Ariad Pharmaceuticals Inc fka ARIA

[jaybe]

Regarding Bafetinib and the BBB...

The PLOS study states a significant "fraction" of INNO-406 crosses the blood-brain barrier, reaching brain concentrations adequate for suppression of Bcr-Abl+ cells. So to be fair the PLOS study might raise Bafetinib's effective crossing of the BBB from 10% to 35% (see figure 1).

Most of what the PLOS study has to say about Bafetinib crossing the BBB was shown in a 2007 study which concluded "the concentration of both INNO-406 and imatinib mesylate in the brain was approximately 10% of the corresponding plasma concentration."

http://bloodjournal.hematologylibrary.org/content/109/1/306.full.pdf


In any case I hope my main point was clear, all other ABL-TKI's cross the BBB in fractions of plasma concentrations, Pona crosses in multiples. Meaning we can dial back an oral dose, not increase, require a combo, or use IV.

By the way Bafetinib was designed as 2nd gen BCR/ABL for PH+CML to be more effective than imatinib and some of its mutations, but it has been in the clinic since 2005 still with no approval in leukemia. I think they missed their window for 2nd gen resistance in CML and now Pona has shut the door on the way out.