Biopharmaceutical Services Agreement



 Exhibit 10.1 
 Cytovance Biologics, Inc. 
 Biopharmaceutical Services Agreement 

for 
 Synageva
BioPharma Corp. 
 This Biopharmaceutical Services Agreement (the “Agreement”) dated Feb. 27, 2012 (the “Effective Date”)
between Synageva BioPharma Corp., (“Synageva”) a company having a place of business at 128 Spring Street, Suite 520, Lexington, MA 02421 and Cytovance Biologics, Inc. a Delaware corporation (“Cytovance”) having its principal
place of business at 800 Research Parkway, Suite 200 Oklahoma City, OK 73104 (each a “Party”, collectively the “Parties”). 

Whereas: 
 Synageva desires Cytovance to
perform services in accordance with the terms of this Agreement and Cytovance desires to perform such services in accordance with the terms of this Agreement. 
 In consideration of the above statements, which form part of this Agreement, and other good and valuable consideration, the sufficiency and receipt of which are hereby acknowledged, the Parties hereto
agree as follows: 
  

	1.	Performance 

 Cytovance will perform the services
(the “Services”) detailed in the “Proposal #SYN 011312 ”, attached hereto as Annex “A” and incorporated by reference herein (the “Proposal”), in connection with the project (the
“Project”) described in the Proposal. The scope of the Project may have expanded beyond the Proposal and all amendments thereto whether in the form of a change order (each, a “Change Order”) or otherwise are hereby incorporated
herein by reference. The Services, including all reports of progress or deliverables, shall be performed or supplied on behalf of Synageva in accordance with the terms and conditions under this Agreement, as well as the Proposal, the detailed
scope-of-work and associated timeline attached hereto as Annex “A” and the Quality Agreement attached hereto as Annex “B” (the “Quality Agreement”). All of the Annexes are incorporated by reference herein and made a
part hereof. In the event of any conflict between the terms and conditions of this Agreement and any Annex, the terms and conditions of this Agreement shall control. In the event of any conflict between the Proposal and the Quality Agreement, the
Quality Agreement shall control. 
 Synageva shall support and cooperate with the execution of the Services and shall not engage in any act or
omission, which may reasonably be expected to prevent or delay the successful execution of the Services. Such support and cooperation shall include, but not be limited to informing Cytovance of global regulatory strategy for development and approval
of the product(s), prompt review and approval of documents requiring Synageva’s signature, timely delivery of methods and materials and prompt response to other similar issues. 

 

	2.	Compliance with Applicable Government Regulations 


Cytovance will undertake the Services and shall assign professionally qualified personnel to perform the Services and shall perform the Services in
compliance in all material respects with the requirements of all applicable laws, including compliance with all material respects of applicable U.S. Food and Drug Administration (FDA) current Good Manufacturing Practice (cGMP) and all statutory and
applicable international regulatory requirements. 

  
  

					
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	3.	Synageva Obligations 

 Unless otherwise agreed to
by the Parties in writing, Synageva is solely responsible for (a) provision of complete and accurate scientific data regarding the Project; (b) provision of all information necessary to effect the reliable transfer of methods to Cytovance;
(c) provision of specific reagents, reference standards or other product specific materials necessary for execution of the Project; (d) if applicable, review and approval of in-process and finished product test results to ensure conformity
of such results with product specifications, regardless of which Party is responsible for finished product release; (e) preparation of all submissions to regulatory authorities; and (f) performance of other obligations of Synageva set
forth in the Proposal. 
  

	4.	Hazardous Materials 

 Synageva warrants to
Cytovance that no specific safe handling instructions are applicable to any substance or material provided by Synageva to Cytovance, except as disclosed to Cytovance in sufficient time for review and training by Cytovance prior to delivery. Where
appropriate or required by law, Synageva shall provide a Material Safety Data Sheet and instructions for proper storage for all Synageva-provided materials, finished product and reference standards. 

 

	5.	Facility Visits and Audits 

 Synageva’s
representatives may visit Cytovance’s facilities during normal business hours and with prior written notice to ensure conformance with cGMPs and to observe the progress of the Project, provided that such access does not compromise cGMP
compliance or safety. Cytovance will assist Synageva in scheduling such visits, which will be in compliance with Cytovance’s requirement to protect confidentiality of Cytovance’s other clients. 

Synageva may conduct one (1) quality assurance audit per calendar year at no cost in accordance with the provisions of the Quality Agreement unless
an audit results in adverse findings in which case Synageva shall be entitled to re-audit Cytovance with respect to such adverse findings without reference to the once per calendar year limitation. Additional audits within a calendar year not
related to adverse findings will be invoiced separately on a time and materials basis at the then current rate for such services. 
  

	6.	Regulatory Inspections 

 Cytovance shall give
Synageva notice within five (5) business days after Cytovance becomes aware of any impending regulatory, governmental, or third party audit of Cytovance that relates to the Project and shall provide Synageva with any material documentation
provided to Cytovance relating to such audit. In the event that any such audit involves an inspection of Cytovance’s facility, then Cytovance shall provide Synageva the opportunity to be present at such inspection. Cytovance shall also provide
Synageva the opportunity to review, prior to submission, any documentation prepared in response to such regulatory, governmental or third party audit and shall immediately provide Synageva with the results of such audit following its conclusion.

  

	7.	Guarantees 

 Due to the investigational nature of
the Services provided and the incomplete information available on the protein, Cytovance does not guarantee their studies, processes, or efforts, will generate any specific results. Cytovance will perform the Services in a professional manner using
the standards 

  
  

					
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usual in the industry and in compliance with all applicable laws, including cGMPs when appropriate. So long as Cytovance conducts the Services in accordance with relevant procedures and processes
provided by Synageva, including but not limited to approved batch records, Standard Operating Procedures and the Quality Agreement, and in a professional manner using the appropriate industry standards and in compliance with all applicable laws,
including but not limited to cGMPs when appropriate, Synageva will assume full responsibility for the outcome of all Services and will pay Cytovance in accordance with the terms and conditions of this Agreement without reduction or offset for
results of Services. 
  

	8.	Budget and Payment Terms 

 The budget and all
payments for all Services, including any pass-through costs for any materials supplied by Cytovance, shall be set forth in the Proposal (the “Budget”) unless otherwise agreed to in writing by Synageva and Cytovance. All work performed
under this Agreement requires prior written authorization from Synageva in the form of a purchase order number, which shall be referenced on all invoices in order for reimbursement to occur. In the event that the cost for the Services exceeds the
approved amount in the Budget, it is Cytovance’s responsibility to get prior written authorization from Synageva for any additional Services in the form of a Change Order. Cytovance shall invoice Synageva for all Services under this Agreement
as set forth in the Proposal. Unless otherwise agreed between the parties, Synageva shall pay such invoiced amounts within thirty (30) days of the receipt of the invoice. All taxes and any penalties thereon imposed on any payment made by
Synageva to Cytovance shall be the responsibility of Cytovance. 
  

	9.	Change Orders 

 The Parties acknowledge that the
nature of the development process is such that modifications to the Project (including modifications relating to the acquisition of additional equipment and materials) may be desirable or reasonably necessary at certain times for regulatory, legal,
commercial or other reasons. In the event that either of the Parties believes that changes to the Project are required, that Party shall promptly notify the other Party in writing of the exact nature of such changes and the specific reasons
therefor. The Parties shall then promptly discuss the changes that may be needed. If the Parties agree that changes in the Project are required, the Parties shall amend the Project to reflect the necessary changes, and also to set out any
appropriate change in cost or time necessary to fulfill such changes. Any mutually agreed increase in cost due to expansion of the Project shall be borne wholly by Synageva who shall have the sole and final decision as to whether any or all such
changes shall be implemented. 
  

	10.	Notice of Delay 

 If Cytovance determines that
any order submitted by Synageva cannot be filled by the date required under the Proposal or the applicable purchase order, Cytovance shall notify Synageva in writing promptly upon making such determination and the parties shall negotiate a
resolution satisfactory to both such parties. 
  

	11.	Samples 

 Cytovance shall undertake to test
samples of each batch of product supplied hereunder for compliance with the specifications and to record the results and keep said results on file for a period of five (5) years, or longer if required by any law, rule, or regulatory requirement
or guideline, after the expiration of the shelf-life of the tested batch of product. Cytovance shall keep retention samples for a period of two (2) years after the expiration of the shelf-life of the tested batch. 

  
  

					
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 12. Records 
 Cytovance shall maintain records detailing the methods by which Cytovance manufactures product on behalf of Synageva, including all standard operating procedures and the details of all characterization
and similar data Cytovance generates relating to any and all compounds Cytovance synthesizes on behalf of Synageva. All records of work performed by Cytovance under this Agreement and all reports required to be delivered by Cytovance to Synageva as
part of the Project shall be “works made for hire” and the exclusive property of Synageva. Cytovance undertakes to maintain sufficient records to permit (i) identification of the batch’s origin, (ii) the cause of any defect,
(iii) confirmation of conformance with the specifications, and its manufacture in accordance with the manufacturing standards and (iv) compliance with any other law, rule, or regulatory requirement or guideline applicable to manufacture of
product. Upon written request from Synageva, Cytovance will promptly and in any event within fifteen (15) days of receipt of such request, provide copies of any and all records and testing methodologies, and/or return all retention samples, to
Synageva at Synageva’s costs. Cytovance shall provide Synageva with at least sixty (60) days written notice prior to the destruction of any such reports, records or samples and shall transfer such reports, records or samples to Synageva if
requested by Synageva at Synageva’s expense. 
  

	13.	Assistance to Transfer Process. 

  

	a.	The parties acknowledge that Synageva may, in its sole discretion, elect to manufacture or have manufactured by one or more third parties product during the term of
this Agreement or thereafter, including in the event of the termination or expiration of this Agreement, and that Synageva may require Cytovance’s assistance in order to enable such manufacturing of no less quality-control standards as
conducted at Cytovance’s manufacturing site. Therefore upon written request of Synageva, Cytovance shall, at the sole cost and expense of Synageva (unless due to an inability to manufacture or failure to supply on the part of Cytovance, or
otherwise due to a material breach of this Agreement by Cytovance, in which case at the sole cost and expense of Cytovance), reasonably cooperate with Synageva or one or more third-party designees and provide such assistance, provided that such
assistance does not unreasonably interfere with Cytovance’s business. 

  

	b.	Such assistance may include, without limitation, allowing Synageva or one or more third-party designees to (i) consult with employees or agents of Cytovance with
expertise in the manufacture of product, and (ii) observe manufacturing runs of product during normal business hours. In addition, Synageva shall have the right to require Cytovance to release, provide right of reference, access, and/or license
to Synageva and/or any third party designated by Synageva in writing, all documentation, laboratory notebooks, regulatory filings, manufacturing standards, manufacturing improvements and any and all other information necessary or reasonably useful
for the manufacture of product. Cytovance shall provide such technical assistance and other cooperation as Synageva may reasonably require in order to fully transfer the manufacture to another location and enable Synageva to manufacture or have a
third party manufacture product in compliance with the manufacturing standards and specifications. Such assistance and cooperation shall be at the expense of Synageva unless such assistance and cooperation is required due to Cytovance’s failure
to meet its manufacture or supply obligations to Synageva hereunder or such other breach of this Agreement, in which case such assistance and cooperation shall be at the expense of Cytovance. 


