Replies to post #61712 on Biotech Values

[curiousgeorgie8]

Anybody know other players in the sirtuins field besides Elixir Pharma?

[microcapfun]

>>GSK Acquires SIRT at 85% Premium to Market<<

Sirna acquired for $1.1B, SIRT for $720M. I suggest that Big Pharma is no longer only interested in companies which have (at least) established P2b proof-of-principle results in man. They are also interested in landgrabbing IP and expertise in wide-open new areas which *might* result in multi-billion dollar cash flow streams 10-20 years from now.

So what follows the pattern of Sirna and Sirtris?

How about Geron for embryonic stem cells??

micro

[genisi]

The Sirtris Compounds: Worthless? Really?

http://pipeline.corante.com/archives/2010/01/12/the_sirtris_compounds_worthless_really.php

Posted by Derek

As followers of the drug industry know, GlaxoSmithKline famously paid $720 million to buy Sirtris Pharmaceuticals in 2008. Sirtris is the most high-profile shop working on sirtuins and resveratrol-like pharmacology, which subject has received a massive amount of press (some accurate, some scrambled). I've been following the story with interest, since the literature has me convinced that the aging process can indeed be modified in a number of model organisms, which makes me think that it could be in humans as well. And I also feel sure that advances in this area could lead to many profound medical, social, and economic effects. (GSK, though, is going after diabetes first with the Sirtris deal, I should add - among other reasons, the FDA has no regulatory framework whatsoever for an antigeronic, if I can coin a word.)

But whatever the state of the anti-aging field, doubts have crept in about the wisdom of the Sirtris purchase. Last fall, a group at Amgen published a study suggesting that some of the SIRT1/resveratrol connections might be due an an experimental artifact caused by a particular fluorescent peptide. Now a group at Pfizer has piled on in the Journal of Biological Chemistry. They're looking over resveratrol and a series of sirtuin activators described by the Sirtris group in Nature.

And unfortunately, they also find trouble due to fluorogenic peptides. The TAMRA fluorophore on their peptide substrates seems to pervert the assay. While the Sirtris compounds looked like activators initially, switching to the native peptide substrates showed them to be worthless. Further study (calorimetry) showed that the activator compounds bind to a complex of SIRT1 and the fluorescent peptide substrate, but not to SIRT1 itself (or in the presence of native substrate without the fluorogenic group). That's not good.

But worse is to come:

"Despite a lack of evidence for the Sirtris series of compounds as direct SIRT1 activators, we investigated whether the in vivo efficacy demonstrated by SRT1720 in several rodent models diabetes could be validated and attributed to indirect activation of SIRT1. We therefore attempted to reproduce the in vivo efficacy for SRT1720 in mouse models of type 2 diabetes previously shown. . ."

That word "attempted" should tell you what comes next. The reported high dose of the compound (100 mpk) resulted in weight effects and death. The reported low dose (30 mpk) showed no effects at all on any diabetic parameters, but instead seemed to lead to increased feeding and weight gain. To complete the debacle, the Pfizer group screened the Sirtris compounds through a broad panel of assays, and found that all of them hit a number of other targets (and appear significantly worse than resvertarol itself, which is no one's idea of a clean compound to start with).

Basically, these folks have thrown down the gauntlet: they claim that the reported Sirtris compounds do not do what they are claimed to do, neither in vitro nor in vivo, and are worthless as model compounds for anything in this area of study. So what is GSK going to have to say about this? And what, if this paper is at all accurate, did they buy with their $720 million?

[DewDiligence]

FLKS IPOs 6.21M* shares @$16.00:

http://finance.yahoo.com/news/flex-pharma-announces-pricing-initial-220000497.html

Flex Pharma, Inc. is a biotechnology company that is developing innovative and proprietary treatments for nocturnal leg cramps and spasms associated with severe neuromuscular conditions. In three randomized, blinded, placebo-controlled, cross-over studies, Flex Pharma's proprietary treatment has shown a statistically significant reduction in the intensity of muscle cramps in healthy normal volunteers. In the second quarter of 2015, the Company intends to initiate at least one human proof-of-concept study of its proprietary treatment for individuals with nocturnal leg cramps.

Flex Pharma was founded by National Academy of Science members Rod MacKinnon, M.D. (2003 Nobel Laureate), and Bruce Bean, Ph.D., recognized leaders in the fields of ion channels and neurobiology, along with Chairman and Chief Executive Officer Christoph Westphal, M.D., Ph.D.

Westphal was the founder and CEO of Sirtris Pharmaceuticals, the high-profile start-up that was munched by GSK in 2008 (#msg-28705020) but was later discredited.

*Assuming exercise of underwriter’s option.