Exhibit
10.27


 


EXECUTION
VERSION


 


Confidential
Materials omitted and filed separately with the

Securities and Exchange Commission. 
Asterisks denote omissions.


 


 


LICENSE AGREEMENT


 


BY AND AMONG


 


IKARIA DEVELOPMENT
SUBSIDIARY TWO LLC


 


AND


 


FIBREX MEDICAL, INC.


 


AND


 


FIBREX MEDICAL RESEARCH &
DEVELOPMENT GESMBH


 


 


DATED


 


AS OF


 


JULY 17, 2009


 

















 


TABLE OF CONTENTS


	
  Article I
  Definitions; Interpretation

  	
  1

  
	
  Section 1.1

  	
  “Affiliate”

  	
  1

  
	
  Section 1.2

  	
  “Business Day”

  	
  1

  
	
  Section 1.3

  	
  “Commercialization” or “Commercialize”

  	
  1

  
	
  Section 1.4

  	
  “Compound”

  	
  2

  
	
  Section 1.5

  	
  “Commercially Reasonable Efforts”

  	
  2

  
	
  Section 1.6

  	
  “Confidential Information”

  	
  2

  
	
  Section 1.7

  	
  “Control”

  	
  2

  
	
  Section 1.8

  	
  “Development” or “Develop”

  	
  2

  
	
  Section 1.9

  	
  “EU”

  	
  3

  
	
  Section 1.10

  	
  “Executive Officers”

  	
  3

  
	
  Section 1.11

  	
  “FDA”

  	
  3

  
	
  Section 1.12

  	
  “Fibrex Know-How”

  	
  3

  
	
  Section 1.13

  	
  “Fibrex Patent Rights”

  	
  3

  
	
  Section 1.14

  	
  “Fibrex Intellectual Property”

  	
  3

  
	
  Section 1.15

  	
  “Field”

  	
  3

  
	
  Section 1.16

  	
  “F.I.R.E. Study”

  	
  3

  
	
  Section 1.17

  	
  “First Commercial Sale”

  	
  3

  
	
  Section 1.18

  	
  “Generic Version”

  	
  3

  
	
  Section 1.19

  	
  “Ikaria Product Improvements”

  	
  3

  
	
  Section 1.20

  	
  “Ikaria Product IP”

  	
  4

  
	
  Section 1.21

  	
  “Indication”

  	
  4

  
	
  Section 1.22

  	
  “Joint Intellectual Property”

  	
  4

  
	
  Section 1.23

  	
  “Joint Know-How”

  	
  4

  
	
  Section 1.24

  	
  “Joint Patent Rights”

  	
  4

  
	
  Section 1.25

  	
  “Know-How”

  	
  4

  
	
  Section 1.26

  	
  “Knowledge”

  	
  4

  
	
  Section 1.27

  	
  “MAA”

  	
  4

  
	
  Section 1.28

  	
  “Manufacturing” or “Manufacture”

  	
  4

  
	
  Section 1.29

  	
  “NDA”

  	
  4

  
	
  Section 1.30

  	
  “Net Sales”

  	
  4

  
	
  Section 1.31

  	
  “Party”

  	
  6

  
	
  Section 1.32

  	
  “Patent Rights”

  	
  6

  
	
  Section 1.33

  	
  “Person”

  	
  6

  
	
  Section 1.34

  	
  “Phase I Clinical Trial”

  	
  6

  
	
  Section 1.35

  	
  “Phase IIa Clinical Trial”

  	
  6

  
	
  Section 1.36

  	
  “Phase IIb Clinical Trial”

  	
  6

  
	
  Section 1.37

  	
  “Phase III Clinical Trial”

  	
  6

  
	
  Section 1.38

  	
  “Product”

  	
  6

  
	
  Section 1.39

  	
  “Regulatory Approval”

  	
  6

  
	
  Section 1.40

  	
  “Regulatory Authority”

  	
  6

  
	
  Section 1.41

  	
  “Royalty Term”

  	
  7

  
	
  Section 1.42

  	
  “Sublicensee”

  	
  7

  
	
  Section 1.43

  	
  “Successful Completion”:

  	
  7

  
	
  Section 1.44

  	
  “Territory”

  	
  7

  



 

















 


Table of Contents


(Continued)


 


	
   

  	
   

  	
  Page

  
	
   

  	
   

  	
   

  
	
  Section 1.45

  	
  “Third Party”

  	
  7

  
	
  Section 1.46

  	
  “Valid Claim”

  	
  7

  
	
  Section 1.47

  	
  Additional Definitions

  	
  7

  
	
  Section 1.48

  	
  Interpretation

  	
  8

  
	
   

  	
   

  	
   

  
	
  Article II Grant of
  Rights

  	
  9

  
	
  Section 2.1

  	
  Fibrex License Grant to Ikaria

  	
  9

  
	
  Section 2.2

  	
  Non-Competition

  	
  9

  
	
  Section 2.3

  	
  Section 365(n) of the Bankruptcy Code

  	
  9

  
	
  Section 2.4

  	
  Sublicenses

  	
  10

  
	
  Section 2.5

  	
  Retained Rights

  	
  10

  
	
   

  	
   

  	
   

  
	
  Article III Development;
  Manufacturing; Commercialization

  	
  10

  
	
  Section 3.1

  	
  General

  	
  10

  
	
  Section 3.2

  	
  Regulatory Matters

  	
  10

  
	
  Section 3.3

  	
  Technology Transfer

  	
  10

  
	
  Section 3.4

  	
  Diligence and Reports

  	
  11

  
	
  Section 3.5

  	
  Manufacturing

  	
  11

  
	
  Section 3.6

  	
  Commercialization

  	
  11

  
	
  Section 3.7

  	
  On-Going Studies

  	
  11

  
	
  Section 3.8

  	
  Consulting Agreements

  	
  12

  
	
   

  	
   

  	
   

  
	
  Article IV Financial
  Provisions

  	
  12

  
	
  Section 4.1

  	
  Milestone Payments

  	
  12

  
	
  Section 4.2

  	
  Royalties on Net Sales of Products

  	
  14

  
	
  Section 4.3

  	
  Reports and Accounting

  	
  15

  
	
  Section 4.4

  	
  Currency Amounts

  	
  16

  
	
  Section 4.5

  	
  Currency Exchange

  	
  16

  
	
  Section 4.6

  	
  Tax Withholding

  	
  16

  
	
  Section 4.7

  	
  Blocked Payments

  	
  16

  
	
  Section 4.8

  	
  Freedom to Operate

  	
  16

  
	
   

  	
   

  	
   

  
	
  Article V Intellectual
  Property Ownership, Protection and Related Matters

  	
  17

  
	
  Section 5.1

  	
  Ownership of Inventions

  	
  17

  
	
  Section 5.2

  	
  Prosecution and Maintenance of Patent Rights

  	
  18

  
	
  Section 5.3

  	
  Third Party Infringement

  	
  18

  
	
   

  	
   

  	
   

  
	
  Article VI
  Confidentiality

  	
  20

  
	
  Section 6.1

  	
  Confidential Information

  	
  20

  
	
  Section 6.2

  	
  Disclosures to Employees, Consultants, Advisors, Etc.

  	
  21

  
	
  Section 6.3

  	
  Terms of this Agreement

  	
  21

  
	
  Section 6.4

  	
  Term

  	
  21

  
	
  Section 6.5

  	
  Publicity

  	
  21

  



 


ii

















 


Table of Contents


(Continued)


 


	
   

  	
   

  	
  Page

  
	
   

  	
   

  	
   

  
	
  Article VII
  Representations and Warranties

  	
  22

  
	
  Section 7.1

  	
  Representations of Authority

  	
  22

  
	
  Section 7.2

  	
  Consents

  	
  22

  
	
  Section 7.3

  	
  No Conflict

  	
  22

  
	
  Section 7.4

  	
  Enforceability

  	
  22

  
	
  Section 7.5

  	
  Additional Fibrex Representations

  	
  22

  
	
  Section 7.6

  	
  Employee, Consultant and Advisor Legal Obligations

  	
  23

  
	
  Section 7.7

  	
  No Warranties

  	
  23

  
	
   

  	
   

  	
   

  
	
  Article VIII Term and
  Termination

  	
  23

  
	
  Section 8.1

  	
  Term

  	
  23

  
	
  Section 8.2

  	
  Termination for Material Breach

  	
  23

  
	
  Section 8.3

  	
  Development-Related Termination by Ikaria

  	
  23

  
	
  Section 8.4

  	
  Effect of Certain Terminations and Expiration

  	
  24

  
	
  Section 8.5

  	
  Survival

  	
  25

  
	
   

  	
   

  	
   

  
	
  Article IX
  Dispute Resolution

  	
  25

  
	
  Section 9.1

  	
  Negotiation

  	
  25

  
	
  Section 9.2

  	
  Escalation

  	
  25

  
	
  Section 9.3

  	
  Litigation

  	
  25

  
	
  Section 9.4

  	
  Equitable Relief

  	
  26

  
	
   

  	
   

  	
   

  
	
  Article X
  Miscellaneous Provisions

  	
  26

  
	
  Section 10.1

  	
  Indemnification

  	
  26

  
	
  Section 10.2

  	
  Governing Law

  	
  27

  
	
  Section 10.3

  	
  Submission to Jurisdiction

  	
  27

  
	
  Section 10.4

  	
  Assignment

  	
  27

  
	
  Section 10.5

  	
  Entire Agreement; Amendments

  	
  27

  
	
  Section 10.6

  	
  Notices

  	
  28

  
	
  Section 10.7

  	
  Force Majeure

  	
  28

  
	
  Section 10.8

  	
  Independent Contractors

  	
  29

  
	
  Section 10.9

  	
  Limitations of Liability

  	
  29

  
	
  Section 10.10

  	
  No Implied Waivers; Rights
  Cumulative; Joint and Several Liability

  	
  29

  
	
  Section 10.11

  	
  Severability

  	
  29

  
	
  Section 10.12

  	
  Fibrex Medical R&D

  	
  29

  
	
  Section 10.13

  	
  Execution in Counterparts; Facsimile Signatures

  	
  30

  
	
  Section 10.14

  	
  Ikaria Affiliates

  	
  30

  
	
  Section 10.15

  	
  Parent Guarantee

  	
  30

  



 


iii

















 


Table of Contents


(Continued)


 


	
   

  	
   

  	
  Page

  
	
   

  	
   

  	
   

  
	
  Schedules

  	
   

  	
   

  
	
  Schedule
  1.4

  	
  Compounds

  	
   

  
	
  Schedule
  3.7

  	
  On-Going
  Studies

  	
   

  
	
  Schedule
  4.3(a)

  	
  Wire
  Transfer Information

  	
   

  
	
   

  	
   

  	
   

  
	
  Exhibits

  	
   

  	
   

  
	
  Exhibit A

  	
  Fibrex
  Patent Rights

  	
   

  
	
  Exhibit B

  	
  Technology
  Transfer Plan

  	
   

  
	
  Exhibit C

  	
  Milestone
  Payment Examples

  	
   

  
	
  Exhibit D

  	
  Form of Guarantee

  	
   

  



 


iv

















 


LICENSE AGREEMENT


 


This License Agreement (the “Agreement”)
is entered into this 17th day of July, 2009 (the “Effective Date”), by
and among Ikaria Development Subsidiary Two LLC, a Delaware limited liability
company having a principal place of business at 6 State Route 173, Clinton, NJ
08809, USA (“Ikaria”), Fibrex Medical, Inc., a Delaware corporation
having a principal place of business at 245 First Street, Suite 1800,
Cambridge, MA 02142 (“Fibrex Medical”), and Fibrex Medical Research &
Development GesmbH, a corporation organized and existing under the laws of the
Republic of Austria, having a principal place of business at Gastgebgasse 5-13,
A-1230 Vienna, Austria (“Fibrex Medical R&D”; together with Fibrex
Medical, “Fibrex”).


 


INTRODUCTION


 


WHEREAS, Fibrex owns or controls certain
intellectual property rights covering an investigational portfolio of compounds
designated by Fibrex as FX06, FX201, FX107, and back-up compounds, which
inhibit the binding of fibrin E1 fragment to vascular endothelial cadherin;


 


WHEREAS, Fibrex desires to grant to Ikaria
the worldwide exclusive rights (except as set forth herein) to Develop,
Manufacture, use, and Commercialize Products (as such capitalized terms are
defined below); and


 


WHEREAS, Ikaria desires to obtain such
exclusive rights in accordance with the terms and conditions of this Agreement.


 


NOW, THEREFORE, Fibrex and Ikaria agree as
follows:


 


Article I


Definitions; Interpretation


 


When used in this Agreement, each of the
following capitalized terms has the meaning set forth in this Article I:


 


Section 1.1             “Affiliate” shall mean, with
respect to a Party, any Person that controls, is controlled by, or is under
common control with such Party.  For
purposes of this Section 1.1, “control” shall refer to (a) in the
case of a Person that is a corporate entity, direct or indirect ownership of
more than fifty percent (50%) of the stock or shares having the right to vote
for the election of a majority of the directors of such Person, and (b) in
the case of a Person that is an entity, but is not a corporate entity, the
possession, directly or indirectly, of the power to direct, or cause the
direction of, the management or policies of such Person, whether through the
ownership of voting securities, by contract or otherwise.


