Replies to post #7782 on Ariad Pharmaceuticals Inc fka ARIA

[DonShimoda]

Not sure I understand your point...are you questioning targeted gene therapies in general or Ariad's ALK inhibitor specifically? As far as your comment that "the idea that there is a whole class of compounds whose path through the clinic is well predicted by in vitro or mouse models seems, well, rather optimistic", well, welcome to the 21st century.

Take CML, for example, which is caused by the BCR-ABL gene. The ABL gene is a signalling molecule and plays an important role in cell proliferation, however, in CML patients the ABL gene is always active and causes the continuous production of cml cells. It is this activity (and the various mutations that may result) which drugs like ponatinib are designed to target and, in general, if they work in vitro there is a much higher likelihood that they will also work in the clinic (as compared to drugs that do not target a specific gene or protein).

[BTH]

Its very diferent IMO than a lot of those petri dish models of other targets where you get, say, a VEGF or EGFR drug which is a targeted drug, however, not in the same way the BCR-abl or ALK (Crizotinib) is directly, absolutely target at a gene which specifically causes a mutation which in turn develops the cancer. GDC449 (CRIS) Hh drug is the same thing....like Ponatinib, and like Crizotinib, 449 specifically targets a gene which is directly responsible for mutations which cause the cancer, in a couple very specific cancers. These drugs, literally, have found the needle in the haystack.

mTORs, VEGF drugs etc., are IMO, just basically next-gen chemo drugs with not so great side-effects, and a targeted at the cancer, but not highly targeting the CAUSE of the cancer..ie, the mutation in the protein which absolutely is the reason for the cancer.

this is why i believe 113 will be successful in the clinic. this is the way, going forward, all oncology drugs should be built.