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

To: Torben Noerup Nielsen who wrote (15123)	2/15/1998 7:10:00 AM
From: Henry Niman	Respond to of 32384

Torben, Yes it is true that a mutation in the 12th codon on the ras gene is one of the most (if not the most) common mutations in human cancer. I haven't kept up with the latest numbers, but I think that the mutation is most frequently found in colon and bladder cancer. It also shows up in breast cancer, but at a lower frequency. Cancer cells usually undergo a series of mutations (or accumulated defects) before they become malignant, but the ras change is a powerful driver. PNU, when administered to this particular stain of rats, produces this change in the vast majority of the tumors. However, the cells undergo additional changes which determine how soon the tumor will arise and how it will behave. That is one of the major strengths of this model (tumors must evolve through additional changes that then represent as a vast array of different phenotypes and genotypes, just as a human population does). The dosing and timing drive the tumor formation toward breast cancer (remember, the tumors develop because of a single IV injection of a chemical) and most remarkably, Targretin causes 72% of the primary tumors (most aggressive) to disappear and 46% of the rats are "cured" (all tumors disappear). This success is quite remarkable, because most of the rats develop several tumors, each of which comes from a separate mutated cell (not a matastisized tumor from the primary). Most humans begin with a single tumor, not combinations which pop up with days of each others. In contrast, human tumor xenograft models take a human tumor (ala Joe Kernan's description on CNBC) and put it into an immunocompromized host (usually nude mice). Success on this model frequently does not translate to humans, because a single tumor type is used as a target in all of the mice (and the tumor usually has been grown in culture, selecting for a genotype that may not even represent the original human tumor), under very artificial conditions (if a normal mouse was used, its immune system would recognize the tumor as "foreign" and rejected it in a manner similar to transplant rejections by unmatched donors and recipients, but the rejection is even stronger because the transplant crosses species lines). In the PNU rat model, many different tumors pop up at different times, and they have different combinations of mutations (like human breast cancers), but the overwhelming majority respond to Targretin (72.2% of the primaries disappear, 16.7% partially regress, and only 11.1% continue to progress). Truely remarkable.

To: Torben Noerup Nielsen who wrote (15123)	2/15/1998 10:54:00 AM
From: tonyt	Respond to of 32384

Finally, someone with a rational rebuttal to Mr. Engelberg (other than, 'he must have invested in the competition' or ' I never even heard of his firm, so it must be wrong'). --Tony

To: Torben Noerup Nielsen who wrote (15123)	2/15/1998 1:56:00 PM
From: Andrew H	Respond to of 32384

>>Consider what happends if you make a rat breathe cyanide gas. I can promise you that it will die even with very low concentrations. So will a human (Tony, if you do not believe me, you might try it... :-))<< Excellent suggestion, Torben. (:>)

To: Torben Noerup Nielsen who wrote (15123)	2/15/1998 4:32:00 PM
From: Henry Niman	Respond to of 32384

Torben, You made some excellent points, include the gas, but the other observations were also justified. Usually, when reporters do a story, they like to hear from both sides. For LGND, they asked analysts from H&Q and Lehman Brothers for comments, because both cover LGND and have BUY ratings on the stock. I'm sure that the reporter wanted to hear what ZEN had to say (since Targretin could significantly impact the $1/2 Billion hormone treatment for breast cancer). I suspect that that is how they came up with a quote from Dr. Charles Engelberg. I was not surprised to find LGND absent from Americal's web site, nor was I surprised to see ZEN present. However, when I uploaded the wire service stories, I did not find find it necessary to highlight positive comments from analysts who cover LGND (although I wholeheartedly agree with their comments, which are consistent with posts that I and others have made previously). I also did not find it necessary to repost the quotes out of context (the positive observations of the other analysts), nor did I have any need to remove the fact that the analysts were from Lehman Brothers or H&Q. As far as the rat/human comment itself, it was very general and wasn't all that applicable to the LGND study. Causing tumors to disappear in rodents is usually done via human tumor xenografts. That is what Joe Kernan thought had happened in this instance. I'm not sure how much research Dr. Engleberg did before commenting. If he just watched CNBC, he might have been mislead (the LGND study did not involve xenografts). A little more detail in his comments would have given them some more credibility (and the detail may have been edited out by the writer or editor of the wire story). However, the data was quite compelling, not only because a tumor induction model was used, but more importantly, Targretin beat Tamoxifen in virtually every assay, by at least a 2-1 margin. Control mice saw 0% of the primaries disappear. Tamoxifen,which is the treatment of choice for human breast cancer, caused regression in an impressive 33%. However, Targretin made 72% of the primaries disappear. The data was compelling. Dr. Engelsberg's printed comments were not (with or without the notation that he was from Americal).

To: Torben Noerup Nielsen who wrote (15123)	2/18/1998 1:06:00 PM
From: Henry Niman	Respond to of 32384

Charles Engelberg showed up again yesterday in a Reuters story on LLY and Evista (not surprisingly, the Americal site lists MRK but not LLY): February 17, 1998 Lilly's Stock Falls After Analysts Report Evista Orders Disappoint By CHARLENE OLDHAM Dow Jones Newswires Shares of Eli Lilly & Co. fell Tuesday after market-research firm IMS America Ltd. reported disappointing new sales numbers for the company's osteoporosis compound, Evista. At the close of composite trading on the New York Stock Exchange, Lilly's stock fell $3.125, or 5%, to $60.5625, with 11.59 million shares changing hands, compared with average daily volume of 2.7 million. In the fifth week since the drug's launch, new prescriptions fell below most analysts' expectations and comparable figures for Merck & Co.'s Fosamax, the leading osteoporosis drug on the market, according to Charles Engelberg, industry analyst for AmeriCal Securities. Mr. Engelberg said he heard from another analyst that IMS America, a pharmaceuticals market-research firm, reported 4,781 new Evista prescription orders for last week. "Fosamax had three times as many" prescriptions at this point, he said. An Eli Lilly spokesman couldn't immediately confirm the number of new prescriptions reported. The spokesman also said it was company policy not to comment on stock activity. Whatever the number, Mr. Engelberg said he isn't surprised it fell below many analysts' estimates. "We have a sell on the stock because we don't think Evista can possibly achieve analysts' expectations," he said. More than 35 million people worldwide have been diagnosed with osteoporosis, so some analysts believe Evista could be a $1 billion drug. The stock is trading lower because Evista sales will be particularly important for Lilly after the main patent on its antidepressant Prozac expires in early 2001, Mr. Engelberg said. Prozac accounted for 43% of Lilly's U.S. drug sales in 1996