To: marc ultra who wrote (13690 ) 5/12/2000 2:04:00 AM From: marc ultra Read Replies (3) | Respond to
OT:ENMD Since I've been posting about ENMD occasionally and it dropped over 12 points or about 30% today, I thought a few remarks would be in order here rather than respond to private messages I received. It's a long story and involves the power of message boards but I'll try to be brief. Some of the things I will say is what I believed happened and may not be 100% correct About the only patient in the trials who became publicly identified in a news article was dropped from the trials the other day due to his tumor increasing 70% in size which was beyond the 50% that the protocol called for being dropped from the trials. As many came to know this situation many people, myself included, were unhappy as he had been allocated to a relatively low dose cohort that was thought likely too low to work. Prior to this it was discussed that people who were at a very low dose and were dropped out should at least have the option of going on high dose off the protocol if they requested. A reporter aware of the situation and the heated discussions going on at Raging Bull etc. about it, confronted a top figure at the NCI about this. Prior to this time many posters went wild complaining to everyone in sight about the situation including Congressmen and Institutional review boards at the trial site and this NCI official was probably bombarded with angry enquiries already when the reporter showed up. Backed against the wall and probably upset he was virtually being acused of being unethical in the treatment of the study patient, the official at the NCI told the reporter there was no evidence of therapeutic efficacy for Endostatin or something like that. That story was picked up by the wires and the stock tanked. Later when questioned by Bloomberg the NCI person moderated his answers a bit and said that did not mean that some patients were not doing better with their cancer no longer progressing nor that some may have had decreases of less than 50% in their tumors. Also he indicated his information was as of March. The CEO was on CNBC later in the day also to discuss the issue. The bottom line is the way these angioinhibitors work you expect them to work very slowly by inhibiting new tumor vasculature first. They may eventually just leave tumors in a state where they are unable to grow or metastasize and shrinkage of a tumor with a single agent if it occurs would be a big deal. The Phase 1 results are likely to be announced in the fall and large multiple Phase 2 and/or 3 trials will likely start toward the end of the year. ENMD also has early trials going on for Angiostatin and 2me2. In mice when Endostatin and Angiostatin were combined cancer was cured in mice. Whether a similar combination be a big deal in humans we won't know for a while but plans are that once Angiostatin does OK in PI trials that a PII trial will be done combining the two. Perhaps the most obvious and early use of Endostatin will be to combine it with conventional chemotherapy which could greater increase efficacy with no additional toxicities. Also I should mention that I believe Judah Folkman who is the father of this whole area of angiogenesis wanted to give the Endostatin by continuous infusion, which will start in Europe shortly, rather than the dosing regimen the FDA apparently wanted in the PI safety trial which is likely to be less effective as there may be too much time between doses that allows new angiogenesis to start to occur. This time includes a long period of time doing multiple tests and evaluations. Anyway I failed to keep this brief so I will just say all the potential still appears there, it will take some time for things to develop but we'll probably get a full PI analysis in the fall sometime with P2's starting in the 4th quarter and today was more part of a short term human story. The fundamentals have not changed but the price has. As usual I am not specifically recommending this for others and obviously if I stuck to the 4% rule I would not have been hurt so much but as Bob always says another way to decrease concentration is have the stock blow up a bit<g>. As a final note I should add when the patient left a message for Folkman about what to do, Folkman himself called back from London and recommended an alternate regimen of using an approved chemotherapy drug but at a low, frequent dose that has primarily an antiangiogenic effect that is a strategy that is becoming a big deal now.
