[Discussion] small community, high signal, let us keep it that way
small community, high signal, let us keep it that way. Change my mind, genuinely — I have no stake in being right about this. Nothing containing this compound is approved anywhere. Research-use-only material is not approved for human use. Imaging-derived liver fat fraction is a surrogate. It correlates with histology…
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.
What does the tolerability table say at that dose?
the titration in the trials was slow and deliberate
biopsy-confirmed is not the same as imaging-suggested
Histological endpoints in this field are scored on biopsy: resolution of steatohepatitis without worsening of fibrosis, or improvement in fibrosis without worsening of steatohepatitis. Both are harder to achieve and to interpret than an imaging surrogate.
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.
What does the tolerability table say at that dose?
This is the framing the board needs. It is a hepatic programme first.
Disagree — that is a weight endpoint from a different programme and you are quoting it in a hepatic context.