Document:

BioSpecifics Technologies Corp.: Exhibit 10.1 - Filed by
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EXECUTION VERSION

 

 

SECOND AMENDED AND RESTATED 

DEVELOPMENT AND LICENSE AGREEMENT 

dated as of August 31, 2011 

by and between

BIOSPECIFICS TECHNOLOGIES CORP.

(a Delaware corporation) 

And

AUXILIUM PHARMACEUTICALS, INC. 

(a Delaware corporation) 

  
  	
      
Confidential treatment requested under 17 C.F.R. §§ 200.80(b)(4) and 240.24b -2. The confidential portions of this exhibit have been omitted and are marked accordingly. The confidential portions have been filed separately with the
Securities and Exchange Commission pursuant to a confidential treatment request.
       

  

 

 

EXECUTION VERSION

SCHEDULES

	
Schedule
1.9
		
BTC Patents
	
	
Schedule
1.23
		
Cost of Goods
	
	
Schedule
1.57
		
Partner Territory
	
	
Schedule
2.2(d)
		
Cellulite Protocols
	
	
Schedule
3.1	
Additional Indication Review Process
	
	
Schedule
3.1(b)(1)
		
Canine Lipoma Protocol
	
	
Schedule
3.1(b)(2)	
Human Lipoma Protocols
	
	
Schedule
3.1(b)(3)
		
Research Proposal Template
	
	
Schedule
3.2	
Clinical Trials
	
	
Schedule
13.1
		
Joint Press Release
	

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EXECUTION VERSION

SECOND AMENDED AND RESTATED DEVELOPMENT AND LICENSE AGREEMENT 

This SECOND AMENDED AND RESTATED DEVELOPMENT AND LICENSE AGREEMENT (this “Agreement”) dated August 31, 2011 is by and between BioSpecifics Technologies Corp., a corporation organized and existing under the laws of Delaware and
having its principal office at 35 Wilbur Street, Lynbrook, New York 11563, and its Affiliates (“BTC”), and Auxilium Pharmaceuticals, Inc., a corporation organized and existing under the laws of the State of Delaware and having its
principal office at 40 Valley Stream Parkway, Malvern, PA 19355 (“Auxilium”). BTC and Auxilium shall sometimes be referred to herein individually as a “Party” and collectively as “Parties.”

INTRODUCTION

WHEREAS, BTC controls certain BTC Patents and BTC Know-How (each as defined below) related to the Enzyme and the Product (each as defined below), and has the right to grant certain rights and licenses thereunder as set forth herein, and 

WHEREAS, Auxilium has certain expertise in the development, manufacture and commercialization of pharmaceutical products, and Auxilium wishes to obtain certain licenses and options to develop, manufacture and commercialize the Product for certain
therapeutic uses in animals and humans, and 

WHEREAS, BTC wishes to convey such licenses to Auxilium, and

WHEREAS, BTC and Auxilium previously entered into that certain Development and License Agreement dated June 3, 2004, as amended by that certain Amendment No. 1 to Development and License Agreement dated May 10, 2005 and that certain letter agreement
dated December 15, 2005 (the “Original Agreement”) involving, among other things, the licensing of intellectual property by BTC to Auxilium, and 

WHEREAS, BTC and Auxilium amended and restated, effective as of December 17, 2008, the Original Agreement in its entirety and replaced the Original Agreement (the “Amended and Restated Agreement”);

WHEREAS, contemporaneously with the execution of this Agreement, BTC and Auxilium shall execute a settlement agreement to settle all disagreements between the Parties existing as of the Amendment Effective Date (the “Settlement
Agreement”); and 

WHEREAS, BTC and Auxilium now desire to amend and restate the Amended and Restated Agreement and to replace the Amended and Restated Agreement with this Agreement. 

NOW, THEREFORE, in consideration of the mutual promises, covenants and agreements hereinafter set forth, the sufficiency of which is hereby acknowledged, the Parties to this Agreement mutually agree as follows: 

 

EXECUTION VERSION

ARTICLE 1 

DEFINITIONS

For purposes of this Agreement, the following initially capitalized terms in this

Agreement, whether used in the singular or plural, shall have the following meanings: 

1.1
“Additional
Indication” shall mean any Indication for a Product outside of the
Field. 

1.2
“Additional
Indication Option” has the meaning set forth in Section 2.2(b). 

1.3
“Adverse Drug Experience” shall mean any of the following as such terms are
defined at either 21 C.F.R. § 312.32 or 21 C.F.R. § 314.80 (or veterinary counterpart, 21 C.F.R. § 514.3): an “adverse drug experience,” a “life-threatening adverse drug experience,” a “serious adverse drug
experience,” or an “unexpected adverse drug experience” and the foreign counterparts thereof.

1.4 “Affiliate” shall mean any corporation, company, partnership, joint venture or firm which controls, is controlled by, or is under common control with a specified person or entity. For purposes of this Section 1.4,
“control” shall be presumed to exist if one of the following conditions is met: (a) in the case of corporate entities, direct or indirect ownership of at least fifty percent (50%) of the stock or shares having the right to vote for the
election of directors, and (b) in the case of non-corporate entities, direct or indirect ownership of at least fifty percent (50%) of the equity interest with the power to direct the management and policies of such non-corporate entities. The
Parties acknowledge that in the case of certain entities organized under the laws of certain countries outside of the United States, the maximum percentage ownership permitted by law for a foreign investor may be less than fifty percent (50%), and
that in such cases such lower percentage shall be substituted in the preceding sentence, provided that such foreign investor has the power to direct the management and policies of such entity. For purposes of clarity, Advance BioFactures Corporation
of New York is an Affiliate of BTC and each of Auxilium International Holdings, LLC and Auxilium US Holdings, Inc. is an Affiliate of Auxilium and such Affiliates are parties to this Agreement. Advance BioFactures of Curacao, NV was an Affiliate of
BTC on June 3, 2004 and May 10, 2005 and was a party to the Original Agreement. 

1.5 “Amendment Effective Date” has the meaning set forth in Section 13.1.

1.6 “Auxilium Remaining Indication” shall mean an Additional Indication for a
Product that Auxilium believes has a reasonable probability of obtaining Regulatory Approval and achieving commercial success, but for which BTC does not wish to undertake Stage I Development.

1.7 “Auxilium Territory” shall mean the Territory excluding (1) the Partner Territory, (2) the Japan Territory and (3) such countries that become part of the Partner II Territory; provided, however, that, regardless of whether
Auxilium Commercializes the Product in the United States itself or through a Sublicensee, the Auxilium Territory will always include the United States. 

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EXECUTION VERSION

1.8 “BTC Know-How” shall mean any proprietary information or materials related to the Manufacture, preparation, formulation, use or development of the Enzyme or the Product Controlled by BTC during the Term and shall include
formulations, processes, techniques, formulas, biological, chemical, assay control and manufacturing, technical, pre-clinical, clinical or other data, methods, know-how, and trade secrets.

1.9 “BTC Patents” shall mean those Patents Controlled by BTC with at least one claim directed to the Enzyme or the Product (or processes, improvements, uses, intermediates, variants or derivatives for the foregoing) including those
listed on Schedule 1.9 attached hereto as it may be amended from time to time. For the sake of clarity, BTC Patents includes U.S. Patent Application Nos. 11/699,302, 60/763,470, 60/784,135 and International Patent Application No.
PCT/07/02654, any applications claiming priority to such applications and any patents issuing or granting therefrom.

1.10 “BTC Product” shall mean any pharmaceutical product that includes Enzyme as an active ingredient and is under development for an Indication (or is indicated for use) outside the Field.

1.11 “Business Day” shall mean any day on which banking institutions in New York, New York are open for business. 

1.12 “Category I Additional Indication” has the meaning set forth in Section 3.1(b)(iii)(A) . 

1.13 “Category II Additional Indication” has the meaning set forth in Section 3.1(b)(iii)(B) . 

1.14 “Category III Additional Indication” has the meaning set forth in Section 3.1(b)(iii)(C) . 

1.15 “Cellulite” has the meaning set forth in Section 2.2(d).

1.16 “Clinical Product Supply Price” has the meaning set forth in Section 6.2.

1.17 “Clinical Trials” shall mean tests and studies in human subjects or patients that
are required to obtain, maintain, or sustain Regulatory Approval in a country in the Territory.

1.18 “Commercialization” or “Commercialize” shall mean activities directed to marketing, promoting, co-promoting, distributing, importing, exporting, offering for sale and selling the Product. When used as a verb,
“Commercialize” means to engage in Commercialization. 

1.19 “Commercially Reasonable Efforts” means, with respect to a Party, the efforts and resources which would be used by that Party relating to a certain activity or activities, consistent with its normal business practices, which
are consistent with the general level of effort and resources in the pharmaceutical industry for a company similar in size and scope.

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EXECUTION VERSION

1.20 “Competing Product” shall mean a product that contains Enzyme and is sold in a country by a Person (other than Auxilium, its Affiliate, Sublicensee or sub-Sublicensee) in an Indication for which Auxilium, its Affiliate,
Sublicensee or sub-Sublicensee is marketing a Product in such country.

1.21 “Confidential Information” has the meaning set forth in Section 10.1.

1.22 “Controlled” or “Controls”, when used in reference to intellectual property, shall
mean for a Party to have an ownership interest in, or the legal authority, or right of a Party hereto (or any of its Affiliates) to grant a license or sublicense of intellectual property rights to another Party, or to otherwise disclose proprietary
or trade secret information to such other Party, without breaching the terms of any agreement with a Third Party, infringing upon the intellectual property rights of a Third Party, or misappropriating the proprietary or trade secret information of a
Third Party. 

1.23 “Cost of Goods” shall mean the total cost of Product in Final Packaging as calculated in accordance with Schedule 1.23.

1.24 “Cover(ed)” shall mean , with respect to any Patent and the subject matter at issue, that, but for a license granted under a Valid Claim of such Patent, the manufacture, development, use, sale, offer for sale or importation of
the subject matter at issue would infringe such Valid Claim, or in the case of a Patent that is a patent application, would infringe a Valid Claim in such patent application if it were to issue as a patent. 

1.25 “Develop” or “Development” shall mean Stage I Development and Stage II Development. When used as a verb, “Developing” means to engage in Development. For purposes of clarity, in no event shall
Development include Manufacture. 

1.26 “Development Costs” shall mean costs associated with Development activities.

1.27 “Development Plan” shall mean the written plan established by the Parties for
Development of an Additional Indication as contemplated by Schedule 3.1.

1.28 “Effective Date” shall mean June 3, 2004.

1.29 “Enzyme” shall mean [**].

1.30 “European Union” shall mean the countries of the European Union, as it is
constituted as of the Effective Date and as it may be expanded from time to time.

1.31 “Exercised Indication” has the meaning set forth in Section 2.2(c).

1.32 “Exercised Indication Date” has the meaning set forth in Section 2.2(c).

1.33 “Exercise Period” has the meaning set forth in Section 2.2(c).

1.34 “FDA” shall mean the U.S. Food and Drug Administration or its successor
agency.

** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

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EXECUTION VERSION

1.35 “Field” shall mean, subject to expansion pursuant to Section 2.2, the prevention or treatment of Dupuytren’s Disease, Peyronie’s Disease and Adhesive Capsulitis (otherwise known as “Frozen
Shoulder”).

1.36 “Final Packaging” means the labeling and packaging to be used in connection with the Product labeled for use in the Field in the Territory, including the packaging of package inserts and components reasonably necessary for sale
of the finished Product to the ultimate consumer. 

1.37 “Indemnified Party” has the meaning set forth in Section 12.3.

1.38 “Indemnifying Party” has the meaning set forth in Section 12.3.

1.39 “Indication” shall mean a pharmaceutical application for the Product.

1.40 “Infringement Claim” has the meaning set forth in Section 8.2(a).

1.41 “Japan Partner” shall mean Asahi Kasei Pharma Corporation, a Japanese
corporation, and its Affiliates.

1.42 “Japan Territory” shall mean Japan.

1.43 “Law” shall mean any applicable statute, law, ordinance, regulation, order, or
rule of any federal, state, local, foreign, or other governmental agency or body or of any other type of regulatory body (including common law) or securities exchange, including those covering pharmaceutical sales, environmental, pollution, energy,
safety, health, transportation, bribery, record-keeping, zoning, antidiscrimination, antitrust, wage and hour, and price and wage control matters.

1.44 “Licensed Technology” shall mean the BTC Patents and the BTC Know-How.

1.45 “Lipomas” shall mean mesenchymal, benign, fatty tumors.

1.46 “Loss” has the meaning set forth in Section 12.1.

1.47 “Major Market Country” shall mean [**].

1.48 “MAA” shall mean an application seeking Regulatory Approval of the
Regulatory Authority in the European Union to market and sell a Product in the Field in the European Union.

1.49 “MAA Acceptance” shall mean the written notification by the applicable Regulatory Authority that the MAA has met all the criteria for filing acceptance. 

1.50 “Manufacture” or “Manufacturing” shall mean manufacturing, filling, processing, testing, engineering, designing, redesigning, packaging, storing, quality control, quality assurance, releasing, disposing,
handling, shipping, and all other activities undertaken or required to be undertaken in order to manufacture and supply the Product in its Final Packaging
and related devices and apparatus for administration thereof, in the case of commercial supplies, or packaged in accordance with Laws, in the case of clinical supplies, or the Enzyme, as the case may be. 

** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

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EXECUTION VERSION

1.51 “NDA” or “New Drug Application” shall mean a new drug application filed with the FDA pursuant to 21 C.F.R. §314, seeking permission to market the Product for a particular Indication in the Field in
interstate commerce in the United States, including any similar or analogous application to be filed with the FDA for biologic products and/or veterinary products.

1.52 “NDA Filing Acceptance” shall mean the written notification by the FDA that the NDA has met all the criteria for filing acceptance. 

1.53 “Net Sales” shall mean the gross amount invoiced by Auxilium and its Affiliates or Sublicensees on account of sales of the Product in Final Packaging to Third Parties in the Territory, less the total of: (a) trade, cash or
quantity discounts not already reflected in the amount invoiced; (b) excise, sales and other consumption taxes and customs duties to the extent included in the invoice price; (c) freight, insurance and other transportation charges to the extent
specifically included in the invoice price; (d) returns or retroactive price reductions; and (e) compulsory payments and rebates directly related to the sale of the Product accrued, paid or deducted pursuant to governmental regulations. For the sake
of clarity, the gross amount will be determined by the amount invoiced by Auxilium, its Affiliates or Sublicensees to Third Parties (other than Sublicensees or their Affiliates or sublicensees thereof) and will exclude any sales between Auxilium and
its Affiliates and Auxilium and its Sublicensees.

1.54 “Orphan Drug Designation” shall mean the special designation of Product by FDA’s Orphan Product Division which provides the Product with the opportunity to obtain additional market exclusivity from the date the drug
receives FDA approval and also possible tax and regulatory approval benefits. The term “Orphan Drug Designation” shall include any foreign counterparts of the foregoing as well as any veterinary counterparts. 

1.55 “Partner” shall mean Pfizer, Inc., a Delaware corporation, and its Affiliates.

1.56 “Partner II” shall mean one or more Persons (excluding any Auxilium Affiliates),
from time to time, to whom Auxilium sublicenses any of the rights granted by BTC hereunder to research, Develop, use, Manufacture, Commercialize, market, sell or distribute the Product in the Field in one or more countries of the Partner II
Territory.

1.57 “Partner Territory” shall mean those countries in the Territory to which Auxilium has granted Partner rights hereunder and which are set forth on Schedule 1.57 as the same may be amended by mutual agreement of BTC and
Auxilium.

1.58 “Partner II Territory” shall mean such country(ies) in the Territory (other than those countries comprising the Partner Territory, the Japan Territory and the United States of America) as Auxilium may notify BTC from
time to time that are or become subject to a sublicense agreement between Auxilium and a Partner II, at which time such country(ies) where such sublicense agreement is in effect shall no longer be part of the Auxilium Territory and shall become part
of the Partner II Territory.

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EXECUTION VERSION

1.59 “Patents” shall mean any patents or patent applications and any continuations, continuations-in-part, divisions, provisionals, substitutions, patents of addition, reissues, reexamination, renewals or extensions thereof
(including any supplemental patent certificates) and any confirmation patent or registration patent and all foreign counterparts of any of the foregoing. 

1.60 “Person” shall mean any individual, corporation, partnership, association, joint-stock company, trust, unincorporated organization or government or political subdivision thereof. 

1.61 “Phase II Clinical Trials” shall mean a Clinical Trial or Veterinary Trial for the Product on a number of subjects, no fewer than the number required to allow for the detection of statistical differences between the control and
treated subjects, for the purposes of determining dose and evaluating safety and efficacy in the proposed therapeutic indication, conducted in accordance with current good clinical practices and in accordance with a protocol that has been reviewed
to the extent required by the FDA or other Regulatory Authority and reflects any comments or concerns raised by the same. 

1.62 “Placebo” shall mean the placebo to be used in each of the relevant protocols.

1.63 “Placebo Supply Price” has the meaning set forth in Section 6.2.

1.64 “Product” shall mean pharmaceutical product containing Enzyme as an active
ingredient and any reformulation, improvement, enhancement, combination, refinement, or modification thereof; provided however, Product shall specifically exclude dermal formulations labeled for topical administration.

1.65 “Product Data” shall mean the physical embodiment, to the extent available of: (a) the know-how, including relevant laboratory notebook information, screening data and synthesis schemes, including descriptions in any form, data
and other information, and (b) all other data including Regulatory Data and any other pre-clinical and clinical data and information, technical, chemical, safety and scientific data, information and know-how, obtained or generated in connection with
Development of the Product in the Field. 

1.66 “Regulatory Approval” shall mean, with respect to a country or group of countries in the Territory, all authorizations by the appropriate governmental entity or entities necessary for commercial sale of the Product in the Field
for a particular Indication in that country or group of countries including, where applicable, approval of labeling, price, reimbursement and manufacturing.

1.67 “Regulatory Authority” shall mean the FDA or any foreign counterpart or additional governmental or regulatory agencies in the Territory responsible for applicable Regulatory Approvals. 

1.68 “Regulatory Data” shall mean any and all research data, pharmacology data, chemistry, manufacturing, and control data, preclinical data, clinical data or all other documentation submitted, or required to be submitted, to
Regulatory Authorities in association
with regulatory filings for the Product in the Field (including any Drug Master Files (DMFs), Chemistry, Manufacturing and Control (“CMC”) data, or similar documentation). 

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EXECUTION VERSION

1.69 “Remaining Indication” shall mean an Additional Indication for which Auxilium has not exercised an Additional Indication Option within the Exercise Period. 

1.70 “Stage I Development” shall mean pre-clinical and clinical drug development activities reasonably necessary to completing all development activities up to and including the completion of Phase II Clinical Trials for the Product
in an Indication, including pre-clinical studies, test method development, statistical analysis, Clinical Trials, Veterinary Trials, regulatory affairs, and activities directed to seeking Regulatory Approvals. 

1.71 “Stage I Development Costs” shall mean costs associated with Stage I Development activities. 

1.72 “Stage II Development” shall mean non-clinical and clinical drug development activities reasonably necessary to the development and submission of Regulatory Data to a Regulatory Authority for the purpose of achieving Regulatory
Approval, including non-clinical studies, test method development, statistical analysis, Clinical Trials, Veterinary Trials, regulatory affairs, and activities directed to seeking Regulatory Approvals.

1.73 “Stage II Development Costs” shall mean costs associated with Stage II Development activities.

1.74 “Sublicense Income” shall mean (a) the upfront payment, if any, received from a Sublicensee by Auxilium upon execution of an agreement with such Sublicensee, and (b) any milestone payments received from a Sublicensee by
Auxilium in consideration for the grant of a sublicense to such Sublicensee under the Licensed Technology in the Field; provided, however, that Sublicense Income shall not include any such consideration received by Auxilium from any such Sublicensee
in return for, as payment for or otherwise in respect of: (i) equity or debt of Auxilium (provided, however, that the exclusion contained in this sub-clause (i) shall not apply to transactions between Auxilium and its Affiliates), (ii) the
manufacture or supply of ingredients or products, (iii) the performance of services (including research and development services other than screening services performed on behalf of a Sublicensee) or other similar payments, (iv) reimbursement of
Auxilium’s out of pocket costs and expenses, including patent expenses, or (v) the sale of Auxilium in whole or in part. For the sake of clarity, Sublicense Income will not be reduced by, and Auxilium will be deemed to have received, any
amount(s) for which a Sublicensee is entitled to a deduction or setoff under the agreement between Auxilium and the Sublicensee and for which BTC is not responsible under the terms of this Agreement. For the sake of further clarity, Sublicense
Income will include any sublicense income received by Auxilium from its Sublicensee pursuant to a sub-sub license agreement entered into by Auxilium’s Sublicensee with a Person in the Territory. 

1.75 “Sublicensee” shall mean a Person to whom Auxilium grants any right or license to use the Licensed Technology to make, use or sell the Product in the Field in the Territory, including the Partner, the Japan Partner and
Partner II.

1.76 “Term” has the meaning set forth in Section 11.1(a) .

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EXECUTION VERSION

1.77 “Territory” shall mean all the countries and territories of the world.

1.78 “Third Party” shall mean any Person or other entity other than Auxilium, BTC or
their respective Affiliates.

1.79 “Valid Claim” shall mean a claim of an issued and unexpired patent, or a pending patent application, included within the Licensed Technology, which has not been held permanently revoked, unenforceable or invalid by a decision
of a governmental agency or court of competent jurisdiction, unappealable or unappealed within the time allowed for appeal and which has not been admitted to be invalid or unenforceable through reissue, disclaimer or otherwise. 

1.80 “Veterinary Trial” shall mean tests or studies in non-human animal subjects that are required to obtain, maintain or sustain Regulatory Approval for treatment of such non-human animal subjects in a country in the Territory. 

1.81 “Vial” shall mean a single dose unit of Product or Placebo, as specified in the provision in which such defined term is used, and in each case, diluent.

ARTICLE 2 

LICENSE AND OPTION

2.1 License Grant to Auxilium.

(a) Subject to the terms and conditions of this Agreement, on the Effective
Date, BTC hereby grants to Auxilium an exclusive license under the Licensed Technology to research, Develop, use, Commercialize, market, sell and distribute the Product in the Field in the Territory.

(b) Subject to the terms and conditions of this Agreement, BTC hereby grants to Auxilium (i) an exclusive right and license under the Licensed Technology to Manufacture or have Manufactured the Product (A) in the Field, (B) for Stage I Development
excluding in vitro research and Development subject to (B)(2) below, and (C) for any Auxilium Remaining Indication, and (ii) a non-exclusive right and license under the Licensed Technology to Manufacture or have Manufactured the Product for supply
to BTC (A) for in vitro Development and (B) for Stage II Development of Remaining Indications and Commercialization of Remaining Indications. Notwithstanding the foregoing, BTC may exercise its retained right to Manufacture only with respect to (A)
the Enzyme for purposes of (1) use as a reagent for tissue disassociation and (2) performing in vitro research and Development unless Product is supplied by Auxilium for such purposes in accordance with the terms hereof and (B) the Product for
purposes of (1) performing Development of any Remaining Indication and Commercialization of any Remaining Indication and (2) any Stage I Development that BTC conducts for Additional Indications if Auxilium fails to supply Product, diluent or Placebo
in accordance with Section 6.2 (provided that the conduct of any such Stage I Development shall be subject to the provisions of Section 3.1(b)(iii)) . Notwithstanding anything to the contrary contained in this Agreement, BTC shall not grant any
right or license under the Licensed Technology to any Third Party to
Manufacture the Enzyme or the Product; provided, however, that BTC may engage a Third Party to perform the permitted Manufacture for BTC’s account. 

9

EXECUTION VERSION

(c) The licenses granted to Auxilium under Sections 2.1(a) and 2.1(b) shall include the right to grant sublicenses (and in the case of Section 2.1(a), distribution rights); provided, however, that all such sublicenses shall contain terms and
conditions which are consistent with the terms and conditions contained in this Agreement.

2.2 Option to License Additional Indications.

(a) Development of Additional Indications for Products. The Parties shall
cooperate in good faith in generating ideas and concepts for Additional Indications for Products in accordance with the process set forth in Section 3.1. For the sake of clarity, tissue disassociation performed by BTC shall not be considered an
Additional Indication for purposes of this Agreement and shall not be subject to the process set forth in Section 3.1. 

(b) Option Grant. Subject to the terms and conditions of this Agreement, BTC hereby grants to Auxilium an exclusive option to an exclusive license to Products in the Territory for each Additional Indication on the same terms and conditions as
provided for Indications in the Field (each, an “Additional Indication Option”).

(c) Exercise Period; Exercise of Option. The period during which Auxilium may exercise an Additional Indication Option (the “Exercise Period”) shall commence on the date on which BTC submits a Phase II Clinical Trial report
to Auxilium for the Product for such Additional Indication and ends one hundred and twenty (120) days thereafter. BTC shall provide Auxilium with a copy of a Phase II Clinical Trial report and any additional data or results in its control. Auxilium
may exercise the Additional Indication Option at any time during the Exercise Period by delivering to BTC a written notice of exercise with regard to such Additional Indication (each, an “Exercised Indication”) that sets forth the
effective date of the exercise (the “Exercised Indication Date”), which must be within the Exercise Period. Upon receipt, BTC shall counter-sign the exercise notice which shall then be appended to and incorporated by reference into
this Agreement effective the Exercised Indication Date.

(d) Option for Cellulite. Notwithstanding the foregoing or anything to the contrary herein, Auxilium shall be responsible for the Stage I Development of Edematous fibrosclerotic panniculopathy, otherwise known as cellulite
(“Cellulite”), including for the costs associated with such Stage I Development in accordance with the protocols attached hereto (Schedule 2.2(d)) . BTC hereby grants Auxilium an exclusive license under the Licensed
Technology to research, Develop, Manufacture and use the Product for purposes of conducting such Stage I Development. Upon the earlier of (i) the initiation of Stage II Development activities with respect to Cellulite or (ii) the date which is one
hundred and twenty (120) days from the completion of the attached protocols for Cellulite, Auxilium shall pay BTC the amount of Five Hundred Thousand Dollars ($500,000) as a one-time license fee in satisfaction of Section 7.4(a) . The date of
payment by Auxilium to BTC of such amount shall be the Exercised Indication Date for Cellulite. If Auxilium fails to pay BTC such amount on or prior to such date due, then Cellulite shall become a Remaining Indication and such license with respect
to Cellulite granted pursuant to this Section 2.2(d) shall terminate. 

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EXECUTION VERSION

(e) License Grant Upon Exercise of Option. Effective on the Exercised Indication Date, the Field definition shall be amended and expanded to include the relevant Exercised Indication.

(f) Auxilium Remaining Indications. Auxilium shall have the right to Develop and Commercialize Auxilium Remaining Indications at its sole cost and expense. Upon notification to BTC of Auxilium’s intent to Develop and Commercialize an
Auxilium Remaining Indication, the Field definition shall be amended and expanded to include such Auxilium Remaining Indication.

2.3 Remaining Indications. BTC may offer Third Parties the right under the Licensed Technology to research, Develop, use, Commercialize, market, sell and distribute the Product for any Remaining Indication in the Auxilium Territory
(the “Remaining Indication Rights”), provided that, prior to executing a definitive agreement with a Third Party for one or more Remaining Indications, BTC must (a) provide Auxilium with a written summary of the material
terms of the proposed agreement (the “Offer Terms”), and (b) grant Auxilium an option, exercisable for seventy-five (75) days after Auxilium’s receipt of the written summary, to agree to equivalent terms, in which case the
Parties shall negotiate in good faith an exclusive license agreement on such terms as promptly as possible thereafter. In the event that Auxilium does not exercise an option to license a Remaining Indication within such seventy-five (75) day period,
the Remaining Indication Rights may be licensed to such Third Party on terms and conditions no less favorable to BTC than the Offer Terms; provided, that [**].

2.4 Transfer of BTC Know-How. Within forty-five (45) days of the Effective Date, BTC shall, or shall cause its Affiliates to, transfer to Auxilium all material Product Data relating to Dupuytren’s Disease and Peyronie’s Diseases,
including preclinical, clinical data, clinical trial protocols, study data tabulations, reports, the right of cross-reference and permission to use in Auxilium Regulatory Data and regulatory filings, investigator-generated data granted by the owners
of such data, etc., in reasonably satisfactory form. Promptly, but in no event more than thirty (30) days, after the Exercised Indication Date, BTC shall, or shall cause its Affiliates to, transfer to Auxilium all Product Data relating to such
Exercised Indication, in reasonably satisfactory form. 

2.5 Exclusivity. During the Term and any extension thereof, and for two years thereafter, neither BTC nor any of its Affiliates shall, except as otherwise set forth and provided in this Agreement, (a) directly or indirectly develop,
manufacture, market, sell, detail or promote any Competing Product or (b) encourage off-label use of a Competing Product that could affect labeled usage of the Product in the Field. In addition, in the event that BTC markets a BTC Product outside
the Field within a country in the Territory where Auxilium is promoting the Product within the Field, BTC shall promote the BTC Product under a trademark different from the Auxilium Trademark, and will not knowingly market, ship, distribute,
promote, sell or otherwise put into circulation the BTC Products within the Field in such country or in any other country within the Territory. In the event that BTC enters into any agreements with its distributors or wholesalers for the BTC
Products in a country in the Territory, it shall include in any and all said agreements appropriate provisions providing, to the extent not prohibited by Law, that the BTC Products must be distributed and sold solely outside the Field within such
country in the Territory. In the event that Auxilium enters into any agreements with its
distributors or wholesalers for the Product in the Field, it shall include in any and all said agreements appropriate provisions providing, to the extent not prohibited by Law, that the Product must be distributed and sold solely within the Field
within such country in the Territory. 

** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

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EXECUTION VERSION

 

ARTICLE 3 

PRODUCT DEVELOPMENT

3.1 Joint Development Committee.

(a) Formation. As soon as practicable after the Amendment Effective Date,
BTC and Auxilium will establish the JDC made up of two (2) representatives designated by each Party hereto to assist in coordinating scientific interactions and resolving potential disagreements between BTC and Auxilium during the course of the
Development of Product. The JDC Chair will be appointed by Auxilium from among the members of the committee designated by Auxilium.

	(b) Process.

(i) General. The process set forth in this Section 3.1(b) is intended to
help the Parties identify proposed Additional Indications for which there is reasonable probability of technical success and commercial potential, and to rule out areas where the probability is too low to justify the necessary resources. Given that
the investments in early stage development are relatively low, the criteria are inclusive and aim not to make false negative recommendations, rather than ruling out options too quickly. In preparation for the submission of a Development Plan to
pursue Development of an Additional Indication, subject to Auxilium’s decision-making authority as provided in Section 3.1(c), the Parties shall engage in the process set forth in Schedule 3.1 with respect to preparing and reviewing such
Development Plans; provided, however, that the Development Plan process set forth in this Section 3.1(b) shall not apply to (i) the protocols for Category I Additional Indications attached hereto as Schedule 2.2(d), Schedule 3.1(b)(1)
and Schedule 3.1(b)(2), (ii) tissue disassociation, or (iii) in vitro Development work conducted by BTC.

(ii) In Vitro Development by BTC. Prior to commencement of in vitro Development work by BTC, BTC shall submit to Auxilium a research proposal substantially in the form attached here to as Schedule 3.1(b)(3). Such
research proposals may be submitted by BTC to Auxilium on a rolling basis without regard to the quarterly JDC meetings. Auxilium shall have sixty (60) days to review and comment on such research proposal, but shall not have the right to veto such
research proposal. In the event that Auxilium presents any questions to BTC during the first forty-five (45) days of such sixty (60) day period, BTC shall respond to such questions within fourteen (14) days; provided, that, in the event that
BTC’s response takes longer than fourteen (14) days, such sixty (60) day period shall be extended by such number of days in excess of fourteen (14). Auxilium shall have the right, at its option, to supply Product to BTC for
such in vitro Development under Section 6.2, which right shall not be exercised so as to delay the prompt initiation of the research proposal following the end of such sixty (60) day review period. BTC agrees that it shall not use any such
Product for any purpose other than performance of research activities in accordance with such research proposal. In the event that Auxilium elects not to supply Product to BTC for such research proposal on a timely basis, BTC may proceed with such
in vitro Development proposal using Enzyme Manufactured by BTC.

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EXECUTION VERSION

(iii) Additional Indications. Prior to commencement of any Development activity by BTC with respect to an Additional Indication other than Category I Additional Indications, the Parties shall consult with respect to creation of a Development
Plan for such Additional Indication, and BTC shall submit such Development Plan for review by and approval of the JDC. The Parties will cooperate and assist each other in the preparation of such Development Plans, with each Party bearing its own
expense in connection therewith. For all Development activities, including the Category I Additional Indications but excluding in vitro Development for which Auxilium is not supplying Product, BTC shall purchase Product, diluent and Placebo
solely from Auxilium in accordance with Section 6.2, and BTC agrees that it shall not use any such Product, diluent or Placebo for any purpose other than performance of Development activities in accordance with the protocols in the case of Category
I Additional Indications and the Development Plans in the case of Category II Additional Indications and Category III Additional Indications approved by the JDC hereunder. The three (3) categories of Additional Indications are as follows: 

(A)Category I Additional Indications. The protocols for (1) Lipomas in canines or (2) Lipomas in humans (together, the “Category I Additional Indications”) have been pre-approved by the Parties as set forth on
Schedule 3.1(b)(1) and Schedule 3.1(b)(2), respectively. The Parties agree to work on a Development Plan for each of the Category I Additional Indications but the creation of such a Development Plan shall not be a condition to the
initiation or continuation of Development activity under such pre-approved protocols.

(B) Category II Additional Indications. Any such Development Plan for (1) keloids, (2) capsular contraction after breast augmentation, (3) arthrofibrosis following total joint replacement in humans and (4) equine suspensory ligament desmitis
(together, the “Category II Additional Indications”) shall be prepared by the Parties and submitted by BTC to the JDC in accordance with this Section 3.1; provided, that, notwithstanding any requirements to the contrary contained
herein, BTC shall have no obligation to submit a marketing study with respect to equine suspensory ligament desmitis. 

(C) Category III Additional Indications. Any such Development Plan for any Additional Indication other than Category I Additional Indications and Category II Additional Indications (“Category III Additional Indications”)
shall be prepared by the Parties and submitted by BTC to the JDC in accordance with this Section 3.1. 

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EXECUTION VERSION

(c) Decision Making.

(i) General. Each of BTC and Auxilium shall have one vote on the
JDC and, in the event of a deadlock with respect to any action, the vote of Auxilium, rendered after reasonable and open discussion among the members of the JDC, shall be final and controlling. For the sake of clarity, this Section 3.1(c) shall not
apply to activities conducted by BTC with respect to tissue disassociation or in vitro Development.

(ii) Additional Indications. In the event of a deadlock regarding the approval, or performance by BTC, of a Development Plan for an Additional Indication, such final and controlling vote of Auxilium may be exercised to withhold such approval
or to prohibit continued Development activities only as follows: 

(A) Category I Additional Indications.

(1) With respect to Category I Additional Indications, the protocols attached as Schedule 3.1(b)(1) and Schedule 3.1(b)(2) may be modified by BTC as may be reasonably necessary; provided, however, that any modification relating to
increased dosing, increased frequency of dosing, increased total dosing, change in route of administration, safety concerns raised by the FDA (including placement of the study on clinical hold) or additional immunogenicity tests requested by the
FDA, in each case shall be subject to additional JDC approval under Section 3.1(c)(i), which approval may only be withheld based on reasonable safety concerns (including scientific, technical or regulatory issues, but for the sake of clarity,
excluding any efficacy concerns or commercial concerns). In the event that Auxilium has any such safety concerns, it shall identify such concerns to BTC and provide BTC the opportunity to present additional information in response to such concerns
and Auxilium will give due consideration to such additional information; provided, however, that Auxilium shall not be required to modify its final and controlling vote. In the event that Auxilium raises in good faith safety concerns that BTC
determines in good faith are not reasonable, then BTC may invoke the dispute resolution procedures set forth in Section 13.2; provided, however, that the decision of the JDC shall govern unless and until such dispute resolution procedures have been
exhausted.

(2) Following the initiation of a study or trial for a Category I Additional Indication, the JDC shall have the right to stop such study or trial only in the following circumstances: In the case of a controlled study or trial, if the rate of serious
adverse events considered by the investigator to be definitely or probably related to Product is statistically significantly higher in the Product treatment group than the placebo group at an unadjusted alpha level of 0.05, the JDC may vote to
suspend such study or trial following a review of the clinical data because of safety concerns. In the event that the JDC suspends such study or trial, it shall identify such safety concerns to BTC and provide BTC the opportunity to present
additional information in response to such concerns and the JDC will give due consideration to such additional information; provided, however, that the JDC shall not be required to modify its final and controlling vote. The JDC shall have the right
following such due consideration of any additional information to either halt or restart such study or trial. In the case of an open label study or trial, if there are fifteen percent (15%) or more of subjects with one or more serious adverse events
considered by the investigator to be definitely or probably
related to Product, the JDC may vote to suspend such study or trial following a review of the clinical data because of safety concerns. In the event that the JDC suspends such study or trial, it shall identify such safety concerns to BTC and provide
BTC the opportunity to present additional information in response to such concerns and the JDC will give due consideration to such additional information; provided, however, that the JDC shall not be required to modify its final and controlling
vote. The JDC shall have the right following such due consideration of any additional information to either halt or restart such study or trial.

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EXECUTION VERSION

(3) If BTC completes such study or trial in accordance with the applicable protocols, subject to any permitted modifications in accordance with this Section 3.1(c)(ii)(A), BTC shall produce a final study report and provide such report to Auxilium
within one hundred and twenty (120) days after completion of such study or trial and such final study report shall qualify as a Phase II Clinical Trial report for purposes of Section 2.2(c) .

(B) Category II Additional Indications. With respect to Category II Additional Indications, Auxilium may exercise such final and controlling vote in the event that Auxilium has determined in good faith that there are reasonable safety
concerns (including scientific, technical or regulatory issues, but for sake of clarity, excluding efficacy concerns or commercial concerns). In the event that Auxilium has any such safety concerns, it shall identify such concerns to BTC and provide
BTC the opportunity to present additional information in response to such concerns and Auxilium will give due consideration to such additional information; provided, however, that Auxilium shall not be required to accept such additional information
and modify its final and controlling vote. In the event that Auxilium raises in good faith safety concerns that BTC determines in good faith are not reasonable, then BTC may invoke the dispute resolution procedures set forth in Section 13.2;
provided, however, that the decision of the JDC shall govern unless and until such dispute resolution procedures have been exhausted.

(C) Category III Additional Indications. Auxilium may exercise such final and controlling vote in the event that Auxilium has safety concerns (including scientific, technical or regulatory issues) or commercial concerns (including commercial
viability or adverse impact on the Product in the Field) with respect to any Development Plan relating to a Category III Additional Indication.

(d) Market Research. With respect to any Category III Additional Indication proposed by BTC, if the JDC determines that it would be beneficial to conduct market research with respect to a given Additional Indication, the Parties shall share
equally the Third Party costs associated with such market research up to an aggregate limit of Fifty Thousand Dollars ($50,000) (or Twenty-Five Thousand ($25,000) for each Party) per Indication; provided, that Auxilium shall be solely
responsible for any costs exceeding the aggregate limit with respect to such market research to the extent conducted by Auxilium or by a Third Party or BTC, in each case at Auxilium’s written request.

(e) Remaining Indications. BTC shall not take any action with respect to Remaining Indications that would be detrimental to the Product or damaging to Auxilium. 

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EXECUTION VERSION

Notwithstanding the foregoing, BTC will advise the JDC of all Development and Commercialization of Remaining Indications. The JDC shall have the right to discuss and comment on such activities but shall not have the final vote with respect to such
activities as they relate to Remaining Indications.  

(f) Quarterly Meetings. While a Product is under Development, the JDC shall meet formally at least quarterly, or with such other frequency, and at such time and location, as may be established by the JDC, for the following purposes, among
others: (i) to oversee and coordinate Development activities of the Parties for Products; (ii) to receive and review reports by the Parties with respect to each Party’s Development activities and in vitro Development activities; (iii) to
review generally the commercial activities for the Product (including for Remaining Indications); and (iv) to discuss matters relating to Patents related to the Product, including issues of inventorship and decisions relating to the filing,
prosecution and maintenance of such Patents, provided, however, that the JDC shall not have a final and controlling vote with respect to inventorship of Patents, which will be determined in accordance with applicable law as provided in Section 13.4.
Meetings of the JDC may be held in person or by teleconference, as may be determined by the JDC. 

3.2 Auxilium’s Stage II Development Activities.

(a) Dupuytren’s Disease, Peyronie’s Disease and Frozen Shoulder. Auxilium
has assumed all responsibility for (including financial responsibility), and has sole discretion over, all continuing Development of the Product for Dupuytren’s Disease, Peyronie’s Disease and Frozen Shoulder, including all Clinical Trials
listed on Schedule 3.2 and underway as of June 3, 2004 in regards to Dupuytren’s Disease and Peyronie’s Disease, and as of December 15, 2005 in regards to Frozen Shoulder. Auxilium shall not have financial responsibility for
Development Costs or any other costs incurred in connection with Development related to Dupuytren’s Disease, Peyronie’s Disease and Frozen Shoulder prior to June 3, 2004 in regards to Dupuytren’s Disease and Peyronie’s Disease,
and prior to December 15, 2005 in regards to Frozen Shoulder. Notwithstanding the foregoing or any other term or condition hereunder, BTC acknowledges and agrees that, as of the Amendment Effective Date, Auxilium has satisfied all of its diligence
obligations with respect to Frozen Shoulder. 