 


Section 1.2             “Business Day” shall mean a day
that is not a Saturday, a Sunday or a day on which banking institutions in New
York, New York, USA or Vienna, Austria are authorized by law to remain closed.


 


Section 1.3             “Commercialization” or “Commercialize”
shall mean any activities directed to marketing, promoting, distributing,
importing, exporting, or selling a product.


 


1

















 


Section 1.4             “Compound” means (a) FX06,
(b) FX201, (c) FX107 (each of (a), (b) and (c) as more
fully described on Schedule 1.4 to this Agreement), and (d) any backup
compounds Controlled by Fibrex during the term of this Agreement that inhibit
the binding of fibrin E1 fragment to vascular endothelial cadherin, including
second generation fibrin E1 fragment inhibitors.


 


Section 1.5             “Commercially Reasonable Efforts”
means the use of efforts and resources commonly used by Ikaria and its
Affiliates with its other pharmaceutical products of similar commercial
potential at a similar stage in its product life, but no less than active commitment
of efforts and resources (financial and otherwise) consistent with those
normally applied in the biopharmaceutical industry to accomplish a similar
objective under similar circumstances for products of similar commercial
potential at a similar stage in their product development.


 


Section 1.6             “Confidential Information”
shall mean, with respect to a disclosing Party, all Know-How or other
information (whether or not patentable) regarding such Party’s technology,
products, business information or objectives (whether disclosed before or after
the Effective Date) that is of a confidential and proprietary nature, including
reports and audits under Section 4.3, 
and all proprietary tangible materials (and data and information
associated therewith) of such Party. 
Notwithstanding the foregoing, Confidential Information shall not
include Know-How or other information that:


 


(a)   was rightfully known or used by the receiving Party or its
Affiliates without an obligation of confidentiality prior to its date of disclosure
to the receiving Party as demonstrated by contemporaneous written records; or


 


(b)   either before or after the date of the disclosure to the receiving
Party is lawfully disclosed to the receiving Party or its Affiliates by sources
other than the disclosing Party rightfully in possession of such information
and not bound by confidentiality obligations to the disclosing Party; or


 


(c)   either before or after the date of the disclosure to the receiving
Party or its Affiliates is or becomes published or otherwise is or becomes part
of the public domain through no breach hereof on the part of the receiving
Party or its Affiliates; or


 


(d)   is independently developed by or for the receiving Party or its
Affiliates without reference to or use of the Confidential Information of the
disclosing Party as demonstrated by contemporaneous written records.


 


Section 1.7             “Control” shall mean, as to
a Party, the legal authority or right of such Party or any of its Affiliates to
grant a license or sublicense of intellectual property rights to the other
Party, or to provide tangible material to or otherwise disclose proprietary or
trade secret information to such other Party, without breaching the terms of
any agreement with a Third Party.


 


Section 1.8              “Development” or “Develop”
shall mean research, discovery, and development activities, including test
method development and stability testing, toxicology, 


 


2

















 


formulation, optimization, quality
assurance/quality control development, statistical analysis, clinical studies,
regulatory affairs, product approval, and registration.


 


Section 1.9             “EU” shall mean the European
Union and all the member states thereof, as it may be comprised from time to
time.


 


Section 1.10            “Executive Officers” shall
mean the Chief Executive Officer of Ikaria (or a senior executive officer of
Ikaria designated by Ikaria) and the Chief Executive Officer of Fibrex (or a
senior executive officer of Fibrex designated by Fibrex).


 


Section 1.11           “FDA” shall mean the United
States Food and Drug Administration or any successor agency thereof.


 


Section 1.12           “Fibrex Know-How” shall mean
all Know-How necessary or useful for the Development, Manufacture, use or
Commercialization of Products that (a) is Controlled by Fibrex as of the
Effective Date or (b) Fibrex comes to Control during the term of this
Agreement.


 


Section 1.13           “Fibrex Patent Rights” shall
mean Patent Rights Controlled by Fibrex that claim or are directed to any of
the Compounds or their method of manufacture or use, including the Patent
Rights listed in Exhibit A.


 


Section 1.14           “Fibrex Intellectual Property”
shall mean, collectively, Fibrex Patent Rights, Fibrex Know-How, and Fibrex’s
rights in and to any Joint Intellectual Property.


 


Section 1.15           “Field” shall mean any and all
therapeutics uses.


 


Section 1.16           “F.I.R.E. Study” shall mean
the Phase II clinical trial conducted by Fibrex using FX06 in AMI patients
using a bolus dosing regimen titled “A Multi-center, Double-blind, Randomized,
Placebo-Controlled Study to Measure the Effect of FX06 on Ischemia-Reperfusion
Injury in Patients Undergoing Primary Percutaneous Coronary Intervention (March 08,
2006),” as amended by Amendments 1- 4.


 


Section 1.17           “First Commercial Sale” shall
mean, with respect to a Product in a country, the first commercial sale of such
Product by Ikaria, its Affiliates, or Sublicensees in such country.  Sales for test marketing, clinical trial
purposes, or compassionate or similar use shall not be considered to constitute
a First Commercial Sale.


 


Section 1.18           “Generic Version” shall mean,
with respect to a Product, a product Developed and Manufactured by one or more
Third Parties not licensed under the Fibrex Intellectual Property or the Ikaria
Product IP that comprises the same compound, and is approved for the same
indication as such Product.


 


Section 1.19           “Ikaria Product Improvements”
shall mean any Ikaria Sole Inventions necessary or useful for the Development,
Manufacture, or use of any Product Developed hereunder, the practice of which
would constitute infringement (with respect to Patent Rights) or unauthorized
use (with respect to Know-How) but for ownership of (with a retained right to
exploit), or a license granted under, the Fibrex Intellectual Property.


 


3

















 


Section 1.20           “Ikaria Product IP” shall
mean, collectively, all Patent Rights and Know-How necessary or useful for the
Development, Manufacture, use, or Commercialization of Products that (a) is
Controlled by Ikaria as of the Effective Date or (b) Ikaria comes to
Control during the term of this Agreement.


 


Section 1.21           “Indication” shall mean any
disease or condition for which Ikaria Develops a Product.


 


Section 1.22           “Joint Intellectual Property”
shall mean Joint Know-How and Joint Patent Rights, collectively.


 


Section 1.23           “Joint Know-How” shall mean
any Know-How, including any Joint Inventions, that is developed or acquired
jointly by the Parties during the term of this Agreement.


 


Section 1.24           “Joint Patent Rights” shall
mean Patent Rights that claim or disclose Joint Know-How.


 


Section 1.25           “Know-How” shall mean any
information, inventions, discoveries, documents and other works of authorship,
copyrights, trade secrets, data, or materials, whether proprietary or not,
including data generated in clinical trials.


 


Section 1.26           “Knowledge” shall mean, with
respect to a Party, the Party’s actual knowledge as of the Effective Date,
together with any knowledge of any of the Party’s officer- or director-level
employees, that a Person in such Party’s position would be expected to obtain
as of the Effective Date, given the exercise of reasonably prudent scientific
and business diligence in accordance with the standards of companies of such
Party’s size in such Party’s industry.


 


Section 1.27           “MAA” shall mean a Marketing
Authorization Application.


 


Section 1.28           “Manufacturing” or “Manufacture”
shall mean any activities associated with the production, manufacture, supply,
processing, filling, packaging, labeling, shipping, or storage of a product or
any components thereof, including process and formulation development, process
validation, stability testing, manufacturing scale-up, development and
commercial manufacture and analytical development, product characterization,
quality assurance and quality control development, testing, and release.


 


Section 1.29           “NDA” shall mean a New Drug
Application submitted to the FDA or Japan’s Ministry of Health, Labor and
Welfare.


 


Section 1.30           “Net Sales” shall mean, with
respect to a Product, the gross amounts billed by Ikaria, its Affiliates, or
Sublicensees in respect of sales of such Product by Ikaria and its Affiliates
or Sublicensees to unrelated Third Parties, in each case less the following
deductions:


 


(a)   Trade, cash, or quantity discounts (including amounts incurred in
connection with government mandated rebate and discount programs, third party
rebates and chargebacks, hospital buying group/group purchasing organization
administration fees, and managed care organization rebates) actually allowed and
taken with respect to such sales;


 


4

















 


(b)   Tariffs, duties, excises, sales taxes or other taxes imposed upon
and paid with respect to the production, sale, delivery, or use of the Product
(excluding national, state, or local taxes based on income);


 


(c)   Amounts repaid or credited by reason of billing corrections,
rejections, defects, recalls, or returns (due to spoilage, damage, expiration
of useful life or otherwise) or because of chargebacks, refunds, rebates or
retroactive price reductions and allowances for wastage replacement;


 


(d)   Portions of invoiced sales amounts included in Net Sales in prior
periods that are actually written off by Ikaria, its Affiliates, or
Sublicensees as uncollectible up to an aggregate of [**]% of such gross sales;
and


 


(e)   Postage, freight, shipping, insurance, and other transportation
related charges incurred in shipping a Product to Third Parties.


 


Such amounts shall be determined from the books and
records of Ikaria, its Affiliates, or Sublicensees, maintained in accordance
with generally accepted accounting principles, consistently applied.


 


If one or more Products is sold as part of a
Combination Product (as defined below), the Net Sales from the Combination
Product, for the purposes of determining royalty payments, shall be determined
by multiplying the Net Sales (as determined above) of the Combination Product,
during the applicable royalty reporting period, by the fraction, A/A+B, where A
is the average sale price of the Product(s) when sold separately in
finished form and B is the average sale price of the other components included
in the Combination Product when sold separately in finished form, in each case
in the applicable country during the applicable royalty reporting period or, if
sales of both the Product(s) and the other components did not occur in
such country in such period, then in the most recent royalty reporting period
in which sales of both occurred.  If such
average sale price cannot be determined for both the Product(s) and all
other components included in such Combination Product, Net Sales for the
purposes of determining royalty payments shall be calculated by multiplying the
Net Sales of the Combination Product by the fraction of C/C+D where C is the fair
market value of the Product(s) and D is the fair market value of all other
components included in the Combination Product. 
In such event, Ikaria shall in good faith make a determination of the
respective fair market values of the Product(s) and all other components
included in the Combination Product, and shall notify Fibrex of such
determination and provide Fibrex with data to support such determination.  Fibrex shall have the right to review such
determination of fair market values and, if Fibrex disagrees with such
determination, to notify Ikaria of such disagreement within sixty (60) days
after Ikaria notifies Fibrex of such determination.  If Fibrex notifies Ikaria that Fibrex
disagrees with such determination within such sixty (60) day period and if
thereafter the Parties are unable to agree in good faith as to such respective
fair market values, then such matter shall be resolved as provided in Article IX.  If Fibrex does not notify Ikaria that Fibrex
disagrees with such determination within such sixty (60) day period, such
determination shall be conclusive and binding on the Parties.


 


5














 


As used above, the term “Combination
Product” means any therapeutic medical product that includes both (i) one
or more Compounds s) and (ii) one or more other therapeutically active
ingredients.


 


Section 1.31           “Party” shall mean Fibrex, or
Ikaria; “Parties” shall mean Fibrex and Ikaria.


 


Section 1.32           “Patent Rights” shall mean
United States and foreign patents and patent applications (including
provisional applications) and all substitutions, divisionals, continuations,
continuations-in-part, reissuances, reexaminations, registrations, renewals,
confirmations, supplementary protection certificates and extensions thereof.


 


Section 1.33           “Person” shall mean any
natural person or any corporation, company, partnership, joint venture, firm,
university, other entity, governmental authority, or subdivision thereof.


 


Section 1.34           “Phase I Clinical Trial” shall
mean a clinical trial in any country to initially evaluate the safety or
pharmacokinetic effect of a Product in humans 
and that satisfies the criteria set forth in U.S. 21 C.F.R. §312.21(a) or
the equivalent laws, rules or regulations in the EU or Japan.


 


Section 1.35           “Phase IIa Clinical Trial”
shall mean a clinical trial in any country to initially evaluate the
effectiveness of a Product (whether as a primary or secondary endpoint) for a
particular Indication in humans with the disease or indication under study and
that satisfies the criteria set forth in U.S. 21 C.F.R. §312.21(b) or the
equivalent laws, rules or regulations in the EU or Japan.


 


Section 1.36           “Phase IIb Clinical Trial”
shall mean a clinical trial in any country (a) the results of which, if
successful, are designed to provide a sufficient basis for designing and
commencing a Phase III Clinical Trial and (b) that satisfies the criteria
set forth in U.S. 21 C.F.R. §312.21(b) or the equivalent laws, rules or
regulations in the EU or Japan.


 


Section 1.37           “Phase III Clinical Trial”
means a clinical trial in any country the results of which could be used to
establish safety and efficacy of a Product to support Regulatory Approval and
that would otherwise satisfy the requirements of 21 CFR § 312.21(c) or the
equivalent laws, rules or regulations in the EU or Japan.


 


Section 1.38           “Product” shall mean any
preparations in final form, bulk form or other form containing as an active
pharmaceutical ingredient one or more Compounds for sale by prescription,
over-the-counter or any other method.


 


Section 1.39           “Regulatory Approval” shall
mean, with respect to a product, jurisdiction and indication, the approval of
the applicable Regulatory Authority required to market and sell such product in
such jurisdiction for such indication.


 


Section 1.40           “Regulatory Authority” shall
mean any national (e.g., the FDA),
supra-national or other regulatory agency or governmental entity involved in
the granting of 


 


6

















 


Regulatory Approval for, or in the regulation
of human clinical studies of, therapeutic pharmaceutical products.


