Replies to post #121187 on Biotech Values

[DewDiligence]

If you can knock down the pathway from the outset, there is less chance of resistance developing. Preclinically, '113 is a way better drug than Crizotinib - more potent by a factor of 10, much more selective against wild-type ALK and having a factor of 10 better therapeutic index.

That’s all well and good, but it doesn’t speak to the point I’m discussing about the size of the addressable market for 113 in the second-line setting, specifically.

[NP1986]

That might stem from the fact that Crizotinib isn't a great ALK-inhibitor in the first place (it was not in fact specifically developed as one - it's actually a dual cMET/ALK drug

This actually raises the question as to whether the high response rates with crizotinib are down to the fact that it inhibits more than one pathway. We know that the MET pathway is a promising target in lung cancer (see Roche's MetMAB and ArQule's ARQ197). The preclinical data on ALK inhibition looks promising to me - but it I'm not convinced that a drug that targets only ALK will be efficacious in the clinic. Crizotinib's high response rates look very promising, but I would be more convinced of its potential if it shows similar response rates in the randomized trial.

I am an ARIA long, but at the moment I'm more bullish about ponatinib than '113. I'd be a lot more optimistic about '113 if it had Phase I data demonstrating safety and at least some evidence of efficacy in actual patients. It may turn out that it has a different side effect profile from crizotinib, and if it is a favorable one, that would open up a niche for patients who are intolerant to crizotinib - assuming crizotinib and '113 both prove to be equally efficacious.