Viking Therapeutics Presents Results from In Vivo Study of VK2809 in Biopsy-Confirmed Non-Alcoholic Steatohepatitis (NASH) at the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD)

Tuesday, October 24, 2017 General News
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Statistically Significant Reductions Observed in Fibrosis, Steatosis and NAS Score Following Eight Weeks of VK2809 Treatment vs Vehicle Controls

SAN DIEGO, Oct. 24, 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 final results from an eight-week study of VK2809 in an in vivo model of non-alcoholic steatohepatitis (NASH).  Data from this study demonstrated statistically significant improvements in several key measures relevant to the development and progression of NASH.  Additionally, an evaluation of gene expression changes demonstrated statistically significant changes in the expression of multiple genes associated with the development and progression of NASH following eight weeks of treatment with VK2809, as compared to vehicle control.  The results were presented in a poster presentation at The Liver Meeting® 2017, the annual meeting of the American Association for the Study of Liver Diseases (AASLD), held October 20-24, 2017, in Washington, D.C. 

Key results from the study included:

  • Treatment with VK2809 resulted in statistically significant reductions in liver triglycerides, liver cholesterol, total lipids and non-alcoholic fatty liver disease activity score (NAS) in treated animals relative to vehicle controls.  As summarized below, VK2809-treated animals demonstrated:
    • An 80% reduction in total lipid content vs. vehicle controls (p < 0.0001)
    • A 70% reduction in liver triglyceride content vs. vehicle controls (p < 0.0001)
    • A 65% reduction in liver cholesterol content vs. vehicle controls (p < 0.0001)
    • A 40% reduction in NAS, a composite of disease activity comprised of steatosis, ballooning and inflammation, vs. vehicle controls (p < 0.0001)
  • Treatment with VK2809 resulted in statistically significant reductions in several key measures of fibrotic activity, including total liver fibrosis, type I collagen and hydroxyproline, relative to vehicle controls.  As summarized below, VK2809-treated animals demonstrated:
    • A 50% reduction in total liver fibrosis vs. vehicle controls (p < 0.01)
    • A 60% reduction in type I collagen vs. vehicle controls (p < 0.005)
    • A 46% reduction in liver hydroxyproline content vs. vehicle controls (p < 0.01)
  • Treatment with VK2809 resulted in statistically significant changes in the expression of key genes associated with NASH development and progression, relative to vehicle controls.  As summarized below, VK2809-treated animals demonstrated:
    • Reductions of 44% and 37% in SREBF1 and SCD1 expression, respectively, and a 74% increase in CYP7a expression (p < 0.01 for each), suggesting improved lipid and cholesterol metabolism
    • Increases of 337% and 64% in FGF21 and PPAR? expression, respectively (p < 0.01 for each), suggesting improved lipid metabolism and insulin sensitivity
    • Reductions of 40%, 42%, and 18% in ANXA2, CK-18, and ASK1 expression (p < 0.01 for each), suggesting reduced inflammation, apoptosis and oxidative stress
    • Reductions of 36%, 37%, and 65% in pro-fibrogenic genes Col1a1, ?SMA, and Galectin 1, respectively (p < 0.01, p < 0.05, p < 0.001, respectively), suggesting reduced fibrotic activity

"These results demonstrate the promise of VK2809 in a biopsy-confirmed model of diet-induced NASH, showing impressive lipid-lowering effects, as well as anti-fibrotic benefits," said Brian Lian, Ph.D., chief executive officer of Viking.  "The observed changes in gene expression are exciting, as they corroborate the histologic improvements and suggest potential benefits on insulin sensitivity and metabolic control.  VK2809's therapeutic and safety profile continue to suggest a promising potential role in settings such as NASH and hyperlipidemia." 

Presented study results also highlighted that treatment with VK2809 was safe and well-tolerated, with no significant changes to liver function tests observed relative to controls.  Additionally, data showed that VK2809 compared favorably to the study's active control treatment, a PPAR-targeting agent that is currently in late-stage clinical development.

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.  Animals were biopsied prior to treatment to ensure disease characteristics consistent with the human form of disease, including the presence of fibrosis.  Changes in gene expression were evaluated by assessing changes in RNA expression at the conclusion of the experiment, compared with vehicle-treated controls.

VK2809 is a novel, orally available small molecule thyroid receptor beta (TR?) 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 GSD Ia and X-linked 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.

 

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SOURCE Viking Therapeutics, Inc.



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