Ligand - LGND - thread for non-PhDs Message Board

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

LGND 195.83

-0.7%

Dec 26 9:30 AM EST

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To: Henry Niman who wrote (41)	1/30/1997 8:14:00 PM
From: Henry Niman	of 57

Since I am STILL being asked if the new diabetes drug has anything to do with LGND, I'll try one more time in the simplest terms. TZDs (like Rezulin) are small hormone-like molecules that diffuse into cells and combine with receptors called PPARs. The PPARs are members of a large family of receptors that are activated by hormones and the act as transcription factors (turn specific genes on and off). The transcription factors form large complexes. In the case of the PPARs, they interact with another set of hormone receptors called RXRs. The RXRs are receptors for retinoids, such as LGND's Targretin. Targretin is like a TZD. Its a small molecule that activates a specific set of receptors. In the case of Targretin, an RXR is activated. The activated RXR then binds to the activated PPAR. This complex causes cells to be sensitive to insulin. It overcomes the insulin resistance. Each drug (TZD or retinoid) will produce three measurable effects. They lower the blood levels of glucose, insulin, and triglycerides. Although each drug works as monotherapy, when given together they produce additive effects (in diabetic mouse models). LGND is well aware of these effects. They presented data on Targretin at Bear Stearns in September and then at H&Q they showed that they had a second generation compound, ALRT268, that not only bound to the receptors (RXRs) more tightly, but also produced a stronger reduction in glucose and triglycereide levels than Targretin (the insulin reduction was the same). It was as effective as a second generation TZD. LGND plans to have Targretin in type II diabetic patients this quarter and use the clinical data as a basis of a mega deal to be signed 3Q. TZDs are projected to be a $2 Billion per year drug. LGND and potential partners are well aware of the potential market for Targretin alone or in combination with TZDs. I think the street is a bit slow on the learning curve. Henry

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