Document:

Exhibit 10.16

 

CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN
THIS DOCUMENT, MARKED BY BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH
THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 OF THE
SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.

 

Biological Service Agreement

 

THIS BIOLOGICAL SERVICE AGREEMENT (the “Agreement”) is made this 27 day of
January 2004 between:

 

(1)                                  AVECIA LIMITED, acting through its Avecia Biotechnology business of
Hexagon House, Blackley, Manchester, M9 8ZS, England (“Avecia”); and

 

(2)                                  STRESSGEN DEVELOPMENT CORPORATION, a Barbados
Corporation with headquarters at Whitepark House, White Park Road, PO Box 806E,
Bridgetown, Barbados (“Stressgen”).

 

WHEREAS

 

A                                      Avecia has
experience and knowledge with regard to process development and manufacture of
recombinant proteins.

 

B                                        Stressgen
is carrying out research and development in relation to HspE7 (as defined
below) with a view to conducting clinical trials and commercial launch of a new
drug.

 

C                                        Stressgen
wishes Avecia to carry out a programme for development of commercial process,
GMP manufacture of phase III clinical supply of API (as defined below),
validation of the process at scale and ancillary activities necessary to
support [* *].

 

D                                       The
Programme (as defined below) was commenced under the Purchase Order (as defined
below) and it is intended that it shall be further carried out and completed
under the terms of this Agreement.

 

NOW IT IS HEREBY AGREED AS FOLLOWS:

 

1                                         Definitions:

 

1.1                                 In this Agreement the following
expressions shall have the following meanings:

 

	
  Affiliate 

  	
   

  	
  any corporation, association or other
  business entity which directly or indirectly controls, is controlled by or is
  under common control with Avecia or Stressgen, where “control” means the legal power to direct or cause the direction
  of the general management and policies of such entity whether through the
  ownership of at least 50% of voting securities or capital stock of such
  business entity or any other comparable equity or ownership interest with
  respect to a business entity other than a corporation.

  
	
   

  	
   

  	
   

  
	
  Active
  Pharmaceutical Ingredient (API)

  	
   

  	
  any substance or mixture of substances
  intended to be used in the manufacture of a drug (medicinal) product and
  that, when used in the production of a drug, becomes an active ingredient of
  such drug product (see 21CFR 210.3(b)(7) and ICH QA7).  In this document, API refers to the active
  ingredient for HspE7 drug product, manufactured in compliance with GMP and
  ready for processing into clinical trials supplies or commercial products.

  
	
   

  	
   

  	
   

  
	
  Avecia
  Default

  	
   

  	
  failure by Avecia to use reasonable
  commercial endeavours to progress the Programme (as defined below).  For the avoidance of doubt, a failure
  which results from discovery of a technical factor which affects the Process
  or production of the API which

  

 

[*] = Confidential Treatment Request(ed).

 

1

 

	
   

  	
   

  	
  was not known and could not reasonably have
  been known at the commencement of the Programme shall not be considered to be
  an Avecia Default.

  
	
   

  	
   

  	
   

  
	
  Background
  Intellectual Property

  	
   

  	
  any Intellectual Property owned by or in
  the possession of a party (and to which that party has the necessary rights):

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  (a)           at the date of this Agreement; or

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  (b)           thereafter either (i) acquired
  independently of the Programme or (ii) Intellectual Property developed
  independently of the Programme by any employee of that party without
  reference to any of the Confidential Information disclosed by the other
  party.

  
	
   

  	
   

  	
   

  
	
  BLA

  	
   

  	
  a Biological License Application for
  marketing approval filed in the United States.

  
	
   

  	
   

  	
   

  
	
  Cell Banks

  	
   

  	
  the master cell bank and the working cell
  bank provided by Stressgen to Avecia pursuant to the Material Transfer
  Agreement dated January 9, 2004, a copy of which is attached as Schedule 1, and any additional
  working cell banks produced by Avecia during the Programme.

  
	
   

  	
   

  	
   

  
	
  Cancellation
  Fee

  	
   

  	
  a sum calculated in accordance with Schedule 2.

  
	
   

  	
   

  	
   

  
	
  Commencement
  Date

  	
   

  	
  January 5, 2004.

  
	
   

  	
   

  	
   

  
	
  Completion

  	
   

  	
  completion of the Programme as defined in
  the Scope Statement.

  
	
   

  	
   

  	
   

  
	
  Confidential
  Information

  	
   

  	
  any technical or commercial information
  relating to the Programme and any other information of a confidential nature
  disclosed (whether disclosed in writing, verbally, by way of sample or by any
  other means and whether directly or indirectly) by either party (“the Disclosing Party”) to the other
  (“the Receiving Party”),
  including and without limitation any information relating to the Disclosing
  Party’s business affairs.

