Document:

Exhibit 10.3

 

CONFIDENTIAL TREATMENT
REQUESTED

UNDER 17 C.F.R §§
200.80(b)4, AND 240.24b-2

 

 

AMENDMENT NUMBER ONE

TO THE

AMENDED AND RESTATED

LICENSE AND COLLABORATION AGREEMENT

 

This
Amendment Number One (the “Amendment”)
to the Amended and Restated License and Collaboration Agreement is entered into
as of the 10th day of June, 2010 (the “Effective Date”)
by and among ALNYLAM PHARMACEUTICALS, INC., a
Delaware corporation, with its principal place of business at 300 Third Street,
Cambridge, Massachusetts 02142 (“Alnylam”), ISIS PHARMACEUTICALS, INC., a Delaware corporation, with its
principal place of business at 1896 Rutherford Road, Carlsbad, California 92008
(“Isis”, and each of Alnylam and Isis,
a “Licensor” and together, the “Licensors”), and REGULUS THERAPEUTICS INC. (formerly Regulus Therapeutics
LLC), a Delaware corporation, with its principal place of business at 1896
Rutherford Road, Carlsbad, California 92008 (“Regulus”).

 

RECITALS

 

WHEREAS, Isis and Alnylam each granted a license to Regulus
in accordance with that certain License and Collaboration Agreement dated
September 6, 2007 (the “Original License Agreement”),
which Original License Agreement was amended and restated on January 1, 2009
(the “Amended License Agreement”);

 

WHEREAS, Isis, Alnylam, and Regulus now desire to amend the
Amended License Agreement as provided herein.

 

AGREEMENT

 

NOW, THEREFORE, in consideration of the mutual covenants
contained herein, and other good and valuable consideration, the receipt and
sufficiency of which is hereby acknowledged, Isis, Alnylam and Regulus each
agrees as follows:

 

1.             DEFINITIONS

 

Capitalized terms used herein and not defined
elsewhere herein have the meanings set forth in the Amended License Agreement.

 

2.             PAYMENTS

 

2.1           The following bullet point shall be added as a new
second bullet point in the definition of “Exclusivity Period” in the Amended
License Agreement:

 

“·    with respect to
a Royalty-Bearing Product being Commercialized by a Collaborator of Regulus
(other than Alnylam or Isis), the Exclusivity Period shall expire at such time
as such Collaborator is no longer required to pay Regulus any royalty (not
including any amounts 

 

 

paid
by Collaborator to Regulus arising from payment obligations to Third Parties)
with respect to such  Royalty-Bearing
Product; or”

 

2.2           Section 5.2 of the Amended License Agreement shall
be deleted and replaced in its entirety by the following:

 

“5.2       Continued Development by Regulus of Development
Projects.

 

(a)       Diligence.  If Regulus notifies Licensors pursuant to
Section 5.1 that Regulus will continue to pursue the Development and
Commercialization of such Development Project (on its own or with a
Collaborator, as defined below), then, without limiting the generality of
Section 4.1, Regulus will use Commercially Reasonable Efforts to Develop and
Commercialize the relevant Development Compounds and Development Therapeutics
in the Field.

 

(b)       Third Party Payments.  Regulus will be responsible for all
milestones, royalties and other payments payable to Third Parties in respect of
the Development, Manufacture and Commercialization of Development Therapeutics
in the Field, by Regulus, its Affiliates and Sublicensees, including any
amounts payable by either Licensor to Third Parties under the Third Party
Rights.  The Parties will use reasonable
efforts to [***].

 

(c)       Net Sales by Regulus.  Regulus will pay to each Licensor a royalty
of [***]% of Net Sales of Development Therapeutics which are Royalty-Bearing
Products which Net Sales are generated by Regulus rather than a Collaborator,
during the relevant Royalty Term (provided, however, that, for
the remainder of the relevant Royalty Term following the end of the relevant
Exclusivity Period, the royalty rate will be [***]%).  Regulus agrees that the royalty described in
Section 5.2(c) is payable to each Licensor, regardless of whether a particular
Royalty-Bearing Product is covered by such Licensor’s Licensed IP.

