Viking Therapeutics Announces Initiation of Phase 1b Clinical Trial of VK0214 in Patients with X-ALD

SAN DIEGO, June 24, 2021 /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 initiation of a Phase 1b clinical trial of VK0214, a novel small molecule agonist of the thyroid hormone receptor beta (TRβ), in patients with X-linked adrenoleukodystrophy (X-ALD).  The study is open to enrollment at clinical sites within the United States.

The Phase 1b trial is a multi-center, randomized, double-blind, placebo-controlled study in adult male patients with the adrenomyeloneuropathy (AMN) form of X-ALD.  The study is initially targeting enrollment across three cohorts: placebo, VK0214 20 mg daily, and VK0214 40 mg daily.  Pending a blinded review of preliminary safety, tolerability, and pharmacokinetic data, additional dosing cohorts may be pursued.

The primary objectives of the study are to evaluate the safety and tolerability of VK0214 administered once-daily over a 28-day dosing period, and to assess the efficacy of VK0214 at lowering plasma levels of very long chain fatty acids (VLCFAs) in patients with AMN.  Secondary objectives include an evaluation of the pharmacokinetics and pharmacodynamics of VK0214 following 28 days of dosing in this population.

VK0214 is a novel, orally available small molecule TRβ agonist that recently completed a successful Phase 1 single ascending dose (SAD) and multiple ascending dose (MAD) study in healthy subjects.  Results from that trial showed that VK0214 demonstrated encouraging safety and tolerability, as well as predictable pharmacokinetics.  In addition, subjects who received VK0214 experienced reductions in low-density lipoprotein cholesterol (LDL-C), triglycerides, and apolipoprotein B following 14 days of treatment.  Based on these results, VK0214 was advanced into the Phase 1b study in patients with AMN.

"We are excited to initiate a proof-of-concept study with our second thyroid agonist, VK0214, and look forward to evaluating its therapeutic potential in setting of adrenomyeloneuropathy.  The results of our recently completed Phase 1 trial demonstrated the compound's promising profile and support our plan for further study in patients with this debilitating disease." said Brian Lian, Ph.D., chief executive officer of Viking Therapeutics.  "We are particularly interested in evaluating VK0214's effect on circulating VLCFAs, which are believed to play a role in the onset and progression of the disease.  VK0214 is the second TRβ agonist from our portfolio to advance into a clinical proof-of-concept study, following VK2809, which is currently being evaluated in our Phase 2b VOYAGE trial in patients with biopsy-confirmed NASH.  We expect data from both studies to be available in 2022." 

Activation of the thyroid beta receptor has been shown to affect the expression of genes that are relevant to the manifestation of X-ALD.  In X-ALD, mutations in the ABCD1 gene lead to dysfunction of the adrenoleukodystrophy protein (ALDP), an important peroxisomal transporter.  This dysfunction leads to an accumulation of VLCFAs, which is believed to contribute to the onset and progression of the disease.  Research in disease models has shown that increasing the expression of a related gene called ABCD2, which encodes a compensatory transporter called the adrenoleukodystrophy related protein (ADLRP), can result in normalization of VLCFA levels.

In preclinical studies, VK0214 has been shown to potently activate the thyroid beta receptor, a regulator of ABCD2 gene expression, leading to increased expression of ABCD2.  Data from in vivo studies have demonstrated that administration of VK0214 produces a significant reduction of VLCFAs in both plasma and tissue, potentially leading to a therapeutic benefit.  VK0214 has been granted orphan drug designation by the FDA for the treatment of 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 the gene for a peroxisomal transporter of VLCFAs, known as ABCD1. As a result, transporter function is impaired, and patients are unable to efficiently metabolize VLCFAs. 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 the gene for 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 is a clinical-stage biopharmaceutical company focused on the development of novel, orally available, first-in-class or best-in-class therapies for the treatment of metabolic and endocrine disorders.  Viking'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 novel, orally available, small molecule selective thyroid hormone receptor beta agonist for the treatment of lipid and metabolic disorders, which is currently being evaluated in a Phase 2b study for the treatment of biopsy-confirmed non-alcoholic steatohepatitis (NASH) and fibrosis.  In a Phase 2 trial for the treatment of non-alcoholic fatty liver disease (NAFLD) and elevated LDL-C, patients who received VK2809 demonstrated statistically significant reductions in LDL-C and liver fat content compared with patients who received placebo.  The company is also developing VK0214, a novel, orally available, small molecule selective thyroid hormone receptor beta agonist for the potential treatment of X-linked adrenoleukodystrophy (X-ALD).  VK0214 is currently being evaluated in a Phase 1b clinical trial in patients with the adrenomyeloneuropathy (AMN) form of X-ALD.  The company holds exclusive worldwide rights to a portfolio of five therapeutic programs, including those noted above, which are based on small molecules licensed from Ligand Pharmaceuticals Incorporated.

For more information about Viking Therapeutics, please visit www.vikingtherapeutics.com. Follow Viking on Twitter @Viking_VKTX.

Forward-Looking Statements
This press release contains forward-looking statements regarding Viking Therapeutics, Inc., under the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995, including statements about Viking's expectations regarding its development activities and plans regarding VK0214 and its prospects and the timing for commencing Viking's Phase 1b study of VK0214 in patients with X-ALD. Forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially and adversely 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 and VK0214; risks that prior clinical and preclinical results may not be replicated; risks regarding regulatory requirements; risks related to the COVID-19 pandemic; and other risks that are described in Viking's most recent periodic reports filed with the Securities and Exchange Commission, including Viking's Annual Report on Form 10-K for the year ended December 31, 2020, and subsequent Quarterly Reports on Form 10-Q, including the risk factors set forth in those filings. These forward-looking statements speak only as of the date hereof.  Viking disclaims any obligation to update these forward-looking statements except as required by law.

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SOURCE Viking Therapeutics, Inc.