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Biotech / Medical : Biotech Valuation -- Ignore unavailable to you. Want to Upgrade?

To: dr.praveen who wrote (21255)	9/13/2006 11:45:16 PM
From: dr.praveen	Respond to of 52153

Full Text: tinyurl.com Summary: Transduction of Multiple Effects of Sphingosine 1-Phosphate (S1P) on T Cell Functions by the S1P1 G Protein-Coupled Receptor1 Glenn Dorsam,2* Markus H. Graeler,2* Christine Seroogy,† Yvonne Kong,* Julia K. Voice,* and Edward J. Goetzl3* Sphingosine 1-phosphate (S1P) in blood, lymph, and immune tissues stimulates and regulates T cell migration through their S1P1 (endothelial differentiation gene encoded receptor-1) G protein-coupled receptors. We show now that S1P1Rs also mediate suppression of T cell proliferation and cytokine production. Uptake of [3H]thymidine by mouse CD4 T cells stimulated with anti-CD3 mAbs plus either anti-CD28 or IL-7 was inhibited up to 50% by 109–106 M S1P. Suppression by S1P required Ca2 signaling and was reduced by intracellular cAMP. S1P decreased CD4 T cell generation of IFN- and IL-4, without affecting IL-2. A Th1 line from D011.10 TCR transgenic mice without detectable S1P1 was refractory to S1P until introduction of S1P1 by retroviral transduction. S1P then evoked chemotaxis, inhibited chemotaxis to CCL-5 and CCL-21, and suppressed Ag-stimulated proliferation and IFN- production. Thus, S1P1 signals multiple immune functions of T cells as well as migration and tissue distribution. The Journal of Immunology, 2003, 171: 3500–3507.

To: dr.praveen who wrote (21255)	9/18/2006 5:59:59 PM
From: dr.praveen	Read Replies (1) \| Respond to of 52153

Tough Targets tinyurl.com Posted by Derek Novartis has been looking pretty impressive lately. They've announced promising data for their odd immunosuppresive drug Fingolimod (FTY720) in multiple sclerosis therapy. The study isn't very large (255 patients), but the statistics versus placebo look pretty strong. The compound is also showing promise in transplantation, and no doubt the company is looking into other autoimmune disorders as well. I should note that the drug's target (which appears to be a sphingosine phosphate receptor) wasn't known for many years. It started out as a structural variation on another compound with known effects, it but turned out to have a different (and more useful) profile. This one, if it works, will be more a triumph of persistance and deep pockets rather than drug design, but we'll take 'em where we can get 'em. The company also has reported data on a new bisphosphonate (Aclasta, aka Reclast) for osteoporosis, notable because it's only dosed once a year. This one had over seven thousand patients, followed for three years, so it's a substantial piece of work, with what appear to be very strong statistics indeed. Novartis appears ready to hammer Fosamax (aledendronate), which has been coining money for Merck for many years now, since they specifically studied a subgroup of patients who were switched from that drug. One of the notable things about these two drugs is that they're addressing chronic, slow-moving diseases with difficult clinical endpoints. These therapeutic areas are tough to work with in the clinic, and very costly to explore. There are many companies in the industry that would immediately try to outlicense a new osteoporosis clinical candidate rather than try to develop it themselves. You won't see many small biotechs trying to go it alone in areas like this, that's for sure. So even though I make fun of Pfizer (especially) for being too huge, Novartis is one of the counterexamples. They (along with Merck and GlaxoSmithKline) show that size can have advantages, if you use some of that muscle in the research buildings. FIguring out why some large research organizations are more productive than others, and what part of that isn't due just to chance, has stumped better pundits than me, though. . .