vTv Therapeutics Inc. · NASDAQ:VTVT
vTv Therapeutics — Technical Presentation (October 2018)
16 slides from vTv Therapeutics's technical presentation, Oct 26, 2018
Slide 1: Safety and efficacy results from the phase 3 STEADFAST trial of azeliragon
Safety and efficacy results from the phase 3, multicenter, 18‐month STEADFAST trial of azeliragon in participants with mild Alzheimer’s disease Marwan Sabbagh MD; Imogene Dunn PhD; Ann Gooch PhD; Tom Soeder MS; Karl Kieburtz MD, MPH; Carmen Valcarce PhD; Larry D Altstiel MD, PhD; Aaron H Burstein Ph
Slide 2: STEADFAST Safety and Efficacy Results: Disclosures
STEADFAST Safety and Efficacy Results: Disclosures Marwan Sabbagh Intellectual property rights (Royalties or patent sales) Harper Collins Ownership interest (stock, stock options) in Versanum Inc., Brain Health Inc, Optimal Cognitive Health Company, uMethod Health, Neurotrope Consultant for Al
Slide 3: RAGE as a Target in Humans
RAGE as a Target in Humans RAGE is a 35kDa membrane protein member of the Ig supergene family that is a receptor for pro‐inflammatory ligands including AGEs, Aβ peptides, S100 proteins, HMGB1 (amphoterin), and oxLDL Analysis of RAGE expression in AD brains indicated that increases in RAGE protei
Slide 4: Azeliragon effects in APP-Tg mice and Phase 2b mild subgroup
Azeliragon effects in APP-Tg mice and in Phase 2b mild subgroup as basis for advancing to Phase 3 Reduction in Amyloid Deposition Phase 2b results in subgroup with mild AD Vehicle Azeliragon ADAS-COG11 Change from Baseline Mild AD (MMSE 21-26) Latency Period (secs) 0 5 mg/d 2 Placebo 4 6 After 4 wee
Slide 5: Azeliragon STEADFAST Study Design
Azeliragon STEADFAST Study Design Randomized, double‐blind, placebo‐controlled, parallel group, 18‐month trial Two identical, independently powered studies operationally conducted under a single protocol Subjects with probable mild AD: 2011 NIA‐AA criteria, Screening MMSE 21‐26, CDR‐global 0.5
Slide 6: Subject Disposition
Subject Disposition A‐Study B‐Study Enrolled and screened N=1733 Randomized Randomized N=405 N=475 Azeliragon Placebo Azeliragon Placebo N=197 N=208 N=247 N=228 Treated 195 (99%) Treated 206 (99%) Treated 246 (99.6%) Treated 228 (100%) Completed Treatment 148 (75%) Completed Treatment 157 (75.5%) Co
Slide 7: Demographics and Baseline Characteristics (full analysis set)
Demographics and Baseline Characteristics (full analysis set) A‐Study B‐Study Azeliragon Placebo Azeliragon Placebo A‐Study Characteristic n=179 n=196 n=238 n=216 • Treatment groups well Age, years 74 ± 9.1 75 ± 7.9 75 ± 8.6 74 ± 8.5 matched Female sex – n (%) 92 (51%) 85 (43%) 102 (43%) 101 (47%)
Slide 8: No identified tolerability concerns with azeliragon 5 mg/day
No identified tolerability concerns with azeliragon 5 mg/day: A and B-Studies Combined No differences between azeliragon and placebo in TEAE, Treatment‐related TEAE, SAE, Deaths TEAEs occurring in >2% of azeliragon treated subjects and more frequent than placebo Overview of Treatment‐Emergent Adve
Slide 9: A-Study failed to demonstrate statistically significant benefit on co-primary endpoints
A-Study failed to demonstrate statistically significant benefit of azeliragon on co-primary endpoints of ADAS-cog and CDR-sb A‐Study Final Analysis: Full Analysis Set*, MMRM *FAS: subjects who received ≥1 dose and had at least one post baseline efficacy assessment Data reported as LSMean (SE) ADAS-c
Slide 10: B-Study failed to demonstrate statistically significant benefit on co-primary endpoints
B-Study failed to demonstrate statistically significant benefit of azeliragon on co-primary endpoints of ADAS-cog and CDR-sb B‐Study Final Analysis: Full Analysis Set*, MMRM *FAS: subjects who received ≥1 dose and had at least one post baseline efficacy assessment Data reported as LSMean (SE) CDR-sb
Slide 11: No indication of effect of azeliragon on MRI volumetric measures
No indication of effect of azeliragon on MRI volumetric measures A‐ and B‐Study Combined: Full Analysis Set* *FAS: subjects who received ≥1 dose and had at least one post baseline efficacy assessment Data reported as LSMean (SE) *Volumes normalized to subject’s intracranial volume 11
Slide 12: Topline Results Chronology and Summary (April 2018 – June 2018)
Topline Results Chronology and Summary (April 2018 – June 2018) A‐Study failed to demonstrate Post‐hoc analysis suggests azeliragon B‐Study failed to demonstrate statistically significant benefit of < 7.5 ng/mL subgroup associated statistically significant benefit of azeliragon on co‐primary aze
Slide 13: Post-hoc analyses ongoing to evaluate for subgroups
Post-hoc analyses ongoing to evaluate for subgroups with expected placebo decline and/or response to a RAGE antagonist / azeliragon Subject with baseline characteristics predicting likely expected to exhibit progressive decline over 12‐18 months Historical data from Thomas RG et al. Alz Dementia 2
Slide 14: In subjects with HbA1c ≥ 6.5% azeliragon delayed decline in cognition and function
In subjects with presumed increased RAGE expression (i.e. baseline HbA1c ≥ 6.5%) azeliragon delayed decline in cognition and function • RAGE‐ligands upregulate the receptor’s expression establishing a forward feedback cycle perpetuating inflammation, inducing vascular damage, and preventing tissue r
Slide 15: Azeliragon STEADFAST study summary
Azeliragon STEADFAST study summary Study failed to demonstrate a statistically significant benefit of azeliragon on co‐primary endpoints of ADAS‐cog and CDR‐sb Placebo decline less than anticipated thereby confounding the ability to demonstrate a treatment effect ― Post‐hoc subgroup analysis ong
Slide 16: Thank you
Thank you We greatly appreciate all the patients, families, investigators and staff for their participation in STEADFAST 16
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