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Isis Reports Strong Financial Results and Highlights for Fiscal Year 2008
Date:2/25/2009

$(0.05) $(0.04) $(0.06) Basic and diluted net loss per share applicable to common stock $(0.09) $(0.08) $(0.13) $(1.63) Shares used in computing basic and diluted net loss per share 96,889 86,970 94,566 83,739

                         Isis Pharmaceuticals, Inc.
                 Reconciliation of GAAP to Pro Forma Basis:
     Condensed Consolidated Operating Expenses and Loss From Operations
                               (In Thousands)

                                    Three months ended,      Years ended,
                                        December 31,          December 31,
                                      2008       2007        2008      2007
                                         (unaudited)          (unaudited)

    As reported operating
     expenses according to GAAP      $37,725    $27,810    $120,250   $91,263
         Excluding compensation
          expense related to stock
          options pursuant to SFAS
          123(R)                      (2,852)    (2,302)    (13,286)   (8,298)

    Pro forma operating expenses     $34,873    $25,508    $106,964   $82,965

    As reported loss from
     operations according to
     GAAP                            $(8,076)   $(6,255)   $(13,060) $(32,919)
        Excluding compensation
         expense related to stock
         options pursuant to SFAS
         123(R)                       (2,852)    (2,302)    (13,286)   (8,298)

    Pro forma income (loss) from
     operations                      $(5,224)   $(3,953)       $226  $(24,621)

    As reported net loss
     according to GAAP               $(8,658)   $(6,957)   $(11,963) $(10,994)
        Excluding compensation
         expense related to stock
         options pursuant to SFAS
         123(R)                       (3,248)    (2,702)    (15,063)   (9,910)
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SOURCE Isis Pharmaceuticals, Inc.
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