Replies to post #122696 on Biotech Values

[biomaven0]

The Pfizer drug looks marginal against T790M.

Afatinib is quite potent against T790M, but it is even more potent against WT EGFR (by a factor of 20):

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2748240/?tool=pubmed

(See Table 1)

Given it is an irreversible inhibitor, you are going to completely wipe out WT EGFR activity before you have any impact on the mutation. So who knows what that might do in the way of tox. I also don't understand why adding Cetuximab on top of Afatinib seemed to improve results (see ASCO presentation).

Given the T790M mutation seems to be present event before Tarceva is given (so here the TKI just selects for the pre-existing resistant strain), one idea might be to first treat with '113 and then add Tarceva if it turns out you do need to inhibit WT.

Peter

[DewDiligence]

I was referring to PF-00299804...was under the impression that it is still in early or mid stage trials.

It’s already well into phase-3—please see #msg-66216526.