 


Section 1.41           “Royalty Term” shall mean, with respect to a Product in a
country of the Territory, the period of time commencing on the First Commercial
Sale of such Product in such country and ending upon the later of (a) the
expiration of the last-to-expire Valid Claim in the Fibrex Patent Rights that
claim the sale or use of such Product in the Field in such country, or (b) the
date on which Regulatory Approval of a Generic Version of any Product has
occurred in such country.


 


Section 1.42           “Sublicensee” means Third
Party granted a right to make, use, sell, offer for sale, or import a Product,
excluding a wholesaler or reseller of a Product that does not market or promote
the sale of such Product.


 


Section 1.43           “Successful Completion” shall
mean:


 


(a)   with respect to the Phase I Clinical Trial, (i) the study has
demonstrated in healthy volunteers that the investigational compound has a
favorable safety profile at the dose levels studied, and that dose and exposure
levels are achieved that are in the range required for expected therapeutic
efficacy or (ii) Ikaria proceeds to continue to Develop the Product
following the completion of such Clinical Trial to the next phase of clinical
development;


 


(b)   with respect to the Phase IIa Clinical Trial, (i) the study
has demonstrated in a target patient population that the investigational
compound has a favorable safety profile at the dose levels studied, that dose
and exposure levels are achieved that are required to mediate therapeutic
efficacy, and has demonstrated biologically meaningful proof-of-concept
efficacy or (ii) Ikaria proceeds to continue to Develop the Product
following the completion of such Clinical Trial to the next phase of clinical
development; and


 


(c)   with respect to the Phase IIb Clinical Trial, (i) the study
has further demonstrated safety and therapeutic efficacy at a dose level range
in a target patient population that enables dose selection and progression to
full (phase III) development or (ii) Ikaria proceeds to continue to
Develop the Product following the completion of such Clinical Trial to the next
phase of clinical development.


 


Section 1.44             “Territory”
shall mean the entire world.


 


Section 1.45           “Third Party” shall mean any
Person other than a Party or any of its Affiliates.


 


Section 1.46           “Valid Claim” shall mean a
claim of any issued, unexpired patent that has not been revoked or held
unenforceable or invalid by a decision of a court or governmental agency of
competent jurisdiction from which no appeal can be taken, or with respect to
which an appeal is not taken within the time allowed for appeal, and that has
not been disclaimed or admitted to be invalid or unenforceable through reissue,
reexamination, disclaimer, or otherwise.


 


Section 1.47           Additional Definitions.  Each of the following terms is defined in the
section of this Agreement indicated below:


 


7

















 


	
  Term

  	
   

  	
  Section

  
	
   

  	
   

  	
   

  
	
  “Agreement”

  	
   

  	
  Preamble

  
	
   

  	
   

  	
   

  
	
  “Bankruptcy
  Code”

  	
   

  	
  Section 2.34

  
	
  “Breaching
  Party”

  	
   

  	
  Section 8.2

  
	
  “Combination
  Product”

  	
   

  	
  Section 1.30

  
	
  “Competitive
  Infringement”

  	
   

  	
  Section 5.3(a)

  
	
  “Effective
  Date”

  	
   

  	
  Preamble

  
	
  “Fibrex”

  	
   

  	
  Preamble

  
	
  “Fibrex
  Medical”

  	
   

  	
  Preamble

  
	
  “Fibrex
  Medical R&D”

  	
   

  	
  Preamble

  
	
  “Fibrex
  Sole Inventions”

  	
   

  	
  Section 5.1(a)

  
	
  “Force
  Majeure Event”

  	
   

  	
  Section 10.7

  
	
  “Ikaria”

  	
   

  	
  Preamble

  
	
  “Ikaria
  Sole Inventions”

  	
   

  	
  Section 5.1(a)

  
	
  “Indemnified
  Party”

  	
   

  	
  Section 10.1(c)

  
	
  “Indemnifying
  Party”

  	
   

  	
  Section 10.1(c)

  
	
  “Invalidity
  Claim”

  	
   

  	
  Section 5.3(d)

  
	
  “Joint
  Inventions”

  	
   

  	
  Section 5.1(b)

  
	
  “Lead
  Party”

  	
   

  	
  Section 5.3(e)

  
	
  “Losses”

  	
   

  	
  Section 10.1(a)

  
	
  “Non-Breaching
  Party”

  	
   

  	
  Section 8.2

  
	
  “On-Going
  Studies”

  	
   

  	
  Section 3.7

  
	
   

  	
   

  	
   

  
	
  “SEC”

  	
   

  	
  Section 6.1

  
	
  “Severed
  Clause”

  	
   

  	
  Section 10.11

  
	
  “Sole
  Inventions”

  	
   

  	
  Section 5.1(a)

  
	
  “Technology
  Transfer”

  	
   

  	
  Section 3.3

  
	
  “Technology
  Transfer Plan”

  	
   

  	
  Section 3.3

  
	
  “Terminated
  Product”

  	
   

  	
  Section 8.4(b)

  
	
  “Third
  Party Payment”

  	
   

  	
  Section 4.2(c)

  



 


Section 1.48           Interpretation.  Whenever the context may require, any pronoun
shall include the corresponding masculine, feminine, and neuter forms.  The words “include”, “includes” and “including”
shall be deemed to be followed by the phrase “without limitation”. The word “will”
shall be construed to have the same meaning and effect as the word “shall”.  The word “or” shall be construed to have the
same meaning and effect as “and/or”. 
This Agreement has been prepared jointly with the assistance of counsel
and shall not be strictly construed against either Party.  The captions or headings of the sections or
other subdivisions hereof are inserted only as a matter of convenience or for
reference and shall have no effect on the meaning of the provisions hereof.  Unless the context requires otherwise, (a) any
definition of or reference to any agreement, instrument, or other document
herein shall be construed as referring to such agreement, instrument, or other
document as from time to time amended, supplemented, or otherwise modified
(subject to any restrictions on such amendments, supplements, or modifications
set forth herein or therein), (b) any reference to any laws herein shall
be construed as referring to any law, statute, rule, regulation, ordinance, or
other 


 


8

















 


pronouncement having the effect of law of any
federal, national, multinational, state, provincial, county, city, or other
political subdivision, domestic or foreign, as they from time to time may be
enacted, repealed, or amended, (c) any reference herein to any Person
shall be construed to include the Person’s successors and assigns, (d) the
words “herein”, “hereof”, and “hereunder”, and words of similar import, shall
be construed to refer to this Agreement in its entirety and not to any
particular provision hereof, (e) any reference herein to the words “mutually
agree” or “mutual written agreement” shall not impose any obligation on either
Party to agree to any terms relating thereto or to engage in discussions
relating to such terms except as such Party may determine in such Party’s sole
discretion, (f) all references herein to Articles, Sections, Exhibits, or
Schedules shall be construed to refer to Articles, Sections, Exhibits, and
Schedules of this Agreement, and (g) wherever this Agreement requires
either Party’s approval or consent, unless otherwise indicated, such approval
or consent shall not be unreasonably withheld, conditioned, or delayed.


 


Article II


Grant of Rights


 


Section 2.1             Fibrex License Grant to Ikaria.  Subject to the terms and conditions of this
Agreement, Fibrex hereby grants to Ikaria the exclusive, irrevocable (except as
provided in Article VIII), royalty-bearing right and license in the
Territory under the Fibrex Intellectual Property to Develop, use, Manufacture
and Commercialize Products for use in the Field.  The foregoing license includes the
unrestricted right to grant sublicenses under the Fibrex Intellectual Property
in accordance with Section 2.4.


 


Section 2.2             Non-Competition.  During the term of and except as provided for
in this Agreement (and provided that Ikaria is complying in all material
respects with its obligations hereunder), Fibrex shall not, directly or
indirectly (including through its Affiliates), Develop, Manufacture,
Commercialize, or grant any rights or options or provide assistance to any
Third Party to Develop, Manufacture or Commercialize, any compound, substance,
or product that inhibits the binding of fibrin E1 fragment to vascular
endothelial cadherin.


 


Section 2.3             Section 365(n) of the
Bankruptcy Code.  All rights and
licenses granted under or pursuant to any Section of this Agreement,
including under this Article II, Section 8.4 and with respect to any
Fibrex Intellectual Property subject to Technology Transfer under Section 3.3,
are rights to “intellectual property” (as defined in Section 101(35A) of
Title 11 of the United States Code (such Title, the “Bankruptcy Code”)).  Each of Ikaria and Fibrex hereby acknowledges
“embodiments” of such intellectual property for purposes of Section 365(n) of
the Bankruptcy Code shall include (a) copies of research data, (b) laboratory
samples, (c) product samples, (d) formulas, (e) laboratory notes
and notebooks, (f) data and results related to clinical studies, (g) regulatory
filings and approvals, (h) rights of reference in respect of regulatory
filings and approvals, (i) research data and results, and (j) marketing,
advertising, and promotional materials, in each case, that relate to such
intellectual property.  Each Party shall
retain and may fully exercise all of its rights and elections under the
Bankruptcy Code or analogous legislation in any other jurisdiction.  Upon the institution by or against a Party
(the “First Party”) of any assignment for the benefit of creditors,
composition, or any bankruptcy, reorganization, arrangement, insolvency, or
similar proceedings under the laws of any jurisdiction, the other Party shall
further be entitled to a complete duplicate of, or complete 


 


9

















 


access to, as appropriate, any such
intellectual property (including embodiments thereof), and such intellectual
property and embodiments, if not already in its possession, shall be promptly
delivered to such other Party, unless the First Party elects to continue, and
continues, to perform all of its obligations under this Agreement; provided ̧that Fibrex’ rights to such intellectual property
rights and embodiments of Ikaria shall be subject to the terms of Section 8.4.


 


Section 2.4               Sublicenses.  The sublicensing of Ikaria’s rights  under Section 2.1 or appointment of other
Sublicensees shall be
subject to the following provisions: (a) Ikaria shall be primarily liable for any
failure by its Sublicensees  to comply with all relevant restrictions, limitations, and obligations in  this Agreement; (b) each Sublicensee
shall comply in all
material respects with the same level of efforts required to be
performed by Ikaria hereunder with respect to the specific rights that are the
subject of the applicable sublicense.


 


Section 2.5             Retained Rights.  Except as otherwise specifically provided for
in this Agreement, each Party retains all rights and licenses to exploit its
own intellectual property.


 


Article III


Development; Manufacturing;
Commercialization


 


Section 3.1             General.  Ikaria shall be solely responsible for
conducting and funding all Development activities, and shall have the sole
right to Develop, Manufacture, and Commercialize Products in the Field in the
Territory.


 


Section 3.2             Regulatory Matters.  Ikaria shall prepare and submit all filings
with Regulatory Authorities relating to Products, which filings shall be in
Ikaria’s name.  With respect to
regulatory matters concerning Products in the Field, Fibrex shall cooperate
with Ikaria in the preparation and support of each application for Regulatory
Approval, and shall provide Ikaria with such reasonable assistance as Ikaria
may request, it being understood that such assistance may include providing
Ikaria with the right to cross-reference INDs or any other filings with
Regulatory Authorities or Regulatory Approval made or held by Fibrex with
respect to the Product or Compounds. Fibrex’ obligations to provide assistance
under this Section 3.2 and Section 3.3 shall continue until December 31,
2009; provided, that such date shall be
accelerated to October 31, 2009 if Ikaria enters into the consulting
agreements referred to in Section 3.8(a) and (b).


 


Section 3.3             Technology Transfer.


 


(a)   As soon as reasonably practicable after Ikaria’s written request,
Fibrex shall complete the activities assigned to Fibrex as set forth on the
technology transfer plan attached hereto as Exhibit B (the “Technology
Transfer Plan”) (“Technology Transfer”).  Fibrex shall make available to Ikaria (or
Ikaria’s designee(s)) such number of technical personnel as may be set forth in
the Technology Transfer Plan to answer any questions or provide instruction as
reasonably requested by Ikaria (or Ikaria’s designee(s)) concerning the items
delivered pursuant to this Section 3.3, in connection with the
Development, use, Manufacture and Commercialization of Products hereunder.  Each Party shall bear its own costs with
respect to the Technology Transfer.


 


10

















 


(b)   One individual nominated by each Party shall be responsible for
coordinating the technology transfer activities under the Technology Transfer
Plan.  Each Party shall cooperate with
the other Party in such other Party’s conduct of technology transfer activities
under the Technology Transfer Plan.


 


(c)   If Ikaria desires that Fibrex provide technology transfer services
beyond the scope of the Technology Transfer Plan and to the extent Fibrex
possesses sufficient capabilities and resources, Fibrex shall provide such
services on terms to be agreed upon in good faith by the Parties.  Notwithstanding the foregoing, Fibrex shall
provide Ikaria with reasonable access to Fibrex’s employees and consultants
involved prior to the Effective Date and during the term of this Agreement with
the Development of any Product.


