Replies to post #246515 on Biotech Values

[Mufaso]

Whalatane- While the studies between VKTX and ENTB are not directly comparable, I made some observations below based on a short review of the ENTB announcement. Be aware I have not studied ENTB’s pegozafermin drug in detail. I welcome additional thoughts on this topic.

-VKTX’s VK2809 has only read out in a small short Phase 2a NAFLD study back in 2018. ENTB has now read out in in a Phase 2b biopsy confirmed NASH study. The main significance is that the patient population of NASH is presumably more difficult to treat as the liver is inflamed/has fibrosis.

-Topline Data from VKTX’s NAFLD study was at 12 weeks while ENTB was 24weeks. Dosing for VKTX was oral QD or QOD while for ENTB was ORAL every week or every two weeks. For VKTX using the median liver fat content by MRI-PDFF they the reductions were -57% for 10mg QOD (n=15), - 60% for 10mg QD (n=16) and -9% for placebo (n=14). ENTB, again using the liver fat content by MRI-PDFF the reductions were -52% for 30mg QW (n= 66), -54% for 44mg Q2W (n= 51) and for placebo -14% (n= 61). The data is roughly the same for both drugs in this metric but the Viking drug got these results in a shorter time frame while the ENTB data was from a tougher to treat population.

-ENTB had five (5) SAE’s leading to study discontinuation that were related to the drug. VKTX has had no study discontinuations related to their drug in any study they have done where they have tested the drug which has been dosed in 300+ to date. (VKTX did have one SAE discontinuation, but that was related to a gallstone event in a patient with a history of gallstones.)

-VKTX’s MOA is the same as MDGL’s which has been proven to work in NASH in Ph3. The FDA has telegraphed that Resmetirom be approved by granting Breakthrough status to it. If VK2809 proves effective/safe in it is likely approvable after the obligatory pivotal trials. To me, this partially de-risks VK2809.

The jury is still out on both drugs. ENTB’s pegozafermin appears to be a good drug and the NASH market is huge likely supporting multiple drugs with different MOA’s. Vikings VK2809 has the potential to be a best in class NASH late entrant from a safety and efficacy perspective.

We will have a lot more data once Vikings phase 2b data becomes available and likely a much better comparison between VK2809 and pegozafermin (and idea how VK2809 compares to Resmetirom which is my main concern.

[Mufaso]

Whaltane- Regarding the VK2809 placebo response in Viking’s 2a study from 2018 , I thought I would comment on this separately. At 12 weeks for the metric of participants who achieved greater than 30% reduction in liver fat, the response was 18.8% in the placebo arm. This compared to the dosed arms where 83.3% had a reduction of greater than 30% of liver fat. (p=<0.01).

I’m not unduly concerned by this seemly high placebo response. The VK2809 2a Study was small (N=14 in the placebo arm) so one patient responder made a big difference. Others including ENTB and MDGL have had low double digit % placebo responses.

There is other data that is more meaningful to me. There was an EASL presentation from 2020 (the 2020 data you were referring to?) that presented on VK2809 16-week data after dosing stopped at 12 weeks. Below are some quotes from the Viking 4th Q 2020 press release. I bolded some things that were particularly interesting that suggest to me that VK2809 will be successful in NASH:

Additionally, at Week 16, 70.4% of all VK2809-treated patients maintained a response, defined as experiencing ≥ 30% relative reduction from baseline in liver fat content (p=0.0083). Of note, 100% of patients receiving 5 mg daily doses of VK2809 demonstrated a response at Week 16.

The presentation also highlighted additional Week 12 results that demonstrated significant reductions in liver fat content among patients receiving VK2809 as compared to placebo regardless of the presence of common risk factors for NASH, including baseline levels of alanine aminotransferase (ALT) above the upper limit of normal (ALT > xULN), body mass index (BMI) ≥ 30, hypertension and Hispanic ethnicity.