The Rising Influence of Rising Affluence

[biotech jim]

My thoughts on MDGL vs the VKTX data reported this morning, though I cannot in a brief post, review all the stuff here that I know. Having worked in the business, I pay attention to liver metabolism and tox issues, more so than most analysts and investors. Sometime it is not good to know too much, as risk comes in many forms. I have held both MDGL and VKTX stocks in the past. I continue to hold MDGL, but not VKTX.

Here is a note I sent to some colleagues early this morning, some 90 min before market opening.

"VKTX data looks very good as far as it is reported.

Outstanding comments/questions for VKTX CC

1. How does long term animal tox data fare for VKTX compound? Only short term animal tox data reported by VKTX? How much tox data in 2 species is at hand for a 36 week study in NASH patients?

2. VKTX data not achieved in NASH patients, but in less severe NAFLD patients. Due to a more compromised liver, risk (esp ALT/AST) could be much greater. Safety not derisked.

3. Due to reactive metabolite species for VKTX, can company comment on the metabolite being a CYP P450 3A4 covalent inhibitor? Data for similar reactive species in literature shows this could be a major problem for concomitant drugs to be source for drug-drug interaction. (Note that 3A4 is the source for the reactive metabolite.)

4. Why do you think the Baker Bros bought MDGL huge this past Q? Do you think they had extensive consultation on the chemical nature of the 2 liver specific THbeta agonists from the 2 companies?

Then, Came the conference call this morning. I will stop at the above comments for now, but will link/copy Miljenko's comments from SI. Miljenko is a mechanism and VKTX bull, but in full disclosure we had discussions of metabolism and tox over the past many months. He is a process chemist with a critical eye to science, as all PhD trainees are supposed to have. Having been in the business and knowing what Q's to ask is part of that 'knowing too much". I may comment more, if Q's arise. Pretty busy these days.

Miljenko's CC comments

RE: VKTX
Just finished CC (I like to sleep longer this days, )

While I am gratified that VK2809 did have positive primary and secondary, and most importantly NO safety (so far NO) issue at 10 mg/day dose (I care less for QOD regime, maybe they can introduce 5 mg/day dose???),....there is several points that make me MAD! IS THERE ANY BIO-COMPANY THAT CAN REPORT STRAIT FORWARD RESULTS???

First, when company switch the importance of the end-points (those are pHeHF subjects , not NASH) and exclude arm as trial progress without reporting,...I PISS ON THEM!

Second, when company report numbers for secondary and no numbers for primary (15-40%LDLc reduction relative to placebo is only range, and not mean/median),...I PISS ON THEM!

Third, when company is talking too-much about option to scale down dose,...THAN I ASK: "WHAT IS FUCKING WRONG WITH CURRENT DOSE/REGIMEN???"

Looking forward to full data presentation.

I was slow this morning, so full position on VKTX is still in place.