SAN DIEGO, Sept. 11, 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 results from a gene expression analysis conducted as part
of its recently completed study of VK2809 in an in vivo
model of diet-induced non-alcoholic steatohepatitis (NASH).
The analysis, which evaluated more than 20,000 genes, demonstrated
that eight weeks of treatment with VK2809 led to statistically
significant changes in the expression of multiple genes associated
with the development and progression of NASH. These findings
align with recently reported histologic results from this study,
which demonstrated statistically significant improvements in
non-alcoholic fatty liver disease activity score (NAS), liver
fibrosis, and liver and plasma lipid levels in animals treated with
VK2809 relative to vehicle-treated controls.
Top-line data from the analysis include the following changes in
the expression of key genes associated with NASH development and
progression:
- 43.7% decrease in SREBF1 expression (p < 0.001), suggesting
reduced SREBP1 expression, reduced de novo lipogenesis
- 64.2% increase in PPARD expression, (p < 0.01), suggesting
improved PPARδ expression, improved lipid metabolism
- 336.8% increase in FGF21 expression (p < 0.001), suggesting
improved insulin sensitivity
- 36.3% decrease in COL1A1 expression (p < 0.05), suggesting
reduced collagen I production
Significant improvements were also observed in other
NASH-related genes of interest, including CYP7A1 (cholesterol
metabolism), MAP3K5 (ASK1, oxidative stress), ANXA2 (inflammation),
KRT18 (CK-18, cell apoptosis), ACTA2 (αSMA, fibrosis) and LGALS1
(Galectin 1, fibrosis). Detailed results from this study will
be presented at the 68th annual meeting of the American
Association for the Study of Liver Diseases (AASLD), October 20-24, 2017 in Washington, D.C.
"The changes in gene expression observed following treatment
with VK2809 provide further evidence of its potential benefit in
the setting of NASH and related diseases," said Brian Lian, Ph.D., chief executive officer of
Viking. "As we reported earlier this year, VK2809
demonstrated potent reductions in liver fat, fibrosis, and the
NAFLD Activity Score in this model of diet-induced NASH. The
genetic analysis results corroborate the histologic data and
suggest that VK2809 achieves this activity by modulating the
expression of genes associated with lipid metabolism, insulin
sensitivity, and fibrosis, all of which are important in the
setting of NASH. This breadth of activity highlights VK2809's
differentiated mechanism of action and exciting potential
therapeutic profile."
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 (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.
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SOURCE Viking Therapeutics, Inc.