Viking Therapeutics Presents Results from Proof-of-Concept Study of VK0214 in In Vivo Model of X-Linked Adrenoleukodystrophy (X-ALD) at the 87th Annual Meeting of the American Thyroid Association

Results Demonstrate Significant Reductions in Plasma and Tissue Very Long Chain Fatty Acids, Potential Biomarkers of Therapeutic Effects, Following Treatment With VK0214

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Viking Therapeutics, Inc.

Oct 23, 2017, 07:05 ET

SAN DIEGO, Oct. 23, 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 25-week proof-of-concept study of VK0214 in an in vivo model of X-linked adrenoleukodystrophy (X-ALD). The final study data were presented in a poster presentation at the 87^th Annual Meeting of the American Thyroid Association (ATA), held October 18-22, 2017, in Victoria, British Columbia.

The results of this study showed that treatment with VK0214 led to statistically significant reductions in plasma levels of multiple very long chain fatty acids (VLCFAs), including the benchmark highly toxic C26 fatty acid, in treated animals compared with vehicle controls. VLCFA levels in CNS tissues were also significantly reduced, suggesting a potential direct benefit in both 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 role of selective thyroid receptor beta (TRb) activation as a potential therapeutic approach to the disease.

Key results from the study included:

Treatment with VK0214 produced robust and durable reductions in plasma levels of the lysophosphatidylcholine (LPC) derived C26:0, C24:0, C22:0 and C20:0 very long chain fatty acid esters throughout the study.

Plasma C26:0-LPC levels were reduced by up to 57% through the course of the study, compared to vehicle controls (p < 0.005 at week 6 and p < 0.0001 at weeks 9, 12, 20 and 25).
Plasma C24:0-LPC levels were reduced by up to 61% compared to vehicle controls (p < 0.0001).
Plasma C22:0-LPC levels were reduced by up to 74% compared to vehicle controls (p < 0.0001).
Plasma C20:0-LPC levels were reduced by up to 82% compared to vehicle controls (p < 0.0001).

Importantly, the reductions in plasma VLCFAs were generally maintained or increased in magnitude over the course of the 25-week study, suggesting a potentially progressive and durable effect.
Treatment with VK0214 also led to significant reductions in C26:0, C24:0, C22:0 and C20:0 VLCFA levels in brain, spinal cord and liver tissue.

Brain levels of C20:0-, C22:0-, and C26:0-LPC were reduced by 34%, 12%, and 11%, respectively (p < 0.001, p < 0.05, and p = 0.07, respectively).
Spinal cord levels of C20:0 and C26:0 were reduced by 9%, and 15%, respectively (p < 0.05 for each).
Liver levels of C20:0, C24:0, and C26:0 were reduced by 59%, 49% and 19%, respectively (p < 0.0001, p < 0.0001, and p < 0.05, respectively).

Treatment with VK0214 stimulated significant increases in ABCD2 transporter expression, as assessed by quantitative polymerase chain reaction (qPCR) analysis. Brain ABCD2 expression increased by 35% (p < 0.05) and liver ABCD2 expression increased by 262% (p < 0.05), compared with vehicle controls. These increases are consistent with the proposed mechanism of TRb-mediated reductions in VLCFA levels, as ABCD2 is regulated by TRb and known to play a role in VLCFA metabolism.

"These results are particularly exciting as they demonstrate the first evidence of VK0214's effects in CNS tissues," said Brian Lian, Ph.D., chief executive officer of Viking. "The observed reductions in brain and spinal cord VLCFAs, combined with the stimulation of brain ABCD2 expression suggest potential benefits in tissues that are difficult to penetrate and especially prone to degeneration in X-ALD. In addition to the potent and durable reductions of plasma VLCFAs, we believe these results provide compelling support for the continued 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 oral 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.