But it seems to me ALNY investors get confused when they buy more ALNY shares. This is good news for ISIS with its antisense drug not for ALNY. ALNY do not have any product yet and nothing in the near future either. Remember news only makes money for insiders.
Potted--I think you may be a little bit of a fraud based upon the subject and timing of your last post. In any case,
1) Response in the body varies by dose, of course. The whole point of finding a more potent compound is that you'll need less of it to do its job. That's why when something comes along that's more active "in the test tube" (as you put it), drug companies get very excited by it--which is why there is a lot more interest by big pharma in RNAi than in antisense 1.0, 2.0, or 2.2. And hence why many people have invested in Alnylam. ISIS's pipeline of second generation antisense is very impressive and the candidates all have chances to be very successful based on their own merits. Mipomersen should draw great bidding interest. But the fact remains that RNAi has garnered much more big pharma interest in general because the technology appears to have much more promise.
2) In light of this there has been something of a huge PR campaign of late to recast ISIS as an RNAi drug company. As you noted, ISIS has an interest in single-stranded antisense compounds to initiate an RNAi response (rather than a response via the RNase H mechanism). But, according to ISIS, this work has only just made it through "feasibility" studies and now the company is the recipient of a $1.5 million dollar award from the NIH to pursue this further--this is not exactly a heck of a lot of money in the pharmaceutical industry and won't go too far. And, any drugs developed would still incur a royalty to Alnylam. Still, this is a very interesting area since single-stranded compounds are be easier to deliver, but it may be eclipsed totally by the advances in ds siRNA delivery that you refuse to acknowledge. We may disagree here, but there is no denying that there are hundreds of millions of research dollars going into ds RNAi delivery now, and I would not bet against major breakthroughs. Is there a particular reason you are so pessimistic? Do you think Alnylam will achieve poor results with its PCSK9 program due to an inability to target it with their systematic lipidoid delivery system (the existence of which, by the way, you seem to deny)?
3) Bottom line: I suspect that ISIS is highly undervalued even with the recent run up because the market doesn't fully appreciate or respect its pipeline. I would be an investor here. But I think that there is even more upside for RNAi, and while you are yelling about "no delivery" you are missing out on a great investment.
Ein . . . First off . . . Potted would like to thank you for this discussion . . . one that will surely enlighten readers on this board. . . . And Potted had to sharpen a couple of pencils for this one!
Oh Ein . . . Potted is not a paid basher! . . . but if you want to wire Potted some $$$ to bash Alnylam after you "come to your senses" - - after reading this post - - well that's OK with Potted!
Ein. . . . the 1 to 100 ratio you mentioned is STALE, old news! . . . and relates to RNAi's power in the test tube - - but unfortunately NOT its power in the human body! . . . and the RNAi comparison was with 1st Generation Antisense, NOT with 2nd Generation Antisense (Potted hopes this is NOT news to you!). . . You see Ein . . . while Alnylam was making hoopla in Nature magazine . . . ISIS was working hard . . . and resolved its POTENCY and DRUG AFFINITY problems with the development of 2nd Gen. Antisense (10 TIMES more potent than 1st Gen.) . . . and the Antisense 2.2 platform is about 10 TIMES more potent than 2nd Gen. - - so Ein . . . that 1 to 100 ratio no longer holds water! . . . and Ein - - when Potted talks about Antisense POTENCY. . . Potted is talking about potency in the BODY! (Potted certainly has to make that distinction when discussing with the Alnylam folks!)
Ein . . . since you think you know so much - - please define for Potted the successful drug delivery system Alnylam has developed for RNAi - - and when you do - - be sure to also tell the folks there at Alnylam! - - Gee! - - that alone should pump the ANLY stock to the heavens!
Ein . . . Potted readily admits that he still has a lot to learn . . . but Potted knows that Antisense and RNAi work via different methods - - but both can work to accomplish some of the same goals - - e.g. silencing genes! . . . But Potted does know ONE thing that Ein should know, and that's the difference between SINGLE-STRANDED technology (ISIS Antisense) . . . and DOUBLE-STRANDED technology (Alnylam's RNAi) . . . because that's one of the KEY complicating factors that is thwarting Alnylam's attempt at successful drug delivery!
