Biotech Values

[iwfal]

ISIS

Highly implausible, IMO; hence, the results in one of the two ISIS-FXIRx trial arms were presumably a fluke.

FYI - the only published animal model dose response data set I can find for FXIRx with useable fidelity* also shows important non-linearity. That said, it is animal model data (with all the caveats) and the animal numbers are small. Nonetheless the non-linearity is strong enough to look both real and potent even with small numbers.

Also, there is literature pre-dating ISIS's work that speculates a key MOA of FXI is allowing positive feedback on clot size - i.e. in the presence of FXI the bigger the clot the larger/faster it grows (obviously at some point there must be a counter factor - but I haven't bumped into speculation on what that is). And inhibition of FXI would thus mitigate/prevent that positive feedback. Feedback loops result in very non-linear behavior.

*There are other dose response data sets - but they consist of 2 or 3 doses (i.e. too few) and thus cannot allow a non-linearity to be seen.

Restatement of my position so no one misinterprets the above:

1) I think there is a very good chance that in fact the VTE rate for FXIRx is much lower than Enox - but not necessarily 7x better or 3x better or ... . (I have little opinion about bleeds other than a good chance it to be comparable to Enox or better)

2) Nota bene: I think it is inherently problematic to compare the efficacy of two different drugs with *very* different time constants (relative to the needed treatment duration).