Paxil CR Clinical Development

<table cellspacing="1" cellpadding="7" width="312" border="1"> <tbody> <tr> <td valign="top" bgcolor="#ffffff" height="16"> <br /> <br /> <p> <b><font face="Times" color="#ff0000" size="5">Paxil CR Clinical Development</font></b> </p> </td> </tr> <tr> <td valign="top" bgcolor="#ffffff" height="16"> <p> <b><font face="Times" size="4">IND Chronology</font></b> </p> </td> </tr> </tbody> </table> <table cellspacing="1" cellpadding="7" width="312" border="1"> <tbody> <tr> <td valign="top" width="27%" height="15"> <p> <b><font face="Helvetica Condensed" size="1">Date</font></b> </p> </td> <td valign="top" width="73%" height="15"> <p> <b><font face="Helvetica Condensed" size="1">Action</font></b> </p> </td> </tr> <tr> <td valign="top" width="27%" height="15"> <p> <font face="Helvetica Condensed" size="2">7/3/1996</font> </p> </td> <td valign="top" width="73%" height="15"> <p> <font face="Helvetica Condensed" size="2">Pre-IND meeting for CR formulation; FDA recommends development plan</font> </p> </td> </tr> <tr> <td valign="top" width="27%" height="15"> <p> <font face="Helvetica Condensed" size="2">7/23/1996</font> </p> </td> <td valign="top" width="73%" height="15"> <p> <font face="Helvetica Condensed" size="2">IND submitted</font> </p> </td> </tr> <tr> <td valign="top" width="27%" height="15"> <p> <font face="Helvetica Condensed" size="2">8/15/1996</font> </p> </td> <td valign="top" width="73%" height="15"> <p> <font face="Helvetica Condensed" size="2">FDA allows GSK to proceed with <i>Phase III</i> safety and efficacy depression study (Protocol 448)</font> </p> </td> </tr> <tr> <td valign="top" width="27%" height="15"> <p> <font face="Helvetica Condensed" size="2">9/5/1996</font> </p> </td> <td valign="top" width="73%" height="15"> <p> <font face="Helvetica Condensed" size="2">Protocol 449 submitted</font> </p> </td> </tr> <tr> <td valign="top" width="27%" height="15"> <p> <font face="Helvetica Condensed" size="2">10/3/1996</font> </p> </td> <td valign="top" width="73%" height="15"> <p> <font face="Helvetica Condensed" size="2">Protocol 487 submitted</font> </p> </td> </tr> <tr> <td valign="top" width="27%" height="15"> <p> <font face="Helvetica Condensed" size="2">10/17/1996</font> </p> </td> <td valign="top" width="73%" height="15"> <p> <font face="Helvetica Condensed" size="2">Protocols 494, 495 and 497 submitted for panic disorder</font> </p> </td> </tr> <tr> <td valign="top" bgcolor="#ffffff" colspan="2" height="16"> <p> <b><font face="Times" size="4">Depression NDA Chronology (#20-936)</font></b> </p> </td> </tr> <tr> <td valign="top" width="27%" height="15"> <p> <b><font face="Helvetica Condensed" size="1">Date</font></b> </p> </td> <td valign="top" width="73%" height="15"> <p> <b><font face="Helvetica Condensed" size="1">Action</font></b> </p> </td> </tr> <tr> <td valign="top" width="27%" height="15"> <p> <font face="Helvetica Condensed" size="2">7/11/1997</font> </p> </td> <td valign="top" width="73%" height="15"> <p> <font face="Helvetica Condensed" size="2">Pre-NDA meeting to discuss format of application</font> </p> </td> </tr> <tr> <td valign="top" width="27%" height="15"> <p> <font face="Helvetica Condensed" size="2">8/12/1997</font> </p> </td> <td valign="top" width="73%" height="15"> <p> <font face="Helvetica Condensed" size="2">FDA Biopharmaceutics staff meeting to discuss "relevant biopharm issues"</font> </p> </td> </tr> <tr> <td valign="top" width="27%" height="15"> <p> <font face="Helvetica Condensed" size="2">12/19/1997</font> </p> </td> <td valign="top" width="73%" height="15"> <p> <font face="Helvetica Condensed" size="2">NDA submitted</font> </p> </td> </tr> <tr> <td valign="top" width="27%" height="15"> <p> <font face="Helvetica Condensed" size="2">2/5/1998</font> </p> </td> <td valign="top" width="73%" height="15"> <p> <font face="Helvetica Condensed" size="2">NDA considered fileable</font> </p> </td> </tr> <tr> <td valign="top" width="27%" height="15"> <p> <font face="Helvetica Condensed" size="2">2/11/1998</font> </p> </td> <td valign="top" width="73%" height="15"> <p> <font face="Helvetica Condensed" size="2">FDA/GSK teleconference to discuss biopharmaceutic review issues</font> </p> </td> </tr> <tr> <td valign="top" width="27%" height="15"> <p> <font face="Helvetica Condensed" size="2">4/21/1998</font> </p> </td> <td