FLURIZAN™ Phase 2 Alzheimer's Disease
Clinical Trial

Myriad conducted a large, placebo-controlled Phase 2 trial for FLURIZAN of 12 months duration in 207 patients with mild to moderate Alzheimer's disease. The study enrolled patients in the UK and Canada. After 12 months, patients in Canada were eligible to enroll in an additional double-blinded 12-month treatment study. Over 80% of the eligible patients elected to continue in this study in which placebo patients were randomized into one of the two treatment groups (400 mg or 800 mg of Flurizan twice daily) and treated patients continued their previous dose. Both the patients and their physicians remained blinded as to their treatment group throughout the study.

The results of this study were presented in July 2006 at the 10th International Conference on Alzheimer's Disease and Related Disorders, in Madrid , Spain , by Dr. Gordon Wilcock, Professor of Clinical Gerontology, University of Oxford , and lead investigator for the Phase 2 trial. See presentations.

The primary outcome measures for the trial were the rate of change (slope of decline) of:

• Activities of Daily Living (includes dressing, bathing, eating, traveling, etc. based on caregiver responses and quantified by the ADCS-ADL)
• Global Function (memory, orientation, community activities, home and hobbies and personal care as measured by the CDR-sb)
• Cognitive Function (memory and thinking skills measured by the ADAS-cog)

FLURIZAN Phase 2 Clinical Trial Results Highlights

• Patients with mild Alzheimer's disease who took 800 mg of FLURIZAN twice a day for 12 months showed a reduced rate of deterioration in Activities of Daily Living, Global Function, and Cognition. See references below.
• At enrollment, the vast majority of patients were receiving stable doses of acetylcholinesterase inhibitors and remained on them throughout the study
• Positive effects increased over time on all scales
• Results are consistent with a Selective Aβ42-Lowering (SALA) strategy in AD
• Patients who achieved a higher plasma concentration had a significantly better response
• Patients treated for 24 months declined more slowly than those treated for only 12 months
• consistent with hypothesis for a disease modifying treatment
• a significant reduction (p<0.05) in the number of and a delay in time to psychiatric events (p<0.05) See presentations.

FLURIZAN Phase 2 Safety Summary

• Overall, Flurizan appeared very well tolerated
• Discontinuations due to adverse events were comparable between those receiving Flurizan and placebo
• In the Flurizan treated groups, there were fewer discontinuations due to Alzheimer's disease progression
• Adverse events (higher frequency than placebo)
• transient eosinophilia, mild anemia, blood pressure elevation, lower respiratory infection, rash
• Fewer events than placebo
• urinary incontinence
• psychiatric events

FLURIZAN Phase 2 Study Summary

• Defined early Alzheimer's disease as optimal target population
• fits hypothesis about role of a anti-amyloid drug in Alzheimer's disease
• Established the dose (800 mg twice a day) for Phase 3 studies
• drug was well-tolerated in this patient population
• Provided data to design highly powered Phase 3 studies

Patients who completed the study were eligible for treatment with Flurizan under an open-label protocol.

FLURIZAN Presentations

	A Responder Analysis of Tarenflurbil (MPC-7869), a Selective Aβ42-Lowering Agent, in Mild Alzheimer's Disease (AD): Analysis from a Phase 2 Study of up to 24 months of Treatment (Zavitz) May 2, 2007 AAN 2007; Boston, MA PDF, 150 KB
	Efficacy and Safety of MPC-7869, a Selective Aβ42-Lowering Agent, in Alzheimer's Disease (AD): Results of a 12-Month Phase 2 Trial and 1-year Follow-on Study (Wilcock) July 19, 2006 ICAD 2006; Madrid, Spain PDF, 221 KB
	MPC-7869, a Selective Aβ42-Lowering Agent, Delays Time to Clinically Significant Psychiatric Adverse Events in Alzheimer’s Disease: Analysis from a 12-Month Phase 2 Trial (Mintzer) July 17, 2006 ICAD 2006; Madrid, Spain PDF, 146 KB