vTv Therapeutics Inc. · NASDAQ:VTVT
vTv Therapeutics — Technical Presentation (March 2019)
16 slides from vTv Therapeutics's technical presentation, Mar 30, 2019
Slide 1: Inflammatory Biomarkers, Brain Volumetric MRI, FDG-PET Results in Patients with Type 2 Diabetes in Azeliragon Phase 3 Trial
INFLAMMATORY BIOMARKERS, BRAIN VOLUMETRIC MRI, FDG-PET RESULTS IN PATIENTS WITH TYPE 2 DIABETES IN AZELIRAGON PHASE 3 TRIAL IN MILD ALZHEIMER’S DISEASE (AD) Carmen Valcarce, Imogene Dunn, Tom Soeder, Aaron Burstein
Slide 2: Disclosure
Disclosure Carmen Valcarce Full time employees of vTv Therapeutics LLC
Slide 3: Targeting RAGE with Azeliragon
Targeting RAGE with Azeliragon • Azeliragon’s novel MOA: antagonizing the Receptor Azeliragon Mechanism of Action for Advanced Glycation Endproducts (RAGE) Azeliragon binds to RAGE, Select ligands bind to RAGE blocking ligands from binding •RAGE is expressed at low levels in healthy tissues (except
Slide 4: RAGE Involved in Diabetic Complications and AD
RAGE Involved in Diabetic Complications and AD Pre-clinical Evidence with Azeliragon Treatment Animal model Main Results: Treatment with Azeliragon Retinal Disease Rat Diabetic Retinopathy Protection Against Vascular and Neuronal Lesions: • Reduces acellular capillaries and improves Kidney Disease p
Slide 5: Phase 3 STEADFAST Study Design
Phase 3 STEADFAST Study Design Two Pivotal Studies Under One Protocol 5mg/day azeliragon (AZL) or Placebo (PBO) + Standard of Care A-Study B-Study 405 Patients Patients with probable mild AD, MMSE 21-26, CDR 475 Patients Readout April 2018 global 0.5-1 Terminated Co-Primary Endpoints: ADAS-cog11 and
Slide 6: Potential Beneficial Effect on Cognition in Patients with Elevated HbA1c
Potential Beneficial Effect on Cognition in Patients with Elevated HbA1c STEADFAST A-Study (FAS) STEADFAST A-Study ADA-T2D Subgroup (FAS) Change from Baseline in ADAS-cog11 (LSMEANS) Change from Baseline in ADAS-cog11 (LSMEANS) p=0.752# ∆=5.5 p=0.006# p=0.0006# Results are LSMeans ± SE based on MMRM
Slide 7: Potential Beneficial Effect on Cognitive Function in Patients with Elevated HbA1c
Potential Beneficial Effect on Cognitive Function in Patients with Elevated HbA1c STEADFAST A-Study (FAS) STEADFAST A-Study ADA-T2D Subgroup (FAS) Change from Baseline in CDR-SB Change from Baseline in CDR-SB p=0.053# ∆=1,1 p=0.16# p=0.0005# Results are LSMeans ± SE based on MMRM model. AD-T2D=HbA1c
Slide 8: Cognitive Improvement Cannot be Explained by Improvement in Glycemic Control
Cognitive Improvement Cannot be Explained by Improvement in Glycemic Control STEADFAST A-Study ADA-T2D Subgroup (FAS) STEADFAST A-Study ADA-T2D Subgroup (FAS) Change in HbA1c (%) at Month 18 Change in Non-fasting Glucose (mg/dL) at Month 18 0.1 15 0.08 10 0.06 5 0.04 0.02 0 0 -5 -0.02 -0.04 -10 -0.0
Slide 9: Demography and Baseline Characteristics: No Notable Imbalance Between Treatment Arms
Demography and Baseline Characteristics: No Notable Imbalance Between Treatment Arms STEADFAST Study ADA-T2D Subgroup STEADFAST Study ADA-T2D Subgroup Demographics (A&B Studies Combined) Baseline Characteristics (A&B Studies Combined) AD-T2D=HbA1c ≥6.5% at anytime during the study March 2019 vTv The
Slide 10: Change in MRI Brain Volume in the ADA-T2D Subgroup
Change in MRI Brain Volume at Month 18 in the ADA-T2D Subgroup: Trend Towards Less Brain Atrophy in the AZL-treated Group ADA-T2D Subgroup ADA-T2D Subgroup ADA-T2D subgroup Change in Total Hippocampus Change in Whole Brain volume (%) Ventricular Enlargement (%) Volume (%) 0 0.6 0 0.5 p=0.0008 # -0.5
Slide 11: Change in FDG-PET SUVR in the ADA-T2D Subgroup
Change in FDG-PET SUVR in the ADA-T2D Subgroup: Less Reduction in Glucose Utilization in AZL-treated Group Month 12 Month 18 0 0 -0.01 -0.01 Change from Baseline in SUVR (LSMeans) -0.02 -0.02 -0.03 -0.03 p<0.001 # -0.04 -0.04 -0.05 -0.05 P=0.02 -0.06 -0.06 -0.07 p<0.001 # -0.07 -0.08 -0.08 P=0.007 S
Slide 12: Inflammatory Marker Panel: Changes at Month 18 in ADA-T2D Subgroup
Inflammatory Marker Panel: Changes at Month 18 of Treatment in ADA-T2D Subgroup • Inflammatory biomarkers were measured in plasma using LincoPlex system and the human cytokine/chemokine full panel (panel 1, Millipore) • No notable differences between placebo and azeliragon at baseline • Statisticall
Slide 13: Changes in Biomarker Profile Consistent with RAGE Inhibition
Changes in Biomarker Profile Consistent with RAGE Inhibition Biomarker Profile Azeliragon treatment significantly decreased the following markers linked to RAGE: • IL6 • IL12 • INFg • CD40L • MIP-1 • IL2 • TNFb Each of these markers is a major player in the neuroinflammatory pathway1 *nominal p<0.05
Slide 14: ADA-T2D Subgroup Data and Ingenuity Software Prediction Support RAGE Inhibition Hypothesis
Data from the ADA-T2D Subgroup and Prediction Using Ingenuity Software Support Hypothesis that Inhibition of RAGE Could Result in Beneficial Effects March 2019 vTv Therapeutics LLC 14
Slide 15: Conclusions
Conclusions ❑ Results from the post-hoc analysis of a subgroup of patients with HbA1c≥6.5% support the hypothesis that treatment with azeliragon may: ▪ Improve/preserve cognition and function ▪ Reduce Whole Brain and Hippocampus atrophy and ventricular enlargement ▪ Preserve glucose uptake ❑ The res
Slide 16: Thank you!
Thank you! We greatly appreciate all the patients, families, investigators and staff for their participation in STEADFAST March 2019 vTv Therapeutics LLC 16
vTv Therapeutics — Technical Presentation (March 2019) on 6ix