valign="top" width="73%" height="15"> <p> <font face="Helvetica Condensed" size="2">Amendment submitted consisting of study report for Protocol 487 and labeling changes</font> </p> </td> </tr> <tr> <td valign="top" width="27%" height="15"> <p> <font face="Helvetica Condensed" size="2">8/12/1998</font> </p> </td> <td valign="top" width="73%" height="15"> <p> <font face="Helvetica Condensed" size="2">FDA letter addressing CMC deficiencies</font> </p> </td> </tr> <tr> <td valign="top" width="27%" height="15"> <p> <font face="Helvetica Condensed" size="2">10/9/1998</font> </p> </td> <td valign="top" width="73%" height="15"> <p> <font face="Helvetica Condensed" size="2">"Approvable" letter</font> </p> </td> </tr> <tr> <td valign="top" width="27%" height="15"> <p> <font face="Helvetica Condensed" size="2">12/21/1998</font> </p> </td> <td valign="top" width="73%" height="15"> <p> <font face="Helvetica Condensed" size="2">Major amendment submitted in response to "approvable" letter; user fee goal set for Feb. 21, 1999</font> </p> </td> </tr> <tr> <td valign="top" width="27%" height="15"> <p> <font face="Helvetica Condensed" size="2">2/16/1999</font> </p> </td> <td valign="top" width="73%" height="15"> <p> <font face="Helvetica Condensed" size="2">Depression NDA approved</font> </p> </td> </tr> <tr> <td valign="top" bgcolor="#ffffff" colspan="2" height="16"> <p> <b><font face="Times" size="4">Panic NDA Chronology (#20-982)</font></b> </p> </td> </tr> <tr> <td valign="top" width="27%" height="15"> <p> <b><font face="Helvetica Condensed" size="1">Date</font></b> </p> </td> <td valign="top" width="73%" height="15"> <p> <b><font face="Helvetica Condensed" size="1">Action</font></b> </p> </td> </tr> <tr> <td valign="top" width="27%" height="15"> <p> <font face="Helvetica Condensed" size="2">4/22/1998</font> </p> </td> <td valign="top" width="73%" height="15"> <p> <font face="Helvetica Condensed" size="2">NDA for panic disorder submitted</font> </p> </td> </tr> <tr> <td valign="top" width="27%" height="15"> <p> <font face="Helvetica Condensed" size="2">3/10/1999</font> </p> </td> <td valign="top" width="73%" height="15"> <p> <font face="Helvetica Condensed" size="2">Initial "approvable" letter, which includes dissolution specifications and requests updates on safety, regulatory status and literature</font> </p> </td> </tr> <tr> <td valign="top" width="27%" height="15"> <p> <font face="Helvetica Condensed" size="2">7/7/1999</font> </p> </td> <td valign="top" width="73%" height="15"> <p> <font face="Helvetica Condensed" size="2">GSK responds to "approvable" letter, including alternative labeling and safety experience from two bioequivalence studies</font> </p> </td> </tr> <tr> <td valign="top" width="27%" height="15"> <p> <font face="Helvetica Condensed" size="2">8/17/1999</font> </p> </td> <td valign="top" width="73%" height="15"> <p> <font face="Helvetica Condensed" size="2">FDA faxes GSK "a slightly modified version of labeling"; at issue is the adverse events section</font> </p> </td> </tr> <tr> <td valign="top" width="27%" height="15"> <p> <font face="Helvetica Condensed" size="2">1/3/2000</font> </p> </td> <td valign="top" width="73%" height="15"> <p> <font face="Helvetica Condensed" size="2">After receiving no response from GSK, FDA issues second "approvable" letter that is similar to the first, but includes FDA's Aug. 17, 1999 labeling</font> </p> </td> </tr> <tr> <td valign="top" width="27%" height="15"> <p> <font face="Helvetica Condensed" size="2">12/18/2001</font> </p> </td> <td valign="top" width="73%" height="15"> <p> <font face="Helvetica Condensed" size="2">GSK responds to second letter with submission including minor labeling changes and information updates</font> </p> </td> </tr> <tr> <td valign="top" width="27%" height="15"> <p> <font face="Helvetica Condensed" size="2">1/31/2002</font> </p> </td> <td valign="top" width="73%" height="15"> <p> <font face="Helvetica Condensed" size="2">GSK agrees to FDA's final labeling changes</font> </p> </td> </tr> <tr> <td valign="top" width="27%" height="15"> <p> <font face="Helvetica Condensed" size="2">2/12/2002</font> </p> </td> <td valign="top" width="73%" height="15"> <p> <font face="Helvetica Condensed" size="2">Panic disorder NDA approved</font> </p> </td> </tr> </tbody> </table>