<SEC-DOCUMENT>0001193125-12-144162.txt : 20120522
<SEC-HEADER>0001193125-12-144162.hdr.sgml : 20120522
<ACCEPTANCE-DATETIME>20120330180447
<PRIVATE-TO-PUBLIC>
ACCESSION NUMBER:		0001193125-12-144162
CONFORMED SUBMISSION TYPE:	CORRESP
PUBLIC DOCUMENT COUNT:		1
FILED AS OF DATE:		20120330

FILER:

	COMPANY DATA:	
		COMPANY CONFORMED NAME:			ARROWHEAD RESEARCH CORP
		CENTRAL INDEX KEY:			0000879407
		STANDARD INDUSTRIAL CLASSIFICATION:	SERVICES-COMMERCIAL PHYSICAL & BIOLOGICAL RESEARCH [8731]
		IRS NUMBER:				460408024
		STATE OF INCORPORATION:			DE
		FISCAL YEAR END:			0930

	FILING VALUES:
		FORM TYPE:		CORRESP

	BUSINESS ADDRESS:	
		STREET 1:		201 SOUTH LAKE AVENUE
		STREET 2:		SUITE 703
		CITY:			PASADENA
		STATE:			CA
		ZIP:			91101
		BUSINESS PHONE:		626-304-3400

	MAIL ADDRESS:	
		STREET 1:		201 SOUTH LAKE AVENUE
		STREET 2:		SUITE 703
		CITY:			PASADENA
		STATE:			CA
		ZIP:			91101

	FORMER COMPANY:	
		FORMER CONFORMED NAME:	INTERACTIVE GROUP INC
		DATE OF NAME CHANGE:	20020509

	FORMER COMPANY:	
		FORMER CONFORMED NAME:	INTERACTIVE INC
		DATE OF NAME CHANGE:	19940224
</SEC-HEADER>
<DOCUMENT>
<TYPE>CORRESP
<SEQUENCE>1
<FILENAME>filename1.htm
<TEXT>
<HTML><HEAD>
<TITLE>SEC Response Letter</TITLE>
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 <P STYLE="margin-top:0px;margin-bottom:0px"><FONT STYLE="font-family:Times New Roman" SIZE="2"><U>VIA EDGAR </U></FONT></P> <P STYLE="margin-top:0px;margin-bottom:0px"><FONT
STYLE="font-family:Times New Roman" SIZE="2">Securities and Exchange Commission </FONT></P> <P STYLE="margin-top:0px;margin-bottom:0px"><FONT STYLE="font-family:Times New Roman" SIZE="2">Division of Corporation Finance </FONT></P>
<P STYLE="margin-top:0px;margin-bottom:0px"><FONT STYLE="font-family:Times New Roman" SIZE="2">100 F Street, N.E. </FONT></P> <P STYLE="margin-top:0px;margin-bottom:0px"><FONT STYLE="font-family:Times New Roman" SIZE="2">Washington, D.C. 20549-4628
</FONT></P> <P STYLE="font-size:12px;margin-top:0px;margin-bottom:0px">&nbsp;</P>
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<TD VALIGN="top"><FONT STYLE="font-family:Times New Roman" SIZE="2">Attention:</FONT></TD>
<TD VALIGN="bottom"><FONT SIZE="1">&nbsp;&nbsp;</FONT></TD>
<TD VALIGN="top"><FONT STYLE="font-family:Times New Roman" SIZE="2">Jeffrey Riedler</FONT></TD></TR>
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<TD VALIGN="top"></TD>
<TD VALIGN="bottom"><FONT SIZE="1">&nbsp;&nbsp;</FONT></TD>
<TD VALIGN="top"><FONT STYLE="font-family:Times New Roman" SIZE="2">Johnny Gharib</FONT></TD></TR>
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<TD VALIGN="top"></TD>
<TD VALIGN="bottom"><FONT SIZE="1">&nbsp;&nbsp;</FONT></TD>
<TD VALIGN="top"><FONT STYLE="font-family:Times New Roman" SIZE="2">John Krug</FONT></TD></TR>
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<TD VALIGN="top"></TD>
<TD VALIGN="bottom"><FONT SIZE="1">&nbsp;&nbsp;</FONT></TD>
<TD VALIGN="top"><FONT STYLE="font-family:Times New Roman" SIZE="2">Daniel Greenspan</FONT></TD></TR>
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<TD HEIGHT="16" COLSPAN="2"></TD></TR>
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<TD VALIGN="top"><FONT STYLE="font-family:Times New Roman" SIZE="2">Re:</FONT></TD>
<TD VALIGN="bottom"><FONT SIZE="1">&nbsp;&nbsp;</FONT></TD>
<TD VALIGN="top"><FONT STYLE="font-family:Times New Roman" SIZE="2">Arrowhead Research Corporation</FONT></TD></TR>
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<TD VALIGN="top"></TD>
<TD VALIGN="bottom"><FONT SIZE="1">&nbsp;&nbsp;</FONT></TD>
<TD VALIGN="top"><FONT STYLE="font-family:Times New Roman" SIZE="2">Form 10-K</FONT></TD></TR>
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<TD VALIGN="bottom"><FONT SIZE="1">&nbsp;&nbsp;</FONT></TD>
<TD VALIGN="top"><FONT STYLE="font-family:Times New Roman" SIZE="2">Filed December&nbsp;20, 2011</FONT></TD></TR>
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<TD VALIGN="bottom"><FONT SIZE="1">&nbsp;&nbsp;</FONT></TD>
<TD VALIGN="top"><FONT STYLE="font-family:Times New Roman" SIZE="2">File No. 000-21898</FONT></TD></TR>
</TABLE> <P STYLE="margin-top:12px;margin-bottom:0px"><FONT STYLE="font-family:Times New Roman" SIZE="2">Ladies and Gentlemen: </FONT></P> <P STYLE="margin-top:12px;margin-bottom:0px; text-indent:4%"><FONT
