Exhibit 10.1


 


AMENDMENT NO. 1 TO COLLABORATIVE RESEARCH, DEVELOPMENT AND LICENSE
AGREEMENT


 


This
AMENDMENT NO. 1 TO COLLABORATIVE RESEARCH, DEVELOPMENT AND LICENSE AGREEMENT
(the “Amendment”) is entered into as of October 8, 2010 (the “Effective Date”) by and between ArQule, Inc. and Daiichi
Sankyo Co., Ltd. (collectively, the “Parties”).


 


WHEREAS,
the Parties have entered into that certain Collaborative Research, Development
and License, Agreement on November 7, 2008, and the Agreement on Milestone
Payments and Royalties (collectively, the “Agreement”), (terms which are
defined in the Agreement being used herein as so defined);


 


WHEREAS,
ARQULE has neared completion of the ARQULE Research Activities with respect to
the two (2) Initial DS Targets;


 


WHEREAS,
the Parties wish to amend the Agreement to add one (1) or two (2) additional
DS Targets to the Research Program, as determined by DS, extend the Research
Collaboration Period, and otherwise modify the Agreement as set forth herein;


 


NOW,
THEREFORE, in consideration of the mutual promises set forth herein and for
other good and valuable consideration, the receipt and sufficiency of which is
acknowledged by the Parties, the Parties hereto, intending to be legally bound,
hereby agree as follows:


 


1.             The new Target set forth on
Schedule 1 to this Amendment and a second new Target if selected by DS as set
forth in this Section 1 (collectively, the “New DS Targets”) are hereby
designated as DS Targets for all purposes of the Agreement and are added to the
DS Target List.  If DS has not given
notice to ARQULE of a decision to replace an Initial DS Target with another
Target, DS may select a second New DS Target by giving written notice of its
decision to do so to the JRC and ARQULE (a “New DS Target Notice”).  The Parties shall then follow the procedures
set forth in Section 3.5.2(b) (with the New DS Target Notice
replacing the notice under Section 3.5.2(a)), 3.5.2(c) and 3.5.2(d) to
select a second New DS Target.


 


2.             Each New DS Target shall be subject
to substitution as set forth in Section 3.5.2.


 


3.             Section 1.64 is modified to
read in full as follows:


 


1.64         “FTE Funding
Commitment” means (a) with respect to the ARQULE Research
Activities conducted in the first Contract Year during the Research
Collaboration Period, the funding of * ARQULE FTEs at the FTE Rate; (b) with
respect to the ARQULE Research Activities conducted by ARQULE in the second
Contract Year during the Research Collaboration Period, the funding of that
number of FTEs as shall be consistent with the Annual Research Plan for such
second Contract Year and agreed to by the Parties not later than * (*) days
prior to the commencement of such Contract Year; (c) with respect to the
ARQULE Research Activities conducted in the third Contract Year during the Research
Collaboration Period, the funding of * ARQULE FTEs at
the FTE Rate, and (d) with respect to the ARQULE Research Activities
conducted in the fourth Contract Year during the Research Collaboration Period,
the funding of that number of FTEs as shall be


 

















 


consistent
with the Annual Research Plan for the fourth
Contract Year and agreed to by the Parties not later than * (*) days prior to
the commencement of the fourth
Contract Year; provided, that, (i) such
number of FTEs is more than * (*),  and (ii) ARQULE’s consent shall be
required to increase the number of FTEs above the number in the third Contract Year.   In the event the Parties cannot agree on the
number of FTEs in the fourth Contract Year, each Party shall give written notice to the JEC of
the number of FTEs it believes is needed to perform the ARQULE Research
Activities in the fourth
Contract Year and the number of FTEs shall be decided in accordance with Section 2.1.5.  Until the number of FTEs is decided, the FTE
Funding Commitment for the fourth
Contract Year shall be the funding at the FTE Rate of a number of FTEs equal to
* (*).


 


4.             Section 1.93 is modified to
read in full as follows:


 


1.93         “Quarterly
FTE Payment” means (i) prior to December 1, 2010, with
respect to the Initial DS Targets and any replacements designated pursuant to
section 3.5.2, the amount payable by DS to ARQULE for FTEs for all ARQULE
Research Activities to be conducted during each Calendar Quarter of the
Research Collaboration Period, which shall equal * (*) of the FTE Funding
Commitment set forth in the Annual Research Plan for the applicable Calendar
Year, provided, that such amount shall be prorated for the first and last
Calendar Quarter based on the number of days in such first or last Calendar
Quarter divided by 365; and (ii) for the period beginning with December 1,
2010, with respect to New DS Targets and/or any replacements designated
pursuant to section 3.5.2 for either the New DS Targets or the Initial DS
Targets, * (*) of the funding of the number of ARQULE FTEs set forth in Section 1.64
at the FTE Rate.