(b) Exercised Indications. On each Exercised Indication Date, Auxilium shall be entitled to assume responsibility for, and have sole discretion over, all continuing Development activities for the Product for each such Exercised Indication. In
furtherance of the foregoing, (i) Auxilium shall have one (1) year after the relevant Exercised Indication Date to initiate Stage II Development for any Exercised Indication for which the Clinical Trial(s) or Veterinary Trial(s) included in the
Phase II Clinical Trial report delivered pursuant to Section 2.2(c) relating to such Exercised Indication met the primary endpoint(s) with statistical significance (provided, however, that such obligations shall not be binding upon Auxilium to the
extent that BTC fails to deliver material Product Data to Auxilium in accordance with Section 2.4) and (ii) Auxilium shall have no obligation to initiate Stage II Development or to perform any other Development or Commercialization activity with
respect to any Exercised Indication for which the Clinical Trial(s) or Veterinary Trial(s) included in the Phase II Clinical Trial report delivered pursuant to Section 2.2(c) relating to such Exercised Indication did not meet the primary endpoint(s)
with statistical significance. 

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EXECUTION VERSION

(c) Cooperation. The Parties agree to cooperate with respect to the transfer of Development activities from BTC to Auxilium including transferring Clinical Trials and Veterinary Trials and making introductions of Auxilium to clinical and
veterinarian investigators and opinion leaders. 

(d) Stage II Development Costs.

(i) Dupuytren’s Disease, Peyronie’s Disease and Frozen Shoulder. Auxilium shall be responsible for all the Development Costs related to the Product for Dupuytren’s Disease, Peyronie’s Disease and Frozen Shoulder incurred
by Auxilium after June 3, 2004 in regards to Dupuytren’s Disease and Peyronie’s Disease, and after December 15, 2005 in regards to Frozen Shoulder; provided, however, that BTC shall continue to be responsible for all Development Costs
which are incurred prior to June 3, 2004 in regards to Dupuytren’s Disease and Peyronie’s Disease, and prior to December 15, 2005 in regards to Frozen Shoulder.

(ii) Other Exercised Indications. In the event Auxilium assumes responsibility for Stage II Development of the Product for an Exercised Indication, Auxilium shall be responsible for all Development Costs related to the Product for such
Exercised Indication and incurred by Auxilium after the Exercised Indication Date; provided, however, that BTC shall continue to be responsible for all Development Costs which are incurred prior to the Exercised Indication Date. 

(iii) Right of Set-Off. To the extent that Auxilium pays any Stage I Development Costs resulting from additional Stage I Development that is requested or required by a Regulatory Authority after assuming responsibility for Development of the
Product for any Indication, Auxilium shall be entitled to set-off the amount of such Stage I Development Costs against any amounts due to BTC pursuant to Section 7.1. For clarity, this Section 3.2(d)(iii) shall not apply to costs associated with
Stage I Development activities for Cellulite that are performed by Auxilium pursuant to Section 2.2(d), which costs shall be borne solely by Auxilium. 

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EXECUTION VERSION

3.3 Data and Records.

(a) Ownership of Data. Auxilium shall retain ownership of all Product Data,information and results related to Development activities for the Product, provided, however, that Auxilium hereby grants to BTC a right of reference with respect to Remaining Indications and permitted Stage I Development to the Regulatory Data
contained in Regulatory Approvals Controlled by Auxilium for the Product in the Field. For the sake of clarity, such right of reference shall include the right of BTC to reference any drug master file (DMF), any biologics license application (BLA),
any investigational new drug (IND) and any investigational new animal drug (INAD) for any Indication of the Product; provided, that such right of reference may only be exercised with respect to those Development activities of BTC that (i) are
approved by Auxilium or the JDC, including the pre-approved protocols attached hereto with respect to Lipomas in canines and Lipomas in humans, and (ii) require such right of reference as a matter of Law. Notwithstanding the foregoing, (a) if
Auxilium’s license rights to the Product terminate with respect to an Indication within the Field, Auxilium shall assign BTC its right, title and interest in and to the Product and Regulatory Data for that Indication, and (b) if Auxilium’s
license rights to a Product hereunder terminate entirely, Auxilium shall, assign BTC its right, title and interest in and to all such Product and Regulatory Data; provided, however, that Auxilium may maintain a copy of such Regulatory Data for legal
and archival purposes.

(b) Development Records. Each Party shall each maintain records in sufficient detail and in good scientific manner appropriate for patent purposes and as will properly reflect all work done and results achieved in the performance of
Development activities hereunder (including all Regulatory Data in the form required to be maintained under any applicable governmental regulations). Such records shall include books, records, reports, research notes, charts, graphs, comments,
computations, analyses, recordings, photographs, computer programs and documentation thereof, computer information storage means, samples of materials and other graphic or written data generated in connection with the Development activities. Subject
to the terms and conditions of Article 10 below, each Party shall provide the other the right to inspect (no more than once a year) such records, to the extent Controlled by such Party, upon reasonable request and during normal business hours, and
shall provide copies of all requested records, to the extent Controlled by such Party and reasonably required for the performance of the requesting Party’s obligations under this Agreement. For the sake of clarity, BTC shall have the right to
inspect and receive copies of records of any Sublicensee described in this Section 3.3(b) to the extent Controlled by Auxilium. The Parties agree that Auxilium will be the single point of contact with respect to records and audit rights provided
that BTC shall have the right to cause Auxilium to conduct an audit or request records on its behalf to the extent that Auxilium has not already requested such records or conducted such audit subject to Auxilium’s right to conduct such audit
once per calendar year. 

ARTICLE 4 

REGULATORY MATTERS

4.1 Efforts. Within twelve (12) months of filing for Regulatory Approval in any Major Market Country, Auxilium will file for Regulatory Approval in all the Major Market Countries; provided, that such obligation shall not apply with respect to
Frozen Shoulder or any other Exercised Indication in any country(ies) in the Partner Territory. Notwithstanding the
foregoing, if a different dossier is required for any such other Major Market Country(ies), Auxilium will exercise Commercially Reasonable Efforts to seek Regulatory Approval with respect to such country(ies). Auxilium may develop additional
formulations, dosage forms or delivery systems for the Product in the Field as may be commercially practicable at its own expense. For the sake of clarity, Remaining Indications shall not be subject to this Article 4; provided, however, that BTC
shall not conduct Development or Commercialization of Product in such Remaining Indications in a manner that jeopardizes Auxilium’s Development or Commercialization of Product in the Field. 

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EXECUTION VERSION

4.2 Regulatory Matters in the Territory. As between the Parties, Auxilium shall be responsible in the Territory for ensuring compliance with all regulatory requirements relating to the Product labeled for use in the Field (i.e., obtaining,
maintaining, and updating all required any Regulatory Approvals). Without limiting the foregoing, Auxilium shall (i) file all regulatory filings and supporting documentation; (ii) serve as the designated regulatory official for purposes of receiving
communications from the Regulatory Authority; and (iii) report any Adverse Drug Experience to Regulatory Authorities.

4.3 Ownership. All Regulatory Approvals relating to the Products labeled for use in the Field shall be the property of Auxilium, and held in the name of Auxilium, or its designee. BTC shall promptly take whatever steps necessary to transition
any existing regulatory filings to Auxilium. In accordance with this provision, BTC has transferred to Auxilium the Investigational New Drug relating to each of Dupuytren’s Disease, Peyronie’s Disease and Frozen Shoulder. 

4.4 Regulatory Interactions for Product.

(a) Communications with Regulatory Authority; Advice of Counsel.

(i) BTC shall not communicate with Regulatory Authorities, or take
any action regarding an investigation or a request by a Regulatory Authority with respect to a Product in the Field, except (i) with the prior written consent of Auxilium, or (ii) upon the advice of legal counsel that such communication is required
by Law. BTC shall cooperate with Auxilium and provide all reasonable assistance and take all actions reasonably requested by Auxilium that are necessary to comply with any Law applicable to a Product in the Field. If BTC is advised by its legal
counsel that it must communicate with any Regulatory Authority, then BTC shall promptly, but in no event more than two (2) Business Days after receipt of such advice of legal counsel, advise Auxilium of the same and provide Auxilium in advance with
a copy of any proposed written communication with such Regulatory Authority and comply with any and all reasonable requests of Auxilium concerning any such communication with such Regulatory Authority. 

(ii) In the event that BTC communicates with Regulatory Authorities regarding the Product outside of the Field (i.e., with respect to an Additional Indication or a Remaining Indication), Auxilium shall cooperate with BTC, at Auxilium’s own
cost, with respect thereto and Auxilium shall be provided an opportunity to participate in all such communications with respect to the Manufacture of the Product; provided, however,
that, in the event Auxilium has Manufactured and supplied such Product to BTC, then Auxilium shall be responsible for and conduct all such communications with respect to the Manufacture of the Product.

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EXECUTION VERSION

(b) Receipt of Correspondence; Inspections. Each Party shall promptly, but in any event within three (3) Business Days, (i) provide to the other copies of any material documents or correspondence sent to or received from any Regulatory
Authority related to Development activities for a Product and (ii) inform the other Party of any inspections, proposed regulatory actions, investigations or requests for information or a meeting by any Regulatory Authority with respect to a Product.
In the event BTC does not have advance notice of an inspection by a Regulatory Authority, it shall immediately notify Auxilium of such inspection and it shall cooperate with such Regulatory Authority.

(c) Recalls and Withdrawals. Auxilium shall have sole responsibility for and shall make all decisions with respect to any recall, market withdrawals or any other corrective action related to the Products labeled for use in the Field in the
Territory; provided however, (i) Auxilium shall immediately notify BTC of any decision to initiate a recall or withdrawal of such Product; (ii) all costs and expenses with respect to a recall, market withdrawal or other corrective action for such
Product shall be borne by Auxilium unless such recall, market withdrawal or other corrective action was due to the negligence, willful misconduct or material breach of this Agreement by BTC; and (iii) BTC shall immediately notify Auxilium of any
decision to initiate a recall or withdrawal of a Product outside of the Field. Each Party shall provide the other Party with recall information received by it in sufficient detail to allow the Parties to comply with Law.

(d) Notice. Each Party shall provide the other Party with notice, in a sufficiently timely basis to enable the other Party to comply in all material respects with Laws, of notification or other information which it receives (directly or
indirectly) from, any Regulatory Authority (and providing, as soon as reasonably possible, copies of any associated written requests) that (i) raises any material concerns regarding the safety or efficacy of a Product; (ii) indicates or suggests a
claim of a Third Party arising in connection with a Product, or (iii) is reasonably likely to lead to a recall or market withdrawal of a Product, provided that neither Party shall be obliged to disclose information in breach of any contractual
restriction which it could not reasonably have avoided or which disclosure would waive any legal privilege.

4.5 Inquiries, Adverse Events, etc. As between the Parties, Auxilium shall be responsible for the surveillance, receipt and evaluation of product complaints for Product labeled for use in the Field in the Territory and reporting to Regulatory
Authorities Adverse Drug Experiences for the Products in the Field. As between the Parties, BTC shall be responsible for the surveillance, receipt and evaluation of product complaints for Product labeled for use outside the Field and reporting to
Regulatory Authorities Adverse Drug Experiences for the Products outside the Field. Each Party shall ensure that, in the Development or Commercialization of the Product, it will record, investigate, summarize, notify, report and review all Adverse
Drug Experiences in accordance with Law. Each Party shall (i) adhere to all requirements of Laws which relate to the reporting and investigation of Adverse Drug Experiences, and (ii) keep the Parties informed of such events. 

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EXECUTION VERSION

(a) Each Party shall submit reports of all Adverse Drug Experiences associated with the use of the Product and other required safety information (e.g., PSUR’s or annual safety reports) to the Regulatory Authorities in accordance with Law. Each
Party shall submit a copy of each such report to the other Party in advance of such submission to permit the other Party to comply with legal requirements applicable to it and comment on such reports. 

(b) Each Party shall submit reports of all Adverse Drug Experiences associated with the use of Product for which Regulatory Approval has not been achieved and other required safety information to the Regulatory Authorities in accordance with Law.
Each Party shall submit a copy of each such report to the other Party in advance of such submission to permit the other Party to comply with legal requirements applicable to it and comment on such reports. 

4.6 Approval of Labeling and Promotional Materials. Auxilium shall be responsible to seek or obtain any necessary Regulatory Authority approvals of any label, labeling, package inserts or outserts, monographs and packaging, and promotional
materials for use in connection with the Products labeled for use in the Field and for determining whether the same requires approval from any Regulatory Authority. The Parties shall cooperate in such efforts to seek and obtain such approvals. 

4.7 Cooperation. The Parties shall cooperate to provide each other all reasonable assistance and take all actions reasonably requested that are necessary to comply with Laws, including safety updates, amendments, annual reports,
pharmacovigilance filings, investigator notifications, facility inspections, and certifications and maintenance and updates for regulatory filings and Regulatory Approvals. Unless otherwise provided under the terms of this Agreement, the Parties
will cooperate, communicate and provide reasonable assistance to each other with regard to all CMC matters related to the Product. 

ARTICLE 5 

COMMERCIALIZATION

5.1 Commercialization. Auxilium shall use Commercially Reasonable Efforts to Commercialize the Product in the Field in each country in the Territory in which Regulatory Approval of the Product has been obtained; provided, that [**]. Auxilium
shall be responsible for and have sole discretion over all aspects of Commercialization of the Product for use in the Field in the Territory.

5.2 Orders, Booking Sales. Auxilium shall have the sole right and responsibility for Product in the Field in each country in the Territory to (a) receive, accept, and fill orders for such Product, (b) control invoicing, order processing, and
collection of accounts receivable for such Product sales, and (c) record such Product sales in its books of account. If, for any reason, BTC receives orders for such Product, BTC shall forward such orders to Auxilium (or, if directed by Auxilium, to
Auxilium’s wholesalers) as soon as practicable. If any quantities of such Product are returned to BTC, BTC shall immediately notify Auxilium and ship them to the facility designated by Auxilium.

** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

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EXECUTION VERSION

ARTICLE 6 

MANUFACTURE AND SUPPLY

6.1 Development and Scale-Up. Auxilium shall, at its own cost and expense, develop the formulation and the finished dosage form and scale up the Manufacture for clinical supply of the Enzyme and the Product for each Indication for use in the
Field, including the lyophilized injection formulation, to be registered with Regulatory Authorities in accordance with Law and in sufficient time prior to anticipated commercial launch of a Product to provide for sufficient supply of Product for
use in the Field in the Territory. Auxilium will have the sole right and responsibility for selecting the finished dosage form and presentation for the Product in the Field. 

6.2 BTC Non-Commercial Supplies. BTC shall purchase from Auxilium, and Auxilium shall sell to BTC, such supplies of Product, diluent and Placebo as BTC may require for Clinical Trials and Veterinary Trials approved or pre-approved by the JDC,
as well as for in vitro Development to the extent Auxilium has agreed to supply Product, diluent and Placebo in accordance with Section 3.1(b)(ii) . From time to time after the Amendment Effective Date, BTC may place purchase orders for, and
Auxilium will use Commercially Reasonable Efforts to provide Vials of Product and Vials of Placebo for Clinical Trials and Veterinary Trials for delivery to a clinical site designated by BTC within sixty (60) days of BTC’s purchase order
request; provided, however, that if BTC requests that Auxilium deliver such Vials to such clinical site after such sixty (60) day period, then Auxilium shall make such delivery within two (2) Business Days after such request and notice by BTC to
make such delivery (or, in the case of in vitro Development, to BTC). There shall be no minimum quantity required for any such BTC purchase order and all Product, diluent and Placebo supplied by Auxilium to BTC shall have a minimum shelf life
sufficient for purposes of conducting such Clinical Trial or Veterinary Trial or in vitro  Development, as the case may be, including as necessary to address reasonable delays. Auxilium will supply such Product, Placebo and diluent at
Auxilium’s Cost of Goods plus [**] percent ([**]%); provided, that such clinical Product, Placebo and diluent supply price shall be no less than [**] dollars ($[**]) per Vial and no more than [**] dollars ($[**]) per Vial (the
“Clinical Product Supply Price”). For example, if Auxilium’s cost to Manufacture a Vial plus [**] percent ([**]%) is less than [**] dollars ($[**]), then such Clinical Product Supply Price shall be deemed to be [**] dollars
($[**]), and if Auxilium’s cost to Manufacture a Vial plus [**]% is greater than [**] dollars ($[**]), then such Clinical Product Supply Price shall be deemed to be [**] dollars ($[**]). Auxilium will supply Placebo at a cost of
[**] dollars ($[**]) per Vial (the “Placebo Supply Price”). Auxilium will invoice BTC for the Clinical Product Supply Price and Placebo Supply Price associated with each given shipment of such supplies, which invoices will be
payable by BTC within sixty (60) days of receipt.

6.3 BTC Commercial Supplies. In the event of a Remaining Indication that enters Stage II Development, the Parties will, unless BTC exercises its right to Manufacture Product for any Remaining Indications, negotiate in good faith to enter into
a commercial supply agreement with respect to such Product pursuant to which Auxilium shall supply, and BTC shall purchase, all of BTC’s requirements for such Product in accordance with forecasting and purchase order mechanisms to be set forth
therein and at Auxilium’s Cost of Goods plus [**]
percent ([**]%). In the event that BTC does not request to purchase all such requirements from Auxilium, BTC may Manufacture such Product itself or through a subcontractor. 

** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

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EXECUTION VERSION

ARTICLE 7 

PAYMENTS

7.1 Royalties.

(a) Royalty. Auxilium will pay BTC on a country-by-country and Product-by-Product basis a royalty payment for the Term equal to (i) [**] percent ([**]%) of Net Sales of Product in the Field in the Auxilium Territory, the Partner Territory and the Japan Territory, and (ii) [**] ([**]) of the royalty received by Auxilium
(it being understood that such royalty for purposes of this Section 7.1 shall be the royalty unaffected by any royalty adjustment, set off or credit provision in any sublicense agreement with such Partner II) from each Partner II on Net Sales of
Products in the Field for any country(ies) in the Partner II Territory, but such amount shall be capped at, and in no event shall BTC be entitled to receive more than, [**]percent ([**]%) of Net Sales of Products in the Field in any country(ies) in
the Partner II Territory. For the sake of clarity, no royalty shall be due under this Section 7.1(a) with respect to Net Sales of Products in any country in the Territory in the event that there is a sublicense agreement for the Product in effect in
such country and the Sublicensee in such country is, in accordance with the provisions of such sublicense agreement, no longer obligated to pay royalties to Auxilium (or its successor or assign if such royalties have been sold or otherwise
transferred by Auxilium) with respect to Net Sales of Products in such country, provided, that, in such event and where Auxilium receives from such Sublicensee consideration under such sublicense agreement in the form of a cross license or the
acquisition of intellectual property or other product development rights, then BTC shall be entitled to receive within thirty (30) Business Days following the receipt or deemed receipt by Auxilium of such consideration an amount calculated by
applying the applicable royalty provision of this Section 7.1(a) to the fair market value of such other consideration. For the further sake of clarity, the provisions of Section 7.1(a)(ii) shall not apply to any direct sales by Auxilium or its
Affiliates in the Partner II Territory. For the further sake of clarity, if the royalty paid by Partner II is reduced in accordance with the terms of the sublicense agreement because of competing product sales or payments of royalties to Third
Parties, then BTC shall bear a proportionate amount of such reduction. By way of example, if Auxilium receives a [**] percent ([**]%) royalty from Partner II, Auxilium would pay BTC a [**] percent ([**]%) royalty, but, if such royalty from Partner
II is reduced in accordance with the terms of the applicable sublicense agreement because of competing product sales or payments of royalties to Third Parties to [**] percent ([**]%), then Auxilium would pay BTC a [**] percent ([**]%) royalty. 

** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

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EXECUTION VERSION

(b) Royalty Rate Reductions. Notwithstanding the provisions of Section 7.1(a)(i) but only with respect to the countries in the Territories covered by Section 7.1(a)(i), any such royalty payable to BTC shall be reduced as follows: 

(i) Competing Product Sales. If a Competing Product is sold in a country in the Territory with a unit based market share of [**] percent ([**]%) or greater, then the royalty due for sales in that country in the Territory shall be reduced to:
[**] percent ([**]%) of Net Sales of Products in such country in the Territory covered by Section 7.1(a)(i) . 

(ii) Third Party Royalties. If the Manufacturing, Development or Commercialization of the Product by the Parties in accordance with this Agreement would, but for a license from a Third Party, infringe on any Patent owned or controlled by such
Third Party, and if there are any royalties or other payments owed by Auxilium to such Third Party pursuant to a license or other arrangement, then the royalty payable to BTC under this Agreement may be reduced by up to [**] percent ([**]%) of such
royalty to compensate for payments to such Third Parties but in no event shall the royalty rate payable to BTC be reduced by more than [**] percentage points; provided, that the royalty rate shall not be reduced below [**] in any case. Auxilium
hereby represents and warrants to BTC that, as of the Amendment Effective Date, to the best of its knowledge, information and belief, there are no such royalty or other payments due to Third Parties. 

(c) Payment of Royalties. Royalties under this Agreement shall be paid within thirty (30) days in the case of no sublicense and sixty (60) days in case of royalties received from a Sublicensee, following the last day of the calendar quarter
in which the royalties and other amounts are received or deemed received by Auxilium. 

(d) Reporting on Royalties. With respect to Auxilium Territory, Auxilium shall report to BTC Net Sales of Products on a country-by-country basis and where such information is available, on an Indication-by-Indication basis. With respect to
Partner Territory, Japan Territory and Partner II Territory, as the case may be, Auxilium shall use Commercially Reasonable Efforts to obtain Net Sales of Products on a country-by-country basis and where such information is available, on an
Indication-by-Indication basis. Such reporting shall be made (1) in the case of royalties in respect of Net Sales of Product in the first, second and third calendar quarters, on the date that is forty-five (45) days after the last day of each such
quarter, and (2) in the case of royalties in respect of Net Sales of Product in the fourth calendar quarter, on the date that is seventy-five (75) days after the last day of each such quarter. To the extent available, such reports shall contain
gross sales less any specifically allowable deductions on a line item by line item basis as provided under the defined term “Net Sales”. 

7.2 Additional Payment Related to Cost of Goods.

(a) In addition to the royalty payments to be made to BTC
under Section 7.1,
Auxilium shall pay to BTC an amount equal to (i) a [**] percent ([**]%) mark-up of Cost of Goods in respect of any sale of Product in the Field in the Auxilium Territory, the Partner Territory and the Japan Territory, and (ii) an amount equal to
[**] ([**]) of the mark-up of Cost of Goods received by Auxilium from each Partner II on Product in the Field for any country(ies)
in the Partner II Territory pursuant to a sublicense agreement, supply agreement or similar
arrangement then in effect, but such amount shall be capped at, and in no event shall BTC be
entitled to receive an amount equal to more than, a [**] percent ([**]%) mark-up of Cost of
 Goods in respect of any sale of Product in the Field in any country(ies) in the Partner II
Territory. 

** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

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** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED
SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION
PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST.
		
EXECUTION VERSION
	

                                       (b)
In the case (i) where Product is Manufactured by or on behalf of Auxilium
and sold by Partner in the Partner Territory, the Japan Partner in the Japan Territory or Partner II
in the Partner II Territory, the aforementioned mark-up shall be paid only once and shall be 
based on Auxilium’s Cost of Goods for sales in the Auxilium Territory unaffected by any cap in 
any sublicense agreement with a Sublicensee, and (ii) where Product is Manufactured by a 
Sublicensee the aforementioned mark-up shall be paid only once and shall be based on 
Sublicensee’s Cost of Goods for sales in such Sublicensee’s Territory.

(c)
The payment described in this Section 7.2 shall be paid within thirty (30)
days in the case of no Sublicensee and sixty (60) days in case of such payments received or
deemed received from a Sublicensee, in each case following the last day of the calendar quarter
in which such payments are received or deemed received by Auxilium. 

                                       (d)
With respect to Auxilium Territory, Auxilium shall report to BTC such
payments on a country-by-country basis and where such information is available, on an
Indication-by-Indication basis. With respect to Partner Territory, Japan Territory and Partner II
Territory, as the case may be, Auxilium shall use Commercially Reasonable Efforts to obtain
such payment information on a country-by-country basis and where such information is
available, on an Indication-by-Indication basis. Such reporting shall be made (1) in the case of
such payments in respect of Product in the first, second and third calendar quarters, on the date
that is forty-five (45) days after the last day of each such quarter, and (2) in the case of such
payments in respect of Product in the fourth calendar quarter, on the date that is seventy-five (75)
days after the last day of each such quarter. 

7.3 Milestone Payments by Auxilium.

(a) Amount of Milestone Payments.

	
#
	

Milestone
	
	

United States Dollars
	

	
1
	
	
The Effective Date
	
	
$2.5 million
	
	
 
	

	
2
	
	
The delivery to Auxilium of the Product Data
	
	
$2.5 million
	
	
 
	

	
 
	
	
relating to Dupuytren’s Disease and Peyronie’s
	
	
 
	
	
 
	

	
 
	
	
Disease in accordance with Section 2.4 of this
	
	
 
	
	
 
	

	
 
	
	
Agreement.
	
	
 
	
	
 
	

	
3
	
	
The one (1) year anniversary of the Effective Date
	
	
$3.0 million
	
	
 
	

	
4
	
	
Upon first of either NDA Acceptance or MAA
	
	
Dupuytren’s
	
	
$0.5 million
	

	
 
	
	
Acceptance for the following Indications on an
	
	
Disease
	
	
 
	

	
 
	
	
Indication by Indication basis:
	
	
Peyronie’s
	
	
$[**]
	

	
 
	
	
 
	
	
Disease
	
	
 
	

	
5
	
	
Receipt by Auxilium, its Affiliate or Sublicensee of
	
	
Dupuytren’s 

Disease
	
	
$1.0 million
	

	
 
	
	
first Regulatory Approval in the United States or
three or more of the United Kingdom, Spain, Germany, France or Italy with labeling approved
for the following Indications on an Indication by Indication basis:
	

Peyronie’s
Disease
	
	
  

$[**]
	

25

	
 	
 
	
** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED
SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION
PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST.
		
EXECUTION VERSION
	

(b) Timing of Milestone Payments. The Parties hereby acknowledge and agree that as of the Amendment Effective Date, Auxilium has satisfied its payment obligations to BTC for Milestones 1, 2 and 3. Auxilium has also satisfied its payment
obligations to BTC for Milestones 4 and 5 with respect to Dupuytren’s Disease. For milestones 4 and 5, payment shall be made within thirty (30) days after the occurrence of the event giving rise to a payment obligation hereunder. All payments
shall be made by wire transfer in United States Dollars to the credit of such bank account as may be designated, from time to time, by BTC in writing. 

7.4 Payments for Exercised Indications.

(a) Upon Exercise of Option. Within ten (10) Business Days of the inclusion
of an Exercised Indication in the Field in accordance with Section 2.2(c) and subject to Section 2.2(d), Auxilium shall make a one-time license fee payment to BTC on a per Indication basis in the amount of Five Hundred Thousand ($500,000).

(b) Upon Approval. Within ten (10) Business Days of receipt by Auxilium, its Affiliate or Sublicensee of the first Regulatory Approval from the FDA for an Exercised Indication, Auxilium shall make the following milestone payments to
BTC on a per Indication basis: 

	 	
    
Amount 
	

Labeling Approved for the following Indication

    
	 	
    [**] 
	[**] 

(c) The Parties hereby acknowledge and agree that as of the Amendment Effective Date, Auxilium has satisfied its payment obligations to BTC for the exercise of its option for Frozen Shoulder under Section 7.3(a) above. 

7.5 Payments Related to Sublicense Income. Within thirty (30) Business Days of receiving Sublicense Income, Auxilium shall make a payment to BTC in the following amount and shall provide to BTC a report showing the basis for the calculation
of such amount: 

(a) In the case of Sublicense Income from Partner, the Parties agree that Auxilium will remit eight and one half percent (8.5%) of the Sublicense Income received from Partner.

(b) In the case of Sublicense Income from the Japan Partner, the Parties agree that Auxilium will remit the following amounts: 

(i) with respect to milestones specifically related to Dupuytren’s Disease, [**] percent ([**]%) of the Sublicense Income;

(ii) with respect to milestones specifically related to Peyronie’s Disease, [**] percent ([**]%) of the Sublicense Income; and                                                         

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PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST.
		
EXECUTION VERSION
	

(iii) with respect to Sublicense Income related to sales based milestones, (1) [**] percent ([**]%) of such Sublicense Income if the only approved
indication in the Japan Territory is Dupuytren’s Disease, or (2) [**] percent ([**]%) of such Sublicense Income if the only approved indication in the Japan Territory is Peyronie’s Disease, or (3) a weighted annual average of the foregoing
based on the estimation of the Japan Partner with respect to the allocation of sales in the Japan Territory attributable to each such Indication. 

The Parties acknowledge and agree that the payments described in this sub-clause 7.5(b) are the only payments related to Sublicense Income in the Japan Territory that remain outstanding as of the Amendment Effective Date (i.e., upfront payments
received from Japan Partner have already been paid by Auxilium to BTC). For clarity, this Section 7.5(b) is without limitation of amounts due from Auxilium to BTC under Sections 7.1 and 7.2. 

(c) In the case of Sublicense Income from each Partner II, the Parties agree that Auxilium will remit the following amounts: 

(i) [**] percent ([**]%) of the Sublicense Income relating to Dupuytren’s Disease and/or Peyronie’s Disease; and 

(ii) with respect to each given Indication other than Dupuytren’s Disease and Peyronie’s Disease, (1) [**] percent ([**]%) of the Sublicense Income if Auxilium has not conducted a Clinical Trial or Veterinary Trial for Product in the
relevant Indication prior to the effective date of the agreement with a Sublicensee in the Partner II Territory; (2) [**] percent ([**]%) of the Sublicense Income if Auxilium has conducted a Clinical Trial or Veterinary Trial for Product in the
relevant Indication prior to the effective date of the agreement with a Sublicensee in the Partner II Territory sublicense but Regulatory Approval for Product in the relevant Indication has not been obtained prior to the effective date of the
agreement with a Sublicensee in the Partner II Territory; or (3) [**] percent ([**]%) of the Sublicense Income if Regulatory Approval for such Indication has been obtained prior to the effective date of the agreement with a Sublicensee in the
Partner II Territory;
provided, that any upfront payment that constitutes Sublicense Income included in a Sublicensee agreement involving multiple Indications shall be allocated on a proportionate basis among the multiple Indications. For example, if Auxilium licenses
(A) ten (10) Indications for the Product to a Third Party and one (1) such Indication is Dupuytren’s Disease, (B) two (2) such Indications are ones for which Auxilium has not conducted a Clinical Trial prior to such sublicense, (C) three (3)
such Indications are ones for which Auxilium has conducted a Veterinary Trial but Regulatory Approval has not been received prior to such sublicense, and (D) four (4) such Indications are ones for which Auxilium has received Regulatory Approval,
then BTC shall receive the sum of (W) [**] ([**]%) of [**] ([**]) of such upfront amount, (X) [**] percent ([**]%) of [**] ([**]) of such upfront amount, (Y) [**] percent ([**]%) of [**] ([**]) of such upfront amount and (Z) [**] percent ([**]%) of
[**] ([**]) of such upfront amount (which sum equals [**] ([**]%) of such upfront amount). 

7.6 Currency. All payments shall be payable in United States Dollars.

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EXECUTION VERSION

7.7 Books and Records. Auxilium agrees to maintain and retain, in accordance with generally accepted accounting practices, complete and accurate records showing all transactions and information relating to this Agreement for a period of three
(3) years from the date of entry to which they pertain. 

7.8 Audit Rights. Upon the written request of BTC and not more than once in each calendar year, Auxilium shall permit an independent certified public accounting firm (other than on a contingency fee basis) selected by BTC and acceptable to
Auxilium (which acceptance by Auxilium shall not be unreasonably withheld) to have access during normal business hours to such records of Auxilium as may be reasonably necessary to verify Auxilium’s compliance with the payment terms of Article
7 of this Agreement or any other payment required by Auxilium under this Agreement. The accounting firm shall enter into an acceptable and customary confidentiality agreement with Auxilium obligating the accounting firm to retain in confidence all
information of Auxilium which it obtains in performing such audits hereunder, and such audit shall be subject to Auxilium’s Third Party confidentiality obligations. Any audit under this Section 7.8 shall be at the expense of BTC, unless a
particular audit reveals an underpayment of five percent (5%) or more of the amount that should have been paid to BTC for the period audited, in which case, Auxilium shall bear the expense of such audit. The Parties agree that Auxilium will be the
single point of contact with respect to the audit rights provided in this Section 7.8 and that BTC shall have the right to cause Auxilium to conduct an audit on its behalf to the extent that Auxilium has not already conducted such audit subject to
Auxilium’s right to conduct such audit once per calendar year. 

7.9 Taxes. Auxilium shall be entitled to deduct from its payments to BTC the amount of any withholding taxes required to be withheld by Auxilium or its Affiliates or Sublicensees to the extent Auxilium or its Sublicensees pay to the
appropriate governmental authority on behalf of BTC such taxes. Auxilium shall deliver to BTC, upon BTC’s request, proof of payment of all such taxes together with copies of all relevant back up documentation evidencing such payment. Each Party
shall provide assistance to the other Party in seeking any benefits available to such Party with respect to government tax withholdings by any relevant law or double tax treaty. 

7.10 Interest. Any payments payable by either Party which are not paid on or before the date such payments are due under this Agreement (other than such payments which are the subject of a good faith dispute between the Parties) shall bear
interest at the prime rate of interest plus 1%, calculated on the number of days that payment is delinquent.

7.11 Blocked Payments. In the event that, by reason of Laws or regulations in any country, it becomes impossible or illegal for Auxilium or an Affiliate or Sublicensee of Auxilium, to transfer, or have transferred on its behalf, distribution
fees or other payments to BTC, Auxilium shall promptly notify BTC of the conditions preventing such transfer and such distribution fees or other payments shall be deposited in local currency in the relevant country to the credit of BTC in a
recognized banking institution designated by BTC or, if none is designated by BTC within a period of thirty (30) days, in a recognized banking institution selected by Auxilium or its Affiliate or Sublicensee, as the case may be, and identified in a
notice given to BTC. 

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EXECUTION VERSION

ARTICLE 8 

INTELLECTUAL PROPERTY

8.1 BTC Patentable Inventions and Know-How.

(a) Patent Prosecution.

(i) During the term of the Agreement, Auxilium shall, on behalf of
BTC and in the reasonable exercise of its commercial discretion, prepare, file, prosecute, maintain, renew and defend BTC Patents in the countries where such BTC Patents are filed as of the Effective Date and any new patents directly relating to the
Enzyme or Product. 

(ii) BTC shall provide such documentation and assistance as is necessary or reasonably useful to enable Auxilium to determine whether it wishes to prepare, file, prosecute, or maintain any proposed or existing BTC Patent, and, if Auxilium does not
intend to file for patent protection or does not wish to continue preparation, prosecution, or maintenance of a BTC Patent, then Auxilium shall give at least thirty (30) days advance notice to BTC of such decision, and in no event less than a
reasonable period of time for BTC to decide to undertake responsibility for such BTC Patent.

(A) In such case, BTC may elect at its sole discretion to continue preparing, filing, prosecuting, or maintaining the discontinued BTC Patent at its sole expense.

(B) Discontinuance may be elected on a country-by-country basis or for a patent application or patent series in total. 

(b) Cooperation. BTC will cooperate with Auxilium and provide Auxilium with all necessary assistance and documentation in connection with the filing, prosecution and maintenance of BTC Patents. Auxilium will consult with BTC and will keep BTC
informed of all matters relating to such filing, prosecution and maintenance of BTC Patents and Auxilium’s Patents covering an Enzyme; provided, however, that such obligation to inform shall not in any manner alter Auxilium’s rights under
this Article 8. Auxilium will provide BTC with copies of intended filings in advance and will consider BTC’s comments in good faith.

(c) Fees and Expenses.

(i) Fees and Expenses which Auxilium incurs while filing, prosecuting and/or maintaining BTC Patents as provided in section 8.1. (a) shall be handled as follows: 

(A) Auxilium shall pay one hundred percent (100%) of fees and expenses in connection with patents for the Product in the Field and/or in connection with Additional Indications for which Auxilium has exercised the Additional Indication Option pursuant
to Section 2.2; provided, however, that
fifty percent (50%) of such fees and expenses will be credited against future royalties payable by Auxilium on Net Sales of the Product. 

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EXECUTION VERSION

(B) In the event Auxilium declines to exercise the Additional Indication Option with respect to any Additional Indication and BTC either by itself or pursuant to an Agreement with a Third Party (a “Partner Agreement”) pursues such
Remaining Indication, BTC shall reimburse Auxilium for one hundred percent (100%) of fees and expenses in connection with the filing, prosecution and/or maintenance of all Patents pertaining to each such Remaining Indication as follows: 

(1) In the event BTC pursues any such Remaining Indication pursuant to a Partner Agreement, BTC shall reimburse Auxilium in full upon execution of such Partner Agreement. 

(2) In the event BTC pursues any such Remaining Indication itself, BTC shall reimburse Auxilium in full on the date BTC first initiates further development activity with respect to any such Additional Indication.

(3) Notwithstanding the foregoing, in the event that any such Patent Covers the Product in the Field as well as in the Remaining Indication, then BTC shall reimburse Auxilium on a pro-rata basis measured by the number of Remaining Indication(s)
covered by the Patent as compared with the number of Exercised Indication(s) (which, for the purposes hereof, shall include Dupuytren’s Disease and Peyronie’s Disease and any other Indications in the Field) covered by the Patent. For the
sake of clarity such cost-sharing shall be in addition to Auxilium’s right to credit its costs under Section 8.1(c)(i)(A) above.

8.2 Infringement Claims by Third Parties.

(a) Notice. If the manufacture, use or sale of the Product under the BTC
Patents results in a claim or a threatened claim by a Third Party against a Party hereto for patent infringement or for inducing or contributing to patent infringement (“Infringement Claim”), the Party first having notice of an
Infringement Claim shall promptly notify the other in writing. The notice shall set forth the facts of the Infringement Claim in reasonable detail.

(b) Third Party Licenses. In the event that practicing under the BTC Patents in connection with manufacture, use or sale of the Product in a country would infringe a Third Party Patent and a license to such Third Party Patent is available and
Auxilium in its sole discretion seeks such a license, the Parties agree: 

(i) Auxilium will be responsible for all costs associated with acquiring any Third Party license to the extent required for Auxilium to continue to make, use and sell the Product and the Enzyme, provided however, Auxilium may offset such costs
against the Royalty, with a minimum floor of [**] percent ([**]%) in accordance with Section 7.1(b)(ii), and prior to commercial launch, offset such costs against any milestones due to BTC pursuant to Article 7; and 

** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

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(ii) Auxilium will use Commercially Reasonable Efforts to obtain any such required licenses under the Third Party’s Patents with a right to sublicense to BTC and if requested by BTC will grant such sublicense, under reasonable sublicense terms
mutually acceptable to both BTC and Auxilium.

(c) Litigation. In the event of the institution of any suit by a Third Party against Auxilium as a result of Auxilium’s Development or Commercialization of the Product or the Enzyme, Auxilium, shall have the right but, not the
obligation, to defend such suit at its expense; BTC shall cooperate and assist Auxilium in any such litigation at Auxilium’s expense. In the event of the institution of any suit by a Third Party against BTC as a result of BTC’s Manufacture
of the Product or manufacture of the Enzyme, BTC shall have the right but, not the obligation, to defend such suit at its expense. Auxilium shall cooperate and assist BTC in any such litigation at BTC’s expense. For purposes of clarity,
notwithstanding anything to the contrary in Article 12, to the extent applicable, Auxilium will be entitled to seek indemnification from BTC for Losses arising in connection with such suit. 

8.3 Infringement Claims Against Third Parties.

(a) Cooperation. BTC and Auxilium each agree to take reasonable actions to
protect BTC Patents from infringement. If one Party brings any such action or proceeding, the second Party may be joined as a Party plaintiff if necessary for the action or proceeding to proceed and, in case of joining, the second Party agrees to
give the first Party reasonable assistance and authority to file and to prosecute such suit. 

(b) Notice. If any BTC Patents are infringed by a Third Party, the Party to this Agreement first having knowledge of such infringement, or knowledge of a reasonable probability of such infringement, shall promptly notify the other in writing.
The notice shall set forth the facts of such infringement in reasonable detail. 

(c) Institution of Proceedings. Auxilium shall have the primary right, but not the obligation, to institute, prosecute, and control with its own counsel at its own expense any action or proceeding with respect to infringement of the claims of
such BTC Patents and BTC shall have the right, but not the obligation at its own expense, to be represented in such action by its own counsel. 

(d) Failure to Institute Proceedings. If Auxilium fails to institute, prosecute, and control such action or prosecution and fails to do so within a period of one hundred twenty (120) days after receiving notice of the infringement, BTC shall
have the right to bring and control any such action by counsel of its own choice, and Auxilium shall have the right, at its own expense, to be represented in any such action by counsel of its own choice. 