 

	14.	Shipment 

 Unless otherwise agreed in writing by
the Parties, all product, raw materials, samples components or other materials shipped by Cytovance are delivered F.O.B. Cytovance’s facilities. Cytovance shall package for shipment such product, raw materials, samples, components or other
materials at Synageva’s expense (including insurance) and in accordance with Synageva’s full written and reasonable instructions. 

  
  

					
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	15.	Limitations of Liability 

 Notwithstanding any
other provision in the Proposal or in any other section of this Agreement (including, but not limited to, the indemnification contemplated by Section 22 hereof), other than Cytovance’s obligations to replace non-conforming batches as set
forth in the Proposal, Cytovance’s liability under the Proposal and/or this Agreement, regardless of the cause of action, shall not exceed the total fees paid to Cytovance under this Agreement. Notwithstanding the foregoing,
Cytovance’s liability for losses to any active pharmaceutical ingredient, bulk drug product, intermediates, samples, reagents or other materials provided by Synageva, whether or not incorporated into finished product, shall not exceed
Synageva’s actual cost of replacement. 
 Notwithstanding anything herein to the contrary, UNDER NO CIRCUMSTANCES SHALL EITHER PARTY BE
ENTITLED TO INCIDENTAL, INDIRECT, CONSEQUENTIAL, EXEMPLARY OR SPECIAL DAMAGES, WHETHER OR NOT FORESEEABLE, ARISING IN CONNECTION WITH THE DEFAULT OR BREACH OF ANY OBLIGATION OF THE OTHER PARTY UNDER THIS AGREEMENT, THE PROPOSAL, THE QUALITY
AGREEMENT, OR ANY ANNEXES OR DOCUMENTS RELATED THERETO. 
  

	16.	Warranties 

 The warranties set forth in the
Proposal and this Agreement are the sole and exclusive warranties made by Cytovance to Synageva and there are no other warranties, representations or guarantees. EXCEPT AS EXPRESSLY STATED HEREIN, NEITHER PARTY PROVIDES TO THE OTHER PARTY HERETO ANY
WARRANTIES, EXPRESS OR IMPLIED WITH RESPECT TO THE MATERIALS AND SERVICES PROVIDED HEREUNDER, AND ALL SUCH WARRANTIES, EXPRESS OR IMPLIED, INCLUDING WITHOUT LIMITATION ANY IMPLIED WARRANTIES OF MERCHANTABILITY, NONINFRINGEMENT OR FITNESS FOR A
PARTICULAR PURPOSE ARE WAIVED. 
  

	17.	Confidentiality 

 Each Party (a “Receiving
Party”) agrees to keep confidential all confidential and proprietary information of the other Party (the “Disclosing Party”) obtained or observed by the Receiving Party during or in connection with the Project (the “Confidential
Information”). Information, if it is in writing or other tangible form, shall be clearly marked as proprietary when disclosed to the Receiving Party, or, if not in tangible form, summarized in a writing so marked and delivered to the Receiving
Party within thirty (30) days of such disclosure. For the duration of the Project and for a period of five (5) years thereafter, a Receiving Party shall not disclose Confidential Information disclosed by the Disclosing Party without prior
written permission unless such disclosure is (i) to an affiliate that is under similar obligation to keep such information confidential; (ii) is or becomes publicly available through no fault of the Receiving Party; (iii) is disclosed
by a third party entitled to disclose it; (iv) is already known to the Receiving Party as shown by its prior written records; or (v) is required to be disclosed by any law, rule, regulation, order, decision, decree, subpoena or other legal
process provided that the Receiving Party shall give prompt notice thereof to the Disclosing Party. 
  

	18.	Intellectual Property 

 All Cytovance Materials,
including without limitation, all improvements, development, derivatives or modifications to the Cytovance Materials, shall be owned exclusively by Cytovance. For the purposes hereof, “Cytovance Materials” means all Cytovance proprietary
information, intellectual property and developments made outside of the course of performing services under this Agreement, including 

  
  

					
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without limitation, all patents, patent applications, know-how, inventions, design, concepts, improvements, technical information, manuals, instructions which are owned, licensed or used by
Cytovance in developing, formulating, manufacturing, processing, packaging, analysis or testing of pharmaceutical or diagnostic products. 
 All
Synageva Materials, including without limitation, all improvements, development, derivatives or modifications to the Synageva Materials, shall be owned exclusively by the Synageva. For the purposes hereof, “Synageva Materials” means all
Synageva proprietary information, intellectual property and developments made by either Party in the course of performing services under this Agreement, including without limitation, all patents, patent applications, know-how, inventions, design,
concepts, improvements, technical information, manuals, instructions which are owned, licensed or used by Synageva relating to pharmaceutical or diagnostic products or the development, formulation, manufacture, processing, packaging, analysis or
testing thereof. 
 Cytovance agrees to assign, and hereby assigns, to Synageva all of its right, title and interest in and to all Inventions
(as defined below). Cytovance agrees to promptly notify Synageva of any and all inventions, discoveries, developments or improvements, whether or not patentable, directly resulting from Cytovance’s performance of this Project (each, an
“Invention”). During and after the term of this Agreement, Cytovance shall cooperate fully with Synageva in Synageva’s obtaining, in the name of Synageva, patent and other proprietary protection for such Inventions. Cytovance has
agreements with its employees, agents, and consultants requiring the assignment of inventions to Cytovance. 
 Cytovance hereby grants Synageva
a non-exclusive, royalty-free, perpetual, fully paid-up right and license, with the right to grant sublicenses, in and to any and all manufacturing standards, manufacturing improvements or inventions, ideas or know-how or other Cytovance Materials
for purposes of the manufacture, use and exploitation of product and/or such products of Synageva containing or used in combination with product. Cytovance shall promptly disclose all manufacturing improvements to Synageva. 

All data, results and information generated by Cytovance in the performance of the Project relating to product or its manufacture shall be the property
of Synageva and be Synageva Confidential Information. 
  

	19.	Indemnification 

 Synageva will indemnify and
hold harmless Cytovance, its affiliates and their officers, directors, agents, and employees against any loss, cost, damage or expense owed by a third party (a “Loss”) from any lawsuit, action, claim, demand, assessment or proceeding (a
“Claim”) arising directly or indirectly from or related to: (i) personal injury to any Cytovance employee caused by materials provided by Synageva or manufactured by Cytovance pursuant to the Project (the “Product”), but
only to the degree that such Cytovance employee has taken appropriate precautions and used proper handling of the Product; (ii) Cytovance’s proper performance of or involvement with the Project, raw materials or product or its obligations
under these terms or the Proposal; (iii) the Agreement, Proposal, Quality Agreement, Project or any aspect thereof violating any applicable law, rule, regulation or ordinance to the extent performed in accordance with the terms of this
Agreement and the Proposal; (iv) a claim based on Synageva or any other person’s use, consumption, sale, distribution or marketing of the Product; (v) the infringement or alleged infringement of the Project (or execution thereof) or
the Product on the intellectual property rights of a third party; or (vi) Synageva’s violation, non-compliance or non-performance of any of the terms of this Agreement; provided that if such Loss or Claim arises in whole or part
from Cytovance’s negligence, gross negligence or intentional misconduct or inaction, then the amount of such loss that Synageva shall indemnify Cytovance for shall be reduced by an amount proportional to Cytovance’s responsibilities for
such Loss as determined by a court of competent jurisdiction. 

  
  

					
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 Subject to the limitations of Section 15 hereof, Cytovance will indemnify and hold harmless Synageva,
its affiliates and their officers, directors, agents, and employees against any Loss or Claim arising directly or indirectly from or related to the conduct of the Project as a result of Cytovance’s negligence, gross negligence or intentional
misconduct or inaction (including violation or non-performance of this Agreement). 
  

	20.	Force Majeure 

 Neither Party will be liable for
any failure to perform or for delay in performance resulting from any cause beyond its reasonable control, including, without limitation, acts of God, fires, floods, or weather, disease, strikes or lockouts, factory shutdowns, embargoes, wars,
hostilities or riots, acts of terrorism, shortages in transportation, government action or power failure, provided that such failure to perform shall be excused only to the extent of and during such disability. Any time specified or estimated for
completion of performance falling due during or subsequent to the occurrence of any such events shall be automatically extended for a period of ninety (90) days to recover from such disability. If any part of the Project is invalid as a result
of such disability, Cytovance will, upon written request from Synageva, but at Synageva’s sole cost and expense, repeat that part of the Project affected by the disability. 

 

	21.	Use and Disposal 

 Synageva represents and
warrants to Cytovance that it has legal title and/or a valid license to materials, process patents and Product necessary to conduct the Project and that Cytovance’s performance of the Project will not violate or infringe on the patents,
trademarks, service marks or copyrights of any third party. Synageva further represents and warrants to Cytovance that it will hold, use and/or dispose of Product and materials provided by Cytovance in accordance with all applicable laws, rules and
regulations. 
  

	22.	Independent Contractor 

 Cytovance shall perform
the Project as an independent contractor of Synageva and shall have complete and exclusive control over its facilities, equipment, employees and agents. The relationship between the Parties shall not constitute a partnership, joint venture or agency
nor constitute either party as the agent, employee or legal representative of the other. 
  

	23.	No Publicity 

 Neither Party will make any press
release or public disclosure or use the name of the other Party or its employees in any advertising or sales promotional material, including without limitation, web content, without the other Party’s express prior written consent. 

 

	24.	Authority 

 Synageva grants Cytovance full
authority to use any Synageva supplied materials or substances. Each Party represents and warrants to the other Party that it has the full right and authority to enter into this Agreement and to perform in accordance with the terms and conditions
set forth herein. Each Party further represents and warrants to the other Party that it has obtained and will at all times during the term of this Agreement, hold and comply with all licenses, permits and authorizations necessary to perform this
Agreement as now or hereafter required under any applicable statutes, laws, ordinances, rules and regulations of the United States and any applicable foreign, state and local governments and governmental agencies. 

  
  

					
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	25.	Amendment and Precedence 

 The Proposal, this
Agreement and any applicable Quality Agreement constitute the entire agreement between the Parties relative to the Project and may not be modified without the mutual written consent of both Parties. 

 

	26.	Choice of Law 

 The Agreement between the Parties
governed by these standard terms and conditions shall be construed and enforced in accordance with the laws of and in the venue of the Commonwealth of Massachusetts except for its rules regarding conflict of laws. 

 

	27.	Dispute Resolution 

 If a dispute arises between
the Parties in connection with this Agreement, the respective presidents or senior executives of Cytovance and Synageva shall first discuss as promptly as practicable and attempt to resolve in good faith such dispute. If such Parties cannot resolve
the dispute, then such dispute shall be referred to mediation in accordance with the rules of the American Arbitration Association. The Parties shall participate in the mediation in a good faith attempt to settle the dispute. The mediation shall be
held in Boston, Massachusetts. If mediation fails to resolve the dispute, such dispute shall be resolved in Boston, Massachusetts, by a neutral arbitrator, under the rules of the American Arbitration Association. 

 

	28.	Assignment 

 The Agreement between the Parties
shall not be assigned in whole or in part by Cytovance without the prior written consent of Synageva. 
  

