[Discussion] MASH is doing more work than we give it credit for
MASH is doing more work than we give it credit for. Change my mind, genuinely — I have no stake in being right about this.
Spent an evening on the histology scoring system and understood the trial literature far better afterwards.
Sent a vial to PeptideMeter because there was nothing on file. 99.2% against a claimed 99.0%. First entry for this compound in my own log.
The escalation schedules in the published protocols are slow and deliberate, and the tolerability tables show why. That is a description of the trials rather than a suggestion for anybody.
Would rather be corrected in public than confident in private.
best — the order this archive was captured in
It is a dual agonist at the GLP-1 and glucagon receptors. The glucagon arm is associated with increased energy expenditure and with effects on hepatic fat, which is why the development programme is oriented towards liver disease.
Which endpoint — histological response, fibrosis improvement, or fat fraction?
Assumed the weight numbers were the point and was corrected. They are secondary to what this is being developed for.
Went slowly because everything published describes a deliberate escalation. That is the extent of what I will say about it.
Asked here what the difference was between the imaging and biopsy endpoints and got a genuinely excellent answer.
Yes — histological endpoints are a far harder bar than the surrogate measures people are used to quoting.
Agreed. The hepatic programme is the point of this compound and the weight discussion is a side effect of the side effect.
Independent result logged. There are almost none for this compound, so it is genuinely valuable.
Not convinced. Imaging-based fat fraction is not the same as a histological response and the paper is explicit about that.
a liver endpoint is not a weight endpoint with better marketing
Read the phase 2 hepatic paper properly and the endpoint definitions were more interesting than the headline response rate.
Independent purity results for this compound are very sparse across the whole site, which means any impression about consistency is built on almost nothing.
Yes — nothing containing this is approved anywhere, which is the first fact and usually the last one mentioned.
Bought small because the evidence base is early. That is the only defensible position I could construct.
glucagon agonism and energy expenditure is the mechanistic thread
Cosigning on the glucagon arm. It is the mechanistic thread that connects the hepatic and the metabolic effects.
That is an escalation schedule for an unapproved compound and this board does not host those.
Careful with the mechanism claim. Glucagon agonism is plausible as an explanation and it has not been isolated as the operative one.
What does the tolerability table say at that dose?
Looked for independent results across this whole site and found almost none. Worth knowing before forming an opinion.
- 1Read the phase 2 hepatic paper properly and the endpoint definitions were…8 comments in this branch · started by u/laila_yilmaz