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 88th 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.
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SOURCE Viking Therapeutics, Inc.