	29.	Termination 

 Synageva may terminate this
Agreement prior to completion of the Project with or without cause by providing sixty (60) days written notice to Cytovance. Upon receipt of such notice of termination, Cytovance will promptly scale down the Project and avoid (or minimize,
where non-cancelable) any further related expenses. Synageva shall be responsible to pay Cytovance for all of Cytovance’s costs incurred or irrevocably obligated related to the Project as of the effective date of termination. 

Synageva may terminate this Agreement prior to completion of the Project upon thirty (30) days written notice to Cytovance in the event of a breach
of this Agreement or Proposal, provided that Cytovance has not cured such breach within such thirty (30) day period. 
 Cytovance may
terminate this Agreement prior to completion of the Project by giving thirty (30) days written notice to Synageva in the event of a material breach of this Agreement by Synageva that is not cured after a thirty (30) day written notice of
such breach. Synageva shall be responsible to pay Cytovance for all of Cytovance’s costs incurred or irrevocably obligated related to the Project as of the effective date of termination. 

  
  

					
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 The termination of this Agreement for any reason shall not relieve either Party of its obligations to the
other in respect of: (i) confidentiality; (ii) consents for advertising purposes and publications; (iii) indemnification (iv) intellectual property; and (v) compensation for Services performed. 

 

	30.	Insurance 

 A. Cytovance
Insurance. Cytovance shall maintain, for the duration of this Agreement (unless specified otherwise in the Proposal), insurance with a reputable insurance provider throughout the Term and for a period of not less than five (5) years
following the termination or expiration of the Agreement, insurance coverage in amounts appropriate for its business and products of the type to be developed and manufactured pursuant to this Agreement, which shall include but not be limited to
comprehensive general liability insurance (including property damage) with minimum limits of liability no less than [***] per any one occurrence and [***] in the aggregate. Upon Synageva’s request, Cytovance shall provide to Synageva with
a certificate of insurance showing that such insurance is in place. . 
 B. Synageva Insurance. Synageva shall, at
its own cost, obtain and maintain, insurance with a reputable insurance provider throughout the Term and for a period of not less than five (5) years following the termination or expiration of the Agreement, insurance coverage in amounts
appropriate for its business and products of the type to be developed and manufactured pursuant to this Agreement, which shall include but not be limited to, product liability and comprehensive general liability insurance (including property damage)
with minimum limits of liability no less than [***] per any one occurrence and [***] in the aggregate Synageva shall provide Cytovance with evidence of such insurance on an annual basis.

 

	31.	Subcontractors 

 Cytovance shall not subcontract,
assign, or delegate any of its obligations under this Agreement or the Proposal to any third party without the prior written consent of Synageva or specified in the Proposal. 

 

	32.	Survival 

 These standard terms and conditions
shall survive termination or expiration of the Agreement. 
  

									
	 Cytovance Biologics, Inc.
	 		 	Synageva BioPharma Corp.
					
	By:	 	 /s/ Darren Head
	 		 	By:	 	 /s/ Eugene J. Kim

					
	Name:	 	Darren Head	 		 	Name:	 	Eugene J. Kim
					
	Title:	 	President & CEO	 		 	Title:	 	Legal Counsel
					
	Date:	 	Feb. 27, 2012	 		 	Date:	 	2/28/2012


  
  

[***] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed
separately with the Commission. 
  
  

					
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 Proposal #Syn-011312 for Technology Transfer and CGMP 

Manufacturing of SBC-102 
  

			
	Prepared For:	  	 Joseph DeCourcey
 VP,
Manufacturing and Technical Operations
 Synageva BioPharma Corp
 128 Spring Street, Suite 520
 Lexington, MA 02421

Phone: (706) 227-1170 ext. 232

joseph.decourcey@synageva.com

		
	Submitted By:	  	 Valerie McDonnell
 Vice
President, Sales and Business Development
 Cytovance Biologics Inc
 800 Research Parkway, Suite 200
 Oklahoma City, OK 73104

 
 Mobile: 252-646-8781
 Office: 405-319-8612
 vmcdonnell@cytovance,com

		
	Issue Date:	  	January 27, 2012
		
	Revision:	  	01
		
	Expiration Date:	  	April 27, 2012

 The content of this document has been developed on a project specific basis based upon information provided by Synageva
and on a number of key assumptions. This proposal is provided for the sole use of Synageva in defining the services to be provided by Cytovance Biologics Inc for the continuing manufacture of SBC-102. 

  
 130398996_1









 SUMMARY 
 Cytovance® Biologics Inc, (“Cytovance”) is a contract
biomanufacturing organization dedicated to meeting the needs of companies seeking to advance products rapidly and cost-effectively into and through clinical development. 
 This proposal is written in response to discussions with Synageva Biopharma regarding SBC-102. SBC-102 is a recombinant human protein under development as an enzyme replacement therapy for Lysosomal Acid
Lipase (LAL) deficiency. Lysosomal acid lipase acts to reduce the build-up of cholesteryl esters and triglycerides in the liver and other organs. The SBC-102 produced by Cytovance is intended for use in Synageva’s human clinical
studies. 
 In keeping with Cytovance’s business philosophy, the proposal has been priced aggressively and incorporates certain
non-standard pricing mechanisms that we believe provide benefit. 
 Cytovance Biologics is fully committed to an entrepreneurial and flexible
approach to the biopharmaceutical contract services marketplace and is in a position to very rapidly execute a suitable services agreement and to commence work. 
 PRICE MATRIX 
 In accordance with Cytovance Biologics’ business strategy we provide the
following pricing estimates for this program below. The estimates are based on information provided by Synageva and on current assumptions. Pricing may be modified after detailed technical review, the receipt of additional information and the mutual
development and agreement of a detailed scope-of-work. 
 Technology Transfer, Process Evaluation and cGMP Manufacture of SBC-102

  

			
	 Work Program Element
	 	 Estimated Price ($)

		
	 1. Technology Transfer (process documentation)
	 	[***]
		
		 	Sub total: [***]
		
	 2a. Process evaluation at bench scale [***]

2b. Process development/optimization
	 	 [***]
 Scope to be determined

		
		 	Sub-total: [***]
		
	 3. Raw material procurement and testing
	 	[***]1
		
	 4. cGMP documentation & pre-production activities
	 	[***]
		
		 	Sub-total: [***]
		
	 5a. Scale up run operated under full cGMP5

5b. In-process testing

5c. Drug Substance QC testing
	 	 [***]
 [***]
 [***]

		
		 	Sub-total: [***]
		
	 6a. [***] cGMP production runs

6b. In-process testing

6c. Drug Substance QC testing
	 	 [***]
 [***]
 [***]



  
  

[***] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed
separately with the Commission. 
 230398996_1 









			
	 	 	Sub-total [***]
	 7. cGMP Drug Product Fill2
	 	[***]
		 	Sub-total [***]
	 8. Program Management (projected weekly average through duration of contract)
	 	[***]
		 	Program Total: $2,035,000

 1. [***] 
 2.
[***] 
 3. [***] 
 4. [***] 

5. [***] 
 Note: The above cGMP manufacturing
pricing is for [***] cGMP manufacturing campaigns. (The pricing for additional manufacturing runs may be reduced dependant upon volume of manufacturing activity,) 
 Payment terms 
 For each program element, Synageva will be invoiced based on a schedule
coinciding with the start and completion of the project activities as described in the Synageva Payment Table below. Milestone start payments are due net 30 days from invoice, such invoice to be sent electronically to Synageva on the same
day. A net [***]% discount will be applied to payments received within 20 days of invoice date, Payments will be submitted via wire transfer or FedEx. A net discount of [***]% will be applied to payments received within 10 days of invoice date.

 Payments are due net 30 days of receipt of invoice for Milestone completions after all documents have been received and reviewed by
Synageva consistent with the Quality Agreement 
 Pass through material costs per manufacturing run are projected to be $[***] based upon
previous experience. The pass through material cost estimates include all project specific materials and out-sourced services. 
 Total
pass through material costs (excluding resins) and outsourced service costs for the entire contract are projected to be $[***] and are broken out as follows; 
  

			
	Development (PD/AD)	 	[***]
	Equipment (e.g. filter housings)	 	[***]
	Filling components	 	[***]
	Single use bags/containers	 	[***]
	Filtration materials	 	[***]
	Tubing/column parts	 	[***]
	Chemicals	 	[***]
	QC testing	 	[***]
	External testing (DP)	 	[***]

 Payments for pass through materials (excluding resins): 

 

	 	1.	An Escrow account will be established at Cytovance Bank. 

  

	 	2.	Cytovance is the owner of Bank account. 

  

	 	3.	Synageva will pay Cytovance for [***] of the projected pass through materials and out-sourced service costs for the entire contract (identified above) upon signature of
the contract and receipt by Synageva of an invoice. 

  

	 	4.	Upon depletion of the initial [***] deposit, Synageva will be invoiced for the next [***] of the pass through costs as applicable, which shall be used until depletion.
Payment must be received before the project can continue. The final [***] of pass through costs will be invoiced upon depletion of the initial [***] 


  
  

[***] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed
separately with the Commission. 
 330398996_1 









	 	5.	Cytovance will provide a monthly reconciliation to Synageva of all pass through materials and out-sourced service costs incurred. 


 

	 	6.	If at any point actual costs exceed projection above Cytovance will obtain Synageva’s prior written approval for the additional costs. 


 

	 	7.	Prior to the third pass through payment, Cytovance will report on the actual costs incurred and adjust estimates prior to invoicing the third payment.


  

	 	8.	Following the final manufacturing run and as part of final invoices for the bulk DS start, Cytovance will report all pass through costs incurred and credit to Synageva
any overpayments. 

 Chromatography resins will be purchased directly by Synageva. 

All Cytovance milestone invoices and pass through material reconciliations will be e-mailed to Synageva Accounts Payable at
Accounts.Pavable@synageva.com with a copy to Joseph DeCourcey at Joseph.DeCourcey@synageva.com. Such invoices shall reference this Work Order, Purchase Order number B120197 , and shall be addressed to: 

Synageva BioPharma Corp. 
 128 Spring Street,
Suite 520 
 Lexington, MA 02421 

Background Information 
 Cytovance
Biologics is a Delaware Corporation. The company was founded to serve the contract process development and clinical phase cGMP manufacturing market. In order to allow clients to fully evaluate the merits of this proposal, we provide the following
background information. 
 Company Background 
 The company was established in 2003 using $1.25 million of founder’s equity and private investments, Operations were established in Oklahoma based on a $16.8 million debt-financing package
provided by Oklahoma City that was announced on July 8, 2004. This financing was in the form of an innovative federal and state tax credit-supported loan from a fund established by Rural Enterprises of Oklahoma, Inc. (REI), a federally
accredited Community Development Financial Institution. This financing package comprised funds for facility construction, process equipment and operating capital. In 2005 a new ownership group led by Dr. William Canfield, acquired the assets of
Cytovance Biologics, Inc. and formed Cytovance Biologics, LLC. These new investors along with the Presbyterian Health Foundation capitalized the new company with $15 million working capital and equipment purchases. Cytovance Biologics enjoys an
existing revenue stream via ongoing customer contracts. 
 Facilities 
 Cytovance’s Oklahoma operations are located within the Presbyterian Health Foundation Research Park, close to the Oklahoma City central business district. Process development labs are located in
11,000 sq. ft. of class A wet lab and office space leased from the Foundation. Cytovance’s 44,000 sq. ft. primary CGMP production facility was custom-designed for multi-product CGMP production and meets US and European regulatory standards.
Facility design was reviewed by the US Food and Drug Administration prior to construction. This facility features independent production suites at 100L, 500L, and 1,000L (w/v) scale plus significant expansion capability. 

