"His point was pretty simple and straight forward, 1202 should have activities at 200mg based on IC90 delta inhibition - he didn't think it should compare to others' Cmax in that chart - but it doesn't, it requires 3 folds increase of dose to 800mg to get response. Is it just PK issue or is it something else?"
OK, I get that, thanks. But if that's his only point, his mysterious calculation wrt Cmax and Ctrough of the drugs at issue that seemed to include MW - but which calculation he didn't supply - would seem to be a red herring. It seems to me he wouldn't need that mumbo jumbo to make the point as you state it.
I think maybe we don't completely understand the biology here, either. Certain B-cell malignancies that have shown in vitro susceptibility to delta isoform inhibition haven't given up a response to all delta isoform inhibitors. Chew points to 1202's failings there - perhaps prematurely - but not to Idelasib's. So it does appear to me he could be talking his book a bit here.
I'd have to dig around to see if any of them work against AML, for example.
"The company is trying micronized formulation to increase exposure, so I assume it thought it was PK issue. If it is just PK issue, it is not unique, for example CLVS CO1686 original formulation had PK issue, new formulation works fine but increased exposure produced more AEs as well which I thought was very mild for NSCLC.?"
Right, so it seems we have to wait for data to mature. Upcoming 1202 presentations this winter are starting to look more binary. Tempted to bail at a reasonable profit, and watch. Breath sigh of relief if bad, buy the next pullback if good.
Anyhow, I agree on your point re emotions. Appreciate your help in cutting through them here.
Regards, RockRat
