Replies to post #117669 on Biotech Values

[DewDiligence]

…higher-than-expected breakthrough data with VRUS's first- generation nuke [RG7128] as stand alone with SOC somewhat lowers my expectation for the 2-nuke combo achieving total success without at least some component of current SOC...

Respectfully, I don’t think RG7128 is a harbinger for what we can expect from the latest-generation HCV nukes. Although these drugs nominally belong to the same class, they are in fact radically different: RG7128 is a prodrug of a nuclesoside (PSI-6130) that has to perform the first phosphorylation step in vivo, while the latest-generation nukes are prodrugs of monophosphate nucleotides in which the first phosphate group is assembled ex vivo. This makes all the difference in the world, IMO.

[iwfal]

i think we're likely to see combos of 3DAAs within a year, which very well may yeild SVRs as good as or better than current treatments

Thoughts:

Agree with first part of sentence, that we will see combo of 3DAAs-only (no SOC) within a year, but disagree the implication that those trials will be out through SVR unless it is BMY pairing. I suspect they will want to do a little more walking (i.e. successful 2 drug combos thru SVR first - which BMY has, but no other company has) before running.

PS One of the VRUS drugs claims to require three mutations in order to create resistance. Do you know number of mutations required to create resistance for BMY NS5A drug? Also, any thoughts on what other factors are at play in breakthrough - e.g. creating mutations in something that is fragile is harder than creating mutations in something that is more flexible and NS5A, by reputation, is more fragile (i.e. a very high percentage of changes are lethal to the virus' ability to replicate).