≤30 mL/min/1.73m2), or hematologic disorders.
5. The following cardiac conditions:

• Unstable angina pectoris or acute ischemic changes on ECG at Screening orBaseline
• History of myocardial infarction (MI), coronary bypass surgery, or anypercutaneous coronary intervention (PCI) within 6 months prior to Screening
• New York Heart Association functional classification IIIIV congestive heartfailure
• Unstable or life-threatening cardiac arrhythmia, chronic stable atrialfibrillation is allowed.
• QTcF>480 msec at Screening or Baseline

6. Subjects with history of malignancy in any organ system within the past 5 years,EXCEPT for the following:

• Localized basal cell or squamous cell carcinoma of the skin.
• Prostate cancer confined to the gland (AJCC stage T2N0M0 or better).
• Cervical carcinoma in situ.
• Breast cancer localized to the breast.

7. Any RTI or acute significant illness (based on the subject's medical history and theclinical judgement of the Investigator) which has not resolved at least two (2) weeksprior to Baseline.
8. Subjects with a history of systemic autoimmune diseases (e.g., lupus, inflammatorybowel disease, rheumatoid arthritis, etc.), or receiving immunosuppressive therapy (such as mycophenolate, tacrolimus, cyclosporine, azathioprine, infliximab) includingchronic use of prednisone >10 mg daily (however, inhaled corticosteroids and the acuteuse of higher doses of prednisone to treat conditions such as exacerbation of asthmaor other acute conditions are allowed).
9. Subjects with Type I diabetes mellitus.
10. Clinically relevant abnormal laboratory values suggesting an unknown disease andrequiring further evaluation.
11. Subjects with any one of the following during Screening:

• white blood cell (WBC) count <2.0 x103/microL.
• neutrophil count <1.0 x 103/microL.
• platelet count <75 x 103/microL..

12. Subjects with a history of alcohol or drug abuse within 2 years of the Screeningvisit.
13. Subjects with any conditions affecting absorption, distribution, or metabolism of thestudy drug (e.g., inflammatory bowel disease, gastric or duodenal ulcers, or hepaticdisease). For subjects with biochemical evidence of liver injury as indicated byabnormal liver function tests:

• Any single parameter of alanine aminotransferase (ALT), aspartateaminotransferase (AST), alkaline phosphatase or serum bilirubin must not exceed 1.5 x upper limit of normal (ULN) in subjects who do not have Gilbert's syndrome.If the subject has a history of Gilbert's syndrome, direct and indirect reactingbilirubin should be differentiated, and the direct bilirubin must be less than 1.5 x ULN.
• Any elevation above ULN of more than one parameter of ALT, AST, alkalinephosphatase or serum bilirubin will exclude a subject from participation in thestudy.

14. Subjects with a history of immunodeficiency diseases, including a positive humanimmunodeficiency virus (HIV) test result.
15. Infection with Hepatitis B virus (HBV) or Hepatitis C virus (HCV).
16. Subjects who require treatment with strong CYP3A4 or CYP1A2 inhibitors or inducers, orsubjects who require treatment with digoxin.
17. Use of any other investigational medication or participation in any otherinvestigational study within 5 half-lives of the investigational medication, or within 30 days, whichever is longer; or longer if required by local regulations.
18. Subjects who have received an organ transplant.
19. Subjects who previously received treatment with RTB101 in another clinical study (e.g., CBEZ235Y2201, RTB-BEZ235-202, or RTB-101-203).