Cytovance also has approximately 6,000 sq. ft. of existing CGMP clean room space at its Oklahoma City location that houses CGMP cell banking
capabilities and which features additional CGMP processing suites suitable for pilot production; customer-specific custom production processes or dedicated production. 

  
 430398996_1









 Cytovance welcomes a visit from appropriate Customer representatives to tour the facilities and undertake a
detailed review of facility design, equipment and validation, process flows, quality systems and so on. 
 Business Philosophy

 The company was founded based on strong client-side experience and the premise that it is necessary to truly understand customer
technical and business needs in order to efficiently serve its market, We offer a comprehensive portfolio of commercial-quality services under reasonable terms, and can provide continuity of manufacturing services over the short and long term. We
believe that the delivery of technical excellence and appropriate compliance is a given. No client should expect anything less than on-time delivery within an agreed budget. We believe based on our experience, however, that to differentiate
ourselves and add significant additional value to our customers we need to do more. Our business model will allow us to truly meet the needs of our customers and to be successful by also providing the following: 

 

	 	•	 	 An attractive cost base. As a service provider it is imperative that we deliver value to our customers. A fundamental business principle for us is to
maintain an attractive cost-of-doing-business and to share that advantage with our customers. This tenet is applied to all aspects of our business, from the design of our organization to the location of operations in Oklahoma City, Oklahoma



  

	 	•	 	 Easy access to our services under reasonable terms. 


  

	 	•	 	 A success-based culture that is reflected in flexible business terms that can be modified to assist customers in reaching development and funding
milestones. 


  

	 	•	 	 Custom-designed and state-of-the-art facilities. Our new CGMP multi-product manufacturing facility is not retro-fitted space or converted from
single/limited product use. 


  

	 	•	 	 Opportunity to grow. Our facility is designed to include expansion space that can deliver larger scale production on either a multi-product or
client-specific basis. 


  

	 	•	 	 A comprehensive-service offering that can provide a turnkey solution, but which allows clients maximum flexibility to take only the services they
require. We are happy to undertake smaller “stand-alone” projects. We strive to allow our clients to focus time and resources on core competencies such as drug discovery. 



 

	 	•	 	 A team of professionals with significant client-side experience supplemented by a sound working knowledge of the biopharmaceutical services market. We
have a great appreciation for the larger picture of the drug development process. We will use these experiences to build strong collaborative relationships and to ensure that we are meeting your needs. 



 

	 	•	 	 Maximum strategic flexibility. We avoid of the use of royalty-bearing intellectual property unless specifically requested and ensure that all methods,
processes and systems are transferable. We hope to develop long-term relationships but will provide our full support if it becomes necessary to transfer a process to an alternative manufacturing site. 



 

	 	•	 	 An understanding that the product we deliver is much more than a therapeutic protein and associated documentation. The processes we develop belong to
our customers and must be economically viable, robust, compliant, scaleable and transferable. In addition, we want to deliver the know-how that will allow customers to fully support their process in future. 



 

	 	•	 	 Easy access to a range of strategic collaborators able to provide “seamless” access to necessary services not offered by Cytovance Biologics.



  

	 	•	 	 Executive level oversight of every customer relationship. 



  
 530398996_1









 Scope of Work-Technology Transfer, Process Evaluation, Process Optimization and cGMP Manufacture of
Synageva’s SBC-102 
 Cytovance® Biologics has developed a preliminary scope of work based upon information provided by Synageva. The estimated pricing and timeline provided in this proposal are
based upon this scope of work. 
 Cytovance has not received a comprehensive package of technical information relating to the revised process.
In order to complete this scope of work it has, therefore, also been necessary to make a number of assumptions which are provided below, Changes to these assumptions may impact the pricing and/or timing estimates provided. 

Should this proposal be acceptable to Synageva, the parties will hold detailed technical meetings to finalize a mutually agreed work program and to
develop final timelines and binding prices. 
 Cytovance shall not proceed to the next work program stage/element of this Project until Synageva
agrees that the prior stage/element has been successfully and fully completed. 
 Program Understanding & Assumptions

 Cytovance Biologics has developed the scope of work on the understanding that Synageva requires cGMP production of SBC-102 protein from
transgenic egg white (EW) for human clinical trials. It is assumed that detailed process information sufficient to allow Cytovance to reproduce the process is available for transfer. Further process development and/or optimization may be necessary
and will be determined jointly by Synageva and Cytovance. 
 Key project assumptions 

 

	 	•	 	 All technology licenses are the responsibility of Synageva BioPharma 



 

	 	•	 	 Procedures for manufacturing bulk drug substance are required to be complete and approved by Synageva a minimum of 6 weeks prior to the start of the
GMP production run in order to provide adequate time for preparation of required documentation and materials. 


  

	 	•	 	 Synageva will provide a tech transfer package sufficient to allow Cytovance to reproduce Synageva’s revised process 



 

	 	•	 	 Cytovance will evaluate the transferred SBC-102 process at bench scale prior to scale up. If it is agreed by Synageva and Cytovance that further
process development or optimization is required, an additional scope of work will be agreed and implemented by Cytovance under a fully executed Change Order 



 

	 	•	 	 Synageva requires the cGMP process performed at a scale of [***] (as defined by the Phenyl HIC column load volume) 



 

	 	•	 	 Cytovance will perform in-process sample analysis [***] to support process evaluation, process development and GMP manufacturing



  

	 	•	 	 Cytovance will produce bulk Drug Substance, formulate bulk Drug Substance and perform Drug Product fills. Bulk Drug Substance will be stored at [***]
prior to formulation. Cytovance will formulate bulk drug substance and fill upon written authorization by Synageva and consistent with Terms agreed in the Quality Agreement. 



 

	 	•	 	 Cytovance will perform release testing consistent with the terms and provisions of the Addendum A. 



 

	 	•	 	 Synageva will be responsible for all QC lot release testing, QA lot release and for providing Cytovance with a Certificate of Analysis for each lot
release 


  

	 	•	 	 Synageva will be responsible for all regulatory activities and requirements associated with these process changes 



 

	 	•	 	 All necessary assay transfer and qualification must be completed and approved by Synageva QA prior to the initiation of the first GMP production run.
Cytovance will not perform in-process or release testing until Synageva written approval of all transferred methods 



  
  

[***] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed
separately with the Commission. 
 630398996_1 









	1.	Technology Transfer (Documentation & Materials) 

 Documentation to be transferred from Synageva: raw materials specifications, process description, development batch records, equipment lists, SOPs, pertinent development reports. 

Objective: 
 Receive documentation and
materials from Synageva necessary to plan and undertake the scope-of-work and the production of SBC-102. Prepare all required documents associated with technology transfer. 
 Activities: 
  

	(i)	Materials 

  

	 	•	 	 Receive process description information from Synageva including bill of materials and raw material specifications (if available), development reports,
SOPs and available information on key process parameters including those outlined in Addendum B below. All received documentation to be controlled by QA documentation department. 



 

	 	•	 	 Receive a) critical reagents (if any), b) qualified interim reference standards with accompanying documentation to support process evaluation and cGMP
manufacturing if applicable. 


  

	(ii)	Documentation 

  

	 	•	 	 Review all documentation & supporting information with Synageva. 



 

	 	•	 	 Clarify any outstanding issues via meeting or teleconferences to ensure a smooth transition of information 



 

	 	•	 	 Prepare a Project Plan for review and approval by Synageva (estimated 1 week) 



Deliverables: 
  

	 	•	 	 Project Plan 


  

	2a.	Process Evaluation 

 Objective

 Perform [***] process runs at bench scale using starting material provided to Cytovance by Synageva. The purpose of the runs is to
demonstrate the process yield and product quality and to evaluate the process for scale up and cGMP manufacturing. 
 Activities

 Perform [***] process runs encompassing the proposed process changes approved by Synageva at bench scale. The process will be evaluated by
Cytovance and by Synageva utilizing appropriate in-process methods with attention to yield, purity, product quality, ability to be scaled, and reproducibility. Process steps may include (process to be transferred from Synageva): 

[***] 
 Deliverables

  

	 	•	 	 Material for analytical testing 


  

	 	•	 	 Process evaluation summary 



  
  

[***] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed
separately with the Commission. 
 730398996_1 









	2b.	Process Development/Optimization 


Objective 
 If it is determined by
Synageva and Cytovance that further process development/optimization is required, Cytovance will perform a process development/optimization study to demonstrate process suitability for scale up and GMP manufacturing of SBC-102. 

Note - a scope of work will be defined and agreed by Synageva and Cytovance following Tech Transfer and Process Evaluation if necessary and an
appropriate Change Order executed. 
  

	3.	Raw Material Procurement and Testing 


Objective: 
 Create necessary raw material
specification documents in conjunction with Synageva. Source required raw materials from qualified vendors, test materials or manage testing at qualified third party facility, and release materials for production. 

Activities: 
  

	 	•	 	 Generate or receive raw materials specification documents and bill of materials from Synageva 



 

	 	•	 	 Review Bill of Materials and raw material specification documents with Synageva 



 

	 	•	 	 Procurement: Qualify vendors as required. For those vendors previously qualified by Synageva or Cytovance, no additional vendor qualification will be
performed. New vendors will be qualified to provide cGMP material to be used in the production of bulk drug substance, for further processing. 


  

	 	•	 	 Testing and Release for any raw materials will be conducted by Cytovance or at audited test laboratories. [***]. 



 

	 	•	 	 Cytovance QA will maintain all vendor and test lab audits, bill of materials, raw material specifications, and test results.



 Note that some raw material testing may need to be outsourced based on methodologies required. Costs for outsourced testing
are not included in this proposal pending receipt/generation of a bill of materials. 
 Deliverables: 

 

	 	•	 	 Raw material specification documents approved by Cytovance and Synageva 



 

	 	•	 	 Vendor and test lab audits 


  

	 	•	 	 Test results for raw materials 


  

	 	•	 	 Released materials 


  

	4.	cGMP Documentation & Pre-Production Activities 

 Objective: 
 Prepare and release all process/product-specific documents necessary for
execution of the scope of work. Modify as necessary. Prepare facilities and equipment for execution of cGMP production. 
 Activities:

  

	 	•	 	 Draft all necessary documentation to support cGMP production and release of SBC-102. This includes [***]. Documents to include batch records,
item/material specifications, standard test methods, bill of materials, product specifications, sampling protocols and changes to Cytovance’s standard operating procedures as necessary. 



  
  

[***] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed
separately with the Commission. 
 830398996_1 









	 	•	 	 Release and maintain all necessary documentation 


  

	 	•	 	 Prepare cGMP facility for production. Equipment set-up etc. 


