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Biotech / Medical : ARIAD Pharmaceuticals -- Ignore unavailable to you. Want to Upgrade?

To: Mike McFarland who wrote (1185)	5/21/2000 7:19:00 AM
From: Mike McFarland	Respond to of 4474

OT (P.S.) Oh, I guess I also own a little Synaptic, SNAP--the one I'd sooner forget I suppose. And Elan, but I don't think of that as a pure neurobiotech obviously. You watch these biotechs for very long, and pretty soon you own so many that there is no way you can outperform the biotech indeces, although I am overweight vphm, tgen and cnsi right now--so any of those do well and I can beat your favorite index. By the way, lurkers might think that late at night, I am really trying to stir up a bioguru hornets nest--god knows the biotechies here on SI don't always agree (Gliatech is the best example I can think of at the moment). I am not trying to push anybody's buttons--I just like to ask a lot of questions. And finally, before I log off for a few days for a much-needed break from what my wife calls the mothership (or the internet nipple--whatever) I do not own Ariad. But that is purely pschcological-- you ride something from a buck to $4--you find you cant buy it back higher. Looking cheap now however after that huge biotech mania run up into the $40s however. fwiw, I did ask tgen's Carter about AAV serotypes, if anybody else has something to say about AAV5 versus AAV2, do speak up. For now I am staying with tgen, but you can find a Wilson/Kurztzman abstract regarding aav5 on Pubmed (Kurztmman left Avigen to go to Genovo, and that is about all I know about him--Wilson is obviously known by all who follow gene therapy).

To: Mike McFarland who wrote (1185)	5/23/2000 6:11:00 AM
From: scott_jiminez	Respond to of 4474

Mike - addressing any one of your questions encompasses a thesis by itself. You must understand that I come from the research side and the behavior I witness by reputedly well-meaning science 'professionals' turned investment advisors, is disconcerting at best. If the phrase 'money changes everything' could ever be permanently attached to a segment of the economy, it would be most apt with biotechnology. I can't address all the companies you listed so I've chosen Cephalon. To keep this as brief as possible, I'll just touch on their narcolepsy drug [provigil (modafinil)] and move on to the stuff I'm more familiar with. Narcolepsy and ADHD are very different clinical syndromes. In an incredibly simplistic view, the former does not require amphetamine-like activity (i.e. provigil) while the latter does. Thus, it would be my stance that provigil is inappropriate for ADHD. But narcolepsy is a tiny market, even worldwide, and ADHD, since it's SO over-diagnosed in the US, is a huge market. So Cephalon goes after ADHD. Am I an expert on ADHD?. NO. But I can assure than ANY company working on a compound even distantly related to attention-enhancement salivates at those Ritalin sales figures. Their experiments will be deigned to enhance EVERY opportunity to show ADHD effectiveness. And every neuro/biotech investment advisor will never fail to mention the dollar figure of Ritalin sales and how CEPH or whatever other company they're touting could 'tap into' that market. The Ritalin-sales figure syndrome is on my top ten list of red flags: these are internalized mega-hype warning signals that I've learned to associate with non-objective presentations. Whenever I see a red flag in a news article, newsletter, etc., I stop reading immediately and move on. Cephalon is also deeply involved in treatments for neurodegenerative diseases (Alzheimer's [AD], Parkinson's, etc.). Their central product here is CEP-1347 (for AD) , a derivative of the indolocarbazole K-252a (an inhibitor of tyrosine kinase) . CEP-1347 was found to modulate a cellular pathway (ERK/JNK) which participates in cellular apoptosis (roughly equivalent to programmed cell death; cell 'suicide'). This modulation, in Cephalon's hands and in the context of neurons, resulted in greater cell survival. Cephalon had developed CEP-1347 because they were, in effect, attempting to mimic the role of nerve growth factor (NGF) in the central nervous system. NGF has been associated with the increased survival of some of the cells that degenerate in AD. However NGF does not cross the blood brain barrier (BBB), thus its use as a non-invasive revenue stream was discounted. CEP-1347 does cross the BBB and has been shown to elevate an index of neuronal survival in a animal lesion model. I can't tell you how many times I've seen this scenario played out. I can't tell you how many times the most obvious questions are not addressed. The ERK/JNK kinase is an EXTREMELY common pathway in cells. What is the consequence of globally inhibiting this pathway in the CNS? Recall that this pathway plays a critical role in apoptosis; despite what the public may think, cell death is a necessary and normal process EVEN IN THE CNS. So the drug is obviously designed to be taken orally, and, unless it functions with phenomenal target specificity (the subpopulation of degenerating cells being addressed, those in the nucleus basalis and the vertical band of Broca, represent a VERY small subset), will effect a fairly broad range of neuronal and, perhaps, non-neuronal, cells. Somewhat nonspecific inhibition of apoptosis is certainly not something I would want going on in my brain. Inhibited apoptosis raises another issue: when NGF was being seriously considered for AD, concerns associated with some highly probable 'unintended' side effects were never resolved. For example, NGF can induce 'ectopic' sprouting of the 'spared' or 'saved' cholinergic neurons to form connections otherwise absent in the normal brain. Previous in vivodata has already shown these connections are abnormal and thus assuredly counterproductive (at best) at even stabilizing dementia. THIS IS NOT TRIVIAL and is not to be dismissed by those claiming the rewards outweigh the risks. Blocked apoptosis would, in all likelihood, produce a non-normal brain as well (beyond the AD related dysfunction). Keep in mind the brain would continue to degenerate with CEP-1347; if the blocking of apoptosis has NGF-like effects, then the dementia may be further exacerbated by the proliferation of connections. This as become far too much of a tome. I'll not comment, publicly or privately, regarding Harry Tracy's newsletter nor his opinions. He has found a niche and there are obviously a population of folks who rely on his advice for investment guidance in this field. You will understand (in the most diplomatic terms I can muster) that those whose careers overlap with the broad swath of Harry Tracy's opinions find them far too general to be of use. Caveat emptor.