 


Section 3.4             Diligence and Reports.  Ikaria shall use Commercially Reasonable
Efforts to Develop and Commercialize at least one (or more in Ikaria’s
discretion) Products for a total of at least [**] Indications in the United
States and at least each of the following countries: France, Germany, Italy,
Spain, and the United Kingdom; provided, that
Ikaria may defer clinical development of the [**] Indications until Successful
Completion of the Phase IIb Clinical Trial for the first Indication.  Ikaria shall establish and maintain a
development plan with respect to each Indication it elects to Develop.  Ikaria shall disclose such plans (including
any amendments) to Fibrex and consider in good faith any comments made by
Fibrex; provided, that Ikaria shall remain
solely responsible for Development. Ikaria shall Develop the Products in
accordance with all applicable regulatory requirements, including then current
cGLP, cGCP and cGMP.   Ikaria shall keep
Fibrex reasonably informed about its efforts to Develop the Products, including
annual written reports containing summaries of all results and data from such
development efforts, progress towards meeting all goals and milestones in each
development plan, significant findings and developments, and any reasons for
any delays in meeting milestones or timelines in any development plan.  Subject to Section 3.8, any reports or
information that Ikaria may provide to Fibrex under this Section 3.4 shall
be deemed Confidential Information of Ikaria and shall be treated as such in
accordance with the provisions of Article VI.


 


Section 3.5             Manufacturing.  Ikaria shall be solely responsible for the
Manufacture of Products for Development use or for Commercialization in the
Field in the Territory, which Ikaria may conduct itself or through Affiliates,
Sublicensees, or contractors.


 


Section 3.6             Commercialization.  Ikaria shall be solely responsible for
conducting, itself or through Affiliates, Sublicensees or contractors, the
Commercialization of Products in the Field in the Territory, including (a) contracting
with customers and booking sales, (b) setting the price and terms and
conditions under which a Product may be sold to customers, and (c) handling
of managed care accounts, and, subject to Section 1.30, Section 4.2(c),
Section 5.2(d), Section 5.3(e) and Section 10.1(b), as
between the Parties, Ikaria shall bear all costs associated therewith. In performing all such Commercialization activities
and disseminating Product information, Ikaria will comply with all applicable
laws, regulations, and guidelines concerning such activities.


 


Section 3.7             On-Going Studies.  Fibrex shall retain control of and shall bear
all costs relating to the on-going studies listed in Schedule 3.7 (the “On-Going
Studies”), and shall exercise commercially reasonable efforts to continue
and complete the On-Going Studies, which 


 


11

















 


shall be managed by Fibrex.  Fibrex shall not modify the On-Going Studies
without the prior written consent of Ikaria. 
Without limiting the generality of Section 2.1, any results or
other information resulting from any of the Ongoing Studies shall be deemed to
be included in the scope of the license rights granted to Ikaria by Fibrex
under Section 2.1.


 


Section 3.8             Consulting Agreements.


 


(a)   Ikaria shall discuss in good faith with Mr. Rainer Henning
whether there are consulting services that Ikaria would like Mr. Henning
to (either directly or through a consulting group) to perform for Ikaria in
connection with the Development of Products.


 


(b)   Ikaria shall discuss in good faith with Mr. Peter Petzelbauer
whether there are consulting services that Ikaria would like Mr. Petzelbauer
(either directly or through a consulting group) to perform for Ikaria in connection
with the Development of Products.


 


(c)   Ikaria shall discuss in good faith with Mr. Peter Petzelbauer
whether there are Development services that Ikaria would like Mr. Petzelbauer’s
laboratory to perform for Ikaria in connection with the Development of
Products.


 


 


 


Article IV


Financial Provisions


 


Section 4.1             Milestone Payments.  With respect to each of the following
milestones (other than the milestone payment specified in Section 4.1(a),
which is addressed in Section 4.8), Ikaria shall pay Fibrex the
corresponding payment set forth below within [**] days after the achievement by
Ikaria, its Affiliates or Sublicensees of such milestone:


 


	
   

  	
  a.

  	
  Signing
  of Definitive Agreement

  	
  $5,250,000

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
  b.

  	
  Successful
  Completion of Phase I Clinical Trial in healthy volunteers per Compound
  (excluding FX06)

  	
  $[**]

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
  c.

  	
  Milestones
  Relating to Development, Regulatory Filing,

  and
  Approval in First Indication

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  Successful Completion of Phase IIa Clinical Trial

  	
  $[**]

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  Successful Completion of Phase IIb Clinical Trial

  	
  $[**]

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  Acceptance of NDA Filing in the U.S.

  	
  $[**]

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  Acceptance of MAA Filing in the EU

  	
  $[**]

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  Approval of the NDA in the U.S.

  	
  $[**]

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  Approval of an MAA in Europe

  	
  $[**]

  



 


12

















 


	
   

  	
   

  	
  Approval of an NDA in Japan

  	
  $[**]

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
  d.

  	
  Milestones
  Relating to Development, Regulatory Filing, and Approval in Second Indication

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  Successful Completion of Phase IIa Clinical Trial

  	
  $[**]

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  Successful Completion of Phase IIb Clinical Trial

  	
  $[**]

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  Acceptance of NDA Filing in the U.S.

  	
  $[**]

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  Acceptance of MAA Filing in the EU

  	
  $[**]

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  Approval of the NDA in the U.S.

  	
  $[**]

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  Approval of an MAA in Europe

  	
  $[**]

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  Approval of an NDA in Japan

  	
  $[**]

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
  e.

  	
  Milestones
  Relating to Development, Regulatory Filing, and Approval in Third Indication

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  Successful Completion of Phase IIa Clinical Trial

  	
  $[**]

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  Successful Completion of Phase IIb Clinical Trial

  	
  $[**]

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  Acceptance of NDA Filing in the U.S.

  	
  $[**]

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  Acceptance of MAA Filing in the EU

  	
  $[**]

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  Approval of the NDA in the U.S.

  	
  $[**]

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  Approval of an MAA in Europe

  	
  $[**]

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  Approval of an NDA in Japan

  	
  $[**]

  



 






(1) If no Phase IIa Clinical
Trial is conducted in this Indication, this milestone payment shall be paid
upon the successful achievement of an interim analysis of a  Phase IIb Clinical Trial in that Indication
or if an interim analysis is not performed, upon Successful Completion of a
Phase IIb Clinical Trial.  This milestone
payment would not be triggered or paid with respect to FX06 at any time.


 


Ikaria shall notify Fibrex promptly after the
achievement of each such milestone. All such payments are non-refundable and,
except as provided in clause (v) below, non-creditable. Payment of
milestones shall be subject to the following:


 


(i)                                     Each of the
milestones set forth in this Section 4.1 (other than Section 4.1(b) shall
be paid only once regardless of the number of Products that achieve such
milestone or the number of times a given Product achieves such milestone.  


 


13

















 


Accordingly,
the maximum amount payable under all of the foregoing milestones is
$104,000,000 (excluding the milestone payment to be paid under (b) above).


 


(ii)                                  Milestone
payments payable under Section 4.1(c) shall be paid for the first
Product to achieve the applicable milestone for any Indication.


 


(iii)                               If a Product reaches a development milestone for
any Indication, and if that milestone was already reached for another
Indication, Ikaria shall pay the applicable amount set forth in Section 4.1(d).


 


(iv)                              If a Product reaches a development milestone for
any Indication, and if that milestone was already reached for two other
Indications, Ikaria shall pay the applicable amount set forth in Section 4.1(e).


 


(v)                                 Notwithstanding the foregoing, any milestone
payment paid in respect of an Indication that is no longer under Development
may be credited against that same milestone for any other Indication that Ikaria
may pursue.


 


(vi)                              Payment of the foregoing milestones
is illustrated by the examples set forth in Exhibit C.


 


Section 4.2             Royalties on Net Sales of
Products.


 


(a)   Royalties on Net Sales of Products.  During the Royalty Term applicable to each
Product, and subject to adjustment as set forth in Section 4.2(c), Ikaria
shall pay to Fibrex royalties on a Product-by-Product basis, with the amount of
such royalties calculated as a percentage of Net Sales in a calendar year for
such Product, as set forth below:


 


	
   

  	
  Aggregate
  Worldwide Calendar Year Net Sales

  	
   

  	
  Royalty

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
  Up to $[**]

  	
   

  	
  [**]

  	
  %

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
  Greater than $[**] to $[**]

  	
   

  	
  [**]

  	
  %

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
  Greater than $[**]

  	
   

  	
  [**]

  	
  %

  	
   

  



 


(b)   Royalties Payable Only Once.  The obligation to pay royalties is imposed
only once with respect to Net Sales of the same unit of a Product.


 


(c)   Royalty Reductions for Third Party Payments.  If Ikaria is required to obtain a license or
immunity from suit from any Third Party in order for Ikaria, its Affiliates, or
any Sublicensee to exercise or use the rights granted to Ikaria herein in
respect of any Product in any country or to Develop or Commercialize Products
in any country, and Ikaria, its Affiliates, or any Sublicensee pays any Third
Party any up-front fee, milestone, royalty, or other payment (each, a “Third
Party Payment”) in consideration of obtaining such license or immunity from
suit, Ikaria shall have the right to offset up to [**] percent ([**]%) of such
Third Party Payments that are allocable to a Product against royalties payable
to Fibrex under this Section 4.2 in respect of sales of such Product; provided, that such offset shall not exceed [**]% of the


 


14

















 


royalties otherwise payable in respect of
sale of such Product; and provided further that any portion of the [**]% of
such Third Party Payments that may be offset against royalties payable to
Fibrex under this Section 4.2 may be applied against royalties to be paid
in respect of such Product in subsequent periods until fully depleted. Not less
than [**] Business Days prior to entering into any agreement providing for
payment of Third Party Payments, Ikaria shall send Fibrex a written notice
describing in reasonable detail the terms of the proposed agreement and reasons
for entering into such agreement.  If
requested by Fibrex, the Parties shall then discuss such terms and Ikaria shall
consider in good faith any views expressed by Fibrex.


 


(d)   Duration of Payments. 
The amounts payable to Fibrex under this Section 4.2 shall be paid
on a Product-by-Product and country-by-country basis until the expiration of
the Royalty Term for such Product in such country.


 


Section 4.3             Reports and Accounting.


 


(a)   Reports; Payments. 
Ikaria shall deliver to Fibrex, within [**] days after the end of each
calendar quarter, reasonably detailed written accountings of Net Sales of
Products that are subject to payment obligations to Fibrex for such calendar
quarter.  Such quarterly reports shall
indicate (i) gross sales and Net Sales on a country-by-country basis, (ii) the
calculation of payment amounts owed to Fibrex from such gross sales and Net
Sales, and (iii) any amounts set off pursuant to Section 4.2(c) against
payments owed to Fibrex.  When Ikaria
delivers such accounting to Fibrex, Ikaria shall also deliver all amounts due
under Section 4.2 to Fibrex for the calendar quarter.  All payments shall be made by wire transfer
to an account to be specified by Fibrex in writing.


 


(b)   Audits by Fibrex. 
Ikaria shall keep, and shall require its Affiliates and Sublicensees to
keep, complete and accurate records of the most recent [**] years relating to
gross sales and Net Sales and all information relevant under Section 4.1
and Section 4.2.  For the sole
purpose of verifying amounts payable to Fibrex, Fibrex shall have the right no
more than [**] per calendar year, at Fibrex’s expense, to engage independent
accountants to review such records in the location(s) where such records
are maintained by Ikaria, its Affiliates, and its Sublicensees upon reasonable
notice and during regular business hours. 
Prior to any review conducted pursuant to this Section 4.3(b),
Fibrex’s accountants shall have entered into a written agreement with Ikaria
limiting the use of such records to verification of the accuracy of payments
due under this Agreement and prohibiting the disclosure of any information
contained in such records to a Third Party and to Fibrex for a purpose other
than as set forth in this Section 4.3(b). 
Results of such review shall be made available to Ikaria.  If the review reflects an underpayment to
Fibrex, such underpayment shall be promptly remitted to Fibrex.  Likewise, if the review reflects an
overpayment, Ikaria shall be entitled to credit such overpayment against any
subsequent payments. The fees charged by such accountants shall be paid by
Fibrex; provided, that if the audit uncovers an
underpayment of royalties by Ikaria in an amount that exceeds [**]% of the
total royalties owed, then the reasonable fees of such accountants shall be
paid by Ikaria.


 


Section 4.4             Currency Amounts.  All dollar ($) amounts specified in this
Agreement are United States Dollar amounts. 
All currency amounts specified in this Agreement are exclusive of VAT.


 


15














 


Section 4.5                                      Currency
Exchange.  With
respect to sales of Products invoiced in U.S. Dollars and other amounts
received or paid by Ikaria, its Affiliates or Sublicensees in U.S. Dollars,
such amounts and the amounts payable hereunder shall be expressed in U.S.
Dollars.  With respect to sales of
Products invoiced in a currency other than U.S. Dollars and other amounts
received or paid by Ikaria, its Affiliates or Sublicensees in a currency other
than U.S. Dollars, such amounts and the amounts payable hereunder shall be
expressed in their U.S. Dollar equivalent calculated using the applicable rate
of exchange reported by The Wall Street Journal
(Eastern U.S. edition) on the last Business Day of the calendar quarter  to which the report under Section 4.3(a) relates.  All payments hereunder shall be made in U.S.
Dollars.


 


Section 4.6                                      Tax Withholding.  The Parties shall use reasonable and legal
efforts to reduce tax withholding on payments made to Fibrex.  The Parties agree to cooperate in good faith
to provide one another with such documents and certifications as are reasonably
necessary to enable Ikaria to minimize any withholding tax obligations.  Ikaria shall provide to Fibrex documentation
of the payment of any withholding taxes that are paid pursuant to this Section 4.6.


