Replies to post #208231 on Biotech Values

[dewophile]

My only comment on the paper is that I think the project gives too much of a pass to, for instance the CD-47 replication study which failed because all the animals had some regressions, even those on naked IGg

I don't think the replication study should be dismissed. There do seem to be issues with this particular model though if 50% of the tumors were essentially cured with placebo - and that applies to the original study as well which has to be interpreted through this same lens. I do continue to believe that the fact CELG and NVS are invested in this space adds far more credibility to at least the preclinical efficacy of the target than one failed replication study in what seems like a problematic preclinical model (there is a reason why the overwhelming majority of the preclinical data for CD47 uses a different mouse model, but is itself limited in that mouse CD47 does not cross react w human CD47 so efforts to test mouse drug in mouse tumors were attempted)

as some people on this board know, I've been skeptical of TRIL for a while. Too many companies pursuing what is, at best, a weak target IMO.

The fact CD47 is expressed widely definitely makes it a riskier target. However, aside from hematological tox, even high doses of drug have never shown any other toxicities in monkeys. Skeptics argue that the MOA is simply via opsonization of CD47 bearing cells, but then why aren't hepatocytes or the many other normal cells being killed off as well? Something more IMO is going on here in terms of the MOA and if the heme tox issues can be managed to me there seems to be a window for efficacy

(I started a bear case post over the Xmas break, but felt bad about posting it)

please please post critiques - it is invaluable. companies are already presenting the bull cases for their drugs so pointing out the flaws is more important in a setting like this IMO