Slide 1: The Simplici-T1 trial: Activation of glucokinase by TTP399 improves glycemic control in T1DM
The Simplici-T1 trial: Activation of glucokinase by TTP399 improves glycemic control in patients with T1DM C. Valcarce1, J.L.R. Freeman1, I. Dunn1, C. Dvergsten1, K.R. Klein2, J. Buse2; 1vTv Therapeutics, High Point, NC 2University of North Carolina School of Medicine, Chapel Hill, NC 1
Slide 2: Disclosures – Carmen Valcarce
Disclosures – Carmen Valcarce • vTv Therapeutics employee 2
Slide 3: Subcutaneous Insulin Alone is Not Enough
Subcutaneous Insulin Alone is Not Enough • Nearly 80% of people with type 1 diabetes Life-threatening, short-term fail to achieve ADA target A1c levels1 complications of poor glycemic control Despite improved and more widely adopted diabetes technology, clinical outcomes continue to decline2 Severe
Slide 4: Hepatic Glucokinase Activation, a New Strategy to Treat T1D
Hepatic Glucokinase Activation, a New Strategy to Treat T1D Glucokinase (GK) is the glucose sensor of the body TTP399: A liver selective Glucokinase Activator1 • Key role in glucose homeostasis supported by strong genetic evidence • Glucose sensitive kinetics TTP399 activates GK in the liver • No in
Slide 5: TTP399-203 (Simplici-T1): Adaptive Phase 1b/2 Study Trial Design
TTP399-203 (Simplici-T1): Adaptive Phase 1b/2 Study Trial Design Phase 1 Phase 2-Part 1 Phase 2-Part 2 (Sentinels) (Learning Phase) (Confirming Phase) 1 site – 4 sites - 13 sites - Study design § Open-label § Randomized, Double-blind, Placebo control § Randomized, Double-blind, Placebo control § 7 d
Slide 6: Simplici-T1 Study Design: Key Differences Between Part 1 and 2
Simplici-T1 Study Design: Key Differences Between Part 1 and 2 Part 1 (Learning Phase) Part 2 (Confirming Phase) 20 Subjects randomized 85 Subjects randomized 3 sites in NC, 1 site in CA (2 sites randomized >70%) 13 sites in US (2 sites randomized =28%) • Eligible participants were adults diagnosed
Slide 7: Simplici-T1 Subject Disposition
Subject SimpliciT-1Disposition: study disposition NoSimilar disposition between Part 1 and Part 2 with very few discontinuations discontinuations in the TTP399 group Learning Phase Confirming Phase Assessed for eligibility Assessed for eligibility n= 31 n= 141 Ineligible n=11 Ineligible n=56 Not mee
Slide 8: Baseline characteristics for the Full Analysis Set (FAS)
Baseline characteristics for the Full Analysis Set (FAS) Learning Phase Confirming Phase Placebo TTP399 Placebo TTP399 (n= 11) (n=8) (n= 43) (n=38) Sex, female 8 (73%) 5 (63%) 24 (56%) 14 (37%) Age (years) 47 (10) 38 (15) 42 (13) 43 (15) Race White 11 (100%) 7 (87%) 41 (95%) 36 (95%) Black or Africa
Slide 9: Primary Endpoints: Statistically significant improvement in glycemic control
Primary Endpoints: Statistically significant improvement in glycemic control Learning Phase Confirming phase Placebo TTP399 Placebo TTP399 (n= 11) (n=8) (n= 43) (n=38) HbA1c % Baseline (SD) 7·4 (0·4) 7·2 (0·4) 7·5 (0·60) 7·6 (0·6) Week 12 change from baseline (SE) 0·08 (0·20) -0·60 (0·20) 0·07 (0·06
Slide 10: Safety: High-level Summary
Safety: High-level Summary The incidence of treatment-emergent adverse events was similar between the groups Learning Phase Confirming Phase Placebo TTP399 Placebo TTP399 (n=11) (n=9) (n=45) (n=40) Number of AEs reported 16 13 83 58 Participants with at least one AE 8 (73%) 6 (67%) 29 (64%) 26 (65%)
Slide 11: Adverse Events of Special Interest
Adverse Events of Special Interest In contrast to other GK activators that have been in clinical development TTP399 did not alter liver function or increase plasma triglycerides Liver Function: Triglycerides: No significant changes in liver function No significant changes in Triglycerides Learning P
Slide 12: Adverse Events of Special Interest: Hypoglycemia
Adverse Events of Special Interest: Hypoglycemia Trends towards reduction of risk of hypoglycemia in the TTP399-treated group while improving HbA1c • Learning phase: • No AEs of symptomatic or severe hypoglycemia were reported in either group • Confirming Phase: Placebo TTP399 Confirming Phase Confi
Slide 13: Subgroup Analysis by Changes in Total Insulin
Subgroup Analysis by Changes in Total Insulin • TTP399 significantly reduced HbA1c compared to placebo in patients that decreased their insulin dose or maintained stable insulin dose throughout the study • Significantly fewer patients in the TTP399 treated group needed to increase their insulin dose
Slide 14: Hypoglycemia Per Insulin Group
Hypoglycemia Per Insulin Group: Trends towards reduction in hypoglycemic events in the TTP399-treated group independent of the changes in insulin dose Reduced Insulin Stable insulin Increased insulin Placebo (n=12) TTP399 (n=15) Placebo (n=13) TTP399 (n=13) Placebo (n=11) TTP399 (n=4)* Number of par
Slide 15: Adverse Events of Special Interest: DKA, Ketosis and Plasma beta-hydroxybutyrate
Adverse Events of Special Interest: DKA, Ketosis and Plasma beta-hydroxybutyrate • No DKA was reported in the study. • In contrast to other adjunctive therapies that have been in clinical development, TTP399, when compared to placebo, did not increase plasma beta-hydroxybutyrate. More details on OP
Slide 16: Conclusions
Conclusions • The collective clinical data from the Simplici-T1 study support the hypothesis that activation of glucokinase by TTP399 improves glycemic control without increasing the risk of hypoglycemia or DKA and without deleterious effects in lipids or liver function. • Significant improvement in
Slide 17: Thank you to the patients, the investigators and their teams
Thank you to the patients, the investigators and their teams, the JDRF and the Simplici-T1 team to make this study possible 17