Viking Therapeutics Announces Promising Top Line Results from In Vivo Study of VK2809 in Non-Alcoholic Steatohepatitis (NASH)

SAN DIEGO, June 6, 2017 /PRNewswire/ -- Viking Therapeutics, Inc. ("Viking") (NASDAQ: VKTX), a clinical-stage biopharmaceutical company focused on the development of novel therapies for metabolic and endocrine disorders, today announced positive top line results from a study of VK2809 in an in vivo model of non-alcoholic steatohepatitis (NASH).  Data from this study demonstrated improvements across several key measures relevant to the development and progression of NASH.  Animals receiving VK2809 experienced statistically significant improvements in non-alcoholic fatty liver disease activity score (NAS), liver collagen content, and liver fibrosis relative to vehicle-treated controls.  NAS is a composite measure of disease activity which is comprised of steatosis, ballooning and inflammation.  These results represent the first evidence of a thyromimetic agent providing histologic benefits in a NASH model, including an improvement in fibrosis.

The study was designed to evaluate VK2809 dosed orally (10 mg/kg/day) for eight weeks in a mouse model of diet-induced NASH.¹  Control cohorts received either vehicle or active control (a metabolic-targeting agent currently in late-stage clinical development for NASH).  Animals were biopsied prior to treatment to ensure disease characteristics consistent with the human form of disease, including the presence of fibrosis. 

A summary of preliminary findings is highlighted below:

• Liver triglyceride content was reduced by 70% compared to vehicle control (p<0.0001), and by 56% compared to active control (p<0.0001)
• Liver cholesterol content was reduced by 65% compared to vehicle control (p<0.0001) and by 58% compared to active control (p<0.0001)
• Liver fibrosis was reduced by 50% compared to vehicle control (p=0.01) and by 21% compared to active control (p=0.3)
• Liver collagen content was reduced by 60% compared to vehicle control (p<0.005) and by 49% compared to active control (p=0.07)
• Liver hydroxyproline content was reduced by 46% compared to vehicle control (p=0.01) and by 36% compared to active control (p=0.06)

Additional data showed that animals treated with VK2809 experienced a 40% mean improvement in NAS after eight weeks, compared to vehicle-treated controls (p<0.0001; average baseline NAS 5.7; n = 12/cohort); and 50% of VK2809-treated animals demonstrated at least a two-point improvement in NAS, compared with no vehicle-treated animals demonstrating at least a two-point improvement (p=0.01).  No animals treated with VK2809 demonstrated a worsening in NAS vs. approximately 60% of vehicle-treated animals demonstrating a worsening (p<0.0001).  Improvements in all subcomponents of NAS (inflammation, ballooning, and steatosis) were observed in VK2809-treated animals relative to vehicle controls.  Consistent with previously-reported data, treatment with VK2809 also produced significant reductions in plasma triglycerides and cholesterol in this study.  In addition, VK2809 demonstrated promising safety and tolerability. All animals received all scheduled doses of drug and there were no unexpected or abnormal laboratory findings.

"The preliminary data from VK2809 in this model of diet-induced NASH demonstrate promising results in the quantitative resolution of collagen, a major component of fibrosis, as well as significant improvements in intracellular fat content," stated Joel Lavine, MD, PhD, Chief of Pediatric Gastroenterology, Hepatology, and Nutrition at New York-Presbyterian/Morgan Stanley Children's Hospital.  "These represent important elements of NASH and it will be interesting to see additional studies conducted with VK2809 in this setting."

"We are excited about the initial results from this study, as they demonstrate promising effects in a model of NASH that we believe reflects many characteristics of the disease in humans," said Brian Lian, Ph.D., chief executive officer of Viking.  "The robust effect across multiple disease metrics, including reductions in collagen and lipotoxic lipids suggests potential benefits on endpoints important in NASH.  The observed reductions in hepatic collagen content and fibrosis, by morphometric analysis, are particularly noteworthy, as these data represent the first quantitative histologic evidence that treatment with a thyromimetic agent can potentially improve NASH-related fibrosis.  These results provide further support for the development of VK2809 in these settings."

Scientific literature suggests that liver fibrosis is associated with long-term outcomes in patients with non-alcoholic fatty liver disease and that hepatic collagen content is correlated with fibrosis staging and outcomes in these patients.^2,3,4  In addition, recently-published data have indicated that a reduction of de novo lipogenesis can produce improvements in markers of liver fibrosis in patients with NASH.⁵  These data provide support for the potential benefits of VK2809 in NASH, as prior data have shown that VK2809 downregulates genes important for de novo lipogenesis, while simultaneously stimulating the expression of genes important for lipid metabolism.  An analysis of genetic markers from the current study is ongoing.