(e) Division of Damages Award. Any recovery made in connection with such infringement claim shall be divided as follows: 

(i) the Party that initiated and prosecuted such action shall recoup all of its costs and expenses (including reasonable attorney’s fees) incurred in connection with such action, whether the recovery is by settlement or otherwise; 

31

EXECUTION VERSION

(ii) the other Party then shall, to the extent possible, recover its costs and expenses (including reasonable attorney’s fees) incurred in connection with such action; 

(iii) if BTC initiated and prosecuted the action, the amount of any recovery remaining shall be retained by BTC; and 

(iv) if Auxilium initiated and prosecuted the action, the amount of any recovery remaining shall be retained by Auxilium, except that BTC shall receive a portion equivalent to the amount it would have received in accordance with the terms of Section
7.1 as if such amount were Net Sales of Auxilium.

(f) Settlement. The Parties shall keep each other informed of the status of and of their respective activities regarding any litigation or settlement thereof concerning Product; provided, however, that no settlement or consent judgment or
other voluntary final disposition of a suit under this Section may be undertaken without the consent of the other Party if such settlement would require the other Party to be subject to an injunction or to make a monetary payment or would otherwise
adversely affect the other Party’s rights under this Agreement or the validity of BTC Patents. 

8.4 Notice of Certification. BTC and Auxilium each shall immediately give notice to the other of any certification filed under the “U.S. Drug Price Competition and Patent Term Restoration Act of 1984” (or its foreign equivalent)
claiming that a BTC Patent is invalid or that infringement will not arise from the manufacture, use or sale of any Product by a Third Party. 

(a) If Auxilium decides not to bring infringement proceedings against the entity making such a certification Auxilium shall give notice to BTC of its decision not to bring suit within twenty one (21) days after receipt of notice of such
certification. For clarity, if Auxilium does bring such infringement proceedings against the entity making such a certification the costs incurred by Auxilium in connection with such suit shall be creditable against milestone payments payable by
Auxilium in accordance with Article 7.

(b) BTC may then, but is not required to, bring suit against the Party that filed the certification. 

(c) Any suit by Auxilium or BTC shall either be in the name of Auxilium or in the name of BTC, or jointly in the name of Auxilium and BTC, as may be required by law. 

(d) For this purpose, the Party not bringing suit shall execute such legal papers necessary for the prosecution of such suit as may be reasonably requested by the Party bringing suit. 

8.5 Patent Term Extensions. As between Auxilium and BTC, Auxilium shall control the right to file for patent term extensions wherever applicable to BTC Patents covering Enzyme or Product. 

8.6 Trademarks.

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EXECUTION VERSION

(a) Each Party and its Affiliates shall retain all right, title and interest in and to its and their respective corporate names and logos. 

(b) Auxilium shall be solely responsible for selecting a trademark (the “Auxilium Trademark”) to use for each country in the Territory. The Product shall be promoted and sold, in accordance with the provisions of this Agreement, in
the Territory under the Auxilium Trademark. Auxilium (or its local Affiliates, as appropriate) shall own and retain all rights to Auxilium Trademark, and all goodwill associated therewith throughout the Territory. Auxilium shall also own rights to
any internet domain names incorporating the Auxilium Trademark or any variation or part of Auxilium Trademark as its URL address or any part of such address. 

ARTICLE 9 

REPRESENTATIONS AND WARRANTIES

9.1 BTC Represents and Warrants. BTC hereby represents and warrants to Auxilium that: 

(a) This Agreement has been duly executed and delivered by BTC and constitutes the valid and binding obligation of BTC, enforceable against BTC in accordance with its terms except as enforceability may be limited by bankruptcy, fraudulent
conveyance, insolvency, reorganization, moratorium and other laws relating to or affecting creditors’ rights generally and by general equitable principles. The execution, delivery and performance of this Agreement have been duly authorized by
all necessary action on the part of BTC, its officers and directors; 

(b) As of the Effective Date, BTC is the owner or licensee of BTC Patents and BTC Know How and all other rights necessary to make, use and sell all technology covered by the BTC Patents. BTC has the full right power and authority to grant the
licenses and other rights granted to Auxilium and the granting of the licenses and other rights to Auxilium hereunder does not violate any right known to BTC of any Third Party; 

(c) BTC represents that to the best of its knowledge, as of the Effective Date it is not aware that the development, manufacture, use or sale of the Enzyme or the Product pursuant to this Agreement may infringe or conflict with any Third Party right
or Patent, and BTC is not aware of any pending patent application that, if issued, would be infringed by the development, manufacture, use or sale of the Enzyme or the Product pursuant to this Agreement; 

(d) The execution, delivery and performance of this Agreement by BTC does not conflict with any agreement, instrument or understanding, oral or written, to which it is a Party or by which it may be bound, and, to the best of its knowledge, does not
violate any material law or regulation of any court, governmental body or administrative or other agency having authority over it; 

(e) BTC has disclosed to Auxilium all material information in its control pertaining to the suitability of Enzyme as a pharmaceutical candidate; 

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EXECUTION VERSION

(f) The Product has valid and effective Orphan Drug Designation under the applicable FDA statutes, rules or regulations, effective, May 23, 1996, and March 12, 1996. As of June 3, 2004, BTC had no reason to believe such Orphan Drug Designation would
be terminated prior to such date. 

(g) BTC is not currently a Party to, and during the Term will not enter into, any agreements, oral or written, that are inconsistent with its obligations under this Agreement; 

(h) BioSpecifics Technologies Corp. is duly organized and validly existing under the laws of the state of Delaware and its Affiliates are validly existing under the laws of the jurisdiction of their respective incorporation and have full legal power
and authority to enter into this Agreement; and 

(i) BTC is not subject to any order, decree or injunction by a court of competent jurisdiction which prevents or materially delays the consummation of the transactions contemplated by this Agreement. 

9.2 Auxilium Represents and Warrants. Auxilium hereby represents and warrants to BTC that: 

(a) The execution, delivery and performance of this Agreement by Auxilium does not conflict with any agreement, instrument or understanding, oral or written, to which it is a Party or by which it may be bound, and, to the best of its knowledge, does
not violate any material law or regulation of any court, governmental body or administrative or other agency having authority over it; 

(b) Auxilium is not currently a Party to, and during the Term will not enter into, any agreements, oral or written, that are inconsistent with its obligations under this Agreement; 

(c) Auxilium is duly organized and validly existing under the laws of the state of Delaware and has full legal power and authority to enter into this Agreement; and 

(d) Auxilium is not subject to any order, decree or injunction by a court of competent jurisdiction which prevents or materially delays the consummation of the transactions contemplated by this Agreement. 

9.3 Disclaimer of Warranties. THE LIMITED WARRANTIES CONTAINED IN THIS ARTICLE ARE THE SOLE WARRANTIES GIVEN BY THE PARTIES AND ARE MADE EXPRESSLY IN LIEU OF AND EXCLUDE ANY IMPLIED WARRANTIES OF MERCHANTABILITY, FITNESS FOR A PARTICULAR
PURPOSE, TITLE, INFRINGEMENT OR OTHERWISE, AND ALL OTHER EXPRESS OR IMPLIED REPRESENTATIONS AND WARRANTIES PROVIDED BY COMMON LAW, STATUTE OR OTHERWISE ARE HEREBY DISCLAIMED BY BOTH PARTIES. 

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EXECUTION VERSION

ARTICLE 10 

CONFIDENTIALITY

10.1 Confidentiality. During the Term, and for a period of five (5) years thereafter, each Party hereto will maintain in confidence all information disclosed, and reasonably believed by the other Party to be confidential whether orally or in
writing, by the other Party hereto (“Confidential Information”). Neither Party shall use, disclose or grant use of such Confidential Information except as required under this Agreement. Each Party shall use at least the same
standard of care as it uses to protect its own Confidential Information to ensure that its and its Affiliates’ employees, agents, consultants, and clinical investigators only make use of Confidential Information for the purpose of this
Agreement and do not disclose or make any unauthorized use of such Confidential Information. Each Party shall promptly notify the other upon discovery of any unauthorized use or disclosure of Confidential Information. Confidential Information shall
not include any information which and to the extent: 

(a) was already known to the receiving Party, other than under an obligation of confidentiality, at the time of disclosure by the other Party; 

(b) was generally available to the public or otherwise part of the public domain at the time of its disclosure to the other Party; 

(c) becomes generally available to the public or otherwise part of the public domain after its disclosure and other than through any act or omission of the receiving Party in breach of this Agreement; 

(d) was disclosed to the receiving Party, other than under an obligation of confidentiality, by a Third Party who had no obligation to the other Party not to disclose such information; or 

(e) was independently developed by the receiving Party without reference to the disclosure by the other Party, as documented by written records. 

10.2 Terms of Agreement. The Parties agree that the material financial terms of the Agreement shall be considered the Confidential Information of both Parties. 

10.3 Permitted Disclosure. Each Party may disclose the Confidential Information to the extent such disclosure is reasonably necessary in filing or prosecuting patent applications, prosecuting or defending litigation, or complying with any
applicable statute or governmental regulation provided such Party has given the disclosing Party prompt written notice in advance allowing it to limit such disclosure. In addition, either Party may disclose Confidential Information to its Affiliates
and to its Sublicensees; provided, however, in connection with any such disclosure the disclosing Party shall secure confidential treatment of such Confidential Information. 

10.4 Employee Obligations. The Parties shall undertake to ensure that all their employees who have access to Confidential Information of the other Party are under obligations of confidentiality fully consistent with those provided in this
Article. 

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EXECUTION VERSION

10.5 Publication. No Party may publish confidential or proprietary information of the other Party, without the consent of the other Party. The reviewing Party shall have thirty (30) days from receipt of the proposed oral disclosure or written
publication to provide comments or proposed changes to the disclosing Party. The review period may be extended for an additional two (2) months to permit the reviewing Party to file one or more patent applications as it deems appropriate. This
Section 10.5 shall be inapplicable to the publication of information presented in substantially the same form in which was previously published or disclosed to the public, and to any other disclosures which, on the advice of counsel, are required by
Law to be disclosed. In addition, BTC shall provide to Auxilium a thirty (30) day right to review any publication relating to BTC’s in vitro research and/or Development activities using the Product or the Enzyme, regardless of whether
such publication includes any confidential or proprietary information of Auxilium; provided, that, in the event such publication includes any confidential or proprietary information of Auxilium, such review period may be extended for an additional
two (2) months to permit Auxilium to file one or more patent applications as it deems appropriate. 

10.6 Prior Agreements. The obligations of confidentiality and nondisclosure set forth in this Section 10 supersede any and all prior and contemporaneous communications, representations, agreements or understandings, whether oral or written
concerning the subject matter of this Section 10.

ARTICLE 11 

TERM AND TERMINATION

11.1 Term.

(a) Term. Unless earlier terminated as provided herein, the Term shall
commence as of the Effective Date and shall remain in full force and effect on a Product by Product and country by country basis until the later of (i) the last to expire Valid Claim of a Patent that Covers such Product, (ii) the expiration of the
regulatory exclusivity period conveyed by Orphan Drug Designation with respect to such Product, and (iii) twelve (12) years from the Effective Date or June 3, 2016 (the “Term”). For the sake of clarity, with respect to clause (i) of
this Section 11.1(a), the term “Patent” shall include any Patents owned or Controlled by Auxilium or BTC and, notwithstanding the absence of a Valid Claim in the country of sale, the Term shall continue for so long as there is a Valid
Claim Covering the Product or the method of Manufacture in the country of Manufacture. 

(b) Accrued Obligations. Except where explicitly provided elsewhere herein, termination of this Agreement for any reason, or expiration of this Agreement, will not affect: (i) obligations, including the payment of any royalties or other sums
which have accrued as of the date of termination or expiration, and (ii) rights and obligations which, from the context thereof, are intended to survive termination or expiration of this Agreement. 

11.2 Termination for Insolvency. Either Party may terminate this Agreement immediately upon delivery of written notice to the other Party (a) upon the institution by or against the other Party of insolvency, receivership or bankruptcy
proceedings or any other proceedings for the settlement of the other Party's debts; provided, however with respect to
involuntary proceedings, that such proceedings are not dismissed within one hundred and twenty (120) days; (b) upon the other Party's making an assignment for the benefit of creditors; or (c) upon the other Party's dissolution or ceasing to do
business.

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EXECUTION VERSION

11.3 Material Breach. Either Party may terminate this Agreement upon ninety (90) days prior written notice to the other Party upon the material breach by the other Party of any of its obligations under this Agreement; provided, however, that
in the case of a material breach by Auxilium, BTC shall only have the right to terminate this Agreement on a territory-by-territory basis, such that BTC may only terminate this Agreement for (a) the Auxilium Territory as a result of a material
breach by Auxilium with respect to the Auxilium Territory and/or (b) the Partner Territory as a result of a material breach by Auxilium with respect to the Partner Territory and/or (c) the Partner II Territory as a result of a material breach by
Auxilium with respect to the Partner II Territory; provided, further, that such termination shall become effective only if the other Party shall fail to remedy or cure the breach within such ninety (90) day period. For the sake of clarity, neither
Party may claim material breach for conduct prior to the Amendment Effective Date, including conduct described in section 1.3 of the Settlement Agreement, regardless of whether such claim is released pursuant to the Settlement Agreement.
Notwithstanding the foregoing, (1) (i) in the event of a material breach by Auxilium with respect to the Partner Territory, BTC shall simultaneously provide the aforementioned written notice to Partner pursuant to Section 11.3 hereof and, (ii) in
the further event that Auxilium has not cured such breach in such ninety (90) day period, such Partner shall have the right to step-in and, within the ninety (90) day period, remedy or cure such breach for purposes of this Section 11.3; and (2) (i)
in the event of a material breach by Auxilium with respect to the Partner II Territory, BTC shall simultaneously provide the aforementioned written notice to Partner II pursuant to Section 11.3 hereof and, (ii) in the further event that Auxilium has
not cured such breach in such ninety (90) day period, such Partner II shall have the right to step-in and, within the ninety (90) day period, remedy or cure such breach for purposes of this Section 11.3. In the event that (3) (x) Partner is the
entity remedying or curing such breach, (y) Partner is not at fault with respect to such material breach, and (z) Partner so requests of BTC in writing in connection with such remedy or cure, BTC shall promptly grant to Partner a license under the
Licensed Technology and otherwise on the same economic and other terms as are contained in this Agreement covering the Partner Territory in substitution for Auxilium; or (4) (x) Partner II is the entity remedying or curing such breach, (y) Partner
II is not at fault with respect to such material breach, and (z) Partner II so requests of BTC in writing in connection with such remedy or cure, BTC shall promptly grant to Partner II a license under the Licensed Technology and otherwise on the
same economic and other terms as are contained in this Agreement covering the Partner II Territory in substitution for Auxilium. For clarity, in the case of a material breach with respect to the Auxilium Territory, any termination of this Agreement
shall be related solely to the Auxilium Territory and this Agreement shall remain in full force and effect with respect to the Partner Territory and the Partner II Territory.

11.4 Termination by Auxilium. Auxilium may terminate this Agreement in its entirety or on a country-by-country basis or on an Indication by Indication basis or on a Product by Product basis at any time upon ninety (90) days prior written
notice to BTC. 

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11.5 Effect Of Termination.

(a) Effect On License. Upon the expiration or earlier termination of this
Agreement, the rights licensed under this Agreement shall be treated as follows:

(i) Upon the expiration of the Term or the termination of this Agreement by Auxilium pursuant to Section 11.2 or Section 11.3, Auxilium shall have a fully paid-up, perpetual, irrevocable, royalty-free, transferable, worldwide, non-exclusive right
and license under the Licensed Technology existing as of the date of such expiration to make, have made, use, offer to sell, and sell the Product in the Territory; provided, however, that, in the event of termination of this Agreement by Auxilium
pursuant to Section 11.3, then such right and license shall be exclusive with respect to the ‘560 Patent (as defined in the Settlement Agreement) and its patent family, unless it has been determined by the Panel (as defined in the Settlement
Agreement) that Bo Yu and/or Thomas Wegman are joint inventors of the ‘560 Patent in which case such right and license shall remain non-exclusive notwithstanding this proviso; and

(ii) Upon termination of this Agreement by BTC pursuant to Section 11.2 or 11.3, or by Auxilium pursuant to Section 11.4, all rights to Product shall revert to BTC. 

(b) Ongoing Obligations.

(i) Upon expiration or termination of this Agreement for any reason,
each Party shall no later than thirty (30) days after such termination return to the other Party or destroy any Confidential Information disclosed by the other Party, except for one copy which may be retained in its confidential files. 

(ii) Upon termination of this Agreement by BTC pursuant to Sections 11.2 or 11.3 or by Auxilium pursuant to Section 11.4, Auxilium shall assign and deliver to BTC all Regulatory Data and information (including registration dossiers) obtained for or
in pursuing Regulatory Approvals, and all Regulatory Approvals (e.g., to BTC; designee in the Territory as permitted under the Law) for Product in the Territory received as of such termination date. 

11.6 Inventory. Notwithstanding the foregoing, upon early termination of this Agreement pursuant to Section 11.2, 11.3 or 11.4, Auxilium shall have the right to sell all remaining Product in its inventory within six (6) months after the date
of termination, but shall be bound to the royalty payments provided by Section 7.1 herein. Thereafter, Auxilium agrees to destroy any remaining supply of Product or return it to BTC at BTC’s request and direction.

ARTICLE 12 

INDEMNIFICATION

12.1 Auxilium. Auxilium shall defend BTC at Auxilium’s cost and expense, and will indemnify and hold BTC and their respective directors, officers, employees, consultants, contractors, representatives, and agents harmless from and against
any and all losses, costs, damages, fees, or expenses (including reasonable attorney’s fees and expenses) (“Losses”)
incurred in connection with or arising out of any Third Party claim (a “Third Party Claim”) directly relating to (i) any material breach by Auxilium of its representations or warranties or obligations pursuant to this Agreement,
(ii) any gross negligence or willful misconduct of Auxilium, its Affiliates, or their respective directors, officers, employees, contractors, consultants, agents, representatives, or Sublicensees in the exercise of any of Auxilium’ rights or
the performance of any of Auxilium’ obligations under this Agreement, and (iii) the handling, packaging, storage, or Commercialization by Auxilium or any of its Affiliates or Sublicensees of any Product in the Territory (excluding all
intellectual property infringement or related claims, which are covered in Section 12.2); provided that notwithstanding the foregoing, in all cases referred to in this Section 12.1, Auxilium shall have no liability to BTC for any Losses to the
extent that such Losses were caused by any item for which BTC is required to indemnify Auxilium pursuant to Section 12.2.

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12.2 BTC. BTC shall defend Auxilium and its Affiliates at BTC’s cost and expense, and will indemnify and hold Auxilium and its Affiliates and their respective directors, officers, employees, consultants, contractors, representatives, and
agents harmless from and against any and all Losses incurred in connection with or arising out of any Third Party Claim directly relating to (i) material breach by BTC of any of its representations, warranties or obligations pursuant to this
Agreement, (ii) gross negligence or willful misconduct of BTC in the exercise of any of its rights or the performance of any of its obligations under this Agreement, (iii) personal injury and other product liability resulting from BTC’s
Development, Manufacture, or Commercialization of any Product, (iv) intellectual property infringement or related claims, including any Third Party Claim and trade secret misappropriation liability relating to the Development, Manufacture, or
Commercialization of any Product, (v) any liability or other claims from the Manufacture, handling, packaging, storage, sale, or other disposition of any Product by BTC or any of its Affiliates, sublicensees or subcontractors, or (vi) any liability
or claims arising from Product Manufactured, or Enzyme manufactured, as the case may be, by BTC or any of its Affiliates or subcontractors; provided that notwithstanding the foregoing, in all cases referred to in this Section 12.2, BTC shall
have no liability to Auxilium for any Losses to the extent (and only to the extent) that such Losses were caused by any item for which Auxilium is required to indemnify BTC pursuant to Section 12.1.

12.3 Claims Procedures. Each Party entitled to be indemnified by the other Party (an “Indemnified Party”) pursuant to Section 12.1 or 12.2 hereof shall give notice to the other Party (an “Indemnifying Party”)
promptly after such Indemnified Party has actual knowledge of any threatened or asserted claim as to which indemnity may be sought, and shall permit the Indemnifying Party to assume the defense of any such claim or any litigation resulting
therefrom; provided:

(a) That counsel for the Indemnifying Party, who shall conduct the defense of such claim or any litigation resulting therefrom, shall be approved by the Indemnified Party (whose approval shall not unreasonably be withheld) and the Indemnified Party
may participate in such defense at such Party’s expense (unless (i) the employment of counsel by such Indemnified Party has been authorized by the Indemnifying Party; or (ii) the Indemnified Party shall have reasonably concluded that there may
be a conflict of interest between the Indemnifying Party and the Indemnified Party in the defense of such action, in each of which cases the Indemnifying Party shall pay the reasonable fees and expenses of one law firm serving
as counsel for the Indemnified Party, which law firm shall be subject to approval, not to be unreasonably withheld, by the Indemnifying Party). 

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EXECUTION VERSION

(b) The failure of any Indemnified Party to give notice as provided herein shall not relieve the Indemnifying Party of its obligations under this Agreement to the extent that the failure to give notice did not result in harm to the Indemnifying
Party. 

(c) No Indemnifying Party, in the defense of any such claim or litigation, shall, except with the approval of each Indemnified Party which approval shall not be unreasonably withheld, consent to entry of any judgment or enter into any settlement
which (i) would result in injunctive or other relief being imposed against the Indemnified Party; or (ii) does not include as an unconditional term thereof the giving by the claimant or plaintiff to such Indemnified Party of a release from all
liability in respect to such claim or litigation. 

(d) Each Indemnified Party shall furnish such information regarding itself or the claim in question as an Indemnifying Party may reasonably request in writing and shall be reasonably required in connection with the defense of such claim and
litigation resulting therefrom. 

12.4 Escrow. In the event of any Third Party Claim against Auxilium for which BTC is obligated to indemnify Auxilium in accordance with Section 12.2, Auxilium shall be entitled, until a final un-appealable decision has been rendered or a
settlement has been reached (a “Final Decision”), to pay an amount equal to fifty percent (50%) of all amounts due to BTC on Net Sales of Products (such aggregate amount, the “Escrowed Amount”) into an escrow account maintained
by a Third Party reasonably acceptable to BTC. To the extent that Auxilium incurs any Losses in connection with such Third Party Claim, an amount equal to the amount of any such Losses shall be distributed to Auxilium out of such escrow account,
with the remainder (if any) to be paid to BTC. In the event that the Escrowed Amount is less than the amount of such Losses, BTC shall pay the difference to Auxilium within thirty (30) days of such Final Decision. 

12.5 Insurance. During the Term, each of Auxilium and BTC shall maintain general liability and product liability insurance in the following amounts: (i) at all times prior to approval of a NDA for a Product, $3,000,000 per occurrence, and
(ii) at all times after approval of a NDA for a Product, $5,000,000.

12.6 Compliance. The Parties shall comply fully with all Laws and regulations in connection with their respective activities under this Agreement. 

ARTICLE 13 

MISCELLANEOUS PROVISIONS

13.1 Amendment Effective Date. Upon the Effective Date (as defined in the Settlement Agreement) this Agreement shall become effective and enforceable (the “Amendment Effective Date”). Upon the Amendment Effective Date the
Parties shall issue the press release set forth on Schedule 13.1. 

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EXECUTION VERSION

13.2 Dispute Resolution. In the event of any controversy or claim between the Parties arising out of relating to or in connection with any provision of this Agreement, or the rights or obligations hereunder, the Parties shall try to settle
their differences amicably between themselves through good faith negotiations by submitting such controversy or claim to the senior management of the respective Parties for resolution. If they are unable to resolve such controversy or claim within
thirty (30) days of initiating such negotiations, the Parties may institute litigation in any court of competent jurisdiction unless they have mutually agreed on some other form of dispute resolution. Such dispute resolution procedures shall not
limit a court from granting a temporary restraining order or a preliminary injunction in order to preserve the status quo of the Parties pending litigation or any other mutually agreed dispute resolution mechanism or to protect a Party’s
intellectual property or confidential or proprietary information.

13.3 Construction. Unless the context of this Agreement clearly requires otherwise, (a) references to the plural include the singular, the singular the plural, the part the whole, (b) references to any gender include all genders, (c)
“or” has the inclusive meaning frequently identified with the phrase “and/or,” (d) “including” has the inclusive meaning frequently identified with the phrase “including but not limited to” or
“including”, and (e) references to “hereunder” or “herein” relate to this Agreement. The section and other headings contained in this Agreement are for reference purposes only and shall not control or affect the
construction of this Agreement or the interpretation thereof in any respect. Section, subsection, and Schedule references are to this Agreement unless otherwise specified. Each accounting term used herein that is not specifically defined herein
shall have the meaning given to it under GAAP. 

13.4 Governing Law; Jurisdiction. This Agreement shall be construed and the respective rights of the Parties determined according to the substantive laws of the State of New York notwithstanding the provisions governing conflict of laws under
such New York law to the contrary, except matters of intellectual property law which shall be determined in accordance with the intellectual property laws relevant to the intellectual property in question. 

13.5 Post-Closing Access to Information. BTC shall afford to representatives of Auxilium reasonable access to offices, plants, properties, books and records of BTC relating to the Product, during normal business hours, in order that Auxilium
may have an opportunity to make such reasonable investigations as it desires with respect to Product. At all times after the Effective Date, each Party will permit the other Party and its representatives (including its counsel and auditors) during
normal business hours, for a proper purpose to have reasonable access to and examine and make copies of, at the expense of the copying Party, all books, records, files and documents in its possession which relate to the Product. 

13.6 Section 365(n) of the Bankruptcy Code. All rights and licenses granted under or pursuant to any section of this Agreement are, and shall otherwise be deemed to be, for purposes of Section 365(n) of the Bankruptcy Code, licenses of rights
to “intellectual property” as defined under Section 101(35A) of the Bankruptcy Code. The Parties shall retain and may fully exercise all of their respective rights and elections under section 365(n) of the Bankruptcy Code. 

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EXECUTION VERSION

13.7 Waiver. The failure on the part of Auxilium or BTC to exercise or enforce any rights conferred upon it hereunder shall not be deemed to be a waiver of any such rights nor operate to bar the exercise or enforcement thereof at any time or
times thereafter. The observance of any Term may be waived (either generally or in a particular instance and either retroactively or prospectively) by the Party entitled to enforce such term, but any such waiver shall be effective only if in writing
signed by the Party against whom such waiver is to be asserted. 

13.8 Force Majeure. Neither Party shall be held liable or responsible to the other Party nor be deemed to have defaulted under or breached this Agreement for failure or delay in fulfilling or performing any Term, other than an obligation to
make a payment, when such failure or delay is caused by or results from fire, floods, embargoes, government regulations, prohibitions or interventions, war, acts of war (whether war be declared or not), insurrections, riots, civil commotions,
strikes, lockouts, acts of God, or any other cause beyond the reasonable control of the affected Party. 

13.9 Severability. It is the intention of the Parties to comply with all Laws domestic or foreign in connection with the performance of its obligations hereunder. In the event that any provision of this Agreement, or any part hereof, is found
invalid or unenforceable, the remainder of this Agreement will be binding on the Parties hereto, and will be construed as if the invalid or unenforceable provision or part thereof had been deleted, and the Agreement shall be deemed modified to the
extent necessary to render the surviving provisions enforceable to the fullest extent permitted by law. 

13.10 Government Acts. In the event that any act, regulation, directive, or law of a government, including its departments, agencies or courts, should make impossible or prohibit, restrain, modify or limit any material act or obligation of
Auxilium or BTC under this Agreement, the Party, if any, not so affected shall have the right, at its option, to suspend or terminate this Agreement as to such country, if good faith negotiations between the Parties to make such modifications to
this Agreement as may be necessary to fairly address the impact thereof, after a reasonable period of time are not successful in producing mutually acceptable modifications to this Agreement. 

13.11 Assignment. This Agreement may not be assigned or otherwise transferred by either Party without the prior written consent of the other Party; provided, however, that either Party may assign this Agreement, without the consent of the
other Party, in connection with the transfer or sale of all or substantially all of its assets or business or in the event of its merger or consolidation with another company. In all cases the assigning Party shall provide the other Party with
prompt notice of any such assignment. Any purported assignment in contravention of this Section shall, at the option of the nonassigning Party, be null and void and of no effect. No assignment shall release either Party from responsibility for the
performance of any accrued obligation of such Party hereunder.

13.12 Counterparts. This Agreement may be executed in duplicate, both of which shall be deemed to be originals, and both of which shall constitute one and the same Agreement. 

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EXECUTION VERSION

13.13 No Agency. Nothing herein contained shall be deemed to create an agency, joint venture, amalgamation, partnership or similar relationship between BTC and Auxilium. Notwithstanding any of the provisions of this Agreement, neither Party
shall at any time enter into, incur, or hold itself out to third Parties as having authority to enter into or incur, on behalf of the other Party, any commitment, expense, or liability whatsoever, and all contracts, expenses and liabilities
undertaken or incurred by one Party in connection with or relating to the development, manufacture or sale of Enzymes or Product shall be undertaken, incurred or paid exclusively by that Party, and not as an agent or representative of the other
Party. 

13.14 Notice. All communications between the Parties with respect to any of the provisions of this Agreement will be sent to the addresses set out below, or to other addresses as designated by one Party to the other by notice pursuant hereto,
by internationally recognized courier or by prepaid certified, air mail (which shall be deemed received by the other Party on the seventh business day following deposit in the mails), or by facsimile transmission or other electronic means of
communication (which shall be deemed received when transmitted), with confirmation by letter given by the close of business on or before the next following business day: 

If to BTC, at: 

Biospecifics Technologies Corp. 

35 Wilbur Street 

Lynbrook, New York 11563 

Attn: Thomas Wegman, President

with a copy to:

Bingham McCutchen LLP 

2020 K Street NW 

Washington, DC 20006 

Attn.: Carl A. Valenstein, Esq.

If to Auxilium at: 

Auxilium Pharmaceuticals Inc. 

40 Valley Stream Parkway 

Malvern, PA 19355 

Attn: Armando Anido, Chief Executive Officer and President

with a copy to:

Morgan, Lewis & Bockius LLP

1701 Market Street 

Philadelphia, PA 19103 

Attn: Michael N. Peterson 

If to Partner at:

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EXECUTION VERSION

Pfizer Inc. 

235 East 42nd Street 

New York, New York 10017-5755 

Attention: Senior Vice President and Associate General Counsel, Business 

Transaction 

Fax: 1-212-573-0768 

with a copy to:

Pfizer Inc. 

235 East 42nd Street 

New York, New York 10017-5755

Attention: General Counsel 

Fax: 1-212-808-8924 

For purposes of Section 11.3, from time-to-time, Auxilium shall provide appropriate contact information for each Partner II.

13.15 Headings. The paragraph headings are for convenience only and will not be deemed to affect in any way the language of the provisions to which they refer. 

13.16 Assurances. Neither Party will take any action, or fail to act in a manner, which would prejudice the rights intended to be granted to the other Party pursuant to this Agreement. 

13.17 Entire Agreement. This Agreement and the Settlement Agreement (together with all exhibits and schedules thereto) contain the entire understanding of the Parties relating to the matters referred to herein and therein, and supersedes all
prior agreements, understandings or arrangements between the Parties with respect thereto, whether oral or written, and may only be amended by a written document, duly executed on behalf of the respective Parties. 

[Signature Page Follows]

 

 

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EXECUTION VERSION

IN WITNESS WHEREOF, the Parties hereto have caused this Agreement to be executed by their duly authorized representatives as of the date first written above. 

AUXILIUM PHARMACEUTICALS, INC.

	
By:
		
/s/ Armando Anido
	
	
 
		
Name:
		
Armando Anido
	
	
 
		
Title:
		
Chief Executive Officer
	

BIOSPECIFICS TECHNOLOGIES CORP.

	
By:
		
/s/ Thomas L. Wegman
	
	
 
		
Name:
		
Thomas L. Wegman
	
	
 
		
Title:
		
President
	

[Signature Page to Second Amended and Restated Development and License Agreement]

 

 

 

Schedule 1.9

 BTC Patents

Title: Methods for Treating Adhesive Capsulitis 

	
Country
		
Sub Case
		
Case Type
		
Status
		
Application Number
		
Filing Date
		
Patent Number
		
Issue Date
		
Expiration 
	
	
 
		
 
		
 
		
 
		
 
		
 
		
 
		
 
		
Date 
	
	
Australia
		
 
		
        PCT
		
Granted
		
2006206393
		
19-Jan-2006
		
2006206393
		
22-Jul-2010
		
19-Jan-2026 
	
	
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Korea, Republic of
		
 
		
        PCT
		
Granted
		
2007-7018990
		
19-Jan-2006
		
10-0989267
		
14-Oct-2010
		
19-Jan-2026 
	
	
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New Zealand
		
 
		
        PCT
		
Granted
		
556160
		
19-Jan-2006
		
556160
		
11-Mar-2010
		
19-Jan-2026 
	
	
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South Africa
		
 
		
        PCT
		
Granted
		
2007/05931
		
19-Jan-2006
		
2007/05931
		
30-Jul-2008
		
19-Jan-2026 
	
	
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** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION
PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

Title: Compositions And Methods For Treating Collagen-Mediated
Diseases

 	
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        Sub Case
		
Case Type
		
Status
		
Application Number
		
Filing Date
		
Patent Number
		
Issue Date
		
Expiration
	
	
 
		
 
		
 
		
 
		
 
		
 
		
 
		
 
		
Date
	
	
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Patent Cooperation Treaty
		
 
		
        ORD
		
Natl Proc
		
US07/02654
		
30-Jan-2007
		
 
		
 
		
 
	
	
South Africa
		
 
		
        PCT
		
Granted
		
2008/07049
		
30-Jan-2007
		
2008/07049
		
 28-Jul-2010 
		
 30-Jan-2027
	
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United States of America
		
                    PRO
		
        Expired
		
60/763,470
		
30-Jan-2006
		
 
		
 
		
  30-Jan-2007
		
  
	
United States of America
		
                    1
		
        PRO
		
Expired
		
60/784,135
		
20-Mar-2006
		
 
		
 
		
 20-Mar-2007
	
	
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** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

	
Country
		
Sub Case
		
Case Type
		
Status
		
Application Number
		
Filing Date
		
Patent Number
		
Issue Date
		
Expiration
	
	
 
		
 
		
 
		
 
		
 
		
 
		
 
		
 
		
Date
	
	
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United States of America
		
  2
		
        ORD
		
Granted
		
11/699,302
		
29-Jan-2007
		
7,811,560
		
12-Oct-2010
		
12-Jul-2028
	
	
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Title: Amelioration Of Dupuytren's Disease

	
Country
		
Sub Case
		
Case Type
		
Status
		
Application Number
		
Filing Date
		
Patent Number
		
Issue Date
		
Expiration
	
	
 
		
 
		
 
		
 
		
 
		
 
		
 
		
 
		
Date
	
	
Australia
		
 
		
        ORD
		
Granted
		
199859661
		
26-Mar-1998
		
733208
		
10-May-2001
		
26-Mar-2018
	
	
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France
		
 
		
        ORD
		
Granted
		
98/03320
		
18-Mar-1998
		
2772273
		
18-Jun-1999
		
18-Mar-2018
	
	
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Sweden
		
 
		
        ORD
		
Granted
		
9800806-3
		
12-Mar-1998
		
522723
		
02-Mar-2004
		
12-Mar-2018
	
	
United Kingdom
		
 
		
        ORD
		
Granted
		
9805050.3
		
11-Mar-1998
		
2323530
		
10-Oct-2001
		
11-Mar-2018
	
	
United States of America
		
 
		
        ORD
		
Granted
		
08/826,015
		
27-Mar-1997
		
6,086,872
		
11-Jul-2000
		
22-Aug-2014
	
	
United States of America
		
REI
		
        REI
		
Granted
		
11/094,753
		
30-Mar-2005
		
RE39,941
		
18-Dec-2007
		
 
	

** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION
PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

Title: Methods For Treating Cellulite

	
Country
		
Sub Case
		
Case Type
		
Status
		
Application Number
		
Filing Date
		
Patent Number
		
Issue Date
		
Expiration
	
	
 
		
 
		
 
		
 
		
 
		
 
		
 
		
 
		
Date
	
	
Australia
		
          1
		
        PCT
		
Granted
		
2007221225
		
22-Feb-2007
		
2007221225
		
27-May-2010
		
22-Feb-2027
	
	
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South Africa
		
          1
		
        PCT
		
Granted
		
2008/07221
		
22-Feb-2007
		
2008/07221
		
29-Jul-2009
		
22-Feb-2027
	
	
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** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION
PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

Title: Reduction of Adipose Tissue

	
Country
		
 Sub Case
		
Case Type
		
Status
		
Application Number
		
Filing Date
		
Patent Number
		
Issue Date
		
Expiration Date 
	
	
Canada
		
 
		
        ORD
		
Granted
		
2,165,271
		
14-Dec-1995
		
2,165,271
		
29-Jun-2010
		
14-Dec-2015 
	
	
European Patent Convention
		
 
		
        ORD
		
Granted
		
95309116.2
		
14-Dec-1995
		
0721781
		
06-Mar-2002
		
14-Dec-2015 
	
	
Germany
		
 
		
        EPC
		
Granted
		
69525728.5
		
14-Dec-1995
		
0721781
		
06-Mar-2002
		
14-Dec-2015 
	
	
United Kingdom
		
 
		
        EPC
		
Granted
		
95309116.2
		
14-Dec-1995
		
0721781
		
06-Mar-2002
		
14-Dec-2015 
	
	
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United States of America
		
 3
		
        CIP
		
Granted
		
10/172,601
		
14-Jun-2002
		
6,958,150
		
25-Oct-2005
		
15-Dec-2014 
	
	
United States of America
		
 4
		
        CON
		
Granted
		
11/237,543
		
28-Sep-2005
		
7,824,673
		
02-Nov-2010
		
20-Dec-2016 
	
	
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Title: Amelioration of Peyronie's Disease 

	
Country
		
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Case Type
		
Status
		
Application Number
		
Filing Date
		
Patent Number
		
Issue Date
		
Expiration Date 
	
	
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France
		
 
		
        ORD
		
Granted
		
06863
		
29-May-2000
		
06863
		
30-Apr-2002
		
29-May-2020 
	
	
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Ireland
		
 
		
        ORD
		
Granted
		
2000/0402
		
23-May-2000
		
84130
		
02-Aug-2006
		
23-May-2020 
	
	
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United Kingdom
		
 
		
        ORD
		
Granted
		
0011969.3
		
19-May-2000
		
2,352,173
		
10-Nov-2004
		
19-May-2020 
	
	
United States of America
		
 
		
        ORD
		
Granted
		
09/325,224
		
03-Jun-1999
		
6,022,539
		
08-Feb-2000
		
03-Jun-2019 
	

** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

Title: High Dosage Topical Forms of Collagenase

 	
Country
		
      Sub Case
		
Case Type
		
Status
		
Application Number
		
Filing Date
		
Patent Number
		
Issue Date
		
Expiration Date 
	
	
European Patent Convention
		
 
		
 PCT
		
Granted
		
92310008.5
		
02-Nov-1992
		
0543521
		
06-May-1999
		
02-Nov-2012 
	
	
France
		
 
		
 EPC
		
Granted
		
0543521
		
02-Nov-1992
		
0543521
		
06-May-1999
		
02-Nov-2012 
	
	
Germany
		
 
		
 EPC
		
Granted
		
92310008.5
		
02-Nov-1992
		
0543521
		
06-May-1999
		
02-Nov-2012 
	
	
Italy
		
 
		
 EPC
		
Granted
		
0543521
		
02-Nov-1992
		
0543521
		
06-May-1999
		
02-Nov-2012 
	
	
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Spain
		
 
		
 EPC
		
Granted
		
0543521
		
02-Nov-1992
		
0543521
		
06-May-1999
		
02-Nov-2012 
	
	
United Kingdom
		
 
		
  EPC
		
Granted
		
0543521
		
02-Nov-1992
		
0543521
		
06-May-1999
		
02-Nov-2012 
	
	
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United States of America
		
 1
		
 CIP
		
Granted
		
07/963,995
		
29-Oct-1992
		
5,393,792
		
28-Feb-1995
		
28-Feb-2012 
	
	
United States of America
		
 2
		
 CIP
		
Granted
		
08/157,935
		
24-Nov-1993
		
5,422,103
		
06-Jun-1995
		
06-Jun-2012 
	

Title:Clositridial Fermentation with Hydrolyzed Fish Gelatin 

	
Country
		
      Sub Case
		
Case Type
		
Status
		
Application Number
		
Filing Date
		
Patent Number
		
Issue Date
		
Expiration Date 
	
	
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** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

Schedule 1.23

Cost of Goods

The cost of Enzyme or a Product manufactured by Auxilium shall be calculated in accordance with U.S. Generally Accepted Accounting Principles and shall mean the fully allocated cost of manufacturing, which shall include the sum of the following
actual costs: 

1. Materials cost, which means the price paid for raw material components and finished goods which are purchased from outside vendors as well as any freight and duty where applicable.

2. Direct labor costs, which means the employment costs including, salary, employee benefits, seminars and training within the relevant manufacturing operating unit. 

