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

To: Andrew H who wrote (10529)	10/31/1997 6:09:00 PM
From: Henry Niman	Read Replies (1) \| Respond to of 32384

Andy, Droloxifene was an interesting story. PFE threw it in with the compounds in their library and had LGND screen it. LGND picked Droloxifene as their #1 choice. When it was decoded and PFE found out that LGND had chosed Droloxifene, they asked LGND to pick another compound since Droloxifene wasn't really PFE's because they hadn't licensed it from Klinge yet. LGND said that they were due milestone payments because Droloxifene was already in trials. PFE said no, and LGND sued and PFE subsequently settled. That's part of the reason the royalty for breast cancer is so low (it starts at 1% of sales). The alliance was really an osteoporosis deal. If Droloxifene is approved for any other indication, including osteoporosis, the royalty rate goes to 3% for all indications, including breast cancer. LGND then selected a second compound, CP-366,156 and the royalty rate for that selection is 6%. After the PFE deal, LGND included a license back deal so any compound it discovers (up to a specified number) can be developed for cancer. The subsequent deals all have double digit royalties. LGND's screening also identified Tazarotene (marketed by AGN) which has been approved for psoriasis, and of course all of LGND's compounds were identified through receptor screening.

To: Andrew H who wrote (10529)	10/31/1997 6:55:00 PM
From: Henry Niman	Read Replies (1) \| Respond to of 32384

Andy, I had a cahnce to review my notes and this is my best guess for the 7 INDs to be filed in the next 15 months: ALRT268 (aka ALRT1268, LGD1268) - The other rexinoid (2nd generation) used in the Nature paper . Like Targretin it lowers glucose, insulin, and triglyceride levels. However, it has a higher binding affinity for the RXRs and is more potent in the animal models. It also synergizes with 2nd generation TZDs (SBH's BRL49653 in diabetes, and Takeda's pioglitazone in human cancer). ALRT324 (aka LG100754?) - Its definitely a rexinoid, possibly LG100754. LG100754 binds to RXRs and produces a conformational change so it will partner with other receptor that do not require prior activation. Thus, LG100754 has the potention of replacing two drugs, a rexinoid like Targretin or ALRT268, and a TZD like Rezulin or BRL49653. ALRT4204 and ALRT326 - Two more rexinoids that are being developed by AGN. AGN has indicated that they will quickly file INDs in preparation for a diabetes and or metabolic disease agreement with another big pharma. ALRT4310 - An anti-retinoid that will be developed by AGN. This compound is slated to be used to counter side effects associated with other commercial retinoids such as Retin-A, Renova, and Accutane. TSE424 - A SERM (aka Tissue Specific Estrogen) dveloped under the women's health alliance with AHP. This compound will be AHP's answer to LLY's Evista/Raloxifene, PFE's Droloxifene and CP366,156, SBH's Idoxifene, etc. Michael Murphy predicted that Evista would be recommended for approval in November, but for a narrow indication. PFE announced than they were filing an NDA for Droloxifene next year (for osteoporosis). GR Modulator - A Glucocorticoid Receptor modulator identified under the ABT alliance for the treatment of inflammation. LDL Modulator - A Low Density Lipid modulator identifed under the GLX alliance for the prevention of atherosclerosis or heart disease.