Vtv Therapeutics Inc. · NASDAQ:VTVT
Vtv Therapeutics — EASD 2017
15 slides from Vtv Therapeutics's conference presentation, 2017
Slide 1: Beyond Topline Results for the Oral (Non-Peptide) GLP-1R Agonist TTP273 in Type 2 Diabetes
Beyond Topline Results for the Oral (Non-Peptide) GLP-1R Agonist TTP273 in Type 2 Diabetes: How Much and When? Jennifer LR Freeman, Imogene Dunn and Carmen Valcarce
Slide 2: Disclaimers
Disclaimers The statements made in this presentation may include forward-looking statements regarding the diabetes market, or the future operations, opportunities or financial performance of vTv Therapeutics Inc. Although we believe that the expectations contained in this presentation are reasonable
Slide 3: TTP273: Oral, Small Molecule GLP-1R Agonist
TTP273: Oral, Small Molecule GLP-1R Agonist Non-peptide, small molecule, GLP-1R Agonist Potential for combination with existing oral agents (including fixed TTP273 Orally bioavailable - no injection required dose combinations) Favorable tolerability profile - Functionally biased ligand, no negligibl
Slide 4: TTP273-201: LOGRA Study
TTP273-201: LOGRA (aLlosteric Oral Glp1 Receptor Agonist) Study 12 week randomized, double-blind, placebo-controlled, parallel group trial in type 2 diabetics on stable doses of metformin Arms: ➢TTP273 150mg dosed once daily in the evening (QPM) Study Goals: ✓ Competitive HbA1c reduction ➢TTP273 1
Slide 5: TTP273: Phase 2 Study Results Met Goals
TTP273: Phase 2 Study Results Met Goals Change in HbA1c at Month 3 (%) Change in Weight at Month 3 (Kg) Safety Profile Lsmeans placebo-subtracted LSmeans placebo-subtracted 0 -0.86 -0.71 • Drug was well tolerated -0.2 • No incidences of vomiting in -0.4 the TTP273 treated arms -0.6 • Nausea less tha
Slide 6: Analysis of Response by Subject Weight
Analysis of Response by Subject Weight (Protocol pre-planned analysis of subjects weighing 100kg or more) Placebo subtracted Change from Baseline at Week 12 HbA1c (%) Body Weight (kg) < 100kg 100kg or greater < 100kg 100kg or greater 0 0 -0.46 -0.5 -0.5 -0.44 -0.78 -1 -0.321 -0.32 -1.3 -1 -1.4 -1.5
Slide 7: Focus on QPM versus PBO: Greatest efficacy with < 1.35 mg/kg
Focus on QPM versus PBO: Greatest efficacy with < 1.35 mg/kg HbA1c (%) Body Weight (kg) Additional Analyses • Confirmed when correlating TTP273 plasma concentration with efficacy • GI AEs did not show an increased incidence rate with efficacy • Trends are not dependent on age, sex, race, duration of
Slide 8: Focus on "less": A1c and Weight (means)
Focus on “less”: A1c and Weight (means*) Trends over time are consistent with LOWER optimal dosing HbA1c (%) Weight (kg) PBO TTP273 (< 1.35 mg/kg) PBO TTP273 (< 1.35 mg/kg) PBO TTP273 (< 1.35 mg/kg) (*Medians are fully consistent with means)
Slide 9: Focus on "less": Mean change from baseline at Week 12
Focus on “less”: Mean change from baseline at Week 12 FPG Insulin Systolic BP Pulse (mg/dL) (mIU/L) (mm Hg) (bpm) PBO TTP273 (< 1.35 mg/kg)
Slide 10: Similar dose-response pattern observed in POC study in predecessor GLP-1R agonist (TTP054)
Similar dose-response pattern observed in POC study in predecessor GLP-1R agonist (TTP054) PBO TTP054 (mg/kg) TTP054-201 POC Study <3 3-4.9 5-6.9 7-9 >9 • 3 month, double-blind, placebo- controlled, parallel group trial in 184 type 2 diabetics on stable doses of metformin • Target population: 8-11%
Slide 11: TTP273 is a small molecule agonist - not a peptide
TTP273 is a small molecule agonist - not a peptide Preclinical evidence: ➢ TTP273 is functionally biased ➢ Signaling occurs through the intestine ➢ c-fos staining indicates vagal neuroendocrine signaling 3 S ta in in g s c o r e 2 1 0 P a r a v e n t r ic u la r N u c le u s A r c u a t e N u c le
Slide 12: TTP273 is a small molecule agonist - not a peptide
TTP273 is a small molecule agonist - not a peptide Preclinical evidence: ➢ TTP273 is functionally biased ➢ Signaling occurs through the intestine ➢ c-fos staining indicates vagal neuroendocrine signaling Literature suggests ➢Long and short acting peptides have different profiles – precedence wit
Slide 13: Hypothesis: Oral Administration of High Concentrations of TTP273 May Alter the Signaling Dynamic
Hypothesis: Oral Administration of High Concentrations of TTP273 May Alter the Signaling Dynamic At any given dose, the total efficacy will be the combination of these two pathways
Slide 14: Conclusions
Conclusions TTP273 has shown efficacy with negligible nausea and vomiting Concentration/effect analysis revealed an unexpected result: lower doses showed more pronounced effects for key efficacy endpoints ➢Observed with both vTv oral, GLP-1 agonists, TTP273 and TTP054 Preclinical characteristi
Slide 15: Acknowledgements
Acknowledgements vTv discovery and development teams Patricia McDonald’s lab at The Scripps Research Institute, Florida