 


Section 4.7                                      Blocked
Payments.  If, by
reason of applicable laws or regulations in any country, it becomes impossible
or illegal for Ikaria or its Affiliates or Sublicensees, to transfer, or have
transferred on its behalf, royalties or other payments to Fibrex, such
royalties or other payments shall be deposited in local currency in the
relevant country to the credit of Fibrex in a recognized banking institution
designated by Fibrex or, if none is designated by Fibrex within a period of
[**] days, in a recognized banking institution selected by Ikaria or its
Affiliate or Sublicensee, as the case may be, and identified in a written
notice given to Fibrex.


 


Section 4.8                                      Freedom to
Operate.


 


(a)          Promptly following the
Effective Date, Ikaria shall conduct a freedom to operate search (the “FTO”)
to verify that the Fibrex Patents Rights do not infringe upon the intellectual
property rights of any Third Party and that Ikaria’s ability to fully exercise
its rights to Develop, use, Manufacture and Commercialize Products for use in
the Field is not otherwise impinged, prevented, blocked, or hindered by or due
to or by the intellectual property rights of a Third Party, other than Patent
Rights relating to the pegylation of any Compound.


 


(b)         Ikaria shall have the sole
right to select counsel to conduct the FTO (so long Fibrex does not reasonably
object to such selection), and shall have the sole right to interact with and
direct such counsel; provided, however, that in order to afford both Ikaria and
Fibrex the benefit of attorney-client privilege with respect to any written
work product resulting from the FTO, Ikaria and Fibrex shall be joint clients
of the counsel selected by Ikaria to conduct the FTO (which shall be reflected
in an engagement letter with the applicable counsel).  Ikaria shall bear the expense of the FTO.


 


(c)          Ikaria shall have [**] days
following the Effective Date in which to complete the FTO (the “FTO Period”).  Ikaria shall provide a copy of the final
results of the FTO to Fibrex and shall discuss such final results with Fibrex.


 


(d)         If Ikaria determines, in its
sole discretion, that the final results of the FTO are acceptable to Ikaria,
Ikaria shall pay to Fibrex the “Signing of the Definitive Agreement” 


 


16

















 


milestone payment specified in Section 4.1(a) in
accordance with Section 4.1.  If
Ikaria determines, in its sole discretion, that the final results of the FTO
are unacceptable to Ikaria, Ikaria shall have the right to terminate this Agreement
upon written notice to Fibrex, provided that such notice is given within the
FTO Period.


 


(e)          During the FTO Period,
Ikaria and Fibrex agree that (i) Fibrex will not (either directly or
indirectly) solicit, encourage, respond to, or discuss any proposal for a
transaction that would conflict with or impede the transaction reflected in
this Agreement, or provide any non-public information to any third party in
connection with such a proposal and (ii) Ikaria and its Affiliates will
not (either directly or indirectly) solicit, encourage, respond to, or discuss
any proposal for, or enter into a transaction under which it acquires rights to
a compound or other biopharmaceutical product or that would conflict with or
impede the transaction reflected in this Agreement, or provide any non-public
information to any third party in connection with such a proposal.


 


Article V


Intellectual Property
Ownership, Protection and Related Matters


 


Section 5.1                                      Ownership of
Inventions.


 


(a)          Sole Inventions.  Each Party shall exclusively own all
inventions made solely by such Party, its employees, agents and consultants in
the conduct of the Parties’ activities pursuant to this Agreement (“Sole
Inventions”).  Sole Inventions made
solely by Ikaria, its employees, agents and consultants are referred to herein
as “Ikaria Sole Inventions”.  Sole
Inventions made solely by Fibrex, its employees, agents and consultants are
referred to herein as “Fibrex Sole Inventions”.


 


(b)         Joint Inventions.  The Parties shall jointly own all inventions
made jointly by Ikaria, its employees, agents, and consultants, on the one
hand, and Fibrex, its employees, agents and consultants, on the other hand, in
the conduct of any joint Development activities conducted by the Parties, on
the basis of each Party having an undivided interest in the whole (“Joint
Inventions”).  The Parties shall
jointly own all Joint Inventions on a worldwide basis in accordance with and
bearing with it the same rights as the joint ownership interests of
co-inventors named on U.S. patents under U.S. patent laws.  Such rights of joint ownership are further
implemented by the Parties on a worldwide basis pursuant to this Article V.


 


(c)          Inventorship.  For purposes of determining whether an
invention is an Ikaria Sole Invention, a Fibrex Sole Invention or a Joint
Invention, questions of inventorship shall be resolved in accordance with
United States patent laws.


 


Section 5.2                                      Prosecution and
Maintenance of Patent Rights.


 


(a)          Jointly Owned Inventions and
Sole Inventions.  Ikaria
shall have the exclusive right and option for the management of the
preparation, filing, prosecution, and maintenance of any and all patents and
patent applications, including any interference proceedings related thereto,
included in Patent Rights under this Agreement that claim or disclose Jointly
Owned Inventions or, to the extent directed to any Compounds (including their
method of manufacture or use), Sole Inventions owned by either Party.


 


17

















 


(b)         Fibrex Intellectual Property.  Upon the Effective Date, Ikaria shall assume
responsibility for the management of the preparation, filing prosecution, and
maintenance of any and all patents and patent applications, including any
interference, opposition, and re-examination proceedings related thereto,
included in the Fibrex Intellectual Property (including, for clarity, the
Fibrex Patent Rights and patents and patent applications that claim or disclose
Fibrex Know-How).


 


(c)          Fibrex Step-in Right.  If Ikaria, on a country-by-country basis,
declines to file and prosecute, or elects not to take actions necessary to
avoid abandonment of, any patent applications or maintain any patent in any
country, in each case for which it has responsibility under Section 5.2(a) or
Section 5.2(b), it shall give Fibrex reasonable notice to this effect
sufficiently in advance to permit Fibrex to undertake such filing and
prosecution without a loss of rights, and thereafter Fibrex may, upon written
notice to Ikaria, file and prosecute such patent applications and maintain such
patents in such country.


 


(d)         Costs and Expenses.  Ikaria shall pay the costs and expenses of
preparing, filing, prosecuting, and maintaining the Patent Rights covered by Section 5.2(a) or
Section 5.2(b) (including any interference, opposition, and
re-examination proceedings related thereto), provided, however,
that Fibrex shall bear such costs and expenses relating to any Patent Right
with respect to which Fibrex has exercised its step-in right under Section 5.2(c).


 


(e)          Cooperation Between Parties.  Each Party agrees to cooperate with the other
with respect to the preparation, filing, prosecution, and maintenance of Patent
Rights pursuant to this Section 5.2, including the execution of all such
documents and instruments and the performance of such acts as may be reasonably
necessary in order to permit the other Party to continue any preparation,
filing, prosecution, or maintenance of such Patent Rights, including Patent
Rights that such Party has elected not to pursue, as provided for in
subsections (a), (b), and (c) above. 
In addition, the filing, prosecuting and maintaining Party in
subsections (a), (b), and (c) above shall promptly forward to the other
Party copies of any substantive correspondence and actions prepared for or
received from the U.S. Patent and Trademark Office or any foreign patent office
that may materially affect the Patent Rights being prosecuted or
maintained.  The other Party’s patent
counsel may provide comments to the filing, prosecuting, and maintaining
Party.  If any comments by the other
Party’s patent counsel, are provided in sufficient time for the filing,
prosecuting and maintaining Party to reflect such comments in its
correspondence or response, and such comments are reasonably directed to maximizing
the coverage of the claims of the Patent Rights being prosecuted or maintained,
the filing, prosecuting and maintaining Party shall reflect such comments in
its correspondence or response, if its patent counsel deems it prudent to do
so.


 


Section 5.3                                      Third Party
Infringement.


 


(a)          Notice.  Each Party shall promptly report in writing
to the other Party during the term of this Agreement any (i) known or
suspected infringement of any of the Joint Patent Rights or Fibrex Patent
Rights or (ii) unauthorized use of any of the Joint Know-How or Fibrex
Know-How of which such Party becomes aware, including, in the case of either
clause (i) or clause (ii) involving, or that may reasonably lead to,
the Development, Manufacture, use or Commercialization of a product or product
candidate that is or may be competitive with a 


 


18

















 


Product in the Field (“Competitive
Infringement”), and shall provide the other Party with all available
evidence supporting such infringement, suspected infringement, unauthorized use
or suspected unauthorized use.


 


(b)         Fibrex Intellectual Property
and Joint Intellectual Property; Step-in Rights.


 


(i)             Ikaria shall have the first
right, but not the obligation, to initiate a suit or take other appropriate
action that either Party reasonably believes is required to protect Fibrex
Intellectual Property from Competitive Infringement or Joint Intellectual
Property from any infringement.  Ikaria
shall give Fibrex sufficient advance notice of its intent to file any such suit
or take any such action, and the reasons therefor, and shall provide Fibrex
with an opportunity to make suggestions and comments regarding such suit or
action.  Thereafter, Ikaria shall keep
Fibrex informed, and shall from time to time consult with Fibrex regarding the
status of any such suit or action and shall provide Fibrex with copies of all
material documents (i.e.,
complaints, answers, counterclaims, material motions, orders of the court,
memoranda of law and legal briefs, interrogatory responses, depositions,
material pre-trial filings, expert reports, affidavits filed in court,
transcripts of hearings and trial testimony, trial exhibits and notices of
appeal) filed in, or otherwise relating to, such suit or action. Any recovery
obtained as a result of any proceeding pursuant to this subsection (b)(i), by
settlement or otherwise, shall be applied in the following order of priority: (A) first,
each Party shall be reimbursed, on a pro rata basis, for all costs incurred by
such Party in connection with such suit; and (B) second, [**]% of any
remainder shall be paid to Fibrex and the balance retained by Ikaria.


 


(ii)          If Ikaria chooses not to
initiate a suit or take other appropriate action under subsection (b)(i) above
to protect Fibrex Intellectual Property from Competitive Infringement or Joint
Intellectual Property from infringement, Ikaria will so notify Fibrex of its
intention, in which case Fibrex shall have the right to initiate such suit or
take such other appropriate action. 
Fibrex shall give Ikaria sufficient advance notice of its intent to file
any such suit or take any such action, and the reasons therefor, and shall
provide Ikaria with an opportunity to make suggestions and comments regarding
such suit or action.  Thereafter, Fibrex
shall keep Ikaria informed, and shall from time to time consult with Ikaria
regarding the status of any such suit or action and shall provide Ikaria with
copies of all material documents (i.e.,
complaints, answers, counterclaims, material motions, orders of the court,
memoranda of law and legal briefs, interrogatory responses, depositions,
material pre-trial filings, expert reports, affidavits filed in court,
transcripts of hearings and trial testimony, trial exhibits and notices of
appeal) filed in, or otherwise relating to, such suit or action.  Any recovery obtained as a result of any
proceeding pursuant to this subsection (b)(ii), by settlement or otherwise,
shall be applied in the following order of priority: (A) first, each Party
shall be reimbursed, on a pro rata basis, for all costs incurred by such Party
in connection with such suit; and (B) second, any remainder shall be
shared equally by the Parties.


 


(c)          Claimed Infringement.  If a Party becomes aware of any claim that
the Development, Manufacture, or Commercialization of Products for use in the
Field in the Territory infringes Patent Rights or any other intellectual
property rights of any Third Party, such Party shall promptly notify the other
Party.  In any such instance, Ikaria shall
have the exclusive right to settle such claim.


 


19

















 


(d)         Patent Invalidity Claim.  If a Third Party at any time asserts a claim
that any Joint Patent Right or Fibrex Patent Rights is invalid or otherwise unenforceable
(an “Invalidity Claim”), whether (i) as a defense in an
infringement action brought by Ikaria or Fibrex pursuant to subsection (b) above,
or (ii) in an action brought against Ikaria or Fibrex referred to in
subsection (c) above, or (iii) otherwise, the Parties shall cooperate
with each other in preparing and formulating a response to such Invalidity
Claim.  Neither Party shall settle or
compromise any Invalidity Claim without the consent of the other Party.


 


(e)          Conduct of Certain Actions;
Costs.  For any action to terminate
any infringement of Joint Patent Rights or Fibrex Patent Rights, or any
misappropriation or misuse of Fibrex Know-How, if either Party is unable to
initiate or prosecute such action solely in its own name or to obtain a more effective
remedy, or if required by applicable law, the other Party shall join such
action voluntarily and shall execute all documents necessary to initiate
litigation to prosecute and maintain such action. In connection with any such
action, the parties shall cooperate fully and will provide each other with any
information or assistance that either reasonably requests. Ikaria shall have
the sole and exclusive right to select counsel for any suit initiated by it
referenced in subsection (b)(i) above or against it referenced in
subsection (c) above, and Fibrex shall have the sole and exclusive right
to select counsel for any suit initiated by it referenced in subsection (b)(ii) above.  If required under applicable law in order for
a Party (the “Lead Party”) to initiate or maintain such suit, the other
Party shall join as a party to the suit. 
Such other Party shall offer reasonable assistance to the Lead Party in
connection therewith at no charge to the Lead Party except for reimbursement of
such other Party’s reasonable out-of-pocket expenses incurred in rendering such
assistance.  The Lead Party shall assume
and pay all of its own out-of-pocket costs incurred in connection with any
litigation or proceedings referenced in the first sentence of this subsection (e),
including the fees and expenses of the counsel selected by it.  Subject to applicable law, the other Party
shall have the right to participate and be represented in any such suit by its
own counsel at its own expense.