Ein . . . here's one more little thing! . . . ISIS recently announced that they are now developing SINGLE-STRANDED RNAi technology! . . . with effective drug delivery! . . . (read no patent infringement with Alnylam!) . . . Yes Ein! . . . ISIS and ALNY are going to go �Head-to-Head� with effective RNAi-based drug therapeutics! - - ISIS must think they've likely given the �newbie� Alnylam enough time to solve their own problems . . . so now �the Veteran� is going to show them just how it should be done! - - the "ISIS Antisense" way!
Oh . . . and one little correction . . . ISIS and ALNY are in collaborations with everything �microRNA�, but will likely remain �competitors� in the single-gene target arena. . . . You see Ein . . . ISIS has the �Gene Silencing� technology that WORKS!! . . . while Alnylam has the �Gene Silencing� technology that DOES NOT WORK!! . . . . Eventually . . . the market, and members on this board, and even possibly you, Ein . . . will come to that realization! . . . (Ein - - Off-Stage Right) . . . Oh! . . . but wait . . . Alnylam�s success is just around the corner! . . . or the next corner! . . . . or the next!
Ein . . . the only BIG question that you have yet to answer is . . . just when do you SELL?
Go to the Head-of-the-Class with ISIS!
Oh you paid basher. It�s so dumb. Ever heard that you need about 1/100 of an siRNA compound to get the effect of an antisense compound? Come on, do some DD on antisense, siRNA, miRNA, drosha, dicer and, and, and. And read about delivery. You can only frighten people with no knowledge of the technology. And no knowledge of the Isis/Alnylam COLLABORATION. Yes my dumb friend, they work together.
I should set you on ignore, but sometimes it�s so funny to read your wishful thinking. When you�ve got that antisense and RNAi is not the same class, but pretty different ALNY may have reached $100 on your strong sell.
OK . . . Big10 . . . Potted was just making a POINT that for a comparable target, apoB, ISIS has been able to MOVE its drug candidate THRU the CLINICAL research stages, e.g. Phase I, II, and eventually III and to the MARKET . . . while ALNYLAM drug candidates must WAIT in the pre-clinical stage. . . . WHY? . . . Alnylam has yet to DEFINE an effective drug delivery system for RNAi! - - thus the drug candidates CANNOT ADVANCE!
Most of the bio press, and many investors have yet to realize this - - and it is a VERY IMPORTANT CONCEPT! . . . it matters NOT how many pre-clinical drug candidates ALNY has . . . or how many NEW pre-clinical programs Alnylam initiates . . . if they CANNOT ADVANCE their drug candidates beyond pre-clinical! - - it is JUST a WASTE of TIME, EFFORT, and MONEY! - IMO. . . In Potted's view, Alnylam should HALT all new drug programs, and FOCUS ALL RESOURCES on developing an effective drug delivery system for RNAi! . . . Potted thinks Alnylam has its PRIORITIES all mixed up! - - and is looking "over its shoulder" at ISIS when determining resource allocations - - A BAD MANAGEMENT MOVE!
In comparison, ISIS now HAS a defined and very successful drug-delivery system for 2nd Generation Antisense drugs - - thus ISIS CAN now develop new drug candidates . . . and then ADVANCE them thru the CLINICAL STAGES! . . . Here comes another Potted Mantra, (but one that has been said before) . . . "First Things First!" - - Sadly a simple LESSON that Alnylam has yet to learn!
Big10 . . . now with BMS's support for ISIS's PCSK-9 Antisense program, it will be interesting to see how ALNY and ISIS advance those "comparable" drug candidates! . . . are you, Big10, willing to place a bet on who achieves a successful Phase III first? . . . you know that Potted has his money on ISIS!!!
Go to the Head-of-the-Class with ISIS!
Allel . . . Potted currently has no position in ALNY, and is NOT short the stock. . . . but Potted may consider a position in Alnylam if the management eventually "comes clean" with their investors. . . . and if they finally identify an effective drug delivery system! . . . and SOON! . . . Yes, Potted thinks that ALNY has done some "shady practices" that have PUMPED the stock in the short-term, but will likely affect Alnylam�s credibility over the longer term.