"The totality of published literature, combined with the effect of VK2809 on hepatic lipids, collagen content, fibrosis and NAS observed in the diet-induced disease model suggest an encouraging potential benefit in NASH," stated Dr. Lian. 

VK2809 is a novel, orally available small molecule thyroid receptor beta (TRβ) agonist that possesses selectivity for liver tissue, as well as the beta receptor subtype, suggesting promising therapeutic potential in a range of lipid disorders.  Viking is currently evaluating VK2809 in a randomized, double-blind, placebo-controlled, parallel group Phase 2 study designed to assess the drug candidate's efficacy, safety and tolerability in patients with elevated LDL-C and non-alcoholic fatty liver disease.  Previously reported clinical data have demonstrated that treatment with VK2809 leads to significant reductions in plasma triglycerides, LDL cholesterol (LDL-C), and atherogenic protein levels in subjects with mild hypercholesterolemia.

About Viking Therapeutics, Inc.
Viking Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on the development of novel, first-in-class or best-in-class therapies for metabolic and endocrine disorders.  The company's research and development activities leverage its expertise in metabolism to develop innovative therapeutics designed to improve patients' lives.  Viking has exclusive worldwide rights to a portfolio of five therapeutic programs in clinical trials or preclinical studies, which are based on small molecules licensed from Ligand Pharmaceuticals Incorporated.  The company's clinical programs include VK5211, an orally available, non-steroidal selective androgen receptor modulator, or SARM, in Phase 2 development for the treatment and prevention of lean body mass loss in patients who have undergone hip fracture surgery, VK2809, a small molecule thyroid beta agonist in Phase 2 development for hypercholesterolemia and fatty liver disease, and VK0612, a first-in-class, orally available drug candidate in Phase 2 development for type 2 diabetes.  Viking is also developing novel and selective agonists of the thyroid beta receptor for adrenoleukodystrophy, as well as two earlier-stage programs targeting metabolic diseases and anemia.

Follow Viking on Twitter @Viking_VKTX.

Forward-Looking Statements
This press release contains forward-looking statements regarding Viking Therapeutics, including statements about Viking's expectations regarding its development activities, timelines and milestones, as well as the company's goals and plans regarding VK2809 and VK2809's prospects. Forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially and reported results should not be considered as an indication of future performance. These risks and uncertainties include, but are not limited to: risks associated with the success, cost and timing of Viking's product candidate development activities and clinical trials, including those for VK2809; risks that prior clinical and pre-clinical results may not be replicated; and risks regarding regulatory requirements, among others. These forward-looking statements speak only as of the date hereof.  Viking disclaims any obligation to update these forward-looking statements.

References:

1. N.M. Kristiansen, S.S. Veidal, et al., Obese diet-induced mouse models of non-alcoholic steatohepatitis-tracking disease by liver biopsy, World J. Hepatology, 2016; 8(16):673-684.  M. Reigh, K.S. Tobol, et al., Comparative effects of liraglutide, elafibranor, and obeticholic acid on NAFLD activity score and fibrosis stage in a diet-induced obese mouse model of biopsy-confirmed NASH; Hepatology 66(1): S599, 2017.

2. P. Angulo, D.E. Kleiner, et al., Liver Fibrosis, but no Other Histologic Features, Associates with Long-term Outcomes of Patients With Nonalcoholic Fatty Liver Disease; Gastroenterology 2015 August; 149(2): 389–397.e10.

3. Z.D. Goodman, L. Alaparthi, et al., Correlations between hepatic morphometric collagen content, histologic fibrosis staging, and serum markers in patients with advanced fibrosis due to nonalcoholic steatohepatitis (NASH); Hepatology 62(2):906A, October 2015.

4. E. Buzzetti, A. Hall, et al., Collagen proportion area is an independent predictor of long-term outcome in patients with non-alcoholic fatty liver disease; Hepatology 66(1): S52, 2017.

5. E.J. Lawitz, F. Poordad, A. Coste et al., Acetyl-CoA carboxylase (ACC) inhibitor GS-0976 leads to significant improvements in MRI-PDFF, MRE, and other markers of fibrosis after 12 weeks of therapy in patients with NASH; Hepatology 66(1): S33, 2017.

SOURCE Viking Therapeutics, Inc.

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