3. In-direct, direct and factory overheads, which means the cost of specific activities that are provided by support functions. Overhead costs include expenses associated with manufacturing support personnel, quality assurance and control testing,
batch review, facility lease and rental costs, facility depreciation (including leasehold improvements, computer, furniture and fixtures, manufacturing equipment), equipment set-up, validation and calibration (including IQ, OQ, DQ and PQ), equipment
repair and maintenance costs, manufacturing process supplies, manufacturing energy and utilities, waste removal, storage, transportation, insurance, management and administrative expenses (including appropriate inter-company allocations), general
facilities costs, environmental engineering, interest expense and property taxes.

4. Contract manufacturing, lyophilization, fill and finish, packaging, labeling and storage 

	
5. 		
Routine quality compliance and quality assurance programs

	
	 	 
	
6. 		
Customs or excise taxes, import duties, sales taxes and other taxes or duties.

	

 

Schedule 1.57 

Partner Territory

The Partner Territory consists of the 27 members of the European Union as of the date of this Agreement, specifically Austria, Belgium, Bulgaria, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Ireland, Italy,
Latvia, Lithuania, Luxembourg, Malta, The Netherlands, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden and the UK, and Croatia, Albania, Armenia, Azerbaijan, Belarus, Bosnia & Herzegovina, Georgia, Kazakhstan, Kirghiz Republic,
Macedonia, Moldova, Serbia & Montenegro, Tajikistan, Uzbekistan, Turkey, Iceland, Switzerland and Norway. 

 

 

 

CONFIDENTIAL INFORMATION 

Auxilium Pharmaceuticals, Inc. 

[**]-Protocol-[**] 

Schedule 2.2(d) 

Cellulite Protocol 

CONFIDENTIAL  

COLLAGENASE CLOSTRIDIUM HISTOLYTICUM

 (AA4500) 

PROTOCOL [**]  

 

A PHASE 1b, OPEN-LABEL, DOSE-ESCALATION 

STUDY OF THE SAFETY, EFFECTIVENESS, 

PHARMACOKINETICS, AND IMMUNOGENICITY 

OF AA4500 FOR THE TREATMENT OF EDEMATOUS 

FIBROSCLEROTIC PANNICULOPATHY  

Date: [**] 

Sponsor: 

Auxilium Pharmaceuticals, Inc. 

40 Valley Stream Parkway 

Malvern, PA 19355 

USA 

** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

CONFIDENTIAL INFORMATION 

Auxilium Pharmaceuticals, Inc. 

[**]-Protocol-[**] 

** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

1. STUDY SYNOPSIS 

	
Name of Sponsor/Company: Auxilium Pharmaceuticals, Inc. 

 
	
Name of Finished Product: XIAFLEX
		
 
	
	
Study Drug: AA4500
		
 
	
	
Name of Active Ingredient:
collagenase clostridium histolyticum
		
Study Number: [**]
	
	
 	
 
	
	
Title of Study: A Phase 1b, open-label, dose-escalation study of the safety, effectiveness, and pharmacokinetics
of AA4500 for the treatment of edematous fibrosclerotic panniculopathy
	
	
 
	
Study Centers: [**]
		
 
	
	
Study Period: [**]
		
Phase of Development: Phase 1b
	

Objectives: The objectives of this study are to assess the safety, effectiveness, pharmacokinetics, and immunogenicity of AA4500 at increasing doses ranging from [**] in the treatment of adult women with edematous fibrosclerotic
panniculopathy (EFP). 

Methodology/Study Design: This study is a Phase 1b, open-label, dose-escalation and pharmacokinetic study. To be eligible for treatment, a subject must have at least an 8 cm x 10 cm area of EFP [**]. Each subject will be screened for study
eligibility within 30 days before injection of study drug on Day [**]. 

Cohort Assignment and Follow-up: In this study, [**] subjects will each receive 10 single injections of AA4500 within the investigator designated 8 cm x 10 cm area of EFP. [**]

Table 1: Proposed Doses for the Phase 1 Study in Subjects With EFP 

	
 
		
 
		
        EFP
		
 
		
 
		
  
	
	
 
		
 
		
 
		
 
		
EFP Dose/
		
EFP Concentration 
	
	
 
		
 
		
 
		
 
		
Designated EFP Area
		
as a Percent of the 
	
	
 
		
Dose AA4500/
		
Volume/
		
 
		
as a Percent of the
		
Approved Dupuytren’s 
	
	
 
		
Designated
		
Designated
		
 
		
Approved Dupuytren’s
		
Concentration 
	
	
  Cohort
		
EFP Areaa
		
EFP Areaa
		
          Concentration
		
Dose (0.58 mg)
		
(2.3 mg/mL) 
	
	
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a -
A total of 10 single injections per the 8 cm x 10 cm area of EFP, as designated by the investigator. 

Safety: The safety of AA4500 will be evaluated through the collection of adverse events, including a targeted assessment of local/systemic reactions to treatment and vital sign measurements at baseline and on Days [**]. Clinical laboratory
testing will also be performed at baseline and on Day [**].

Effectiveness: The effectiveness of AA4500 will be evaluated on Days [**] and [**] through the use of an investigator assessment of the treated area using a [**]. Physician and subject satisfaction with treatment will also be recorded at the
Day [**] and Day [**] follow-up visits.

	
Name of Sponsor/Company: Auxilium Pharmaceuticals, Inc. 

 
	
Name of Finished Product:
XIAFLEX
		
 
	
Study Drug: AA4500
		
 
	
	
Name of Active Ingredient:
		

Study Number: 
[**]
	

	
collagenase clostridium histolyticum
	

Pharmacokinetics: Subjects in Cohorts [**] will have blood samples collected for the determination of [**] plasma concentrations before dosing and 5 minutes, 10 minutes, 20 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, and 24 hours
after dosing. 

Immunogenicity: Blood samples for follow-up [**] testing and neutralizing antibody testing to [**] will be collected before dosing and at the Day [**] and Day [**] follow-up visits.

** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

 

 

 

	
CONFIDENTIAL INFORMATION
		
 
		
 
	
	
Auxilium Pharmaceuticals, Inc.
		
 
		
 
	
	
[**]-Protocol-[**]
		
 
		
 
	

	
 
	
Name of Sponsor/Company: Auxilium Pharmaceuticals, Inc. 

 
	
Name of Finished Product:
XIAFLEX
		
 
	
Study Drug: AA4500
		
 
	
	
Name of Active Ingredient:
		

Study Number: 
[**]
	

	
collagenase clostridium histolyticum
	

Number of Subjects Planned: The sample size of [**] subjects is considered adequate and relevant for this proof of concept study. This sample size permits observation of dose-response trends, if present. The study is not statistically
powered. Subjects who withdraw following injection of study drug, for any reason, will not be replaced. 

Study Interruption Rules: If 2 or more subjects within a dosing cohort develop an adverse event that is clinically significant [**], the [**] will assess the available safety information and determine if the events are drug related. The [**]
will then provide a recommendation as to whether it is safe to allow the remaining subjects in this or later cohorts to proceed with treatment or whether to discontinue further dosing. All decisions will be documented in writing, and where required,
submitted to the IRB/IEC/HREC for their review or information. 

Inclusion Criteria: No subject should be assigned to treatment until all eligibility criteria have been satisfied. To qualify for the study a subject must: 

	
1. 		
Be a female and be ≥ 18 years of age and ≤ 65 years of age.

	
	 	 
	
2. 		
Have EFP that is [**].

	
	 	 
	
3. 		
Have EFP within [**] before the screening visit.

	
	 	 
	
4. 		
Have an area of EFP that is at least 8 cm x 10 cm within the [**].

	
	 	 
	
5. 		
Have a Body Mass Index (BMI) between 20.0 and 30.0 kg/m2, and intend to maintain stable weight throughout the duration of the study (variation of maximum of 5% baseline weight permitted).

	
	 	 
	
6. 		
Be judged to be in good health, based upon the results of a medical history, physical examination, and laboratory profile at screening.

	
	 	 
	
7. 		
Have a negative urine pregnancy test at screening and before injection of AA4500 and be using an effective contraception method (ie, abstinence, intrauterine device [IUD], hormonal [estrogen/progestin] contraceptives, or
barrier control) for at least one menstrual cycle prior to study enrollment and for the duration of the study, or be surgically sterile.

	
	 	 
	
8. 		
Voluntarily sign and date an informed consent agreement approved by the Institutional Review Board/Independent Ethics Committee/Human Research Ethics Committee (IRB/IEC/HREC). The subject must also sign an authorization form to
allow disclosure of his protected health information (PHI). The PHI authorization form and informed consent form may be an integrated form or may be separate forms depending on the institution.

	
	 	 
	
9. 		
Be able to complete and understand the various rating instruments in English.

	

** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

CONFIDENTIAL INFORMATION

Auxilium Pharmaceuticals, Inc. 

[**]-Protocol-[**] 

	
Name of Sponsor/Company: Auxilium Pharmaceuticals, Inc. 

 
	
Name of Finished Product:
XIAFLEX
		
 
	
Study Drug: AA4500
		
 
	
	
Name of Active Ingredient:
		

Study Number: 
[**]
	

	
collagenase clostridium histolyticum
	

Exclusion criteria: A subject will be excluded from study participation if she:

	
1. 		
Has any of the following conditions:

	
	 	 	 
		
	 

	
[**]

	
	 	 	 
		
	 

	
Other significant medical condition, which in the investigator’s opinion would make the subject unsuitable for enrollment in the study

	

** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

 

 

	
CONFIDENTIAL INFORMATION
		
 
		
 
	
	
Auxilium Pharmaceuticals, Inc.
		
 
		
 
	
	
[**]-Protocol-[**]
		
 
		
 
	

 	
Name of Sponsor/Company: Auxilium Pharmaceuticals, Inc. 

 
	
Name of Finished Product:
XIAFLEX
		
 
	
Study Drug: AA4500
		
 
	
	
Name of Active Ingredient:
		

Study Number: 
[**]
	

	
collagenase clostridium histolyticum
	

Exclusion criteria (continued)

	
2. 		
Has used any of the following for the treatment of EFP of the legs or buttock or intends to use any of the following at any time during the study:

	

[**]

** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

 

 

CONFIDENTIAL INFORMATION 

Auxilium Pharmaceuticals, Inc. 

[**]-Protocol-[**] 

	
Name of Sponsor/Company: Auxilium Pharmaceuticals, Inc. 

 
	
Name of Finished Product:
XIAFLEX
		
 
	
Study Drug: AA4500
		
 
	
	
Name of Active Ingredient:
		

Study Number: 
[**]
	

	
collagenase clostridium histolyticum
	

Selection of the Area to be Treated, Test Product, Dose and Mode of Administration: The investigator will select an area of EFP either within [**] or within [**] that is at least 8 cm x 10 cm [**]. The investigator will center the
Sponsor’s injection template within the selected area and mark the area to be treated with a surgical marker. 

Immediately after reconstitution of the commercial drug product (ie, AA4500) with [**] each subject will receive 10 injections of AA4500 (according to cohort assignment) in the designated 8 cm x 10 cm area of EFP [**]. 

[**]

 

 

 

[**]. 

 ** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

	

Name of Sponsor/Company: Auxilium Pharmaceuticals, Inc. 

 
	
Name of Finished Product:
XIAFLEX
		
 
	
Study Drug: AA4500
		
 
	
	
Name of Active Ingredient:
		

Study Number: 
[**]
	

	
collagenase clostridium histolyticum
	

Reference Therapy, Dose and Mode of Administration: None.

Statistical Methods

Analyses Population:  The intent-to-treat (ITT) and safety population is defined as all subjects who received 1 injection of AA4500. Modified intent-to-treat (MITT) population is defined as all intent-to-treat subjects with a baseline and at
least one post-injection efficacy evaluation. 

Safety: The following variables are safety endpoints:

	
Adverse events: Mapped to preferred term using the Medical Dictionary for Regulatory Activities (MedDRA)
	
Vital signs
	
Clinical laboratory testing

Adverse events, including a targeted assessment of local/systemic reactions to treatment, will be summarized by proportion of subjects reporting each event within each cohort and injection volume, within each cohort, and overall. Descriptive
statistics will be presented for each clinical laboratory test and vital signs for the actual and change from baseline at each visit by dose/designated EFP area [**] and volume/designated EFP area [**] and by dose/designated EFP area [**]. 

Effectiveness Analyses: Primary endpoints are:

	
A responder analysis based on proportion of subjects (by dose and volume) with a [**]
	
A responder analysis based on proportion of subjects (by dose and volume) with a [**]

Secondary endpoints are:

	
A responder analysis based on proportion of subjects (by dose and volume) with a [**]
	
A responder analysis based on proportion of subjects (by dose and volume) with a [**]
	
The absolute change (mean value) in [**] severity scale from baseline
	
The absolute change in surface topographical characteristics of the treated area based on the 3 digital photography
	
Subject satisfaction with treatment
	
Physician satisfaction with treatment

The primary time point for analyses will be Day 90. For subjects who do not have an evaluation at Day 90, the evaluation at Day 90 will be carried forward and used for these analyses. All effectiveness analyses will be performed for Day 60 and Day
90. Data will be summarized with descriptive statistics by dose/designated EFP area [**] and volume/designated EFP area [**] and by dose/designated EFP area [**] at Days [**] and [**]. Pharmacokinetics: Plasma concentrations will be evaluated
using a validated enzyme-linked immunoabsorbent assay (ELISA). Actual blood sampling times will be used in all pharmacokinetic analyses. The following pharmacokinetic parameters will be determined for each subject with quantifiable plasma
concentrations: [**]. For pharmacokinetic profiles with missing values or measurements below the limit of quantitation (LOQ) appropriate statistical methods will be employed. The lower limit of quantification for [**] in human plasma is 

** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

 

	
Name of Sponsor/Company: Auxilium Pharmaceuticals, Inc. 

 
	
Name of Finished Product:
XIAFLEX
		
 
	
Study Drug: AA4500
		
 
	
	
Name of Active Ingredient:
		

Study Number: 
[**]
	

	
collagenase clostridium histolyticum
	

[**], respectively. Pharmacokinetic data will be summarized through data tabulations, descriptive statistics, and graphic presentations within Cohorts [**], as appropriate. 

Immunogenicity: [**] antibodies levels and neutralizing antibodies to [**] will be summarized using descriptive statistics by dose/designated EFP area [**] and volume/designated EFP area [**] and by dose/designated EFP area [**]. 

Rationale for the evaluation time points: Following injection, the pharmacologic activity of AA4500 is local, rapid and is essentially complete in a period of 12 to 24 hours. Virtually all local AEs associated with AA4500 are resolved within
the first 30 days after injection. Thus, any potential benefit as it relates to the designated EFP area should be apparent within the first the [**] days following injection. The Day 90 time point was added to this study to evaluate long term
treatment effect. 

** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

Table 2:
Study AUX-CC-830 Assessments

	
 	
 	
 
		
 
		
 
		
 
		
 
		
 
		
 
	
	
 
		
Screening
		
Treatment
		
 
		
 
		
    Follow-up
		
 
		
 
		
End of
	
	
 
		
Period
		
 
		
 
		
 
		
 
		
 
		
 
		
Study
	
	
 
		
Day -30 to -
		
Day 1
		
Day 2
		
Day 7
		
Day 14
		
Day 30
		
Day 60
		
Day 90
	
	
Procedures
		
1
		
 
		
 
		
(T 2 days)
		
(T 2 days)
		
(T 5 days)
		
(T 5 days)
		
(T 5 days)
	
	
[**]
		
 
		
 
		
 
		
 
		
 
		
 
		
 
		
 
	
	
 	
 	
 	
 	
 	
 	
 	
 	
 
	
 	
 	
 	
 	
 	
 	
 	
 	
 
	
 	
 	
 	
 	
 	
 	
 	
 	
 
	
 	
 	
 	
 	
 	
 	
 	
 	
 
	
 	
 	
 	
 	
 	
 	
 	
 	
 
	
 	
 	
 	
 	
 	
 	
 	
 	
 
	
 	
 	
 	
 	
 	
 	
 	
 	
 
	
 	
 	
 	
 	
 	
 	
 	
 	
 
	
 	
 	
 	
 	
 	
 	
 	
 	
 
	
 	
 	
 	
 	
 	
 	
 	
 	
 
	
 	
 	
 	
 	
 	
 	
 	
 	
 
	
 	
 	
 	
 	
 	
 	
 	
 	
 
	
 	
 	
 	
 	
 	
 	
 	
 	
 

	
a 		
[**].

	
	 	 	 
	
b 		
The investigator will select an area of EFP either within the [**] that is at least 8 cm x 10 cm [**]. The investigator will center the Sponsor’s injection template within the selected area and mark the area to be treated
with a surgical marker. The investigator will also measure the distance from the edge of the injection template to the coccyx and to the anterior superior iliac spine as define din the protocol.

	
	 	 	 
	
c 		
Before injection.

	
	 	 	 
	
d 		
Up to [**]. Vital signs must be stable for a period of at least 60 minutes.

	
	 	 	 
	
e 		
Cohorts [**] will have blood samples collected for the determination of [**] plasma concentrations before dosing; [**] minutes and [**] hours after dosing.

	

** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

Schedule 3.1 

Additional Indication Review Process

Objectives 

In accordance with Section 3.1(c) of the Agreement to which this Schedule is attached, Auxilium and BTC will develop a joint review plan through a structured process described below (all defined terms used in this Schedule, and not defined herein,
shall have the meaning ascribed to such term in the Agreement). The objective of this process is to review proposals for proposed Additional Indications that may become Additional Indications and related Development Plans in order to develop the
Product in an optimal set of indications to help patients address unmet needs and to maximize the value of the asset. The review process for proposed Additional Indications and related Development Plans will take place in time for review at any
Joint Development Committee (JDC) meeting. 

Introduction 

The process described below is designed specifically as an evaluation tool for helping the JDC make decisions about proposed Additional Indications when they are at an early stage of development and where there is limited information available on
the probability of technical success or the market potential of such proposed Additional Indications. The process will help to identify areas where there is some reasonable probability of the required combination of technical success and commercial
potential, and conversely to rule out areas where the probability is too low to justify spending money, time and resources. 

However, given that the investments in early stage development are relatively low, the criteria are inclusive and aim not to make false negative recommendations, rather than ruling out options too quickly. If a proposed Additional Indication
becomes an Additional Indication and proceeds through Development and the likely profile becomes clearer and the market situation continues to evolve, the value of continuing to Develop such Additional Indication will need to be assessed using more
detailed financial analysis based on future quantitative market research, and precise cost and time projections for Development activities. 

Description of the Process 

The process occurs in four steps (each a “Step”): 

Step 1

	
(a) 		
Brainstorm Potential Additional Indications – the list of proposed Additional Indications to be evaluated are identified in a joint brainstorming session with representatives (commercial and medical) from both Parties.
The full list of proposed Additional Indications are then placed into one of three (3) buckets:

	

Wave 1 – Proposed Additional Indications about which enough is currently known, both medically and commercially, to do an assessment based on the information possessed by both Parties 

Wave 2 – Proposed
Additional Indications of possible interest within the next three (3) years about which more needs to be learned. Next steps in terms of further scientific or market research should be agreed, with timelines and responsibilities for each of these
proposed Additional Indications 

Wave 3 – Proposed Additional Indications which are not going to be in the next three (3)-year plan and remain on the list for evaluation in future review. 

	
(b) 		
Confirm Evaluation Criteria – the default criteria for evaluating proposed Additional Indications have been agreed by the Parties. Each of the criteria in the medical/scientific and commercial groupings has been
equally weighted within each group; provided, that the Parties can discuss the need to change these criteria or weighting from time to time. Any change to the criteria or the weighting needs to be agreed by both Parties. In the absence of agreement
the current criteria and weightings will continue to operate.

	

The current criteria and weightings are: 

	
 Scientific/Medical Criteria
		
 
	
	
 
		

Weight
	

	
 [**]
		
[**]
	
	
 Commercial Criteria
		
 
	
	
 [**]
		
[**]
	

 

** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

Step 2

	
(a) 		
Evaluate Proposed Additional Indications – in advance of the JDC meeting to evaluate proposed Additional Indications, the Parties will share with each other any scientific/clinical and market research data with respect
to the proposed Additional Indications that meet the Wave 1 criteria. [**]

	
	 	 
	
(b) 		
Prioritize Proposed Additional Indications Based on Criteria – the ratings of the proposed Additional Indications will be used to prioritize and define future actions using the grid show below:

	

[**]

Step 3

	
(a) 		
Establish Development Plan for Prioritized Additional Indications – based on the decisions reached through the prioritization grid in Step 2(b), the Chief Medical Officer of each Party (or, in the event that a Party
does not have a Chief Medical Officer, a physician designee on behalf of such Party) (“CMO”) will prepare a Development Plan for each of the Additional Indications for which it has been agreed they are responsible for Stage 1 Development.
The plans will address:

	
	 	 	 
		
	 

	
Trial design to reach agreed Proof Of Concept;

	
	 	 	 
		
	 

	
Possible end-points;

	
	 	 	 
		
	 

	
Identify investigators for studies who are leaders in the specific field;

	
	 	 	 
		
	 

	
Responsibilities for trial deliverables;

	
	 	 	 
		
	 

	
Regulatory pathway;

	
	 	 	 
		
	 

	
Timeline; and

	
	 	 	 
		
	 

	
Commercial assessment.

	

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Specific protocols will be put together based on the plans for the indication. The CMOs will share protocols in order to get feedback and input from their counterpart. 

Step 4

	
(a) 		
JDC approval of Development Plan – the Development Plan for each Additional Indication will be presented to the JDC for approval. Once approved, protocols will be developed by the responsible Party, in collaboration
with the other Party, based on the Development Plan approved by JDC, and such protocols shall form a part of such Development Plan. Once completed, the protocols will be reviewed for approval by the JDC.

	
	 	 
	
(b) 		
Execute Development Plan and Track Progress – the Development Plan for each approved Additional Indication will be monitored by the CMOs. The CMOs will have standing update meetings/calls to discuss progress against
the Development Plans. The CMOs will report to the JDC on a quarterly basis on performance versus plan. Development Plans for Step 1 indications will be incorporated into an overall three (3)- year strategic development plan for the Product that
will be shared between the Parties.

	

Schedule 3.1(b)(1) Canine Lipoma Protocol

	Advance Biofactures Corp. 
      	 	 
	35 Wilbur Street, Lynbrook NY 11563 
    	 DRAFT 
	(516) 593-7000 • Fax:  (516) 593-7039 
    	 
	 	 CONFIDENTIAL 	 
	 	 	 

	Confidential treatment requested under 17 C.F.R. §§ 200.80(b)(4) and 240.24b-2. The confidential portions of this exhibit have been omitted and are marked accordingly. The confidential portions have been filed separately with the Securities and Exchange Commission pursuant to a confidential treatment request.
    

DOUBLE BLIND STUDY TO EVALUATE THE EFFICACY OF

COLLAGENASE CLOSTRIDIUM HISTOLYTICUM FOR THE

TREATMENT OF CANINE LIPOMA 

Protocol Number: Chien-804 

[**] 

PROTOCOL APPROVALS 

	Originated by 	 	 	/ 	 
	                                                                         	 	  Jean-Marie Soma, Mgr Clinical Affairs 	           
       Date 	 
	Approved by 	 		/ 	 
		 	 Thomas
      Wegman, President 	           
       Date 	 
	Approved by 	 	 	/ 	 
		 	 Sarit Dhupa,
      Investigator 	           
       Date 	 

	** 	CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN
      OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
      COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST.

	Double Blind Study to Evaluate the Efficacy of
      Collagenase Clostridium Histolyticum for the 
	Treatment of Canine Lipoma 
	Chien-804 
	
                   
                         
                         
                         
                         
                         
                         
                         
                         
                         
                       DRAFT 110826
    

TABLE OF CONTENTS 

	1.0 	SYNOPSIS 
    	5 
	2.0 	STUDY CONTACTS	7 
	3.0 	STUDY SITE	7 
	4.0 	STUDY OBJECTIVE	8 
	5.0 	BACKGROUND AND
      RATIONALE 	8 
	  	5.1 	Chien-801 	8 
	  	5.2 	Chien-802 	9 
	  	5.3 	Chien-803	10 
	  	5.3 	Study Rationale 	12 
	  	5.4 	Investigational Veterinary Product	12 
	  	5.5 	Rationale for Dosage Selection
    	12 
	6.0 	STUDY DESIGN	12 
	  	6.1 	Study Structure	12 
	  	  	6.1.1 Study Type	12 
	  	  	6.1.2 Sample Size
    Determination	12 
	  	  	6.1.3 Control Group	13 
	  	  	6.1.4 Blinding	13 
	  	  	6.1.5 Randomization	13 
	  	  	6.1.6 Study Duration	13 
	7.0 	STUDY ANIMAL SELECTION	14 
	  	7.1 	Population Base	14 
	  	7.2 	Inclusion Criteria	14 
	  	7.3 	Exclusion Criteria	14 
	8.0 	ANIMAL MANAGEMENT PRACTICES	15 
	  	8.1 	Food and Water	15 
	  	8.2 	Housing	15 
	  	8.3 	Study Animal Care	15 
	  	8.4 	Concomitant Medications	15 
	9.0 	ASSESSMENTS	15 
	  	9.1 	Physical Examination	15 
	 	9.2  	Laboratory Analyses 	16 
	  	9.3 	Efficacy Assessment	16 
	  	9.4 	Safety Assessments	17 
	  	9.5 	Additional Parameters	17 

2 

	Double Blind Study to Evaluate the Efficacy of
      Collagenase Clostridium Histolyticum for the 
	Treatment of Canine Lipoma 
	Chien-804 
	
                   
                         
                         
                         
                         
                         
                         
                         
                         
                         
                       DRAFT 110826
    

	10.0 	SCHEDULE OF STUDY
      EVENTS	17 
	11.0 	TRIAL MEDICATION	19 
	  	11.1 	Investigational Veterinary
      Product 	19 
	  	11.2 	Control product (Placebo) 	20 
	  	11.3 	Reconstitution	21 
	  	11.4 	Injection Medication	21 
	  	11.5 	Drug Dispensation	21 
	  	11.6 	Drug Accountability	21 
	12.0 	ADMINISTRATION OF
      STUDY MEDICATION	21 
	  	12.1 	Treatment Allocation	21 
	  	12.2 	Dose	22 
	  	12.3 	Route of Administration and Frequency	22 
	  	12.4 	Injection Technique	22 
	13.0 	SAFETY EVALUATION / ADVERSE
      EVENTS	22 
	  	13.1 	Definition	22 
	  	13.2 	Reporting Adverse Events	23 
	  	13.3 	Monitoring Adverse Events	23 
	  	13.4 	Death of a Subject	23 
	14.0 	STATISTICAL
      ANALYSIS	23 
	  	14.1 	Analysis Population	23 
	  	14.2 	Efficacy Analysis 	24 
	  	14.3 	Safety Analysis 	24 
	  	14.4 	Visit Windows 	24 
	  	14.5 	Missing Data	25 
	15.0 	REGULATORY AND
      ADMINISTRATIVE ASPECTS	25 
	  	15.1 	Regulatory	 25
	  	15.2 	Informed Consent	 25
	  	15.3 	Departures from Protocol/Amendments	25 
	  	15.4 	Handling of Records	26 
	  	15.5 	Monitoring of the Study	26 
	16.0 	SIGNATURE
    PAGE	24 
	  	STUDY FORMS 	  
	  	Client Questionnaire
    	  
	  	Request for Preparation of Drug 	  

3 

	Double Blind Study to Evaluate the Efficacy of
      Collagenase Clostridium Histolyticum for the 
	Treatment of Canine Lipoma 
	Chien-804 
	
                   
                         
                         
                         
                         
                         
                         
                         
                         
                         
                       DRAFT 110826
    

Drug Dispensation Form 

4 

	Double Blind Study to Evaluate the Efficacy of
      Collagenase Clostridium Histolyticum for the 
	Treatment of Canine Lipoma 
	Chien-804 
	
                   
                         
                         
                         
                         
                         
                         
                         
                         
                         
                       DRAFT 110826
    

 	1.0 	
      SYNOPSIS

	Title 	
    Double blind study to evaluate the
      efficacy of Collagenase Clostridium Histolyticum for the treatment of
      canine lipoma 

	Sponsor 	
    Advance Biofactures Corporation 

	  	
    35 Wilbur Street, Lynbrook, New York
      11563 

	Investigator 	
    [**] 

	Investigative Site
    	
    [**] 

	Indication 	
    Lipoma 

	Target Animal 	
    Dogs 

	Objective 	
    To assess the efficacy and safety of Collagenase Clostridium
      Histolyticum compared with placebo in the treatment of subcutaneous,
      benign lipoma in dogs 

	Study Design 	
    Protocol Chien-804 is a single site, randomized, double-blind,
      placebo controlled, Phase II study. 

	Planned Sample
      Size 	
    Thirty-two (32) study animals 

	Test Articles 	
    Investigational Veterinary Product: FDA approved
      Collagenase Clostridium Histolyticum (XIAFLEX®, manufactured by Auxilium
      Pharmaceuticals, Inc.) 

	  	
    Placebo: 
	
    Control
      product manufactured by Auxilium Pharmaceuticals, Inc.  

	 	
    Diluent: 
	
    [**]%
      sodium chloride containing [**]% calcium chloride  

	Test Drug Dosage 	
    [**] mg Collagenase Clostridium Histolyticum (CCH) administered
      per square centimeter surface area of the lipoma per single injection The
      maximum surface area allowed is [**] resulting in a maximum dosage of [**]
      mg per single injection 

	Route of
      Administration 	
    Injections are administered directly into
      the lipoma 

	Schedule of Administration 	
    Study animals will receive a single injection of either CCH or
      placebo 

	  	
    Follow-up visits: 

	Follow-Up 	
    Days: 
	
    [**]
      days post injection 

	  	
    Months: 
	
    [**] months post injection 

	Study Duration 	
    Study animals will be followed for [**]
      months post injection 

	Efficacy Assessment 	
    Primary Efficacy Endpoint 

	  	
    [**] 

	  	
     

	  	
    Secondary Efficacy Endpoints 

	  	
    Responders at [**] days and [**] months.
      A responder is an animal with 

 	** 	CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN
      OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
      COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

	Double Blind Study to Evaluate the Efficacy of
      Collagenase Clostridium Histolyticum for the 
	Treatment of Canine Lipoma 
	Chien-804 
	
                   
                         
                         
                         
                         
                         
                         
                         
                         
                         
                       DRAFT 110826
    

	 	 
	  	
    [**]
  

	  	
      

	Additional Information 	
    Lipoma
      [**] 

	  	
    [**] 

	Safety Parameters
    	
    Adverse Event Assessment on the day of injection
      and at each follow-up visit 

	  	
    Efficacy Population 

	Statistical Analysis 	
    Analysis
      of efficacy parameters will be based on the Intent To Treat population
  

	  	
    Analysis of Primary Variable 

		
    The
      primary statistical analysis will use the two sample t-test to compare the
      control group and the treated group 

	  	
    Analysis of Secondary Variables 

	  	
    [**]
  

	  	
    Relative
      change will be percent change from baseline 

	 	
    [**]
      test will be used for the responder analysis 

		
    Analysis
      of the relative change from baseline will use the two sample t-test and in
      exploratory analyses, analysis of variance or covariance Client
      satisfaction will be determined from the questionnaire and analyzed with
      [**] Test. 

	  	
    Safety: 

		
    Tables of adverse events and local site reactions
      will be constructed by treatment 

	** 	CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN
      OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
      COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

6 

	Double Blind Study to Evaluate the Efficacy of
      Collagenase Clostridium Histolyticum for the 
	Treatment of Canine Lipoma 
	Chien-804 
	
                   
                         
                         
                         
                         
                         
                         
                         
                         
                         
                       DRAFT 110826
    

	 	 	 	
       
	2.0	STUDY CONTACTS
	 	 	 	
       
	 	2.1	Investigator
	 	 	 	
       
	 	2.2	Sponsor Representative
	 	 	 
	 	 	[**]
	 	 	Advance Biofactures Corporation 
	 	 	35 Wilbur Street
	 	 	Lynbrook, New York 1156
	 	 	(516) 593-7000
	 	 	 
	 	2.3	Study Monitor
	 	 	 	
       
	 	2.4	Statistician
	 	 	 	
       
	 	 	[**]
	 	 	 	
       
	3.0	STUDY SITE
	 	 	 	
       
	 	3.1	[**]
	 	 	 	
       
	 	3.2	[**]

	 	 
	** 	CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN
      OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
      COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

7

	Double Blind Study to Evaluate the Efficacy of
      Collagenase Clostridium Histolyticum for the 
	Treatment of Canine Lipoma 
	Chien-804 
	
                   
                         
                         
                         
                         
                         
                         
                         
                         
                         
                       DRAFT 110826
    

	4.0 	
      STUDY OBJECTIVE

	 	 
		
      The objective of this study is to assess the efficacy and
      safety of Collagenase Clostridium Histolyticum compared with placebo in
      the treatment of subcutaneous, benign lipoma in dogs.

	 	 
	5.0 	
      BACKGROUND AND JUSTIFICATION

	 	 
		
      Two preliminary studies have been completed and one
      controlled study has been initiated assessing the efficacy of Purified
      Collagenase for Injection (PCI), a Collagenase Clostridium Histolyticum
      manufactured by Advance Biofactures Corporation, in canine subjects with
      lipoma. Study designs and results are summarized
below:

	5.1 	
      Chien-801

	 	 	 	 
		
      This study, sponsored by Advance Biofactures Corporation,
      was a pilot study designed to evaluate the safety and efficacy of PCI as a
      non- operative treatment of canine lipoma. Six animals were enrolled in
      the study.

	 	 	 	 
		
      Working concentrations of [**] of PCI were used in this
      study. Total mg study drug per subject for one injection ranged from [**]
      which was approximately [**] the total mg used in [**]. The dose of drug
      injected ranged from [**]. A single injection was administered to [**]
      study animals and [**] injections were administered to [**].

	 	 	 	 
		
      [**].

	 	 	 	 
		[**]  were taken at all visits using [**]
      were taken initially and [**].
	 	 	 	 
			5.1.1 	
      Study Results

	 	 	 	 
				
      Data from Chien-801 is summarized in the following table
      [**].

	 	 
	** 	CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN
      OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
      COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

8 

	Double Blind Study to Evaluate the Efficacy of
      Collagenase Clostridium Histolyticum for the 
	Treatment of Canine Lipoma 
	Chien-804 
	
                   
                         
                         
                         
                         
                         
                         
                         
                         
                         
                       DRAFT 110826
    

Data from Chien-801 

	[**]  	[**]  	  	[**] 	  	[**] 	  	[**] 	  	[**] 
	  	[**]  	[**]  	[**] 	[**] 	[**] 	[**] 	[**] 	[**]  	[**] 
	[**]  	[**]  	[**]  	[**] 	[**] 	[**] 	[**] 	[**] 	[**]  	[**] 
	[**]  	[**]  	[**]  	[**] 	[**] 	[**] 	[**] 	[**] 	[**]  	[**] 
	[**]  	[**]  	[**]  	[**] 	[**] 	[**] 	[**] 	[**] 	[**]  	[**] 
	[**]  	[**]  	[**]  	[**] 	[**] 	[**] 	[**] 	[**] 	[**]  	[**] 
	[**]  	[**]  	[**]  	[**] 	[**] 	[**] 	[**] 	[**] 	[**]  	[**] 
	[**]  	[**]  	[**]  	[**] 	[**] 	[**] 	[**] 	[**] 	[**]  	[**] 

	 	5.1.2 	
      Adverse Reactions

	 	 	 	 
	 		
      The following adverse events were reported during this
      protocol:

	 	 	 	 
	 		5.1.2.1 	
      [**].

	 	 	 	 
	 		5.1.2.2 	
      [**].

	 	 	 	 
	 		5.1.2.3 	
      [**].

	 	 	 	 
	 		5.1.2.4 	
      [**].

	 	 	 	 
	 		5.1.2.5 	
      [**].

	 	5.2 	
      Chien-802

	 	 	 
	 		
      A follow-up study to Chien-801 was sponsored by Advance
      Biofactures Corporation to further evaluate the efficacy of PCI and to
      gather data regarding the appropriate dosage and frequency of injections
      necessary to significantly reduce the size of canine lipoma. [**] study
      animals were enrolled in the study, Chien-802.

	 	 	 
	 		
      Working concentrations of [**] were used in this study.
      The dose of drug injected was [**] and the allowable total mg study drug
      per subject was [**] per single injection. An additional injection was
      allowed to be administered at [**] days post [**]. Based upon the decision
      of the investigator, [**].

	 	 	 
	 		
      [**].

	 	 	 
	 		
      5.2.1 Study Results

	Data from Chien-802 is summarized in the following table
    
	               
                         
             % Reduction in Lipoma Size 

	 	 
	** 	CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN
      OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
      COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

9 

	Double Blind Study to Evaluate the Efficacy of
      Collagenase Clostridium Histolyticum for the 
	Treatment of Canine Lipoma 
	Chien-804 
	
                   
                         
                         
                         
                         
                         
                         
                         
                         
                         
                       DRAFT 110826
    

	
    Pt  
	
    Baseline  
	
      
	
    30 Day  
	
      
	
    % Reduction 
	
    90 Day 
	
      
	
    % Reduction 

	
      
	
    Caliper
    
	
    CT 
	
    Caliper
    
	
    CT 
	
    Caliper
    
	
    CT 
	
    Caliper
    
	
    CT 
	
    Caliper 
	
    CT 

	
      
	
    (cm2)  
	
    Scan 
	
    (cm2)  
	
    Scan 
	
     

	
    Scan  
	
    (cm2)  
	
    Scan( 
	
      
	
    Scan  

	
      
	
      
	
    (cm3)  
	
      
	
    (cm3)  
	
      
	
      
	
      
	
    cm3)  
	
      
	
      

	
    #7  
	
    7.07  
	
    10.11  
	
    3.9  
	
    2.78 
	
    45 
	
    72.5 
	
    3.06 
	
    0  
	
    57  
	
    100 

	
    #8  
	
    18.7  
	
    N/A  
	
    5.04  
	
    N/A 
	
    73 
	
    N/A 
	
    3.1 
	
    6.19  
	
    83  
	
    N/A 

	
    #9  
	
    42.5  
	
    11.14  
	
    0  
	
    0.23 
	
    100 
	
    97.9 
	
    0 
	
    0.77  
	
    100  
	
    93 

	
    #10  
	
    44.48  
	
    18.28  
	
    11.3  
	
    3.3 
	
    75 
	
    81.9 
	
    0 
	
    0  
	
    100  
	
    100 

NOTE: Due to a software malfunction,
the CT scan data for patient #8 was not available (N/A) 

	 	5.2.2 	
      Adverse Reactions

	 	 	 	 
	 		
      The following adverse events were reported during this
      study:

	 	 	 	 
	 		5.2.2.1 	
      [**].

	 	 	 	 
	 		5.2.2.2 	
      [**].

	 	 	 	 
	 		5.2.2.3 	
      [**]

	 	 	 	 
	 		
      [**]

	 	 	 	 
	 	5.2.3 	
      Client Questionnaire [**].

	 	5.3 	
      Chien-803

	 	 	 
	 		
      Based upon the [**] results from Chien-802, a double
      blind study to evaluate the efficacy of treatment with PCI versus placebo
      in reducing the size of subcutaneous, benign lipomas, was sponsored by
      Advance Biofactures Corporation.

	 	 	 
	 		
      [**] study animals were to be enrolled with each subject
      having at least two lipomas. [**]. The trial was suspended [**].
    [**].

	 	 	 
	 		
      5.3.1 Study Results

	 	 	
       

	
    [**]  
	
    [**]  
	
      
	
    [**] 
	
      
	
    [**] 
	
      
	
    [**] 
	
      
	
    [**] 

	
    [**]  
	
    [**]  
	
    [**]  
	
    [**] 
	
    [**] 
	
    [**] 
	
    [**] 
	
    [**] 
	
    [**]  
	
    [**] 

	
    [**]  
	
    [**]  
	
    [**]  
	
    [**] 
	
    [**] 
	
    [**] 
	
    [**] 
	
    [**] 
	
    [**]  
	
    [**] 

	
    [**]  
	
    [**]  
	
    [**]  
	
    [**] 
	
    [**] 
	
    [**] 
	
    [**] 
	
    [**] 
	
    [**]  
	
    [**] 

	
    [**]  
	
    [**]  
	
      
	
    [**] 
	
      
	
    [**] 
	
      
	
    [**] 
	
      
	
    [**] 

	
    [**]  
	
    [**]  
	
    [**]  
	
    [**] 
	
    [**] 
	
    [**] 
	
    [**] 
	
    [**] 
	
    [**]  
	
    [**] 

	
    [**]  
	
    [**]  
	
    [**]  
	
    [**] 
	
    [**] 
	
    [**] 
	
    [**] 
	
    [**] 
	
    [**]  
	
    [**] 

	
    [**]  
	
    [**]  
	
    [**]  
	
    [**] 
	
    [**] 
	
    [**] 
	
    [**] 
	
    [**] 
	
    [**]  
	
    [**] 

	 	 
	** 	CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN
      OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
      COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

10 

	Double Blind Study to Evaluate the Efficacy of
      Collagenase Clostridium Histolyticum for the 
	Treatment of Canine Lipoma 
	Chien-804 
	
                   
                         
                         
                         
                         
                         
                         
                         
                         
                         
                       DRAFT 110826
    

	 		
      [**].

