Biotech Values

[Mufaso]

SGMT/MDGL/VKTX NASH comparison of results for Fibrosis reduction and Liver Fat reduction.

After seeing the market’s positive reaction to Sagimet’s ph2b results last week (which is now muted some after the secondary of approx. $112 million (done at $12.50 PPS), I put together a comparison of results between the NASH drugs by SGMT/MDGL/VKTX for my own use and have decided to share that analysis to invite comments/spark discussion.

I picked SGMT for the analysis because based upon positive market reaction to SGMT data. Also, I was curious how SGMT's denifanstat, a fatty acid synthase (FASN) inhibitor compared to MDGL resmetirom a TRß agonist. MGDL was picked because most analysts think will get approval in March and it is years ahead of everyone else. I added VKTX VK2809, another TRß agonist as they will report 52 week biopsy confirmed fibrosis data very soon (MGMT said "1H24" but I believe they will likely report data early in q2 or possibly even q1- best guess is early April 24. Additionally, all of these companies had done or are doing studies for a patient population that was similar (F2/F3 Biopsy confirmed Nash, study length of 52 weeks) making an rudimentary comparison possible.

With the usual disclaimer that you can't compare studies from different companies at different times, comparisons are inevitable. I have put my comparison at the end of this post and have summarized my observations first. Feel free to take issue with any of the info presented or how it is presented. Anyone who wants to research compounds from other companies on the criteria presented (or new criteria) should feel free to post that data. (e.g. - 89BIO, AKRO, ALT all have compounds that merit attention in the NASH space).

Summary of my opinion observations: ( Note: Full disclosure - I have significant long positions in VKTX and MDGL and no position in SGMT.) :

• For the key metric of Fibrosis improvement, Sagimet’s Denifanstat appears to be competitive with MDGL’s resmetirom having about the same performance for Fibrosis improvement (as well as for NAS resolution). It isn’t as good from a liver fat reduction but does offer decent efficacy there. Given it has a different MOA and phase 3 results may show other benefits/efficacy it certainly looks like it will proceed to ph3. Is denifanstat a resmetirom beater given resmetirom will have a 1st mover advantage of several years? Probably not but it could have a place in a large NASH market. We won't have an indication of V2809 fibrosis performance until they report 52 week data from their 2B study so the jury is out there.
  
  
• With regard to safety and tolerability, I did not include measurable numbers as it probably better to wait for phase 3 to do comparisons. My early analysis just looking at prior studies is that SGMT’s drug bests MDGL’s drug and VKTX’s VK2809 is better than both of the aforementioned in this area.
  
  
• Liver fat% reduction is known to be a predictor of NAS resolution and fibrosis improvement for TRß agonists. I contend the same can’t be said for other MOA’s yet such as those that are GLP1 based in the area of fibrosis improvement. (https://www.nature.com/articles/s41591-023-02603-1#:~:text=Reduction%20in%20hepatic%20fat%20of,reported%20outcomes%20(PROs)14.) Yes, GLP1's have shown they can provide NAS resolution and likely can prevent fibrosis to some degree but once present, Fibrosis improvement has proven elusive for the GLP based class of drugs. We will see if this changes as more data gets released later this year.
  
  
• Both 2.5mg QD and 10MG QOD doses were included for VK2809. Assuming VK2809 proceeds to Ph3, I expect a 5 mg QD dose to be studied then.
  
  
• VKTX’s VK2809 has yet to report from their 52week Voyage phase 2B study on NAS resolution and Fibrosis performance. They reported 12 week top line results on May 16th , 2023. Adding 36 weeks plus 4 (to account for more complexity in analyzing liver biopsies) for a total of 40 added weeks yields Feb 20th, 2024 but given VKTX’s size and everything else they have going on, management has been conservative in estimating readout dates and hence the 1st half 2024 commit for data readout. Best guess is March April for results readout on VK2809 Fibosis data. Since VKTX VK2809 Liver fat data has consistently outperformed resmetirom liver fat reduction data by a wide margin, I expect it to outperform resmetirom liver fibrosis reduction data also by a considerable margin. Given the large short position in VKTX that is currently 15.8% of float, an outsized share appreciation is likely IMO if good fibrosis data with no safety concerns is released on VK2809 1st half 2024.

Here is the admittedly flawed but potentially informative comparison (Green is best, Yellow is second best, Red is 3rd in this comparison):