Safety Study of PPI-1019 in Patients With Mild-Moderate Alzheimer’s Disease

Inclusion Criteria:

• Patient has the ability to understand the requirements of the study, provide writteninformed consent, and abide by the requirements of the study.

• Patient has a caregiver willing to assist the patient’s involvement in the study.

• Patient is a male or female between the ages of 50 and 80 with a body mass index (BMI)below 31. Females must be post-menopausal at least

1 year or surgically sterilized.

• Patient must have a cognitive deficit present for at least one year and meet DSM IVcriteria for Alzheimer’s Disease and meet National Institute of Neurological andCommunicative Disorders and Stroke/Alzheimer’s Disease and Related DisordersAssociation (NINCDS/ADRDA) criteria for the presence of probable Alzheimer’s Disease.

• Patient’s severity of Alzheimer’s disease must be mild-moderate, documented with aMini Mental State Exam (MMSE) score of 12-26.

• Patient has a computerized tomography (CT) scan or magnetic resonance imaging (MRI)within the prior 12 months which is compatible with a diagnosis of probable AD.

• If a patient is being treated for Alzheimer’s disease, it must be with a single agent (donepezil, rivastigmine, galantamine, or memantine) and with a dose which has beenstable for at least 3 months.

• Patient is otherwise in good general health. Treatment of hypertension with no morethan 2 medications and for hyperlipidemia with one agent is acceptable provided drugsand dosages have been stable for at least 30 days.

• Patient agrees to abstain from alcohol and not take any other drugs, dietarysupplements, or herbal therapies other than Mylanta®, ibuprofen, or a multivitamin forthe length of the study (screening to follow-up visit Day 22).

• Patient agrees not to donate blood or blood products while participating in this studyand for at least 60 days after discontinuing from the study.

Exclusion Criteria:

• Patient has participated in a clinical trial of another investigational drug ordevice, or has taken any experimental drug within 30 days prior to screening.

• Patient has a history compatible with vascular dementia as evidenced by a score of 5or greater on the modified Hachinski Ischemia Scale.

• Patient has evidence of clinically significant cardiovascular, renal, hepatic,gastrointestinal, neurological, or metabolic disease within the past 6 months (asdetermined by medical history, ECG results, chest x-ray, or physical examination).Findings of potential significance must be discussed with an appropriate sponsorclinician (or PRAECIS’ designee) prior to patient entry.

• Patient has a systolic blood pressure (sitting) of greater than 150 mmHg, a diastolic (sitting) greater than 95 mmHg, a decrease in systolic blood pressure of more than 30mmHg upon standing for 2 minutes from a sitting or supine position, or a pulse (sitting or supine) less than 55 or greater than 85.

• Patient has any visual, hearing, or communication disabilities impairing his or herability to participate in the study.

• Patient intends to use any concomitant medications during the study other than thosedescribed in Inclusion Criteria.

• Patient has taken any concomitant medication without the approval of the investigatorwithin 7 days prior to Day 1.

• Patient has tested positive for drugs of abuse (benzodiazepines, narcotics,amphetamines, barbiturates, sedatives, hypnotics, cocaine, phencyclidine, alcohol, orcannabinoids) on drug screening or Day -1.

• Patient has any elevations (> 1.2 x ULN) on screening or Day -1 for ALT, AST,bilirubin, creatinine, blood urea nitrogen, or alkaline phosphatase.

• Patient has any other screening or Day -1 laboratory values outside the normal rangesthat are deemed clinically significant by the investigator.