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Biotech / Medical : Rigel Pharmaceuticals, Inc. (RIGL) -- Ignore unavailable to you. Want to Upgrade?

To: mopgcw who wrote (401)	12/14/2008 10:51:32 AM
From: mcbio	Read Replies (1) \| Respond to of 566

I posted the information below on Investors Hub. Do you feel this is an accurate assessment of the efficacy of the Phase II RA trial data for R788?: In the 100 mg twice/daily dose, which is the likely dose to be carried forward (RIGL will test 150mg once/daily), 65% of patients attained an ACR20 (meaning 65% of patients reported a 20% improvement in their RA symptoms), 49% of patients attained an ACR50, and 33% attained an ACR70. However, just 38%, 19%, and 4% of placebo patients, respectively, attained ACR20, ACR50, and ACR70. The results were statistically significant. The aforementioned results are the pooled results from U.S. and Mexico patients. The numbers are admittedly a little skewed due to the significantly better results reported in Mexico. Specifically, those ACR20, ACR50, and ACR70 scores in Mexican patients at 100mg were 75%, 64%, and 46%, respectively. However, even if you just isolate the U.S. results, they are much better than placebo and statistically significant at ACR20, ACR50, and ACR70 scores of 52%, 29%, and 14%, respectively. Enbrel, by contrast, has demonstrated ACR20, ACR50, and ACR70 scores of 66%, 42%, and 15%, respectively. So, the drug clearly showed activity in this Phase II trial. The robustness of that activity depends on how you view the results. If you just look at the U.S. patients, then the ACR scores appear to be a bit lower than Enbrel although the ACR70 score is almost a dead heat. If you take into account all patients, then R788 had an essentially equivalent ACR20 score but a much more robust ACR50 and ACR70 score than Enbrel. Of course R788 is an oral drug too which should offer a big advantage.

To: mopgcw who wrote (401)	12/26/2008 11:57:42 AM
From: tuck	Read Replies (3) \| Respond to of 566

[R788: Developmental toxicity associated with receptor tyrosine kinase Ret inhibition in reproductive toxicity testing] >>Birth Defects Res A Clin Mol Teratol. 2008 Dec 23. [Epub ahead of print] Developmental toxicity associated with receptor tyrosine kinase Ret inhibition in reproductive toxicity testing. Clemens GR, Schroeder RE, Magness SH, Weaver EV, Lech JW, Taylor VC, Masuda ES, Baluom M, Grossbard EB. Rigel Pharmaceuticals, Inc., 1180 Veterans Blvd., South San Francisco, California 94080. BACKGROUND:: Urogenital abnormalities are among the most common of all human birth defects. In developmental toxicity studies with the Syk kinase inhibitor R788, a spectrum of findings, including renal agenesis, were observed. R788 has also been found to inhibit the receptor tyrosine kinase Ret. Ret kinase is known to be an essential component in the signaling pathway required for renal organogenesis and ureteric duct formation. Previously known is that mutant mice without the c-ret gene, develop urogenital malformations including renal agenesis. METHODS:: In GLP developmental toxicity studies, gravid rabbits were treated orally with R788 at doses of 0, 10, 22, and 50 mg/kg/day (gestation days 7-19) and gravid rats received 0, 5, 12.5, and 25 mg/kg/day (gestation days 6-17) by the same route. The activity of R406 against Ret kinase was assessed in biochemical and cell-based assays. RESULTS:: A dose-dependent increase in malformations, including renal and ureteric agenesis and a specific major vessel anomaly, retroesophageal right subclavian artery, was observed in both the rat and rabbit. R788 proved to be a potent inhibitor of Ret kinase. CONCLUSIONS:: R788 promoted a spectrum of developmental toxicity, including renal and ureteric agenesis and a specific major vessel abnormality, retroesophageal right subclavian artery, in two different species. These effects are likely the result of inhibition of Ret kinase given its importance in the normal ontogeny of the urogenital and cardiovascular systems across species.<< I suppose this means R788 will be contraindicated for pregnant women, probably not a big marketing blow. If it implies anything else, I'm all ears. Cheers, Tuck

To: mopgcw who wrote (401)	8/19/2010 11:45:39 AM
From: tuck	Respond to of 566

[(R788) inhibits tumor growth in CLL by blocking antigen-dependent B cell receptor signaling.] >>Blood. 2010 Aug 17. [Epub ahead of print] The Syk inhibitor fostamatinib disodium (R788) inhibits tumor growth in the E{micro}-TCL1 transgenic mouse model of CLL by blocking antigen-dependent B cell receptor signaling. Suljagic M, Longo PG, Bennardo S, Perlas E, Leone G, Laurenti L, Efremov DG. ICGEB Molecular Hematology Group, Campus "A. Buzzati-Traverso", Rome, Italy; Abstract Inhibition of antigen-dependent B-cell receptor (BCR) signaling is considered a promising therapeutic approach in CLL, but experimental in vivo evidence to support this view is still lacking. We have now investigated whether inhibition of BCR signaling with the selective Syk inhibitor fostamatinib disodium (R788) will affect the growth of the leukemias that develop in the Emu-TCL1 transgenic mouse model of CLL. Similar to human CLL these leukemias express stereotyped BCRs that react with autoantigens exposed on the surface of senescent or apoptotic cells, suggesting that they are antigen-driven. We show that R788 effectively inhibits BCR signaling in vivo, resulting in reduced proliferation and survival of the malignant B-cells and significantly prolonged survival of the treated animals. The growth-inhibitory effect of R788 occurs despite the relatively modest cytotoxic effect in vitro and is independent of basal Syk activity, suggesting that R788 functions primarily by inhibiting antigen-dependent BCR signals. Importantly, the effect of R788 was found to be selective for the malignant clones, as no disturbance in the production of normal B-lymphocytes was observed. Collectively, these data provide further rationale for clinical trials with R788 in CLL and establish the BCR signaling pathway as an important therapeutic target in this disease.<< Cheers, Tuck