It's down more than 20% on over 750,000 shares traded in pre-market. Piper Jaffrey has just downgraded to neutral with a $10 price target. I'm not sure you are seeing the bigger picture and are kidding yourself if you think this is just some manipulation to get cheap shares. The briefing doc calls into question whether or not an Adomm will recommend for approval, not something anyone would have anticipated 24 hours ago, especially after the positive AEGR briefing docs. This is going down today and tomorrow, especially if the adcomm goes well for AEGR tomorrow. If the adcomm does go well for ISIS on Thursday, you'll see a big pop, but then get out as the REMS suggested by the FDA is VERY limiting. ISIS is still a good long-term play, so think of anything under $10 as a buying opportunity, but I wouldn't buy before the adcomm unless you have a very high risk tolerance.