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

To: tuck who wrote (2679)	8/9/2006 3:08:34 PM
From: Ian@SI	Respond to of 3044

A somewhat weird abstract... ... a new irreversible proteasome inhibitor (NPI-0052) on 20S chymotryptic proteasome activity and apoptosis in isolated CLL cells in vitro ... Our results show that NPI-0052 is a more effective proapoptotic agent than bortezomib in isolated CLL cells Then without any claims about safety or efficacy in animals, it goes on to say, "Based on its in vitro and animal data, Nereus hopes to file an investigational new drug application..." This makes me suspect that the animal data didn't exist at the time the article was published. I'll probably google it and see if anything pops up or whether this molecule has undergone apoptosis. ;-) Personally I'd be very concerned about systemic delivery of an irreversible toxin. Ian

To: tuck who wrote (2679)	8/9/2006 3:21:56 PM
From: Ian@SI	Read Replies (2) \| Respond to of 3044

Clinical trial was started this May -- or at least, a PR stated that a Ph I has been initiated. nereuspharm.com Web site sucks. Nevertheless, with MDA and Sloan Kettering involved in an FDA approved Clinical Trial, I have to tone down my earlier comment about safety of irreversible proteasome inhibitor. Obviously far more knowledgeable people than me feel NPI-0052 has merit. Ian

To: tuck who wrote (2679)	10/20/2006 12:53:16 PM
From: tuck	Respond to of 3044

Nereus now claims effectiveness against MM resistant to Velcade: >>Br J Cancer. 2006 Oct 23;95(8):961-5. A novel proteasome inhibitor NPI-0052 as an anticancer therapy. Chauhan D, Hideshima T, Anderson KC. 1Department of Medical Oncology, Harvard Medical School, Dana Farber Cancer Institute, The Jerome Lipper Multiple Myeloma Center, Boston, MA 02115, USA. Proteasome inhibitor Bortezomib/Velcade has emerged as an effective anticancer therapy for the treatment of relapsed and/or refractory multiple myeloma (MM), but prolonged treatment can be associated with toxicity and development of drug resistance. In this review, we discuss the recent discovery of a novel proteasome inhibitor, NPI-0052, that is distinct from Bortezomib in its chemical structure, mechanisms of action, and effects on proteasomal activities; most importantly, it overcomes resistance to conventional and Bortezomib therapies. In vivo studies using human MM xenografts shows that NPI-0052 is well tolerated, prolongs survival, and reduces tumour recurrence. These preclinical studies provided the basis for Phase-I clinical trial of NPI-0052 in relapsed/refractory MM patients.<< Cheers, Tuck