 Deliverables: 
  

	 	•	 	 Released documentation 


  

	 	•	 	 Facility release for production 


  

	5.	Scale Up Run Operated Under Full cGMP 


Objective 
 Synageva requires cGMP
production of SBC-102 for use in human clinical studies and the filing of regulatory submissions to the US Food and Drug Administration or EU using Synageva’s manufacturing process. 
 The purpose of the scale up run is to demonstrate the SBC-102 manufacturing process at scale. 

Activities 
  

	 	•	 	 Scale-up the bench scale process up to [***] scale (Phenyl HIC load volume). 



 

	 	•	 	 Control and monitor key parameters. Representative process parameters are outlined in Addendum B. 



 

	 	•	 	 Perform the SBC-102 manufacturing process run at up to [***] scale using final documentation and released raw materials under cGMP conditions within
the cGMP production facility. 


  

	 	•	 	 Perform in-process sample testing using qualified assays [***]. 



 

	 	•	 	 Perform drug substance formulation by [***]. 


  

	 	•	 	 Aseptically fill bulk drug substance into sterile bulk containers. 



 

	 	•	 	 Storage of formulated bulk cGMP drug product at [***]. 



 

	 	•	 	 Release testing for DS, bulk, formulated DP and finished DP will be performed according to the specifications listed in Exhibit C (Certificate of
Analysis). 


 Deliverables 
  

	 	•	 	 Bulk cGMP Drug Substance 


  

	 	•	 	 Completed batch records 


  

	 	•	 	 Certificate of Conformance 


  

	6.	cGMP Production 

 Objective

 Synageva requires cGMP production of SBC-102 for use in human clinical studies and the filing of regulatory submissions to the US Food and
Drug Administration or EU using Synageva’s manufacturing process. 
 Activities 

 

	 	•	 	 Perform the SBC-102 manufacturing process run at up to [***] scale using final documentation and released raw materials under cGMP conditions within
the cGMP production facility. 


  

	 	•	 	 Control and monitor key parameters. Representative process parameters are outlined in Addendum B. 



 

	 	•	 	 Perform in-process sample testing using qualified assays [***]. 



 

	 	•	 	 Perform drug substance formulation by [***]. 


  

	 	•	 	 Aseptically fill bulk drug substance into sterile bulk containers. 



 

	 	•	 	 Storage of formulated bulk cGMP drug product at [***]. 



  
  

[***] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed
separately with the Commission. 
 930398996_1 









	 	•	 	 Release testing for DS, bulk, formulated DP and finished DP will be performed according to the specifications listed in Exhibit C (Certificate of
Analysis). 


 Deliverables 
  

	 	•	 	 Bulk cGMP Drug Substance 


  

	 	•	 	 Completed batch records 


  

	 	•	 	 Certificate of Conformance 


  

	7.	Drug Product Fill 

 Synageva has requested
fill/finish services. The concentration, vial configuration, and fill volume will be agreed to prior to the fill. 
 Objectives

  

	 	•	 	 Perform GMP fill of SBC-102 Drug Product 


 Activities 
  

	 	•	 	 Perform GMP fill. It is assumed for the purpose of this proposal that the drug manufacturing process may include: 



 

	 	•	 	 Performance of pre filtration bioburden test on bulk drug substance 



 

	 	•	 	 Perform sterile filtration 


  

	 	•	 	 Aseptic fill into sterile vials 


  

	 	•	 	 Label vials as directed by Synageva 


  

	 	•	 	 QA review of drug product manufacturing and testing records 



 

	 	•	 	 Storage of Drug Product Vials for up to 30 days 


  

	 	•	 	 Package and Ship vialed drug product as directed by Synageva 



 

	 	•	 	 Perform sterility testing (outsourced). 


 Deliverables: 
  

	 	•	 	 Filled cGMP Drug Product Lot 


  

	 	•	 	 Certificate of Sterility 


  

	 	•	 	 Completed batch records 


  

	 	•	 	 Certificate of Conformance 


  

	 	•	 	 Synageva shall use its best commercial efforts to deliver the Tech Transfer documents to Cytovance no later than March 9, 2012



  

	 	•	 	 Cytovance shall use its best commercial efforts to fill cGMP Drug Product Lots to be completed no later than the following schedule:



  

	 	•	 	 [***] 


  

	8.	Program Management 

 Cytovance strives for
excellence in the performance of client programs. The Project Manager assigned to the program plays a primary role in driving program goals and objectives consistent with client expectations and Cytovance’s business philosophy. Cytovance
shall not change the Project Manager assigned to the program without Synageva’s prior consent, such consent not to be unreasonably withheld. 
 Objectives: 
  

	 	•	 	 Provide overall management of the program according to the agreed scope and terms of the contract. 



 

	 	•	 	 Ensure project team alignment with regard to program objectives, milestones and deliverables. 



 

	 	•	 	 Ensure project team alignment with regard to program objectives, milestones and deliverables. 



 

	 	•	 	 Ensure client satisfaction with all aspects of the program through effective and timely communication. 



  
  

[***] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed
separately with the Commission. 
 1030398996_1 








 Activities: 
  

	 	•	 	 Serve as primary contact for Synageva 


  

	 	•	 	 Manage and coordinate communications between the companies and project team members 



 

	 	•	 	 Host project team meetings weekly or as required (via teleconference or at Cytovance facilities) 



 

	 	•	 	 Manage and report costs on a “spend vs. budget” basis 



 

	 	•	 	 Anticipate and report deviations from project scope and timeline 



 

	 	•	 	 Plan and manage activities, timelines and project deliverables 



 

	 	•	 	 Plan and manage appropriate resource availability 


 Deliverables: 
  

	 	•	 	 Timely communications on project progress and events 


  


	 	•	 	 Project updates 


  

	 	•	 	 Project team alignment 



Notes 
  

	 	•	 	 This proposal is based on Cytovance’s understanding of Synageva’s requirements. Additional information obtained during the course of work, as
a result of work performed or changes to the project assumptions, may impact the scope of work and project costs. Such changes will be agreed upon by Synageva and Cytovance in writing, in advance of the work’s performance.



  

	 	•	 	 Cytovance guarantees compliance with appropriate GMP standards but does not guarantee that it will meet target batch quantities.



  

	 	•	 	 Any assay not performed by Cytovance or subcontracted by Cytovance will not appear on the draft specification sheet unless a Cytovance QA
representative has audited the laboratory where the testing will take place. Such audit will be performed at Synageva’s request and cost. 


  

	 	•	 	 Synageva is responsible for the cost of project-related shipping and Cytovance will use Synageva’s designated shipper & account number.
Transfer of title of any material shipped from Cytovance will take place at shipping point (FOB Shipping Point). 


  

	 	•	 	 Synageva agrees to pay reasonable travel expenses for Cytovance staff attending meetings requested by Synageva, other than those on Cytovance’s
premises. 


  

	 	•	 	 Cytovance and/or Synageva may wish to issue a press release relating to this contract. Written approval must be obtained from the other party prior to
any information being disclosed. 


 Cytovance contacts: 
 Valerie McDonnell 
 Vice President, Sales and Business Development 

405-319-8612 
 vmcdonnell@cytovance.com

 Mark Adams 
 Director, Program
Management 
 405-319-8351 

madams@cytovance,com 

  
 1130398996_1









 Synageva Payment Schedule 

 

									
	 Milestone
	  	% to be billed	 	Activity Total	 	Invoice Amount	 	 Deliverable

					
	 Prepayment Excludes storage and program management fees. No activities will begin until upfront payment is
received.
	  	[***]	 	[***]	 	[***]	 	
					
	 1. Technology transfer
	  	[***]	 	[***]	 	[***]	 	Development study plan
					
	 2a. Process evaluation at bench scale

 
 2b. Process
development/optimization
	  	[***]	 	[***]	 	[***]	 	 Study start-column preparation
  

Process evaluation summary, TBD

					
	 4. cGMP documentation & pre- production activities
	  	[***]	 	[***]	 	[***]	 	
1st Draft Batch Record
  

Client-approved Batch

Records

					
	 5a. Scale up run operated under full cGMP

 
 5b. In-process testing

 
  
 5c. Drug Substance QC testing
	  	[***]	 	[***]	 	[***]	 	 Initiation of scale up run – buffer preparation start

 
 Bulk filled drug substance

 
 Initiation of scale up run – buffer preparation start

 
 Bulk drug substance upon release by Client

 
 Client-approved executed Batch Records Certificate of
Conformance



  
  

[***] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed
separately with the Commission. 
 1230398996_1 









									
	6a. cGMP production of Bulk Drug Substance	  	[***]	  	[***]	  	[***]	  	Initiation of cGMP run –buffer preparation start
					
		  		  		  		  	Bulk filled drug substance
					
	6b. In-process testing	  		  		  		  	Initiation of cGMP run -buffer preparation start
		  		  		  		  	 Bulk drug substance upon release by Client

					
	 6c. Drug Substance QC testing

*perbatch
	  		  		  		  	 Client-approved Batch

Records
 Certificate of
Conformance

					
	7. cGMP Drug Product Fill	  	[***]	  	[***]	  	[***]	  	Initiation of Drug Product Fill –start
					
	¿ per 1,000 vial batch	  		  		  		  	 Client approved executed

batch record
 Certificate of
Conformance

					
	8. Program Management	  	[***]	  	[***]	  	[***]	  	billed monthly

 AUTHORIZATION 
  

									
	Cytovance Biologics, Inc.	 		 	Synageva BioPharma Corp.
					
	 By:
	 	 /s/ Darren Head
	 		 	By:	 	 /s/ Eugene J. Kim

					
	 Name:
	 	Darren Head	 		 	Name:	 	Eugene J. Kim
					
	 Title:
	 	President & CEO	 		 	Title:	 	Legal Counsel
					
	 Date:
	 	Feb. 27, 2012	 		 	Date:	 	2/28/2012


  
  

[***] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed
separately with the Commission. 
 1330398996_1 








 Exhibit A 
 Quality Agreement 
  

  
 1430398996_1









 GMP QUALITY AGREEMENT 

FOR CONTRACT MANUFACTURE OF 
 SBC-102 
 BY 

CYTOVANCE BIOLOGICS LLC 
 FOR 
 SYNAGEVA BIOPHARMA CORP. 