 


Article VI


Confidentiality


 


Section 6.1                                      Confidential
Information.  Each Party
agrees that all Confidential Information disclosed to it or its Affiliates by
the other Party (a) shall not be used by the receiving Party or its
Affiliates except to fulfill its obligations or exercise its rights under this
Agreement, (b) shall be maintained in confidence by the receiving Party
and its Affiliates, and (c) shall not be disclosed by the receiving Party
or its Affiliates to any Third Party who is not a consultant of, or an advisor
to, the receiving Party or its Affiliates without the prior written consent of
the disclosing Party, which consent the disclosing Party may withhold in its
sole discretion.  Notwithstanding the
foregoing, either Party may disclose Confidential Information of the other Party
if such Party is required to make such disclosure by applicable law, regulation
or legal process, including by the rules or regulations of the United
States Securities and Exchange Commission (the “SEC”) or similar
regulatory agency in a country other than the United States or of any stock
exchange, in which event such Party shall provide prior notice of such intended
disclosure to such other Party, if possible under the circumstances, and shall
disclose only such Confidential Information of the other Party as is required
to be disclosed and to the extent practicable under the circumstances, such
Party shall provide the other Party with a copy of the proposed text of such
statements or disclosure (including any exhibits containing this 


 


20

















 


Agreement) sufficiently in advance of the
scheduled release or publication thereof to afford such other Party a
reasonable opportunity to review and comment upon the proposed text (including
redacted versions of this Agreement).  If
this Agreement shall be included in any report, statement or other document
filed by either Party or an Affiliate of either Party pursuant to the preceding
sentence, such Party shall use, or shall cause its Affiliate, as the case may
be, to use, reasonable efforts to obtain confidential treatment from the SEC,
similar regulatory agency or stock exchange of any financial information or
other information of a competitive or confidential nature, and shall include in
such confidentiality request such provisions of this Agreement as may be
reasonably requested by the other Party.


 


Section 6.2                                      Disclosures to
Employees, Consultants, Advisors, Etc.  Each Party agrees that it and its Affiliates
shall provide Confidential Information received from the other Party only to
the receiving Party’s respective employees, consultants, advisors, licensees
and potential licensees, and to the employees, consultants and advisors of the
receiving Party’s Affiliates, who have a need to know such Confidential
Information to assist the receiving Party in fulfilling its obligations under
this Agreement and only under conditions of confidentiality and non-use at
least as stringent as the conditions imposed by this Agreement, provided
that Fibrex and Ikaria shall each remain responsible for any failure by
its and its Affiliates’ respective employees, consultants, advisors, licensees
and potential licensees to treat such information and materials as required
under Section 6.1.  Additionally,
each party is permitted to disclose Confidential Information to actual or
potential licensees, licensors, acquirors or equity or other financing sources;
provided  that any such disclosure subjects the receiving Third
Party to conditions of confidentiality and non-use at least as stringent as the
conditions imposed by this Agreement.


 


Section 6.3                                      Terms of this
Agreement.  Except as
required by applicable laws, treaties, and regulations (including securities
laws), the Parties agree that the terms of this Agreement will be considered
Confidential Information of both Parties to which this Article VI applies.


 


Section 6.4                                      Term.  All obligations of confidentiality imposed
under this Article VI shall survive until the date that is [**] years
after the expiration or termination of this Agreement.


 


Section 6.5                                      Publicity.  During the term of this Agreement, the
content of any press release or public announcement relating to this Agreement
or a Product shall be mutually approved by the Parties, except that (a) a
Party may issue such press release or public announcement if the contents of
such press release or public announcement have previously been made public
other than through a breach of this Agreement by the issuing Party, (b) a
Party may issue such a press release or public announcement if it is advised by
counsel that such press release or public announcement is required by
applicable law, regulation or legal process, including by the rules or
regulations of the SEC or similar regulatory agency in a country other than the
United States or of any stock exchange and (c) Ikaria shall remain free to
issue press releases and public announcements regarding the Development,
Manufacturing, Commercialization, and use of Products in the Field.


 


21

















 


Article VII


Representations and
Warranties


 


Section 7.1                                      Representations
of Authority.  Fibrex and
Ikaria each represents and warrants to the other Party that it has full
corporate right, power and authority to enter into this Agreement and to
perform its respective obligations under this Agreement and that it has the
right to grant to the other Party the rights and licenses granted pursuant to
this Agreement.


 


Section 7.2                                      Consents.  Fibrex and Ikaria each represents and
warrants to the other Party that all necessary consents, approvals and
authorizations of all government authorities and other Persons required to be
obtained by it have been obtained.


 


Section 7.3                                      No Conflict.  Fibrex and Ikaria each represents and
warrants to the other Party that, notwithstanding anything to the contrary in
this Agreement, the execution and delivery of this Agreement, the performance
of such Party’s obligations in the conduct of the collaboration and the
licenses and rights to be granted pursuant to this Agreement (a) do not
conflict with or violate any requirement of applicable laws or regulations
existing as of the Effective Date and (b) do not conflict with, violate,
breach or constitute a default under any contractual obligations of such Party
or any of its Affiliates existing as of the Effective Date.


 


Section 7.4                                      Enforceability.  Fibrex and Ikaria each represents and
warrants to the other Party that this Agreement is a legal and valid obligation
binding upon it and is enforceable against it in accordance with its terms.


 


Section 7.5                                      Additional
Fibrex Representations. 
Fibrex represents and warrants to Ikaria that as of the Effective Date:


 


(a)          Fibrex has the right to
grant the licenses granted to Ikaria on the terms set forth in this Agreement;


 


(b)         Fibrex is not engaged with
any Third Party in any Development efforts directed to Products in the Field in
the Territory other than with respect to the On-Going Studies;


 


(c)          to Fibrex’s Knowledge, the
issued patents included in the Fibrex Patent Rights listed in Exhibit A
are valid and enforceable;


 


(d)         to Fibrex’s Knowledge, the
Fibrex Patent Rights are not being infringed and the Fibrex Know-How is not
being misappropriated by any Third Party;


 


(e)          Fibrex owns the entire
right, title, and interest in and to the Fibrex Intellectual Property free and
clear of any liens, charges, claims and encumbrances, and no other Person has
any claim of ownership or right to obtain compensation with respect to such
Fibrex Intellectual Property;


 


(f)            to Fibrex’s Knowledge, there
are no anticipated or pending oppositions or re-examinations with respect to
any Fibrex Patent Right;


 


22

















 


(g)         to Fibrex’s actual
Knowledge, (i) practice under the Fibrex Patent Rights does and will not
infringe Patent Rights of Third Parties, and (ii) Fibrex did not
misappropriate any intellectual property rights of any Third Party in its
Development of the Products; provided, that this subsection (g) shall not
apply to Patent Rights relating to the pegylation of any Compound.


 


(h)         Fibrex has not received and
has no Knowledge of any claim or demand of any Person pertaining to, or any
proceeding which is pending or threatened that asserts, the invalidity, misuse
or unenforceability of the Fibrex Patent Rights or that challenges Fibrex’s ownership
of the Fibrex Intellectual Property or that makes any adverse claim with
respect thereto, and, to the Knowledge of Fibrex, there is no basis for any
such claim, demand or proceeding.


 


Section 7.6                                      Employee,
Consultant and Advisor Legal Obligations.  Fibrex and Ikaria each represents and
warrants that each of its and its Affiliates’ employees, consultants, and
advisors who is or will be involved in performing any obligations hereunder has
executed or will have executed an agreement or have an existing obligation
under law requiring assignment to such Party of all intellectual property made
during the course of and as the result of his, her or its association with such
Party or such Affiliate, and obligating such employee, consultant or advisor to
maintain the confidentiality of Confidential Information to the extent required
under Article VI.  Fibrex and Ikaria
each represents and warrants that, to its Knowledge, none of its or its
Affiliates’ employees, consultants or advisors who is or will be involved in
performing any obligations hereunder is, as a result of the nature of such
obligations to be performed by the Parties, in violation of any covenant in any
contract relating to non-disclosure of proprietary information, non-competition
or non-solicitation.


 


Section 7.7                                      No Warranties.  EXCEPT AS OTHERWISE EXPRESSLY SET FORTH IN
THIS AGREEMENT, THE PARTIES MAKE NO REPRESENTATIONS AND EXTEND NO WARRANTIES OF
ANY KIND, EITHER EXPRESS OR IMPLIED, INCLUDING THAT ANY PRODUCTS WILL BE
ECONOMICALLY OR TECHNICALLY UTILIZABLE, THAT ANY SALES OF ANY PRODUCTS WILL
OCCUR, OR THAT THE DEVELOPMENT ACTIVITIES WILL BE COMPLETED IN THE EXPECTED
TIMEFRAME.


 


Article VIII


Term and Termination


 


Section 8.1                                      Term.  The term of this Agreement shall begin on the
Effective Date, may be terminated as set forth in this Article VIII, and
shall expire upon the date of expiration of the last-to-expire Royalty Term for
all Products in all countries in the Territory.


 


Section 8.2                                      Termination for
Material Breach.  Upon any
breach of a material provision of this Agreement by a Party (the “Breaching
Party”), the other Party (the “Non-Breaching Party”) may terminate
this Agreement by providing ninety (90) days written notice to the Breaching
Party specifying the material breach. 
Such termination shall become effective at the end of the notice period
unless the Breaching Party cures such breach during such notice period.


 


Section 8.3                                      Development-Related
Termination by Ikaria. 
Ikaria shall have the right to terminate this Agreement, on a Product-by-Product
basis, upon sixty (60) days prior written 


 


23

















 


notice, if Ikaria at any time determines, in
its sole judgment, that the results of the Development do not warrant further
Development of such Products.


 


Section 8.4                                      Effect of
Certain Terminations and Expiration.


 


(a)          If this Agreement is
terminated by Ikaria under Section 8.2:


 


(i)             The licenses granted by
Fibrex to Ikaria under Section 2.1 and, notwithstanding any other
provision in this Agreement to the contrary, Ikaria’s obligations under Article IV,
shall survive;


 


(ii)          Section 2.2 shall
survive until Ikaria is no longer obligated to pay royalties to Fibrex under Section 4.2;
and


 


(iii)        Section 5.1, 5.2 and
5.3 shall survive.


 


(b)         If this Agreement is
terminated either by Fibrex under Section 8.2, or by Ikaria under Section 8.3
with respect to a specific Product (the “Terminated Product,” which
shall include all Products in the case of such termination under Section 8.2),


 


(i)                                     the licenses granted under Section 2.1
to the Terminated Product shall terminate as of the effective date of such
termination; provided, that Ikaria, its
Affiliates, and its Sublicensees shall be afforded a commercially reasonable
period of time (but no more than [**] months) to complete any goods in progress
and to sell off any then existing or resulting inventories for finished goods
of the Terminated Product, subject to all royalty and other obligations
hereunder to Fibrex;


 


(ii)                                  Ikaria shall assign and
promptly transfer to Fibrex (A) all regulatory filings, Regulatory
Approvals, and clinical trial agreements (to the extent assignable and not
cancelled) relating to Terminated Product, to the extent that Fibrex elects to
continue Development of such Products; (B) all data, including clinical
data, materials, and information Controlled by Ikaria related to the Terminated
Product; and (C) all trademarks for the Terminated Product (if such
termination occurs after approval of such trademark by a Regulatory Authority);
and (D) other material information, and any other information reasonably
requested and required by Fibrex in order to manufacture the Terminated
Product;


 


(iii)                               Fibrex shall revoke (and
Ikaria shall allow revocation of) all rights granted to Ikaria under Section 5.2
to prosecute and maintain any Fibrex Patent Rights or Joint Patent Rights that
relate solely to the Terminated Product;


 


(iv)                              Subject to commercial
reasonable compensation and for no longer than [**] months after the effective
date of termination with respect to the Terminated Product, Ikaria shall supply
(or use reasonable efforts to cause its Third Party manufacturers to supply the
Terminated Product) to Fibrex to the extent Ikaria or any of its Affiliates
had, prior to such termination, been manufacturing the Terminated Product and,
at Fibrex’s request, shall assist in the transfer of manufacturing processes to
new suppliers; and


 


24

















 


(v)                                 if requested by Fibrex,
Ikaria and Fibrex shall negotiate promptly a mutually agreeable license
agreement under which Ikaria would license to Fibrex the exclusive license
under the Ikaria Product Improvements solely to Develop, manufacture and
Commercialize the Terminated Product; provided, however, that,
any such license would be subject to the payment of a reasonable royalty to be
negotiated by the Parties taking into account the development stage of the
terminated Product, the reasons and circumstances for termination, development
costs incurred or estimated to be incurred by each Party and other relevant
factors. If requested by Fibrex, Ikaria shall also provide reasonable
assistance to allow Fibrex to obtain the benefit of any intellectual property
rights embodied in the Terminated Product (or otherwise required for its Manufacture
or Commercialization) that were acquired by Ikaria from Third Parties; provided, that Fibrex shall be responsible for all financial
obligations.


 


(c)          Upon any termination or
expiration of this Agreement, each Party shall return to the other Party any
tangible property owned by the other Party, in accordance with the reasonable
instructions given by the other Party, with any shipping costs to be borne by
the other Party, provided that a Party may retain any such tangible property
owned by the other Party to the extent included within, or reasonably necessary
to exercise, any of such Party’s surviving rights and licenses.


