Myriad Genetics, Inc. · NASDAQ:MYGN

Myriad Genetics — Technical Presentation (2006)

17 slides from Myriad Genetics's technical presentation, 2006

  1. Slide 1: Efficacy and Safety of MPC-7869, a Selective Aβ42-Lowering Agent, in Alzheimer's Disease

    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 Gordon K. Wilcock*, University of Oxford, UK Sandra E. Black, Judith Haworth, Suzanne Hendrix, Mark Laughlin, Kenton Zavitz, Daniel Christens

  2. Slide 2: MPC-7869 Clinical Rationale

    MPC-7869 Clinical Rationale „ Selective Aβ42-Lowering Agent (SALA) in vitro & in vivo – Allosteric modulation of γ-secretase, not inhibition „ Reduces insoluble amyloid in mouse brain „ Improves spatial reference learning and memory performance in mice „ Effective concentrations achievable in humans

  3. Slide 3: Phase 2 Study of MPC-7869 in Subjects with Mild to Moderate AD

    Phase 2 Study of MPC-7869 in Subjects with Mild to Moderate AD (MMSE 15-26) „ Randomized, Double-Blind, Placebo-Controlled – 31 sites in Canada and the United Kingdom „ 207 Subjects in 3 treatment groups (1:1:1) – 400 mg BID – 800 mg BID – Placebo BID „ 12 months study / stable AChEI allowed „ ADAS-

  4. Slide 4: Pre-specified Statistical Analysis Plan

    Pre-specified 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: (Slope analysis) Primary Outcomes: (Slope analysis)

  5. Slide 5: Mean Baseline Characteristics in Mild AD (MMSE ≥20)

    Mean Baseline Characteristics in Mild AD (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 % AChEI Use 97% 94% 94% MMSE 22.9 23.1 22.8 ADAS-cog 27.5 28.6 28.3 (*80 point) ADCS-ADL 58.9 61.4 59.8 CDR-sb 5.7 5.0 6.0 5 MPC-7869

  6. Slide 6: Optional 12 Month Follow-on Study

    Optional 12 Month Follow-on Study „ Treatment groups remained blinded to subject/investigator Eligible Subjects n=106 Enrolled n=86 Moderate Subjects Mild Subjects n=24 n=62 Continue: Continue: Placebo 400 mg BID 800 mg BID n=21 n=18 n=23 Randomization 400 mg BID 800 mg BID n=9 n=12 „ Study Complete

  7. Slide 7: Change in Cognition—Mild Subjects

    Cognition—Mild Subjects (MMSE ≥ 20 at Baseline) ITT analysis Mean Change in ADAS-cog Effect Size (d=52%) Slope Comparison*: (n=48) p=0.109 (800 vs. placebo 0-12) 0 p=0.013 (800 vs. 400) (n=36) 2 (n=23) (n=46) 800 mg BID 4 Placebo (n=18) Change 6 400 mg BID 8 10 12 0 3 6 9 12 15 18 21 24 Month *Mixed

  8. Slide 8: Change in Activities of Daily Living—Mild Subjects

    Activities of Daily Living—Mild Subjects (MMSE ≥ 20 at Baseline) ITT analysis Mean Change in ADCS-ADL 0 Effect Size (d=67%) Slope Comparison*: p=0.015 (800 vs. placebo 0-12) -6 Change Placebo 800 mg BID -1 2 400 mg BID -1 8 0 3 6 9 12 15 18 21 24 Month *Mixed Model 8 MPC-7869

  9. Slide 9: Change in Global Function—Mild Subjects

    Global Function—Mild Subjects (MMSE ≥ 20 at Baseline) ITT analysis Mean Change in CDR-sb 0 Effect Size (d=72%) 0 .5 Slope Comparison*: p=0.0005 (800 vs. placebo 0-12) 1 1 .5 800 mg BID Change 2 Placebo 2 .5 3 400 mg BID 3 .5 4 0 3 6 9 12 15 18 21 24 Month *Mixed Model 9 MPC-7869

  10. Slide 10: Placebo Patients Re-randomized to Drug at 12 months

    Placebo Patients Re-randomized to Drug at 12 months (“Randomized Start”) „ Patients treated for 24 months decline more slowly than those treated for only 12 months – Consistent with hypothesis for a disease modifying treatment Annual Decline Rate Over 24 Months 24 months treatment at: 12 months plac

  11. Slide 11: Exploratory: Drug Concentration Effect

    Exploratory: Drug Concentration Effect „ Patients who achieved a higher concentration* had a significantly better response p-values Cmax AUC ADCS-ADL 0.034 0.037 CDR-sb 0.023 0.019 ADAS-cog 0.289 0.291 *Population Pharmacokinetic Analysis 11 MPC-7869

  12. Slide 12: Discontinuations Over Time (ITT)

    Discontinuations Over Time (ITT) Cumulative Discontinuations Over Time Number of 20 Subjects 18 3 months 16 6 months 14 9 months 12 months 12 10 8 6 4 2 0 Placebo 400 mg BID 800 mg BID Overall discontinuations in 12 months ~ 20% 12 MPC-7869

  13. Slide 13: Most Common AEs Leading to Discontinuation

    Most Common AEs Leading to Discontinuation MedDRA Body Placebo 400 mg BID 800 mg BID Total System (n=66) (n=71) (n=70) (n=207) 3 2 2 7 Gastrointestinal (4.5%) (2.8%) (2.9%) (3.4%) Metabolism and 1 2 2 5 nutrition (1.5%) (2.8%) (2.9%) (2.4%) 3 0 2 5 Psychiatric (4.5%) (2.9%) (2.4%) 13 MPC-7869

  14. Slide 14: Discontinuations Due to Disease Progression

    Discontinuations Due to Disease Progression Placebo 400 mg 800 mg BID BID All patients 6 2 1 (9.1%) (2.8%) (1.4%) Mild patients 4 1 0 (8.7%) (2.8%) 14 MPC-7869

  15. Slide 15: Safety Summary

    Safety Summary „ Overall, MPC-7869 appeared very well tolerated „ Discontinuations due to AEs were comparable between 800 mg BID and placebo „ Adverse events (higher frequency than placebo) – transient eosinophilia, mild anemia, bp elevation, lower respiratory infection, rash „ Fewer events than pla

  16. Slide 16: Time to Psychiatric Event by Treatment Group

    Time to Psychiatric Event by Treatment Group (Mild Patients, MMSE ≥ 20) 100% Patients without a Psychiatric Event (%) 90% 800 mg BID 80% 70% 400 mg BID Placebo 60% 50% # of Patients p value Median Time p value 40% with AE to Event 30% Placebo 18 106 days 0.020 0.011 800 mg BID 7 >333 days 20% 10% 0%

  17. Slide 17: Conclusions

    Conclusions „ Subjects with mild AD on 800 mg BID showed a reduced rate of decline (slope) At 12 months At 24 months Activities of Daily Living d=44% (p=0.033) d=67% (p=0.015) Global Function d=42% (p=0.042) d=72% (p=0.0005) Cognition (positive trend) d=20% (p=0.327) d=52% (p=0.109) „ Positive effec

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