Vtv Therapeutics Inc. · NASDAQ:VTVT
Vtv Therapeutics — EASD 2020
15 slides from Vtv Therapeutics's conference presentation, 2020
Slide 1: Mechanism matters: activation of glucokinase by TTP399 does not increase ketones in type 1 diabetes
Mechanism matters: preliminary evidence that activation of glucokinase by TTP399 does not increase plasma or urine ketones in type 1 diabetes Jennifer LR Freeman, Imogene Dunn, Carmen Valcarce vTv Therapeutics, High Point, NC, USA Simplici-T1 trial was funded in partnership with JDRF
Slide 2: Disclosures – Jennifer LR Freeman
Disclosures – Jennifer LR Freeman • vTv Therapeutics employee • vTv Therapeutics stockholder 2
Slide 3: Improved treatments needed for type 1 diabetes
Improved treatments needed for type 1 diabetes • Despite improvements in insulin delivery devices and glucose monitoring, nearly 80% of people with type 1 diabetes fail to achieve target A1c (Foster, et al. Diabetes Technol Ther. 2019 Feb;21(2):66-72) • Oral adjunctive therapies inhibiting SGLT1-2s
Slide 4: SGLT1-2 inhibitors decrease glucose absorption and increase ketogenesis
SGLT1-2 inhibitors decrease glucose absorption and increase ketogenesis * * 4 Modified from Taylor, et al. J Clin Endocrinol Metab, August 2015, 100(8):2849 –2852
Slide 5: Activation of Glucokinase increases glucose utilization in liver, decreases ketogenesis
Activation of Glucokinase increases glucose utilization in liver, decreases ketogenesis TTP399 5
Slide 6: TTP399-203 (Simplici-T1): Adaptive Phase 1b/2 Study Trial Design
TTP399-203 (Simplici-T1): Adaptive Phase 1b/2 Study Trial Design 1 site - 4 sites - 13 sites - Phase 1 Phase 2-Part 1 Phase 2-Part 2 (Sentinels) (Learning Phase) (Confirming Phase) § Open-label § Double-blind Placebo control § Double-blind Placebo control Study design § 7 day dose escalation up to 1
Slide 7: Study Design: Treat-to-target
Study Design: Treat-to-target Patient contact, central lab and insulin data collection Insulin-data collection from pumps or smart insulin pen (InPen) Basal Insulin Day 1 Treatment 12 Weeks Screening Optimization PBO Run in ADJUST INSULIN TO Treatment GOALS: Follow- Lower To target ~80-130mg/dL peri
Slide 8: Demographics: No imbalance between groups
Demographics: No imbalance between groups Part 1 Part 2 Placebo TTP399 800 mg Placebo TTP399 800 mg Trait Statistic (N=11) (N=8) (N=45) (N=40) Mean [Median] 47 [43.0] 38 [34.5] 42.4 [38.0] 43.4 [43.5] Age (Years) (min, max) (35, 68) (23, 66) (24, 70) (20, 69) Gender Female (%) 8 (72.5%) 5 (62.5%) 25
Slide 9: Simplici-T1 Study: Improved glycemic control while lowering insulin
Simplici-T1 Study Improved glycemic control while lowering insulin Key Results Insulin Change from Baseline § Statistically significant reduction in HbA1c under a treat-to-target design (i.e. compared to intensive insulin treatment) § No report of diabetic ketoacidosis, trends towards reduction in k
Slide 10: Trends towards reduction in ketone events in the TTP399-treated group
Trends towards reduction in ketone events in the TTP399-treated group Part 1 Part 2 Combined Placebo TTP399 Placebo TTP399 Placebo TTP399 (n=11) (n=9) (n=45) (n=40) (n=56) (n=49) DKA events 0 0 0 0 0 0 Ketone Monitoring Ketosis Treatment Emergent 0 0 1 1* 1 1* Adverse Events Patients with at least o
Slide 11: Cumulative incidence of subjects with abnormal ketones
Cumulative incidence of subjects with abnormal ketones BOHB > 0.4 and 0.6 mmol/L as determined by Central Lab Central lab ketone values Central lab ketone values >0.4mmol/L > 0.6 mmol/L 30 Cummulative incidence (%) 800mg TTP399 15 Cummulative incidence (%) 800mg TTP399 PBO PBO 20 10 10 5 0 0 0 14 28
Slide 12: Abnormal Ketones By Insulin Group
Abnormal Ketones By Insulin Group Trends towards reduction in abnormal ketones in the TTP399- treated group with improved glycemic control Changes in Total Insulin Reduced Insulin Stable insulin Increased insulin Subjects with: Placebo TTP399 Placebo TTP399 Placebo TTP399 (n=12) (n=15) (n=13) (n=13)
Slide 13: Abnormal ketones in undetectable C-peptide subgroup
Abnormal ketones in undetectable C-peptide subgroup Trend toward reduction of abnormal ketones in TTP399-treated group with improvement in glycemic control C-peptide Placebo TTP399 Treatment P value effect 0.13 ± 0.07 -0.31 ± 0.07 HbA1c Undetectable -0.44±0.07 p<0.01 (n=24) (n=23) Abnormal BOHB 8 (3
Slide 14: Conclusions: Mechanism DOES matter
Conclusions: Mechanism DOES matter Liver Selective GKA shows potential as an adjunctive therapy for T1D • Trends towards reduction in ketone events were observed in the TTP399 treated group compared to placebo. This finding was not due to imbalance in baseline characteristics • Trend toward reductio
Slide 15: Thank you to the patients, the investigators, the JDRF and the Simplici-T1 team
Thank you to the patients, the investigators, the JDRF and the Simplici-T1 team for making this study possible 15