UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549

FORM 8-K

CURRENT REPORT
PURSUANT TO SECTION 13 OR 15(D) OF THE
SECURITIES EXCHANGE ACT OF 1934

Date of Report (date of earliest event reported):  March 29, 2017

vTv Therapeutics Inc.
(Exact name of registrant as specified in its charter)

 

 

(336) 841-0300

(Registrant’s telephone number, including area code)  

NOT APPLICABLE

(Former name or former address, if changed since last report)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):

 

 

 

 

---

Item 7.01Regulation FD Disclosure

 

Representatives of vTv Therapeutics Inc. (the “Company”) are scheduled to display a poster entitled “TTP399: A Liver-Selective and Therapeutically Viable Glucokinase Activator: Results from a 6-Month Phase 2 Study” at the Seventeenth Annual Levine-Riggs Diabetes Research Symposium in Orlando, FL on March 29, 2017.  The poster presentation is attached hereto as Exhibit 99.1 and the associated abstract is attached hereto as Exhibit 99.2.

The information in Item 7.01 of this Form 8-K (including Exhibit 99.1 and 99.2) shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference under the Securities Act of 1933, as amended, except as expressly set forth by specific reference in such a filing, regardless of any general incorporation language in any such filing, unless the Company expressly sets forth in such filing that such information is to be considered “filed” or incorporated by reference therein.  The information set forth in the exhibits to this Form 8-K relating to this item 7.01 shall not be deemed an admission as to the materiality of any information in this report that is required to be disclosed solely to satisfy the requirements of Regulation FD.

Item 9.01Financial Statements and Exhibits

(d) Exhibits

---

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned, hereunto duly authorized.

VTV THERAPEUTICS INC.

 

Dated: March 29, 2017

 

 

---

EXHIBIT INDEX

 

 

Introduction RESULTS TTP399: A Liver-Selective and Therapeutically Viable Glucokinase Activator: Results from a 6-Month Phase 2 Study Adrian Vella1, Jennifer Freeman2, Chris Dvergsten2, Imogene Dunn2, and Carmen Valcarce2 1Mayo Clinic, Rochester, MN, USA. 2vTv Therapeutics LLC, High Point, NC, USA Safety Overview For the first time, a hepato-selective GKA has resulted in significant and sustained A1c lowering in T2DM after 6-months of treatment Additional benefits may include low risk of hypoglycemia, weight loss, increase in HDL, decrease in glucagon and paucity of adverse effects These findings also demonstrate the importance of tissue selectivity and the preservation of physiological regulation when targeting key metabolic regulators such as GK. This novel MOA is expected to be complementary to those of currently available diabetes drugs and expand treatment options Additional research on the clinical effects of TTP399 in a larger clinical trial is needed to confirm these promising results The therapeutic promise of glucokinase activators (GKAs) for type 2 diabetes has been limited by adverse events such as hypoglycemia and steatohepatitis, and lack of durability. The clinical characteristics of patients with GK-activating mutations or GK regulatory protein (GKRP) loss of function mutations suggest that liver-selective GKAs that do not activate GK in β-cells or affect the GK-GKRP interaction would present a superior profile. Guided by this evidence, we discovered and have developed TTP399. Aim Demography – Baseline Characteristics Disposition of Patients Liver selective: TTP399 does not activate GK in the beta-cells, reducing risk of hypoglycemia MOA preserves the natural interaction of GK-GKRP in the liver, reducing risk of increase in lipids Clinically relevant reduction in HbA1c Sustained effect over six months of treatment Negligible hypoglycemia and hyperlipidemia The goals of this 6 month, randomized, double-blind, placebo- and active-controlled, parallel group trial in type 2 diabetics on stable doses of metformin were to prove: AGATA Study Design 190 subjects randomized 7.0-9.5% baseline HbA1c Arms (1:1:1:1) Placebo TTP399 400mg once daily TTP399 800mg once daily Active comparator (sitagliptin / DPP-4 inhibitor) Primary endpoint: Change from baseline in HbA1c at 6 months 1Full Analysis Set (FAS): All randomized subjects who took at least one dose of study drug and had at least one efficacy endpoints evaluation post-baseline (N=171). ANCOVA adjusted for baseline HbA1c. Multiple imputation used for missing data. In this study, no alpha was allocated to comparisons with sitagliptin. LS-means (±SEM). ***p<0.001, **p<0.01, *p<0.05, compared to placebo. 2 Protocol Pre-specified . CFB= Change From Baseline. Goal 1: Clinically relevant reduction in HbA1c Change from BL in A1c (%) (LS means Placebo-subtracted) Goal 2: Sustained effect over 6 months Goal 3: Negligible hypoglycemia and hyperlipidemia Conclusions Other Study Outcomes Change in Weight at month 6 in subjects ≥100kg2 (N=69) CFB in Glucagon (pg/mL) (LS means Placebo-subtracted) Change in Weight at month 6 All subjects (FAS) Change in Fasting Plasma Glucagon at month 6 (FAS) CFB in Weight (Kg) (LS means Placebo-subtracted) * Month Month Change from BL in TG (mg/dL) ( LS means ) Change from BL in HDL (mg/dL) ( LS means ) * No Significant changes in plasma total Cholesterol, LDL or Non-HDL Cholesterol (not shown) Month Month Exhibit 99.1

