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Biotech / Medical : Ionis Pharmaceuticals (IONS) -- Ignore unavailable to you. Want to Upgrade?

To: Scott H. Davis who wrote (2069)	7/6/1998 3:05:00 PM
From: makin_dough99	Respond to of 4676

CYGS re: ISIP !!! Could be more than meets the eye for antisense technologies ! President's Technical Update: July 4, 1998 As you all know, CSI has been a scrawny and scrappy OTC:BB company competing with some serious NASDAQ powerhouses. We therefore had to allocate our sparse resources, first to product development with the remainder for corporate subsistence. Our product has now been tested, and we're ready to take it to market. As our company moves from diligence and endurance to prosperity we can tidy up loose ends, pacify our corporate concerns with regulatory authorities, and get in step as a key player in the industry. Our history is interesting, but our product is the exciting news. We have sponsored the successful development of a plasmid that can be cloned into an RNA expression vector that will synthesize sequence specific DNA oligo's (ssDNA). These oligo's can be produced with or without flanking regions and are ideal for antisense or ribozyme applications. We own the patent and use rights for several broad applications of the technology. Antisense is the most exciting use currently contemplated. The biotech industry is replete with companies that have identified antisense DNA oligo's which produce a desired effect in cell culture. Unfortunately, DNA oligo delivery in living animals with acceptable results has proved elusive. Vector mediated intercellular synthesis of the desired DNA oligo utilizing existing RNA expression vectors for targeting is the solution to that problem, and that is what our product does. We hope it will catalyze the transition from cell culture to living animal experiments for a number of biotechs that already own brilliantly conceived antisense sequences but have lacked delivery means for the molecules. We are evaluating our exploitation options regarding the ssDNA vector. We currently favor collaborative agreements which will utilize our technology to build on a research partners' cell culture successes. We prefer this arrangement because it will hopefully lead to prosperous relationships wherein we can pursue our other technologies, some of which are significant in their own right. We realize that this communiqu‚ may be overly technical for the non-scientist. However, as mentioned above, we have extraordinarily limited financial resources. These can be allocated to public relations or to product development. We elect to continue our commitment to the product. After all, we have a product that our industry needs in order to mature, that has no competition, and that should prove to be quite profitable. When we have realized that profitability, we can expand our PR. This course is, after all, in everyone's best interest. Again, we thank you, our shareholders, for your support and we can all be thankful that our major hurdles are cleared and our objectives are within sight, if not within reach. Mike Skillern President 713 780-1399 Investor Relations Update: July 4, 1998 Over the past few months we have been quietly completing our research in expressing single strands of DNA (ssDNA) in living cells (in vivo), and plotting our corporate course through uncharted waters. As there are no historic comparables to our product, there are no dependable models to follow. Since we started our first sponsored research project early last year, other scientific advancements have revealed that there are many more applications for our ssDNA vector technology than originally thought. The first to come to light were the independent studies indicating the anti cancer therapies as reported in our press release on Nov, 12, 1997. Since then, other applications have been suggested, not the least of which is the antisense therapies that are generating a lot of excitement and gaining a great deal of support by the biotech community. The efficacy of antisense technology is being demonstrated in laboratories worldwide, but the practical application of antisense depends on a reliable delivery mechanism. In other words, how can they get the antisense molecule into the target cell where it can do its work? The ssDNA expression vector is the most promising candidate for that job, in fact, right now it's the only reasonable candidate. As a gross analogy, many companies have patented warheads that will destroy various diseases, but they have no rocket or guidance system to get it where it needs to be. CSI's ssDNA vector is the rocket. CSI has renewed and expanded the scope of its vector research with a new sponsored research agreement that is hoped to result in future products. We have also expanded our staff to include a specialist in commercialization and product development. The successful development of the ssDNA vector will also allow us to accelerate progress on the RegeniDerm and MariCulture fronts. Stay tuned... the fun has just begun. Dell Gibson Investor Relations 713-780-1399

To: Scott H. Davis who wrote (2069)	7/7/1998 10:42:00 AM
From: sds	Read Replies (2) \| Respond to of 4676

Protease and the new CMV, Scott, I don't know what to make of the new info. Ya know, they talk about PI resistance, but I haven't heard any specific side-effects mentioned. I would THINK that CMV-retinitis would go hand-in-hand with the PI resistance, but I haven't seen info. to support that. Have you? Here's my emerging take on CMV -- who cares? Whether it is $100 million, $200 million, or $300 million, it doesn't really matter. Either way, this won't be THE drug that makes Isis worth owning. You are very right about the Isis administration -- you can't forget. Also, from what I hear, the injection is actually not very painful and some people prefer it to pills (I guess if I were swallowing 12 pills a day, a poke in the eye might not seem so bad). In any case, I'm glad to see Isis get a drug out, but I'm still concerned about the pipeline and its translation into money. sds P.S. Got a question, and MZ is probably the best to ask -- how/why is it that a drug that treats Crohn's will usually have some effect with R.Arthritis (and vice versa). Are the both affected by the same ICAM?