28 FEBRUARY 2012 

  

					
		 	Page 1 of 21	 	









 TABLE OF CONTENTS 

 

							
	GMP Quality Agreement	  	1	 
	TABLE OF CONTENTS	  	 	2	  
	1.	  	PURPOSE	  	 	3	  
	2.	  	SCOPE	  	 	3	  
	3.	  	DEFINITIONS AND ABBREVIATIONS	  	 	3	  
	4.	  	QUALITY AGREEMENT	  	 	4	  
	5.	  	COMMUNICATION	  	 	5	  
	6.	  	ADMINISTRATIVE INFORMATION	  	 	6	  
	7.	  	REGULATORY CONTROLS	  	 	7	  
	8.	  	DOCUMENT CONTROL SYSTEM	  	 	8	  
	9.	  	CALIBRATION AND PREVENTATIVE MAINTENANCE PROGRAM	  	 	9	  
	10.	  	VALIDATION PROGRAM	  	 	9	  
	11.	  	GMP SUPPLIER QUALITY ASSURANCE PROGRAM	  	 	10	  
	12.	  	ENVIRONMENTAL CONTROL PROGRAM	  	 	10	  
	13.	  	MATERIAL AND COMPONENT PROCUREMENT AND RELEASE	  	 	11	  
	14.	  	MATERIAL CONTROL	  	 	11	  
	15.	  	LABORATORY CONTROLS	  	 	12	  
	16.	  	NON-CONFORMING EVENTS(DEVIATIONS) AND INVESTIGATIONS	  	 	12	  
	17.	  	PRODUCT PROCESSING AND RELEASE	  	 	13	  
	18.	  	RETAIN SAMPLES	  	 	14	  
	19.	  	PRODUCT COMPLAINTS (NON-MEDICAL)	  	 	14	  
	20.	  	SHIPPING	  	 	14	  
	21.	  	VALIDITY AND DISCLOSURE	  	 	15	  
		  	APPENDIX I - Products Covered by Quality Agreement	  	 	16	  
		  	APPENDIX II - Key Information	  	 	17	  
		  	APPENDIX III - Key Contacts	  	 	18	  
		  	APPENDIX IV - Agreement Overview	  	 	20	  


  

					
		 	Page 2 of 21	 	









 CYTOVANCE BIOLOGICS QUALITY
AGREEMENT 
  
  

	1.	PURPOSE 

 This Quality
Agreement is a working agreement between Cytovance Biologics, Inc. (CYTOVANCE) and (CLIENT) to define quality responsibilities and deliverables and to ensure products are manufactured according to CLIENT specifications, federal, state, and local
regulations and guidelines. 
 CLIENT has contracted CYTOVANCE to manufacture the product listed in Appendix I under this Quality
Agreement. To the extent that this Quality Agreement may conflict with the Biopharmaceutical Services Agreement, the Quality Agreement shall take precedence over the Biopharmaceutical Services Agreement. 

 

	2.	SCOPE 

 This Quality
Agreement applies to manufacturing and testing operations at CYTOVANCE located in Oklahoma City, OK, for the product listed in Appendix I (sometimes referred to herein as the “Product”). 

This Quality Agreement shall be subject to all of the terms of the Biopharmaceutical Services Agreement including, but not limited to, the
provisions regarding confidentiality. Any specific reference to the terms of the Biopharmaceutical Services Agreement shall be for emphasis only, and any failure to reference such provisions shall be of no import. This Quality Agreement will be
effective at the time that all required signatures are captured. 
  

	3.	DEFINITIONS AND ABBREVIATIONS 

 Audit: A planned, independent, documented objective assessment per written procedures to verify that systems and/or processes have been developed, and are currently being followed to achieve
quality system objectives and/or regulatory requirements. 
 Batch Record: The original source documentation
completed during the production of a batch or lot of CLIENT product that gives specific instructions on the procedures, calculations, criteria, sampling, storage conditions and testing performed on that quantity of product. The batch record includes
the date, equipment and raw materials used during the process, each operator signature, initials and date and, when applicable, the verifier initials and date at critical steps in the process, the accountability of the material produced and any
deviations from the approved procedure. The original, approved batch record that serves as the template to be completed for each production run is referred to as the “Master Batch Record.” 

  

					
		 	Page 3 of 21	 	









 CAPA: A corrective/preventative action plan that is initiated to correct or
prevent a product or compliance failure and is considered essential to support GMP operations. 
 cGMP: Current
Good Manufacturing Practices. Regulations that set forth the minimum current good manufacturing practice for methods to be used in and the facilities or controls to be used for the manufacture, processing, packing, or holding of a drug to assure
that the drug meets the requirements of the act as to safety, and has the identity and strength to meet the quality and purity characteristics that it purports or is represented to possess. 

Contract Manufacturer: An organization contracted to perform manufacturing, laboratory testing, fill/finish, labeling,
packaging, storage, distribution, or other services and/or processes related to a product. 
 Nonconforming Event
(Deviation): An occurrence that is a departure from documented procedures or specifications. Any deviation from established procedures are documented and explained. Critical deviations must be investigated, and the investigation and
conclusions documented. 
  

	4.	QUALITY AGREEMENT 

  

	 	4.1.	Audit Right and Document Access 

  

	 	4.1.1.	Subject to the provisions regarding confidentiality set forth in the Biopharmaceutical Services Agreement, on a periodic basis, CLIENT may conduct audits of the
CYTOVANCE units. CYTOVANCE shall permit CLIENT to review all documents, records, systems, policies and procedures related to the manufacture, testing and packaging of CLIENT products to evaluate, to the extent applicable, compliance with
regulations, guidelines, policies, procedures and this Quality Agreement. 

  

	 	4.1.1.1.	Audits require 15 business days notice with not more than one per calendar year unless there is a specific, legal or reasonable cause for more frequent
inspections, in which case the parties will agree to the frequency and terms of such audits. 

  

	 	4.1.1.2.	At the conclusion of an audit, an exit meeting will be held with representatives of CLIENT and CYTOVANCE to discuss audit findings. A written list of audit observations
will be provided to CYTOVANCE within 20 business days. 


  

					
		 	Page 4 of 21	 	










	 	4.1.1.3.	CYTOVANCE will respond to audit observations within 30 calendar days and detail necessary corrective actions and the time frames for their correction.


  

	 	4.1.1.4.	CYTOVANCE will provide periodic reports (not less than every 6 months) on the progress of any corrective actions that require an extended period to correct,
as specified in the written list of audit observations. 

  

	 	4.1.2.	CYTOVANCE and CLIENT shall take necessary steps to ensure that Product associated documents, records, policies or procedures are available to each party upon FDA
or other regulatory agency request. 

  

	 	4.1.3.	CYTOVANCE shall allow appropriate regulatory agencies to inspect its facilities and all records as required under cGMP in connection with production and/or testing of
the product covered by this agreement. 

  

	 	4.2.	Subcontracting 

  

	 	4.2.1.	Written approval from CLIENT is required before subcontracting any portions of the manufacturing, finishing, testing, or holding of CLIENT Products.


  

	 	4.2.2.	Subcontractors selected by CLIENT shall be qualified by CLIENT; however, this responsibility may be contracted to CYTOVANCE. 


 

	 	4.2.3.	Subcontractors selected by CYTOVANCE shall be qualified by CYTOVANCE. Upon request, CYTOVANCE shall provide access to relevant subcontractor qualification documents for
CLIENT review. 

  

	5.	COMMUNICATION 

  

	 	5.1.	Names and contact information for CLIENT and CYTOVANCE are provided in Appendix III. 


 

	 	5.2.	Each party will notify the other party’s Manufacturing contact and Quality Assurance contact as soon as reasonably possible, within one (1) business day, of
any issues that impact CYTOVANCE’s ability to conduct CLIENT-contracted activities. 

  

	 	5.3.	Events that require notification between parties include, but not are limited to, the events listed below. Communication may occur via telephone, FAX, or electronic
mail. All communications that do not generate a written record (e.g., telephone) must be followed with a written notification within 2 business days. 


  

					
		 	Page 5 of 21	 	










					
	 Required Notifications

	 Event
	  	 Contact
	  	 Time Frame (Business Days)

	Events that would impact CYTOVANCE’s ability to conduct CLIENT-contracted activities	  	Manufacturing Contact and QA	  	1 business day
			
	Discussion of quality issues	  	QA	  	As needed
			
	Discussion of technical issues	  	Manufacturing Contact	  	As needed
			
	Need anticipated for reprocessing/rework	  	Manufacturing Contact and QA	  	CLIENT and CYTOVANCE must mutually approve all rework or reprocessing plans in advance
			
	Initiation of OOS investigation	  	QA	  	3 business days
			
	Verified OOS event	  	QA	  	3 business days
			
	Initial disclosure of nonconforming Event (deviations): Major and Critical deviations which have adverse product impact or might cause termination or rejection of a product
batch	  	Manufacturing Contact and QA	  	3 business days
			
	Initiation of regulatory inspection specific to manufacture of CLIENT product	  	QA	  	24 hours
			
	Copy of observations for inspections specific to manufacture of CLIENT product	  	QA	  	24 hours
			
	Response available for review to regulatory inspection observations specific to manufacture of CLIENT product	  	QA	  	5 business days
			
	Initiation of regulatory inspection not specific to manufacture of CLIENT product	  	QA	  	3 business days
			
	Redacted copy of observations for inspections not specific to manufacture of CLIENT product	  	QA	  	3 business days after receipt of observations
			
	Redacted response to regulatory inspection observations not specific to manufacture of CLIENT product	  	QA	  	3 business days
			
	Deviations or errors detected by CLIENT during review	  	QA	  	Prior to CLIENT release of product, NMT 60 days

  

	6.	ADMINISTRATIVE INFORMATION 

  

	 	6.1.	Organizational Structure 


  

					
		 	Page 6 of 21	 	










	 	6.1.1.	CYTOVANCE shall maintain an adequate number of qualified personnel to perform and supervise CLIENT project-related activities and to meet cGMP requirements.


  

	 	6.1.2.	Personnel must have the appropriate combination of education, experience and training applicable to their responsibilities for the manufacture and testing of CLIENT
products. 

  

	7.	REGULATORY CONTROLS 

  

	 	7.1.	Filing/Registration Change Control 

 CYTOVANCE and CLIENT QA shall jointly notify one another of any proposed change that might, in reasonable judgment, affect regulatory filing/registrations. These changes may include, but are not limited
to, formulation change to Product or components, changes in manufacturing/packaging/testing site, equipment, batch size or process, test methods, etc. Prior approval from CLIENT QA/Regulatory Affairs is required prior to implementation of the
changes that may impact the filing/registration. Any changes to CYTOVANCE documents and information contained in CLIENT’S regulatory Filings must be reviewed and approved by CLIENT QA/Regulatory Affairs prior to implementation at
CYTOVANCE. 
  

	 	7.2.	Regulatory Filings 

 CLIENT is
responsible for all Product Regulatory Filings and for providing CYTOVANCE with portions of any filings related to CYTOVANCE activities as described in this Agreement. At the request of CLIENT, CYTOVANCE may be requested to review CYTOVANCE-related
submission information for accuracy to current operations. 
  

	 	7.3.	Government Agency Communication and Inspections 

  

	 	7.3.1.	CLIENT will be responsible for all FDA (and other regulatory agency) communications regarding CLIENT Product with the exception of regulatory inspections of the
CYTOVANCE facility. CYTOVANCE will assist and provide appropriate documentation as reasonably required in support of agency inquiries. 

  

	 	7.3.2.	Any regulatory authority inspections of CYTOVANCE facilities will be managed by CYTOVANCE. CYTOVANCE will notify CLIENT within twenty-four (24) hours after the
initiation of any general regulatory inspection. A redacted copy of any inspection observations will be provided to CLIENT within 3 business days after issuance to CYTOVANCE. Redacted copies of written responses to regulatory inspections will
be provided within 3 business days after being finalized. 


  

					
		 	Page 7 of 21	 	










	 	7.3.3.	CYTOVANCE will notify CLIENT the same day the inspection is initiated of any regulatory inspections directly involving CLIENT product. If desired by CLIENT, a
Quality Representative may be on site during any regulatory inspection that applies to CLIENT product and reasonable consideration will be given to requests for direct participation in the inspection during product-related inspection activities. A
redacted copy of any inspection observations will be provided to CLIENT 3 days after they are issued to CYTOVANCE. Unredacted copies of written responses to regulatory inspections directly involving CLIENT product will be provided 1 week
following receipt of observations. 

