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Re: masterlongevity post# 133204

Sunday, 12/18/2011 2:50:55 AM

Sunday, December 18, 2011 2:50:55 AM

Post# of 257439

Pfizer discontinued their gsi program

That was my guess eventhough I didn't see any official PR, the prolong silence makes it pretty much certain and as speculated in #msg-70004168, begacestat was discontinued for the same reasons semagacestat failed. On Bristol's avagacestat, I posted there that data from phase II suggest to me it still suffers from the same malady - selectivity is not good enough i.e. margin between lowering Aß42 and affecting Notch is too small, so risk of Notch related AEs is still too high, even at lower dose in which efficacy is probably too weak. However, I don't think the GSI class is dead yet, perhaps a more selective gamma secretase inhibitor or modulator will demonstrate a better profile.

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