Myriad Genetics, Inc. · NASDAQ:MYGN

Myriad Genetics — Technical Presentation (2008)

21 slides from Myriad Genetics's technical presentation, 2008

  1. Slide 1: Safety and Efficacy of Tarenflurbil in Subjects With Mild Alzheimer's Disease

    Safety and Efficacy of Tarenflurbil in Subjects With Mild Alzheimer’s Disease: Results From an 18-month Multicenter Phase 3 Trial Robert C. Green, MD, MPH Lon S. Schneider, MD Kenton H. Zavitz, PhD David A. Amato, PhD Andrew P. Beelen, MD Edward A. Swabb, MD, PhD & the Tarenflurbil Phase 3 Study Gro

  2. Slide 2: Tarenflurbil Clinical Rationale

    Tarenflurbil Clinical Rationale Tarenflurbil (Flurizan™, formerly R-flurbiprofen)  Selective A 42-lowering agent in vitro & in vivo1,2 ─ -secretase modulator (GSM) via substrate targeting of APP, resulting in a less amyloidogenic A profile ─ No effect on other substrates (eg, Notch)  Improves spat

  3. Slide 3: US Phase 3 Protocol Overview

    US Phase 3 Protocol Overview  Mild Alzheimer’s disease (MMSE 20-26)  Stratified at randomization – Stable (≥6 months) cholinesterase inhibitor use/nonuse – Stable (≥3 months) memantine use/nonuse  Two-arm study: 800 BID vs. placebo BID  18 months treatment, 30-day off-drug follow-up  Efficacy e

  4. Slide 4: 133 Trial Sites in the US

    133 Trial Sites* in the US *Having enrolled ≥ 1 subject 4 tarenflurbil

  5. Slide 5: Trial Profile

    Trial Profile Assessed n=2408 Excluded n=724 Randomized n=1684 Assigned to tarenflurbil Assigned to tarenflurbil Assigned to placebo 800 mg BID 400 mg BID n=822 n=862 n=42 Excluded Excluded Moderate Moderate n=12 n=20 ITT Population ITT Population Placebo 800 mg BID n=809 n=840 Discontinued Disconti

  6. Slide 6: Pre-specified Analysis Plan

    Pre-specified Analysis Plan  Change from baseline (CFB) at 18 months – z-score, LOCF  Slopes analysis (SA) – repeated measures linear mixed model  ‘Gatekeeper’ approach to control for multiple comparisons 1. ADAS-cog and ADCS-ADL, CFB p ≤ 0.05 2. ADAS-cog SA, p ≤ 0.05 3. ADCS-ADL SA, p ≤ 0.05 4.

  7. Slide 7: Imputation Method: Z-score LOCF

    Imputation Method: Z-score LOCF  a missing value at a given time point will be replaced with a value that is the same number of standard deviations from the treatment group mean at that time point as that subject’s last observed value z-score = (observed value – treatment group mean) / treatment gr

  8. Slide 8: Baseline Characteristics (ITT)

    Baseline Characteristics (ITT) Placebo 800 mg BID (n=809) (n=840) Age, yr mean (SD) 74.7 (8.4) 74.6 (8.5) range 53 – 100 53 – 100 % Female 52.5% 49.4% Ethnicity (% white) 94.1% 94.9% Weight, kg (mean BMI) 72.5 (26.3) 72.7 (26.1) Time since diagnosis (months) 20.5 20.4 Education (% ≥ any college) 61.

  9. Slide 9: Mean Baseline Characteristics (ITT)

    Mean Baseline Characteristics (ITT) Placebo 800 mg BID (n=809) (n=840) ADAS-cog (*80 point) 25.7 (8.9) 26.1 (8.5) ADAS-cog (70 point) 17.8 (7.7) 18.2 (7.4) ADCS-ADL 63.6 (11.1) 63.6 (11.5) CDR-sb 5.0 (2.4) 4.9 (2.3) *Includes delayed recall subscale Mean (SD) Preliminary analysis 9 tarenflurbil

  10. Slide 10: Concomitant AD Therapy

    Concomitant AD Therapy (18.0, 19.2) (33.1, 33.3) (5.9, 6.5) (placebo, tarenflurbil) (42.9, 40.8) Preliminary analysis 10 tarenflurbil

  11. Slide 11: Cognition — Change in ADAS-cog

    Cognition — Change in ADAS-cog ITT Analysis Change from Baseline ADAS-cog (Mean±SE) 0 2 4 Tarenflurbil Placebo 6 p=0.860 8 0 3 6 9 12 15 18 Month Preliminary analysis 11 tarenflurbil