  

	 	7.4.	Product Recall 

  

	 	7.4.1.	CLIENT is responsible for administration of a product recall. CLIENT is responsible for the traceability of each distributed lot. If CYTOVANCE becomes aware of any
condition that may result in a product recall, CYTOVANCE shall notify CLIENT immediately. The final decision to proceed with a recall shall be made by CLIENT. 


 

	8.	DOCUMENT CONTROL SYSTEM 

  

	 	8.1.	Quality Agreement 

 Issuance of
revisions of this Quality Agreement shall require approval of both CYTOVANCE and CLIENT. 
  

	 	8.2.	CYTOVANCE Documentation 

 All
master batch records, Product specifications and CLIENT specific standard operating procedures or test methods require review and approval by CYTOVANCE and CLIENT. CLIENT approval is required for revisions. 

  

					
		 	Page 8 of 21	 	










	 	8.3.	CYTOVANCE will provide CLIENT with final, approved copies of the above-listed master documents at least 5 business days prior to manufacture and testing
of the Product. 

  

	 	8.4.	When CYTOVANCE initiates a revision to a mutually approved document as described in 8.2, CLIENT QA shall be provided with a document redline of the proposed changes and
documentation that summarizes and justifies each change. CLIENT QA shall review and process the change request within five business days. 

  

	 	8.5.	CYTOVANCE will make completed executed documents available to CLIENT. Photocopies or electronic PDF copies of executed batch records and corresponding testing data
will be provided to CLIENT within 30 business days of completion of batch production; with the assumption that all test and investigation reports have been completed and received by CYTOVANCE QA. CLIENT will be notified if circumstances require
an extension to the 30 business day time frame, Record retention at CYTOVANCE will be as outlined below. 

  

	 	8.6.	Record Retention 

 Documentation
for all completed batch records and release testing will be retained by CYTOVANCE for one year beyond the project closing date. At the end of one year, retained documentation will be sent to CLIENT for continued retention. Retained documentation
will include all product-specific documentation related to the operations performed subject to this agreement. 
  

	9.	CALIBRATION AND PREVENTATIVE MAINTENANCE PROGRAM 

 CYTOVANCE shall maintain a calibration and preventative maintenance program for all equipment, instruments, facilities and utilities. Calibrations will be performed using traceable/certified standards.
Records of calibrations and preventative maintenance are documented and maintained per CYTOVANCE standard operating procedures. 
  

	10.	VALIDATION PROGRAM 


CYTOVANCE shall maintain a validation program that includes a change control process for equipment, facilities, utilities, and
computer systems. Validation protocols describe the validation objectives, the equipment or system, data to be collected, test methods, sampling requirements and predefined acceptance criteria. 

CLIENT is responsible for validating processing hold times; buffer stability; column reuse and longevity studies; process validation;
analytical validation; and for development and justification of all processing parameters at the point at which such is warranted. If agreed, some or all of the listed activities may be contracted to CYTOVANCE. 

  

					
		 	Page 9 of 21	 	










	 	10.1.	Equipment Validation 

 CYTOVANCE
shall qualify equipment according to CYTOVANCE procedures, CYTOVANCE shall notify CLIENT QA of any proposed changes to process equipment used in production of CLIENT product to assure appropriate impact assessment on CLIENT Product. Copies of
validation/qualification reports will be made available for CLIENT review during site audit or upon request. 
  

	 	10.2.	Methods Qualification 


Methods/assays will be qualified as described in the Scope of Work. Copies of method/assay qualification reports will be provided to
CLIENT QA for approval. 
  

	 	10.3.	Cleaning Verification 

 Cleaning
of individual equipment will be verified through appropriate testing as defined in CYTOVANCE standard operating procedures. CYTOVANCE will provide copies of cleaning verification reports to CLIENT QA upon request. 

 

	11.	GMP SUPPLIER QUALITY ASSURANCE PROGRAM 

 CYTOVANCE shall have a program to assure procured materials and components are of the appropriate quality they purport to be. Records shall be maintained to demonstrate that procured materials were
purchased and received from suppliers that are approved or under qualification as defined by CYTOVANCE procedures. 
  

	12.	ENVIRONMENTAL CONTROL PROGRAM 

  

	 	12.1.	Environmental Controls 

 Controls
will be exercised to assure CLIENT product is manufactured and stored according to required environmental conditions as defined in specifications, MBRs, and SOPs. Excursions documented as an exceptional event will be
reported to CLIENT QA through the non-conforming event procedures within 1 business day of the event. 
  

	 	12.2.	Cleaning Program 

  

	 	12.2.1.	CYTOVANCE procedures shall define an effective cleaning program for facilities, equipment and support systems. Documentation shall be generated to demonstrate that
cleaning requirements have been met prior to the manufacturing of a CLIENT product. 


  

					
		 	Page 10 of 21	 	










	 	12.2.2.	CYTOVANCE shall notify CLIENT QA of failed cleaning or re-cleaning operations that have potential impact on CLIENT products within 1 business day after the failure
is recognized. 

  

	 	12.3.	Environmental Monitoring Program 


Facilities, utilities, and personnel utilized during the manufacture of CLIENT product will be monitored for particulate and
microbial levels if such monitoring is required. 
  

	13.	MATERIAL AND COMPONENT PROCUREMENT AND RELEASE 

  

	 	13.1.	CYTOVANCE Materials 

  

	 	13.1.1.	CYTOVANCE shall procure, receive, test and approve all materials according to CYTOVANCE procedures to assure compliance with CYTOVANCE and the CLIENTS specifications
when defined. 

  

	 	13.1.2.	Materials will be released for use per current Cytovance SOP’s for material and product release. 


 

	 	13.2.	CLIENT Materials 

  

	 	13.2.1.	All material supplied by CLIENT will be released and provided for use at CYTOVANCE with appropriate testing. CLIENT bears the responsibility for appropriateness
for use of such materials. 

  

	 	13.2.2.	CLIENT will ensure that materials that could potentially come into contact with the Product are assessed for transmissible spongiform encephalopathy (TSE) risk.


  

	14.	MATERIAL CONTROL 

  

	 	14.1.	Lot Identity 

 Materials
manufactured at CYTOVANCE will be identified at CYTOVANCE using a CYTOVANCE batch record identifier (lot number or equivalent). 
  

	 	14.2.	Material Storage 

 CYTOVANCE
shall securely store all materials, components, and product in compliance with specifications, regulations, and CYTOVANCE procedures. 

  

					
		 	Page 11 of 21	 	










	15.	LABORATORY CONTROLS 

  

	 	15.1.	Method Review 

 CLIENT will be
allowed to review all test methods prior to use by CYTOVANCE. 
  

	 	15.2.	Testing 

 CYTOVANCE shall conduct
quality control testing on materials and products as described in the mutually approved master batch records and Material Specification documents to ensure that they comply with product specifications. 

 

	 	15.3.	Sample Control and Sample Storage 


CYTOVANCE will procure and test all materials and products per CYTOVANCE procedures or current compendia, whichever applies to ensure
compliance with appropriate requirements. CYTOVANCE shall securely store all samples to ensure protection from unauthorized personnel and extremes in temperature and humidity in order to comply with specifications and/or material labeling.

  

	 	15.4.	Reference Standards 

 CLIENT will
provide Product reference standard for quality control testing. 
  

	16.	NON-CONFORMING EVENTS (DEVIATIONS) AND INVESTIGATIONS 

  

	 	16.1.	CYTOVANCE shall fully inform CLIENT of any major or critical planned or unplanned deviations that may have adverse product impact or cause batch termination or
rejection, investigations, or out of specification test results within 3 business days according to CYTOVANCE standard procedures. 

  

	 	16.2.	To the extent any deviations (including justification, impact on SBC-102 quality and resolution thereof) constitute planned excursions, Cytovance must obtain
Synageva’s written approval prior to use in the manufacture of a given lot or batch of SBC-102. 

  

	 	16.3.	Initiation of and Out of Specification result occurring at CYTOVANCE or a CYTOVANCE contract testing facility will be communicated to CLIENT as soon as possible, but no
later than 3 business days after the investigation is initiated. 

  

	 	16.4.	Confirmed Out of Specification results occurring at CYTOVANCE or a CYTOVANCE contract testing facility will be communicated to CLIENT as soon as possible, but no
later than 3 business days after the result is confirmed to be Out of Specification. 


  

					
		 	Page 12 of 21	 	










	 	16.5.	Investigations will be performed and documented per CYTOVANCE applicable nonconforming event procedures. Investigation require CLIENT input, review and approval.
Synageva shall promptly determine, in its sole discretion, whether or not to allow a batch or lot of SBC-102 impacted by a deviation to continue in the manufacturing process, or require its destruction. 


 

	17.	PRODUCT PROCESSING AND RELEASE 

  

	 	17.1.	Processing 

 CYTOVANCE shall
allow CLIENT personnel to be present during processing of CLIENT product according to CYTOVANCE procedures, which include Client training prior to entry into the manufacturing suites. 

 

	 	17.2.	Rework / Reprocessing 

 CLIENT
and CYTOVANCE QA must mutually approve any rework or reprocessing plan before any rework or reprocessing activities may commence. The reprocessing/rework must be conducted with mutually approved procedures. 

 

	 	17.3.	Batch Record Review 

 CYTOVANCE
QA shall complete batch record audits for each lot of product manufactured according to CYTOVANCE standard operating procedures within 30 business days of completion of the final batch. This review shall confirm records are satisfactory for,
including but not limited to, applicable analytical test results for products, in-process material, and component testing, production records, and all batch related deviation and investigation documentation. (CYTOVANCE will notify CLIENT if it is
determined that testing or investigation activities will exceed the 30 business day time frame.) CYTOVANCE shall provide written certification that the batch record has been satisfactorily reviewed prior to batch record transfer. CYTOVANCE
shall also provide written certification that the batch was manufactured under cGMP conditions. 
  

	 	17.4.	Batch Record Transfer 

 Complete
manufacturing and testing batch documentation will be transferred to CLIENT QA within 35 business days of completion of batch production; with the assumption that all test and investigation reports have been completed and received by CYTOVANCE
QA. CLIENT will be notified if circumstances require an extension to the 35 business day time frame. 

  

					
		 	Page 13 of 21	 	










	 	17.5.	Final Lot Release 

 CLIENT QA
shall be responsible for final lot approval and release of bulk drug substance and drug product. 
  

	 	17.6.	Prohibited Activities 

 CYTOVANCE
will not manufacture sensitizing agents such as cytotoxic materials or beta-lactam antibiotics in the facilities used to manufacture CLIENT Product. 
  

	18.	RETAIN SAMPLES 

  

	 	18.1.	CYTOVANCE will store retain samples of CLIENT product and CLIENT required raw materials for one year after their release date under the conditions stated in the
material specification. At the end of one year, QA will contact the CLIENT and request written permission to transfer the retain samples to the CLIENT or have the retain samples destroyed. 


 

	 	18.2.	The amount of retain sample withdrawn is at least twice that required to perform all requisite release analyses excluding [***] testing. Product sampling will be
performed as specified in Master Batch Records and Specifications, and product will be stored at the proper storage temperature. 