Case in point . . . most ALNY investors think that ALNY developed the "2-MOE gapmers" which Alnylam called "Antagemeres" for their much ballyhooed microRNA developments. . . but this very important technology was actually licensed from ISIS - - it is ISIS's 2nd Generation Antisense technology! - - but Alnylam could NOT tell THAT to their investors in the research releases! . . . so Alnylam developed a NEW name for the ISIS technology . . . and IMPLIED that it was their own technology to investors!
And today - - investors continue to cite the "Antagameres" technology as a KEY developmental milestone for Alnylam! . . . and Alnylam NEVER sets the record straight! . . . Now some may call that being SMART! . . . but Potted calls that being STUPID! - - and FOOLING the investment community! - - NOT good BEHAVIOR for an emerging bio - - IMO!
Allel . . . Merck spent over $1 billion for Sirna - - and with NO defined effective drug delivery system! . . . and now Roche spent over $400 million for Alnylam�s RNAi IP - - and again with NO defined effective drug delivery system! . . And you ask . . . �do you say people just throw money around mindlessly?� . . . Well . . . YES! . . . All Potted has to say is . . . look at AOL-TimeWarner! . . . and the two (ALNY & AOL) are very similar, IMO . . . Both are (were) chasing a DREAM! . . . and both face(d) problems EXECUTING on that dream. . . . For Alnylam . . . they are trying to harness the RNAi �explosion release� in the body . . . and while some say it is just a matter of time . . . man has yet to successfully harness the terrific power in a bolt of lightning - - and make that power useable - - it is just too POWERFUL and too FAST! - - but hey! . . . that�s the same problem Alnylam faces with RNAi!
The future for Alnylam is NOT exemplified in today�s press release about their new PCSK-9 target in pre-clinical testing. . . another Alnylam drug target deemed to WAIT for years in the pre-clinical stage. . . with about 8 others! . . . No! . . . Potted believes the future for Alnylam will be determined over the next few years . . . and if an effective drug delivery system is NOT well defined for RNAi by then - - well . . . it will be TOO LATE! . . . Why? . . . because ISIS�s 2nd generation Antisense will have gained so much TRACTION by then, with successful RNA-based drugs entering the marketplace, and with several candidates in Phase III and Phase II trials . . . the market will largely IGNORE the dozen Alnylam drug candidates that have waited ENDLESSLY in pre-clinical - - WAITING for a drug-delivery system that eventually NEVER materialized!
That�s just how Potted sees it! . . . and nothing Alnylam released today changes that one bit! . . . in fact, the research article exemplifies just how far behind Alnylam is, when compared with ISIS. . . and how far ALNY needs to progress in its research programs! . . . an effective drug delivery system for RNAi is still just a DREAM!
Go to the Head-of-the-Class with ISIS! . . . as the Doctor at DALM expressed . . . "Antisense: from PROMISE to PRACTICE!"
Sure, I can see your annoyance with this person, you can safely ignore him. But for me, like lots of people new to the board, there is usefulness in exposure to all sides of the story before forming one's own judgement.
I've owned ALNY for a while but have posted here very little. I'm surprised that you folks have not used the "ignore user" feature. The stock goes up because 99% of investors believe it should. Why waste time and energy (as I am doing now ) on the loser 1%? The "ignore user" click is next for me.
1. Credibility of the witness. Don't you have an emotinal ax to grind? Are you short ALNY? Let me know so I can do proper discounting on your opinion.
2. Why do you keep saying where is the beef? If I my elementary school reading skill still intact, Yahoo! source says: $4M in FY04, $6M in 05, $27M in 06, and at a $53M going rate for FY07. Drugs or no drugs, is this growth not good? Or do you say people just throw money around mindlessly?
3. If you care about the effectiveness of your argument, then you should not let style get in the way - just like the fashion gurus say, don't wear mini skirt and ask them to pay attention to your chart, and nothing but the chart.