 


Section 8.5                                      Survival.  In the event of any expiration or termination
of this Agreement, (a) all financial obligations under Article IV and
Article V owed as of the effective date of such expiration or termination
shall remain in effect, including such obligations that have accrued, but have
not been invoiced, as of such effective date, and (b) the provisions set
forth in Section 4.3(b), Section 5.1, Article I, Article VI,
Article IX, Article VIII and Article X, and all other terms,
provisions, representations, rights and obligations contained in this Agreement
that by their express terms survive expiration or termination of this Agreement
(including Section 8.4 and this Section 8.5), shall survive and all
other terms, provisions, representations, rights and obligations contained in
this Agreement shall terminate.


 


Article IX


Dispute Resolution


 


Section 9.1                                      Negotiation.  Any controversy, claim or dispute arising out
of or relating to this Agreement shall be settled, if possible, through good
faith negotiations between the Parties.


 


Section 9.2                                      Escalation.  If the Parties are unable to settle any
dispute after good faith negotiations pursuant to Section 9.1 after [**]
days, such dispute shall be referred to the Executive Officers to be resolved
by negotiation in good faith as soon as is practicable but in no event later
than [**] days after referral.


 


Section 9.3                                      Litigation.  If the Executive Officers are unable to
settle any dispute after good faith negotiations pursuant to Section 9.2
within [**] days after referral, either Party may seek resolution of the
dispute through remedies available at law or in equity from any court of
competent jurisdiction as set forth in Section 10.3.


 


25














 


Section 9.4             Equitable Relief.  Each Party acknowledges and agrees that the
other Party would be damaged irreparably if any of the provisions of Article II,
Article V and Article VI are not performed in accordance with their
specific terms or otherwise are breached. 
Accordingly, each Party agrees that the other Party shall be entitled to
an injunction or other equitable relief to prevent breaches of such provisions,
to preserve status quo, and to enforce specifically such provisions in any
action instituted in any court having jurisdiction over the Parties and the
matter, in addition to any other remedy to which it may be entitled, at law or
in equity.


 


Article X


Miscellaneous Provisions


 


Section 10.1           Indemnification.


 


(a)   By Ikaria.  Ikaria
agrees to defend Fibrex, its Affiliates and their respective directors,
officers, employees and agents at Ikaria’s cost and expense, and shall
indemnify and hold harmless Fibrex and its Affiliates and their respective
directors, officers, employees and agents from and against any liabilities,
losses, costs, damages, fees or expenses (collectively, “Losses”)
arising out of any Third Party claim to the extent relating to (i) any
breach by Ikaria of any of its representations, warranties, or obligations
pursuant to this Agreement, or (ii) personal injury, property damage, or
other damage or other Losses resulting from the Development, Manufacture, use,
or Commercialization of a Product by or on behalf of Ikaria or its Affiliates
or Sublicensees, excluding any claim for which Fibrex indemnifies Ikaria under
subsection (b) below.


 


(b)   By Fibrex.  Fibrex
agrees to defend Ikaria, its Affiliates and their respective directors,
officers, employees and agents at Fibrex’s cost and expense, and shall
indemnify and hold harmless Ikaria and its Affiliates and their respective
directors, officers, employees and agents from and against any Losses arising
out of any Third Party claim to the extent relating to (i) any breach by
Fibrex of any of its representations, warranties, or obligations pursuant to
this Agreement, (ii) personal injury, property damage, or other damage or
other Losses resulting from the conduct of the F.I.R.E. Study, (iii) any
Losses arising out of the shutdown of operations or winding up or dissolution
of Fibrex Medical R&D or (iv) any allegation that the practice of the
Fibrex Intellectual Property in the Development of the Products under Article III
infringes or misappropriates any Third Party intellectual property rights, to
the extent (x) resulting from Fibrex’s intentional or grossly negligent
acts or omissions or (y) Fibrex had Knowledge on the Effective Date that
such practice would infringe or misappropriate such Third Party intellectual
property rights; provided, that this clause (iii) shall
not apply to any Patent Rights relating to the pegylation of any Compound.


 


(c)   Claims for Indemnification. 
A Person entitled to indemnification under this Section 10.1 (an “Indemnified
Party”) shall give prompt written notification to the Party from whom
indemnification is sought (the “Indemnifying Party”) of the commencement
of any action, suit or proceeding relating to a Third Party claim for which
indemnification may be sought or, if earlier, upon the assertion of any such
claim by a Third Party (it being understood and agreed, however, that the
failure by an Indemnified Party to give notice of a Third Party claim as
provided in this Section 10.1(c) shall not relieve the Indemnifying
Party of its indemnification obligation under this Agreement except and only to
the extent that such Indemnifying Party is 


 


26

















 


actually damaged as a result of such failure
to give notice).  Within [**] days after
delivery of such notification, the Indemnifying Party may, upon written notice
thereof to the Indemnified Party, assume control of the defense of such action,
suit, proceeding or claim with counsel reasonably satisfactory to the
Indemnified Party.  If the Indemnifying
Party does not assume control of such defense, the Indemnified Party shall
control such defense.  The Party not
controlling such defense may participate therein at its own expense.  The Party controlling such defense shall keep
the other Party advised of the status of such action, suit, proceeding or claim
and the defense thereof and shall consider recommendations made by the other
Party with respect thereto.  The
Indemnified Party shall not agree to any settlement of such action, suit,
proceeding or claim without the prior written consent of the Indemnifying
Party.  The Indemnifying Party shall not
agree, without the prior written consent of the Indemnified Party, to any
settlement of such action, suit, proceeding or claim or consent to any judgment
in respect thereof that does not include a complete and unconditional release
of the Indemnified Party from all liability with respect thereto or that
imposes any liability or obligation on the Indemnified Party.


 


Section 10.2           Governing Law.  This Agreement shall be construed and the
respective rights of the Parties determined in accordance with the laws of the
State of New York, USA (other than any principle of conflict or choice of laws
that would cause the application of the laws of any other jurisdiction).


 


Section 10.3             Submission to Jurisdiction.  Each Party (a) submits to the
jurisdiction of any federal court sitting in the Borough of Manhattan in New
York, New York, USA in any action or proceeding arising out of this Agreement, (b) agrees
that all claims in respect of such action or proceeding may be heard and
determined in any such court, (c) waives any claim of inconvenient forum
or other challenge to venue in such court, and (d) agrees not to bring any
action or proceeding arising out of or relating to this Agreement in any other
court, unless such federal courts decline to exercise jurisdiction over any
such action or proceeding or if those courts lack proper jurisdiction, then any
action or proceeding arising out of this Agreement may be brought in state
courts sitting in the Borough of Manhattan in New York, New York, USA, or if
such courts decline to exercise jurisdiction over any such action or proceeding
or if those courts lack proper jurisdiction, any other U.S. court of competent
jurisdiction.  Each Party agrees to
accept service of any summons, complaint or other initial pleading made in the
manner provided for the giving of notices in Section 10.6, provided
that nothing in this Section 10.3 shall affect the right of either
Party to serve such summons, complaint or other initial pleading in any other
manner permitted by law.


 


Section 10.4           Assignment.  Each Party may assign this Agreement or any
right hereunder, or delegate any obligation hereunder, in its sole discretion,
to (a) any of its Affiliates, (b) any entity with which or into which
it may consolidate or merge, or (c) any entity acquiring all or
substantially all of its business or assets relating to this Agreement.  Fibrex may also assign its right to receive
payments hereunder.  Neither Party shall
otherwise be permitted to assign this Agreement, in whole or in part, without
the prior written consent of the other Party. 
Any assignments in contravention of this Section 10.4 shall be null
and void.


 


Section 10.5           Entire Agreement; Amendments.  This Agreement constitutes the entire
agreement between the Parties with respect to the subject matter hereof, and
supersedes all 


 


27

















 


previous arrangements between the Parties
with respect to the subject matter hereof, whether written or oral, except for
that certain Mutual Non Disclosure Agreement between the Parties.  To the extent that any provision of this
Agreement conflicts with any provisions of such Mutual Non Disclosure
Agreement, the provision of this Agreement shall control.  Any amendment or modification to this Agreement
shall be made in writing signed by both Parties.


 


Section 10.6           Notices.


 


Notices to Ikaria shall be addressed to:


 


Ikaria
Development Subsidiary Two LLC

6 State Route 173

Clinton, NJ 08809, USA

Attention: Chief Executive Officer


 


with
copy to:


 


Ikaria
Holdings, Inc.

6 State Route 173

Clinton, NJ 08809, USA

Attention: General Counsel


 


Notices to Fibrex Medical shall be addressed
to:


 


Fibrex
Medical Inc.

245 First Street, Suite 1800


Cambridge,
MA 02142, USA


Attention:  Chief Executive OfficerNotices to Fibrex
Medical R&D shall be addressed to (with a copy to Fibrex Medical)::


 


Fibrex
Medical Research & Development GesmbH

Gastgebgasse 5-13


A-1230
Vienna, Austria

Attention:  Chief Executive Officer


 


Any Party may change its address by giving notice to
the other Party in the manner herein provided. 
Any notice required or provided for by the terms of this Agreement shall
be in writing and shall be (a) sent by registered or certified mail,
return receipt requested, postage prepaid, (b) sent via a reputable
international courier service, (c) sent by facsimile transmission with an
original to be followed the same day via a reputable international courier
service, or (d) personally delivered, in each case properly addressed in
accordance with the paragraph above.  The
effective date of notice shall be the actual date of receipt by the Party
receiving the same.


 


Section 10.7           Force Majeure.  No failure or omission by a Party in the
performance of any obligation of this Agreement shall be deemed a breach of
this Agreement or create any liability if the same shall arise from any cause
or causes beyond the control of such Party, including the following: acts of
God; acts or omissions of any government; fire; storm; flood; 


 


28

















 


earthquake; accident; war; rebellion;
insurrection; riot; and invasion (each such event, a “Force Majeure Event”)
and provided  that such Party cures such failure or omission
resulting from one of the above causes as soon as is practicable after the
occurrence of one or more of the above-mentioned causes.


 


Section 10.8           Independent Contractors.  It is understood and agreed that the
relationship between the Parties hereunder is that of independent contractors
and that nothing in this Agreement shall be construed as authorization for
either Fibrex or Ikaria to act as agent for the other.


 


Section 10.9           Limitations of Liability.  NEITHER PARTY SHALL BE LIABLE FOR ANY
INDIRECT, INCIDENTAL, CONSEQUENTIAL, SPECIAL, EXEMPLARY OR PUNITIVE DAMAGES
ARISING OUT OF THIS AGREEMENT OR THE EXERCISE OF ITS RIGHTS HEREUNDER, OR FOR
LOST PROFITS ARISING FROM OR RELATING TO ANY BREACH OF THIS AGREEMENT,
REGARDLESS OF ANY NOTICE OF SUCH DAMAGES. 
NOTHING IN THIS SECTION 10.9 IS INTENDED TO LIMIT OR RESTRICT (A) THE
INDEMNIFICATION RIGHTS OR OBLIGATIONS OF EITHER PARTY WITH RESPECT TO THIRD
PARTY CLAIMS; (B) ANY LOSSES, INCLUDING LOST PROFITS, ARISING FROM ANY (I) BREACH
OF A PARTY’S OBLIGATIONS WITH RESPECT TO THE OTHER PARTY’S CONFIDENTIAL
INFORMATION, (II) BREACH BY FIBREX OF THE EXCLUSIVE RIGHTS GRANTED IN SECTION 2.1
OR THE COVENANT CONTAINED IN SECTION 2.2, OR (III) USE OF ANY PATENT
RIGHTS OR KNOW-HOW LICENSED HEREUNDER BEYOND THE SCOPE OF SUCH LICENSE; OR (C) ANY
LOSSES ARISING AS A RESULT OF A PARTY’S FRAUD, GROSS NEGLIGENCE, OR WILLFUL
MISCONDUCT.


 


Section 10.10         No Implied Waivers; Rights
Cumulative; Joint and Several Liability. 
No failure on the part of Fibrex or Ikaria to exercise, and no delay in
exercising, any right, power, remedy or privilege under this Agreement, or
provided by statute or at law or in equity or otherwise, shall impair,
prejudice or constitute a waiver of any such right, power, remedy or privilege
or be construed as a waiver of any breach of this Agreement or as an
acquiescence thereto, nor shall any single or partial exercise of any such
right, power, remedy or privilege preclude any further or other exercise
thereof or the exercise of any other right, power, remedy or privilege.  Fibrex Medical and Fibrex Medical R&D
shall be jointly and severally liable for any breach of this Agreement by
either or both of them.


 


Section 10.11         Severability.  If, under applicable law or regulation, any
provision of this Agreement is invalid, incomplete or unenforceable, or
otherwise directly or indirectly affects the validity of any other material
provision(s) of this Agreement (such invalid, incomplete, or unenforceable
provision, a “Severed Clause”), this Agreement shall endure except for
the Severed Clause.  The Parties shall
consult one another and use reasonable efforts to agree upon a valid, complete
and enforceable provision that is a reasonable substitute for the Severed
Clause in view of the intent of this Agreement.


