GENAERA CORP
FIRST AMENDMENT TO LEASE AGREEMENT
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<DESCRIPTION>FIRST AMENDMENT TO LEASE AGREEMENT
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 <P STYLE="margin-top:0px;margin-bottom:0px" ALIGN="right"><FONT FACE="Times New Roman" SIZE="2"><B>Exhibit 10.49 </B></FONT></P> <P STYLE="margin-top:12px;margin-bottom:0px" ALIGN="center"><FONT
FACE="Times New Roman" SIZE="2"><B><U>FIRST AMENDMENT TO </U></B></FONT></P> <P STYLE="margin-top:0px;margin-bottom:0px" ALIGN="center"><FONT FACE="Times New Roman" SIZE="2"><B><U>LEASE AGREEMENT </U></B></FONT></P> <P
STYLE="margin-top:12px;margin-bottom:0px; text-indent:4%"><FONT FACE="Times New Roman" SIZE="2">THIS FIRSTAMENDMENT TO LEASE AGREEMENT (this <B><U>&#147;Amendment&#148;</U>) </B>is made and entered as of <U>February&nbsp;6,</U> 2004 (the
<B><U>&#147;Effective Date&#148;</U>) </B>by and between ARE-5100/5110 CAMPUS DRIVE, L.P., a Delaware limited partnership <B>(<U>&#147;Landlord&#148;</U>) </B>and GENAERA CORPORATION, a Delaware corporation <B>(<U>&#147;Tenant&#148;</U>).</B>
</FONT></P> <P STYLE="margin-top:18px;margin-bottom:0px" ALIGN="center"><FONT FACE="Times New Roman" SIZE="2"><B><U>RECITALS </U></B></FONT></P> <P STYLE="margin-top:12px;margin-bottom:0px; text-indent:4%"><FONT FACE="Times New Roman" SIZE="2"><B>A.
</B>Landlord and Tenant have previously entered into that certain Lease Agreement dated as of December&nbsp;13, 2001 (the <B><U>&#147;Agreement</U>&#148;), </B>whereby Tenant extended its right to occupy the certain premises located at 5110 Campus
Drive, Plymouth Meeting, Pennsylvania, as more particularly described in the Agreement, beyond the term of the &#147;Prior Lease&#148; (as such term is defined in the Agreement). </FONT></P> <P
STYLE="margin-top:12px;margin-bottom:0px; text-indent:4%"><FONT FACE="Times New Roman" SIZE="2">B. Landlord and Tenant now desire to amend the Agreement on and subject to the terms and conditions set forth herein to confirm the &#147;Term&#148; of
the Agreement. </FONT></P> <P STYLE="margin-top:12px;margin-bottom:0px; text-indent:4%"><FONT FACE="Times New Roman" SIZE="2">NOW, THEREFORE, in consideration of the mutual covenants and agreements contained herein, Landlord and Tenant agree as
follows: </FONT></P> <P STYLE="margin-top:12px;margin-bottom:0px; text-indent:4%"><FONT FACE="Times New Roman" SIZE="2">1. <B><U>Term</U>. </B>The &#147;Commencement Date&#148; shall be December&nbsp;1, 2001 and the &#147;Term&#148; shall be the
&#147;Base Term&#148; (as such terms are defined in the Agreement). The Agreement shall therefore expire on November&nbsp;30, 2007. </FONT></P> <P STYLE="margin-top:12px;margin-bottom:0px; text-indent:4%"><FONT FACE="Times New Roman" SIZE="2">2.
<B><U>Miscellaneous</U></B> </FONT></P> <P STYLE="margin-top:6px;margin-bottom:0px; margin-left:4%; text-indent:4%"><FONT FACE="Times New Roman" SIZE="2">(a) This Amendment shall be construed under and in accordance with the laws of the State where
the real property is located. </FONT></P> <P STYLE="margin-top:6px;margin-bottom:0px; margin-left:4%; text-indent:4%"><FONT FACE="Times New Roman" SIZE="2">(b) This Amendment shall be binding upon and inure to the benefit of the parties hereto,
their respective heirs, executors, administrators, legal representatives, successors, and permitted assigns. </FONT></P> <P STYLE="margin-top:6px;margin-bottom:0px; margin-left:4%; text-indent:4%"><FONT FACE="Times New Roman" SIZE="2">(c) Except as
modified herein, the Agreement is hereby ratified and confirmed and shall remain in full force and effect. In the event of a conflict between the terms of this Amendment and the terms of the Agreement, the terms of this Amendment shall prevail.