STYLE="font-family:Times New Roman" SIZE="2">Set forth below is the response of Arrowhead Research Corporation, a Delaware corporation (the &#147;Company&#148;), to the comment letter, dated March&nbsp;16, 2012 (the &#147;Comment Letter&#148;), of
the staff of the Division of Corporation Finance (the &#147;Staff&#148;) of the Securities and Exchange Commission (the &#147;Commission&#148;) to the Company&#146;s Form 10-K (File No. 000-21898) (the &#147;Form 10-K&#148;). The Form 10-K was filed
with the Commission on December&nbsp;20, 2011. </FONT></P> <P STYLE="margin-top:12px;margin-bottom:0px; text-indent:4%"><FONT STYLE="font-family:Times New Roman" SIZE="2">For reference purposes, the Staff&#146;s comments as reflected in the Comment
Letter are reproduced in bold and the corresponding responses of the Company are shown below the comments. </FONT></P> <P STYLE="margin-top:18px;margin-bottom:0px"><FONT STYLE="font-family:Times New Roman" SIZE="2"><B><U>Form 10-K, filed
December&nbsp;20, 2011 </U></B></FONT></P> <P STYLE="margin-top:6px;margin-bottom:0px"><FONT STYLE="font-family:Times New Roman" SIZE="2"><B><U>Cyclosert Technology&nbsp;&amp; CRLX101 (Formerly IT-101), page 6 </U></B></FONT></P>
<P STYLE="font-size:6px;margin-top:0px;margin-bottom:0px">&nbsp;</P>
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<TD WIDTH="4%" VALIGN="top" ALIGN="left"><FONT STYLE="font-family:Times New Roman" SIZE="2"><B>1.</B></FONT></TD>
<TD ALIGN="left" VALIGN="top"><FONT STYLE="font-family:Times New Roman" SIZE="2"><B>We note that you have included as an exhibit your license agreement with Cerulean Pharma, Inc. Please revise your disclosure to describe the material terms of this
agreement including, but not limited to, duration, termination provisions, obligations or rights to defend, other material obligations that must be met to keep the agreement in place, aggregate potential milestone payments, and a range of royalty
payments not to exceed ten percent, e.g. &#147;single digits,&#148; &#147;teens,&#148; &#147;twenties,&#148; etc. </B></FONT></TD></TR></TABLE>
<P STYLE="margin-top:18px;margin-bottom:0px"><FONT STYLE="font-family:Times New Roman" SIZE="2"><U>RESPONSE TO COMMENT 1 </U></FONT></P> <P STYLE="margin-top:6px;margin-bottom:0px"><FONT STYLE="font-family:Times New Roman" SIZE="2">We confirm that
for future periods we will revise the disclosure to read substantially as follows: </FONT></P> <P STYLE="margin-top:12px;margin-bottom:0px"><FONT STYLE="font-family:Times New Roman" SIZE="2">Cyclosert Technology&nbsp;&amp; CRLX101 (Formerly IT-101)
</FONT></P> <P STYLE="margin-top:12px;margin-bottom:0px; text-indent:4%"><FONT STYLE="font-family:Times New Roman" SIZE="2">The other linear cyclodextrin-based drug delivery platform, Cyclosert, was designed by Calando&#146;s scientists for the
delivery of small molecule drugs. Cyclosert provides many of the </FONT></P>

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 <P STYLE="margin-top:0px;margin-bottom:0px"><FONT STYLE="font-family:Times New Roman" SIZE="2">
same benefits as the RONDEL system. In December 2008, Calando completed a Phase I trial with IT-101, a conjugate of Calando&#146;s linear cyclodextrin polymer and Camptothecin, a potent
anti-cancer drug, with a positive safety profile and indications of efficacy. </FONT></P> <P STYLE="margin-top:12px;margin-bottom:0px; text-indent:4%"><FONT STYLE="font-family:Times New Roman" SIZE="2">On June&nbsp;23, 2009, Calando entered into a
transaction with Cerulean related to Cyclosert and IT-101 (the &#147;Cerulean Transaction&#148;). In the Cerulean Transaction, Calando granted Cerulean an irrevocable, perpetual, royalty bearing worldwide license with the right to sublicense, under
certain patent rights and know-how in the field of human diseases solely in order to solely: (a)&nbsp;conduct research and development on Calando&#146;s Linear Cyclodextrin System, including making improvements thereto, in order to research and
commercialize Calando&#146;s clinical asset IT-101 (now known as &#147;CRLX101&#148;), as well as certain other products in which no therapeutic agent is specifically defined (the &#147;Cerulean Products&#148;); (b)&nbsp;research, develop, make,
have made, use, market, offer to sell, distribute, sell and import CRLX101 and Cerulean Products; and (c)&nbsp;use, copy, modify and distribute certain Calando Know-How for those purposes. Calando retained all rights with respect to products in