  
	
   

  	
   

  	
   

  
	
  Confidentiality
  Agreement

  	
   

  	
  the confidentiality agreement entered into
  between Stressgen Biotechnologies, Inc. (covering corporate affiliates
  including Stressgen) and Avecia dated July 18, 2002.

  
	
   

  	
   

  	
   

  
	
  Defective
  API

  	
   

  	
  a quantity of the API which (i) has not
  been manufactured in accordance with GMP and any other Regulatory Standards,
  if required pursuant to the Scope Statement, or (ii) in any case, API which
  does not comply with the Specifications.

  
	
   

  	
   

  	
   

  
	
  Force
  Majeure

  	
   

  	
  any cause beyond the reasonable control of
  the party in question which for the avoidance of doubt and without prejudice
  to the generality of the foregoing shall include governmental actions, war,
  riots, terrorism, civil commotion, fire, flood, epidemic, labour disputes
  (excluding labour disputes involving the work force or any part thereof of
  the party in question), restraints or delays affecting shipping or carriers,
  inability or delay in obtaining

  

 

[*] =
Confidential Treatment Request(ed).

 

2

 

	
   

  	
   

  	
  supplies of adequate or suitable materials,
  currency restrictions, and act of God.

  
	
   

  	
   

  	
   

  
	
  GMP

  	
   

  	
  current good manufacturing practice and
  standards as provided for (and as amended from time to time) in European
  Community Directive 91/356/EEC (Principles and guidelines of good manufacturing
  practice for medicinal products) and in the Current Good Manufacturing
  Practice Regulations to the US Code of Federal Regulations Title 21 (21 CFR
  210 and 21 CFR 211) in relation to the production of pharmaceutical
  intermediates and active pharmaceutical ingredients, as interpreted by ICH
  Harmonised Tripartite Guideline, Good Manufacturing Practice Guide for Active
  Pharmaceutical Ingredients, Q7A and subject to any arrangements, additions or
  clarifications agreed from time to time between the parties in the QA
  Agreement.

  
	
   

  	
   

  	
   

  
	
  HspE7

  	
   

  	
  the trivial name for SGN-00101 (CAS#
  295371-00-5), the fusion protein consisting of the [* *]  heat shock protein of Mycobacterium bovis var. BCG (Hsp65)
  coupled [* *] to the E7 protein of the HPV type 16.

  
	
   

  	
   

  	
   

  
	
  Intellectual
  Property

  	
   

  	
  all know-how, inventions, discoveries,
  devices, data, patents, designs, copyrights, or other industrial or
  intellectual property and all applications therefor.

  
	
   

  	
   

  	
   

  
	
  Latent
  Defect

  	
   

  	
  a defect in the API delivered to Stressgen
  by Avecia, the existence of which was not reasonably capable of discovery at
  the point of acceptance and which indicates that such API was not
  manufactured in accordance with GMP and any other Regulatory Standards, if
  required pursuant to the Scope Statement.

  
	
   

  	
   

  	
   

  
	
  New Intellectual
  Property

  	
   

  	
  Intellectual Property that is made,
  conceived or reduced to practice during and as a direct result of the
  Programme.

  
	
   

  	
   

  	
   

  
	
  Nominated
  Manufacturer

  	
   

  	
  any manufacturer other than Avecia,
  nominated by or partnered with Stressgen to carry out manufacture of HspE7.

  
	
   

  	
   

  	
   

  
	
  Process

  	
   

  	
  The process for manufacture of the API.

  
	
   

  	
   

  	
   

  
	
  Programme

  	
   

  	
  the activities and deliverables described
  in the Scope Statement (as defined below) and the QA Agreement.

  
	
   

  	
   

  	
   

  
	
  Programme
  Amendment Order

  	
   

  	
  means a document in the form set out in Schedule 3 detailing changes to the
  Programme agreed and signed by both parties.

  
	
   

  	
   

  	
   

  
	
  Programme
  Management Plan

  	
   

  	
  the document that contains the terms and
  conditions by which the Programme will be managed.  The Programme Management Plan is attached as Schedule 4 hereto and hereby
  incorporated into this Agreement by reference.  The Parties may modify or amend the Programme Management Plan
  by execution of a Programme Amendment Order.

  

 

[*] =
Confidential Treatment Request(ed).

 

3

 

	
  Programme Timeline

  	
   

  	
  The
  estimated timeline for the conduct of the Programme, attached as Schedule 5.  The Parties may modify or amend the
  Programme Timeline by execution of a Programme Amendment Order.

