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

To: Andrew H who wrote (15075)	2/14/1998 2:43:00 PM
From: Henry Niman	Read Replies (1) \| Respond to of 32384

Andy, I suspect that more is known about the translation from rats to humans, and maybe everyone will know after the ASCO meeting in May. The same animal model has been used to test Panretin and Tamoxifen for chemoprevention in 1994 and I strongly suspect that the positive results led to the two ongoing Phase I trails involving Panretin and Tamoxifen. Since the RXR activating activity seems to be responsible for the in vivo effect, I would expect better results for Targretin than Panretin (and probably better results for LGD1268 than Targretin). Since both Phase I trials were started many (12?) months ago, I suspect that some of the clinical data is known (and will be presented at ASCO). I also suspect that these results are pushing LGND's Phase II breast cancer schedule and it is why employees think the stock price is far too cheap.

To: Andrew H who wrote (15075)	2/14/1998 2:46:00 PM
From: Henry Niman	Respond to of 32384

Panretin also synergizes with Raloxifene (Evista) which may be why LLY is so interested in Rexinoids and SERMs. Here's the abstract for Panretin and Tamoxifen: Cancer Res 1994 Sep 1;54(17):4614-4617 Prevention of breast cancer in the rat with 9-cis-retinoic acid as a single agent and in combination with tamoxifen. Anzano MA, Byers SW, Smith JM, Peer CW, Mullen LT, Brown CC, Roberts AB, Sporn MB Laboratory of Chemoprevention, National Cancer Institute, Bethesda, Maryland 20892. We show that 9-cis-retinoic acid (9cRA) is a potent inhibitor of mammary carcinogenesis induced by N-nitroso-N-methylurea in Sprague-Dawley rats. Rats were first treated with a single dose of N-nitroso-N-methylurea (50 mg/kg body weight) and then fed non-toxic levels of 9cRA (120 or 60 mg/kg of diet). 9cRA was highly effective in reducing tumor incidence, average number of tumors per rat, and average tumor burden, as well as extending tumor latency. The combination of 9cRA with low levels of tamoxifen (TAM; fed at either 1.0 or 0.5 mg/kg of diet) was particularly effective; addition of 9cRA to a TAM regimen doubled the number of animals that were tumor-free at autopsy and significantly diminished tumor number and tumor burden. For suppression of carcinogenesis in vivo, 9cRA was much more potent than all-trans-retinoic acid, both as a single agent or in combination with TAM, although both retinoids had equivalent inhibitory effects on DNA synthesis in cultured human breast cancer cell lines. Both 9cRA and all-trans-retinoic acid induce the expression of the adhesion molecule, E-cadherin, in the SK-BR-3 cell line. We suggest that clinical evaluation of the combination of 9cRA and TAM, either for chemoprevention or for adjuvant therapy, should be considered. PMID: 8062253, UI: 94340584

To: Andrew H who wrote (15075)	2/17/1998 11:29:00 AM
From: Henry Niman	Read Replies (1) \| Respond to of 32384

Speaking of potential large markets, here's a recent report on skin cancer (in humans): P H I L A D E L P H I A, Feb. 17 - People with light skin and fair hair may be asking for trouble if they think sunscreen can protect them from deadly skin cancer, medical researchers warned today. A study by the Sloan-Kettering Cancer Center suggests the risk for melanoma, one of the fastest-rising forms of cancer in the United States, depends mainly on genetic factors such as hair, skin and eye color, and the number of moles a person has. For example, the study estimated that people with blond or red hair, light-colored eyes and pale complexions were almost six times more likely to contract melanoma than those with darker features. But the sun still poses a danger, especially for those who are genetically susceptible to the disease, and researchers said sunscreens may compound the problem by eliminating sunburn and allowing fair-skinned sunbathers to stay outdoors for longer stretches. "Based on the evidence, we conclude that sunburn itself probably does not cause melanoma, but that it is an important sign of excessive sun exposure, particularly among those who are genetically susceptible because of their skin-type," said Dr. Marianne Berwick, a Sloan-Kettering epidemiologist. Melanoma Rates Up, But People Inside Her study, due to be presented to the American Association for the Advancement of Science today, also suggests paradoxically that incidence rates for melanoma may be rising because people nowadays go outside less often. "Chronic sun exposure may be protective for the development of melanoma because the skin has adapted to the sun," Berwick said. "On the other hand, intermittent sun exposure appears to increase risk, making it much less protective." Once a very rare disease, malignant melanoma has been rising at alarming rates among whites in recent decades. Melanoma is the 10th most common cancer in the United States. But it is the fastest-rising form of cancer for American men and the second for women, after lung cancer. In Australia and New Zealand, melanoma is the fourth most common form of the disease. Ozone Layer Depletion Usual Scapegoat Rising skin-cancer rates have been attributed to a depletion in the Earth's ozone layer, which allows more of the sun's harmful ultraviolet rays to penetrate the atmosphere. But Richard Setlow, a biologist with the Brookhaven National Laboratory, said in a scientific paper that 90 percent of the sunlight linked to malignant melanoma belonged to a spectrum of ultraviolet radiation known as UVA. Ozone depletion, which involves a form of ultraviolet light known as UVB, would be inconsequential to the incidence of melanoma, he said. Another researcher, Honnavara Ananthaswamy of the M.D. Anderson Cancer Center, said UVB radiation may cause other forms of skin cancer by inducing mutations in a tumor suppressor gene known as P53, which normally controls the proliferation of skin cells. In a study funded by sunscreen manufacturers, the researcher found that 96 percent of laboratory mice treated with Sun Protection Factor 15 and exposed to UVB radiation failed to develop the genetic mutation. Ananthaswamy suggested sunscreens could be graded for consumers according their ability to stop the genetic mutation that leads to some forms of skin cancer. "In addition to SPF...it may be possible to develop an "MPF", or mutation protection factor, for sunscreens based on their ability to inhibit P53 mutation," the researcher said.

To: Andrew H who wrote (15075)	2/18/1998 12:22:00 AM
From: Henry Niman	Respond to of 32384

Bear, Stearns analyst Scott Shevick said Merck was also helped Tuesday by industry data showing Lilly's Evista generated only 4,920 new U.S. prescriptions during its fourth week on drugstore shelves. He said that figure compared unfavorably with the 10,000 new prescriptions Merck's osteoporosis drug Fosamax generated during its fourth week on the market in 1995.