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Biotech / Medical : XOMA. Bull or Bear? -- Ignore unavailable to you. Want to Upgrade?

To: Bluegreen who wrote (10777)	7/14/1999 8:16:00 AM
From: Robert K.	Read Replies (1) \| Respond to of 17367

If you insist. VBG. In summary fashion. Backround> cd14 seems to mediate may of the sepsis cascades. Bpi "seems to" act as a off switch, while lbp seems to act as a on switch. The theory (to me) was that give enough bpi and you can block or overwhelm the detrimental effects of lbp some regarding cascades. The theory from the baboons study (which still may be incorrect)( I still have doubts), is that bpi is beneficial for its antibacterial effects (primarily) and NOT for its anti-endotoxin actions. IN FACT they claim bpi does NOT eliminate or clear endotxin. (so what does?)(more later). Both groups of baboons got antibiotics and LIVE e-coli. One of the groups also got bpi.(pretreated) (think surgery and trauma uses) In summary, the bpi treated baboons obtained "significantly" reduced circulating bacteria, but not significant difference in plasma endotoxin. Soooo, they claim bpi doesnt eliminate endotoxin, but dampens or "neutralizes" its actions. BUTTTT, they claim its due to REDUCED circulating bacteria (what is meningococcemia anyway?) Anyway, the bpi treated had reduced bacteria, reduced tnf,reduced Il-1 (think amgen and antril),better cardiopulmonary dynamics,better kidney function,better liver function,better lung function, and to a lesser extent other organs. They claim the summary of those effects is probably the reason for the zero mortality of the bpi treated baboons (was very small sample size) those vs death in 5 of 8 non bpi-treated But the CLAIM is "more related to" the antibacterial effects of bpi. Now my words> but if bpi doesnt rid the circulation of LPS(endotoxin) then what does. IMO its lbp. LBP is in fact protective IMO. Recent research has shown that lbp can either "turn on" the cascades, or alternately can TURN LPS into HDL. (think about that) Now enter a morphed molecule of bpi/lbp that does NOT kick off LBP. and YES xoma has a patent on it. And lets ALSO remember the Horowitz paper in 95 that claims LBP greatly POTENTIATES the killing effect of bpi. Addition or co-administration of a lbp dummy molecule may potentiate bpi killing (think baboons) and further block the cascades, and further eliminate LPS. All speculation on my part. Really. I have so many "facts" here that many may be or are in error. Ditto that for all those opinions/guesses. I sure hope bpi works in p3, cause if it does its a wide open market. All disclaimers always apply, Consider nothing as fact. (above was a summary of opinions). never invest based on what I say. ever.

To: Bluegreen who wrote (10777)	7/14/1999 2:12:00 PM
From: Cacaito	Read Replies (2) \| Respond to of 17367

Bluegreen, I read the whole baboon article. The conclusions are a little different. They included the word "maybe". The bactericidal property of bpi was determined by blood culture colony count (nice trick)but they killed the monkeys at 72 hours? The monkey sepsis model is very drastic, infusing lots of bacteria in the veins, it was modified for the bpi experiment. They proof decrease colony counts (potent bactericidal property), they also proof similar endotoxin/lps levels.... but they also proof much lower levels of citokines,tnf,paf (down regulation of the inflammatory pathway)... I agree the main activity is to kill bacteria, but the second property is the one I am investing in Xoma, downregulation of the inflammatory chain. The Lpb patent is a modified lpb to avoid citokine stimulation. Same concept as bpi. They are many peptides antibiotics in the making, but only one bpi, and only one modified lpb (or several all of them from Xoma).