Biotech Values

[jellybean]

Thanks for the post, Dew. A few comments.

---Last fall at the AASLD meeting, it was reported that ITMN-A and ITMN-B were 1,000x more potent against HCV mutants that VX-950 or BILN-2061. What that means exactly, I can't say until numbers are published for the rate of HV resistance with ITMN-A/B. Here's the link. You will hve to scroll through all the preclinical abstracts to find Intermune, but if you are truly interested in HCV the scroll is worth it. http://www.hcvadvocate.org/news/reports/AASLD_2005/11%2013%20HCV%20Tx%20Pre%20and%20Early%

---the report did not mention Kamakura's work which has identified sphinoglipid biosynthesis as a new target for HCV and a secondary fungal metabolite which disrupts the viral assembly process. Maybe the development is too early on or the project has been discontinued, but the company had an abstract at the AASLD meeting linked above. A nature abstract follows at the bottom.

--Finally, many people have questioned which animal showed the severe immune response in the Anadys tox studies. The link below is the PR from anadys' AASLD report last fall, and the actual abstract can be found in the AASLD meeting link above (although, I have to say that the abstract is poorly written in some places). Cynomolgus monkeys are the only preclinical animal mentioned in either of these. I do not know how similar monkey innate immune systems are to humans. However, I can say that rat and human innate immune systems diverge dramatically when it comes to toll-like receptors; and so, a severe resonse in a rat would leave room for hope. 20Dev.htmhttp://ir.anadyspharma.com/phoenix.zhtml?c=148908&p=irol-newsArticle_Print&ID=782461&hig...

Nature Chemical Biology 1, 333-337 (2005)
doi: 10.1038/nchembio742

Host sphingolipid biosynthesis as a target for hepatitis C virus therapy
Hiroshi Sakamoto1, Koichi Okamoto1, Masahiro Aoki1, Hideyuki Kato1, Asao Katsume1, Atsunori Ohta1, Takuo Tsukuda1, Nobuo Shimma1, Yuko Aoki1, Mikio Arisawa1, Michinori Kohara2 and Masayuki Sudoh1

Top of pageAn estimated 170 million individuals worldwide are infected with hepatitis C virus (HCV), a serious cause of chronic liver disease. Current interferon-based therapy for treating HCV infection has an unsatisfactory cure rate1, 2, and the development of more efficient drugs is needed. During the early stages of HCV infections, various host genes are differentially regulated3, and it is possible that inhibition of host proteins affords a therapeutic strategy for treatment of HCV infection. Using an HCV subgenomic replicon cell culture system, here we have identified, from a secondary fungal metabolite, a lipophilic long-chain base compound, NA255 (1), a previously unknown small-molecule HCV replication inhibitor. NA255 prevents the de novo synthesis of sphingolipids, major lipid raft components, thereby inhibiting serine palmitoyltransferase, and it disrupts the association among HCV nonstructural (NS) viral proteins on the lipid rafts. Furthermore, we found that NS5B protein has a sphingolipid-binding motif in its molecular structure and that the domain was able to directly interact with sphingomyelin. Thus, NA255 is a new anti-HCV replication inhibitor that targets host lipid rafts, suggesting that inhibition of sphingolipid metabolism may provide a new therapeutic strategy for treatment of HCV infection.