Myriad Genetics, Inc. · NASDAQ:MYGN
Myriad Genetics — Technical Presentation (June 2005)
17 slides from Myriad Genetics's technical presentation, Jun 20, 2005
Slide 1: A Placebo-controlled, Double-blind Trial of the Selective Aβ-42 Lowering Agent, MPC-7869
A Placebo-controlled, Double-blind Trial of the Selective Aβ-42 Lowering Agent, MPC-7869 (R-flurbiprofen) in Patients with Mild to Moderate Alzheimer’s Disease Gordon Wilcock*, University of Bristol, UK Sandra Black, Judy Haworth, Mark Laughlin, Suzanne Hendrix, Mary-Helen Binger, Kenton Zavitz, Edw
Slide 2: MPC-7869 Clinical Rationale
MPC-7869 Clinical Rationale ! Selective Aβ42-lowering agent in vitro & in vivo – Allosteric modulation of γ-secretase ! Reduces insoluble amyloid in mouse brain ! Improves spatial reference learning and memory performance in mice ! Effective concentrations achievable in humans at clinically safe dos
Slide 3: Effect of MPC-7869 in Subjects with Mild to Moderate AD: Phase 2 Study
Effect of MPC-7869 in Subjects with Mild to Moderate AD Phase 2 Study – Multi-center, Randomized, Double-Blind, Placebo-Controlled – 207 Subjects in 3 treatment groups (1:1:1) • 400 mg BID • 800 mg BID • Placebo BID – 12 months treatment – 31 sites in Canada and the United Kingdom 3 MPC-7869
Slide 4: Effect of MPC-7869 in Subjects with Mild to Moderate AD
Effect of MPC-7869 in Subjects with Mild to Moderate AD ! Mild to moderate Alzheimer’s (MMSE 15-26) ! Stable cholinesterase inhibitor allowed ! Primary Efficacy outcomes (measured throughout) – Cognition • ADAS-cog – Activities of Daily Living • ADCS-ADL – Global Function • CDR Sum of Boxes 4 MPC-78
Slide 5: Prospective Statistical Analysis Plan
Prospective Statistical Analysis Plan ITT Population Primary Analysis Assumption: No Treatment by Severity Interaction Assumption Not Met (p= 0.03) Planned Analysis of MMSE < and > 20 Mild AD (MMSE > 20) Moderate AD (MMSE < 20) Primary Outcomes: Primary Outcomes: ADAS-cog 800 mg BID ADAS-cog 800 mg
Slide 6: Demographics by Treatment Group
Demographics by Treatment Group Mild patients (MMSE ≥20) Placebo 400 mg BID 800 mg BID (n=46) (n=36) (n=48) % of Total Patients 75% 58% 73% Age 76 75 76 Gender (%M) 59% 58% 50% % AChEI Use 100% 94% 94% Education 43% 39% 29% % College 6 MPC-7869
Slide 7: Baseline Scales
Baseline Scales Mild patients (MMSE ≥20) Placebo 400 mg BID 800 mg BID Scale (n=46) (n=36) (n=48) ADAS-cog 27.5 28.6 28.3 (*80 point) ADAS-cog 19.1 19.9 19.4 (70 point) ADCS-ADL 58.7 61.4 59.8 CDR-sb 5.7 5.0 6.0 MMSE 22.9 23.1 22.8 *Includes delayed recall subscale 7 MPC-7869
Slide 8: Cognition—Mild Subjects
Cognition—Mild Subjects* Mean Change in ADAS-cog -2 0.215 0.201 0.036 0 34% Effect 0.305 2 Change 800 mg BID (n=48) 4 400 mg BID (n=36) Placebo (n=46) 6 8 0 1 2 3 4 5 6 7 8 9 10 11 12 Month *MMSE ≥ 20 Score Patients Over Time, LOCF 8 MPC-7869
Slide 9: Activities of Daily Living—Mild Subjects
Activities of Daily Living—Mild Subjects* Mean Change in ADCS-ADL 2 0 0.090 -2 45% Effect 0.059 -4 Change 800 mg BID (n=48) -6 400 mg BID (n=36) -8 Placebo (n=46) -10 -12 0 1 2 3 4 5 6 7 8 9 10 11 12 Month *MMSE ≥ 20 Score Patients Over Time, LOCF 9 MPC-7869
Slide 10: Global Function—Mild Subjects
Global Function—Mild Subjects* Mean Change in CDR-sb -1.0 -0.5 0.545 0.0 0.211 0.5 0.291 36% Effect Change 0.069 1.0 1.5 800 mg BID (n=48) 2.0 Placebo (n=46) 2.5 400 mg BID (n=36) 3.0 0 1 2 3 4 5 6 7 8 9 10 11 12 Month *MMSE ≥ 20 Score Patients Over Time, LOCF 10 MPC-7869
Slide 11: Exploratory: Drug Concentration Effect
Exploratory: Drug Concentration Effect ! There was a significant concentration response relationship (p= 0.038) ! High concentration was defined as plasma drug concentration above 75 µg/ml ! 29 mild patients had high drug concentrations (60% of 800 mg BID group) 11 MPC-7869
Slide 12: Cognition—Mild Patients, High Drug Group
Cognition—Mild Patients*, High Drug Group Mean Change in ADAS-cog -3 0.013 -2 0.329 0.380 -1 0 36% Effect 0.371 1 Plasma Change 2 Concentration: 3 High (n=29) 4 None (n=46) 5 6 7 0 1 2 3 4 5 6 7 8 9 10 11 12 Month *MMSE ≥ 20 Score Patients Over Time, LOCF 12 MPC-7869
Slide 13: Activities of Daily Living—Mild Patients, High Drug Group
Activities of Daily Living— Mild Patients*, High Drug Group Mean Change in ADCS-ADL 2 1 0.057 62% Effect 0 0.025 -1 -2 Plasma -3 Concentration: -4 High (n=29) Change -5 -6 -7 -8 -9 None (n=46) -10 -11 -12 0 1 2 3 4 5 6 7 8 9 10 11 12 Month *MMSE ≥ 20 Score Patients Over Time, LOCF 13 MPC-7869
Slide 14: Global Function—Mild Patients, High Drug Group
Global Function—Mild Patients*, High Drug Group Mean Change in CDR-sb -0.1 0.593 51% Effect 0.0 0.178 0.287 0.035 0.5 Plasma Concentration: 1.0 High (n=29) Change 1.5 2.0 None (n=46) 2.5 3.0 3.5 0 1 2 3 4 5 6 7 8 9 10 11 12 Month *MMSE ≥ 20 Score Patients Over Time, LOCF 14 MPC-7869
Slide 15: Discontinuations Over Time
Discontinuations Over Time Cumulative Discontinuations Over Time 20 18 3 months 16 6 months 9 months 14 Number of Subjects 12 months 12 10 8 6 4 2 0 Placebo 400 mg BID 800 mg BID 15 MPC-7869
Slide 16: Safety Summary
Safety Summary ! Overall, MPC-7869 appeared very well tolerated ! Discontinuations over time were similar between treatment groups ! Observed transient dose-related eosinophilia – No apparent clinical significance ! No obvious safety differences between mild and moderate patients ! No obvious safety
Slide 17: Effect of MPC-7869 in Subjects with Mild to Moderate AD Over 12 Months
Effect of MPC-7869 in Subjects with Mild to Moderate AD Over 12 Months Phase 2 Summary: ! Mild and moderate AD subjects responded differently to treatment over 12 months – Mild subjects responded; moderate subjects did not ! Mild AD subjects on 800 mg twice daily showed positive trends in all 3 outc