Viking Therapeutics Presents Positive Proof-of-Concept Data for VK0214 in In Vivo Model of X-Linked Adrenoleukodystrophy (X-ALD) at the 86th Annual Meeting of the American Thyroid Association

SAN DIEGO, Sept. 26, 2016 /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 proof-of-concept study of VK0214 in a mouse model of X-linked adrenoleukodystrophy (X-ALD).  The study successfully achieved its primary objective, which was to demonstrate the ability of VK0214 to lower plasma very long chain fatty acid (VLCFA) levels after six weeks of treatment.  The detailed study results were presented at the 86^th Annual Meeting of the American Thyroid Association (ATA), held in Denver, Colorado on September 21-25, 2016.

In this study, mice lacking the ABCD1 VLCFA transporter were treated once-daily with VK0214 or vehicle for six weeks, and assessed for changes in VLCFA levels at various time points.  This model was selected due to similarities in the biochemical abnormalities displayed by these mice and patients with X-ALD.  Following six weeks of treatment with VK0214, mean plasma levels of C26:0-lysophosphatidylcholine (LPC) were reduced by 29% compared to vehicle-treated controls (p < 0.0001).  C26:0-LPC is a key diagnostic biomarker for X-ALD.  In whole blood, treatment with VK0214 led to a 52% greater reduction from baseline C26:0-LPC levels vs. vehicle-treated controls (p < 0.005).  Importantly, the response to VK0214 appeared to be progressive, with reductions in C26:0-LPC generally increasing in both magnitude and statistical significance over time.  The reduction of VLCFA levels is considered an attractive goal for therapeutic approaches to X-ALD, as their accumulation is believed to contribute to the underlying pathology of the disease.

Treatment with VK0214 also resulted in robust effects on multiple additional VLCFAs that may play a role in X-ALD.  After six weeks of treatment, significant reductions were observed in plasma levels of C20:0-LPC (-54%, p < 0.0001), C22:0-LPC (-43%, p < 0.0001), and C24:0-LPC (-21%, p < 0.005).  Reducing the levels of these shorter chain VLCFAs may suggest enhanced reductions in C26:0-LPC over time, via depletion of the pool for chain elongation.

"This important proof-of-concept study successfully met its goal, demonstrating the potent impact of VK0214 across a range of VLCFAs, including the key C26:0-LPC biomarker, in a relevant model of disease," said Brian Lian, Ph.D., chief executive officer of Viking.  "The impressive reductions observed in VLCFA levels provide support for the potential role of VK0214 in combatting the debilitating effects of X-ALD through selective activation of the thyroid beta receptor." 

VK0214 is a novel, orally available thyroid receptor beta (TRβ) agonist that selectively regulates the expression of genes believed to be relevant to the manifestation of X-ALD.  The proof-of-concept study, conducted at the Kennedy Krieger Institute under a sponsored research agreement with Viking, was designed to evaluate changes in VLCFA levels in the ABCD1 knockout mouse model following exposure to VK0214.  This model is intended to mirror the loss of ABCD1 transporter activity that is considered the hallmark of X-ALD in humans.  Mice received VK0214 or vehicle once-daily for six weeks.  VLCFA levels were determined by measuring unsaturated lysophosphatidylcholine fatty acid esters, which are biomarkers for VLCFAs in X-ALD. 

About X-ALD
X-ALD is a rare and often fatal metabolic disorder characterized by a breakdown in the protective barriers surrounding brain and nerve cells; a process known as demyelination.  The disease, for which there is no approved treatment, is caused by mutations in a peroxisomal transporter of VLCFAs, known as ABCD1.  As a result, transporter function is impaired and patients are unable to efficiently metabolize VLCFA.  The resulting accumulation can trigger a rapid, inflammatory demyelination, which leads to cognitive impairment, motor skill deterioration, and even death.  X-ALD is estimated to occur in approximately 1 in 17,000 births.

The thyroid beta receptor is known to regulate expression of an alternative VLCFA transporter, known as ABCD2.  Various preclinical models have demonstrated that increased expression of ABCD2 can lead to normalization of VLCFA metabolism.

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 entering 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.

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 VK0214. 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; 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.