 


Section 10.12         Fibrex Medical R&D.  Fibrex Medical may shut down the operations
of Fibrex Medical R&D, including the winding down and dissolution of such
entity; provided, that 


 


29

















 


all of its rights to all Fibrex Intellectual
Property owned by Fibrex Medical R&D are assigned to Fibrex Medical.


 


Section 10.13         Execution in Counterparts; Facsimile
Signatures.  This Agreement may be
executed in counterparts, each of which, when so executed and delivered, shall
be deemed to be an original, and all of which, taken together, shall constitute
one and the same instrument even if both Parties have not executed the same
counterpart.  Signatures provided by
facsimile transmission shall be deemed to be original signatures.


 


Section 10.14         Ikaria Affiliates.  If any
portion of the Development, use, Manufacture, or Commercialization of the
Products is carried out for or behalf of Ikaria by any Affiliate of Ikaria (the
“Affiliate Services”), Ikaria shall, prior to the commencement of the
Affiliate Services, obtain a written assignment by such Affiliate to Ikaria of
all intellectual property and intellectual property rights that may be created
or arise as a result of the Affiliate Services. 
All intellectual property and intellectual property rights that may be
created or arise as a result of the Development, use, Manufacture, or
Commercialization of the Products and that is assigned to an Affiliate of
Ikaria shall be deemed owned by Ikaria for the purpose of this Agreement.


 


Section 10.15         Parent Guarantee.  This Agreement shall not become binding upon
the parties unless and until Ikaria Holdings, Inc. has signed and
delivered the “guarantee” attached hereto as Exhibit D.


 


REMAINDER
OF PAGE LEFT EMPTY; NEXT PAGE IS THE SIGNATURE PAGE


 


30

















 


IN WITNESS WHEREOF, the Parties have executed
this License Agreement as of the Effective Date.


 


	
   

  	
  IKARIA
  DEVELOPMENT SUBSIDIARY TWO LLC

  
	
   

  	
   

  
	
   

  	
  By:

  	
  /s/
  Matthew M. Bennett

  
	
   

  	
   

  	
   

  
	
   

  	
  Name:

  	
  Matthew
  M. Bennett

  
	
   

  	
   

  	
   

  
	
   

  	
  Title:

  	
  Senior
  Vice President

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  
	
   

  	
  FIBREX
  MEDICAL INC.

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  
	
   

  	
  By:

  	
  /s/
  Rainer Henning

  
	
   

  	
   

  	
   

  
	
   

  	
  Name:

  	
  Rainer
  Henning

  
	
   

  	
   

  	
   

  
	
   

  	
  Title:

  	
  President
  and CEO

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  
	
   

  	
  FIBREX
  MEDICAL RESEARCH &

  
	
   

  	
  DEVELOPMENT
  GESMBH

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  
	
   

  	
  By:

  	
  /s/
  Rainer Henning

  
	
   

  	
   

  	
   

  
	
   

  	
  Name:

  	
  Rainer
  Henning

  
	
   

  	
   

  	
   

  
	
   

  	
  Title:

  	
  CEO

  



 


31

















 


SCHEDULE 1.4


 


COMPOUNDS


 


FX06


 


[**]


 


FX201


 


[**]


 


FX107


 


[**]


 


32

















 


SCHEDULE 3.7


 


ON-GOING STUDIES


 


[**]


 


33

















 


SCHEDULE 4.3(a)


 


FIBREX WIRE TRANSFER
INFORMATION


 


	
  Bank Name:

  	
   

  	
  [**]

  
	
   

  	
   

  	
   

  
	
  Bank
  Address:

  	
   

  	
  [**]

  
	
   

  	
   

  	
   

  
	
  ABA
  or Routing Number:

  	
   

  	
  [**]

  
	
   

  	
   

  	
   

  
	
  SWIFT
  Number:

  	
   

  	
  (if
  paid to a bank outside of the U.S.)

  
	
   

  	
   

  	
   

  
	
  IBAN
  Number:

  	
   

  	
  (if
  available)

  
	
   

  	
   

  	
   

  
	
  Account
  Number:

  	
   

  	
  [**]

  
	
   

  	
   

  	
   

  
	
  Account Name:

  	
   

  	
  Fibrex Medical, Inc.

  



 


34














 


EXHIBIT A


 


FIBREX PATENT RIGHTS


 


 


	
  Application
  #’s

  	
   

  	
  Patent #

  	
   

  	
  Owner

  	
   

  	
  Title

  	
   

  	
  Countries/Comments/Publication

  No.’s

  	
   

  
	
  [**]

  	
   

  	
  [**]

  	
   

  	
  [**]

  	
   

  	
  [**]

  	
   

  	
  [**]

  	
   

  
	
  [**]

  	
   

  	
   

  	
   

  	
  [**]

  	
   

  	
  [**]

  	
   

  	
  [**]

  	
   

  
	
  [**]

  	
   

  	
  [**]

  	
   

  	
  [**]

  	
   

  	
  [**]

  	
   

  	
  [**]

  	
   

  
	
  [**]

  	
   

  	
   

  	
   

  	
  [**]

  	
   

  	
  [**]

  	
   

  	
   

  	
   

  
	
  [**]

  	
   

  	
   

  	
   

  	
  [**]

  	
   

  	
  [**]

  	
   

  	
  [**]

  	
   

  



 


A
total of two pages were omitted pursuant to a request for confidential
treatment.


 


35

















 


EXHIBIT B


 


TECHNOLOGY TRANSFER PLAN


 


Upon Ikaria’s request, the following will be
provided by Fibrex to Ikaria or its designee:


 


1.                                       All materials
(original or copies as appropriate) in Fibrex’s possession and Control relating
to Product, including documentation relating to Development and all regulatory
filings, clinical information, and data and other documents; provided, that, such materials relating to the F.I.R.E.
Study shall consist of such materials as, within a reasonable period of time
following the Effective Date, the Parties shall establish that are reasonable
necessary for Ikaria to Develop FX06.


 


2.                                       Copies of all
documents and available information in Fibrex’s possession and Control
necessary for Manufacturing of Product at the time of technology transfer.
These documents will include information necessary to assist Ikaria or its
designee in setting up Manufacturing operations for such things as:


 


·                  raw material test methods, specifications,
qualification and justification for use


·                  raw material vendor lists with part numbers


·                  analytical methods stated purpose,
development, qualification, and validation reports


·                  process development reports, laboratory
notebooks and associated electronically stored data


·                  Manufacturing summary including


·                  detailed process description with process
schematics, operating parameters and target ranges, flow charts outlining
critical process controls and steps, cartoons, verbal description including
abbreviations, process scale, yield, and standard process instructions


·                  in-process controls/tests and acceptance
criteria including stated purpose of in-process tests


·                  filling/packaging process


·                  aseptic and process development and
validation documents


·                  facility and equipment requirements and
design documents


·                  descriptions of process equipment, including
suppliers, part numbers, and historic invoices


·                  product test methods, specifications, and
justification of specifications


·                  product stability, test methods and
qualification/validation reports, stability reports, shelf life recommendations


 


As available and agreed upon by the Parties
at the time of a technology transfer, Fibrex shall provide requested technical
manufacturing or engineering advice to Ikaria or its designee. Ikaria shall
ensure designee has necessary expertise in place to transfer the documentation
and expertise in an orderly fashion.


 


36

















 


EXHIBIT C


 


MILESTONE PAYMENT EXAMPLES


 


Solely for the purposes of the examples provided
below to illustrate Ikaria’s payment obligations under Section 4.1, (a) any
three separate Indications will be called “Indication A”, “Indication B” and “Indication
C” and (b) Products containing FX201, FX107 or FX06 Compounds (for uses in
the Field) will be called “FX201 Product”, “FX107 Product”, or “FX06 Product,”
respectively.  For the avoidance of
doubt, the examples provided below are not exhaustive and where FX201 Product,
FX107 Product or FX06 Product is used, such Product may be substituted for a
Product containing any other Compound unless otherwise specified.


 


1)  If an
FX201 Product being Developed for Indication A is the first Product to achieve
Successful Completion of a Phase IIb Clinical Trial, Ikaria would pay Fibrex
$[**] under Section 4.1(c).  If
another FX201 Product or a Product containing any other Compound subsequently
achieves Successful Completion of a Phase IIb Clinical Trial for Indication A,
then Ikaria would not be required to pay Fibrex an additional payment for such
achievement.


 


2)  If an
FX107 Product being Developed for Indication A is the first Product to achieve
Acceptance of NDA Filing in the U.S., Ikaria would pay Fibrex $[**] under Section 4.1(c).  If that same FX107 Product or another FX107
Product or a Product containing any other Compound subsequently becomes the
first Product to achieve that same milestone for Indication B, Ikaria will pay
Fibrex $[**] under Section 4.1(d). 
If that same FX107 Product or another FX107 Product or a Product
containing any other Compound then subsequently becomes the first Product to
achieve that same milestone for Indication C, Ikaria will pay Fibrex $[**]
under Section 4.1(e).


 


3) If any Product (other than an FX06 Product) has
achieved Successful Completion of Phase IIa Clinical Trial for Indication A
(and Fibrex has been paid in accordance with Section 4.1(c) for such
achievement) and an FX201 Product subsequently becomes the first Product (other
than an FX06 Product) to achieve Successful Completion of Phase IIa Clinical
Trial for Indication B, Ikaria would pay Fibrex $[**] under Section 4.1(d).  If that same FX201 Product or another FX201
Product or a Product containing any other Compound is Developed for Indication
C and subsequently achieves Successful Completion of Phase IIb Clinical Trial
for Indication C before that FX201 Product Developed for Indication B achieves
Successful Completion of Phase IIb Clinical Trial, then Ikaria would pay Fibrex
$[**] under Section 4.1(d).  If that
FX201 Product (or any other Product Developed for Indication B) subsequently
achieves Successful Completion of Phase IIb Clinical Trial, then Ikaria would
pay Fibrex $[**] under Section 4.1(e).


 


4)  If an
FX201 Product is the first Product to achieve Successful Completion of a Phase
IIb Clinical Trial for Indication A, Ikaria would pay Fibrex $[**] under Section 4.1(c).  If further Development of that FX201 Product
for Indication A is subsequently terminated, then such amount shall be credited
toward the next achievement of such milestone for any other Indication.


 


37

















 


EXHIBIT D


 


FORM OF GUARANTEE


 


GUARANTEE


 


In consideration of Fibrex Medical, Inc. and
Fibrex Medical Research and Development GesmbH (collectively, “Fibrex”)
entering into that certain License Agreement by and among Ikaria Development
Subsidiary Two LLC (“Ikaria”) and Fibrex dated as of July 17, 2009
(the “Agreement”), Ikaria Holdings, Inc., a corporation organized and
existing under the laws of the State of Delaware and the ultimate sole owner of
Ikaria (“Ikaria Parent”), hereby unconditionally and irrevocably
guarantees to Fibrex the payment of all financial obligations of Ikaria,
including milestones and royalty payments set forth in Sections 4.1 and 4.2 of
the Agreement (assuming that any triggering events for such payments have been
met in accordance with the terms and conditions of the Agreement), the
indemnification obligations under Article X and any judgment against
Ikaria in respect to any breach of the Agreement (the “Guaranteed
Obligations”), upon the failure of Ikaria to satisfy a Guaranteed
Obligation when due and payable; provided, that
if Ikaria has failed to satisfy any Guaranteed Obligation, Fibrex shall (a) first
notify both Ikaria and Ikaria Parent of such failure, and provide Ikaria with
the opportunity to cure such failure as set forth in Section 8.2 of the
Agreement, and (b) if Ikaria has not satisfied the Guaranteed Obligation
by the end of the applicable cure period, then Ikaria Parent shall satisfy such
Guaranteed Obligation within fifteen (15) Business Days after written request
therefor from Fibrex. Except as provided above, (a) Ikaria Parent’s
obligations shall in no way be conditioned upon any requirement that Fibrex
first attempt to collect any of the Guaranteed Obligations from Ikaria or
resort to any security or other means of obtaining its payment and (b) to
the extent permitted by law, Ikaria Parent waives presentment, demand, protest,
notice of acceptance, notice of Guaranteed Obligations incurred and all other
notices of any kind, all defenses that may be available by virtue of any
valuation, stay, moratorium law or other similar law now or hereafter in
effect, any right to require the marshaling of assets of Ikaria, and all
suretyship defenses generally.  Without
limiting the generality of the foregoing, Ikaria Parent agrees to the
provisions of the Agreement and agrees that the obligations of Ikaria Parent
hereunder shall not be released or discharged, in whole or in part, or
otherwise affected by (a) any extensions or renewals of any Guaranteed
Obligation; or (b) any rescissions, waivers, amendments or modifications
of any of the terms or provisions of the Agreement or other agreements executed
hereafter evidencing, securing, or otherwise executed in connection with any
Guaranteed Obligation.


 


Ikaria Parent hereby agrees that any and all
disputes, claims, actions, or proceedings arising out of the execution,
delivery, or performance of this Guarantee shall be subject to the provisions
of Article IX and Section 10.2 and 10.3 of the Agreement.


 


	
   

  	
  Ikaria
  Holdings, Inc.

  
	
   

  	
   

  
	
   

  	
   

  
	
   

  	
   

  
	
   

  	
  By:
  Matthew M. Bennett

  
	
   

  	
   

  
	
   

  	
  Its:
  Senior Vice President

  
	
   

  	
   

  
	
   

  	
  Date: July 17, 2009

  



 


38