which a therapeutic agent is a (i)&nbsp;tubulysin, (ii)&nbsp;cytolysin, (iii)&nbsp;second generation epothilone or (iv)&nbsp;nucleic acid (hereinafter &#147;Calando Products&#148;). </FONT></P>
<P STYLE="margin-top:12px;margin-bottom:0px; text-indent:4%"><FONT STYLE="font-family:Times New Roman" SIZE="2">The Cerulean Transaction also involved the sale and assignment by Calando of certain patents directed to Cyclosert and CRLX101 (the
&#147;Cerulean Assigned Patents&#148;) to Cerulean. Cerulean then granted back to Calando an exclusive, irrevocable, perpetual, royalty free, worldwide license, with the right to grant sublicenses, under the Cerulean Assigned Patents solely to the
extent necessary to research and commercialize products in which each therapeutic agent is a cytolysin, tubulysin, second generation epothilone or any nucleic acid. </FONT></P> <P STYLE="margin-top:12px;margin-bottom:0px; text-indent:4%"><FONT
STYLE="font-family:Times New Roman" SIZE="2">As such, Calando retains the rights to its RONDEL siRNA delivery platform, as well as the siRNA-based Calando products, CALAA-01 and CALAA-02. </FONT></P>
<P STYLE="margin-top:12px;margin-bottom:0px; text-indent:4%"><FONT STYLE="font-family:Times New Roman" SIZE="2">The Cerulean Transaction resulted in an initial payment to Calando of $2.4 million. Cerulean is obligated to pay development milestone
payments of up to $2.75 million if CRLX101 progresses through clinical trials and receives marketing approval. If approved, Calando is also entitled to receive up to an additional $30 million in sales milestone payments, plus single digit royalties
on net sales. Should Cerulean sublicense CRLX101 to a third party, Calando shall receive a percentage of any sublicensing income at rates between 10% and 40%, depending on the stage of the drug&#146;s development at the time of sublicensing.
</FONT></P> <P STYLE="margin-top:12px;margin-bottom:0px; text-indent:4%"><FONT STYLE="font-family:Times New Roman" SIZE="2">Cerulean will further pay development milestone payments of up to $3 million for each Cerulean Product that progresses
through clinical trials and receives marketing approval. If Cerulean Products are approved, Calando is entitled to receive up to an additional $15 million in sales milestone payments, plus single digit royalties on net sales. Should Cerulean
sublicense a Cerulean Product to a third party, Calando shall receive a percentage of any sublicensing income at a rate in the tens. </FONT></P> <P STYLE="margin-top:12px;margin-bottom:0px; text-indent:4%"><FONT
STYLE="font-family:Times New Roman" SIZE="2">The terms of the agreements of the Cerulean Transactions are tied to the expiration of certain Calando-controlled patent rights and Cerulean Assigned Patents. Cerulean may terminate the agreements on
thirty (30)&nbsp;days&#146; notice and unless there is a drug safety concern, would be obligated to re-assign the CRLX101 IND back to Calando and provide it with an exclusive license thereto under the Cerulean Assigned Patents. Calando is
responsible for the costs associated with prosecution of the patents it controls and has licensed to Cerulean. </FONT></P>

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 <P STYLE="margin-top:0px;margin-bottom:0px"><FONT STYLE="font-family:Times New Roman" SIZE="2"><B><U>Intellectual Property, page 7 </U></B></FONT></P>
<P STYLE="font-size:6px;margin-top:0px;margin-bottom:0px">&nbsp;</P>
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<TD WIDTH="4%" VALIGN="top" ALIGN="left"><FONT STYLE="font-family:Times New Roman" SIZE="2"><B>2.</B></FONT></TD>
<TD ALIGN="left" VALIGN="top"><FONT STYLE="font-family:Times New Roman" SIZE="2"><B>Please expand the discussion concerning your material patents or groups of patents to identify the jurisdiction(s) where you have obtained patent protection,
identify the products, product candidates, or technology that are dependent on the patent(s) or groups of patents, and disclose when the patents expire. </B></FONT></TD></TR></TABLE> <P STYLE="margin-top:18px;margin-bottom:0px"><FONT
STYLE="font-family:Times New Roman" SIZE="2"><U>RESPONSE TO COMMENT 2 </U></FONT></P> <P STYLE="margin-top:6px;margin-bottom:0px"><FONT STYLE="font-family:Times New Roman" SIZE="2">We confirm that for future periods we will revise the disclosure to