 


5.             Section 1.97 is modified to
read in full as follows:


 


1.97         “Research
Collaboration Period” means the period beginning on the Effective
Date and ending at the end of  the fourth
Contract Year, as such period may be
extended by the mutual written agreement of the Parties; provided, that, if this Agreement is terminated prior to the end of the
Research Collaboration Period, the effective date of such early termination
shall become the last day of the Research Collaboration Period.


 


6.             Section 3.10 is modified to
read in full as follows:


 


3.10         Research Collaboration
Period.  The Research
Program shall commence on the Effective Date and continue until the expiration
of the Research Collaboration Period. 
Notwithstanding the foregoing, the Research Program may be terminated
prior to the expiration of the Research Collaboration Period (a) by either
Party on * (*) days’ prior written notice to the other Party at any time
following the exercise by DS of (i) * (*) DS Options in the event that DS
names * (*) New DS Targets or (ii) * (*) DS Options in the event that DS
substitutes a new DS Target for an Initial DS Target as set forth in Section 3.5.2
prior to naming a * New DS Target; and (b) by DS at any time upon not less
than * (*) days’ prior written notice to ARQULE and payment in full with such
notice of the amount which would have been payable for the remainder of the
Research Collaboration Period pursuant to Section 5.3.1 if the Research Program were conducted for the entire four (4) year
Research Collaboration Period.


 


7.             Section 1.48 is modified to
read in full as follows:


 


1.48         “DS Option Period”
means, with respect to any Primary Development


 

















 


Compound
and the related Backup Compounds, the period commencing on the date of
designation by DS of a Primary Development Compound, and continuing until sixty
(60) days following the date of receipt by the JRC of the Toxicology Studies
Results with respect to such Primary Development Compound, or up to * (*)
subsequently evaluated Backup Compounds provided that DS has designated such
Backup Compounds prior to the start of the first Toxicology Study; provided
that the DS Option Period shall end no later than * * (*) months after * with
respect to any Primary Development Compound and the related Backup Compounds
whose DS Target is an Initial DS Target and shall end no later than * (*)
months after the end of the Research Collaboration Period with respect to any
Primary Development Compound and the related Backup Compounds whose DS Target
is a New DS Target or a replacement to an Initial DS
Target or a New DS Target designated
pursuant to Section 3.5.2.


 


8.             Section 3.5.2(e) is
modified to read in full as follows:


 


(e)           Limitation on
DS Targets. 
Notwithstanding anything to the contrary set forth in this Agreement, (A) in
the event that DS names * (*) New DS Targets, DS shall have the right to
designate an aggregate of up to * (*) DS Targets pursuant to this Agreement,
consisting of (i) the * (*) Initial DS Targets designated by the Parties
on the Effective Date, (ii) the * (*) New DS Targets, and (iii) up to
* (*) Validated Targets designated by DS to replace Abandoned DS Targets pursuant to Section 3.5.2(d); and (B) in the event
that DS designates a substitute for an Initial DS Target as set forth in Section 3.5.2
prior to naming a * New DS Target, DS shall have the right to designate an
aggregate of up to * (*) DS Targets pursuant to this Agreement, consisting of (i) the
* (*) Initial DS Targets designated by the Parties on the Effective Date, (ii) the
* (*) New DS Target, and (iii) up to *  (*) Validated
Targets designated by DS to replace Abandoned DS Targets
pursuant to Section 3.5.2(d).  For
clarity, in no event shall ARQULE be obligated to conduct ARQULE Research
Activities on more than * (*) DS Targets at any given time.


 


9.             Section 5.2  is modified to read in full as follows:


 


5.2 License Fee. For each DS Option
exercised by DS pursuant to Section 7.1, DS shall pay ARQULE a license fee (the “License Fee”):  (i) in the case of the Initial DS Targets
and any replacement thereof designated pursuant to Section 3.5.2, *Dollars (US $*)
shall be paid within * (*) days of the execution of the License Agreement for
the Primary Development Compound and related Backup Compounds that were the
subject of such DS Option, and * Dollars (US $*) shall be paid within * (*)
days of the Initiation of the first Phase II Clinical Trial of any Licensed
Product under such License Agreement; or
(ii) in the case of the New DS Targets and any replacement thereof
designated pursuant to Section 3.5.2, * Dollars (US $*) shall be
paid within * (*) days of the execution of the License Agreement for the
Primary Development Compound and related Backup Compounds that were the subject
of such DS Option, and * Dollars (US *) shall be paid within * (*) days of the
Initiation of the first Phase II Clinical Trial of any Licensed Product under
such License Agreement.


 


10.             The following Section 5.5
is added to the Agreement:


 


5.5
FTE Payment Advance.  On *, DS shall pay ARQULE * Dollars (US $*) as an advance payment of
the first * Dollars (US $*) payable by DS pursuant to Section 5.3.1 for the * Contract Year
during the Research Collaboration Period. 
Once payments due under Section 5.3.1 for the * Contract Year
during the Research Collaboration Period reach * Dollars (US *),
DS shall resume making payments as set forth in Section 5.3.1.