 

(d)       Net Sales by a Collaborator
of Regulus.  With
respect to Net Sales by a Collaborator of Regulus (other than Alnylam or Isis),
Regulus will pay to each Licensor a royalty of [***]% of Net Sales of such
Development Therapeutics which are Royalty-Bearing Products; provided, that (i)
the agreement with such Collaborator requires such Collaborator to make royalty
payments to Regulus of at least [***]% of Net Sales (after any payments
required to be made by Regulus to Third Parties) and (ii) the length of the
Exclusivity Period with respect to such Collaborator is no shorter than the
Exclusivity Period which would apply to Net Sales by Regulus under Section
5.2(c) above ((i) and (ii) being collectively referred to as “Consistent Sublicense Terms”).  Notwithstanding the foregoing, if the
agreement with such Collaborator does not contain Consistent Sublicense Terms
or if Regulus chooses at the time of, or prior to, entering into such agreement
to have this sentence apply in lieu of the first sentence of this Section
5.2(d), such choice to be delivered in writing to Alnylam and Isis within
thirty (30) days of entering into such sublicense agreement (a “Sublicense Income Agreement”), then
(x) Isis, Alnylam and Regulus will each receive the [***] of (I) [***]% of
[***] (A) [***] received by Regulus on the basis of such [***] pursuant to such
Sublicense Income Agreement, and (B) [***] made to Third Parties as described
in [***], and (II) [***]% 

 

 

of Net Sales of such Development Therapeutics, and
(y) Alnylam and Isis will be entitled to receive additional payments from
Regulus in accordance with Section 5.2(e) below.  “Collaborator”
means a Third Party sublicensee or
other partner of Regulus which partner receives from Regulus a
sublicense, participates with Regulus in a collaboration, receives from Regulus a technology transfer or otherwise
obtains from Regulus rights related to Develop or Commercialize miRNA
Compounds, miRNA Therapeutics, or miRNA Antagonists. A “Collaborator” will be
considered a “Sublicensee” for purposes of this Agreement.

 

(e)           Sublicense Income.  With respect to each Sublicense Income
Agreement, Regulus shall pay [***] of Sublicense Income received by Regulus to
Alnylam and [***] of Sublicense Income received by Regulus to Isis.  “Sublicense Income”
means all fees and other payments received by Regulus from a Collaborator in connection with a Sublicense Income
Agreement, but excluding (i)
debt, credit or lease financing
(provided, however, that (x) any discount to market will not be excluded from
the definition of Sublicense Income and (y) in the event that any portion of
such debt, credit or lease is forgiven, such debt, credit, or lease will be
deemed Sublicense Income in the amount of such forgiveness), (ii) the fair market value of any equity
investments in Regulus, (iii) the bona fide reimbursement of future research and development funding by a
third party (as specified in the Sublicense Income Agreement) at direct cost, (iv) the bona fide
reimbursement of future out-of-pocket costs
of patent filing, prosecution and maintenance, and patent defense, and (v) royalties for which compensation is paid to Alnylam and Isis pursuant
to Section 5.2(d).  For purposes of
clarity, payments for specific events associated with sales such as net
sales-based milestones or unit-based milestones will not be excluded from Sublicense Income.  Notwithstanding the foregoing, the $[***]
[***] payments to Regulus from [***] pursuant to [***] research collaboration
will not be considered Sublicense Income.

 

(f)            Full Consideration.  Regulus agrees that the royalties described
in Sections 5.2(c) and 5.2(d) and the Sublicense Income provisions contained in
Section 5.2(e) are payable to each Licensor, regardless of whether a particular
Royalty-Bearing Product is covered by such Licensor’s Licensed IP.  Each Party agrees and acknowledges that such
royalty structure (i) is freely entered into by such Party, (ii) is a fair
reflection of the value received by Regulus from the licenses granted by the
Licensors, and (iii) is a reasonable allocation of the value received by
Regulus from each Licensor, due to the difficulty of determining the extent to
which Licensor’s Licensed IP covers or has enabled each Royalty-Bearing
Product.”

 

3.             BUY OUT

 

3.1           Buy-Out.  Any and all references in the Amended License
Agreement to the term “Buy-Out” are null and void.

 

 

4.             MISCELLANEOUS

 

4.1           Other Terms.  All other terms and conditions of the Amended
License Agreement shall remain in full force and effect.  The Amendment Number One to the Amended and
Restated License and Collaboration Agreement entered into among Regulus and the
Licensors on June 7, 2010 is superseded and replaced by this Amendment and is
deemed void ab initio.

 

4.2           Counterparts.  This Agreement may be executed in any number
of counterparts, each of which will be deemed an original, and all of which
together will constitute one and the same instrument.

 

[Remainder of Page Intentionally Left Blank]

 

 

IN
WITNESS WHEREOF, the Parties hereby execute this Amendment Number One to the
Amended and Restated License and Collaboration Agreement as of the date first
written above.

 

 

	
   

  	
   

  	
  ALNYLAM
  PHARMACEUTICALS, INC.

