It is not always perfectly clear what Peter Mueller says in a Q&A session, but it has been perfectly clear because he stated more than once, that the preferred objective is to develope VX-661, not merely as a better alternative to VX-809, but as a component of a truly second generation drug candidate to repair all F508del CFTR. If you compare VX-809 as a single hit in baseball, 661 belongs to a class of triple-base hit that brings in a runner, not because 661 is so good by itself, but because it can be combined with other correctors which may debut in the near future.
A single CFTR protein has at least two NBDs (nucleotide binding domains), but the 508 mutation is defective in the first two NBDs. So, to repair 508 CFTR fully it may take more than one corrector. This is the insight of van Goor. It is much much harder to find a right molecular pair to repair 508 than to screen for a single molecule. There are millions of drug candidates one can screen to find singles, but it takes screening of multiple trillion molecular pairs to find right duo combo drugs.(because if you had 10 single candidates, there would be 10x9/2 pairs to test)
Sorry, what I was referring to was the timeframe for a new combined drug (661 + Kalydeco + additional correctors) which would have a dramatic effect on the health of DD508 CF patients, to come to market.
Thanks third. That makes a lot of sense. I was surprised because this was first time they seemed to say 661 is the corrector for combo correctors...I assumed it would also be 809 and others. But that to me is hopeful because that must mean they have some other correctors that they know in vitro will work with 661. They mentioned having in vitro multiple correctors working as well as 770 does for 551, but knowing it is with 661 is exciting because that's seems to me that they have a theory for perfecting the corrector combos close in hand. Al always appreciate you insights!