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

To: sds who wrote (1895)	4/6/1998 5:45:00 PM
From: emil	Respond to of 4676

In terms of performance, ISIP has been less than my hopes to this point. But in all the doubts and worry over the trials you refer to, I am still quite long on Antisense. ISIP is the antisense leader, as MSFT is the pc-software leader. ISIP now needs to go from the 'DOS' phase, to the modern day 'office 97 and windows 95' phase (where the rubber hit the road and profit kicked in!). I dont think with all the less than ideal priced-in factors discussed, that this changes my opinion with ISIP. Although, patience and meditation have been a must up until this juncture.

To: sds who wrote (1895)	4/7/1998 3:02:00 AM
From: Miljenko Zuanic	Respond to of 4676

To sds, Perry, Amateur, Emil,.. sds: I do share your concern about ISIP future and long-term investment. I am disappointed with Isis lagging 12-16 months results. Also, I did reduce (now by 50%) my large ISIP holding. But, I am not ready to give-up on ISIP. Also, Isis is not the only company in which am disappointed. So, here is my view: 1. CMV Retinitis: Why ISIP is developing and conducting trials with sec. generation antisense when market is shrinking? Does not make any sense, unless HIV infected individuals (even now with promising therapy for delay of diseases progression and opportunistic infection development) will at one point develop non-response to therapy and disease will take its deadly course. I think that we are not yet done with AIDS. 2. Cells adhesion (ICAM-1): i.v. 2302 for psoriasis would never had large market, only ones who do not have other choice. Regime and therapy (i.v.) are not for this type of chronic diseases. So, topical formulation (I hope with sec. gen.) is logical step forward (if drug show therapeutic effects in i.v. trials?). This will delay for at least one year(~1 1/2) clinical development ( PI/II will be first for topical formulation), but better delay than non-sense module/regime. This is positive news for ISIP, imo. Chron's, RA, renal transplant....Crohn's and RA can proceed with current formulation, but for favorable market penetration (when is efficiency comparable to other drugs) subcutaneous injection will be more appropriate. This can be solved only with significant smaller drug dose (plasma stable antisense, no high blood pressure, and more potent drug....sec. generation?). 3. Cancer: I am not pleased with current results. Only ovarian cancer (small market) show some promise. But, there are preclinical results which can improve antisense cancer potency. This should be balanced with current and new clinical trials. Novartis commitment will be main factor. Things to look in future is new revised agreement with Novartis. Because current deal do not cover sec. gen. molecules, will be interesting how deal will be formulated. If Novartis like antisense, cancer market is warrant for any substantial financial commitment. And, if you check Novartis deals, they are not cheap with $$$. BI: Their interest in inflammation market is great support to ISIP. Still, Isis will have to sacrifice bit of profit sharing (decrease of the drug royalty with more credit line finance from BI, against future royalty) if they wont to be in game. So, Is ISIP next Microsoft? NO, NOT YET! But it is not ISIP from 94/95 when they drooped PV antisense or from 96 when Eisay cancel 2922 deal. ISIP is now more mature bt company with two products ( I do not have any second thought that 2302 will fail in Crohn's) which revenue will help offset high development expense. I was hopping for high eps by 2000, but it is now dream. Still I do not evaluate company by its projected eps, it is more her potential for eps grow and drugs discovery potential. Hope, at Open House will have some answers. Amateur: Instead repeated (and non completed) news on Fomivirsen, why Isis didn't report (and present at conf.) update on HCV antisense? Where is PI trials? This will be of much great interest for investors. At least for me. Last year, preclinical data looked good to me! mz