Biotech Values

[mcbio]

I don't know the potentcy of Letaris but it doesn't bind to the B nor does (did) Encysives drug Thelin (Sitaxentan) which was pulled for safety (I forget what tox but sure could easily google). I heard Martin say its the safest ETA well 1 was pulled and the biggest selling one has a black box so everything is relative smile.

I don't know enough about the disease but what level of reduction is clinically meaningful? Having a letter from someone at FDA may be nice but for ETA's we've seen SPA's meet and not get approval (Encysive first 2 times around). And why doesn't/didn't GSK/Pfizer/Gilead pursue? On twitter he said that Actelion told him Tracleer wouldn't work. His theory is because it binds to A&B which could very well be (he certainly knows a lot more about the disease then me) but doesn't change the case for others. I think there may have been a few other ETA's developed too (none approved that I can think of) so its not as if its an empty field.

Just want to follow up on this prior post from you on RTRX and not sure if you caught my reply to your post in #msg-83250954 . As you know, the big advantage RTRX is claiming for its drug for FSGS is that it's selective for ET-A and doesn't bind to ET-B, which purportedly confers a big safety benefit (don't think efficacy is really the question here). You state that Letairis (ambrisentan) and sitaxsentan also don't bind to ET-B whereas RTRX claims that zibotentan is the only other drug advanced into the clinic that doesn't bind ET-B. It's obviously important to know which is correct.

Check out the most current presentation on RTRX's Web site at: http://retrophin.com/retrophin/News/Retrophin%20Feb%2012%202013%20Presentation . In particular, slide 15 shows potency of all ERAs and affinity to ET-B, among other things. You'll see that both ambrisentan and sitaxsentan, along with all others except RTRX's RE-021 and zibotentan (slide says zibosentan but I think that's an error), have ET-B affinity in the nanomolar range whereas both RE-021 and zibotentan have affinity in the micromolar range. So, presumably this is further support for what RTRX is doing though it would be interesting to know why AZN isn't pursuing further development of zibotentan in, say, FSGS. (Their failed Phase 3 trial was apparently in CRPC.)