Dose Finding Study to Determine if BEZ235 Alone or in Combination With RAD001 Decreases the Incidence of Respiratory Tract Infections in the Elderly

This is a randomized, blinded, placebo-controlled, multicenter, parallel-group, dose finding
24-week study to assess the safety, tolerability and efficacy of up to 3 doses of BEZ235
alone and in combination with RAD001 as compared to placebo in elderly subjects who are at
increased risk of respiratory tract infection related-morbidity and mortality. The study will
be composed of up to a 6-week screening and run-in period, a 16-week treatment period and an
8-week follow-up period.

Inclusion Criteria:

- Male and female subjects

- Age ≥ 85 years

- Age ≥ 65 and < 85 years with one or more of the following conditions:

- Asthma

- Chronic Obstructive Pulmonary Disease (COPD)

- Chronic bronchitis

- Type 2 Diabetes Mellitus (T2DM)

- Congestive Heart Failure (CHF) New York Heart Association (NYHA) functional
classification I-II

- Current smoker

- One or more emergency room visits or hospitalizations for a RTI during the
previous 12 months

Exclusion Criteria:

- Subjects with medically significant cardiac conditions including NYHA functional
classification III-IV

- Subjects with Type I diabetes mellitus.

- Subjects with clinically significant underlying pulmonary disease other than asthma,
GOLD Class I and II COPD or chronic bronchitis

- 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, cervical carcinoma in situ, breast cancer localized to the
breast.

- Subjects with any one of the following:

- hemoglobin < 10.0 g/dL for males and < 9.0 for females

- white blood cell (WBC) count < 3,500/mm3,

- neutrophil count < 2,000/mm3

- platelet count < 125,000/mm3

- Subjects with a history of a systemic autoimmune disease or receiving
immunosuppressive therapy

- Recent surgery other than minor skin surgery

- Liver disease or liver injury

- History or presence of impaired renal function

- History of immunodeficiency diseases

- Subjects with active infection

- Subjects with a Mini Mental Status Examination (MMSE) score <24 at screening.

- Significant illness (based on the subject's medical history and the clinical judgement
of the investigator) which has not resolved within two (2) weeks prior to initial
dosing.