	 	 	 	 
	 	5.3.2 	
      Adverse Reactions

	 	 	 	 
	 		5.3.2.1 	
      [**]

	 	 	 	 
	 		5.3.2.2 	
      [**]

	 	 	 	 
	 	5.3.3 	
      Client Questionnaire [**].

	 	5.3 	
      Study Rationale

	 	 	 
	 		
      The conclusion from the studies conducted to date using
      PCI for treatment of canine lipoma, indicate [**] months post collagenase
      injection.

	 	 	 
	 		
      [**]. Based on these results as well as the safety
      experience in human clinical trials and the potential therapeutic benefits
      of CCH, an additional controlled study is justified.

	 	 	 
	 	5.4 	
      Investigational Veterinary Product

	 	 	 
	 		
      Collagenase Clostridium Histolyticum (CCH) manufactured
      by Auxilium Pharmaceuticals, Inc. has been approved by the FDA for use in
      humans for Dupuytren’s Contracture. [**].

	 	 	 
	 	5.5 	
      Rationale for Dosage Selection

	 	 	 
	 		
      Based upon the [**] results achieved in Chien-802, [**]
      mg drug will be administered per square centimeter of the lipoma. Data
      from the Chien-802 study supports the continued use of a maximum dose of
      [**] mg per single injection.

	6.0 	
      STUDY DESIGN

	 	 	 
		6.1 	
      Study Structure

	 	 	 
			
      6.1.1 Study Type

	 	 
	** 	CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN
      OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
      COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

11 

	Double Blind Study to Evaluate the Efficacy of
      Collagenase Clostridium Histolyticum for the 
	Treatment of Canine Lipoma 
	Chien-804 
	
                   
                         
                         
                         
                         
                         
                         
                         
                         
                         
                       DRAFT 110826
    

	 	 	
       
	 	6.1.2 	
      Sample Size Determination

	 	 	 
	 		
      Based on the results from the previous study using PCI,
      the sample size for the proposed study is conservatively based on the
      assumption that [**].

	 	 	 
	 		
      [**].

	 	 	 
	 	6.1.3 	
      Control Group

	 	 	 
	 		
      Since there is no proven effective, non-surgical
      treatment for lipoma, and spontaneous remission does not occur, a placebo
      will be administered to the control animals. The control group and the
      test group will be treated and observed the same throughout the
    trial.

	 	 	 
	 	6.1.4 	
      Blinding

	 	 	 
	 		
      To minimize the risk of biased study outcomes this
      protocol will be conducted as a double blind study. The level of blinding
      will extend to the client, the investigator, and anyone involved in
      determining subject eligibility, evaluation of endpoints, and assessment
      of compliance to the protocol. All precautions will be taken to insure
      that this level of blinding is maintained throughout the trial until all
      such opportunities for bias have passed. Unblinding will only be permitted
      in the case of a medical emergency or to provide adequate medical
    care.

	 	 	 
	 	6.1.5 	
      Randomization

	 	 	 
	 		
      To minimize the possibility of bias, the same subject
      population will be randomly allocated to study treatment (CCH or Placebo).
      A randomization table will be provided by the statistician to the
      treatment dispenser prior to the start of the study. On the day of
      injection, the study animal will receive the next available treatment
      sequence listed in the randomization table.

	 	 	 
	 	6.1.6 	
      Study Duration

	 	 	 
	 		
      Subject accrual in this study is scheduled to start in
      [**] of [**]. The projected study end will be
[**].

	 	 
	** 	CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN
      OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
      COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

12 

	Double Blind Study to Evaluate the Efficacy of
      Collagenase Clostridium Histolyticum for the 
	Treatment of Canine Lipoma 
	Chien-804 
	
                   
                         
                         
                         
                         
                         
                         
                         
                         
                         
                       DRAFT 110826
    

	 	 	
       
	 	7.0 	
      STUDY ANIMAL SELECTION

	 	 	 	 	 	 
	 		7.1 	
      Population Base

	 	 	 	 	 	 
	 			
      Thirty-two, client owned dogs with subcutaneous, benign
      lipomas will be used in this study. [**]. Subjects must meet all of the
      inclusion criteria and none of the exclusion criteria to be eligible for
      entry into this study.

	 	 	 	 	 	 
	 		7.2 	
      Inclusion Criteria

	 	 	 	 	 	 
	 			7.2.1 	
      [**].

	 	 	 	 	 	 
	 			7.2.2 	
      [**].

	 	 	 	 	 	 
	 			7.2.3 	
      [**].

	 	 	 	 	 	 
	 			7.2.4 	
      [**].

	 	 	 	 	 	 
	 		7.3 	
      Exclusion criteria

	 	 	 	 	 	 
	 			7.3.1 	
      [**].

	 	 	 	 	 	 
	 			7.3.2 	
      [**].

	 	 	 	 	 	 
	 			7.3.3 	
      [**].

	 	 	 	 	 	 
	 			7.3.4 	
      [**].

	 	 	 	 	 	 
	 			7.3.5 	
      [**].

	 	 	 	 	 	 
	 			7.3.6 	
      [**].

	 	 	 	 	 	 
	 				7.3.6.1 	
      [**]

	 	 	 	 	 	 
	 				7.3.6.2 	
      [**]

	 	 	 	 	 	 
	 				7.3.6.3 	
      [**]

	 	 	 	 	 	 
	 			7.3.7 	
      [**].

	 	8.0 	
      ANIMAL MANAGEMENT PRACTICES

	 	 	 	 
	 		8.1 	
      Food and Water

	 	 	 	 
	 			
      Food and water will be provided as is customary by
      owners.

	 	 	 	 
	 		8.2 	
      Housing

	 	 	 	 
	 			
      Dogs will be kept in their home environment during the
      study although dogs may be kept in the clinic for short periods of time
      for owner convenience.

	 	 	 	 
	 		8.3 	
      Study Animal Care

	 	 	 	 
	 			
      The study animal will remain at the clinic site for a
      minimum of [**] post-injection to be monitored for safety and immediate
      adverse events. Clients will be instructed not to put pressure on the
      injected lipoma, and to contact the investigator or clinic immediately,
      if they notice any problems. Instructions will be provided to the
client for completion of a diary for recording adverse events.

		
	** 	CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN
      OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
      COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

13 

	Double Blind Study to Evaluate the Efficacy of
      Collagenase Clostridium Histolyticum for the 
	Treatment of Canine Lipoma 
	Chien-804 
	
                   
                         
                         
                         
                         
                         
                         
                         
                         
                         
                       DRAFT 110826
    

	 	 	
       
	 	8.4 	
      Comcomitant Medication

	 	 	 
	 		
      Dogs may be treated with medication that the dog is
      taking for control of an ongoing pre- existing medical condition that is
      well stabilized. [**]. These and all other concomitant medications must be
      recorded on the Case Report Form (CRF). Additionally, any diagnostic,
      therapeutic, or surgical procedure performed during the study period must
      be recorded including date, indication, description of procedure performed
      and any clinical findings.

	 	9.0 	
      STUDY ASSESSMENTS 9.1 Physical
  Examination

	 	 	 
	 		
      [**]

	 	9.2 	
      Laboratory Analyses

	 	 	 	 	 
	 		9.2.1 	
      Serum Chemistry

	 	 	 	 	 
	 			[**] 	
      

	 	 	 	 	 
	 		9.2.2 	
      Hematology

	 	 	 	 	 
	 			[**] 	
      

	 	 	 	 	 
	 		9.2.3 	
      Urinalysis

	 	 	 	 	 
	 			[**] 	
      

	 	9.3 	
      Efficacy Parameters

	 	 	 
	 		
      [**] will be used as the primary assessment of
      efficacy.

	 	9.3.1 	
      Primary Efficacy Endpoint [**].

	 	 	 	 
	 	9.3.2 	
      Secondary Efficacy Endpoints:

	 	 	 	 
	 		9.3.2.1 	
      [**]

	 	 	 	 
	 		9.3.2.2 	
      [**]

	 	 	 	 
	 		9.3.2.3 	
      [**]

	 	 	 	
       
	 	 	9.3.2.4 	
      [**] 

	 	 
	** 	CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN
      OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
      COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

14 

	Double Blind Study to Evaluate the Efficacy of
      Collagenase Clostridium Histolyticum for the 
	Treatment of Canine Lipoma 
	Chien-804 
	
                   
                         
                         
                         
                         
                         
                         
                         
                         
                         
                       DRAFT 110826
    

	 	 	 
	 	9.4 	
      Safety Parameters

	 	 	 	 	 
	 		
      Adverse events and local site reactions will be assessed
      for each follow-up visit and may group subjects by the treatment dose for
      local site reactions.

	 	 	 	 	 
	 	9.5 	
      Additional Information

	 	 	 	 	 
	 		9.5.1 	
      Lipoma Characteristics

	 	 	 	 	 
	 			[**] 	
      

	 	 	 	 	 
	 		9.5.2 	
      Client Questionnaire

	 	 	 	 	 
	 			[**] 	
      

	10.0 	
      SCHEDULE OF STUDY
EVENTS

	 	10.1 	
      Screening

	 	 	 	 
	 		
       	
      [**]

	 	 	 	 
	 		
      10.1.1	
       Subject Information: [**] 

	 	 	 	 
	 	 	10.1.2	
       Medical History: [**] 

	 	 	 	 
	 	 	10.1.3	 Physical Examination: [**] 
	 	 	 	 
	 	 	10.1.4 	Laboratory Analysis: [**] 
	 	 	 	 
	 	 	10.1.5	Biopsy: [**] 
	 	 	 	 
	 	 	10.1.6	CT Scan: [**].
	 	 	 	 
	 	10.2 	
      (Day [**]) Administration study
      drug

	 	 	 	 
	 		
      10.2.1	
      [**]. 

	 	 	 	 
	 	 	10.2.2	
      [**] 

	 	 	 	 
	 	 	10.2.3	[**] 
	 	 	 	 
	 	 	10.2.4	[**] 
	 	 	 	 
	 	 	10.2.5	[**] 
	 	 	 	 
	 	 	10.2.6	[**]
	 	 	 	 
	 	10.3 	
      Day 	
      [**] 

	 	 	 	 
	 	 	10.3.1 	
      [**] 

	 	 	 	 
	 	 	10.3.2	
      [**] 

	 	 	 	 
	 	 	10.3.3	
      [**] 

	 	 	 	 
	 	 	10.3.4	
      [**]

	 	 	 	 
	 	10.4 	
      Day 	
      [**] 

	 	 	
       	
       
	 	 	
      10.4.1	
      [**]

	 	 
	** 	CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN
      OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
      COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

15 

	Double Blind Study to Evaluate the Efficacy of
      Collagenase Clostridium Histolyticum for the 
	Treatment of Canine Lipoma 
	Chien-804 
	
                   
                         
                         
                         
                         
                         
                         
                         
                         
                         
                       DRAFT 110826
    

	 	 	
       
	 	10.4.2 	
      [**]

	 	 	 
	 	10.4.3 	
      [**]

	 	 	 
	 	10.4.4 	
      [**]

	 	 	 
	 	10.4.5 	
      [**]

	 	 	 
	 	10.4.6 	
      [**]

	 	10.5 	
      Month [**] (Day [**]) or at time of
      removal from study

	 	 	 	 
	 		10.5.1 	
      [**]

	 	 	 	 
	 		10.5.2 	
      [**]

	 	 	 	 
	 		10.5.3 	
      [**]

	 	 	 	 
	 		10.5.4 	
      [**]

	 	 	 	 
	 		10.5.5 	
      [**]

	 	 	 	 
	 		10.5.6 	
      [**]

	 	10.6 	
      Early Termination

Study animals may be removed from the
study by the investigator or may be withdrawn from the study by the client at
any time and for any reason. It is understood that an excessive rate of
withdrawals can jeopardize the analysis of the study and therefore unnecessary
withdrawals should be avoided. At the time of discontinuation, all efforts will
be made to complete the procedures and evaluations scheduled for the [**] month
follow-up visit. 

If a subject withdraws or is removed
from the study, the reason for and date of the discontinuation should be
recorded in the CRF Study Termination page. 

Any subject that does not reach the
[**] day post injection visit may be replaced. 

	11.0 	
      TRIAL MEDICATION

	 	 	 	 
		11.1 	
      Investigational Veterinary Product

	 	 	 	 
			11.1.1 	
      Trade Name XIAFLEX®

	 	 	 	 
			11.1.2 	
      Active Ingredient

	 	 	 	 
				
      Collagenase Clostridium Histolyticum

	 	 	 	 
			11.1.3 	
      Dosage Form

	 	 	 	 
				
      Sterile, lyophilized formulation containing [**], [**],
      [**], and [**] mg of Collagenase Clostridium Histolyticum. The drug is
      reconstituted with a diluent consisting of [**]% sodium chloride
      containing [**]% calcium chloride.

	 	 
	** 	CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN
      OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
      COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

16 

	Double Blind Study to Evaluate the Efficacy of
      Collagenase Clostridium Histolyticum for the 
	Treatment of Canine Lipoma 
	Chien-804 
	
                   
                         
                         
                         
                         
                         
                         
                         
                         
                         
                       DRAFT 110826
    

	 	 	
       
	 	11.1.4 	
      Packaging

	 	 	 
	 		
      The drug product is supplied in glass vials as a sterile
      product. The diluent is also sterile and will be supplied in glass
      vials.

	 	 	 
	 	11.1.5 	
      Lot/Batch Number/Expiration Date

	 	 	 
	 		
      The lot and/or batch number and expiration and/or retest
      date will be included on each shipment and recorded in the drug inventory
      forms.

	 	 	 
	 	11.1.6 	
      Labeling

	 	 	 
	 		
      Labeling on each vial will include the identity of the
      product, storage conditions and the federal caution statement cited in
      21CFR511.1[b](1).

	 	 	 
	 	11.1.7 	
      Storage Condition

	 	 	 
	 		
      The drug will be shipped under refrigerated conditions
      (2-8oC) and must also be stored refrigerated at the site in an area with
      restricted access. The diluent for reconstitution may be shipped at 2-30
      oC and stored at 2-8oC.

	 	11.2 	
      Control Product [Placebo]

	 	 	 	 
	 		11.2.1 	
      Active Ingredient None

	 	 	 	 
	 		11.2.2 	
      Dosage Form

	 	 	 	 
	 			
      Sterile, lyophilized formulation containing [**]. The
      placebo is reconstituted with a diluent consisting of [**].

	 	 	 	 
	 		11.2.3 	
      Packaging

	 	 	 	 
	 			
      The placebo is supplied in glass vials as a sterile
      product. The diluent is also sterile and will be supplied in glass
      vials.

	 	 	 	 
	 		11.2.4 	
      Lot/Batch Number/Expiration Date

	 	 	 	 
	 			
      The lot and/or batch number and expiration and/or retest
      date will be included on each shipment and recorded in the drug inventory
      forms.

	 	 	 	 
	 		11.2.5 	
      Labeling

	 	 	 	 
	 			
      Labeling on each vial will include the identity of the
      product, storage conditions and the federal caution statement cited in
      21CFR511.1[b](1).

	 	 
	** 	CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN
      OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
      COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

17 

	Double Blind Study to Evaluate the Efficacy of
      Collagenase Clostridium Histolyticum for the 
	Treatment of Canine Lipoma 
	Chien-804 
	
                   
                         
                         
                         
                         
                         
                         
                         
                         
                         
                       DRAFT 110826
    

	 	 	 
	 	11.2.6 	Storage Condition  
	 	 
	 	The placebo will be shipped under refrigerated
      conditions (2-8oC) and must also be stored refrigerated at the site in an
      area with restricted access. The diluent for reconstitution may be shipped
      at 2-30 oC and stored at 2-8oC. 

	 	11.3 	
      Reconstitution

	 	 	 
	 		
      The dispenser will follow the procedures for
      reconstitution of CCH provided by Advance Biofactures Corporation, and
      maintain a record of the date(s) and time(s) of reconstitution and
      dispensation of the assigned treatment.

	 	 	 
	 		
      Once reconstituted with diluent, study drug and placebo
      (contained in the vial or syringe) can be kept at room temperature (25oC)
      for up to 1 hour or refrigerated (2-8oC) for up to 4 hours prior to
      administration. If refrigerated, the reconstituted product must remain at
      room temperature for approximately 15 minutes prior to use.

	 	 	 
	 	11.4 	
      Injection Medication

	 	 	 
	 		
      Syringes containing either study drug or placebo will be
      prepared by the dispenser and delivered to the investigator. They will
      appear identical and provide no indication as to the contents. Labeling of
      the injection syringe should be limited to date of preparation, study
      animal number and name.

	 	 	 
	 		
      The dispenser shall keep accurate records of dates of
      reconstitution in addition to data required for the determination of drug
      administered.

	 	 	 
	 	11.5 	
      Drug Dispensation

	 	 	 
	 		
      The dispenser and investigator agree neither to dispense
      the study drug from, nor store it, at any site(s) other than the one
      listed on the cover page. The investigator also agrees that the study
      drug(s) will be administered only to study subjects as per this
      protocol.

	 	 	 
	 	11.6 	
      Drug Accountability

	 	 	 
	 		
      Documentation of dates and numbers of product shipped and
      received will be kept as well as records of product returned. All
      containers of study drug, whether empty or containing used or unused study
      drug are to be available for inspection by the Clinical Trial
    Monitor.

	12.0 	
      ADMINISTRATION OF STUDY MEDICATION 

	 	 
	 	12.1 	Treatment Allocation

18 

	Double Blind Study to Evaluate the Efficacy of
      Collagenase Clostridium Histolyticum for the 
	Treatment of Canine Lipoma 
	Chien-804 
	
                   
                         
                         
                         
                         
                         
                         
                         
                         
                         
                       DRAFT 110826
    

	 	 	
       
	 	12.1.1 	
      On the day of treatment, the investigator will provide
      the dispenser with the study animal number scheduled for treatment and the
      dimensions of the lipoma to be treated [**] by completing a Request For
      Preparation of Drug.

	 	 	 
	 	12.1.2 	
      The study animal will be randomized to the next available
      treatment sequence, either CCH or PLACEBO, on the day of treatment
      provided they have been found to be eligible for the trial. Randomization
      will be closely monitored by the clinical monitor to assure that the
      randomization sequence has been assigned in the correct
  order.

	 	12.2 	
      Dose

	 	 	 
	 		
      The pharmacist will calculate the dose to be administered
      as [**] mg per cm2. Calculations, reconstitution and
      dispensation will be recorded on the Drug Dispensation Form.

	 	 	 
	 		
      The dose will be administered in a single
    injection.

	 	 	 
	 		
      NOTE: Study medication may not be administered
      less than [**] hours after [**]

	 	 	 
	 	12.3 	
      Route of Administration and Frequency

	 	 	 
	 		
      The test article will be administered once directly into
      the lipoma.

	 	 	 
	 		
      12.4 Injection Technique

	 	 	 
	 		
      The specific technique for injection of study drug into
      the lipoma will be left to the discretion of the investigator.
  [**].

	 	 	 
	 		
      [**].

	13.0 	
      SAFETY EVALUATION/ADVERSE EVENTS

	 	 	 
		13.1 	
      Definition

	 	 	 
			
      An adverse event (AE) is any unfavorable and unintended
      observation which occurs after the use of the investigational veterinary
      product whether or not considered to be product
related.

	 	 
	** 	CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN
      OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
      COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

19 

	Double Blind Study to Evaluate the Efficacy of
      Collagenase Clostridium Histolyticum for the 
	Treatment of Canine Lipoma 
	Chien-804 
	
                   
                         
                         
                         
                         
                         
                         
                         
                         
                         
                       DRAFT 110826
    

	 	 	 
	 	13.2 	Reporting Adverse Events 
	 	 	 
	 	 	All adverse events must be recorded in the
      subject animal’s medical records and on the Case Report Form. All serious
      adverse events (SAEs), i.e. those events that are life- threatening or
      requiring veterinary intervention, must be reported to the sponsor
      immediately or within 24 hours of observing. 

	 	13.3 	
      Monitoring Adverse Events:

	 	 	 	 
	 		
      Adverse events will be assessed and followed for [**]
      months post injection with the exception of related events which must be
      followed until resolution.

	 	 	 	 
	 		13.3.1 	
      The onset and end dates, severity, affect on study drug
      administration (e.g., discontinuation), relationship to study drug, and
      administration of any other drug(s) to treat this event will be recorded
      for each adverse event.

	 	 	 	 
	 		13.3.1 	
      Any actions taken and follow-up results must be recorded
      on the appropriate page of the Case Report Form.

	 	 	 	 
	 		13.3.2 	
      For all adverse events which require the study animal to
      be discontinued from the study, relevant clinical assessments must be
      recorded.

	 	 	 	 
	 	13.4 	
      Death of a Subject

	 	 	 	 
	 		
      Should any dog die during the course of this study, a
      necropsy will be conducted (pending consent by the owner) by a veterinary
      pathologist if possible. If unavailable, the necropsy may be conducted by
      the Investigator or other veterinarian. Tissue samples for histopathology
      are to be collected as warranted by the circumstances surrounding the
      death. Findings and conclusions will be filed with the subject source
      data. Disposition of the subject remains will be left to the Owner’s
      discretion.

	14.0 	
      STATISTICAL ANALYSIS

	 	 	 	 
		14.1 	
      Analysis Population

	 	 	 	 
			14.1.1 	
      The intent-to-treat (ITT) population will consist of all
      randomized subjects that receive at least one dose of study
  article.

	 	 	 	 
			14.1.2 	
      The per-protocol (PP) population will consist of all
      subjects who are eligible for the study, receive the protocol-mandated
      study treatment and complete study procedures, including visits from
      screening to the [**] month visit without major protocol violations or
      violations that can affect measurement of the primary endpoint. This
      includes the [**] month CT Scan.

	 	 
	** 	CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN
      OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
      COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

20

	Double Blind Study to Evaluate the Efficacy of
      Collagenase Clostridium Histolyticum for the 
	Treatment of Canine Lipoma 
	Chien-804 
	
                   
                         
                         
                         
                         
                         
                         
                         
                         
                         
                       DRAFT 110826
    

	 	 	
       
	 	14.1.3 	
      The safety population (SP) will consist of all randomized
      subjects that receive at least one dose of investigational veterinary
      product.

	 	14.2 	
      Efficacy Analysis

	 	 	 	 
	 		
      Statistical significance will be evaluated at a two-sided
      alpha = 0.05 level for all tests.

	 	 	 	 
	 		14.2.1 	
      The primary efficacy parameter is [**]. The primary
      statistical analysis will use the [**].

	 	 	 	 
	 		14.2.2 	
      Secondary efficacy parameters will include the
      measurements below.

	 		14.2.2.1 	
      Responders at [**] days and [**] months. [**] Test will
      be used for the responder analysis.

	 	 	 	 
	 		14.2.2.2 	
      [**]

	 	 	 	 
	 		14.2.2.2 	
      [**]

	 	 	 	 
	 		14.2.2.4 	
      [**]

	 	 	 	 
	 	14.2.3 	
      [**]

	 	14.3 	
      Safety Analysis

	 	 	 
	 		
      Tables of adverse events and local site reactions will be
      constructed by treatment.

	 	 	 
	 	14.4 	
      Visit Windows

	 	 	 
	 		
      All scheduled visits are to be included in the
      statistical analysis. Visits after Day [**] will be assigned to the
      nearest scheduled time point for the statistical analysis. If a visit is
      equidistant from two time points then it will be assigned to the later of
      the two time points. Only one visit can be assigned to a time point. If
      two visits are candidates for a time point than the nearer of the two will
      be assigned and the other may be assigned to the later time
  point.

	 	14.5 	
      Missing Data

	 	 	 	 
	 		14.5.1 	
      Primary Efficacy Assessment

	 	 	 	 
	 			
      For the primary efficacy endpoint, if the [**] month
      follow-up visit observation is missing then the [**] day visit observation
      will be carried forward to the [**] month visit. If a [**] day follow-up
      visit observation is not available to carry forward, then that subject
      will be dropped from the analysis.

	 	 	 	 
	 		14.5.2 	
      Secondary Efficacy Variables

	 	 	 	 
	 			
      For the secondary variables, analysis at a visit will use
      only data collected at that visit. Observations will not be carried
      forward from an earlier visit to replace missing values at a later
      visit.

	 	 
	** 	CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN
      OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
      COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

21

	Double Blind Study to Evaluate the Efficacy of
      Collagenase Clostridium Histolyticum for the 
	Treatment of Canine Lipoma 
	Chien-804 
	
                   
                         
                         
                         
                         
                         
                         
                         
                         
                         
                       DRAFT 110826
    

	 	
       
	15.0 	
      REGULATORY AND ADMINISTRATIVE
  ASPECTS

	 	15.1 	Regulatory 
	 	 	 
	 		The investigator will ensure that this trial
      will be conducted in the spirit of Good Clinical Practice, VICH GL9, May
      09, 2001, Center for Veterinary Medicine Guidance #85. The investigator
      and dispenser must sign the signature page prior to subject treatment or
      dispensation of drug. 
	 	 	 
	 	15.2 	Informed Consent 
	 	 	 
	 		It is the responsibility of the investigator to
      obtain written informed consent from each client prior to performing any
      study-related procedure. The client must sign a statement which indicates
      that they have given their consent for the study animal to participate in
      the trial. 
	 	 	 
	 	15.3 	Departures from Protocol/Amendments
  
	 	 	 
	 		When circumstances arise, whereby a departure
      from this protocol should be considered, the investigator or other
      veterinarian in attendance, or the study coordinator must contact the
      study monitor by telephone as soon as possible prior to implementation.
      Any departure from the agreed protocol will pertain only to the individual
      study animal involved. The Case Report Form will describe the
      circumstances and identify the pertinent protocol procedure. 
	 	 	 
	 		In the event that a protocol change is proposed
      for all study animals, then a prior discussion between the investigator
      and Advance Biofactures Corporation should be made prior to the protocol
      amendment. 
	 	 	 
	 	15.4 	Handling of Records 
	 	 	 
	 		The investigator must maintain adequate and
      accurate records on the forms provided for this study to enable the
      conduct of the study to be fully documented and the study data to be
      subsequently verified. Raw data will be recorded at the time of
      observation. A copy of records (labs, pathology, imaging reports) provided
      to the investigator must be reviewed and signed by the investigator.

	 	 	 
	 		All study data must be kept on file by the
      Investigator or at a site approved by ABC. No study document should be
      destroyed without prior written agreement between ABC and the
      Investigator. Clinical samples will be disposed of as per normal
      laboratory procedures. 

22 

	Double Blind Study to Evaluate the Efficacy of
      Collagenase Clostridium Histolyticum for the 
	Treatment of Canine Lipoma 
	Chien-804 
	
                   
                         
                         
                         
                         
                         
                         
                         
                         
                         
                       DRAFT 110826
    

	 	 	
       
	 	15.5 	
      Monitoring of the Study

	 	 	 
	 		
      It is understood that the Advance Biofactures Corporation
      monitor or representative will contact and visit the investigator/site
      regularly. It will be the monitor’s responsibility to inspect the
      documentation at regular intervals throughout the study, to verify the
      completeness, consistency and accuracy of the data being entered on them,
      and to verify adherence to the protocol. The monitor should have access to
      laboratory test reports and other subject records needed to verify the
      entries on the Case Report Form. The investigator and study coordinator
      agree to cooperate with the monitor to ensure that any problems detected
      in the course of these monitoring visits are
resolved.

23 

	Double Blind Study to Evaluate the Efficacy of
      Collagenase Clostridium Histolyticum for the 
	Treatment of Canine Lipoma 
	Chien-804 
	
                   
                         
                         
                         
                         
                         
                         
                         
                         
                         
                       DRAFT 110826
    

	 	
       
	16.0 	
      SIGNATURE PAGE

	 	 
		I have thoroughly read and reviewed the study protocol.
      Having read and understood the requirements and conditions of the study
      protocol, I agree to adhere to the protocol and perform the clinical study
      according to the spirit of Good Clinical Practice, VICH GL9, May 09, 2001,
      Center for Veterinary Medicine Guidance #85.
	 	 
		I agree to use the study material, including medication and
      diluent, only as specified in the protocol.
	 	 
		I understand that changes to the protocol must be made in
      the form of an amendment which has prior written approval from the
      Sponsor. I understand that any violation of the protocol may lead to early
      termination of the Study.
	 	 
		I agree to follow the study time schedule as outlined in
      the protocol.
	 	 
		I agree to report to the Sponsor, within one working day,
      any clinical adverse event that is serious, whether considered
      treatment-related or not.

	Investigator 	 	 	/ 	 
		 	[**] 	Date 	 
	  	 	 	  	 
	Dispenser 	 	 	/ 	 
		 	[**]  	Date 	 

	 	 
	** 	CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN
      OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
      COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

24 

 

	Double Blind Study to Evaluate the Efficacy of
      Collagenase Clostridium Histolyticum for the 
	Treatment of Canine Lipoma 
	Chien-[**] 

DRAFT 110826

CLIENT QUESTIONNAIRE 

	Subject #	 	 	Study Animal Name  	 
	 	 	 	 	 
	Study Visit	 	 	Date 	 
	 	 	 	 	 
	Location of Lipoma  	 	 	 	 

To Be Completed by the Client: Please provide the
requested information regarding the lipoma to be treated. Enter the number of
the best response. Feel free to write comments at the end

[   ] Initial Screening Visit:

	1. What is the [**] the lipoma? 	1 = [**] 
2 = [**] 
3 = [**] 
4 =
      Other, please cite reason 	
	2. How [**]does the lipoma to be treated [**]? 	1 = [**] 
2 = [**] 
3 = [**] 
4 = [**]
    	
	
      3. If the location of the lipoma is on one side, [**]? 

      (Record N/A if this is not applicable to your dog) 
	1 = [**] 
2 = [**] 
3 = [**] 
4 = [**]
    	

[   ] All Follow-Up Visits:

	1. Is your dog experiencing any [**]? 	1 = [**] 
2 = [**] 
3 = [**] 
4 = [**]
    	
	2. How [**]does the lipoma to be treated [**]? 	1 = [**] 
2 = [**] 
3 = [**] 
4 = [**]
    	

 

	** 	
      CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED
      AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT
      TO A CONFIDENTIAL TREATMENT REQUEST.

	Double Blind Study to Evaluate the Efficacy of
      Collagenase Clostridium Histolyticum for the 
	Treatment of Canine Lipoma 
	Chien-[**] 

DRAFT 110826

	3. If the location of the lipoma is on one side, [**]?
      (Record N/A if this is not applicable to your dog)
	1 = [**] 
2 = [**] 
3 = [**] 
4
      = [**] 	
	4. Considering your reason for treatment, how [**]? 	1 = [**] 
2 = [**] 
3 = [**] 	
	5. Would you participate in this trial again? 	1 = Yes
2 = No 
3 = Undecided
      
Explain Below in Comments	

 

	Comment: 	 	 
	 	 	 
	 	 	 
	 	 	 
	 	 	 

Client Signature__________________________________ /
Date_______________

	** 	
      CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED
      AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT
      TO A CONFIDENTIAL TREATMENT REQUEST.

	 	
       

	
      PROTOCOL CHIEN-[**] 

      REQUEST FOR PREPARATION OF
      DRUG
  

	  	DATE:_________________ 
	 	 
	SUBJECT#_____________ 	SUBJECT
      NAME:_____________________________ 
	 	 

Dose: ([**] lipoma)

Lipoma Location:________________________

Lipoma [**] ([**]
measurement):       ___________________[**]

Total Drug to be Injected (area x dose
):           ___________________
mg

Volume to be Injected (total
drug/0.58mg):       ___________________
mL

 

PI
Signature:__________________________________       Date:__
__ / __ __ __ / __ __

	** 	
      CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED
      AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT
      TO A CONFIDENTIAL TREATMENT REQUEST.

Page 1 of 1

  
	DRUG DISPENSATION RECORD
      
	 
	PROTOCOL Chien-[**]
      
	 	 
	
    Investigator: [**] 
	
    Site: [**] 

	
    Drug:
      XIAFLEX® 
	
    Indication: Lipoma 

	
     
	
     

	
    Patient
      Name: 
	
    Patient Study Number 

  

LIPOMA RANDOMIZED
TO:_______________________ SEQUENCE # ____  

	
    RECONSTITUTION: Add [**] mL
      Reconstitution Diluent to the Vial of XIAFLEX® = 0.58 mg/mL 

	  	Time removed from refrigeration _________ hrs 

  
	
    Date  	XIAFLEX® 

    Lot #  	Diluent 

    Lot #  	Volume 

    Diluent 

    Added  	Date / Time of Reconstitution
     	
    Prepared
      By:
	 	 	 	 	 	  

  

DOSE: [**] lipoma

  
	
    

    Syringe #1 filled with:
      ____________________________________
	 

    (CCH or PLACEBO) 

 
	
    
     Lipoma [**] 
	Total 	Volume to Be Injected 	Actual 	
    Dispensed By / Date  
	
      	Medication 	(Total Medication /0.58) 	Volume Filled 	 
     
	
      	to Be 	  	in 	 
     
	
      	Injected 	  	Syringe #1 	 
     
	
      	(area x 0.02) 	  	  	   
	
     
                         
           cm2 
	
    mg 
	
    mL 
	  	   

  

** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN
OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION
PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST.

 

Schedule 3.1(b)(2) Human Lipoma Protocol 

  
  	
      

      Confidential treatment requested under 17 C.F.R. §§ 200.80(b)(4)
and 240.24b -2. The confidential portions of this exhibit have been omitted and
are marked accordingly. The confidential portions have been filed separately
with the Securities and Exchange Commission pursuant to a confidential treatment
request. 

 

  

 

A DOSE ESCALATION STUDY USING COLLAGENASE

CLOSTRIDIUM HISTOLYTICUM IN THE
TREATMENT
OF LIPOMA 

Lipoma [**]

 

 

 

BB IND 8486

 

Investigator/Sponsor:       
[**]

[**]

The information contained in this document is provided to you
in confidence for review by you, your staff, an applicable Ethics
Committee/Institutional Review and regulatory authorities. It is understood that
the information will not be disclosed to others without prior written approval
from Advance Biofactures Corporation except to the extent necessary to obtain
informed consent from those persons to whom the medication may be administered.

** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND
FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A
CONFIDENTIAL TREATMENT REQUEST. 

A Dose Escalation Study Using Collagenase Clostridium
Histolyticum 

in the Treatment of Lipoma

 Lipoma [**] 

110718 

	   TABLE OF
      CONTENTS   
	  	SYNOPSIS
      	5  
	1. 	INTRODUCTION	7  
	2. 	USE OF
      PURIFIED COLLAGENASE FOR INJECTION	8  
	  	2.1 	Pre-Clinical Studies 	8  
	  	2.2 	Clinical
      Studies 	9  
	  	2.3 	Treatment of Lipoma 	9  
	  	  	2.3.1 	Study Design	9  
	  	  	2.3.2 	Study Results	10  
	  	  	2.3.3 	Adverse Reactions	10  
	3. 	USE OF COLLAGENASE
      CLOSTRIDIUM HISTOLYTICUM	10  
	4. 	REFERENCES	12  
	5. 	RATIONALE	12  
	  	5.1 	Study
    Rationale	12  
	  	5.2 	Rationale for Dosage	12  
	  	5.3 	Injection
      technique	13  
	6. 	OBJECTIVE	13  
	7. 	STUDY
      DESIGN	13  
	  	7.1 	Study Center	13  
	  	7.2 	Sample Size	13  
	  	7.3 	Efficacy Parameters	13  
	  	  	7.3.1 	Primary Efficacy
    Outcome	13  
	  	  	7.3.2 	Secondary Efficacy Outcome	13  
	  	7.4 	Additional
      Information	14  
	  	7.5 	Safety Parameters	14  
	  	7.6 	Investigational Plan	14  
	  	7.7 	Subject Care	15  
	  	7.8 	Follow-Up	15  
	  	7.9 	Assessments	15  
	  	7.10 	Handling
      Samples	17  
	  	7.11 	Safety Reports	17  

2

A Dose Escalation Study Using Collagenase Clostridium
Histolyticum 
in the Treatment of Lipoma 
Lipoma [**] 

110718 

	8.0 	STUDY
      POPULATION 	17  
	  	8.1 	Inclusion Criteria	17  
	  	8.2 	Exclusion
      Criteria	18  
	9.0 	TRIAL MEDICATIONS	19  
	  	9.1 	Study Drug
      (XIAFLEX®) 	 19  
	  	9.2 	Reconstitution Diluent	19  
	  	9.3 	Injection
      Medications	19  
	  	9.4 	Drug Storage	19  
	  	9.5 	Drug
      Accountability	19  
	  	9.6 	Administration of Study
      Medication	19  
	  	  	9.6.1 	Reconstitution 	19  
	  	  	9.6.2 	Route of Administration	20  
	  	9.7 	Concomitant
      Treatment	20  
	10.0 	STUDY METHODOLOGY	21  
	  	10.1 	Measurements
      and Evaluation	21  
	  	10.2 	Schedule of Testing /
      Follow-Up Visits	21  
	  	10.3 	Early
      Termination 	24  
	 11.0 	SAFETY EVALUATION / ADVERSE
      EVENTS 	24  
	  	11.1 	Adverse
    Events	24  
	  	11.2 	Recording Adverse Events	24  
	  	11.3 	Monitoring
      Adverse Events	25  
	  	11.4 	Known Potential Toxicity of
      Study Drug(s)	25  
	  	11.5 	Serious
      Adverse Events	25  
	 12.0 	STATISTICAL ANALYSIS
	26  
	  	12.1 	Safety
    Analysis	26  
	  	12.2 	Efficacy Analysis 	27  
	 13.0 	ETHICAL,
      REGULATORY AND ADMINISTRATIVE ASPECTS	27  
	  	13.1 	Declaration of Helsinki	27  
	  	13.2 	Regulatory	27  
	  	13.3 	Informed Consent	27  
	  	13.4 	Institutional
      Review Board	28  

3

A Dose Escalation Study Using Collagenase Clostridium
Histolyticum 
in the Treatment of Lipoma 
Lipoma [**] 

110718 

	  	13.5 	Disclosure of Data	28 
	  	13.6 	Confidentiality of Documents / Subject
      Records	28 
	14.0 	STUDY
      DOCUMENTATION	28 
	  	14.1 	 Investigator’s Statement	28 
	  	14.2 	 Investigator’s
      Record Requirements	29 
	  	14.3 	 Departures from Protocol	29 
	  	14.4 	 Study
    Documentation	29 
	  	14.5 	 ABC or Health Authority Queries	31 
	  	14.6 	 Inspections	31 
	  	14.7 	 Monitoring of the Study 	32 

	15.0 	APPENDICES 
	  	Attachment 1: Investigator Statement
  
	  	Attachment 2: Subject
  Questionnaire

4

A Dose Escalation Study Using Collagenase Clostridium
Histolyticum 
in the Treatment of Lipoma 
Lipoma [**] 

110718 

** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND
FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A
CONFIDENTIAL TREATMENT REQUEST. 

	SYNOPSIS 	  
	Title 	A Dose Escalation Study Using Collagenase
      Clostridium Histolyticum in the Treatment of Lipoma 
	Investigator / Sponsor 	[**] 
	Clinical Site 	  
	Project Phase 	Clinical Phase II 
	Indication 	Lipoma 
	Objectives 	To evaluate the safety and efficacy of
      Collagenase Clostridium Histolyticum for the nonsurgical treatment of
      lipoma. 
	Study Design 	Lipoma [**] is a single injection, open
      label, Phase II, dose escalation 
	 study to be conducted at a single study center 
	Planned Total Sample Size 	Fourteen (14) subjects 
	Formulations 	Drug: FDA approved Collagenase Clostridium Histolyticum
      (XIAFLEX®, manufactured by Auxilium Pharmaceuticals, Inc.) 
	Test Drug Dosage 	Dose #1 
	  	[**] Clostridium Collagenase
      Histolyticum ([**] dose for marketed indication) 
	  	
	  	Dose #2 
	  	[**] Clostridium Collagenase
      Histolyticum ([**] dose for marketed indication) 
	  	
	  	Dose #3 
	  	[**] Clostridium Collagenase
      Histolyticum ([**] dose for marketed indication) administered per single
      injection 
	 
	  	Dose #4 
	  	[**] Clostridium Collagenase Histolyticum ([**] dose for
      marketed indication) administered per single injection 
	Route of Administration 	Injections are administered directly
      into the lipoma 
	and Volume 	Volume administered: 
	  	     [**] for lipomas
      ranging from [**] 
	  	     [**] for lipomas ranging from [**] 
	Schedule of Administration 	[**] subjects will be treated with Dose #1 and
      [**] subjects will be treated with Dose #2. 
		Upon satisfactory completion of the safety
      review at [**] month post injection using Dose #2, [**] additional
      subjects will be treated with Dose #3. 
		Upon
      satisfactory completion of the safety review, at [**] month post injection
      using Dose #3, [**] additional subjects will be treated with Dose #4.
  
