Noxafil Clinical Development

<table cellspacing="1" cellpadding="7" width="100%" border="1"> <tbody> <tr> <td valign="top" colspan="2" height="16"> <br /> <br /> <p> <b><font color="#ff0000" size="5">Noxafil Clinical Development</font></b> </p> </td> </tr> <tr> <td valign="top" width="15%" height="15"> <p> <b><font face="Helvetica Condensed" size="2">Date</font></b> </p> </td> <td valign="top" width="85%" height="15"> <p> <b><font face="Helvetica Condensed" size="2">Action</font></b> </p> </td> </tr> <tr> <td valign="top" bgcolor="#ffffff" colspan="2" height="16"> <p> <b><i><font size="4">IND Chronology (51,662)</font></i></b> </p> </td> </tr> <tr> <td valign="top" width="15%" height="15"> <p> <font face="Helvetica Condensed" size="3">10/4/1996</font> </p> </td> <td valign="top" width="85%" height="15"> <p> <font face="Helvetica Condensed" size="3">IND submission</font> </p> </td> </tr> <tr> <td valign="top" width="15%" height="15"> <p> <font face="Helvetica Condensed" size="3">12/13/2000</font> </p> </td> <td valign="top" width="85%" height="15"> <p> <font face="Helvetica Condensed" size="3">End-of-Phase II meeting</font> </p> </td> </tr> <tr> <td valign="top" width="15%" height="15"> <p> <font face="Helvetica Condensed" size="3">10/6/2003</font> </p> </td> <td valign="top" width="85%" height="15"> <p> <font face="Helvetica Condensed" size="3">Pre-NDA meeting for NDA for treatment of certain refractory invasive fungal infections (IFI)</font> </p> </td> </tr> <tr> <td valign="top" width="15%" height="15"> <p> <font face="Helvetica Condensed" size="3">5/2004</font> </p> </td> <td valign="top" width="85%" height="15"> <p> <font face="Helvetica Condensed" size="3">NDA for refractory IFI treatment indication submitted</font> </p> </td> </tr> <tr> <td valign="top" width="15%" height="15"> <p> <font face="Helvetica Condensed" size="3">3/2005</font> </p> </td> <td valign="top" width="85%" height="15"> <p> <font face="Helvetica Condensed" size="3">Original user fee goal for IFI treatment NDA, extended by FDA</font> </p> </td> </tr> <tr> <td valign="top" width="15%" height="15"> <p> <font face="Helvetica Condensed" size="3">6/10/2005</font> </p> </td> <td valign="top" width="85%" height="15"> <p> <font face="Helvetica Condensed" size="3">"Approvable" letter issued for IFI treatment NDA</font> </p> </td> </tr> <tr> <td valign="top" width="15%" height="15"> <p> <font face="Helvetica Condensed" size="3">10/25/2005</font> </p> </td> <td valign="top" width="85%" height="15"> <p> <font face="Helvetica Condensed" size="3">Pre-NDA meeting for IFI prophylaxis and oropharyngeal candidiasis (OPC) indications</font> </p> </td> </tr> <tr> <td valign="top" bgcolor="#ffffff" colspan="2" height="16"> <p> <b><i><font size="4">NDA Chronology (22-003)</font></i></b> </p> </td> </tr> <tr> <td valign="top" width="15%" height="15"> <p> <font face="Helvetica Condensed" size="3">12/22/2005</font> </p> </td> <td valign="top" width="85%" height="15"> <p> <font face="Helvetica Condensed" size="3">NDA submission (actually submitted 12/21 and rec'd 12/22)</font> </p> </td> </tr> <tr> <td valign="top" width="15%" height="15"> <p> <font face="Helvetica Condensed" size="3">2/8/2006</font> </p> </td> <td valign="top" width="85%" height="15"> <p> <font face="Helvetica Condensed" size="3">FDA notifies Schering-Plough that NDA 22-003 will be split into two applications: 22-003 (priority review) for prophylaxis of invasive fungal infections and 22-027 (standard review) for treatment of oropharyngeal candidiasis (OPC)</font> </p> </td> </tr> <tr> <td valign="top" width="15%" height="15"> <p> <font face="Helvetica