read substantially as follows: </FONT></P> <P STYLE="margin-top:12px;margin-bottom:0px; text-indent:4%"><FONT STYLE="font-family:Times New Roman" SIZE="2">In total, we currently control approximately 155 issued patents (including European
validations) and 292 patent applications. The pending applications have been filed throughout the world, including, for example, in the United States, Argentina, Australia, Brazil, Canada, Chile, China, Europe, Arab States of the Gulf, Israel,
India, Japan, Republic of Korea, Mexico, Peru, Philippines, Russian Federation, Singapore, Thailand, Taiwan and Venezuela. </FONT></P>
<P STYLE="margin-top:12px;margin-bottom:0px; text-indent:4%"><FONT STYLE="font-family:Times New Roman" SIZE="2">Calando controls an intellectual property portfolio of patents directed to certain linear cyclodextrin polymers and related technology
(the &#147;Linear Cyclodextrin System&#148;). The portfolio is directed to both RONDEL and Cyclosert. In June 2009, Calando sold and assigned to Cerulean certain patents (&#147;Cerulean Assigned Patents&#148;) directed toward linear cyclodextrin
polymers conjugated to drugs. Additionally, Calando granted Cerulean an exclusive license under its rights to the Linear Cyclodextrin System to develop and commercialize CRLX101 and Cerulean Products. Calando retained rights to use the Linear
Cyclodextrin System to develop drugs in which a therapeutic agent is (i)&nbsp;a nucleic acid (e.g., siRNA), (ii)&nbsp;a second generation epothilone, (iii)&nbsp;tubulysin or (iv)&nbsp;cytolysin (collectively, the &#147;Calando Products&#148;).
</FONT></P> <P STYLE="margin-top:12px;margin-bottom:0px; text-indent:4%"><FONT STYLE="font-family:Times New Roman" SIZE="2">The issued patents include approximately 55 patents directed to the RONDEL&#153; and CYLCOSERT&#153; drug delivery platforms.
Included in these 55 patents are approximately 34 patents covering linear cyclodextrin copolymers utilized in RONDEL&#153; and CYCLOSERT&#153;, issued in the United States, Europe (Austria, Belgium, Switzerland, Germany, Denmark, Spain, Finland,
France, the United Kingdom, Greece, Ireland, Israel, Italy, Luxembourg, Monaco, Netherlands, Portugal, Sweden), Australia, Brazil, Canada, China, Cyprus, Japan, Republic of Korea, Mexico, Russian Federation, Singapore and South Africa. Approximately
14 patents are directed to inclusion complexes and drug-cyclodextrin complexes utilized in the RONDEL&#153; and CYLCOCERT&#153; platforms. These patents have issued in the United States, Australia, China, Israel, Japan, Republic of Korea, Russian
Federation, Singapore, Taiwan and South Africa. Approximately seven additional patents issued in the United States, and Europe (Austria, Switzerland, Germany, France and the United Kingdom) are directed to supramolecular complexes containing
therapeutic agents. </FONT></P>

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 <P STYLE="margin-top:0px;margin-bottom:0px; text-indent:4%"><FONT STYLE="font-family:Times New Roman" SIZE="2">Calando also owns a U.S. issued patent (in addition to 15 patents in Europe, i.e., Austria,
Belgium, Switzerland, Germany, Denmark, Spain, Finland, France, the United Kingdom, Hungary, Italy, Netherlands, Poland and Sweden) directed to the siRNA active ingredient in CALAA-01, as well as a U.S. patent directed to the siRNA active ingredient
of CALAA-02. </FONT></P> <P STYLE="margin-top:12px;margin-bottom:0px; text-indent:4%;padding-bottom:0px;"><FONT STYLE="font-family:Times New Roman" SIZE="2">We also control patents covering our homing peptide platform, including approximately 18
patents. Approximately five of these patents are United States patents and the remaining are European patents validated in Belgium, Switzerland, Germany, Spain, France, the United Kingdom, Ireland, Greece, Italy, Netherlands, Portugal, Sweden and
Turkey. These patents are directed to ADIPOTIDE</FONT><FONT STYLE="font-family:Times New Roman" SIZE="1"><SUP STYLE="vertical-align:baseline; position:relative; bottom:.8ex">TM</SUP></FONT><FONT STYLE="font-family:Times New Roman" SIZE="2">, our
treatment for obesity and related metabolic disorders. </FONT></P> <P STYLE="margin-top:12px;margin-bottom:0px; text-indent:4%"><FONT STYLE="font-family:Times New Roman" SIZE="2">In addition, we control approximately 11 patents directed to our
dynamic polyconjugate (DPC) drug delivery platform. These patents have issued in the United States, Australia, Canada, India, Mexico, Russia and South Africa. We also control approximately 41 patents directed to hydrodynamic nucleic acid delivery
which issued in the United States, Australia and Europe (Austria, Belgium, Switzerland, Germany, Denmark, Spain, Finland, France, the United Kingdom, Hungary, Ireland, Italy, Netherlands and Sweden). </FONT></P>
<P STYLE="margin-top:12px;margin-bottom:0px; text-indent:4%"><FONT STYLE="font-family:Times New Roman" SIZE="2">The additional approximately 13 patents are directed to various precursors to our DPC delivery platform, and other membrane active
polymers, as well as additional drug and gene delivery methodologies and carriers (e.g., lipid- and micelle-based systems). </FONT></P>
<P STYLE="margin-top:12px;margin-bottom:0px; text-indent:4%"><FONT STYLE="font-family:Times New Roman" SIZE="2">The approximate year of expiration for each these various groups of patents are set forth below in the following table. </FONT></P>
<P STYLE="font-size:12px;margin-top:0px;margin-bottom:0px">&nbsp;</P>
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<TD VALIGN="bottom" NOWRAP> <P STYLE="border-bottom:1px solid #000000;width:46pt"><FONT STYLE="font-family:Times New Roman" SIZE="1"><B>Patent Group</B></FONT></P></TD>
<TD VALIGN="bottom"><FONT SIZE="1">&nbsp;&nbsp;</FONT></TD>
<TD VALIGN="bottom" ALIGN="center" STYLE="border-bottom:1px solid #000000"><FONT STYLE="font-family:Times New Roman" SIZE="1"><B>Estimated&nbsp;Year&nbsp;of&nbsp;Expiration</B></FONT></TD></TR>


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<TD VALIGN="top"> <P STYLE="margin-left:1.00em; text-indent:-1.00em"><FONT STYLE="font-family:Times New Roman" SIZE="2">RONDEL&#153; and CYCLOCERT&#153;</FONT></P></TD>
<TD VALIGN="bottom"><FONT SIZE="1">&nbsp;&nbsp;</FONT></TD>
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<TD VALIGN="top"> <P STYLE="margin-left:1.00em; text-indent:-1.00em"><FONT STYLE="font-family:Times New Roman" SIZE="2">Linear cyclodextrin copolymers</FONT></P></TD>
<TD VALIGN="bottom"><FONT SIZE="1">&nbsp;&nbsp;</FONT></TD>
<TD VALIGN="bottom" ALIGN="center"><FONT STYLE="font-family:Times New Roman" SIZE="2">2018</FONT></TD></TR>
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<TD HEIGHT="8"></TD>
<TD HEIGHT="8" COLSPAN="2"></TD></TR>
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<TD VALIGN="top"> <P STYLE="margin-left:1.00em; text-indent:-1.00em"><FONT STYLE="font-family:Times New Roman" SIZE="2">Inclusion complexes</FONT></P></TD>
<TD VALIGN="bottom"><FONT SIZE="1">&nbsp;&nbsp;</FONT></TD>
<TD VALIGN="bottom" ALIGN="center"><FONT STYLE="font-family:Times New Roman" SIZE="2">2021</FONT></TD></TR>
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<TD HEIGHT="8" COLSPAN="2"></TD></TR>
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<TD VALIGN="top"> <P STYLE="margin-left:1.00em; text-indent:-1.00em"><FONT STYLE="font-family:Times New Roman" SIZE="2">Drug-cyclodextrin complexes</FONT></P></TD>
<TD VALIGN="bottom"><FONT SIZE="1">&nbsp;&nbsp;</FONT></TD>
<TD VALIGN="bottom" ALIGN="center"><FONT STYLE="font-family:Times New Roman" SIZE="2">2024</FONT></TD></TR>
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<TD HEIGHT="8"></TD>
<TD HEIGHT="8" COLSPAN="2"></TD></TR>
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<TD VALIGN="top"> <P STYLE="margin-left:1.00em; text-indent:-1.00em"><FONT STYLE="font-family:Times New Roman" SIZE="2">Supramolecular complexes containing therapeutic agents</FONT></P></TD>
<TD VALIGN="bottom"><FONT SIZE="1">&nbsp;&nbsp;</FONT></TD>
<TD VALIGN="bottom" ALIGN="center"><FONT STYLE="font-family:Times New Roman" SIZE="2">2019</FONT></TD></TR>
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<TD VALIGN="top"> <P STYLE="margin-left:1.00em; text-indent:-1.00em"><FONT STYLE="font-family:Times New Roman" SIZE="2">CALAA-01</FONT></P></TD>
<TD VALIGN="bottom"><FONT SIZE="1">&nbsp;&nbsp;</FONT></TD>
<TD VALIGN="bottom"></TD></TR>
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<TD HEIGHT="8"></TD>
<TD HEIGHT="8" COLSPAN="2"></TD></TR>
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<TD VALIGN="top"> <P STYLE="margin-left:1.00em; text-indent:-1.00em"><FONT STYLE="font-family:Times New Roman" SIZE="2">Patent directed to RRM2 siRNAs</FONT></P></TD>
<TD VALIGN="bottom"><FONT SIZE="1">&nbsp;&nbsp;</FONT></TD>
<TD VALIGN="bottom" ALIGN="center"><FONT STYLE="font-family:Times New Roman" SIZE="2">2028</FONT></TD></TR>
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<TD HEIGHT="8"></TD>
<TD HEIGHT="8" COLSPAN="2"></TD></TR>
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<TD VALIGN="top"> <P STYLE="margin-left:1.00em; text-indent:-1.00em"><FONT STYLE="font-family:Times New Roman" SIZE="2">CALAA-02</FONT></P></TD>
<TD VALIGN="bottom"><FONT SIZE="1">&nbsp;&nbsp;</FONT></TD>
<TD VALIGN="bottom"></TD></TR>
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<TD VALIGN="top"> <P STYLE="margin-left:1.00em; text-indent:-1.00em"><FONT STYLE="font-family:Times New Roman" SIZE="2">Patent directed to HIF-2 alpha (EPAS1) siRNAs</FONT></P></TD>
<TD VALIGN="bottom"><FONT SIZE="1">&nbsp;&nbsp;</FONT></TD>
<TD VALIGN="bottom" ALIGN="center"><FONT STYLE="font-family:Times New Roman" SIZE="2">2030</FONT></TD></TR>
<TR>
<TD HEIGHT="8"></TD>
<TD HEIGHT="8" COLSPAN="2"></TD></TR>
<TR>
<TD VALIGN="top"> <P STYLE="margin-left:1.00em; text-indent:-1.00em"><FONT STYLE="font-family:Times New Roman" SIZE="2">Adipotide</FONT><FONT STYLE="font-family:Times New Roman" SIZE="1"><SUP
STYLE="vertical-align:baseline; position:relative; bottom:.8ex">TM</SUP></FONT><FONT STYLE="font-family:Times New Roman" SIZE="2"></FONT></P></TD>
<TD VALIGN="bottom"><FONT SIZE="1">&nbsp;&nbsp;</FONT></TD>
<TD VALIGN="bottom"></TD></TR>
<TR>
<TD VALIGN="top"> <P STYLE="margin-left:1.00em; text-indent:-1.00em"><FONT STYLE="font-family:Times New Roman" SIZE="2">Targeting moieties and conjugates</FONT></P></TD>
<TD VALIGN="bottom"><FONT SIZE="1">&nbsp;&nbsp;</FONT></TD>
<TD VALIGN="bottom" ALIGN="center"><FONT STYLE="font-family:Times New Roman" SIZE="2">2021</FONT></TD></TR>
<TR>
<TD HEIGHT="8"></TD>
<TD HEIGHT="8" COLSPAN="2"></TD></TR>
<TR>
<TD VALIGN="top"> <P STYLE="margin-left:1.00em; text-indent:-1.00em"><FONT STYLE="font-family:Times New Roman" SIZE="2">Dynamic polyconguates (DPC)</FONT></P></TD>
<TD VALIGN="bottom"><FONT SIZE="1">&nbsp;&nbsp;</FONT></TD>
<TD VALIGN="bottom"></TD></TR>
<TR>
<TD VALIGN="top"> <P STYLE="margin-left:1.00em; text-indent:-1.00em"><FONT STYLE="font-family:Times New Roman" SIZE="2">Various iterations</FONT></P></TD>
<TD VALIGN="bottom"><FONT SIZE="1">&nbsp;&nbsp;</FONT></TD>
<TD VALIGN="bottom" ALIGN="center"><FONT STYLE="font-family:Times New Roman" SIZE="2">2027</FONT></TD></TR>
<TR>
<TD HEIGHT="8"></TD>
<TD HEIGHT="8" COLSPAN="2"></TD></TR>
<TR>
<TD VALIGN="top"> <P STYLE="margin-left:1.00em; text-indent:-1.00em"><FONT STYLE="font-family:Times New Roman" SIZE="2">Hydrodynamic delivery</FONT></P></TD>
<TD VALIGN="bottom"><FONT SIZE="1">&nbsp;&nbsp;</FONT></TD>
<TD VALIGN="bottom"></TD></TR>
<TR>
<TD VALIGN="top"> <P STYLE="margin-left:1.00em; text-indent:-1.00em"><FONT STYLE="font-family:Times New Roman" SIZE="2">Various iterations</FONT></P></TD>
<TD VALIGN="bottom"><FONT SIZE="1">&nbsp;&nbsp;</FONT></TD>
<TD VALIGN="bottom" ALIGN="center"><FONT STYLE="font-family:Times New Roman" SIZE="2">2015</FONT></TD></TR>
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 <P STYLE="margin-top:0px;margin-bottom:0px; text-indent:4%"><FONT STYLE="font-family:Times New Roman" SIZE="2">Calando has licensed patents from Alnylam relevant to siRNA therapeutics for both CALAA-01
and CALAA-02. Calando has out licensed to R&amp;D Biopharmaceuticals GmbH, the use of the linear cyclodextrin system for delivering second generation synthetic epothilone drugs. Calando has also out-licensed to Tube Pharmaceuticals GmbH, the use of
the linear cyclodextrin system for delivering tubulysin and cytolysin. </FONT></P> <P STYLE="margin-top:12px;margin-bottom:0px; text-indent:4%"><FONT STYLE="font-family:Times New Roman" SIZE="2">The RNAi and nanoparticle drug delivery patent
landscapes are complex and rapidly evolving. As such, we may need to obtain additional patent licenses prior to commercialization of our lead drug candidates. </FONT></P> <P STYLE="margin-top:18px;margin-bottom:0px"><FONT
STYLE="font-family:Times New Roman" SIZE="2"><B><U>Our Approach to the Treatment of Obesity, page 8 </U></B></FONT></P> <P STYLE="font-size:6px;margin-top:0px;margin-bottom:0px">&nbsp;</P>
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<TD WIDTH="4%"><FONT SIZE="1">&nbsp;</FONT></TD>
<TD WIDTH="4%" VALIGN="top" ALIGN="left"><FONT STYLE="font-family:Times New Roman" SIZE="2"><B>3.</B></FONT></TD>
<TD ALIGN="left" VALIGN="top"><FONT STYLE="font-family:Times New Roman" SIZE="2"><B>We note that you have included as an exhibit your patent and technology license agreement with the Board of Regents of the University of Texas System. Please revise
your disclosure to describe the material terms of this agreement including, but not limited to, duration, termination provisions, obligations or rights to defend, other material obligations that must be met to keep the agreement in place, aggregate
potential milestone payments, and a range of royalty payments not to exceed ten percent, e.g. &#147;single digits,&#148; &#147;teens,&#148;, &#147;twenties,&#148; etc. If the duration of the agreement is conditioned on the expiration of a patent,
please provide the name of the patent and its expiration date. </B></FONT></TD></TR></TABLE> <P STYLE="font-size:6px;margin-top:0px;margin-bottom:0px">&nbsp;</P>
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<TD WIDTH="4%"><FONT SIZE="1">&nbsp;</FONT></TD>
<TD WIDTH="4%" VALIGN="top" ALIGN="left"><FONT STYLE="font-family:Times New Roman" SIZE="2"><B>4.</B></FONT></TD>
<TD ALIGN="left" VALIGN="top"><FONT STYLE="font-family:Times New Roman" SIZE="2"><B>Please revise your disclosure to describe Ablaris Therapeutics Inc.&#146;s material patent or groups of patents, identify the jurisdiction(s) where Ablaris obtained
patent protection, identify the products, product candidates, or technology that are dependent on the patent(s) or groups of patents, and disclose when the patents expire. </B></FONT></TD></TR></TABLE> <P STYLE="margin-top:18px;margin-bottom:0px"><FONT
STYLE="font-family:Times New Roman" SIZE="2"><U>RESPONSE TO COMMENTS 3 AND 4 </U></FONT></P> <P STYLE="margin-top:6px;margin-bottom:0px"><FONT STYLE="font-family:Times New Roman" SIZE="2">We confirm that for future periods we will revise the
disclosure to read substantially as follows: </FONT></P> <P STYLE="margin-top:12px;margin-bottom:0px"><FONT STYLE="font-family:Times New Roman" SIZE="2">Our Approach to the Treatment of Obesity </FONT></P>
<P STYLE="margin-top:12px;margin-bottom:0px; text-indent:4%"><FONT STYLE="font-family:Times New Roman" SIZE="2">Ablaris&#146; lead compound, Adipotide &#153;, includes a targeting moiety which allows it to bind to a receptor expressed by the
endothelial cells lining the blood vessels of white adipose (fat) tissue. This targeting technology was developed by Drs. Wadih Arap and Renata Pasqualini at the University of Texas MD Anderson Cancer Center (UTMDACC) in Houston, Texas. </FONT></P>
<P STYLE="margin-top:12px;margin-bottom:0px; text-indent:4%"><FONT STYLE="font-family:Times New Roman" SIZE="2">This targeting moiety was discovered using a technique in which a randomly generated phage display library of peptides was injected into
an animal, and sequences that homed to white fat were isolated and amplified. The targeting moiety was fused to an apoptotic agent. This apoptosis-inducing peptidomimetic has not been shown to have an effect on mammalian cells in systemic
circulation, but it induces cell death upon internalization by targeted endothelial cells through the disruption of their mitochondrial membranes. Because adipose tissue requires a continuous turnover of new capillaries to supply oxygen and maintain
storage capacity, targeted destruction of these blood vessels leads to the gradual resorption of adipose tissue and corresponding weight loss in treated animals (the &#147;UTMDACC Technology&#148;). </FONT></P>

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 <P STYLE="margin-top:0px;margin-bottom:0px; text-indent:4%"><FONT STYLE="font-family:Times New Roman" SIZE="2">In December 2010, we obtained an exclusive world-wide license from UTMDACC related to
Adipotide technology (the &#147;UTMDACC License&#148;). The UTMDACC license granted us a royalty-bearing, exclusive right (with the right to sublicense) under certain UTMDACC patents to develop and commercialize certain products in the fields of: 1)
therapeutics, diagnostics and research services that both (i)&nbsp;incorporate peptides that specifically target adipose tissue, and (ii)&nbsp;are used to treat, diagnose or research solely either (a)&nbsp;obesity, overweight and/or
(b)&nbsp;metabolic conditions related to, caused by and/or associated with obesity and overweight, e.g., diabetes; and 2) cancer therapies, diagnostics and research products associated with a specific targeting moiety. We also have rights to certain
improvements to the UTMDACC technology arising in the lab of Drs. Wadih Arap and Renata Pasqualini (&#147;UTMDACC Improvements&#148;). </FONT></P> <P STYLE="margin-top:12px;margin-bottom:0px; text-indent:4%"><FONT
STYLE="font-family:Times New Roman" SIZE="2">In consideration for the license, we paid UTMDACC an upfront fee of $2 million and pay annual fees initially equal to $50,000 increasing up to a maximum of $100,000, with such annual fees creditable
against milestone payments. </FONT></P> <P STYLE="margin-top:12px;margin-bottom:0px; text-indent:4%"><FONT STYLE="font-family:Times New Roman" SIZE="2">Development milestone payments of up to $8.3 million for each UTMDCC licensed product that
progresses through clinical trials and receives U.S. marketing approval are required. Additional EU and Japanese approval milestone payments are in the low single digit million dollar range. Royalty payments on net sales of UTMDACC licensed products
are in the low single digit range. Should we sublicense or partner a UTMDACC licensed product, UTMDACC would receive partnering fee percentages in the range of single digits to the twenties, depending on the stage of development of the partnered
UTMDACC licensed product. </FONT></P> <P STYLE="margin-top:12px;margin-bottom:0px; text-indent:4%"><FONT STYLE="font-family:Times New Roman" SIZE="2">The term of the UTMDACC License is linked to the last to expire patents licensed therein or 15
years if a licensed product contains only licensed know how. We are obligated to actively and effectively attempt to commercialize the UTMDACC Technology and submit to UTMDACC a Phase II clinical trial protocol within two (2)&nbsp;years of obtaining
an approved IND. We are also obligated to commence a Phase II clinical trial within four (4)&nbsp;years and a Phase III clinical trial within seven (7)&nbsp;years of approval of an IND. However, we may obtain yearly extensions of time upon the
payment of an increasing fee in the range of tens of thousands of dollars up to several hundred thousand dollars. We also have diligence obligations with respect to any UTMDACC Improvements later added to the license. The UTMDACC license shall
automatically terminate if we file for bankruptcy or are unable to pay our bills as they come due. </FONT></P> <P STYLE="margin-top:12px;margin-bottom:0px; text-indent:4%"><FONT STYLE="font-family:Times New Roman" SIZE="2">The Company hereby
acknowledges that (i)&nbsp;the Company is responsible for the adequacy and accuracy of the disclosure in its filing, (ii)&nbsp;Staff comments or changes to disclosure based on Staff comments does not foreclose the Commission from taking any actions
with respect to the Company&#146;s filing, and (iii)&nbsp;it is the Staff&#146;s position that the Company may not assert Staff comments as defense in any proceeding initiated by the Commission or any person under the federal securities laws of the
United States. </FONT></P> <P STYLE="margin-top:12px;margin-bottom:0px; text-indent:4%"><FONT STYLE="font-family:Times New Roman" SIZE="2">If you should have any questions about this letter or require any further information, please call the
undersigned at (626)&nbsp;304-3400 or Ryan Murr at (415)&nbsp;315-6300. </FONT></P>

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<TD VALIGN="top"><FONT STYLE="font-family:Times New Roman" SIZE="2">Sincerely,</FONT></TD></TR>
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<TD HEIGHT="16"></TD></TR>
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<TD VALIGN="top"><FONT STYLE="font-family:Times New Roman" SIZE="2">Christopher Anzalone, Ph.D.</FONT></TD></TR>
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<TD VALIGN="top"><FONT STYLE="font-family:Times New Roman" SIZE="2">Chief Executive Officer</FONT></TD></TR>
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<TD WIDTH="5%" VALIGN="top" ALIGN="left"><FONT STYLE="font-family:Times New Roman" SIZE="2">cc:</FONT></TD>
<TD ALIGN="left" VALIGN="top"><FONT STYLE="font-family:Times New Roman" SIZE="2">Ryan Murr, Esq. (Ropes&nbsp;&amp; Gray LLP) </FONT></TD></TR></TABLE>
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