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  By:

  	
  /s/
  Barry Greene

  
	
   

  	
   

  	
   

  	
  Name:
  Barry Greene

  
	
   

  	
   

  	
   

  	
  Title:
  President and Chief Operating Officer

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  ISIS
  PHARMACEUTICALS, INC.

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  By:

  	
  /s/
  B. Lynne Parshall

  
	
   

  	
   

  	
   

  	
  Name:
  B. Lynne Parshall

  
	
   

  	
   

  	
   

  	
  Title:
  Chief Operating Officer and CFO

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  REGULUS
  THERAPEUTICS INC.

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  By:

  	
  /s/
  Kleanthis G. Xanthopoulos

  
	
   

  	
   

  	
   

  	
  Name:
  Kleanthis G. Xanthopoulos, Ph.D.

  
	
   

  	
   

  	
   

  	
  Title:
  President and Chief Executive OfficerExhibit 10.4

 

AMENDMENT NUMBER ONE

TO THE

FOUNDING INVESTOR RIGHTS AGREEMENT

 

This
Amendment Number One (the  “Amendment”) to the Founding Investor
Rights Agreement dated January 1, 2009 (the “Investor
Rights Agreement”) is entered into as of the 7th  day of June, 2010 (the “Effective
Date”) by and among ALNYLAM PHARMACEUTICALS, INC.,
a Delaware corporation, with its principal place of business at 300 Third
Street, Cambridge, Massachusetts 02142 (“Alnylam”), ISIS PHARMACEUTICALS, INC., a Delaware corporation,
with its principal place of business at 1896 Rutherford Road, Carlsbad,
California 92008 (“Isis”, and each of Alnylam
and Isis, a “Licensor” and together, the “Licensors”), and REGULUS THERAPEUTICS INC. (formerly Regulus Therapeutics
LLC), a Delaware corporation, with its principal place of business at 1896
Rutherford Road, Carlsbad, California 92008 (“Regulus”).

 

RECITALS

 

WHEREAS, Regulus, Isis and Alnylam entered into the
Investor Rights Agreement;

 

WHEREAS, Isis, Alnylam, and Regulus now desire to amend
the Investor Rights Agreement as provided herein.

 

AGREEMENT

 

NOW, THEREFORE, in consideration of the mutual covenants
contained herein, and other good and valuable consideration, the receipt and
sufficiency of which is hereby acknowledged, Isis, Alnylam and Regulus
each agrees as follows:

 

1.             DEFINITIONS

 

Capitalized terms used herein and not defined
elsewhere herein have the meanings set forth in the Investor Rights Agreement.

 

2.                                       DELETION OF
BUY-OUT PROVISION

 

2.1           Elimination of Buy-Out Provision.  Section 4 of the Investor Rights
Agreement shall be deleted in its entirety and replaced with the following: “[Deliberately
Omitted]”

 

2.2           Elimination of Exhibit D.  Exhibit D of the Investor Rights
Agreement shall be deleted in its entirety and replaced with the following: “[Deliberately
Omitted]”

 

 

3.                                       MISCELLANEOUS

 

3.1           Other Terms.  All other terms and conditions of the
Investor Rights Agreement shall remain in full force and effect.

 

3.2           Counterparts.  This Agreement may be executed in any number
of counterparts, each of which will be deemed an original, and all of which
together will constitute one and the same instrument.

 

[Remainder of Page Intentionally Left Blank]

 

2

 

IN
WITNESS WHEREOF, the Parties hereby execute this Amendment Number One to the
Founding Investor Rights Agreement as of the Effective Date.

 

 

	
   

  	
  ALNYLAM
  PHARMACEUTICALS, INC.

  
	
   

  	
   

  
	
   

  	
  By:

  	
  /s/
  Barry Greene

  
	
   

  	
   

  	
  Name:
  Barry Greene

  
	
   

  	
   

  	
  Title:
  President and Chief Operating Officer

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  
	
   

  	
  ISIS
  PHARMACEUTICALS, INC.

  
	
   

  	
   

  
	
   

  	
   

  	
   

  
	
   

  	
  By:

  	
  /s/
  B. Lynne Parshall

  
	
   

  	
   

  	
  Name:
  B. Lynne Parshall

  
	
   

  	
   

  	
  Title:
  Chief Operating Officer and CFO

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  
	
   

  	
  REGULUS
  THERAPEUTICS INC.

  
	
   

  	
   

  
	
   

  	
   

  	
   

  
	
   

  	
  By:

  	
  /s/
  Kleanthis G. Xanthopoulos

  
	
   

  	
   

  	
  Name:
  Kleanthis G. Xanthopoulos, Ph.D.

  
	
   

  	
   

  	
  Title:
  President and Chief Executive Officer

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