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Biotech / Medical : Sangamo Therapeutics, Inc. SGMO -- Ignore unavailable to you. Want to Upgrade?

To: loonalone who wrote (26)	4/11/2000 12:04:00 AM
From: Mike McFarland	Respond to of 368

I don't have a background in biotech, have only played the sector these past couple years...but nobody has answered yet, so I'll mark down something. Maybe that will spur somebody else to correct me if I am way off base and help you out a bit: In my mind companies like SGMO, ARIA fit under the header "Chemical Genetics" --and since Pseudo felt my point about antisense was okay, let's throw a dozen of those in there too. I suppose any company that uses these small molecule activators would fit in the catagory. So Ligand certainly fits, plenty more I'm sure. Anyway, there seem to be a set of the older biotechs, such as Amgen, that have sort of sprung up around a single protein therapy. But activating a protein with a chemical ligand, or gene therapy seems like the next big thing for biotech--seems so to me, for what that is worth. Sangamo might be the sort of company that could go into therapeutic gene regulation, although for now, their website and such seems to make them look like more of a drug discovery company or a tool company. Probably need to read the prospectus more carefully, most of the answers are all there. As far as comparing to Ariad...well I have not owned Ariad for awhile (gave it up way too early before the really good hype hit it) but one of the more interesting things I ever came across when I was looking into Ariad was the website for this fellow, Schreiber--one of half a dozen research scientists I found named in the Ariad annual report: Chemical Genetics Resulting from a Passion for Synthetic Organic Chemistry www-schreiber.chem.harvard.edu Anyway, getting back to your question: Ariad should be looking for a partner for their gene therapy regulation systems, I think hGH was one of the uses, EPO the other for ARGENT, and that other was insulin. I think they need a new vector however--Adenovirus seems to have been put on the back burner. Even Merck isn't letting Baylor work with their naked Ad (whoops, see I am such a newbie still--I should have said "gutless" Adenovirus.) For now, if you have to be in on gene therapy, the AAV companies seem to be the way to go--although you cant deliver large genes with AAV. I own Tgen, many folks seem to own CEGE and AVGN. I don't think SGMO really fits in there with the gene therapy companies yet, although the link to Tgen had me excited for a minute. I'd hoped for a post IPO move up today, but got stopped out of extra shares pretty quick. But I'm willing to bet that this ZFP technology leads to a few good leads in the years ahead--you only need one blockbuster to get big. I sure hope Sangamo gets a blockbuster someday--and if not, they seems to have this platform as the fall back part of their business model, with royalites from the big boys who do come up with new drugs. Good luck loonalone! There is no lack of extremely cool sounding tech in this sector. Too back everybody seems to be selling their biotech shares right now--much harder to be faithful to the sector, which up til recently, has really rewarded folks this past year.

To: loonalone who wrote (26)	4/11/2000 8:53:00 AM
From: scott_jiminez	Read Replies (1) \| Respond to of 368

Loanalone - While on the surface Ariad and Sangamo may appear to addressing similar targets with parallel technologies, the two approaches are quite different. In a nutshell, Sangamo targets the modification of activity of endogenous genes by altering the zinc-finger transcription factor binding activity. Thus let's say the insulin gene has a ZFP site in its promoter which is critical for activation of the gene. SGMO might design a ZFP that can specifically interact with the insulin promoter, supplanting and/or enhancing the normal levels of the insulin-promoter-specific ZFP, thereby potentially raising the insulin titer. In contrast Ariad's ARGENT and RAPID systems do not interact with endogenous promoters but rely on their own 'manufacturing plant' to deliver a compound. With ARGENT, for example, a set of vectors (adeno-associated virus containing specific genes) are delivered to a cell. The genes inserted into the vectors fall into two categories: 1. A construct containing a promoter upstream of a gene whose protein product is the drug to be delivered. This construct is inactive unless stimulated; 2. Constructs containing promoter-activator genes. These constructs are continuously expressed. The promoter-activator genes, whose protein products exist in the cell at all times, do not bind to the 'drug-construct' promoter due to the requirements of proximity and orientation on the promoter which does not occur randomly. However, when a 'dimerizer' is given to the cell, the promoter activator proteins ARE brought into the proper alignment, they bind to the promoter, activate the gene, and the protein is expressed. This entire scenario can be applied to the insulin example: deliver a drug construct containing the insulin gene (usually placed in muscle cells) together with the promoter activator genes. When insulin demand becomes manifest, apply the dimerizer (a pill, orally), and insulin levels will rise. Ariad has successfully achieved this mice. Thus Sangamo 'designs' compounds to activate 'endogenous' promoters while Ariad applies a completely artificial system using 'exogenous' constructs to deliver drugs. The question whether these two approaches represent different platforms is, IMO, unanswerable and mostly likely, not critical. I cannot state with certainty whether one approach outflanks another for certain diseases or under certain circumstances. I cannot state for certain as well whether, in the end, the more successful methodology will be the result of better marketing, more cash, etc. on the one hand, or better fundamental science on the other. One can only hope the latter prevails. I hope this helps.