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Biotech / Medical : Ligand (LGND) Breakout! -- Ignore unavailable to you. Want to Upgrade?

To: Henry Niman who wrote (22076)	6/11/1998 1:10:00 PM
From: Peter Singleton	Read Replies (1) \| Respond to of 32384

whoa, Henry, slow down! : ) doesn't anybody read these abstracts? for example, let's listen to what this says: "Abstract #: 0111 Presentation Date: 6/14/97 Activation of RXR with Rexinoids (RXR Selective Ligands) Function as Insulin Sensitizers in Type II Diabetic Mice DIANE L. CROMBIE 1,2, JAMES R. PATERNITI 1,2, RICHARD A. HEYMAN1,2, San Diego, CA, USA. ... In mouse models of non-insulin dependent diabetes mellitus (NIDDM) and obesity, including the ob/ob and db/db mice, RXR agonists function as insulin sensitizers decreasing hyperglycemia, hypertriglyceridemia and hyperinsulinemia. Combination treatment with the thiazolidinedione, BRL49653, further enhances the maximal response of either agent alone. When RXR agonists are used during early stages of insulin resistance they block the progression of NIDDM. At late stages of insulin resistance, these agents signficantly reduce the amount of exogenous insulin required to reduce the hyperglyemic state to the euglycemic levels. These data suggest that activation of the RXR:PPARg heterodimer with rexinoids may provide a new therapeutic approach as monotherapy or combination therapy for the treatment of insulin resistance." So, 1 - In mouse models of Type 2 diabetes and obesity, RXR agonists (e.g., 268, 1324) reduce insulin, glucose, and triglyceride levels. We know this already from the Nature article last year, but it's worth repeating. 2 - Combination with a TZD (PPARg agonists - best known example is Rezulin) enhances the effect of either used alone. Also known from the Nature article (this may be a presentation of the same study), but worth repeating. This is important data. 3 - During the early stages the disease (in mice), RXR agonists block the development of insulin resistance, and hence the progression of the disease. huh?! very, very good news. 4 - During late stages of insulin resistance, RXR agonists reduce the amount of insulin required to reduce glucose levels (and hence treat hyperglycemia). Also known, but worth restating. The net is if LGND were able to produce a drug that were tolerable enough for chronic use (still don't know yet ... but major SE with Targretin appears to be triglyceride elevation ... and the earlier stage products appear to reduce triglycerides), one that showed efficacy across the life cycle of Type 2 diabetes, and were marketed by the leading player in diabetes treatments (LLY) ... we could have a very big product on our hands in a number of years. Peter

To: Henry Niman who wrote (22076)	6/11/1998 3:35:00 PM
From: Peter Singleton	Read Replies (4) \| Respond to of 32384

Another point about BRL49563, the TZD (PPARg agonist) mentioned in the ADA abstract (and tested in mouse models of Type 2 diabetes vs and in combination with LGND268). I believe this SBH's Avandia, which is in PIII testing. A couple of mentions of Avandia worthy of note: from a very long article in streetnet.com streetnet.com Key quote: "Avandia, an oral drug for diabetes, is highly anticipated and addresses a multi-billion-dollar market. The drug is currently in phase III clinical trials and is considered to be 100 times more potent than Warner-Lambert's Rezulin." and today in Reuters, on SBH, key quote by CEO: "Company chief executive Jan Leschly told Reuters in an interview in April that Avandia, as one of SmithKline's four leading development products, would take the company into a new therapeutic area. He said that all four new products "could be what the market talks about as blockbusters" and stated that the potential market for Avandia was much larger than that for insulin." whole article follows: SmithKline<SB.L> up again ahead of U.S. conference LONDON, June 11 (Reuters) - Shares in British drugs company SmithKline Beecham Plc <SB.L> rose again on Thursday ahead of a U.S. diabetes conference and after positive broker comment and ongoing bid speculation, traders said. The American Diabetes Association is due to hold a weekend conference, at which SmithKline will push its new diabetes drug Avandia, market sources said. Sources at BT Alex Brown said the brokerage had issued positive comment on the stock on Thursday ahead of the conference, and reiterated its "buy" rating. The stock bucked a weaker market trend to rise 9p, or 1.3 percent, to 724p by 0900 GMT in volume of 2.9 million shares, making it once again one of the most actively traded FTSE stocks. The share price has risen 13 percent since hitting a five-month closing low of 642 pence on June 2. Its recovery has been aided by fresh bid speculation since news last week that Sweden's Astra AB <ASTRa.ST> was in talks to buy U.S. pharmaceutical company, Merck & Co <MRK.N>, out of a U.S. joint venture. Company chief executive Jan Leschly told Reuters in an interview in April that Avandia, as one of SmithKline's four leading development products, would take the company into a new therapeutic area. He said that all four new products "could be what the market talks about as blockbusters" and stated that the potential market for Avandia was much larger than that for insulin. A market source said Goldman Sachs repeated its "market performer" rating on SmithKline on Thursday, but no one at the brokerage was available to give confirmation. 05:22 06-11-98