Ligand - LGND - thread for non-PhDs Message Board

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Biotech / Medical : Ligand - LGND - thread for non-PhDs

LGND 195.83

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Dec 26 9:30 AM EST

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To: Henry Niman who wrote (55)	3/12/1997 9:42:00 AM
From: Henry Niman	of 57

Since my previous posts on the upcoming Nature article may be too complicated, here's another version: The posts are designed to be read at several different levels (many would have trouble with the actual abstract, but my summary is supposed to clear things up). I'll try one more time (the Nature article will also be hard to understand by the public, but there may be an associated "News and Views" article which is usually written for the non-specialist). The upcoming paper will show that two of LGND's drugs (Targretin and ALRT 268) can be used to treat diabetes in two mouse models of the disease. The treatment reduces elevated blood levels of glucose, insulin, and triglycerides. Targretin's results are on a par with a second generation TZD. Rezulin (to be sold by WLA's subsidiary Parke-Davis) was been hailed as the first drug that actually targets the cause (insulin resistance) of type II diabetes. LGND (or AGN) scientists have made analogs of Targretin (ALRT268 is the most potent), and the analog (which binds to its corrsponding hormone receptor more tightly tham Targretin) produces even greater reductions than Targretin. Targretin and ALRT268 are retinoids and when either of them is given in conjuction with a 2nd generation TZD (the 2nd generation TZD is more potent that the recently approved Rezulin), the results are even more striking. This data supports and earlier (1992) Nature paper by Ligand scientists that showed that the retinoid receptor (RXR) actually binds to the TZD receptor (PPAR). Thus,, the animal data supports the cell data and provides support for the molecular mechanism of Rezulin and more potent TZDs and Targretin and the more potent ALRT268 (the activate their corrsponding receptors and then the activated receptors bind to each other to reverse or delay insulin resistance). LGND is expected to announce the start of Phase II trials for the treament of diabetics with Targretin (in Europe this month). Targretin is already in 3 phase III trials for treating a cancer (CTCL) and it is many phase II trials for treating sevearl other cancers and skin diseases. It has been shown to be safe in humans and may be available as early as the beginning of 1998 (for CTCL). Rezulin is expected to go on sale this month. Thus it is conceivable that doctors will be ordering Targretin or Targretin plus Rezulin for their diabetic patients (it would be an off-label use for diabetes) as early as next year (and the market is over $3 Billion).

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