Exhibit 99.2

 

TTP399: A liver‐selective and Therapeutically Viable Glucokinase Activator. Results for a 6‐Month Phase 2 Study

Adrian Vella¹, Jennifer Freeman², Chris Dvergsten², Imogen Dunn² and Carmen Valcarce².

¹Mayo Clinic, Rochester, MN, USA. ²vTv Therapeutics LLC, High Point, NC, USA

The critical role of glucokinase (GK) in the regulation of glucose homeostasis is reinforced by the fact that mutations in the gene encoding GK can cause both hyper‐and hypoglycemia. Furthermore, direct and indirect evidence suggest that a defect in hepatic glucose phosphorylation might underlie the lack of suppression of hepatic glucose production during hyperglycemia in human diabetes. Based on this, strategies to increase the activity of GK have been proposed as a novel approach for the treatment of type 2 diabetes. However, the therapeutic promise of glucokinase activators (GKAs) for type 2 diabetes has been limited by adverse events such as hypoglycemia and steatohepatitis, and lack of durability.

The clinical characteristics of patients with GK‐activating mutations or GK regulatory protein (GKRP) loss of function mutations suggest that liver‐selective GKAs that do not activate GK in β‐cells or affect the GK‐GKRP interaction would present a superior profile. Moreover, data from transgenic animals shows that a selective increase in hepatic GK is the only requirement for the normalization of the metabolic profile in insulin deficient animals. Guided by this evidence, we discovered and have developed TTP399, a liver‐selective GKA that does not appear to disrupt the interaction between GK and GKRP.

In the Phase 2 AGATA study, a six‐month, randomized, double‐blind, placebo‐and active‐controlled parallel group trial of TTP399 in type 2 diabetes, 190 patients with type 2 diabetes on stable doses of metformin were randomized (1:1:1:1) to TTP399 400 mg once daily; TTP399 800 mg once daily; sitagliptin 100 mg once daily; or placebo once daily. The patient population was approximately half male (53%), predominantly white (82%), and majority white non‐Hispanic or non‐Latino (59%). The mean (±SD) age, HbA1c and BMI at baseline were 55 years ±10, 8.0% ±0.7% and 32.8 kg/m² ± 5.6 kg/m², respectively.

Placebo‐subtracted changes in HbA1c at month 6 were –0.9% for TTP399 800 mg (p<0.01), –0.2% for TTP399 400 mg, and –1.0% for sitagliptin. Treatment with TTP399 800 mg, but not with placebo, sitagliptin or TTP399 400mg, was associated with a significant increase in HDL‐C (3.2 mg/dL; p< 0.05), decrease in fasting plasma glucagon (19.6 pg/dL; p=0.012), and decrease in weight (–3.4kg, p < 0.05, in patients weighing ≥100 kg). More significantly, TTP399 did not cause hypoglycemia or adversely affect blood pressure or lipid profiles.

The totality of the evidence from our preclinical and clinical data suggest that TTP399 may be the first therapeutically viable member of this class. These findings also demonstrate the importance of tissue selectivity and the preservation of physiological regulation when targeting key metabolic regulators such as GK. Additional research on the clinical effects of TTP399 in a larger clinical trial is needed to confirm these promising results.