Viking Therapeutics Announces Top-Line Results from Proof-of-Concept Study of VK0214 in In Vivo Model of X-Linked Adrenoleukodystrophy (X-ALD)

SAN DIEGO, Oct. 4, 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 top-line results from a 25-week proof-of-concept study of VK0214 in an in vivo model of X-linked adrenoleukodystrophy (X-ALD). The results of this study showed that VK0214 led to statistically significant reductions in plasma levels of multiple very long chain fatty acids (VLCFAs) in treated animals compared with vehicle controls. Additionally, VK0214-treated animals demonstrated statistically significant reductions in VLCFA levels within key tissues, including liver, brain and spinal cord. As the accumulation of VLCFAs is believed to contribute to the underlying pathology of X-ALD, these data provide additional support for the continued evaluation of VK0214 in this indication. 

The results showed that 25 weeks of treatment with VK0214 led to robust effects on multiple VLCFAs, including statistically significant reductions in plasma levels of saturated C26, C24, C22, and C20 fatty acids ranging from 45% to 82% relative to controls. Importantly, these reductions were generally maintained or increased in magnitude over the course of the 25-week study, suggesting a potentially progressive and durable effect. These data compare favorably to results from a prior six-week study, with improvements observed on all key VLCFA measures relative to the prior study. These results further support the thesis that activation of the thyroid beta receptor can lead to an improved metabolic profile in this setting.

The study also evaluated the effect of VK0214 on VLCFA levels in various tissues.  After 25 weeks of treatment, VK0214 was shown to reduce levels of VLCFAs in liver, brain and spinal cord.  This suggests an added potential therapeutic benefit, as elevated tissue VLCFA levels may contribute to the underlying cerebral and myelotoxicities observed in X-ALD.  Detailed results will be presented at the upcoming 87^th Annual Meeting of the American Thyroid Association, October 18-22 in Victoria, British Columbia.

"This is the second study in which we have generated encouraging evidence of the therapeutic potential of VK0214 in this debilitating disease. The impressive effects on plasma VLCFAs strengthen our belief that activation of the thyroid beta receptor can lead to improved lipid processing.  The reduction in tissue VLCFAs is particularly exciting, as it suggests a potential direct benefit on tissue-related toxicities," said Brian Lian, Ph.D., chief executive officer of Viking. "Importantly, these longer-term results demonstrate improved pharmacologic effects relative to the prior six-week study, with no evidence of safety or tolerability issues. We look forward to continuing our evaluation of VK0214 in this setting."

The 25-week 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.  This model is intended to mirror the loss of ABCD1 transporter activity that is considered the hallmark of X-ALD.  Mice received VK0214 or vehicle daily for 25 weeks.  Plasma VLCFA levels were determined by measuring unsaturated lysophosphatidylcholine fatty acid esters, which are biomarkers for VLCFAs in X-ALD.  Additional work is underway to better understand VK0214's therapeutic effect in models of this disease, including an elucidation of anti-inflammatory properties that have been observed in preliminary studies in human macrophages.

About VK0214
VK0214 has been granted orphan drug status by the U.S. Food and Drug Administration for the treatment of X-linked adrenoleukodystrophy.  The molecule is a novel, orally available thyroid receptor beta (TRβ) agonist that selectively modulates lipoprotein and triglyceride levels in liver tissue.  This mechanism has been demonstrated to affect the expression of the genes that are relevant to the manifestation of X-ALD.  In X-ALD, mutations in the ABCD1 gene lead to the accumulation of very long-chain fatty acids (VLCFAs) which is believed to be a fundamental cause of the disease.  Research has shown that increasing the expression of the ABCD2 gene can counteract this process and lead to normalization of VLCFA levels.  In preclinical studies, VK0214 has been shown to induce expression of ABCD2 by increasing TRβ activity, leading to the belief that it may provide therapeutic benefit to X-ALD patients. 

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 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 VK0214 and VK0214'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 VK5211 and VK2809; risks that prior clinical and pre-clinical results, including those for VK0214, 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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