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Biotech / Medical : Texas Biotech (TXB) -- Ignore unavailable to you. Want to Upgrade?

To: JOEBT1 who wrote (812)	6/22/2001 12:04:45 PM
From: keokalani'nui	Read Replies (1) \| Respond to of 834

Nice to have some company. Know that I have 0 medical/scientific knowledge and that it can not be made up for by trying hard. Nevertheless, I am spending some time reading about Endothelin. And here are some cautions: 1. Everyone's got a program, so txb/icos are mice hoping to lead a parade of elephants. And I mean just about everyone has a composition of matter claim on an ET antagonist. 2. Specific vs non-sppecific inhibition seems to be generally accepted as preferrable, but it seems to come with its own set of issues. Is a systemic treatment desirable when ET production appears to occur locally? Fortunately it looks like they know ET-A is primarily expressed on cardio vasculature. 3. Sitaxsentan had some problems in PII. They are not taking it forward in some obvious indications and have some weird qualifications about which PH diagnosis it may succeed in--"may provide clinical benefit to patients diagnosed with some types of pulmonary arterial hypertension". Generation 2 is being pushed into the big market indications, but Phase I ongoing will be critical to evaluating the program. ICOS is the most miserly BT I have seen about sharing info with nobodies like me, so I'm not optimistic I'll even learn what's necessary when the study is over. 4. Abbott is showing the way with a non-specific ET inhibitor in advanced prostate cancer and its acquistion of Knoll also brought in some very nice, supporting IP in the indication and composition. TXB/ICOS seems to think ET-A may work here. I hope so, but that is not as logical as are the cardio indications. 5. The stock buyback is stupid grandstanding. I doubt there is near term hope for milestones from the JV. Can't bank on stroke. Aggatraban sales modest. I don't get it, but maybe they actually are from texas. BTW, I own a little, and have more work to do. That's me: buy first think second! Best advice I can offer: note the absence of anyone else over here. Wilder

To: JOEBT1 who wrote (812)	7/16/2001 4:05:02 PM
From: keokalani'nui	Read Replies (1) \| Respond to of 834

JOEBT1. Just to close things off for a while. I've burned some time on ET inhibitors, and I am now less enthusiastic than before. TXB is not just about ET, and I am not dissing argatroban for stroke, but imo ET is txb's most hopeful/prominent program for $$$. So why the caution? The benefits of overall--much less hyper-- ET-A specificity is not yet obvious and there are side effect issues with all the et inhibitors. Headache and liver tox, neither of which is well explained or elaborated on by the sponsors inspite of Bosentan's stab at it in a recent journal. The good and bad news is that the liver side effects are likely compound-dependent. Almost all the work in the area falls on Bosentan's back, and the only near-term data that counts will be available soon from the ac meeting on Bosentan in August. Sitaxsentan and Bosentan's hemodynamics are largely indistinguishable, but Sitaxsentan may have killed one of the few patients who have taken it. Bosentan has had it's dose dialed back radically. Sitax probably has also before entering PII/III. They all want the chronic CHF (but CHF livers are already not processing enough fluid to handle these drugs) or hypertension markets, but data on long term effects is nonexistant. Would you trade a 6-hour headache (OK, could be at the higher dose, can't tell) daily for being able to walk a little farther? This is a wild guess but I can't see the ac having enough data on B to make a recommendation. Although I would like nothing better than to see the ac's analysis, if I were them I would want to see at a minumimum the results of the second ongoing PIII--without it they are being asked to look at either small studies or large ones diluted by use of a broad spectrum of doses. The company announced that the PIII met its primary endpoints just this May and that it will supplement the filing made in Nov. This last part--me predicting what an Fda ac might do--I'll be the first to admit is an hysterical conceit. Hey, whatever...be honest first is my motto. Be correct at the same time my goal. As an aside I'd remark that DNA's association with Actelion is no validation, since B was Roche's drug originally. And ICOS did not pay up for anything when they entered the JV with txb. Bottom line is I'm pulling for the boys from texas, but I'm keeping only a token amount in my account. There is hope that generation 2, claimed to be greatly more potent, will be easier on the liver. Abbott's got the best program overall, for all indications. Still, I'm anxious to watch developments, especially what the ac says about bosentan which should also provide some interesting reading about the fda's interest in endpoints and safety. For what its worth, Wilder