	Subject Follow-Up 	Follow-up visits: 
	  	Days: [**] post injection 
	  	Months: [**] post injection 
	Study Duration 	Subjects will be followed for [**] months post injection
  

5

A Dose Escalation Study Using Collagenase Clostridium
Histolyticum 
in the Treatment of Lipoma 
Lipoma [**] 

110718 

	Efficacy Parameters 	Primary EfficacyVariable 
	  	Reduction in [**] of the lipoma 
	  	Secondary Variables 
	  	Reduction in [**] of the lipoma 
	  	Greatest dimension of the lipoma (length) as measured by
      caliper 
	Additional Information 	Lipoma [**] 
	  	Lipoma [**] 
	  	Subject Questionnaire 
	Safety Parameters 	Adverse Event Assessment 
	  	Vital Signs 
	  	Laboratory evaluations 
	  	Immunogenicity Testing 

** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND
FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A
CONFIDENTIAL TREATMENT REQUEST. 

 

 

 

6

A Dose Escalation Study Using Collagenase Clostridium
Histolyticum 
in the Treatment of Lipoma 
Lipoma [**] 

110718 

1. INTRODUCTION

Lipomas are common mesenchymal, benign, fatty tumors of varying sizes that occur in the general adult population and are rare in children and infants. They usually manifest as painful or annoying lumps that are palpable and often visible in the
subcutaneous tissues.  They are uncommon on the hands and feet, but widely distributed elsewhere. The incidence of these masses in the deep tissues is unknown as they are usually asymptomatic or the symptoms never lead to investigation and/or
diagnosis. Subcutaneous lipomas are extremely variable in size and shape ranging from barely palpable to very large sizes of 15 cm or more in diameter.  The incidence of subcutaneous lipomas in the general population is unknown; however, they are
very common. Solitary lipomas are seen predominately in women, while multiple lipomas occur more frequently in men.(1) 

The fat within a lipoma is microscopically indistinguishable from normal fat.  The fibrous encapsulation represents the only abnormality.  Benign lipomas contain normal fat that is encapsulated within a fibrous “shell” thus often
compressing the fat and causing it to feel more firm than the surrounding fat.  A lipoma is best described to the lay public as a clear water balloon floating under water in a swimming pool. The water inside the balloon is the same as to the
surrounding water. The only reason that it feels different is the capsule. 

Many subcutaneous lipomas are asymptomatic and are removed for non-medical reasons. However, a significant number of them cause the subject pain or discomfort and they interfere with normal activity.  In rare cases multiple large lipomas cause a
significant and/or disabling symptom complex (Madelung’s disease).  It is not clear whether a lipoma may ever become malignant (liposarcoma) as malignant transformation of lipoma to liposarcoma has not been documented. Liposarcomas arise by
malignant transformation of adipocytes, not necessarily adipocytes from within a lipoma. (2) 

Spontaneous remission of lipomas has not been reported.  A lipoma, once it presents itself, remains there for the lifetime of a person who carries it and may stay small or become larger.(3)

At present, lipomas are usually treated in one of the following ways:  1)  wide excision with large incision, 2) limited incision with limited dissection or 3) liposuction.  If a large excision is performed there is the problem of having a very
large scar and the accompanying issues of healing such a scar. In addition, removing a large mass from the subcutaneous tissues will leave behind a potential space which could fill with blood resulting in hematoma, followed
by consolidation of the hematoma and the remnants of a mass of scar tissue. This is often painful and may be more problematic than the original lipoma. 

7

A Dose Escalation Study Using Collagenase Clostridium
Histolyticum 
in the Treatment of Lipoma 
Lipoma [**] 

110718 

Liposuction of a lipoma allows a smaller incision, therefore resulting in a smaller scar which carries a smaller risk of infection. However, the potential for hematoma formation followed by scar mass residual, remains an issue of concern. 

To avoid the complications discussed above, a non-invasive method of treatment, [**], would be desirable. 

Collagenase Clostridium Histolyticum (CCH)  is a collagen specific enzyme that is being marketed in the United States for the treatment of adult Dupuytren’s Contracture patients with a palpable cord. It is manufactured from
Clostridium histolyticum by Auxilium Pharmaceuticals, Inc and marketed as XIAFLEX®. The drug substance, Purified Collagenase for Injection (PCI), is manufactured from Clostridium histolyticum by Advance Biofactures Corporation.  PCI has been
shown in [**]. 

The primary aim of this study is to perform a step-wise approach in dosing to evaluate the safety and efficacy of CCH as a non-operative treatment for lipoma.

	
2.0 		
USE OF PURIFIED COLLAGENASE FOR INJECTION

	
	 	 	 
		
2.1 		
Pre-Clinical Studies

	
	 	 	 
			
PCI has been used in pre-clinical safety/efficacy studies for Dupuytren’s disease, [**]. Toxicity studies performed [**] indicate that the dosage form has a wide margin of safety systemically as well as in local tissues.

	
	 	 	 
			
PCI did not induce [**] was not induced. [**] administration of [**].

	
	 	 	 
		
2.2 		
Clinical Studies

	
	 	 	 
			
PCI has been used in clinical trials for the following clinical indications: Peyronies’ disease, Dupuytren’s contracture, [**]. This drug product has been used in the treatment of [**] and has a good safety profile.

	
	 	 	 
			
During pharmacokinetic studies conducted during the treatment of Dupuytren’s contracture, no collagenase was detected in the plasma of subjects receiving therapeutic doses.

	

** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

8

A Dose Escalation Study Using Collagenase Clostridium
Histolyticum 
in the Treatment of Lipoma 
Lipoma [**] 

110718 

** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

 While antibodies develop in nearly all subjects injected with PCI, it does not appear to affect the safety profile. No correlation has been observed between AEs and antibody titer.

Adverse events related to the study drug PCI have been reported as mild to moderate in severity and consist mainly of injection site tenderness, edema, and ecchymosis. These events resolve spontaneously without medical intervention. [**]. 

There is no known drug abuse potential, no known drug-drug interactions nor manifestations of overdose.

	
2.3 		
Purified Collagenase For Injection in the Treatment of Lipoma

	
	 	 	 
		
2.3.1 		
Study Design [**]

	
	 	 	 
			
This open-label study sponsored by Advance Biofactures Corporation, was designed to evaluate the safety and efficacy of PCI as a non-operative treatment for Lipoma. [**] subjects were enrolled in the study with one discontinuation
after the 3 days post injection visit due to travel distance.

	
	 	 	 
			
Concentration of PCI administered in this study was [**]. Injection volume
 was based on the largest dimension of lipoma in cm [**]. The volume injected ranged from [**]. [**] injection of PCI was administered. Dimensions of the lipoma were taken at baseline, [**] post injection. 

	

	
 	
 	
 
	
 	
2.3.2 		
Study Results

	
	 	 	 	 
	 		
At the [**] post injection follow-up visit, a significant diminution in the size of the [**] completing the study was noted. [**] subjects responded [**] on the subject questionnaire although greater than [**] the subjects met the
success criterion [**].

	
	 	 	 	 
	
 	
2.3.3 		
Adverse Reactions

	
	 	 	 	 
	 		
Adverse events were limited to local reactions at the treatment site (swelling, bruising, tenderness and erythema). None had an intensity more severe than “mild” on a mild-moderate-severe scale, and [**] (one lost to
follow-up) resolved without medical intervention within two weeks.

	
	 	 	 	 
	 		
[**] 		
experienced swelling

	
	 		
[**] 		
experienced bruising

	
	 		
[**] 		
experienced tenderness

	
	 		
[**] 		
experienced erythema

	

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A Dose Escalation Study Using Collagenase Clostridium
Histolyticum 
in the Treatment of Lipoma 
Lipoma [**] 

110718 

	
3.0 		
CLINICAL STUDIES WITH COLLAGENASE CLOSTRIDIUM HISTOLYTICUM

	
	 	 	 
		
This drug substance (CCH) is manufactured by Auxilium Pharmaceuticals, Inc.

	
	 	 	 
		
3.1 		
Dupuytren’s Contracture

	
	 	 	 
			
CCH® has been approved by the FDA for use in Dupuytren’s Contracture.

	

Common Adverse Events reported during clinical trials included:

	
Peripheral edema (77.0%), Contusion (51%), Injection Site Pain (40.0%), Extremity Pain (37.4%), Injection Site Hemorrhage (34.5%), Tenderness (29.3%), Injection Site Swelling (24.7%), Ecchymosis (18.1%), Skin Laceration (12.7%), Pruritis (12.7%),
Lymphadenopathy (11.0%), Blood Blister (9.0%), Axillary Pain (6.7%), Hematoma (5.5%), Arthralgia (5.3%), Injection Site Pruritis (5.3%).

Common adverse events were mostly confined to the treated extremity, non-  serious/mild or moderate intensity, and resolved before the next injection  without intervention. The median duration of all AEs was 10 days. 

Serious Adverse Events included:

	
Tendon rupture (0.3%), Ligament injury (0.04%), Tendonitis (0.04%), Finger Deformity / Boutonniere Deformity (0.04%), Deep Vein Thrombosis (0.04%), Proliferation of Dupuytren’s Disease* (0.04%), Sensory Disturbance of hand* (0.04%), Complex
regional Pain Syndrome (0.04%).

Note: *These SAE’s occurred in the same subject

No consistent pattern was demonstrated between AE rates and antibody titers. There were no events or signals indicative of systemic anaphylaxis in the clinical program. 

	
 	
3.2 		
Peyronie’s Disease

	
	 	 	 
	 		
Results from a Phase 2b study show that treatment with CCH significantly reduced penile curvature in men with Peyronie’s disease. The studies also demonstrated that CCH was well tolerated with no serious adverse events
related to study drug. The majority of AEs are transient, non-serious, mild to moderate in intensity resolving without sequelae. No
clinically meanful effects on laboratory or vital sign parameters were noted. No systemic immunologic events were reported. 

	

10

A Dose Escalation Study Using Collagenase Clostridium
Histolyticum 
in the Treatment of Lipoma 
Lipoma [**] 

110718 

	
4.0 		
REFERENCES

	
	 	 	 
		
1. 		
Moraru RA. Lipomas. eMedicine Journal, Volume 2, Number 6, June 2001.

	
	 	 	 
		
2. 		
Moraru RA. Lipomas. eMedicine Journal, Volume 2, Number 6, June 2001.

	
	 	 	 
		
3. 		
Ackerman B,, Kerl H., Sanchez J. et al. A Clinical Atlas of 101 Common Skin Diseases with Histophathologic Correlation. January 2000

	
	 	 	 
		
4. 		
An Exloratory Study on the Effect of Injected Nucleolysin(R) on the Subcutaneous Fat Pads of Female Zucker Rats. Study No.95-2384. Pharmaco LSR (for Advanced Biofactures Corporation) 1995.

	
	 	 	 
		
5. 		
Briefing document for Collagenase Clostridium Histolyticum (AA4500) in the Treatment of Advanced Dupuytren’s Disease. Presented to Arthritis Advisory Committee Meeting, September 16, 2009.

	
	 	 	 
		
6. 		
BB IND 8486

	

 

 

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A Dose Escalation Study Using Collagenase Clostridium
Histolyticum 
in the Treatment of Lipoma 
Lipoma [**] 

110718 

	
5.0 		
RATIONALE

	
					
		
5.1 		
Study Rationale [**].

	
					
			
This study will be an open label, [**] injection, dose escalation study.

	
					
		
5.2 		
Rationale for Dosage Selection and Study Design

	
					
			
5.2.1 		
The safety and efficacy of CCH will be evaluated by using a step-wise approach for administration of study drug. The dose of CCH administered for the marketed indication of Dupuytren’s contracture is 0.58 mg into a
Dupuytren’s cord, and for Peyronie’s disease, 0.58 mg per injection of a plaque. The proposed dose of CCH to be administered into a lipoma will be [**], provided the safety evaluations are acceptable.

	
					
			
5.2.2 		
Volumes injected into a lipoma in the previous human study ranged from [**] to
[**] based upon the length of the lipoma. In this clinical trial, the dose of study drug will be injected into the lipoma in [**] for lipomas ranging in size from
[**] lipomas ranging in size from [**].

	
					
			
5.2.3 		
Based upon our previous experience evaluating the use of PCI in humans and pre-clinical trials, the efficacy evaluation will be performed at [**] months post injection.

	
					
			
5.2.4 		
Measurement of efficacy will be based upon the [**] of the lipoma as measured by caliper due to investigator familiarity with caliper measurements and clinical practice.

	

 

			
5.2.4 		
[**] of the lipoma is taken as the [**] times the [**]. This measurement will be an acceptable, approximate value for all lipomas including oval and circular shaped lipomas.

	

	 	 	
 	
 
			
5.2.5 		
An [**] will be performed prior to injection to confirm the diagnosis of benign lipoma, and again at study end to provide an objective assessment of [**] as compared to pre-injection.

	
					
		
5.3 		
Injection Technique

	
					
			
Lipomas are to be treated by injecting study drug through a [**] into the [**] of the lipoma and then [**] within the lipoma will be performed in a manner that will not cause damage to any peripheral areas.

	

	
 	
 
	
6. 		
OBJECTIVE 

	

The objective of this study is to assess the efficacy and safety of CCH in reducing the area of a subcutaneous, benign lipoma, in a step-wise approach using [**] of the marketed dose. 

** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST.

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A Dose Escalation Study Using Collagenase Clostridium
Histolyticum 
in the Treatment of Lipoma 
Lipoma [**] 

110718 

	
7. 		
STUDY DESIGN

	
	 	 	 	 	 
		
7.1 		
Study Center

	
	 	 	 	 	 
			
This Phase II clinical trial protocol (Lipoma [**]) will be carried out at [**] clinical site and will be reviewed by an approved Institutional Review Board.

	
	 	 	 	 	 
		
7.2 		
Sample Size

	
	 	 	 	 	 
			
Fourteen subjects will be enrolled in the study: [**] initial subjects will receive [**] injection of study drug equivalent to [**] of the dose for the marketed indication followed by [**] subjects, [**] receiving one injection of
study drug equivalent to [**] receiving [**], and [**] receiving [**] of the marketed dose.

	
	 	 	 	 	 
		
7.3 		
Efficacy Parameters

	
	 	 	 	 	 
			
7.3.1 		
Primary Efficacy Outcome (Endpoint)

	
	 	 	 	 	 
				
7.3.1.1 		
Visible [**] of Lipoma

	
	 	 	 	 	 
					
The [**] of the target lipoma will be measured at all visits using a caliper as described in Section 5.2.4. Determination of efficacy will be performed at [**] months post injection.

	
	 	 	 	 	 
			
7.3.2 		
Secondary Efficacy Outcomes:

	
	 	 	 	 	 
				
7.3.2.1 		
Greatest [**] lipoma [**]

	
	 	 	 	 	 
				
7.3.2.2 		
Relative change in lipoma [**]:

	
	 	 	 	 	 
					
The [**] from baseline for lipoma [**] month [**] months

	
	 	 	 	 	 
				
7.3.2.3 		
Relative change in [**] of lipoma as determined by [**]

	
	 	 	 	 	 
		
7.4 		
Additional Information

	
	 	 	 	 	 
			
7.4.1 		
Lipoma Characteristics

	
	 	 	 	 	 
				
The investigator will record the [**] of the lipoma using a [**], and perform an evaluation of lipoma [**] and relation to surrounding skin at each follow-up visit.

	
	 	 	 	 	 
			
7.4.2 		
Subject Questionnaire

	
	 	 	 	 	 
				
A questionnaire will be completed by each subject prior to injection and at each follow-up visit to gather information regarding patient assessment of treatment in relation to reason for lipoma [**].

	
	 	 	 	 	 
		
7.5 		
Safety Parameters

	
	 	 	 	 	 
			
7.5.1 		
Adverse Event Assessment

	

** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

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A Dose Escalation Study Using Collagenase Clostridium
Histolyticum 
in the Treatment of Lipoma 
Lipoma [**] 

110718 

	 	 	
7.5.2 		
Vital Signs
	
	 	 	
 	
 
	 	 	
7.5.3 		
Laboratory Analysis
	
	 	 	
 	
 
	 	 	
7.5.4 		
[**] antibody and neutralizing antibody testing. Antibody levels will be
measured through the completion of this study ([**] Post-injection)
	
	 	 	
 	
 

	
 	
 	
 
	
 	
7.6 		
Investigational Plan

	
	 	 	 	 
	 		
7.6.1 		
Subjects must present with at least one lipoma meeting inclusion criteria.

	
	 	 	 	 
	 		
7.6.2 		
Two subjects will receive a [**] injection of [**] study drug. [**] additional subjects will receive a [**] injection [**] study drug. A safety report will be generated after the [**] Month Post Injection follow-up visit for these
[**] patients. The report will include both local site reactions, laboratory results, and systemic adverse events.

	
	 	 	 	 
	 		
7.6.3 		
Upon a satisfactory safety report, the investigator will administer a [**] injection of dose #3 [**] to [**] additional subjects. A safety report will be generated after the [**] Month Post Injection follow-up visit for these [**]
subjects as well as updated information for the first [**] subjects. The report will include both local site reactions, laboratory results, and systemic adverse events.

	
	 	 	 	 
	 		
7.6.4 		
Upon a satisfactory safety report, the investigator will administer a [**] injection of dose #4 [**] to [**] additional subjects. A safety report will be generated after the [**] Month Post Injection follow-up visit for these [**]
subjects as well as updated information for the first [**] subjects. The report will include both local site reactions, laboratory results, and systemic adverse events.

	
	 	 	 	 
	 		
7.6.5 		
No [**] of the lipoma will be performed either before or after administration of study drug.

	
	 	 	 	 
	
 	
7.7 		
Subject Care

	
	 	 	 	 
	 		
The subject will remain at the clinic site for a minimum [**] post-injection to be monitored for safety and immediate adverse events. In addition to evaluating the injection site, the investigator will assess the subject following
study drug administration for findings consistent with a [**]. If a [**] is suspected, this event should be recorded as an adverse event.

	
	 	 	 	 
	 		
The Investigator will be prepared to address [**] should it occur. [**]. The investigator/nursing staff is familiar with their use, and treatment procedure.

	

** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

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A Dose Escalation Study Using Collagenase Clostridium
Histolyticum 
in the Treatment of Lipoma 
Lipoma [**] 

110718 

 

Subjects may be discharged after a minimum of [**] provided that the subject does not exhibit any signs of [**] nor any clinically significant systemic or local adverse reactions, and vital signs are stable.

Subjects will be instructed not to put pressure on the injected lipoma, and to contact the investigator immediately, by 24 hour emergency answering service, if they notice any problems.

	
7.8 		
Follow-Up

	
	 	 	 	 
		
The schedule for follow-up visits post injection is [**] days, [**] months post injection.

	
	 	 	 	 
	
7.9 		
Assessments

	
	 	 	 	 
		
7.9.1 		
Informed Consent

	
	 	 	 	 
			
Each subject must voluntarily sign the informed consent before any study procedures may be performed.

	
	 	 	 	 
		
7.9.2 		
The initial visit will include a review of the disease history (duration of the disease; previous treatments, number of lipomas), and evaluation of the lipoma to be treated [**].

	
	 	 	 	 
		
7.9.3 		
Screening procedures prior to injection will include:

	
	 	 	 	 
			
7.9.3.1 		
A physical exam by body system, measurement of height and body weight, ECG

	
	 	 	 	 
			
7.9.3.2 		
[**] of the lipoma [**] diagnose the lipoma as benign

	
	 	 	 	 
			
7.9.3.3 		
An [**] to confirm the benign diagnosis and as a baseline measurement of lipoma [**]

	
	 	 	 	 
			
7.9.3.4 		
Laboratory testing including: routine hematology and chemistry including liver function testing and urinalysis; serum PT/PTT levels

	
	 	 	 	 
			
7.9.3.5 		
Immunogeniciy testing (anti-drug (anti-AUX-1 and anti-AUX-II) antibodies and neutralizing antibodies)

	
	 	 	 	 
		
7.9.4. 		
On the Day of Injection the following procedures will be performed:

	
	 	 	 	 
			
7.9.4.1 		
Urine HCG test to determine pregnancy on women of child bearing age

	
	 	 	 	 
			
7.9.4.2 		
Measurement of vital signs

	
	 	 	 	 
			
7.9.4.3 		
A questionnaire will be completed by each subject

	
	 	 	 	 
			
7.9.4.3 		
Administration of [**] injection of study drug

	
	 	 	 	 
			
7.9.4.4 		
Active examination by the investigator for injection site adverse events

	

** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

 15

A Dose Escalation Study Using Collagenase Clostridium
Histolyticum 
in the Treatment of Lipoma 
Lipoma [**] 

110718 

	
 	
7.9.5 		
At each post-treatment visit (Day [**], and Months [**]) the following procedures will be performed:

	
	 	 	 	 
	 		
7.9.5.1 		
Measurement of vital signs

	
	 	 	 	 
	 		
7.9.5.2 		
A questionnaire will be completed by each subject

	
	 	 	 	 
	 		
7.9.5.3 		
Approximately [**] blood will be collected for routine hematology and chemistry, including liver function testing and urinalysis, immunogenicity testing and serum PT/PTT levels

	
	 	 	 	 
	 		
7.9.5.4 		
Evaluation of the treated lipoma including caliper measurements and lipoma [**]

	
	 	 	 	 
	 		
7.9.5.5 		
Active examination by the investigator for injection site adverse events including [**]and other signs of
local tolerability 

	
	 	 	
 	
 
	 	7.9.6 	
At the end of the study a repeat [**] and a physical exam by body system,
measurement of height and body weight, and ECG will be taken 	

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A Dose Escalation Study Using Collagenase Clostridium
Histolyticum 
in the Treatment of Lipoma 
Lipoma [**] 

110718 

	
 	
7.10 		
Handling of Samples

	
	 	 	 
	 		
Certified laboratories will be used for all testing not performed on site. Specimens will be processed and results provided to the study investigator. The investigator or qualified designee will evaluate each laboratory value and
determine whether or not any values exceeding laboratory norms are clinically significant.

	
	 	 	 
	 		
Serum samples to be used for analyzing [**] antibody levels and neutralizing potential of antibodies to [**] will be split into three vials, frozen, and stored at the site until forwarded to AUXILIUM Pharmaceuticals, Inc., or
their designee for testing.

	
	 	 	 
	
 	
7.11 		
Safety Reports

	
	 	 	 
	 		
Safety reports will be generated and reviewed by the clinical investigator when the four subjects receiving a dose have completed the [**] Month post injection follow-up visit, including all testing required, and prior to the
administration of the next dose escalation. Reports will include a review of all laboratory data for clinical significance. If a laboratory value exceeds laboratory norms, the investigator must determine whether or not it is a clinically significant
change from baseline (adverse event) and its relation to study drug.

	
	 	 	 
	 		
The review will also address any systemic or local reactions in relation to expected severity and duration.

	
	 	 	
 

	
8.0 		
STUDY POPULATION

	
	 	 	 	 
		
Subjects must meet all of the inclusion and none of the exclusion criteria specified below for entry into this study.

	
	 	 	 	 
		
8.1 		
Inclusion Criteria

	
	 	 	 	 
			
8.1.1 		
Subjects must be 18-65 years of age, of either sex or any race.

	
	 	 	 	 
			
8.1.2 		
Subjects must have a clinical history for the lipoma to be treated of [**], with no treatment of the lipoma [**].

	
	 	 	 	 
			
8.1.3 		
Lipoma must be diagnosed as benign.

	
	 	 	 	 
			
8.1.4 		
Lipomas must have an area [**] with easily definable edges and a single mass.

	
	 	 	 	 
			
8.1.5 		
Subjects must be willing to participate in and complete the study, and comply
with its procedures by voluntarily signing an IRB approved written consent form. 

	

** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

 17

A Dose Escalation Study Using Collagenase Clostridium
Histolyticum 
in the Treatment of Lipoma 
Lipoma [**] 

110718 

	
8.1.6 		
Subjects must understand and be able to adhere to the visit schedule, follow study procedures and instructions, and agree to report concomitant medications and adverse events accurately and consistently.

	
	 	 
	
8.1.7 		
Women of childbearing potential must use an acceptable method of birth control or be surgically sterilized (e.g., hysterectomy or tubal ligation).

	
	
 	
 

		
8.2	
Exclusion Criteria 

	

	 	 	
 	
 
			
8.2.1	
[**] 

	
	 	 	
 	
 
	 	 	
8.2.2	
[**]
	
	 	 	
 	
 
	 	 	
8.2.3	
[**]
	
	 	 	
 	
 
	 	 	
8.2.4	
[**]
	
	 	 	
 	
 
	 	 	
8.2.5	
[**]
	
	 	 	
 	
 
	 	 	
8.2.6	
[**]
	
	 	 	
 	
 
	 	 	
8.2.7	
[**]
	
	 	 	
 	
 
	 	 	
8.2.8	
[**]
	
	 	 	
 	
 
	 	 	
8.2.9	
[**]
	
	 	 	
 	
 
	 	 	
8.2.10	
[**]
	
	 	 	
 	
 
	 	 	
8.2.11	
Subjects having the following laboratory abnormalities:
	 	 	
 	
 
	 	 	
 	
 [**]
	

** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST.

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Histolyticum 
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	9. 	
      TRIAL MEDICATION

	 	 	 	 
		9.1 	
      Study Drug: XIAFLEX®

	 	 	 	 
			
      This is a purified collagenase derived from
      Clostridium histolyticum. It is supplied as a sterile, lyophilized
      powder in a single-use glass vial. Each vial contains 0.9 mg
    protein.

	 	 	 	 
		9.2 	
      Reconstitution Diluent

	 	 	 	 
			
      Supplied by Auxilium Pharmaceuticals, Inc. Sterile
      diluent consists of [**] sodium chloride containing [**] calcium
      chloride. Study drug is to be reconstituted only with the supplied diluent.

	 	 	 	 
		9.3 	
      Injection Medications

	 	 	 	 
			
      Syringes will be prepared by the investigational
      pharmacist and delivered to the investigator. The investigational
      pharmacist shall keep accurate records of dates of reconstitution in
      addition to data required for the determination of drug
    administered.

	 	 	 	 
		9.4 	
      Drug Storage

	 	 	 	 
			
      CCH must be kept refrigerated (2-8oC) in an area with
      restricted access. [**]. If refrigerated, the reconstituted product must
      remain at room temperature for approximately [**] prior to use.

	 	 	 	 
			
      The investigator agrees neither to dispense the study
      drug from, nor store it, at any site(s) other than those listed on the
      Form FDA 1572. The investigator agrees that study drug(s) will be
      administered by the investigator or sub-investigator(s) named on the Form
      1572. The investigator also agrees that the study drug(s) will be
      administered for this protocol only and to study subjects who have
      provided written informed consent.

	 	 	 	 
		9.5 	
      Drug Accountability

	 	 	
       
	 	 	
      A Drug Dispensing Form/Inventory must be kept current by
      the investigative pharmacist. All containers of study drug, whether empty or containing
      used or unused study drug are to be available for inspection by the
      Clinical Trial Monitor.

	 	 	
       
		9.6 	
      Administration of Study Medication 9.6.1
      Reconstitution

      The pharmacist will follow the procedures for
      reconstitution of CCH provided by the manufacturer and dilution
      instructions as provided in a separate procedure. The pharmacist will
      maintain a record of the date(s) and time(s) of
  reconstitution and dispensation of the study drug.

** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND
FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A
CONFIDENTIAL TREATMENT REQUEST. 

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A Dose Escalation Study Using Collagenase Clostridium
Histolyticum 
in the Treatment of Lipoma 
Lipoma [**] 

110718 

NOTE:  The syringe contents must be administered within [**] hours of reconstitution of CCH.

	 	 	
9.6.2 		
Route of Administration
	
	 	 	
 	
 
	 	 	
 	
 Injections will be administered [**].

	
 	
 	
 
	
 	
9.7 		
Concomitant Treatment

	
	 	 	 
	 		
[**]. All other concomitant medication must be recorded on the Case Report Form (CRF). Additionally, any diagnostic, therapeutic, or surgical procedure performed during the study period should be recorded including the date,
indication, and description of the procedure(s) and any clinical findings.

	

** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

 

 

 

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Histolyticum 
in the Treatment of Lipoma 
Lipoma [**] 

110718 

	
10. 		
STUDY METHODOLOGY

	
	
 	
 

	
 	
10.1 		
Measurements and Evaluations

	
	
 	
 	
 

	
 Efficacy Evaluation
	
	
Measurement
		
 Measured By
	

	
Reduction in visible
	
	
[**]
	
	
Caliper, Study Site
	

	
lipoma [**]
	
	
 
	
	
 
	

	
[**] lipoma
	
	
[**]
	
	
Outside laboratory
	

	
Other Information
		
Measurement
		
 Measured By
	

	
Lipoma [**]
	
	
[**]
	
	
[**], Study Site
	

	
 
	
	
 
	
	
Investigator
	

	
 
	
	
 
	
	
Investigator 

 

	
Subject Satisfaction
	
	
Questionnaire
	
	
Subject, study site
	

	
Safety Evaluation
		
Measurement
		
 Measured By
	

	
Adverse Events
	
	
Provided by Subject
	
	
Study Site
	

	
Vital Signs:
	
	
 
	
	
Study Site
	

	
    Blood Pressure
	
	
mm Hg
	
	
 
	

	
    Pulse/Heart Rate
	
	
#/minute
	
	
 
	

	
    Respiration
	
	
#/minute
	
	
 
	

	
    Temperature
	
	
Degrees (Farenheit/Celsius)
	
	
 
	

	
Laboratory Testing
	
	
CBC
	
	
Outside Laboratory
	

	
 
	
	
Blood chemistries
	
	
 
	

	
 
	
	
Urinalysis
	
	
 
	

	
Radiography
	
	
[**]
	
	
Outside Lab
	

	
Pregnancy Test
	
	
Urine HCG
	
	
Study Site
	

	
Immunogenicity
	
	
[**]
	
	
Auxilium Pharmaceuticals, Inc. or
	

	
 
	
	
 
	
	
designee
	

	
 	
10.2 		
Schedule of Testing/Follow-Up Visits

	
	 	 	 
	 		
The schedule of testing and standard follow-up visits with the actions to be taken at each time point is summarized in Table A.

	

** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

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    Table A 
	
	
Visit #
		
  Visit Name
		
  Time Point
		
 
		
 
		
Actions 
	
	
1
	
	
[**]
	
	
[**]
	
	
a.	
 Informed consent will be discussed and obtained/signed:

	
	
 
	
 
	
 
	
 	
1. One copy of signed consent form will be given to the
subject
	
 
	
 
	
 
	
 	
2.
Second copy retained in with subject’s study
documents 
	
	
 
	
 
	
 
	
b. 
		
Review of Inclusion/Exclusion Criteria 
	
	
 
	
 
	
 
	
c. 
		
Past medical history, review of systems, review of lipoma
history, onset, progression and treatment
	
 
	
 
	
 
	
d. 
		
[**] 
	
	
 
	
 
	
 
	
e. 
		
Measurement of [**] 
	
	
 
	
 
	
 
	
f. 
		
Review of medications used in the past [**]; information
recorded in study documents 
	
	
 
	
 
	
 
	
g. 
		
Return appointment scheduled for treatment ([**] of
screening visit) 
	
	
 
	
 
	
 
	
h. 
		
Subjects assigned a unique subject study number 
	
	
 

		
[**]
	
	
[**]
	
	
a. 
		
Physical exam 
	
	
 
	
 
	
 
	
b.	
ECG 
	
	
 
	
 
	
 
	
c.	
Routine hematology and chemistry
	
 
	
 
	
 
	
d.	
Liver function and urinalysis 
	
	
 

		
[**]
	
	
 
	
e.	
Serum PT/PTT 
	
	
 
	
 
	
 
	
f.	
Baseline immunogenicity test 
	
	
 
	
 
	
 
	
g.	
[**] 
	
	
2.

		
[**]
	
	
[**]
	
	
a. 
		
Vital signs are measured prior to injection 
	
	
 
	
 
	
 
	
b.	
Subject questionnaire completed 
	
	
 
	
 
	
 
	
c.	
The target lipoma evaluated [**] 
	
	
 
	
 
	
 
	
d.	
Urine collected for HCG, if applicable 
	
	
 

		
 
	
 
	
e.	
Study drug administered 
	
	
 
	
 
	
 
	
f.	
Vital signs are measured immediately post-injection and
prior to discharge 
	
	
 
	
 
	
 
	
g.	
Subject instructed to contact the investigator immediately
regarding any side effects/adverse events 
	
	
3.

		
[**]
	
	
[**]
	
	
a. 
		
Vital signs measured and recorded 
	
	
 
	
 
	
 
	
b.	
Subject questionnaire completed
	
 
	
 
	
 
	
c.	
The injected lipoma evaluated [**] 
	
	
 
	
 
	
 
	
d.	
Adverse events reported by the subject and those actively
monitored are recorded 
	
	
 

		
 
	
 
	
e.	
All changes in medication used since the last visit recorded

	
	
 
	
 
	
 
	
f.	
[**] blood collected for lab and immunogenicity testing

** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

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4
	
	
[**]
	
	
[**]
	
	
a.
		
Vital signs measured and recorded 
	
	
 
	
	
 
	
	
 
	
	
b.
		
Subject questionnaire completed 
	
	
 
	
	
 
	
	
 
	
	
c.
		
The injected lipomas evaluated [**] 
	
	
 
	
	
 
	
	
 
	
	
d.
		
Adverse events reported by the subject and those actively
monitored are recorded 
	
	
 
	
	
 
	
	
 
	
	
e.
		
All changes in medication used since the last visit recorded 
	
	
 
	
 
	
 
	
f.
		
[**] blood collected for lab and immunogenicity testing 
	
	
5.
	
[**].
	
	
[**]
	
	
a.
		
Vital signs will be measured and recorded 
	
	
 
	
	
 
	
	
 
	
	
b.
		
Subject questionnaire completed 
	
	
 
	
	
 
	
	
 
	
	
c.
		
The injected lipomas evaluated [**] 
	
	
 
	
	
 
	
	
 
	
	
d.
		
Adverse events reported by the subject and those actively
monitored are recorded 
	
	
 
	
	
 
	
	
 
	
	
e.
		
All changes in medication used since the last visit recorded 
	
	
 
	
	
 
	
	
 
	
	
f.
		
[**] blood collected for lab and immunogenicity testing 
	
	
6.
	
[**].
	
	
[**]
	
	
a.
		
Vital signs will be measured and recorded 
	
	
 
	
	
 
	
	
 
	
	
b.
		
Subject questionnaire completed 
	
	
 
	
	
 
	
	
 
	
	
c.
		
The injected lipomas evaluated [**] 
	
	
 
	
	
 
	
	
 
	
	
d.
		
Adverse events reported by the subject and those actively
monitored are recorded 
	
	
 
	
	
 
	
	
 
	
	
e.
		
All changes in medication used since the last visit recorded 
	
	
 
	
	
 
	
	
 
	
	
f.
		
20 mL blood collected for lab and immunogenicity testing 
	
	
7
	
	
[**]
	
	
[**]
	
	
a.
		
Vital signs will be measured and recorded 
	
	
 
	
	
 
	
	
 
	
	
b.
		
Subject questionnaire completed 
	
	
 
	
	
 
	
	
 
	
	
c.
		
The injected lipomas evaluated [**] 
	
	
 
	
	
 
	
	
 
	
	
d.
		
Adverse events reported by the subject and those actively
monitored are recorded 
	
	
 
	
	
 
	
	
 
	
	
e.
		
All changes in medication used since the last visit recorded 
	
	
 
	
	
 
	
	
 
	
	
f.
		
[**] blood collected for lab and immunogenicity testing 
	
	
8.
	
[**].
	
	
[**]
	
	
a.
		
Vital signs will be measured and recorded 
	
	
 
	
	
 
	
	
 
	
	
b.
		
Subject questionnaire completed 
	
	
 
	
	
 
	
	
 
	
	
c.
		
The injected lipomas evaluated [**] 
	
	
 
	
	
 
	
	
 
	
	
d.
		
Adverse events reported by the subject and those actively
monitored are recorded 
	
	
 
	
	
 
	
	
 
	
	
e.
		
All changes in medication used since the last visit recorded 
	
	
 
	
	
 
	
	
 
	
	
f.
		
[**] blood collected for lab and immunogenicity testing 
	
	
 	
 	
 	
g.
		
Physical exam 
	
	
 
		
 
		
 
		
h.
		
ECG 
	
	
 
		
 
		
 
		
i.
		
[**] 
	

** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

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10.3 		
Early Termination

	
	 	 	 
	 		
Subjects may voluntarily withdraw from the study at any time and for any reason.

	
	 	 	 
	 		
The investigator may discontinue the subject’s participation in the study if he believes it necessary for any reason including adverse events, clinically significant adverse changes in laboratory testing or failure to comply
with the protocol. At the time of withdrawal or discontinuation of a subject, all efforts will be made to complete the procedures and evaluations scheduled for the [**] month follow-up visit (See Table A).

	
	 	 	 
	 		
If a subject withdraws or is discontinued from the study for any reason, the reason for and date of the discontinuation should be recorded in the appropriate section of the Case Report Form on the Study Termination page.

	
	 	 	 
	 		
Subjects may be replaced if they have not reached the [**] month post injection follow- up visit.

	
	 	 	
 

	
11. 		
SAFETY EVALUATION/ADVERSE EVENTS

	
	 	 	 
		
11.1 		
Adverse Events

	
	 	 	 
			
An adverse event is any undesired medical occurrence which occurs during study participation once the subject consent is signed. This includes any physical or clinical change regardless of the relationship to study drug. Abnormal
laboratory findings and exacerbation of pre-existing conditions are also considered to be adverse events.

	
	 	 	 
		
11.2 		
Recording Adverse Events

	
	 	 	 
			
The Investigator must report on the Case Report Form all adverse signs and symptoms which are volunteered by subjects or observed by the Investigator. The onset and end dates, severity, duration, effect on study drug
administration (e.g., discontinuation), relationship to study drug, and administration of any other drug(s) to treat this event will be recorded for each adverse event.

	
	 	 	 
			
Subjects will be questioned and/or examined by the investigator or his/her designee for occurrence of adverse events. The questioning of adverse events should be general and open-ended such as "How have you been feeling since your
last visit?" The presence or absence of specific adverse events will not be solicited from subjects.

	

** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

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11.3 		
Monitoring Adverse Events:

	

Adverse events will be assessed, graded and followed for [**] months post injection with the exception of related events which must be followed until resolution or stabilization. Immunogenicty testing will be performed until levels return to
baseline.

Intensity Rating for Adverse Events:

0 = None, not aware of adverse event 

1 = Mild, aware of adverse event but easily tolerated 2 = Moderate, adverse event interferes with usual activities 

3 = Severe, adverse event is incapacitating; unable to perform usual activities 

Subjects having adverse events will be monitored with relevant clinical assessments and laboratory tests as determined by the investigator.  Any actions taken and follow-up results must be recorded on the appropriate page of the Case Report Form.
Follow-up laboratory results should be filed with the subject's source documentation. 

	
 	
11.4 		
Known Potential Toxicity of Study Drug(s)

	
	 	 	 	 
	 		
There have been no toxicity experiences in previous clinical trials. Refer to the Package Insert for XIAFLEX®.

	
	 	 	 	 
	
 	
11.5 		
Serious Adverse Events

	
	 	 	 	 
	 		
11.5.1 		
All serious adverse events, treatment-related or not, must be reported to the study monitor and to Auxilium Pharmaceuticals, Inc. immediately if feasible, or within 24 hours. A written report must be made including a full
description of the event and sequelae. Such notification shall be made as soon as possible and in no event later than 5 working days after the sponsor's initial receipt of the information. The FDA, via form 3500A, and the institutional IRB will be
notified in a written IND safety report of any adverse experience associated with use of the drug that is both serious and unexpected.

	
	 	 	 	 
	 			
In each written report, the sponsor shall identify all safety reports previously filed with the IND concerning a similar adverse experience, and shall analyze the significance of the adverse experience in light of the previous,
similar reports.

	

** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

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11.5.2 		
A serious adverse event is one that suggests a significant hazard, contraindication, side effect, or precaution. With respect to human clinical experience, this includes any event that:

	
	 	 	 	 	 
	 	 		
11.5.2.1 		
Results in death

	
	 	 	 	 	
   

	 	 		
11.5.2.2 		
Is life-threatening

	
	 	 	 	 	
   

	 	 		
11.5.2.3 		
Requires hospitalization or prolongs existing hospitalization

	
	 	 	 	 	
   

	 	 		
11.5.2.4 		
Results in persistent, or significant disability/incapacity

	
	 	 	 	 	
   

	 	 		
11.5.2.5 		
Important medical events that may not result in death, etc. But may be considered a serious adverse event and jeapardize the subject and may require medical or surgical intervention to prevent one of the outcomes listed in this
definition.

	
	 	 	 	 	 
	
 	
 	
11.5.3 		
Telephone report: FDA will be notified by telephone of any unexpected fatal or life-threatening experience associated with use of the drug in the clinical studies conducted under the IND no later than 3 working days after receipt
of the information. Each telephone call to FDA shall be transmitted to the Center for Drug Evaluation and Research, which has responsibility for review of the IND. For purposes of this section, life-threatening means that the subject was, in view of
the investigator, at immediate risk of death from the reaction as it occurred, i.e., it does not include a reaction that, had it occurred in a more serious form, might have caused death. For example, drug induced hepatitis that resolved without
evidence of hepatic failure would not be considered life threatening even though drug-induced hepatitis can be fatal.