  

	19.	PRODUCT COMPLAINTS (NON-MEDICAL) 

 Product complaints are the responsibility of CLIENT. All product complaints received by CLIENT that are related to the manufacturing or testing operations performed by CYTOVANCE will be communicated
in writing to CYTOVANCE. CYTOVANCE will provide written investigation reports, regarding complaints of a quality nature, to CLIENT within 15 business days of receiving written notification of the complaint. If additional time is required to complete
the investigation, an interim report and timeline will be provided. 
  

	20.	SHIPPING 

 CYTOVANCE will
package Product for shipment in compliance with procedures specified by CLIENT. CLIENT will provide CYTOVANCE with written authorization to ship product prior to shipment. 

  
  

[***] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed
separately with the Commission. 
 Page 14 of 21 









	21.	VALIDITY AND DISCLOSURE 


This AGREEMENT is made for an undefined time and remains valid as long as the product liability of CLIENT, as defined in the
Biopharmaceutical Services Agreement, will last. 
 All provisions of the Biopharmaceutical Services Agreement between CLIENT and
CYTOVANCE are hereby incorporated by reference. Any previous agreement or understanding not covered in this AGREEMENT or in the Biopharmaceutical Services Agreement, whether oral, written or implied is superseded. In case of any conflict
between this AGREEMENT and the Biopharmaceutical Services Agreement, the Biopharmaceutical Services Agreement shall govern. 

This AGREEMENT may be disclosed to Regulatory Authorities during the course of either routine compliance or Pre-Approval inspections.

 This AGREEMENT may only be amended by the procedures described herein and signed by the duly authorized representatives of
CLIENT and CYTOVANCE. 
  

									
	Cytovance Biologics, Inc.	  		 	Synageva BioPharma Corp.
					
	By:	 	 /s/ Darren Head
	  		 	By:	 	 /s/ Eugene J. Kim

					
	Name:	 	Darren Head	  		 	Name:	 	Eugene J. Kim
					
	Title:	 	President & CEO	  		 	Title:	 	Legal Counsel
					
	Date:	 	Feb. 27, 2012	  		 	Date:	 	2/28/2012


  

					
		 	Page 15 of 21	 	









 APPENDIX I 
 Products Covered by Quality Agreement 
 The Quality Agreement covers
the following products: 
  

					
	 Product Name
	  	 CLIENT, Code
	  	 CYTOVANCE

Identifier

	SBC-102	  	SYN - 102	  	To Be determined


  

					
		 	Page 16 of 21	 	









 APPENDIX II 
 KEY INFORMATION 
 Shipping Addresses/Fax Numbers/Key Contact Name 

Product will be shipped to: 
 Dawn Eberhardt

 111 Riverbend Road 
 Athens GA, 30605

 Send copies of work orders, certifications (certificates of analysis, attestations, etc.), exception documents for review and approval,
and change request proposals to: 
 Dawn Eberhardt 
 111 Riverbend Road 
 Athens GA, 30605 

  

					
		 	Page 17 of 21	 	









 APPENDIX III 
 KEY CONTACTS 
 Client 

 

							
	 Function
	  	 Name/Title
	  	 Phone / Fax
	  	 E-mail

	QA	  	Dawn Eberhardt, Ph.D. Director, Quality Assurance	  	Synageva BioPharma Corp. 111 Riverbend Road Athens, GA, 30605 Tel: 706-227-1170 ext 224 Fax: 706-227-2180 Synageva BioPharma Corp. 111 Riverbend Road Athens, GA, 30605 Tel:
706-227-1170 ext 232 Fax: 706-227-2180	  	dawn.eberhardt@synageva.com
				
	Manufacturing Contact	  	Joseph DeCourcey VP Manufacturing and Technical Operations	  	128 Spring St Suite 520 Lexington MA, 02421 Tel: 781-357-9918 Cell: 781-786-1272	  	joseph.decourcey@synageva.com

 CMO 
 Cytovance Biologics, Inc 

  

					
		 	Page 18 of 21	 	










							
	 Function
	  	 Name/Title
	  	 Phone / Fax
	  	 E-mail

	QA	  	Bill Minshall VP of Quality Systems	  	 Tel: (405) 319-8316
 Fax: (405)
319-8339
	  	bminshall(a)cvtovance.com
				
	Manufacturing Contact	  	Ulrich Ernst SVP Manufacturing Operations	  	 Tel: (405) 319-8643
 Fax: (405)
319-8339
	  	uernst@cytovance.com
				
	Business Development	  	Valerie McDonnell VP Business Development	  	 Tel: (405) 319-8612
 Fax: (405)
319-8339
	  	vmcdonnell@cytovance.com


  

					
		 	Page 19 of 21	 	









 APPENDIX IV 
 Agreement Overview 
 This is an overall guide covering quality responsibilities for products
governed by this agreement. For specific information, refer to the specific section in the body of the Quality Agreement. 
  

					
	 Quality Attribute
	  	Responsibility
	  	CYTOVANCE	  	CLIENT
	 QUALITY AGREEMENT
	  		  	
	 Compliance with Regulations
	  	X	  	X
	 Audit Right and Document Access
	  		  	X
	 Subcontracting
	  	X	  	X
	 COMMUNICATION
	  	X	  	X
	 ADMINISTRATIVE INFORMATION
	  		  	
	 Organizational Structure
	  	X	  	
	 REGULATORY CONTROLS
	  		  	
	 Filing/Registration Change Control
	  	X	  	X
	 Government Agency Communication & Inspections
	  	X	  	X
	 Product Recall
	  	X	  	X
	 DOCUMENT CONTROL SYSTEM
	  		  	
	 Quality Agreement
	  	X	  	X
	 Master Batch Record Approval and Revision
	  	X	  	X
	 Product Specification Approval and Revision
	  	X	  	X
	 Client-Specific SOP Approval and Revision
	  	X	  	X
	 Client-Specific Test Method Approval and Revision
	  	X	  	X
	 Copies of Master Documents
	  	X	  	
	 Record Retention
	  	X	  	
	 CALIBRATION AND PREVENTIVE MAINTENANCE PROGRAM
	  	X	  	
	 VALIDATION PROGRAM
	  		  	
	 Equipment/Facilities/Utilities/Computer Validation
	  	X	  	
	 Copies of Method/Assay Qualification Reports
	  	X	  	
	 Cleaning Verification
	  	X	  	
	 GMP SUPPLIER QUALITY ASSURANCE PROGRAM
	  	X	  	
	 ENVIRONMENTAL CONTROL PROGRAM
	  		  	
	 Temperature/Humidity Controls
	  	X	  	
	 Cleaning Program
	  	X	  	
	 Environmental Monitoring Program
	  	X	  	
	 MATERIAL & COMPONENT PROCUREMENT AND RELEASE
	  		  	
	 CYTOVANCE Materials
	  	X	  	
	 CLIENT Materials
	  		  	X


  

					
		 	Page 20 of 21	 	










					
	 Quality Attribute
	  	Responsibility
	  	CYTOVANCE	  	CLIENT
	 MATERIAL CONTROL
	  		  	
	 Lot Identity
	  	X	  	
	 Material Storage
	  	X	  	
	 LABORATORY CONTROLS
	  		  	
	 Method Review
	  	X	  	X
	 Testing
	  	X	  	X
	 Sample Control and Sample Storage
	  	X	  	
	 Reference Standards
	  		  	X
	 NON-CONFORMING EVENT (DEVIATION) & INVESTIGATION REPORTS
	  		  	
	 General Content
	  	X	  	
	 Notification of Confirmed OOS/Deviation/Investigation Events
	  	X	  	
	 Confirmed OOS/Deviation/Investigation Event Status Reports
	  	X	  	
	 Confirmed OOS/Deviation/Investigation Documents
	  	X	  	X
	 PRODUCT PROCESSING & RELEASE
	  		  	
	 Processing
	  	X	  	X
	 Rework / Reprocessing
	  	X	  	X
	 Batch Record Review
	  	X	  	X
	 Batch Record Transfer
	  	X	  	
	 Final Batch/Lot Release
	  		  	X
	 RETAIN SAMPLES
	  	X	  	
	 PRODUCT COMPLAINTS
	  	X	  	X
	 SHIPPING
	  	X	  	X

 END OF DOCUMENT 

  

					
		 	Page 21 of 21	 	









 Exhibit B 
 Certificate of Conformance 
 CERTIFICATE OF CONFORMANCE 

 

			
	Product Name:	  	
	Client Part #:	  	Client Lot #:
	Cytovance Item #:	  	Cytovance Lot #:
	Date of Manufacture:	  	
	Material Specification #:	  	Revision:
	Quantity:	  	
	Non-Conformances:	  	

 This is to certify that the product identified above conforms to all applicable specifications as evidenced by
reports and documentation on file. This product was manufactured in compliance with The Code of Federal Regulations, Title 21, Parts 210 and 211. 
 Materials used in the manufacture of this product were of a non-animal source and pose no risk of Bovine Spongiform Encephalopathy (BSE) / Transmittable Spongiform Encephalopathy (TSE).

  

			
	  
	  	  

	Quality Assurance Management	  	Date


  
 15 

 








 Exhibit C 

Certificate of Analysis (lf applicable) 
 CERTIFICATE OF ANALYSIS 
  

			
	Product Name:	  	
	Cytovance Item #:	  	Cytovance Lot #:
	Date of Manufacture:	  	
	Expiration Date:	  	

  

							
	 ASSAY
	  	 METHOD
	  	SPECIFICATION	  	RESULT
	 [***]
	  	Cytovance SOP [***]	  	[***]	  	
	 [***]
	  	Cytovance SOP [***]	  	[***]	  	
	 [***]
	  	Cytovance SOP [***]	  	[***]	  	
	 [***]
	  	Cytovance SOP [***]	  	[***]	  	

 (Continued on next page) 

  
  

[***] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed
separately with the Commission. 
 16 

 








 (Continued from Page 1) 
 Exceptions/Non-Conformances: 
 None 

 
  

 
  

 
  

 
 This is to certify that the
results obtained above conform to all applicable tests, assays, and/or analytical methods and the required specifications have been met. Testing was performed in accordance to US FDA GMP Regulations (21CFR 211 Subparts I and J). 

 

			
	  
	  	  

	 Quality Control Management
	  	Date
		
	  
	  	  

	 Quality Assurance Management
	  	Date


  
 17 

 








 Addendum A: 
 The projected pass through materials costs and outsourced analytical costs per lot of SBC-102 are as follows; 
  

					
	 Equipment (e.g. filter housings)
	  	$	[***]	  
	 Filling components
	  	$	[***]	  
	 Single use bags/containers
	  	$	[***]	  
	 Filtration materials
	  	$	[***]	  
	 Tubing/column parts
	  	$	[***]	  
	 Chemicals
	  	$	[***]	  
	 [QC testing
	  	$	[***]	  
	 [External testing (DP)
	  	$	[***]	  
		
	 Total
	  	$	[***]	  

 These amounts are preliminary estimates and may be revised after experience with performance of the new manufacturing
process. 

  
  

[***] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed
separately with the Commission. 
 18 

 








 Addendum B: 
 Technology Transfer Guidance Document 
 [***] 

  
  

[***] = Portions of this exhibit have been omitted pursuant to a confidential treatment request. An unredacted version of this exhibit has been filed
separately with the Commission. 
 19