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Biotech / Medical : Smithkline Beecham (SBH)

SBH 10.05

-2.1%

1:00 PM EDT

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To: Mike Battin who wrote (48)	7/28/1998 10:54:00 AM
From: Henry Niman	of 61

Ruzlin is a TZD that activates a receptor, PPARgamma, that turns on genes which overcome insulin resistance. The activated receptor partners with another hormone receptor, RXRalpha. LGND's and AGN's rexinoids activate RXRalpha. Thus in animal models of type II diabetes, they have been shown to synergize with TZDs like WLA's Rezulin and SBH's Avandia (and TZDs are effective at lower concentrations which may avoid the liver problems). Some details at home.att.net LLY is supposed to begin Phase II clinical trials in the US soon using Targretin as monotherapy (and possibly combination therapy with Rezulin and other approved treatments for diabetes). LLY is also supposed to file INDs for one of LGND's second generation rexinoids (LGD1268 or LGD1324). A few days ago, AGN announced a deal with WLA to develop AGN's rexinoids (LGND gets royalties). The Rezulin problems may have helped seal the AGN/WLA deal. LGND had talked extensively with WLA last summer, but WLA did not want to give LGND up front funds. Consequently, LGND signed a $200 million deal with LLY, including $50 million up front and $75 million tied to early milestones such as starting US trials with Targretin or filing INDs for LGD1268 or LGD1324.

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