</FONT></P> <P STYLE="margin-top:6px;margin-bottom:0px; margin-left:4%; text-indent:4%"><FONT FACE="Times New Roman" SIZE="2">(d) The invalidity or unenforceability of any provision of this Amendment shall in no way affect the validity or
enforceability of any other provision hereof. </FONT></P> <P STYLE="margin-top:6px;margin-bottom:0px; margin-left:4%; text-indent:4%"><FONT FACE="Times New Roman" SIZE="2">(e) The parties may execute this Amendment in one or more identical
counterparts, all of which when taken together will constitute one and the same instrument. </FONT></P> <P STYLE="margin-top:12px;margin-bottom:0px" ALIGN="center"><FONT FACE="Times New Roman" SIZE="2">[Signatures begin on following page]
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 <P STYLE="margin-top:0px;margin-bottom:0px; text-indent:4%"><FONT FACE="Times New Roman" SIZE="2">EXECUTED in multiple originals as of the Effective Date. </FONT></P> <P
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<TD VALIGN="top" COLSPAN="9"><FONT FACE="Times New Roman" SIZE="2"><B>LANDLORD:</B></FONT></TD></TR>
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<TD VALIGN="top" COLSPAN="9"> <P STYLE="margin-top:0px;margin-bottom:0px"><FONT FACE="Times New Roman" SIZE="2">ARE-5100/5110 CAMPUS DRIVE, L.P., a</FONT></P> <P STYLE="margin-top:0px;margin-bottom:1px"><FONT FACE="Times New Roman" SIZE="2">Delaware
limited partnership</FONT></P></TD></TR>
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<TD VALIGN="top"><FONT FACE="Times New Roman" SIZE="2">By:</FONT></TD>
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<TD VALIGN="top" COLSPAN="7"><FONT FACE="Times New Roman" SIZE="2">AREE-HOLDINGS, L.P., a Delaware limited partnership, managing member</FONT></TD></TR>
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<TD VALIGN="top"><FONT FACE="Times New Roman" SIZE="2">By:</FONT></TD>
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<TD VALIGN="top" COLSPAN="5"><FONT FACE="Times New Roman" SIZE="2">ARE-GP HOLDINGS QRS CORP., a Delaware corporation, general partner</FONT></TD></TR>
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<TD VALIGN="top" COLSPAN="3" STYLE="BORDER-BOTTOM:1px solid #000000"><FONT FACE="Times New Roman" SIZE="2">/s/ Peter J. Nelson</FONT></TD></TR>
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<TD VALIGN="top"><FONT FACE="Times New Roman" SIZE="2">Name:</FONT></TD>
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<TD VALIGN="top" COLSPAN="3"><FONT FACE="Times New Roman" SIZE="2">Peter J. Nelson</FONT></TD></TR>
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<TD VALIGN="top"><FONT FACE="Times New Roman" SIZE="2">Title:</FONT></TD>
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<TD VALIGN="top" COLSPAN="3"><FONT FACE="Times New Roman" SIZE="2">Senior Vice President and</FONT></TD></TR>
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<TD VALIGN="top" COLSPAN="3"><FONT FACE="Times New Roman" SIZE="2">Chief Financial Officer</FONT></TD></TR>
</TABLE></DIV> <P STYLE="margin-top:12px;margin-bottom:0px" ALIGN="center"><FONT FACE="Times New Roman" SIZE="2">[Signatures continued on following page] </FONT></P> <P
STYLE="margin-top:0px;margin-bottom:0px"><FONT SIZE="1">&nbsp;</FONT></P>
 <P STYLE="margin-top:0px;margin-bottom:0px" ALIGN="center"><FONT FACE="Times New Roman" SIZE="2">-2- </FONT></P>


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 <P STYLE="margin-top:0px;margin-bottom:0px" ALIGN="center"><FONT FACE="Times New Roman" SIZE="2">[Signatures continued from previous page] </FONT></P> <P
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<TD VALIGN="top" COLSPAN="3"><FONT FACE="Times New Roman" SIZE="2"><B>TENANT:</B></FONT></TD></TR>
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<TD VALIGN="top" COLSPAN="3"> <P STYLE="margin-top:0px;margin-bottom:0px"><FONT FACE="Times New Roman" SIZE="2">GENAERA CORPORATION,</FONT></P> <P STYLE="margin-top:0px;margin-bottom:1px"><FONT FACE="Times New Roman" SIZE="2">a Delaware
corporation</FONT></P></TD></TR>
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<TD VALIGN="top"><FONT FACE="Times New Roman" SIZE="2">By:</FONT></TD>
<TD VALIGN="bottom" STYLE="BORDER-BOTTOM:1px solid #000000"><FONT SIZE="1">&nbsp;</FONT></TD>
<TD VALIGN="top" STYLE="BORDER-BOTTOM:1px solid #000000"><FONT FACE="Times New Roman" SIZE="2">/s/ John A. Skolas</FONT></TD></TR>
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<TD VALIGN="top"><FONT FACE="Times New Roman" SIZE="2">Name:</FONT></TD>
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<TD VALIGN="bottom"><FONT FACE="Times New Roman" SIZE="2">John A. Skolas</FONT></TD></TR>
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<TD VALIGN="top"><FONT FACE="Times New Roman" SIZE="2">Title:</FONT></TD>
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<TD VALIGN="bottom"><FONT FACE="Times New Roman" SIZE="2">Senior Vice President</FONT></TD></TR>
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<TD VALIGN="bottom"><FONT SIZE="1">&nbsp;</FONT></TD>
<TD VALIGN="bottom"><FONT FACE="Times New Roman" SIZE="2">Chief Financial Officer</FONT></TD></TR>
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<TD VALIGN="bottom"><FONT FACE="Times New Roman" SIZE="2">and General Counsel</FONT></TD></TR>
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 <P STYLE="margin-top:0px;margin-bottom:0px" ALIGN="center"><FONT FACE="Times New Roman" SIZE="2">-3- </FONT></P>

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