 

















 


11.           Section 6.3 is modified to read
in full as follows:


 


6.3           Publications
and Presentations.  The
Parties acknowledge that scientific publications and presentations must be
strictly monitored to prevent any adverse effect from premature publication or
dissemination of results of the activities hereunder.  Each Party agrees that, except as required by
Applicable Laws, it shall not publish or present, or permit to be published or
presented, the results of the Research Program or the Development Program
without the prior review by the other Party. 
Each Party shall provide to the other Party the opportunity to review
each of the submitting Party’s proposed abstracts, manuscripts or presentations
(including, without limitation, information to be presented verbally) that
relate to the Research Program or the Development Program at least * (*) days
prior to its intended presentation or submission for publication, and such
submitting Party agrees, upon written request from the other Party given within
such * (*) day period, not to submit such abstract or manuscript for
publication or to make such presentation until the other Party is given up to *
(*) days from the date of such written request to seek appropriate patent
protection for any material in such publication or presentation that it
reasonably believes may be patentable. 
In the event that the Parties disagree on a proposed publication or presentation,
they will discuss the matter in good faith and
the matter shall be decided in accordance with Section 2.1.5 as a Unanimous
Decision, provided that if such Disputed Matter is not
resolved by the Designated Senior Officers within * (*) days after the date the
Designated Senior Officers first met to consider such Disputed Matter or * (*)
days after the date the JEC first met to consider such Disputed Matter,
whichever is later, then the Disputed Matter shall not be resolved in
accordance with Section 13.1, but instead, ARQULE shall have the right to
make the final decision on publication or presentation of the results of the
Research Program and DS shall have the right to make the final decision on
publication or presentation of the results of the Development Program.  Once such abstracts, manuscripts or
presentations have been published or presented by each Party,
the same abstracts, manuscripts or presentations do not have to be provided
again to the other Party for review for a later submission for
publication.  Each Party also shall have
the right to require that any of its Confidential Information that is disclosed
in any such proposed publication or presentation be deleted prior to such
publication or presentation; provided, that, ARQULE shall be permitted to use
data generated by ARQULE and information about the Target in any such
publication or presentation.  In any
permitted publication or presentation by a Party, the other Party’s
contribution shall be duly recognized, and co-authorship shall be determined in
accordance with customary standards. 
Each Party expressly acknowledges that the other Party’s business may be
substantially dependent on its ability to publish results in scientific
journals, presentation at scientific conferences and meetings.


 


12.           Notwithstanding anything to the
contrary in the Agreement, this Amendment or any Annual Research Plan, ARQULE
shall perform the *studies for the DS Target * and DS shall bear all costs
associated with such * studies, including, but not limited to, *, as requested
by DS and agreed by ARQULE.  A plan for
the * studies for the DS Target *, including the costs, shall be agreed upon by
the Parties.  Any amendment, modification
and/or update to such plan shall be discussed and agreed by the Parties.  ARQULE shall invoice DS (a) quarterly in
advance, at least * (*) days prior to each Calendar Quarter, for all ARQULE
FTEs involved in performing or managing external performance of such * studies and (b) quarterly in arrears for all Third Party Costs associated
with such * studies, including without limitation, * costs. DS shall pay such
invoices for ARQULE FTEs at least * (*) days before the first day of each
Calendar Quarter and shall pay such invoices for Third Party Costs within * (*)
days after receipt thereof.


 

















 


13.           The Parties agree to issue a press
release relating to this Amendment in the form attached hereto as Exhibit 1
within seven (7) days after the Effective Date.


 


14.           In all other respects, the Agreement
shall remain in full force and effect and shall not be modified hereby.


 


This
Amendment may be executed as of the date first
written above in any number of counterparts, each of which shall
be an original, but all of which together shall constitute one and the same
agreement.


 


*   *   *   *   *  
*   *   *


 




	
   

  	
   

  	
  ArQule, Inc.

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  By:

  	
   

  
	
   

  	
   

  	
   

  	
  /s/
  Paolo Pucci

  
	
   

  	
   

  	
   

  	
  Name:
  Paolo Pucci

  
	
   

  	
   

  	
   

  	
  Title:
  Chief Executive Officer

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  Daiichi
  Sankyo Co., Ltd.

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  By:

  	
   

  
	
   

  	
   

  	
   

  	
  /s/Kazunori
  Hirokawa

  
	
   

  	
   

  	
   

  	
  Name:
  Kazunori  Hirokawa

  
	
   

  	
   

  	
   

  	
  Title:
  Senior Executive Officer and Head of R&D Division

  






 

















 


SCHEDULE 1


 


NEW DS TARGETS LIST


 


*



 

















 


EXHIBIT 1


 


FORM OF JOINT PRESS RELEASE