	
	
 	
 	
 	
 

	
12. 		
STATISTICAL ANALYSIS

	
	 	 	 	 
		
12.1 		
Safety Analysis

	
	 	 	 	 
			
12.1.1 		
Adverse Events

	
	 	 	 	 
				
Tables of adverse event rates will be constructed including severity, and relationship to study treatment. Additionally, separate tables may be created for localized adverse events that occur at the treated lipoma.

	
	 	 	 	 
			
12.1.2 		
Clinical Labs and Vitals

	
	 	 	 	 
				
Descriptive statistics at baseline and changes over the course of the study will be tabulated.

	

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12.1.3 		
Immunogenicity

	
	 	 	 	 
	 	 		
[**] levels and [**] of antibodies to [**]will be summarized using descriptive statistics for the actual value at each visit.

	
	 	 	 	
 

		
12.3  		
Efficacy Analysis 

	
	 	 	 	 
			
12.3.1	
The primary efficacy outcome is lipoma [**] measured as [**] times the [**].
[**] will be analyzed as the percent change from baseline at the[**] month visit. 

	
	 	 	
 	
 
	 	 	
12.3.2 		
A secondary efficacy outcome is [**] of the lipoma, that is, the [**] alone.
This will be analyzed as the percent change from baseline at the [**] month
visit. [**] at the other visits will also be evaluated.
	
	 	 	
 	
 
	 	 	
12.3.3 		
Relative change from baseline will be evaluated at [**] Months post injection.
	
	 	 	
 	
 
	 	 	
12.3.4 		
Relative [**] the lipoma (as determined by [**]) from baseline will be evaluated
at [**] months post injection.
	
	 	 	
 	
 

	
13. 		
ETHICAL, REGULATORY AND ADMINISTRATIVE ASPECTS

	
	 	 	 
		
13.1 		
Declaration of Helsinki

	
	 	 	 
			
The investigator will ensure that this study is conducted in full conformance with the principles of the Declaration of Helsinki-Ethical Principles for Medical Research Involving Human Subjects as amended by the 59th WMA General
Assembly in Seoul, October 2008.

	
	 	 	 
		
13.2 		
Regulatory

	
	 	 	 
			
The investigator will ensure that this trial will be conducted in compliance with the protocol and that the basic principles of “Good Clinical Practices” and applicable regulatory requirements are adhered to.

	
	 	 	 
		
13.3 		
Informed Consent

	
	 	 	 
			
It is the responsibility of the investigator to obtain written informed consent from each subject prior to performing any study-related procedure. The subject must sign a statement (complying with the requirements of the U.S. Code
of Federal Regulations, Title 21 CFR Part 50) which indicates that they have given their consent to participate in the study.

	
	 	 	 
		
13.4 		
Institutional Review Board

	

** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

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This protocol and any accompanying material provided to the subject will be submitted by the investigator to the Institutional Review Board (IRB).  Approval from the committee must be obtained before starting the study and should be documented in a
letter to the investigator specifying the date on which the committee met and granted the approval. 

Any modifications made to the protocol after initial IRB approval must be likewise submitted and approved. 

Notification will be given to the IRB in the event any serious adverse events occur. 

	
 	
13.5 		
Disclosure of Data

	
	 	 	 
	 		
It is understood by the investigator that the information and data included in this protocol may be disclosed to and used by the investigator's staff and associates as may be necessary to conduct this clinical trial.

	
	 	 	 
	 		
The information derived from this clinical study will be used by Advance Biofactures Corporation and therefore, may be disclosed by Advance Biofactures Corporation as required to other clinical investigators, to the Food and Drug
Administration, and to other government agencies. In order to allow for the use of the information derived from this clinical study, it is understood by the investigator that there is an obligation to provide Advance Biofactures Corporation with
complete test results and all data from this clinical study.

	
	 	 	 
	
 	
13.6 		
Confidentiality of Documents / Subject Records

	
	 	 	 
	 		
The investigator must assure that subject’s anonymity will be maintained and that their identities are protected from unauthorized parties. CRFs or other documents submitted to the sponsor should not be identified by their
names but by an identification code. Documents not submitted to the sponsor shall be maintained by the investigator in strict confidence.

	
	 	 	
 

	
14. 		
STUDY DOCUMENTATION

	
	 	 	 
		
14.1 		
Investigator’s Statement

	
	 	 	 
			
The investigator must sign the investigator’s statement (Attachment 1) prior to performing an examination or treatment of a subject.

	
	 	 	 
		
14.2 		
Investigator’s Record Requirements

	
	 	 	 
			
Federal regulations require that copies of case report forms and other pertinent documentation (i.e., photographs, laboratory reports, hospital or office subject's records,
etc.) be retained by the investigator for a period of two years following either the approval of the BLA or withdrawal of the BLA. 

	

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The investigator is aware of the fact that he/she may be subjected to a field audit by FDA inspectors in order to validate the participation of subjects in the study and to verify the data reported on the case report forms.  With this in mind,
careful attention should be paid to seeing that records of medications received and copies of original photographs, laboratory tests, etc., are filed, and retained, in the investigator's file along with the Case Report Form. Documentation should be
made on the office/hospital chart and transferred to the Case Report Form.  The participation of all subjects in Lipoma [**] should be noted in the office/hospital chart. The signed informed consent should be filed with the subject's source document
chart. 

	
 	
14.3 		
Departures from Protocol

	
	 	 	 	 	 
	 		
When circumstances arise, which suggest that a departure from this protocol should be considered, the investigator or other physician in attendance must contact the study monitor by telephone as soon as possible prior to
implementation. Any departure from the agreed protocol will pertain only to the individual subject involved. The Case Report Form will describe the circumstances and identify the pertinent protocol procedure.

	
	 	 	 	 	 
	 		
In the event that a protocol change is proposed for all subjects, then the procedure for protocol amendment should be followed. In either case, any modification of the protocol that may become necessary during the course of this
study, other than to protect subjects from an immediate hazard, is subject to prior discussion between the clinical investigator and Advance Biofactures Corporation.

	
	 	 	 	 	 
	
 	
14.4 		
Study Documentation: Case Report Forms (CRFs), Standardized Source Documents and Record Keeping.

	
	 	 	 	 	 
	 		
The investigator must maintain adequate and accurate records to enable the conduct of the study to be fully documented and the study data to be subsequently verified. These documents should be classified into two different
separate categories: (1) Investigator’s Study File, and (2) Subject Clinical Source Documents.

	
	 	 	 	 	 
	 		
14.4.1 		
The Investigator’s Study File will contain the following:

	
	 	 	 	 	 
	 			
a. 		
The Protocol / Amendments

	
	 	 	 	 	 
	 			
b. 		
FDA 1572

	
	 	 	 	 	 
	 			
c. 		
Signed Investigator’s Agreement

	

** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

 29

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110718 

	
 	
 	
 	
d. 		
Ethical Committee / Institutional Review Board and Governmental Approval with Correspondence

	
	 	 	 	 	 
	
 	
 	
 	
e. 		
Informed Consent

	
	 	 	 	 	 
	
 	
 	
 	
f. 		
Investigator Brochure

	
	 	 	 	 	 
	
 	
 	
 	
g. 		
Safety Reports

	
	 	 	 	 	 
	
 	
 	
 	
h. 		
Drug Records (including shipment records and accountability log)

	
	 	 	 	 	 
	
 	
 	
 	
i. 		
Randomization Schedule / Treatment Code

	
	 	 	 	 	 
	
 	
 	
 	
j. 		
Site Study Personnel Curriculum Vitae

	
	 	 	 	 	 
	
 	
 	
 	
k. 		
Study Correspondence Between Site and Sponsor

	
	 	 	 	 	 
	
 	
 	
 	
l. 		
Laboratory Certification and Normal Ranges

	
	 	 	 	 	 
	
 	
 	
 	
m. 		
Site Study Personnel Signature Log

	
	 	 	 	 	 
	
 	
 	
 	
n. 		
Screening and Enrollment Log

	
	 	 	 	 	 
	
 	
 	
 	
o. 		
Monitor’s Visit / Signature Log

	
	
 	
 	
 	
 	
 

	
 	
 	
14.4.2 		
Subject’s Clinical Source Documents which may include:

	
	 	 	 	 	 
	 	 		
a. 		
Standardized Source Document

	
	 	 	 	 	 
	 	 		
b. 		
Subject Hospital / Clinic Records

	
	 	 	 	 	 
	 	 		
c. 		
Physician / Nurse’s Notes

	
	 	 	 	 	 
	 	 		
d. 		
Original Laboratory Reports

	
	 	 	 	 	 
	 	 		
e. 		
ECG, MRI, Pathology and Special Assessment Reports

	
	 	 	 	 	 
	 	 		
f. 		
Photo of Subject’s Lipoma(s)

	
	 	 	 	 	 
	 	 		
g. 		
Consultant Letters

	

These two categories of documents must be kept on file by the Investigator for at least two years following either the approval of the BLA or withdrawal of the BLA. No study document should be destroyed without prior written agreement between ABC
and the Investigator. Should the Investigator wish to assign the study records to another party or move them to another location, ABC must be notified in advance. 

If the Investigator cannot guarantee this archiving requirement at the investigational site for any or all of the documents, special arrangements must be made to store these in a sealed container(s) outside of the site so that they can be returned
sealed to the Investigator in case of a regulatory audit. When source documents are required for the continued care of the subject, appropriate copies should be made for storing outside of the site.

30

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14.5 		
Monitor or Health Authority Queries 

	

The investigator shall supply the monitor on request with any required background data from the study documentation or clinic records. This is particularly important when Case Report Forms are illegible or when errors in data transcription are
suspected. In case of special problems and/or governmental queries or requests for audit inspections, it is also necessary to have access to the complete study records, provided that subject confidentiality is protected. 

	
 	
14.6 		
Inspections

	
	 	 	 	 	 
	 		
The investigator should understand that source documents for this trial should be made available to the study monitor or to health authority inspectors after appropriate notification. The verification of the Case Report Form data
may be by direct inspection of source documents (where permitted by law) or through an interview technique.

	
	 	 	 	 	 
	 		
The minimal requirement for the source data checks include:

	
	 	 	 	 	 
	 		
14.6.1 		
All subjects to be 100% SDV

	
	 	 	 	 	 
	 		
14.6.2 		
Each subject should have the following data points SDV:

	
	 	 	 	 	 
	 			
14.6.2.1 		
Subject’s existence

	
	 	 	 	 	 
	 			
14.6.2.2 		
Informed consent

	
	 	 	 	 	 
	 			
14.6.2.3 		
Inclusion/exclusion criteria

	
	 	 	 	 	 
	 			
14.6.2.4 		
All adverse events and Serious Adverse Events

	
	 	 	 	 	 
	 			
14.6.2.5 		
Study medication & dispensing

	
	 	 	 	 	 
	 			
14.6.2.6 		
Date of visits

	
	 	 	 	 	 
	 		
14.6.3 		
Case Report Forms and Standardized Source Documents

	
	 	 	 	 	 
	 			
For each subject enrolled, Case Report Form as well as a standardized source document must be completed and signed by the principal investigator or co- investigator. This also applies to the records of those subjects who fail to
complete the study (even during the screening period if a Case Report form is
initiated). If a
subject withdraws from the study because of a treatment-limiting adverse event,
thorough efforts must be made to clearly document the outcome. All forms must be typed or filled-out using black ballpoint pen, and must
be legible. Errors should be crossed out but not obliterated, the correction inserted and the change initialed and dated by the investigator or his/her
authorized delegate.

	

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14.7 		
Monitoring of the Study 

	

It is understood that the responsible monitor will contact and visit the investigator/site regularly and that he/she will be allowed, on request, to inspect the various records of the trial (Case Report Forms, Standardized Source Documents and other
pertinent data), provided that subject confidentiality is maintained in accordance with local requirements. It will be the monitor’s responsibility to inspect the Case Report Forms at regular intervals throughout the study, to verify the
completeness, consistency and accuracy of the data being entered on them, and to verify adherence to the protocol.  The monitor should have access to laboratory test reports and other subject records needed to verify the entries on the Case Report
Form.  The investigator (or his/her deputy) agrees to cooperate with the monitor to ensure that any problems detected in the course of these monitoring visits are resolved. 

For this study, the expected average monitoring frequency is every [**]weeks.

** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

 

 

 

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ATTACHMENT 1

INVESTIGATOR’S SIGNATURE PAGE

I have thoroughly read and reviewed the study protocol.  Having read and understood the requirements and conditions of the study protocol, I agree to perform the clinical study according to the international Good Clinical Practice principles and
regulatory authority requirements for source document verification and auditing / inspection of the study. 

I agree to use the study material, including medication and diluent, only as specified in the protocol. 

I understand that changes to the protocol must be made in the form of an amendment, which has prior written approval of the Sponsor. 

I understand that any violation of the protocol may lead to early termination of the study. 

I agree to follow the study time schedule as outlined in the protocol. 

I agree to report to the Sponsor, within one working day, of any clinical adverse event that is serious, whether considered treatment-related or not. 

	
Signature
	
	
 	
Date
	

	
 	
 	
 
	
 	
 	
 
	
Signature
	
	
 	
Date
	

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Lipoma DE/01 

110718

	
      ATTACHMENT 2 

      SUBJECT QUESTIONNAIRE 

 

	Subject #________ 	Subject Initials__________ 
	Study Visit____________________________ 	Date__________________

	 	 
	Location of Lipoma #1_________________  	Location of Lipoma #2_________________
	 	 

To Be Completed by the Subject: Please provide the
requested information regarding the two lipomas under treatment for the
appropriate visit. Enter the number of the best response. 

 	[    ] 	
     Initial Screening Visit: 
	
      
	  	  
	 	
     
	
     
	 	 
	  	
    1. Reason for treating
      lipomas 
	
    1 = [**] 
	Lipoma #1 	Lipoma #2 
	  	
      
	
    2 = [**] 
	  	  
	  	
      
	
    3 = [**] 
	  	  
	  	
    2. How [**] are the lipomas
      to be treated? 
	
    1 = Not at all 
	Lipoma #1 	Lipoma #2 
	  	
      
	
    2 = Somewhat
	  	  
	  	
      
	
    3 = Very 
	  	  
	 	
     
	
     
	 	 
	Subject
      Signature_______________________________/ Date_______________

	 
	[    ] 	
     All Other Visits: 
	
      
	  	  
	 	
     
	
     
	 	 
	  	
    1. How [**] are the lipomas
      to be treated? 
	
    1 = Not at all 
	Lipoma #1 	Lipoma #2 
	  	
      
	
    2 = Somewhat
	  	  
	  	
      
	
    3 = Very 
	  	  
	  	
    2. How [**] ?
	
    1 = [**] 
	Lipoma #1
    	Lipoma #2
    
	  	
      
	
    2 = [**] 
	  	  
	  	
      
	
    3 = [**] 
	  	  
	  	
    3.  If this is your final
      visit, would you participate in  
	
    1 = Yes
	Lipoma #1
    	Lipoma #2
    
	  	
          this trial again?  
	
    2 = No
	  	  
	  	
      
	
    3 = N/A
	  	  

Subject Signature_______________________________/
Date_______________

** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND
FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO
A CONFIDENTIAL TREATMENT REQUEST. 

1

A Dose Escalation Study Using Collagenase Clostridium
Histolyticum 

in the Treatment of Lipoma 

Lipoma DE/01 

110718

	
      ATTACHMENT 2 

      SUBJECT QUESTIONNAIRE 

 

	Subject #________ 	Subject Initials__________ 
	Study Visit____________________________ 	Date__________________

	 	 
	Location of Lipoma #1_________________  	Location of Lipoma #2_________________
	 	 

To Be Completed by the Subject: Please provide the
requested information regarding the two lipomas under treatment for the
appropriate visit. Enter the number of the best response. 

 	[    ] 	
     Initial Screening Visit: 
	
      
	  	  
	 	
     
	
     
	 	 
	  	
    1. Reason for treating
      lipomas 
	
    1 = [**] 
	Lipoma #1 	Lipoma #2 
	  	
      
	
    2 = [**] 
	  	  
	  	
      
	
    3 = [**] 
	  	  
	  	
    2. How [**] are the lipomas
      to be treated? 
	
    1 = Not at all 
	Lipoma #1 	Lipoma #2 
	  	
      
	
    2 = Somewhat
	  	  
	  	
      
	
    3 = Very 
	  	  
	 	
     
	
     
	 	 
	Subject
      Signature_______________________________/ Date_______________

	 
	[    ] 	
     All Other Visits: 
	
      
	  	  
	 	
     
	
     
	 	 
	  	
    1. How [**] are the lipomas
      to be treated? 
	
    1 = Not at all 
	Lipoma #1 	Lipoma #2 
	  	
      
	
    2 = Somewhat
	  	  
	  	
      
	
    3 = Very 
	  	  
	  	
    2. How [**] ?
	
    1 = [**] 
	Lipoma #1
    	Lipoma #2
    
	  	
      
	
    2 = [**] 
	  	  
	  	
      
	
    3 = [**] 
	  	  
	  	
    3.  If this is your final
      visit, would you participate in  
	
    1 = Yes
	Lipoma #1
    	Lipoma #2
    
	  	
          this trial again?  
	
    2 = No
	  	  
	  	
      
	
    3 = N/A
	  	  

Subject Signature_______________________________/
Date_______________

** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND
FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO
A CONFIDENTIAL TREATMENT REQUEST. 

1

Schedule 3.1(b)(3)

In Vitro Research Proposal Template

Introduction

The proposal states the purpose and potential importance of the project.

Research Questions and Hypotheses

In this section, the proposal states a research question and hypotheses. The research question should be of potential significance. This section will describe and provide references for currently available technology and/or therapeutic options. It
will include a brief discussion of the study objectives including benefits that may ultimately result if the in vitro research is successful. It also will define “success” of the project and how the data generated may be used. 

Methods and Procedures

This section gives the details on the experimental design, test methods, materials, analytical techniques, and data collection. This section also outlines next steps, if applicable. 

 

 

 

Schedule 3.2 

Clinical Trials

Dupuytren’s Disease

[**]  

Peyronie’s Disease

[**]

Frozen Shoulder

[**] 

** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST. 

Schedule 13.1 Joint Press Release

Auxilium Pharmaceuticals, Inc. and BioSpecifics Technologies
Corp. 
Announce Plans to Develop Additional Indications using
XIAFLEX®

- Parties Dismiss All Pending Litigation -

-Auxilium to Initiate Studies for the Treatment of Cellulite;
BioSpecifics to Initiate Studies 
for the Treatment of Human and Canine
Lipomas-

-Auxilium Conference Call with Investors Scheduled for 9:00 am
ET September 1; 
BioSpecifics Conference Call with Investors Scheduled for
10:30 am ET 
September 1-

MALVERN, PA and LYNBROOK, NY.,  August 31, 2011--Auxilium
Pharmaceuticals, Inc. (NASDAQ: AUXL), a specialty biopharmaceutical company, and
BioSpecifics Technologies Corp. (NASDAQ: BSTC), a biopharmaceutical company,
today announced that they have dismissed all pending litigation between the
Companies and announced plans to move XIAFLEX forward in the clinic for
cellulite and human and canine lipoma as well as to collaborate on the
initiation of further studies for XIAFLEX for additional indications. Through an
amendment and restatement of the Companies’ 2008 development and license
agreement, the Companies have clarified the rights and responsibilities of the
Joint Development Committee. 

Auxilium has been granted the right to initiate studies for the
treatment of edematous fibrosclerotic panniculopathy, more commonly known as
cellulite, and expects to begin phase Ib clinical studies in early 2012.
BioSpecifics will initiate studies for the treatment of human and canine lipomas
and plans to initiate clinical studies for both human and canine lipomas
shortly. Auxilium will continue to have the option to exclusively license these
indications upon completion of BioSpecifics’ development work. Auxilium and
BioSpecifics also plan to collaborate on identifying further indications for
treatment with XIAFLEX. 

Based on the terms of the amended agreement, Auxilium will pay
BioSpecifics an opt-in fee at the time of completion by Auxilium of Stage I
development of cellulite and will be responsible for all development costs
associated with cellulite. Auxilium’s opt-in rights remain unchanged with
respect to the two lipoma indications. In addition to the opt-in fees,
BioSpecifics will continue to be entitled to regulatory milestones, low double
digit royalties and a markup of cost of goods on all indications.

“We are pleased that we have reached a mutually beneficial
settlement with our partner BioSpecifics, and we are excited to move forward
with the development of XIAFLEX in cellulite,” said Armando Anido, Chief
Executive Officer and President of Auxilium. “We look forward to a close
collaboration with BioSpecifics on the development of additional indications
that could result in new opportunities for XIAFLEX.” 

“We are very happy to be collaborating with Auxilium as we
explore promising new indications for XIAFLEX that could have significant
potential benefit for patients,” commented Thomas L. Wegman, President of
BioSpecifics. “We are very enthusiastic about the positive study results we have
already seen for both human and canine lipoma and look forward to advancing
these indications in the clinic as soon as possible.”

Auxilium Conference Call

Auxilium will hold a conference call tomorrow, September 1,
2011 at 9:00 am ET, to discuss these developments. The presentation slides to be
used during the call are now available on the “For Investors” section of the
Company’s web site under the “Presentations” tab. A question and answer session
will follow the presentation. The conference call and the presentation slides
will be simultaneously web cast on the “For Investors” section of its web site
under the “Events” tab. The conference call will be archived for future review
until October 1, 2011.

	Conference call details: 	  
	Date: 	Thursday, September 1, 2011 
	Time: 	9:00 a.m. ET 
	Dial-in (U.S.): 	XXX-XXX-XXXX 
	Dial-in (International): 	XXX-XXX-XXXX 
	Web cast: 	http://www.auxilium.com 
	Passcode: 	AUXILIUM 
	  	  
	To access an audio replay of the call: 	  
	Access number (U.S.): 	XXX-XXX-XXXX 
	Access number (International): 	XXX-XXX-XXXX 
	Replay Passcode #: 	XXXXXX 

BioSpecifics Conference Call

BioSpecifics will hold a conference call tomorrow, September 1,
2011 at 10:30 a.m. ET, to discuss these developments. The conference call will
be simultaneously web cast on BioSpecifics’ website and archived for future
review until October 1, 2011.

	Conference call details: 	  
	Date: 	Thursday, September 1, 2011 
	Time: 	10:30 a.m. ET 
	Dial-in (U.S.): 	XXX-XXX-XXXX 
	Dial-in (International): 	XXX-XXX-XXXX 
	Web cast: 	http://www.biospecifics.com 
	Passcode: 	XXXXXXXX 
	  	  
	To access an audio replay of the call: 	  
	Access number (U.S.): 	XXX-XXX-XXXX 
	Access number (International): 	XXX-XXX-XXXX 
	Replay Passcode #: 	XXXXXX 

About Auxilium

Auxilium Pharmaceuticals, Inc. is a specialty biopharmaceutical
company with a focus on developing and marketing products to predominantly
specialist audiences, such as urologists, endocrinologists, certain targeted
primary care physicians, hand surgeons, subsets of orthopedic, general, and
plastic surgeons who focus on the hand, and rheumatologists. Auxilium markets
XIAFLEX® (collagenase clostridium histolyticum) for the treatment of
adult Dupuytren's contracture patients with a palpable cord and Testim® 1%, a
testosterone gel, for the topical treatment of hypogonadism in the U.S. Pfizer
Inc. has marketing rights for XIAPEX® (the EU tradename for
collagenase clostridium histolyticum) in 46 countries in Eurasia and Asahi Kasei
Pharma Corporation has development and commercial rights for XIAFLEX in Japan.
Ferring International Center S.A. markets Testim in the EU and Paladin Labs Inc.
markets Testim in Canada. Auxilium has three projects in clinical development.
XIAFLEX is in phase III of development for the treatment of Peyronie's disease,
in phase II of development for the treatment of Frozen Shoulder syndrome
(Adhesive Capsulitis) and is in phase I of development for the treatment of
cellulite (edematous fibrosclerotic panniculopathy). Auxilium also has rights to
pursue additional indications for XIAFLEX. For additional information, visit
http://www.auxilium.com. 

About BioSpecifics Technologies Corp.

BioSpecifics Technologies Corp. is a biopharmaceutical company
that has developed injectable collagenase for twelve clinical indications, five
of which include: Dupuytren's contracture; Peyronie's disease; Frozen Shoulder (Adhesive Capsulitis) and human and
canine lipoma. Its strategic partner Auxilium Pharmaceuticals, Inc. markets
XIAFLEX® in the U.S. for the treatment of Dupuytren's contracture.
Pfizer, Inc. is responsible for marketing XIAPEX® in 46 countries in
Eurasia and Asahi Kasei Pharma Corporation has development and commercial rights
for XIAFLEX in Japan. More information about the Company may be found on its
website at www.biospecifics.com.

About Cellulite

Cellulite, also known medically as edematous fibrosclerotic
panniculopathy, describes a pathologic inflammatory condition, in which lobules
of subcutaneous adipose tissue extend into the dermal layer. These changes can
visibly affect the shape of the epidermis and resemble an orange peel-like
dimpling of the skin.1

In the normal subcutaneous fat layer directly under the skin,
there are both perpendicular columnar and net-like fibrous connective tissue
called septae. These fibrous septae, made of types I and III collagen, connect
the epidermis to the dermis and create a network of compartmentalized adipose
deposits. Women tend to have a higher proportion of columnar septae that are
perpendicular to the epidermis, while men tend to have more of the net-like
system. In cellulite, the subcutaneous fat cells swell and push upwards. 2
As a result, the skin between the septae is pushed up and the
perpendicular septae act as an anchor to pull the epidermis downwards and form
the classic cellulite dimple. The surrounding adipose tissue forms small bulges
under the epidermis around the dimple that can give skin a "cottage cheese"
texture. 

Cellulite has been reported to occur in 85 to 98% of
post-pubertal females and rarely in men. The condition is prevalent in women of
all races. 1

1 Avram, Cellulite: a review of its physiology
and treatment, Journal of Cosmetic Laser Therapy 2004; 6: 181–185 
2
Querleux, Anatomy and physiology of subcutaneous adipose tissue by in
vivo MRI and spectroscopy: Relationship with sex and presence of cellulite,
Skin Research and Technology; 8: 118-124

About Human and Canine Lipoma

Lipomas are encapsulated fat deposits that occur under the skin
and they are common in both humans and dogs. Approximately 1% of the general
human population has a lipoma.1 Subcutaneous lipomas are the most
common lipomas found in humans.

In addition, lipomas that restrict motion in older dogs are a
serious problem. The only proven therapy for this condition is surgical excision
of the lipoma, which necessarily involves the use of general anesthesia. It has
been estimated that up to 2% of dogs die as a complication of general
anesthesia.2 Lipomas occur in 2.3% of the dog population, 3
or in approximately 1.7 million dogs in the U.S.4

1 Nickloes E-Medicine 2010 March 
2
Brodbelt Vet J 2009 Dec; 182 (3): 375-6 
3 Lund JAVMA Vol.
214, No. 9, May 1, 1999
4 U.S. Pet Ownership & Demographics
Sourcebook (2007 Edition)

AUXILIUM SAFE HARBOR STATEMENT UNDER THE PRIVATE SECURITIES
LITIGATION REFORM ACT OF 1995

This release contains "forward-looking-statements" within the
meaning of The Private Securities Litigation Reform Act of 1995, including
statements regarding the timing of phase Ib clinical studies for XIALFEX®
for the treatment of edematous fibrosclerotic panniculopathy, more
commonly known as cellulite; the number of people with cellulite; the
identification of additional indications for XIAFLEX and their market potential
and products in development for Peyronie's disease and Frozen Shoulder syndrome;
and all other statements containing projections, statements of future
performance or expectations, our beliefs or statements of plans or objectives
for future operations (including statements of assumption underlying or relating
to any of the foregoing). Forward-looking statements can generally be identified
by words such as "believe," "appears," "may," "could," "will," "estimate,"
"continue," "anticipate," "intend," "should," "plan," "expect," and other words
and terms of similar meaning in connection with any discussion of projections,
future performance or expectations, beliefs, plans or objectives for future
operations (including statements of assumption underlying or relating to any of
the foregoing). Actual results may differ materially from those reflected in
these forward-looking statements due to various factors, including further
evaluation of clinical data, results of clinical trials, decisions by regulatory
authorities as to whether and when to approve drug applications, and general
financial, economic, regulatory and political conditions affecting the
biotechnology and pharmaceutical industries and those discussed in Auxilium's
Annual Report under the heading "Risk Factors” on Form 10-K for the year ended
December 31, 2010 and Form 10-Q for the quarter ended June 30, 2011, which are
on file with the Securities and Exchange Commission (the "SEC") and may be
accessed electronically by means of the SEC's home page on the Internet at
http://www.sec.gov or by means of Auxilium's home page on the Internet at
http://www.Auxilium.com under the heading "For Investors -- SEC Filings." There may be additional risks
that Auxilium does not presently know or that Auxilium currently believes are
immaterial which could also cause actual results to differ from those contained
in the forward-looking statements. Given these risks and uncertainties, any or
all of these forward-looking statements may prove to be incorrect. Therefore,
you should not rely on any such factors or forward-looking statements.

In addition, forward-looking statements provide Auxilium's
expectations, plans or forecasts of future events and views as of the date of
this release. Auxilium anticipates that subsequent events and developments will
cause Auxilium's assessments to change. However, while Auxilium may elect to
update these forward-looking statements at some point in the future, Auxilium
specifically disclaims any obligation to do so. These forward-looking statements
should not be relied upon as representing Auxilium's assessments as of any date
subsequent to the date of this release.

Auxilium disclaims responsibility for statements above in
“About BioSpecifics”, which were provided by BioSpecifics for inclusion in this
release.

BioSpecifics Forward-Looking Statements

This press release contains forward-looking statements within
the meaning of The Private Securities Litigation Reform Act of 1995. Any
statements, other than statements of historical fact, including statements
regarding BioSpecifics’ strategy, future operations, future financial position,
future revenues, projected costs, prospects, plans and objectives of management,
its expected revenue growth, and any other statements containing the words
“believes,” “expects,” “anticipates,” “plans,” “estimates” and similar
expressions, are forward-looking statements. There are a number of important
factors that could cause its actual results to differ materially from those
indicated by such forward-looking statements, including the statements made by
BioSpecifics concerning the likelihood of success of future clinical trials in
new indications, and other risk factors identified in the BioSpecifics' Form
10-K for the year ended December 31, 2010 and its reports on Form 8-K filed with
the SEC. All forward-looking statements included in this press release are made
as of the date hereof, and BioSpecifics assumes no obligation to update these
forward-looking statements.

BioSpecifics disclaims responsibility for statements above in
“About Auxilium”, which were provided by Auxilium for inclusion in this
release.

Auxilium Contacts: 

James E. Fickenscher
Chief Financial
Officer
+1-484-321-5900
jfickenscher@auxilium.com
or 
William Q.
Sargent Jr.
Vice-President, Investor Relations and Corporate
Communications
+1-484-321-5900
wsargent@auxilium.com 

BioSpecifics contact:

BioSpecifics Technologies Corp.
Thomas L. Wegman,
President
(516) 593-7000
thomas_wegman@biospecifics.comBioSpecifics Technologies Corp.: Exhibit 10.2 - Filed by
   newsfilecorp.com

	
Confidential treatment requested under 17 C.F.R. §§ 200.80(b)(4) and 240.24b-2. The
		
 
	
	
confidential portions of this exhibit have been omitted and are marked accordingly.
		
EXECUTION COPY 
	

	
The confidential portions have been filed separately with the Securities and Exchange
		
 
	
	
Commission pursuant to a confidential treatment request.
		
 
	
	
                                                                      
                                   	
 
	

 SETTLEMENT AGREEMENT

  This Settlement Agreement (this “Agreement”) is made as of the last date upon which a Party hereto signs this Agreement (“Execution Date”), by and between BioSpecifics Technologies Corp., a corporation organized and existing
under the laws of the State of Delaware and having its principal office at 35 Wilbur Street, Lynbrook, New York 11563, and its affiliates (collectively, “BTC”), and Auxilium Pharmaceuticals, Inc., a corporation organized and existing under
the laws of the State of Delaware and having its principal office at 40 Valley Stream Parkway, Malvern, PA 19355 (“Auxilium”). BTC and Auxilium shall sometimes be referred to herein individually as a “Party” and collectively as
“Parties.” 

RECITALS

 WHEREAS, the Parties were engaged in a mediation to settle, inter alia, their disagreements relating to the inventorship of U.S. Patent No. 7,811,560 (the “’560 Patent”) and the Amended and Restated Development
and License Agreement between the Parties dated December 11, 2008 (the “License”), which mediation terminated without resolution on December 31, 2010 (the “IP Mediation”);

WHEREAS, on February 15, 2011, Auxilium filed a complaint in the Court of Common Pleas of the Commonwealth of Pennsylvania, Chester County (the “Court of Common Pleas”), against BTC, captioned Auxilium Pharmaceuticals, Inc. v.
BioSpecifics Technologies Corp., No. 11-01620, alleging that BTC breached the License by its commencement of clinical trials for the use of injectable collagenase to treat canine lipomas without the prior knowledge and approval of the
parties’ Joint Development Committee (the “February Pennsylvania Litigation”); 

WHEREAS, on May 2, 2011, BTC filed a complaint in the Supreme Court of the State of New York, Nassau County, Commercial Division (the “Supreme Court”), against RecipharmCobra Holdings Limited (“RCHL”), Recipharm AB,
(“RAB” and together with RCHL, “Recipharm”) and Auxilium, captioned BioSpecifics Technologies Corp. v. Recipharm AB, RecipharmCobra Holdings Limited and Auxilium Pharmaceuticals, Inc., No. 600341/2011, claiming Auxilium
breached an oral contract with BTC, converted BTC’s intellectual property, and interfered with a contract BTC has with Recipharm (the “NY Litigation”); 

WHEREAS, on June 28, 2011, Auxilium filed a complaint in the Court of Common Pleas, against BTC, captioned RecipharmCobra Holdings Limited and Auxilium Pharmaceuticals, Inc. v. BioSpecifics Technologies Corp., No. 11-07184,
requesting declaratory judgment with respect to BTC’s allegations set forth in the NY Litigation (the “June Pennsylvania Litigation”); 

WHEREAS, on April 28, 2011, pursuant to Section 13.2 of the License, BTC demanded mediation of a dispute regarding the amount BTC owes Auxilium for BTC’s share of lyophilization development costs under Section 6.2 of the License (the
“Lyophilization Dispute”); 

EXECUTION COPY

WHEREAS, the Parties have articulated or referred to various other disagreements arising from or relating to the License (together with all foregoing disagreements defined herein as the “Matters in Dispute”); and 

 WHEREAS, the Parties desire to settle the Matters in Dispute, and any other dispute that each may now have against the other, on the terms and conditions set forth below; 

 WHEREFORE, in consideration of the mutual covenants and undertakings set out herein, as well as in the Second Amended and Restated Development and License Agreement executed concurrently herewith (the “Second Amended and Restated
DLA”) and other good and valuable consideration the sufficiency of which is hereby acknowledged, the Parties, intending to be bound, agree as follows: 

Section 1. Releases, [**] Agreement and Dismissal of Litigations 

1.1 Except as provided for in Section 1.3, as of the Effective Date, each Party, on behalf of itself and its present and former affiliates, agents, directors, officers, employees, attorneys, and the successors and assignees of each
does hereby release, waive, forever discharge, and hold harmless each other and their present and former affiliates, agents, directors, officers, employees, consultants, attorneys, and the successors and assignees of each, of, from, and with respect
to, any and all liabilities, losses, damages, charges, complaints, claims, counterclaims, obligations, promises, agreements, controversies, actions, causes of action, suits, rights, demands, costs, debts and expenses (including attorneys fees and
court costs) of any nature whatsoever, known or unknown, suspected or unsuspected that may have arisen before the Effective Date, which the Parties at any time hereafter may have, own or hold, or claim to have, own or hold against each other,
including but not limited to any claims or counterclaims that were brought or could have been brought in the IP Mediation, the February Pennsylvania Litigation, the NY Litigation, the June Pennsylvania Litigation, the Lyophilization Dispute, or any
other of the Matters in Dispute. 

1.2 As of the Effective Date, BTC, on behalf of itself and its present and former affiliates, agents, directors, officers, employees, attorneys, and the successors and assignees does hereby release, waive, forever discharge, and hold
harmless Cobra Manufacturing Plc, RecipharmCobra Biologics Limited, Recipharm (collectively referred to as “Cobra”) and their present and former affiliates, agents, directors, officers, employees, consultants, attorneys, and the successors
and assignees, of, from, and with respect to any and all liabilities, losses, damages, charges, complaints, claims, counterclaims, obligations, promises, agreements, controversies, actions, causes of action, suits, rights, demands, costs, debts and
expenses (including attorneys fees and court costs) of any nature whatsoever, known or unknown, suspected or unsuspected that may have arisen before the Effective Date relating to the Materials Transfer Agreement dated February 29, 2004 between BTC
and Cobra (“MTA”), which BTC at any time hereafter may have, own or hold, or claim to have, own or hold against Cobra, including but not limited to, any claims that were brought or could have been brought in the NY Litigation or the June
Pennsylvania Litigation. For the avoidance of doubt, BTC hereby waives and releases any claims that the MTA conveys patent or inventorship rights from Cobra to BTC. BTC and Auxilium warrant that the
provisions of this paragraph are not subject to any actions of either BTC or Auxilium other than those set forth in Section 4 herein. 

	
** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST.

2

EXECUTION COPY

1.3 Auxilium [**], and the Parties shall execute a [**] agreement [**] in the form attached as Exhibit A (the “[**] Agreement”), which [**] Agreement shall be incorporated herein by reference. 

1.4 Within one (1) business day after the Execution Date and the execution of the Second Amended and Restated DLA, in connection with (a) the February Pennsylvania Litigation, Auxilium agrees to execute and file with the Chester County
Court of Common Pleas the Praecipe to Settle, Discontinue and End the February Pennsylvania Litigation with prejudice, in the form attached hereto as Exhibit B, and (b) the June Pennsylvania Litigation, Auxilium agrees to, and cause RCHL, to
execute and file with the Chester County Court of Common Pleas the Praecipe to Settle, Discontinue and End the June Pennsylvania Litigation with prejudice, in the form attached hereto as Exhibit C (the “June Pennsylvania Stipulation of
Dismissal”). 

1.5 Within one (1) business day after the Execution Date and execution of the Second Amended and Restated DLA, in connection with the NY Litigation, BTC agrees to execute and file with the Supreme Court the Stipulation of
Discontinuance of the NY Litigation with prejudice, in the form attached hereto as Exhibit D. 

Section 2. Patents

2.1 Within one (1) business day after the Execution Date and the execution of the Second Amended and Restated DLA, Auxilium will cause the execution of assignments of all patents and patent applications claiming priority to either U.S.
Application No. 60/763,470 or U.S. Application No. 60/784,135 in the two (2) forms attached as Exhibit E to this Agreement, and BTC shall execute an assignment of certain intellectual property rights in the form attached as Exhibit F
(with the foregoing assignments collectively referred to as the “Assignments”).Upon the Effective Date, BTC acknowledges that it has a duty to disclose material information to Auxilium regarding such patent applications. The Parties
acknowledge and agree that the Assignments are not effective or legally binding until the Effective Date. 

2.2 BTC will file with the U.S. Patent and Trademark Office (“USPTO”), a request to expressly abandon in the form of USPTO’s Form PTO/SB/24 U.S. Application Nos. 12/759,065 and 12/837,933 within one (1) day after the
Effective Date. 

2.3 Auxilium, in the reasonable exercise of its commercial discretion and in accord with Section 8.1 and Section 13.4 of the License (as amended and restated in the Second Amended and Restated DLA) shall continue to make all decisions
regarding whether and how to file, prepare, prosecute, maintain, renew, and defend any and all subsequent applications claiming priority to U.S. Application No. 60/763,470 or U.S. Application No. 60/784,135, including any reissue, reexamination,
divisional, continuation-in-part, extension or continuation thereof and all rights of priority under the International Convention arising from said applications. 

	
** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST.

3

EXECUTION COPY

Section 3. Credits Against Royalties; Waiver

3.1 BTC agrees that it owes Auxilium $[**] in full and final settlement for its share of the Parties’ lyophilization costs under the License, with Auxilium to credit this amount against Auxilium’s future royalty payments
to BTC. The Parties recognize that this resolves the Lyophilization Dispute, and BTC hereby and accordingly cancels its April 2011 request to mediate the Lyophilization Dispute. 

3.2 BTC agrees that it owes Auxilium $[**] in full and final settlement of its share of the Parties’ patent costs arising under § 8.1(c)(i)(A) of the License through June 30, 2011, with Auxilium to credit this
amount against Auxilium’s future royalty payments to BTC. 

3.3 The Parties agree that, as of June 30, 2011, Auxilium already has credited $[**] against Auxilium’s past royalty payments to BTC, and thus shall credit $[**] from future royalty payments to BTC to satisfy Sections 3.1
and 3.2 herein. 