  12. Slide 12: Cognition — Change in ADAS-cog

    Cognition — Change in ADAS-cog Per Protocol Analysis Change from Baseline ADAS-cog (Mean±SE) 0 2 4 Tarenflurbil Placebo 6 p=0.865 8 0 3 6 9 12 15 18 Month Preliminary analysis 12 tarenflurbil

  13. Slide 13: Activities of Daily Living — ADCS-ADL

    Activities of Daily Living — ADCS-ADL ITT Analysis Change from Baseline ADCS-ADL (Mean±SE) 0 -3 -6 Tarenflurbil Placebo -9 p=0.479 -12 0 3 6 9 12 15 18 Month Preliminary analysis 13 tarenflurbil

  14. Slide 14: Global Function — CDR-sb

    Global Function — CDR-sb ITT Analysis Change from Baseline CDR-sb (Mean±SE) 0 0.5 1 1.5 Tarenflurbil 2 Placebo 2.5 p=0.0036 3 3.5 0 3 6 9 12 15 18 Month Preliminary analysis 14 tarenflurbil

  15. Slide 15: Additional Analyses

    Additional Analyses  Pre-specified in SAP  Post-hoc – Baseline scale severity – Gender – Baseline MMSE – BMI – ‘Improver’ analysis – CYP2C9 genotype (full – ‘Progresser’ analysis analysis pending) – Concomitant AD med use – APOE genotype – PK (full analysis pending) Preliminary analysis 15 tarenfl

  16. Slide 16: APOE4 Carriers vs Non-carriers

    APOE4 Carriers vs Non-carriers ADAS-cog ITT Analysis APOE e4 Carriers Change from 0 Baseline ADAS-cog (Mean ±SE) 3 6 Tarenflurbil (n = 363) 58.5% Placebo (n = 345) e4 Carriers 9 Month 0 3 6 9 12 15 18 Change from Baseline 0 ADAS-cog (Mean ±SE) 3 Tarenflurbil (n = 259) 41.5% Placebo (n = 244) e4 Non-

  17. Slide 17: APOE4 Carriers vs Non-carriers

    APOE4 Carriers vs Non-carriers ADCS-ADL ITT Analysis APOE e4 Carriers Change from 0 Baseline ADCS-ADL (Mean ±SE) -3 -6 Tarenflurbil (n = 348) 58.1% -9 Placebo (n = 335) e4 Carriers -12 Month 0 3 6 9 12 15 18 Change from Baseline ADCS-ADL 0 (Mean ±SE) -3 -6 Tarenflurbil (n = 253) 41.9% Placebo (n = 2

  18. Slide 18: Overall Adverse Events (0-18 months)

    Overall Adverse Events (0-18 months) Placebo 800 mg BID (n=821) (n=860) Subjects w/ AE 85.7% 704 88.5% 761 Discontinued for AE 11.6% 95 18.4% 158 Subjects w/ SAE 19.9% 163 22.7% 195 Deaths 2.2% 18 2.8% 24 Preliminary analysis 18 tarenflurbil

  19. Slide 19: Key Safety Findings

    Key Safety Findings  AEs in general reflect the expected symptom profile of a population with Alzheimer’s disease – In most, AEs were well balanced between tarenflurbil and placebo  However, there were a few signals for increased AEs: Adverse Event Placebo 800 mg BID (n=821) (n=860) Anemia 4.5% 9.

  20. Slide 20: Conclusions

    Conclusions  Well-powered, well-designed, and well-conducted trial in mild AD (MMSE 20-26) – Treatment groups were well matched at baseline – Placebo decline rates were as expected for 18 months • ADAS-cog 7.1 points (SD 9.2) • ADCS-ADL 9.8 points (SD 14.0) • CDR-sb 2.5 points (SD 3.1)  No differe

  21. Slide 21: Safety and Efficacy of Tarenflurbil in Subjects With Mild Alzheimer's Disease

    Safety and Efficacy of Tarenflurbil in Subjects With Mild Alzheimer’s Disease: Results From an 18-month Multicenter Phase 3 Trial Robert C. Green, MD, MPH Lon S. Schneider, MD Kenton H. Zavitz, PhD David A. Amato, PhD Andrew P. Beelen, MD Edward A. Swabb, MD, PhD & the Tarenflurbil Phase 3 Study Gro

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