Condensed" size="3">3/10/2006-4/6/2006</font> </p> </td> <td valign="top" width="85%" height="15"> <p> <font face="Helvetica Condensed" size="3">Directed clinical inspection of an investigator conducted in response to a complaint</font> </p> </td> </tr> <tr> <td valign="top" width="15%" height="15"> <p> <font face="Helvetica Condensed" size="3">5/26/2006</font> </p> </td> <td valign="top" width="85%" height="15"> <p> <font face="Helvetica Condensed" size="3">Teleconference to discuss "impressive difference" in clinical outcome and incidence of proven/probable IFI in lowest quartile of patients (based on posaconazole levels)</font> </p> </td> </tr> <tr> <td valign="top" width="15%" height="15"> <p> <font face="Helvetica Condensed" size="3">6/6/2006</font> </p> </td> <td valign="top" width="85%" height="15"> <p> <font face="Helvetica Condensed" size="3">Pre-approval safety conference</font> </p> </td> </tr> <tr> <td valign="top" width="15%" height="15"> <p> <font face="Helvetica Condensed" size="3">6/16/2006</font> </p> </td> <td valign="top" width="85%" height="15"> <p> <font face="Helvetica Condensed" size="3">Teleconference to discuss plasma concentration concerns</font> </p> </td> </tr> <tr> <td valign="top" width="15%" height="15"> <p> <font face="Helvetica Condensed" size="3">6/21/2006</font> </p> </td> <td valign="top" width="85%" height="15"> <p> <font face="Helvetica Condensed" size="3">Teleconference to discuss postmarketing commitments</font> </p> </td> </tr> <tr> <td valign="top" width="15%" height="15"> <p> <font face="Helvetica Condensed" size="3">6/22/2006</font> </p> </td> <td valign="top" width="85%" height="15"> <p> <font face="Helvetica Condensed" size="3">User fee goal for NDA 22-003; teleconference to inform sponsor that no action will be taken</font> </p> </td> </tr> <tr> <td valign="top" width="15%" height="15"> <p> <font face="Helvetica Condensed" size="3">8/8/2006</font> </p> </td> <td valign="top" width="85%" height="15"> <p> <font face="Helvetica Condensed" size="3">Division of Scientific Investigations notifies review division that data from a site is not reliable and recommends the data be excluded</font> </p> </td> </tr> <tr> <td valign="top" width="15%" height="15"> <p> <font face="Helvetica Condensed" size="3">8/18/2006</font> </p> </td> <td valign="top" width="85%" height="15"> <p> <font face="Helvetica Condensed" size="3">FDA notifies Schering-Plough that data from the site will be excluded</font> </p> </td> </tr> <tr> <td valign="top" width="15%" height="15"> <p> <font face="Helvetica Condensed" size="3">8/29/2006</font> </p> </td> <td valign="top" width="85%" height="15"> <p> <font face="Helvetica Condensed" size="3">Schering-Plough asks that data rejected by DSI be maintained with monitoring, verification</font> </p> </td> </tr> <tr> <td valign="top" width="15%" height="15"> <p> <font face="Helvetica Condensed" size="3">9/15/2006</font> </p> </td> <td valign="top" width="85%" height="15"> <p> <font face="Helvetica Condensed" size="3">NDA 22-003 approved for IFI prophylaxis in severely immunocompromised patients</font> </p> </td> </tr> <tr> <td valign="top" width="15%" height="15"> <p> <font face="Helvetica Condensed" size="3">10/20/2006</font> </p> </td> <td valign="top" width="85%" height="15"> <p> <font face="Helvetica Condensed" size="3">NDA 22-027 approved for treatment of OPC</font> </p> </td> </tr> <tr> <td valign="top" width="15%" height="15"> <p> <font face="Helvetica Condensed" size="3">10/22/2006</font> </p> </td> <td valign="top" width="85%" height="15"> <p> <font face="Helvetica Condensed" size="3">User fee goal for OPC indication</font> </p> </td> </tr> </tbody> </table>