Section 4.Conditions

4.1 The Parties acknowledge and agree that this Agreement, and the Assignments, shall neither be effective nor legally binding upon the Parties unless and until all of the following occur (the date on which the last occurs shall be the
“Effective Date”): 

 (a) the Parties shall have executed the Second Amended and Restated DLA, in the form attached as Exhibit G to this Agreement, to further amend the License, and the other documents attached as Exhibits A-F;

 (b) the Parties shall have (i) filed with the Pennsylvania Court of Common Pleas, Chester County, signed Praecipes to Settle, Discontinue and End with prejudice (in the form attached hereto as Exhibits B and C), so as to dismiss the
February Pennsylvania Litigation and the June Pennsylvania Litigation with prejudice, and (ii) filed with the Supreme Court of the State of New York, County of Nassau, a signed Stipulation of Discontinuance with prejudice (in the form attached
hereto as Exhibit D), so as to dismiss the NY Litigation with prejudice; and 

(c) The Parties shall have executed the Assignments. 

Section 5. Arbitration of Inventorship 

5.1 Following the Effective Date, the Parties agree to arbitrate the following issues: (1) whether Bo Yu and/or Thomas Wegman should be added as joint inventors of the ‘560 Patent (and its foreign equivalents) under 35 U.S.C.
§ 256, and (2) whether Bo Yu and/or Thomas Wegman should be listed as joint inventors for certain Proposed Claims (as defined below) (the “Arbitration”). The Parties further agree that inventorship will be the only issue submitted in
the Arbitration. 

5.2 For purposes of the Arbitration, each Party may propose an initial list of up to five (5) claims (both lists together are referred to as the “Proposed Claims”) that will be arbitrated to determine whether Bo Yu and/or
Thomas Wegman should be listed as joint inventors for
each Proposed Claim. Each Party shall have the right to add to or modify its initial list within ten (10) days after receiving the other Party’s initial list, but in no event may a Party propose more than five (5) claims. 

	
** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST.

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EXECUTION COPY

5.3 The Parties agree to use their reasonable commercial efforts to conclude the Arbitration within nine (9) months of the Effective Date. 

5.4 The Parties will select one arbitrator (the “Arbitrator”) having appropriate expertise in U.S. Patent Law by mutual agreement no later than the date that is ten (10) business days after the Effective Date, or such later
date as the Parties may mutually agree (the “Selection Date”). If the Parties fail to mutually agree upon the Arbitrator by the Selection Date, the Arbitrator will be chosen by the International Institute for Conflict Prevention and
Resolution (“CPR”). CPR will choose the Arbitrator by requiring the Parties to agree on a list of no more than five (5) candidates for Arbitrator and for each Party then to submit to CPR within ten (10) business days after the Selection
Date its ranking of the candidates on the list, in order of preference. CPR will compute the candidates’ combined scores, break any ties at CPR’s discretion, and advise the Parties of the chosen Arbitrator. 

5.5 For the economy of the proceedings, each side will be limited to three (3) hours combined for opening and closing statements and to twenty (20) hours of testimony (including direct, cross, re-direct, etc., for the entirety of the
proceeding). Each Party is free to submit written materials to the Arbitrator in addition to those materials submitted to Harrie Samaras in connection with the Mediation. The Parties agree that the materials submitted to the Arbitrator will be
limited to the issue of inventorship. 

	
5.6 		
The Parties will limit discovery and pre-arbitration proceedings as follows:

	
	 	 	 
		
(a) 		
Within sixty (60) days after selecting the Arbitrator, the Parties will exchange documents that they intend to rely upon to prove or disprove that Bo Yu and/or Thomas Wegman should be listed as joint inventors on the ‘560 Patent and the Proposed Claims. The Parties agree to produce complete documents and
not excerpts thereof. Within thirty (30) days of such production, each Party may request the production of additional documents pertaining to the documents produced, or may produce additional documents.

	
	 	 	 
		
(b) 		
Within sixty (60) days after the Parties’ exchange of documents concludes, the Parties shall exchange their lists of fact and expert witnesses, and BTC shall submit to Auxilium
any expert reports it intends to submit

	
	 	 	 
		
(c) 		
Sixty (60) days thereafter, Auxilium shall submit to BTC any expert reports it intends to submit.

	
	 	 	 
		
(d) 		
The Parties shall determine with the Arbitrator the dates upon which they shall (i) each submit a pre-arbitration brief of no more than forty (40) pages, (ii) jointly submit a final pre-arbitration order setting forth the order of witnesses and exhibit lists, and (iii) schedule the arbitration hearing.

	
	 	
 	
 
	 	
(e) 		
The Parties agree that the Arbitrator shall have the power throughout to resolve
any disputes regarding the production of documents or testimony of the Parties’
witnesses. The Parties agree to comply with any discovery order of the
Arbitrator.

	 
	
** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST.

5

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5.7 The Parties stipulate to (1) the admissibility of documentary evidence over hearsay objections and (2) the admissibility of documentary evidence in the arbitration without the need for authentication. 

5.8 The Arbitrator will produce a reasoned written decision of no more than ten (10) pages concerning the inventorship issues submitted to Arbitration. Such decision will be confidential except to the extent the Parties agree
otherwise. Within five (5) days after a final decision is rendered by the Arbitrator, the Parties shall file a letter, substantially in the form provided in Exhibit H to this Agreement, with the USPTO Board of Patent Appeals and Interferences
informing the Board of BTC’s request for the declaration of an interference and of the Parties’ agreement settling all issues that could have been adjudicated had such an interference been declared, and offering to file this Agreement and
the Second Amended and Restated DLA, under seal, in the USPTO. If requested or authorized by the USPTO, the Parties shall file this Settlement Agreement and the Second Amended and Restated DLA, in the USPTO within five (5) days after the
Board’s response to the letter. 

5.9 If the Arbitrator decides that Bo Yu and/or Thomas Wegman are joint inventors of the ‘560 Patent, Auxilium agrees to execute and file the necessary documents to add him or them as inventors of the ‘560 Patent, and BTC
shall cause Bo Yu and/or Thomas Wegman to execute all documents reasonably necessary in conjunction with this section. 

5.10 If the Arbitrator decides that Bo Yu and/or Thomas Wegman are joint inventors of any of the Proposed Claims, Auxilium agrees to list Bo Yu and/or Thomas Wegman on any continuation, divisional, or continuation-in-part application
that includes any such Proposed Claim. Auxilium shall have the right to designate any such Proposed Claim as being a BTC Patent subject to Section 8.1 of the Second Amended and Restated DLA and indicate whether Auxilium does or does not intend to
file for patent protection, or does or does not wish to continue preparation, prosecution, or maintenance of an application that contains any such Proposed Claim. If Auxilium does not intend to file or to continue preparation, prosecution, or
maintenance of such application, BTC shall have the rights set forth in that Section 8.1(a) to elect at its sole discretion to continue preparing, filing, prosecuting, or maintaining the discontinued BTC Patent at its sole expense. BTC shall cause
Bo Yu and/or Thomas Wegman to assign all of their rights, title and interest in such applications and the inventions claimed therein jointly to Auxilium and BTC. 

5.11 Irrespective of the decision of the Arbitrator, there will be no change to (i) the Parties’ co-ownership of the ‘560 Patent as conferred herein and by the Assignments, and (ii) the Parties’ rights and limitations as
set forth in the Second Amended and Restated DLA.

	
** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST.

6

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Section 6.General

6.1 Governing Law The Parties agree that this Agreement will be governed by and construed in accordance with the laws of the State of New York, without regard to conflict of laws principles. 

6.2 Fees and Costs The Parties agree to pay their own attorneys fees and costs related to settlement of the Matters in Dispute, the Arbitration, and the preparation of this Agreement. Auxilium and BTC will share equally
the fees charged by the Arbitrator.

6.3 Entire Agreement This Agreement, together with the Second Amended and Restated DLA, the [**] Agreement and the Assignments, expresses the Parties’ entire understanding regarding the subject matter of this
Agreement. This Agreement is final and may not be amended, modified, or changed, and no waiver of any provision of this Agreement shall be effective, except by an instrument in writing signed by the Party(ies) against whom the amendment,
modification, change, or waiver is sought to be enforced.

6.4 Waiver No relaxation, forbearance, delay, or indulgence by any Party in enforcing its rights hereunder or the granting of time by such Party shall prejudice or affect its rights hereunder, and no waiver by any Party
shall operate as a waiver of any subsequent or continuing breach. 

6.5 Severability If any provision of this Agreement is determined by a court of competent jurisdiction to be invalid or unenforceable, such determination shall not affect the validity or enforceability of any other
provision of this Agreement. Upon such determination that any such provision, or any portion thereof, is invalid or unenforceable, the Parties shall negotiate in good faith to modify this Agreement so as to effect the original intent of the parties
as closely as possible in an acceptable manner to the end that the transactions contemplated hereby are consummated to the fullest extent possible. 

6.6 Consultation with Counsel The Parties each acknowledge that they have had the opportunity to consult with legal counsel of their choice prior to execution of this Agreement, have in fact done so, and have been
specifically advised by counsel of the consequences of this Agreement and their respective rights and obligations hereunder. 

6.7 Construction The Parties each acknowledge that the terms of this Agreement are the result of negotiations between them, and that this Agreement shall not be construed in favor of, or against, any Party by reason of
the extent to which a Party or its counsel participated in its drafting, or by reason of the extent to which this Agreement may be inconsistent with prior drafts thereof. 

6.8 Confidentiality The Parties agree to keep the terms of this Agreement and any documents or other information delivered pursuant to the terms of this Agreement (collectively, “Information”) confidential for
the term of Second Amended and Restated DLA, except with regard to (i) the Assignments, (ii) disclosures in accordance with Section 5.8 hereof, and/or (iii) as otherwise may be required by law (including compliance with the requirements of United
States and foreign governmental authorities) or the rules of any United States or foreign stock exchanges. If a Party is required by judicial or administrative
process to disclose any Information, it shall, to the extent possible, promptly notify the other Party and allow the other Party a reasonable time to oppose such process or seek a protective order from a court of competent jurisdiction.

	
** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST.

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6.9 Counterparts This Agreement may be executed in counterparts, delivered by fax or electronic mail, each of which shall be deemed an original, but all of which together shall constitute one and the same instrument
representing the agreement of the Parties to this Agreement. 

6.10 Authority Each person signing this Agreement in a representative capacity expressly represents that the signatory has the subject Party’s authority to so sign and that the subject Party will be bound by the
signatory’s execution of this Agreement. Each Party expressly represents that such Party does not require any third party’s consent to enter into this Agreement, including, without limitation, the consent of any spouse, insurer, assignee,
licensee, secured lender, or regulatory agency. 

6.11 Headings and Captions Headings and captions used in this Agreement are for ease of reference only, and do not constitute part of this Agreement, nor shall they be used as an aid in the construction hereof. 

 

 

 

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IN WITNESS WHEREOF, intending to be legally bound, the Parties hereto have caused this Agreement to be executed by their duly authorized representatives as of the date last written below. 

	
AUXILIUM PHARMACEUTICALS, INC.
		
 
	
	
 	
 	
 
	
By:
		
/s/ Armando Anido                                                  

		
Dated: August 31, 2011
	
	
 
		
Name:
		
Armando Anido
		
 
	
	
 
		
Title:
		
Chief Executive Officer and President
	
	
 	
 
	
BIOSPECIFICS TECHNOLOGIES CORP.
		
 
	
	
on behalf of itself and its affiliates
		
 
	
	
 	
 	
 
	
By:
		
/s/ Thomas L. Wegman                                         

		
Dated: August 31, 2011
	
	
 
		
Name:
		
Thomas L. Wegman
		
 
	
	
 
		
Title:
		
President
		
 
	

9

EXHIBIT A 

[**] 
Agreement  

[**] AGREEMENT 

This [**] Agreement is entered into between and among BioSpecifics Technologies Corp., a corporation organized and existing under the laws of Delaware and having its principal office at 35 Wilbur Street, Lynbrook, New York 11563, and its affiliates
(“BTC”), and Auxilium Pharmaceuticals, Inc., a corporation organized and existing under the laws of the State of Delaware and having its principal office at 40 Valley Stream Parkway, Malvern, PA 19355 and its affiliates
(“Auxilium”). 

WHEREAS, [**]; and 

WHEREAS, BTC and Auxilium (collectively “the Parties”) agree to [**]. 

NOW, THEREFORE, in consideration of the mutual covenants herein contained, and intending to be legally bound hereby, the Parties hereto agree as follows: [**].

The Parties [**]. 

 

 

	
** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST.

A-1

This [**] Agreement may be modified, amended, or supplemented only by a
written instrument signed by all of the Parties.

IN WITNESS WHEREOF, and intending to be legally bound, the Parties hereto
execute this [**] Agreement. 

AUXILIUM PHARMACEUTICALS, INC.

on behalf of itself and its affiliates 

	
By:
		
/s/ Armando Anido                                                         

		
Dated: August 31, 2011
	
	
 
		
Name:
		
Armando Anido
		
 
	
	
 
		
Title:
		
Chief Executive Officer and President
	
	
 	
 
	
BIOSPECIFICS TECHNOLOGIES CORP.
		
 
	
	
on behalf of itself and its affiliates	
 
	
 	
 
	
	
By:
		
/s/ Thomas L. Wegman                                                 

		
Dated: August 31, 2011
	
	
 
		
Name:
		
Thomas L. Wegman
		
 
	
	
 
		
Title:
		
President
		
 
	

 

	
** CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A CONFIDENTIAL TREATMENT REQUEST.

A-2

EXHIBIT B 

Praecipe to Settle, Discontinue and End 

for February Pennsylvania Litigation 

	
 
		
                                                      FILINGS UNDER SEAL
	
	
 
		
                                                      BY ORDER OF COURT
	
	
 
		
                                      DATED FEBRUARY 16, 2011
	
	
LAMB McERLANE PC
		
          BALLARD SPAHR LLP
	
	
Joel L. Frank (ID No. 46601)
		
          Robert R. Baron, Jr. (ID No. 67084)
	
	
John J. Cunningham, IV (ID No. 70975)
		
          Marc S. Segal (ID No. 84474)
	
	
24 E. Market St., Box 565
		
          Marcel S. Pratt (ID No. 307483)
	
	
West Chester, PA 19381
		
          1735 Market Street, 51st Floor
	
	
(610) 430-8000
		
          Philadelphia, PA 19103
	
	
 
		
          (215) 665-8500
	
	
Attorneys for Auxilium Pharmaceuticals, Inc.
		
 
	
	
 
		
          Attorneys for Auxilium Pharmaceuticals, Inc.
	
	
AUXILIUM PHARMACEUTICALS, INC.
		
:
	
	
40 Valley Stream Parkway
		
:
	
	
Malvern, PA 19355,
		
:
	
	
 
		
: COURT OF COMMON PLEAS
	
	
                                                                      
           Plaintiff,
		
: CHESTER COUNTY
	
	
                       
vs.
	
	
:
	
	
 
		
:
	
	
BIOSPECIFICS TECHNOLOGIES CORP.
		
: No. 11-01620
	
	
35 Wilbur Street
		
:
	
	
Lynbrook, New York 11563,
		
:
	
	
 
		
:
	
	
                                                                      
           Defendant.
		
:
	

PRAECIPE TO SETTLE, DISCONTINUE AND END WITH PREJUDICE

TO THE PROTHONOTARY:

Kindly mark the above-captioned action as settled, discontinued and ended, with
prejudice.

B-1

Respectfully submitted,

By: _________________________

Joel L. Frank 

John J. Cunningham, IV 

LAMB McERLANE PC 

24 East Market Street, P.O. Box 565 

West Chester, PA 19381-0565 

(610) 430-8000

Robert R. Baron, Jr. 

Marc S. Segal 

Marcel S. Pratt 

BALLARD SPAHR LLP 

1735 Market Street, 51st Floor 

Philadelphia, PA 19103 

(215) 665-8500 

Attorneys for Plaintiff 

Auxilium Pharmaceuticals, Inc. 

 

 

B-2

	
LAMB McERLANE PC
		
          BALLARD SPAHR LLP
	
	
Joel L. Frank (ID No. 46601)
		
          Robert R. Baron, Jr. (ID No. 67084)
	
	
John J. Cunningham, IV (ID No. 70975)
		
          Marc S. Segal (ID No. 84474)
	
	
24 E. Market St., Box 565
		
          Marcel S. Pratt (ID No. 307483)
	
	
West Chester, PA 19381
		
          1735 Market Street, 51st Floor
	
	
(610) 430-8000
		
          Philadelphia, PA 19103
	
	
 
		
          (215) 665-8500
	
	
Attorneys for Auxilium Pharmaceuticals, Inc.
		
 
	
	
 
		
          Attorneys for Auxilium Pharmaceuticals, Inc.
	
	
AUXILIUM PHARMACEUTICALS, INC.
		
:
	
	
40 Valley Stream Parkway
		
:
	
	
Malvern, PA 19355,
		
:
	
	
 
		
: COURT OF COMMON PLEAS
	
	
                                                                      
           Plaintiff,
		
: CHESTER COUNTY
	
	
            
vs.
	
	
:
	
	
 
		
:
	
	
BIOSPECIFICS TECHNOLOGIES CORP.
		
: No. 11-01620
	
	
35 Wilbur Street
		
:
	
	
Lynbrook, New York 11563,
		
:
	
	
 
		
:
	
	
                                                                      
           Defendant.
		
:
	

CERTIFICATION OF SERVICE

This is to certify that a complete copy of the foregoing Praecipe to Settle, Discontinue
and End With Prejudice has been served upon the following individuals, by the following means

	
and on the date stated below:
		
 
		
 
	
	
Name:
		
Means of Service:
		
Date of Service:
	
	
Anthony R. Twardowski, Esq.
		
via First Class Mail
		
 
	
	
Zarwin, Baum, DeVito, Kaplan
		
 
		
 
	
	
Schaeer & Toddy, PC
		
 
		
 
	
	
1818 Market Street, 13th Floor
		
 
		
 
	
	
Philadelphia, PA 19103
		
 
		
 
	
	
artwardowski@zarwin.com
		
 
		
 
	
	
(Attorneys for BioSpecifics
		
 
		
 
	
	
Technologies Corp.)
		
 
		
 
	

B-3

	
 	
 

	
Gerald Zingone, Esquire  

Carl A. Valenstein, Esquire 

Bingham McCutchen LLP 

2020 K Street, NW 

Washington, D.C. 20006-1806 

gerald.zingone@bingham.com

(Attorneys for BioSpecifics 

Technologies Corp.) 
		
via First Class Mail       
_____________________________
	
 	
 
	
 	
LAMB McERLANE PC
	
 	
 

	
By:
	
	
_______________________________

Joel L. Frank
	
	
 
		
John J. Cunningham, IV
	
	
 	
24 East Market Street, P.O. Box 565
	
	
 
		
West Chester,PA 19381-0565
	
	
 
		
(610) 430-8000
	
	
 	
 
	
 
		
Attorneys for Plaintiff
	
	
 
		
Auxilium Pharmaceuticals, Inc.
	

 

 

 

B-4

EXECUTION COPY

EXHIBIT C 

Praecipe to Settle, Discontinue and End 

for June Pennsylvania Litigation 

	
LAMB McERLANE PC
		
VOLPE AND KOENIG PC
	
	
Joel L. Frank (ID No. 46601)
		
Anthony S. Volpe (ID No. 24733)
	
	
John J. Cunningham, IV (ID No. 70975)
		
Ryan W. O’Donnell (ID No. 89775)
	
	
24 East Market Street, P.O. Box 565
		
30 South 17th Street
	
	
West Chester, PA 19381-0565
		
Philadelphia, PA 19103
	
	
(610) 430-8000
		
(215) 568-6400
	
	
BALLARD SPAHR LLP
		
Attorneys for Plaintiff
	
	
Robert R. Baron, Jr. (ID No. 67084)
		
RecipharmCobra Holdings Limited
	
	
Marc S. Segal (ID No. 84474)
		
 
		
 
	
	
Marcel S. Pratt (ID No. 307483)
		
 
		
 
	
	
1735 Market Street, 51st Floor
		
 
		
 
	
	
Philadelphia, PA 19103
		
 
		
 
	
	
(215) 665-8500
		
 
		
 
	
	
Attorneys for Plaintiff Auxilium Pharmaceuticals, Inc.
		
 
	
	
RECIPHARMCOBRA HOLDINGS LIMITED,
		
:
		
COURT OF COMMON PLEAS OF
	
	
and AUXILIUM PHARMACEUTICALS, INC.
		
:
		
CHESTER COUNTY
	
	
 
		
:
		
 
	
	
                                                                      
           Plaintiffs,
		
:
		
NO. 11-07184
	
	
 
		
:
		
 
	
	
v.
		
:
		
 
	
	
 
		
:
		
 
	
	
BIOSPECIFICS TECHNOLOGIES CORP.
		
:
		
 
	
	
 
		
:
		
 
	
	
                                                                      
           Defendant.
		
 
		
 
	

PRAECIPE TO SETTLE, DISCONTINUE AND END WITH PREJUDICE

TO THE PROTHONOTARY:

Kindly mark the above-captioned action as settled, discontinued and ended, with
prejudice.

 

C-1

EXECUTION COPY

	
 
		
                                                              
  
	
	
By:            
_______________________________	
By:            
_____________________________
	
                    Anthony S. Volpe
		
                    Joel L. Frank
	
	
                    Ryan W. O’Donnell
		
                    John J. Cunningham, IV
	
	
                    VOLPE AND KOENIG PC
		
                    LAMB McERLANE PC
	
	
                    30 South 17th Street
		
                    24 East Market Street, P.O. Box 565
	
	
                    Philadelphia, PA 19103
		
                    West Chester, PA 19381-0565
	
	
                    (215) 568-6400
		
                    (610) 430-8000
	
	
  	
  
	
                    Attorneys for Plaintiff RecipharmCobra
		
                    Robert R. Baron, Jr.
	
	
                    Holdings Limited
		
                    Marc S. Segal
	
	
 
		
                    Marcel S. Pratt
	
	
 
		
                    BALLARD SPAHR LLP
	
	
 
		
                    1735 Market Street, 51st Floor
	
	
 
		
                    Philadelphia, PA 19103
	
	
 
		
                    (215) 665-8500
	
	
 	
  
	
 
		
                    Attorneys for Plaintiff
	
	
 
		
                    Auxilium Pharmaceuticals, Inc.
	

 

 

 

C-2

EXECUTION COPY

	
LAMB McERLANE PC
		
VOLPE AND KOENIG PC
	
	
Joel L. Frank (ID No. 46601)
		
Anthony S. Volpe (ID No. 24733)
	
	
John J. Cunningham, IV (ID No. 70975)
		
Ryan W. O’Donnell (ID No. 89775)
	
	
24 East Market Street, P.O. Box 565
		
30 South 17th Street
	
	
West Chester, PA 19381-0565
		
Philadelphia, PA 19103
	
	
(610) 430-8000
		
(215) 568-6400
	
	
BALLARD SPAHR LLP
		
Attorneys for Plaintiff
	
	
Robert R. Baron, Jr. (ID No. 67084)
		
RecipharmCobra Holdings Limited
	
	
Marc S. Segal (ID No. 84474)
		
 
		
 
	
	
Marcel S. Pratt (ID No. 307483)
		
 
		
 
	
	
1735 Market Street, 51st Floor
		
 
		
 
	
	
Philadelphia, PA 19103
		
 
		
 
	
	
(215) 665-8500
		
 
		
 
	
	
Attorneys for Plaintiff Auxilium Pharmaceuticals, Inc.
		
 
	
	
RECIPHARMCOBRA HOLDINGS LIMITED,
		
:
		
COURT OF COMMON PLEAS OF
	
	
and AUXILIUM PHARMACEUTICALS, INC.
		
:
		
CHESTER COUNTY
	
	
 
		
:
		
 
	
	
                                                                      
           Plaintiffs,
		
:
		
NO. 11-07184
	
	
 
		
:
		
 
	
	
v.
		
:
		
 
	
	
 
		
:
		
 
	
	
BIOSPECIFICS TECHNOLOGIES CORP.
		
:
		
 
	
	
 
		
:
		
 
	
	
                                                                      
           Defendant.
		
 
		
 
	

CERTIFICATE OF SERVICE

This is to certify that a complete copy of the foregoing Praecipe to Settle, Discontinue
and End With Prejudice has been served upon the following individuals, by the following means
and on the date stated below: 

	
Name:
		
Means of Service:
		
Date of Service:
	
	
BioSpecifics Technologies Corporation
		
via First Class Mail
		
 
	
	
35 Wilbur Street
		
 
		
 
	
	
Lynbrook, New York 11563
		
 
		
 
	

C-3

	
 	
 

EXECUTION COPY

	

	
 	
 
	
Anthony R. Twardowski, Esq. 

Zarwin, Baum, DeVito, Kaplan 

Schaeer & Toddy, PC 

1818 Market Street, 13th Floor 

Philadelphia, PA 19103 

artwardowski@zarwin.com 

(Attorneys for BioSpecifics 

Technologies Corp.) 
		
 
via First Class Mail       
_____________________________
	
 	
 
	
Gerald Zingone, Esquire  

Carl A. Valenstein, Esquire 

Bingham McCutchen LLP 

2020 K Street, NW 

Washington, D.C. 20006-1806 

gerald.zingone@bingham.com

(Attorneys for BioSpecifics 

Technologies Corp.)  
	
via First Class Mail       
_____________________________

LAMB McERLANE PC

By:____________________________

      
Joel L. Frank 

      
John J. Cunningham, IV 

       24 East Market Street, P.O. Box 565 

       West Chester, PA 19381-0565 

      (610) 430-8000

      Attorneys for Plaintiff 

      Auxilium Pharmaceuticals, Inc. 

 

 

C-4

EXECUTION COPY

EXHIBIT D 

Stipulation of Discontinuance for NY Litigation 

	
SUPREME COURT OF THE STATE OF NEW YORK
		
 
	
	
COUNTY OF NASSAU
		
 
	
	
----------------------------------------------------------X
		
 
	
	
BIOSPECIFICS TECHNOLOGIES CORP.,
		
Index No. 600341/2011
	
	
                                                                      
           Plaintiff,
		
 
	
	
-against-
		
STIPULATION
	
	
 
		
OF DISCONTINUANCE
	
	
RECIPHARM AB, RECIPHARMCOBRA
		
 
	
	
HOLDINGS LIMITED, and AUXILIUM
		
 
	
	
PHARMACEUTICALS, INC.,
		
 
	
	
                                                                      
           Defendants.
		
 
	
	
----------------------------------------------------------X
		
 
	

IT IS HEREBY STIPULATED AND AGREED, by and between the attorneys for the
undersigned parties that whereas no party hereto is an infant or incompetent person for whom a committee has been appointed, and no person not a party has an interest in the subject matter of the action, the above entitled action be, and the same
hereby is, discontinued as against the defendants with prejudice, and without costs to any party. This stipulation may be filed with the
Court without further notice.

Dated: August __, 2011 

	
BINGHAM McCUTCHEN LLP	
CULLEN AND DYKMAN LLP

	
	
  	
 
	
By: _________________________
            Daniel Gimmel      
 

         Attorneys for Plaintiff 

            399 Park Avenue      

         New York, New York 10022
		

By: _________________________

      
Douglas J. Bohn

       Attorneys for Defendant 

      Auxilium Pharmaceuticals, Inc.

      100 Quentin Roosevelt Blvd. 

      Garden City, New York 11530  

 

FARRELL FRITZ, P.C.

	
By:
	
	
                    John P. McEntee
	
	
                    Attorneys for Defendants
	
	
                    RecipharmCobra Holding
	
	
                    Limited and Recipharm AB
	

D-1

EXECUTION COPY

1320 RXR Plaza 

Uniondale, New York 11556

 

 

D-2

EXECUTION COPY

EXHIBIT E 

Assignments from Auxilium to Auxilium and BTC

ASSIGNMENT 

WHEREAS, Auxilium US Holdings, LLC, a limited liability company organized and existing under the laws of the State of Delaware and having its principal office at 1105 N. Market Street, Suite 1300, Wilmington, DE 19801 (“Auxilium”),
a wholly owned subsidiary of Auxilium Pharmaceuticals, Inc., is owner of the entire right, title and interest in the invention entitled “Compositions and Methods for Treating Collagen-Mediated Diseases” for which a United States Patent
Application was filed on January 29, 2007, and assigned Application No. 11/699,302, which issued as U.S. Patent No. 7,811,560 on October 12, 2010 (the “’560 Patent”), and is also the owner of the right to claim priority to U.S.
Application No. 60/763,470 and U.S. Application No. 60/784,135 (“Provisional Applications”); and 

WHEREAS, BioSpecifics Technologies Corp., a corporation organized and existing under the laws of Delaware and having its principal
office at 35 Wilbur Street, Lynbrook, New York 11563 (“BTC”), desires to acquire an undivided interest in the ‘560 Patent along with Auxilium (Auxilium and BTC are collectively referred to as the “Assignees”); 

NOW,
THEREFORE, for good and valuable consideration as set forth in separate agreements between Auxilium Pharmaceuticals, Inc. and BTC, the receipt of which is hereby acknowledged, Auxilium and BTC agree as follows:

1. Auxilium does hereby sell, assign and transfer unto said Assignees, the entire right, title and interest in and to said invention and application throughout the world, including, without limitation, the ‘560 Patent, the right to claim
priority to the Provisional Applications, and any subsequent application claiming priority to the Provisional Applications, reissue, reexamination, divisional, continuation-in-part, extension or continuation thereof. 

 E-1 

EXECUTION COPY

2. Auxilium hereby binds itself, its legal representatives and assigns properly to execute without further consideration any and all applications, petitions, oaths and assignments or other papers and instruments that may be necessary in order to
carry into full force and effect, the sale, assignment, transfer and conveyance hereby made or intended to be made. 

3. Nothing in this assignment shall change the limitations on the rights of BTC as set forth in Auxilium Pharmaceuticals, Inc.’s and BTC’s contemporaneous Second Amended and Restated Development and License Agreement. 

IN WITNESS WHEREOF, I have executed this Assignment this   ____day of,
____________________20___.

	
Assignor, Auxilium US Holdings, LLC
	
	
 
	
By: ____________________________________-
(L.S.)
	
	
 
	
Title: __________________________________

State of  _________________________

County of _______________________

On this _______day of ____________________, 20___, before me, a Notary Public came     , to me known and known to be the individual described in and who executed the foregoing assignment, and he/she duly acknowledged the same
to be his/her free act and deed. 

__________________________________

Notary Public  

My Commission Expires: _________________

IN WITNESS WHEREOF, I have executed this Assignment this   ____day of,
____________________20___. 

 Assignee, Auxilium US Holdings, LLC 

 By:  ____________________________________(L.S.)

 Title:   __________________________________

  

 E-2 

EXECUTION COPY

State of  _________________________

County of _______________________

On this _______day of ____________________, 20___, before me, a Notary Public came     , to me known and known to be the individual described in and who executed the foregoing assignment, and he/she duly acknowledged the same
to be his/her free act and deed. 

__________________________________

Notary Public  

My Commission Expires: _________________

IN WITNESS WHEREOF, I have executed this Assignment this   ____day of,
____________________20___.

Assignee, BioSpecifics Technologies Corp. 

By:__________________________(L.S.)

Title: _________________________

State of  _________________________

County of _______________________

On this _______day of ____________________, 20___, before me, a Notary Public came     , to me known and known to be the individual described in and who executed the foregoing assignment, and he/she duly acknowledged the same
to be his/her free act and deed. 

__________________________________

Notary Public  

My Commission Expires: _________________

E-3

EXECUTION COPY

ASSIGNMENT 

WHEREAS, Auxilium International Holdings, Inc., a corporation organized and existing under the laws of the State of Delaware and having its principal office at 1105 N. Market Street, Suite 1300, Wilmington, DE 19801 (“Auxilium”), a
wholly owned subsidiary of Auxilium Pharmaceuticals, Inc., is owner of the entire right, title and interest in the invention entitled “Compositions and Methods for Treating Collagen-Mediated Diseases” for which a International Patent
Application was filed on January 29, 2007, and assigned Application No. PCT/US07/02654 (the “PCT Application”), and is also the owner of the right to claim priority to U.S. Application No. 60/763,470 and U.S. Application No. 60/784,135
(“Provisional Applications”); and 

WHEREAS, BioSpecifics Technologies Corp., a corporation organized and existing under the laws of Delaware and having its principal office at 35 Wilbur Street, Lynbrook, New York 11563
(“BTC”), desires to acquire an undivided interest in the PCT Application along with Auxilium (Auxilium and BTC are collectively referred to as the “Assignees”); 

NOW, THEREFORE, for good and valuable consideration as set
forth in separate agreements between Auxilium Pharmaceuticals, Inc. and BTC, the receipt of which is hereby acknowledged, Auxilium and BTC agree as follows:

1. Auxilium does hereby sell, assign and transfer unto said Assignees, the entire right, title and interest in and to said invention and the PCT Application throughout the world, the right to claim priority to the Provisional Applications, and any
subsequent application claiming priority to the Provisional Applications, including the applications listed on the Attached Exhibit A. 

2. Auxilium hereby binds itself, its legal representatives and assigns properly to execute without further consideration any and all applications, petitions, oaths and assignments
or other papers and instruments that may be necessary in order to carry into full force and effect,
the sale, assignment, transfer and conveyance hereby made or intended to be made. 

 E-4 

EXECUTION COPY

3. Nothing in this assignment shall change the limitations on the rights of BTC as set forth in Auxilium Pharmaceuticals, Inc.’s and BTC’s contemporaneous Second Amended and Restated Development and License Agreement. 

IN WITNESS WHEREOF, I have executed this Assignment this   day of    , 20___. 

Assignor, Auxilium International Holdings, Inc.  

By:  ____________________________  (L.S.)  

Title: ___________________________

State of  _________________________

County of _______________________

On this _______day of ____________________, 20___, before me, a Notary Public came     , to me known and known to be the individual described in and who executed the foregoing assignment, and he/she duly acknowledged the same
to be his/her free act and deed. 

__________________________________

Notary Public  

My Commission Expires: _________________

IN WITNESS WHEREOF, I have executed this Assignment this   ____day of,
____________________20___.

Assignee, Auxilium International Holdings, Inc. By:  (L.S.) Title:  

State of  _________________________

County of _______________________

E-5

EXECUTION COPY

On this _______day of ____________________, 20___, before me, a Notary Public came     , to me known and known to be the individual described in and who executed the foregoing assignment, and he/she duly acknowledged the same
to be his/her free act and deed. 

__________________________________

Notary Public  

My Commission Expires: _________________

IN WITNESS WHEREOF, I have executed this Assignment this   ____day of,
____________________20___.

Assignee, BioSpecifics Technologies Corp.

By: _____________________________(L.S.)

Title: ___________________________

State of  _________________________

County of _______________________

On this _______day of ____________________, 20___, before me, a Notary Public came     , to me known and known to be the individual described in and who executed the foregoing assignment, and he/she duly acknowledged the same
to be his/her free act and deed. 

__________________________________

Notary Public  

My Commission Expires: _________________

E-6

EXECUTION COPY

EXHIBIT F 

Assignment from BTC to Auxilium and BTC

ASSIGNMENT 

WHEREAS, BioSpecifics Technologies Corp., a corporation organized and existing under the laws of Delaware and having its principal office at 35 Wilbur Street, Lynbrook, New York 11563, and its affiliates (“BTC”) may have certain
rights to inventions disclosed in United States Application No. 11/699,302, which issued as U.S. Patent No. 7,811,560, and applications claiming priority thereto including U.S. Application Nos. 12/759,065 and 12/837,933 (collectively the
“’560 Patent”) and International Application No. PCT/US07/02654 (the “PCT Application”), both of which claim priority to U.S. Application No. 60/763,470 and U.S. Application No. 60/784,135 (“Provisional
Applications”); and 

WHEREAS, Auxilium US Holdings, LLC, a limited liability company organized and existing under the laws of the State of Delaware and having its principal office at 1105 N. Market Street, Suite 1300, Wilmington, DE 19801
(“Auxilium US”), and Auxilium International Holdings, Inc., a corporation organized and existing under the laws of the State of Delaware and having its principal office at 1105 N. Market Street, Suite 1300, Wilmington, DE 19801
(“Auxilium International”) desire to acquire an undivided interest in any such inventions along with BTC; 

NOW, THEREFORE, for good and valuable consideration as set forth in separate agreements between Auxilium Pharmaceuticals, Inc.
and BTC, the receipt of which is hereby acknowledged, BTC, Auxilium US, and Auxilium International agree as follows:

1. BTC does hereby sell, assign and transfer unto Auxilium US and BTC, BTC’s rights in the United States to said inventions, including, without limitation, the ‘560 Patent, the
right to claim priority to the Provisional Applications, and any subsequent
application claiming
priority to the Provisional Applications, reissue, reexamination, divisional, continuation-in-part,
extension or continuation thereof. 

F-1 

EXECUTION COPY

 

2. BTC does hereby sell, assign and transfer unto Auxilium International and BTC, BTC’s rights outside the United States to said inventions, including, without limitation, the PCT Application, the right to claim priority to the Provisional
Applications, and any subsequent application claiming priority to the Provisional Applications, reissue, reexamination, divisional, continuation-in-part, extension or continuation thereof. 

3. BTC hereby binds itself, its legal representatives and assigns properly to execute without further consideration any and all applications, petitions, oaths and assignments or other papers and instruments that may be necessary in order to carry
into full force and effect, the sale, assignment, transfer and conveyance hereby made or intended to be made. 

4. Nothing in this assignment shall change the limitations on the rights of BTC as set forth in Auxilium Pharmaceuticals, Inc.’s and BTC’s contemporaneous Second Amended and Restated Development and License Agreement. 

IN WITNESS WHEREOF, I have executed this Assignment this
_______________day of    __________, 20___. 

 

	
Assignor, BioSpecifics Technologies Corp.
	
	
 
	
By: ________________________(L.S.)
	
	
 
	
Title: _______________________

State of _________________________

County of _______________________

On this _______day of ____________________, 20___, before me, a Notary Public came     , to me known and known to be the individual described in and who executed the foregoing assignment, and he/she duly acknowledged the same
to be his/her free act and deed. 

F-2

EXECUTION COPY

__________________________________

Notary Public  

My Commission Expires: _________________

IN WITNESS WHEREOF, I have executed this Assignment this
_______________day of    __________, 20___. 

	
Assignee, Auxilium US Holdings, LLC

	
	
 
	
By: ________________________(L.S.)
	
	
 
	
Title: _______________________

State of _________________________

County of _______________________

On this _______day of____________________, 20___, before me, a Notary Public came     , to me known and known to be the individual described in and who executed the foregoing assignment, and he/she duly acknowledged the same
to be his/her free act and deed. 

__________________________________

Notary Public  

My Commission Expires: _________________

IN WITNESS WHEREOF, I have executed this Assignment this
_______________day of    __________, 20___. 

	
Assignee, Auxilium US Holdings, LLC

	
	
 
	
By: ________________________(L.S.)
	
	
 
	
Title: _______________________

State of _________________________

County of _______________________

F-3

EXECUTION COPY

On this _______day of ____________________, 20___, before me, a Notary Public came     , to me known and known to be the individual described in and who executed the foregoing assignment, and he/she duly acknowledged the same
to be his/her free act and deed. 

__________________________________

Notary Public  

My Commission Expires: _________________

IN WITNESS WHEREOF, I have executed this Assignment this
_______________day of    __________, 20___. 

	
Assignor, BioSpecifics Technologies Corp.
	
	
 
	
By: ________________________(L.S.)
	
	
 
	
Title: _______________________

State of _________________________

County of _______________________

On this _______day of ____________________, 20___, before me, a Notary Public came     , to me known and known to be the individual described in and who executed the foregoing assignment, and he/she duly acknowledged the same
to be his/her free act and deed. 

__________________________________

Notary Public  

My Commission Expires: _________________

F-4

EXECUTION COPY

EXHIBIT G 

Second Amended and Restated Development and License Agreement

EXECUTION COPY

EXHIBIT H 

Letter to USPTO Requesting Filing of this Agreement and the Second Amended and Restated DLA

__________(Name)___________________________

Chief Administrative Patent Judge 

Board of Patent Appeals and Interferences 

U.S. Patent and Trademark Office 

P.O. Box 1450 

Alexandria, VA 22313-1450

Dear ____________________________:

This request is jointly submitted by Auxilium Pharmaceuticals, Inc. (“Auxilium”) and BioSpecifics Technologies Corp. (“BTC”). 

During prosecution of one of its patent applications, BTC copied the claims of a now issued patent owned by Auxilium and requested that an interference be declared. In addition, Auxilium copied claims from a related BTC application into an
application filed by Auxilium. Before the declaration of an interference, Auxilium and BTC entered into agreements settling all issues that could have been adjudicated had such an interference been declared, including common ownership of the subject
matter of the applications, such that an interference would not normally be declared pursuant to 37 CFR 41.206. 

Section 135(c) of the Patent Statute specifies that any agreement or understanding between parties to an interference, including any collateral agreements referred to therein, made in connection with or in contemplation of the termination of an
interference, must be in writing and a copy filed in the PTO. While an interference was not declared in response to BTC’s request and Auxilium having copied other claims in a BTC application, Auxilium and BTC seek to comply with Section 135(c)
and the implementing PTO rules. Accordingly, Auxilium and BTC are willing to file, under seal, copies of the agreements settling their dispute. The agreements would be accompanied by a request that the agreements be kept separate from application
and patent files and that they be made available only to Government agencies on written request or to any person on a showing of good cause. 

Auxilium and BTC respectfully request that they be informed whether the PTO authorizes the filing of such settlement agreements when an interference has been requested, but not declared. 

 

 

H-1

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