Sign up to SCR Digest, our FREE weekly newsletter, and receive our Notes emailed directly to you.
Email Address *
First Name
Mailing Lists *




















































































































VKTX: Poster Presentations on VK2809 and VK0214 Highlight Positive Preclinical Data for Both Compounds

10/26/2017
By David Bautz, PhD

NASDAQ:VKTX

Business Update

Full Data Set for VK2809 in Diet-Induced NASH Model Presented at AASLD

On October 24, 2017, Viking Therapeutics, Inc. (NASDAQ:VKTX) announced the presentation of results from a study of VK2809 in an in vivo model of non-alcoholic steatohepatitis (NASH). Statistically significant improvements in a number of key measures were seen during the study and gene expression analysis showed statistically significant changes in expression for genes associated with the development and progression of NASH.

Male wild-type C57BL/6J mice were maintained on a high fat diet for 37 weeks prior to initiation of the study. Liver biopsies were performed and the mice were stratified according to steatosis score and fibrosis stage. Treatment with once daily vehicle control, 30 mg/kg elafibranor (active control), or 10 mg/kg VK2809 continued for eight weeks while continuing the high fat diet. At the end of the study, plasma and liver lipids, liver steatosis, collagen, fibrosis, and hydroxyproline content as well as NAFLD activity score (NAS) were all evaluated. RNAseq analysis was performed on liver samples. An outline of the study is provided below.

Similar to what was seen in previous studies of VK2809, there was a significant decrease in plasma triglycerides (-50%) and plasma cholesterol (-73%) for mice treated with VK2809 compared to vehicle control. There was also a statistically significant decrease in plasma cholesterol for mice treated with VK2809 compared to elafibranor. There was no significant difference in plasma ALT levels for VK2809-treated mice. 

In addition, levels of liver triglycerides (-70%), liver total cholesterol (-65%) and liver total lipid content (-80%) were all significantly lower in mice treated with VK2809 compared to vehicle control mice. The difference in liver triglycerides and liver cholesterol was also significant between VK2809- and elafibranor-treated mice. 

There was 50% less liver fibrosis in VK2809-treated mice compared to vehicle control-treated mice, as assessed by quantitative histological assessment of picrosirius red stain. The following figures show the level of fibrosis (red areas) in liver sections after eight weeks of treatment. 

Lastly, the changes seen in lipid content and fibrosis translated to improvements in the NAFLD Activity Score (NAS) for mice treated with both VK2809 and elafibranor.

VK0214 Shows Promise in Treating X-ALD

On Oct. 23, 2017, Viking announced results from a 25-week proof-of-concept study of VK0214 in an in vivo model of X-linked adrenoleukodystrophy (X-ALD) were presented at the 87th Annual Meeting of the American Thyroid Association. Treatment with VK0214 led to statistically significant reductions in plasma levels of very long chain fatty acids (VLCFAs) compared to vehicle controls. There was also a reduction seen in brain and spinal cord VLCFAs, an exciting observation as those tissues are especially prone to degeneration in X-ALD.

The study used the Abcd1 knock-out (KO) mouse model, which while not displaying the inflammatory characteristics of the more severe forms of X-ALD, does recapitulate a phenotype similar to those with adrenomyeloneuropathy (AMN), the less severe form of X-ALD. As shown in the following figure, Abcd1-/- mice have elevated levels of VLCFAs compared to wildtype mice. 

Patients with X-ALD have a mutation(s) in the ABCD1 gene that renders its product, the adrenoleukodystrophy protein (ALDP), non-functional. ALDP is responsible for transporting VLCFAs into peroxisomes for degradation, thus without proper ALDP function the VLCFAs accumulate to toxic levels. The theory behind using VK0214 to treat X-ALD is that it induces the expression of ALDR (encoded by the ABCD2 gene), which is also a VLCFA transporter, thus compensating for the loss of ALDP. 

The following charts show the level of VLCFAs over the course of the 25-week study. Treatment with VK0214 results in a dramatic decrease in VLCFA levels only six weeks after initiating treatment, and this decline is held relatively steady through the entire 25-week treatment period. 

The following table shows that the greatest reductions in VLCFA levels were for shorter chain lengths, as C20:0, C22:0, and C24:0 VLCFAs showed progressive declines from week 12 to week 25, while levels of C26:0 were similar between week 12 and week 25.

Perhaps most importantly, tissue levels of VLCFAs were shown to be lower in mice treated with VK0214 compared to mice treated with vehicle control. The following figure shows there was a statistically significant decrease in the level of C26:0 in both the liver and spinal cord. In addition, in the brain there was a statistically significant decrease in C20:0 and an 11% decrease in C26:0 that trended toward significance (P=0.07).

Lastly, as would be expected, and supporting the theory behind the use of VK0214 for treating X-ALD, there was a significant increase in the expression of the Abcd2 gene in both the liver and the cortex. 

Conclusion

The data presented by Viking for both VK2809 and VK0214 provides nice support to each program. For VK2809, it is clear that the drug is highly effective at altering plasma lipid levels and it is encouraging to see a change in liver lipid levels as well. The fact that there was an improvement in fibrosis and NAS is also important, as one criticism of using a TRβ agonist for NASH was that it would only affect lipid levels and not fibrosis, which is clearly not the case. We will be very interested to review the data from the Phase 2 study of VK2809 in patients with hepatic steatosis/NAFLD, which we anticipate in the first half of 2018. 

For VK0214, the theory behind its potential use in X-ALD has been validated through the increased expression of the Abcd2 gene in Abcd1-/- mice along with significantly decreased levels of VLCFAs in both plasma and tissue. These data fully support the continued development of VK0214 and a proof-of-concept study in humans, which we anticipate initiating in 2018.  

Viking’s stock price has had a nice run over the past couple of months, however we continue to believe the company is undervalued and that there is considerable upside left for investors heading into the release of Phase 2 data for VK5211 in the fourth quarter of 2017 and VK2809 in the first half of 2018. Our current valuation is $7.00 per share.   

READ THE FULL RESEARCH REPORT HERE

SUBSCRIBE TO ZACKS SMALL CAP RESEARCH to receive our articles and reports emailed directly to you each morning. Please visit our website for additional information on Zacks SCR and to view our disclaimer.

 
User ID:
Password:
Remember my ID: