Exhibit
10.8


 


Second
Amendment to the Exclusive License Agreement Between 

Yale University and Cardium Therapeutics, Inc.


 


This second amendment to the exclusive license
agreement (the “License Agreement”) related to an invention entitled “eNOS
Mutations Useful for Gene Therapy and Therapeutic Screening” between Yale
University (“YALE”) and Cardium Therapeutics, Inc. (“CARDIUM” or “LICENSEE”)
is effective immediately following that date (the “Transfer Date”) upon which
CARDIUM assumed all rights and obligations as Licensee under the License
Agreement pursuant to the terms of that “Transfer, Consent to Transfer,
Amendment and Assumption of License Agreement” which was entered into by and
among YALE, CARDIUM and Schering Aktiengesellschaft (“Schering AG”) on August 31,
2005.  YALE and CARDIUM are each referred
to herein as a Party, collectively as the Parties.


 


RECITALS


 


Whereas, Schering AG had previously conducted
certain testing and development of eNOS mutants having potential for the
treatment of disease (the “eNOS Program”) but subsequently elected to
discontinue such research and development despite having made considerable
investments in the eNOS Program;


 


Whereas, Schering AG and CARDIUM have agreed
pursuant to the terms of a separate agreement between them to transfer to
CARDIUM certain proprietary rights and know-how developed by Schering AG and/or
its affiliates in connection with the eNOS Program;


 


Whereas, the Parties wish that CARDIUM will continue
the testing and development of eNOS mutants following its assumption of all
rights and obligations under the License Agreement as of the Transfer Date;


 


Whereas, the Parties wish to make certain
adjustments to the terms of the License Agreement which are designed to
facilitate the development of potential products by CARDIUM;


 


AGREEMENT


 


Now, therefore, in consideration of the promises and
covenants contained herein, and other good and valuable consideration, the
receipt of which is hereby acknowledged, and intending to be legally bound, the
Parties agree to amend the terms of the License Agreement as follows (no other
terms being amended):


 


1.             In Section 3.3, (i) the phrase “reaching
the ‘B3’ decision, that is to file an IND and initiate” is replaced by “filing
an NDA”; (ii) the phrase “LICENSEE enters into a sublicense with” is
replaced with the phrase “LICENSEE enters into a sublicense with or assigns
rights to”; (iii) the phrase “or advance payment received by LICENSEE from
any sublicensee” is replaced with the phrase “equity, or advance payment
received by LICENSEE from any sublicensee or assignee”; and (iv) the
following sentences are added at the end of Section 3.3: “Provided that
said rate of Thirty Percent shall be reduced to Fifteen Percent in the event
that LICENSEE has completed at least one Phase I human clinical trial prior to
such sublicense or assignment.  Provided
further, that the Parties acknowledge and agree that LICENSEE is a
development-stage company the growth of which (and the corresponding development
of its technologies and product candidates) will likely involve merger with one
or more other corporate entities which


 





















 


shall constitute a successor LICENSEE.  Although such reorganizations or mergers are
not generally considered to constitute or require a sublicense or assignment,
in order to avoid any potential ambiguity, no corporate reorganization or
merger of LICENSEE with another entity shall require payments under this Section 3.3.”.


 


2.             In Section 4.2.1, the phrase “upon
entering LICENSEE’S ‘B2’ phase of drug development (preclinical development and
regulatory toxicity)” is replaced by “upon filing the first IND for the first
LICENSED PRODUCT in any one of the United States, or Japan or a country in the
European Union”.


 


3.             In section 4.2.2, the phrase “upon
filing the first IND for the first LICENSED PRODUCT in any one of the United
States, or Japan or a country in the European Union” is replaced by “upon
treating the first patient in the second clinical trial in any one of the
United States, or Japan or a country in the European Union.


 


4.             Section 6 is replaced in its entirety
with the following underlined text:


 


6.1.          LICENSEE has designed a plan for developing
and commercializing the LICENSED INTELLECTUAL PROPERTY that includes a
description of research and development, testing, government approval,
manufacturing, marketing and sale or lease of LICENSED PRODUCTS and/or LICENSED
METHODS (“PLAN”).  A copy of the PLAN
(which has been approved by YALE) is attached to this Agreement as Appendix C-1
and incorporated herein by reference. 


 


6.2.          LICENSEE shall use all reasonable commercial
efforts, within ninety (90) days after November 30, 2005, to begin to
implement the PLAN at its sole expense and thereafter to diligently
commercialize and develop markets for the LICENSED PRODUCTS and LICENSED
METHODS.


 


6.3.          LICENSEE shall provide YALE with an updated
and (if necessary) revised copy of the PLAN on each anniversary date of the
EFFECTIVE DATE.  YALE shall review and
approve or disapprove of any changes to the annually updated PLAN in writing
within thirty (30) days of its receipt, such approval not to be unreasonably
withheld.  If YALE does not approve or
disapprove of the PLAN within such thirty (30) day period, YALE shall be deemed
to have approved the PLAN.  In the event
that YALE reasonably disapproves of any changes to the PLAN, YALE will consult
with LICENSEE with respect to revisions requested by YALE to cause the PLAN to
be reasonably acceptable to YALE. 
LICENSEE shall have thirty (30) days from the date of YALE’s disapproval
to amend the PLAN and resubmit it to YALE for reconsideration.  If approved, the updated and revised plan
shall be substituted into this Agreement as Appendix C.  If YALE does not approve such
revised PLAN, YALE, in its sole discretion, may elect to (i) permit LICENSEE
to amend the PLAN and resubmit the PLAN for reconsideration by YALE or (ii) require
that LICENSEE follow, to the extent reasonably practicable, the PLAN prior to
the proposed but disapproved amendment or revision. If YALE permits LICENSEE to
amend the PLAN pursuant to clause (i), LICENSEE shall submit an amended PLAN to
YALE within 30 days, or such other longer or shorter time period specified by
YALE.  YALE shall review and approve or
disapprove the revised PLAN within thirty (30) days of its receipt.  


 


6.4.          Within thirty (30) days of each anniversary
of the EFFECTIVE DATE of this Agreement, LICENSEE shall provide a written
report to YALE, indicating LICENSEE’s progress


 





















 


and
problems to date in performance under the PLAN, commercialization of LICENSED
PRODUCTS and LICENSED METHODS, and a forecast and schedule of major events
required to market the LICENSED PRODUCTS. 
Within thirty (30) days following any assignment by LICENSEE pursuant to
Section 16.6, the assignee shall provide YALE with an updated and revised
copy of the PLAN. YALE shall review and by notice in writing to assignee may
approve or disapprove of the revised PLAN in its sole discretion.


 


6.5.          LICENSEE shall immediately notify YALE if at
any time LICENSEE (a) abandons or suspends its research, development or
marketing of the LICENSED PRODUCTS and or LICENSED METHODS, or its intent to
research, develop and market such products or methods, or (b) fails to
comply with its due diligence obligations under this Article, in each case for
a period exceeding ninety (90) days.


 


6.6.          LICENSEE agrees that YALE shall be entitled
to terminate this Agreement pursuant to Article 12.5 upon the occurrence
of any of the following:


 


 (a)      LICENSEE gives notice pursuant to Section 6.5
(which shall be deemed a material breach not capable of being cured); or


 


 
b)  LICENSEE has failed to file an
IND by January 1, 2009.


 


6.7           LICENSEE’s
obligations pursuant to this Section 6 shall be to apply commercially
reasonable diligence to initiating and completing the PLAN as approved,
including any potential amendments thereto as proposed by LICENSEE and
reasonably approved by YALE.  In the
event that (i) LICENSEE materially fails to meet its diligence obligations
and the Parties cannot reasonably agree on a revised PLAN as proposed by
LICENSEE, or (ii) LICENSEE gives notice pursuant to Section 6.5, or (iii) fails
to file an IND according to Article 6.6, then YALE shall be entitled to
terminate this Agreement in accordance with Article 12.5.  Notwithstanding the foregoing, YALE shall not
be entitled to terminate this Agreement pursuant to the diligence obligations
of this Section if, in any calendar year after the date of IND filing in Article 6.6
above, LICENSEE and/or an AFFILIATE and/or a sublicensee and/or a collaborator
of LICENSEE, alone or together has performed any one of the following with
respect to LICENSED PRODUCT: 


 


(i)                                     has expended in excess of five hundred
thousand dollars ($500,000.00) for development of LICENSED PRODUCT per year
prior to filing an IND or one million dollars ($1,000,000) per year thereafter;


 


(ii)                                  is manufacturing LICENSED PRODUCT for a
clinical trial under an approved IND;


 


(iii)                               is actively conducting a Phase I clinical
trial with respect to LICENSED PRODUCT;


 


(iv)                              is actively conducting a Phase II clinical
trial with respect to LICENSED PRODUCT;


 


(v)                                 is actively conducting a Phase III clinical
trial with respect to LICENSED PRODUCT;


 


(vi)                              prepared documents for an NDA OR BLA FILING
with respect to


 





















 


LICENSED PRODUCT;


 


(vii)                           filed an NDA OR BLA for LICENSED PRODUCT;


 


(viii)                        after NDA OR BLA FILING, is pursuing NDA OR
BLA APPROVAL for LICENSED PRODUCT;


 


(ix)                                has obtained NDA OR BLA APPROVAL for LICENSED
PRODUCT;


 


(x)                                   has launched or is selling LICENSED PRODUCT
in the United States.”


 


5.             In section 9.5, the phrase “said
independent patent counsel shall be ultimately responsible to LICENSEE” is
replaced with the phrase “said independent patent counsel shall be ultimately
responsible to YALE”.


 


6.             Section 12.5 is replaced in its entirety
with the following underlined text:


 


12.5         YALE shall have the right to terminate this
Agreement upon written notice to LICENSEE in the event LICENSEE:


 


a)  fails to make any payment
whatsoever due and payable pursuant to this Agreement unless LICENSEE shall
make all such payments (and all interest due on such payments under Article 5.6)
within the thirty (30) day period after receipt of written notice from YALE; or


 


b)  commits a material breach of
any other provision of this Agreement which is not cured (if capable of being
cured) within the sixty (60) day period after receipt of written notice thereof
from YALE, or upon receipt of such notice if such breach is not capable of
being cured; or


 


c)  fails to obtain or maintain
adequate insurance as described in Article 13, whereupon YALE may
terminate this Agreement to be effective immediately upon written notice to
LICENSEE (unless LICENSEE shall establish within thirty (30) days of such
notice that it has obtained adequate insurance covering any period of lapse, in
which case this Agreement shall automatically be re-instated); or 


 


d)  this Agreement shall
terminate automatically without any notice to LICENSEE in the event LICENSEE
shall cease to carry on its business or becomes insolvent, or a petition in
bankruptcy is filed against LICENSEE and is consented to, acquiesced in or
remains undismissed for sixty (60) days, or LICENSEE makes a general assignment
for the benefit of creditors, or a receiver is appointed for LICENSEE.”


 


7.             Replace Article 13.2 with the following
underlined text:


 


LICENSEE
shall purchase and maintain in effect and shall require its SUBLICENSEES to
purchase and maintain in effect a policy of commercial, general liability
insurance to protect YALE with respect to events described in Article 13.1.
 Such insurance shall:


 





















 


(a)           list “YALE, its trustees, directors,
officers, employees and agents” as additional insureds under the policy;


 


(b)           provide that such policy is primary and not
excess or contributory with regard to other insurance YALE may have;


 


(c)           be endorsed to include product liability
coverage in amounts no less than $2 Million
Dollars per incident and $5 Million
Dollars annual aggregate; and


 


(d)           be endorsed to include contractual liability
coverage for LICENSEE’s indemnification under Article 13.1; and


 


(e)           by virtue of the minimum amount of insurance
coverage required under Article 13.2(c), not be construed to create a
limit of LICENSEE’s liability with respect to its indemnification under Article 13.1.


 


 


By
signing this Agreement, LICENSEE certifies that the requirements of this Article 13.2
will be met on or before the earlier of (a) the date of FIRST SALE of any
LICENSED PRODUCT or LICENSED METHOD or (b) the date any LICENSED PRODUCT,
or LICENSED METHOD is tested or used on humans, and will continue to be met
thereafter.  Upon YALE’s request,
LICENSEE shall furnish a Certificate of Insurance and a copy of the current
Insurance Policy to YALE.  LICENSEE shall
give thirty (30) days’ written notice to YALE prior to any cancellation of or material
change to the policy.


 





















 


This
Amendment may be signed in counterparts, each of which shall be deemed an
original and which shall together constitute one agreement.


 


IN
WITNESS WHEREOF, each of the Parties, intending to amend the terms of the License
Agreement, have caused the execution of this Amendment by their respective
duly-authorized officers who have signed below, to be effective as of the date
noted above.


 


 


	
  YALE UNIVERSITY

  	
   

  	
  CARDIUM THERAPEUTICS, INC.

  
	
   

  	
   

  	
   

  
	
  By:

  	
    / S /Jon Soderstom

  	
   

  	
   

  	
  By:

  	
    / S / Christopher J. Reinhard

  	
   

  
	
   

  	
   

  	
   

  
	
  Name:  Jon Soderstom

  	
   

  	
  Name: Christopher J. Reinhard

  
	
  Title:   Managing Director,

  	
   

  	
  Title:   CEO

  
	
              Office
  Cooperative Research

  	
   

  	
   

  
	
  Date: August 31, 2005

  	
   

  	
  Date: September 16, 2005