Viking Therapeutics Announces Data from In Vivo Study of VK2809 Presented at Oral Plenary Session of the 88th Annual Meeting of American Thyroid Association (ATA)

SAN DIEGO, Oct. 8, 2018 /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 the presentation of positive data from a study of VK2809 in an in vivo model of glycogen storage disease type Ia (GSD Ia) at the 88^th Annual Meeting of the American Thyroid Association (ATA) in Washington, D.C.  The results demonstrated that treatment with VK2809 led to an overall improvement in liver health highlighted by restoration of autophagy, reduction in steatosis, and improvements in inflammation and liver size.  The study investigators concluded that these histological improvements are potentially relevant to non-alcoholic fatty liver disease (NAFLD), including non-alcoholic steatohepatitis (NASH), due to certain similarities between those conditions and GSD Ia.

Study results were summarized in an oral presentation titled, "Liver-selective Thyromimetic, VK2809, Reduces Hepatosteatosis in Mouse Model of the Glycogen Storage Disease GSD Ia," by professor Paul Yen, M.D., head of the Laboratory of Hormonal Regulation, Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, Singapore.  GSD Ia is a rare genetic disease that results in excess accumulation of glycogen and lipids in liver tissue.  This study utilized the glucose-6-phosphatase (G6PC) knockout mouse model, which is intended to replicate the impairment of this enzyme's activity in patients with GSD Ia.  G6PC knockouts develop enlarged livers due to elevated fat content.

The results demonstrated decreases in steatosis, liver mass, and triglyceride concentration in VK2809-treated cohorts compared with vehicle controls.  Significant improvements in LC3B-II protein density, an important mediator of fat disposal, as well as reduced levels of p62 protein, were also observed.  These data suggest that, in addition to stimulation of beta-oxidation via increased PGC1-alpha and CPT1-alpha expression, restoration of autophagy may be contributing to the reduction of fat content in this setting.

Importantly, this study also demonstrated indications of reduced inflammatory signalling following treatment with VK2809.  The expression of inflammatory markers such as tumor necrosis factor alpha (TNF alpha) and interleukin 6 (IL-6) were normalized or reduced in the livers of VK2809-treated cohorts compared with vehicle controls, suggesting an overall reduction in inflammation.  These data may be of interest for other indications in which inflammation plays a role in disease progression and severity.

"These results are exciting not only in the context of GSD Ia but also, as Dr. Yen highlighted, due to their relevance to settings like NAFLD and NASH.  The impressive reduction in steatosis observed in this model is supported by improved expression of genes important for autophagy and fat metabolism.  The normalization of inflammatory gene expression is of particular interest due to role of inflammation in the onset of hepatocyte damage, and ultimately fibrosis, in various liver diseases," said Brian Lian, Ph.D., chief executive officer of Viking.  "We believe the GSD I data presented at ATA, combined with our recently reported Phase 2 results in NAFLD, provide compelling support for VK2809 as a best-in-class thyroid beta receptor agonist with significant therapeutic potential in NAFLD and NASH."

The proof-of-concept study was conducted under a sponsored research agreement between Duke University and Viking Therapeutics and designed to evaluate the effects of VK2809 in Duke University's G6PC knockout mouse model.  The G6PC knockout model is intended to replicate many of the same biochemical and physiological characteristics present in GSD Ia patients.

About VK2809
VK2809 is an orally available, tissue and receptor-subtype selective agonist of the thyroid beta receptor (TRβ) that possesses selectivity for liver tissue, as well as the beta receptor subtype, suggesting promising therapeutic potential in a range of lipid disorders. The compound successfully achieved primary and secondary endpoints in a Phase 2 study for the treatment of patients with elevated LDL-C and non-alcoholic fatty liver disease (NAFLD).  The company is also preparing to evaluate VK2809 in a Phase 1 study for the treatment of patients with GSD Ia.  VK2809 belongs to a family of novel prodrugs, which are cleaved in vivo to release potent thyromimetics.  Selective activation of the TRß receptor in liver tissue is believed to favorably affect cholesterol and lipoprotein levels via multiple mechanisms, including increasing the expression genes associated with lipid metabolism and clearance.  

About GSD Ia
Glycogen storage disease Ia (GSD Ia) is a rare, orphan genetic disease caused by a deficiency of glucose-6-phosphatase (G6PC), an enzyme responsible for the liver's production of free glucose from glycogen and gluconeogenesis.  The disease, for which there is no approved treatment, results in an excess accumulation of glycogen and lipids in the liver, potentially leading to hepatosteatosis, liver failure, development of hepatic adenomas, and hepatocellular carcinoma.  Increased triglyceride production and elevated hepatic triglyceride levels are characteristic of GSD Ia and associated with many manifestations of the disease.  GSD Ia is estimated to occur in approximately 1 in every 50,000 – 100,000 births in the United States.  As manifestations of the disease begin to present themselves at birth, a sizeable portion of GSD Ia patients are children.

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.  The company's clinical programs include VK2809, a small molecule thyroid beta agonist.  In a Phase 2 trial for the treatment of non-alcoholic fatty liver disease and elevated LDL-C, patients who received VK2809 demonstrated statistically significant reductions in LDL-C and liver fat content. VK2809 was shown to be safe and well-tolerated in the study.  The company's second clinical program is VK5211, an orally available, non-steroidal selective androgen receptor modulator.  In a Phase 2 trial in patients recovering from hip fracture, patients who received VK5211 experienced significant improvements in measures of lean body mass compared to patients who received placebo.  The company is also developing VK0612, a first-in-class, orally available drug candidate in Phase 2 development for type 2 diabetes.  Additional programs include 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.  Viking holds exclusive worldwide rights to a portfolio of five therapeutic programs in clinical trials or preclinical studies, including those noted above, which are based on small molecules licensed from Ligand Pharmaceuticals Incorporated.

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.

SOURCE Viking Therapeutics, Inc.

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