Silicon Investor (SI) -- The First Internet Community

STOCKTALK

We've detected that you're using an ad content blocking browser plug-in or feature. Ads provide a critical source of revenue to the continued operation of Silicon Investor. We ask that you disable ad blocking while on Silicon Investor in the best interests of our community. If you are not using an ad blocker but are still receiving this message, make sure your browser's tracking protection is set to the 'standard' level.

Biotech / Medical : Alexion Pharmaceuticals, Inc. (ALXN) -- Ignore unavailable to you. Want to Upgrade?

To: tuck who wrote (219)	8/29/2002 12:55:18 PM
From: keokalani'nui	Respond to of 824

Both MI trials took longer than expected. I can not explain why, but they are large and perhaps the entry criteria made it cumbersome to enroll. Surprisingly, lytic completed enrollment earlier than pci (1/15 vs. 4/08). I've heard that until recently noone thought anti-C5 would be of any use. I'm quite sure we are near to the point PnG and alxn have the data, at a minimum for the lytic arm. Alnx says full data set will be released at AHA in Nov; clearly its preference given its experience with releasing the P2 cabg data which was poorly handled, misunderstood and clumsy. But frankly, I do not see how they can withhold top-line results if they have it simply because they prefer a scientific forum. I will consider the results a success, first, if the drug is safe. There is a substantial trial in 900 cabg pts where the conclusion was that it is safe and well tolerated (the multi-center, intn'l p3 in 3k cabg patients commenced late last year), however, there was a dose-dependent trend (small numbers, mind you) to infections incl sepsis in p2. I will also consider it a success if there is a trend in morbidity, especially above ckmb 5x ULN. Put another way, I will consider it a failure if there is no trend in morbidity with either dose or all doses combined. I expect the bolus-only to fail in both trials. So far you might be wondering why I have a substantial position. I do believe there is a chance bolus+ will hit--at least using morbidity EPs--in the pci group. The CKMB EPs will be low, like the cabg EPs were, but there is less likely to be raw tissue damage from surgical manipulation (which I believe overwhelmed the EPs in P2) and there is a good chance for microemboli and other ischemic consequences from the procedure which pexeli is designed to ameliorate. There has been human data (small trial with complement inh) and human pathology data (complement deposits from cadavers with MI as COD) that support my hopes for success. Nevertheless, with AMI (vs cabg) the drug is admin post-ischemia, and though most damage and complement activation occurs during reperfusion, some drug benefit that was evident in the cabg procedure will be lost in AMI. PnG's participation in P3 is back-loaded, and it can pull out based on P2 results and not have spent a dime in P3. This was made clear to me by another SIer--thank you. THIS would be the worst consequence for the stock price--not that alxn doesn't have the $$ to finish P3, it has more than enough--for obvious reasons. The market expects nothing from the trial and clearly thinks the drug won't work, long term. Ultimately, however, the P3 EPs are four-square with statistically significant results in 300 cabg patients. After the FDA accepted the company's EP definitions, the stock price showed strength against almost all indices. 30 days later it fell apart again and as you noticed, has languished. BTW, that pexeli 'abstract' is useless and has at least one prominent mistake. Alxn licensed the sca technology from Enzon, not the Mab. Wilder

To: tuck who wrote (219)	8/29/2002 1:28:13 PM
From: keokalani'nui	Read Replies (1) \| Respond to of 824

As for RA, there is not much value attached to this program, but there is clearly therapeutic activity in certain patients. "Certain" patients is a scary notion. It may involve testing for serum complement activity, and no one really knows what percentage of RA patients this represents. Nor does anyone know if this group might also include anti-tnf failures. I haven't given up, but there is some intelligent clinical design work to be done here. More interesting will be the MN results. This trial has also taken too long, troublingly so since this is clearly a complement-implicated disease--whether too much or too little WTFK. I can not longer articlulate my enthusiasm for this indication, but it sure seems likely that inhibiting the membrane attack complex would have value in the autoimmune destruction of the kidney, especially in later stages. Expecting results this year. I hope, therefore I invest. Would love to hear negative opinions from others.