Vtv Therapeutics Inc. · NASDAQ:VTVT
Vtv Therapeutics — IPO Roadshow (July 2015)
13 slides from Vtv Therapeutics's IPO roadshow presentation, Jul 20, 2015
Slide 1: Azeliragon (TTP488): From Futility to Fast Track
An examination of the risks of futility analysis and the precautions that should be taken when executing and interpreting these analyses Marwan Sabbagh , MD; Aaron H Burstein, PharmD ; Imogene Grimes, PhD; Carmen Valcarce , PhD; Eric A. Rose, MD; Rachelle Doody , MD, PhD; Mary Sano, PhD; Lon S. Schn
Slide 2: Disclosures and offering legend
Dr Sabbagh receives research support from Lilly, Avid, Navidea, Functional Neuromodulation, Neuronix, Merck, Takeda, AstraZeneca, Roche, and Genentech. He is an advisor for Biogen, Lilly, vTv therapeutics, Avid, and Piramal. He receives royalties from TenSpeed/Random House. vTv Therapeutics Inc. (th
Slide 3: RAGE Inhibition: A Novel Mechanism of Action for AD Treatment
3 RAGE Inhibition: A Novel Mechanism of Action for AD Treatment AZELIRAGON INHIBITS THE RECEPTOR FOR ADVANCED GLYCATION ENDPRODUCTS (RAGE) ▪ Role of RAGE – Pre - and post - natal neuronal development – Low expression under normal conditions ▪ RAGE is a key upstream factor that we believe is responsi
Slide 4: Study Design
4 Azeliragon Phase 2b Study Design ▪ Randomized, double - blind, placebo - controlled trial ▪ Mild to moderate AD (MMSE 14 - 26); N= 399 – Power of 80% to detect a treatment benefit of 3 points on the ADAS - COG 11 ▪ Stable background therapy with cholinesterase inhibitors and/or memantine ▪ Three a
Slide 5: Analysis
5 Azeliragon Phase 2b Analysis ▪ Pre - specified i nterim a nalyses – Safety: 50% of subjects completed 6 months; 100% completed or withdrew prior to12 months – Futility: 12 months after all subjects randomized ▪ Primary analysis specified in protocol and SAP – Analysis of covariance (ANCOVA) with m
Slide 6: Futility Analysis Decision Rules
6 Terminate Study Terminate Study Continue Trial Continue Trial Continue Trial Conditional Probability ≥20% Conditional Probability <10% Yes Yes No Conditional Probability ≥10% but <20% Yes No 12mo ADAScog consistent with 1 pt improvement Yes No Any 12mo biomarker “very favorable” Yes Continue Trial
Slide 7: Interim Analysis Results
7 Azeliragon Phase 2b 12 - Month Interim Analysis Results ▪ Conditional probability = 9.3% – Decision made to terminate study with subjects to discontinue dosing at next scheduled visit – While not a consideration in the futility decision algorithm, 5mg/day was associated with numerical favorable di
Slide 8: Final Protocol Planned Analysis Demonstrates Azeliragon Met Pre-specified Primary Endpoint
8 Final Protocol Planned Analysis Demonstrates Azeliragon Met Pre - specified ADAS - COG 11 Primary Endpoint Galasko et al. Neurology 2014;82:1536 - 1542 ▪ Protocol - planned analyses, using different methodologies to cope with missing data, all show statistically significant differences in ADAS - C
Slide 9: On-Treatment Analysis
9 Azeliragon Phase 2b On - Treatment Analysis ▪ On - treatment analysis included all available on - treatment data where “on - treatment” defined as date of last dose plus 45 days (taking into account half - life of ~18 days ) – Note: the 6 subjects receiving 5 mg/d excluded from this analysis had m
Slide 10: Mild (MMSE 21-26) Sub-group
10 Azeliragon Phase 2b Mild (MMSE 21 - 26) Sub - group ▪ Evaluation shows more pronounced efficacy in mild AD patients, including statistically significant improvement in both ADAS - COG 11 and CDR - SB ADAS-COG 11 Change from Baseline Mild AD (MMSE 21-26) Month of Treatment C h a n g e f r o m B a
Slide 11: Futility Analysis
11 Futility Analysis ▪ The discordance between the positive results of the final analysis and the prediction from the futility analysis is most likely resolved understanding the specific attributes of the futility analysis ▪ Data were used only from patients who had completed 18 months of treatment
Slide 12: STEADFAST Study: Phase 3 Clinical Trial Under SPA
12 STEADFAST Study: Phase 3 Clinical Trial Under SPA ▪ Randomized , double - blind, parallel group, 18 - month trial in 800 patients with mild AD (MMSE 21 - 26) – Enrollment commenced in April 2015 ▪ Two independently powered sub - studies (sub - study A and sub - study B) under a single protocol: –
Slide 13: Conclusions
13 Conclusions ▪ Futility analyses in AD trials may be misleading and argue for conducting the full analysis plan even when futility criteria are met ▪ The results of the ITT analysis, the four sensitivity analyses, the on - treatment analysis and the mild sub - group analysis justify further invest