  
	
   

  	
   

  	
   

  
	
  Project Steering Committee or PSC

  	
   

  	
  the
  steering committee established pursuant to Clause 2.4, with each party having
  an equal say, regardless of the number of members such party has in the
  committee.

  
	
   

  	
   

  	
   

  
	
  Purchase
  Order

  	
   

  	
  Stressgen’s purchase order number PAD0071
  dated December 19, 2003, a copy of which is attached as Schedule 6.

  
	
   

  	
   

  	
   

  
	
  QA
  Agreement

  	
   

  	
  the document agreed by the parties setting
  out: (i) the mutually agreed quality standards applicable for the manufacture
  of the API; and (ii) the roles and responsibilities of each party’s personnel
  in relation to quality assurance matters, a copy of which is attached as Schedule 7.

  
	
   

  	
   

  	
   

  
	
  Regulatory Standards

  	
   

  	
  any standards of any governmental
  authority, whether within or outside the United Kingdom, that are agreed by
  the PSC or as set forth in the QA Agreement to apply to Avecia’s facilities
  or Avecia’s production, storage or handling of the API.

  
	
   

  	
   

  	
   

  
	
  Release

  	
   

  	
  certification by Avecia that the API has
  been manufactured in accordance with GMP and that the API conforms to the
  Specifications based on the results of all API tests as per the QA Agreement,
  as evidenced by Avecia’s issuance of signed certificates of analysis and of
  compliance with GMP.

  
	
   

  	
   

  	
   

  
	
  Scope
  Statement

  	
   

  	
  the document attached as Schedule 8 that describes in
  detail the work to be conducted and the deliverables to be provided by Avecia
  in connection with the Programme.

  
	
   

  	
   

  	
   

  
	
  Specifications

  	
   

  	
  with respect to the API, the specifications
  to be agreed by the parties in accordance with the QA Agreement.

  
	
   

  	
   

  	
   

  
	
  Third
  Party

  	
   

  	
  any person other than the parties or their
  respective Affiliates.

  

 

1.2                                 Any reference to “day” or “days” means any day other
than a Saturday, Sunday or Bank Holiday in the United Kingdom.

 

2              Performance of the Programme

 

2.1                                 QA Agreement. 
Avecia will carry out the work as detailed in the Programme in
accordance with the terms of the QA Agreement. 
In order for Avecia to carry out the Programme, each party shall fulfil
its responsibilities as set out in the QA Agreement.

 

2.2                                 Programme Details. 
Avecia shall use reasonable commercial endeavours to carry out the
Programme in accordance with the Scope Statement, the QA Agreement, the
Programme Management Plan and the Programme Timeline.

 

2.3                                 Conduct of the Programme.  Avecia will assemble and maintain a project team dedicated to the
Programme having members with appropriate training and expertise in order to

 

[*] =
Confidential Treatment Request(ed).

 

4

 

apply
a sufficient full time equivalent (FTE) commitment to the conduct of the
Programme as required under this Agreement. 
For the avoidance of doubt, it shall not be considered a breach of this
Agreement by Avecia if an objective of the Programme is not achieved:

 

(a)                                  so long as Avecia uses reasonable commercial endeavours
to perform its obligations; or

 

(b)                                 due to delay caused or contributed to substantially by
Stressgen.

 

The parties acknowledge that,
having regard to the fact that the work to be performed hereunder is [* *].

 

2.4                                 Information Exchange and Programme Management.  The parties shall conduct regular
information exchanges in a manner set forth in the Programme Management Plan to
enable ongoing review of the Programme and its continuation.  Pursuant to the Programme Management Plan,
the parties will establish a Project Team composed of members appointed by each
Party, which will have day-to-day responsibility for the technical design and
supervision of Programme activities (including the production of deliverables),
and communication and management related to the Programme.  Project Team meetings must be attended by
representatives from each party having sufficient decision-making authority
with respect to the issues to be agreed upon or resolved by the Project Team.  The parties will also establish a Project Steering
Committee having the responsibility and authority to discuss and resolve large,
overarching questions or issues pertaining to the Programme; to amend Programme
Timelines where appropriate; to authorize the completion of milestones, and to
monitor the progress of the Programme, discuss future plans, and the
relationship between the parties.

 

2.5                                 Programme Amendment Orders.  The parties may agree to vary the Programme or sums to be paid
under Clause 3, provided that such variation is made in writing in a Programme
Amendment Order.  The parties recognise
that, in the event that:

 

(a)                                  Stressgen requires Avecia to carry out additional or
different work to that specified in the Scope Statement; or

 

(b)                                 Stressgen requires additional quantities of API or HspE7;
or

 

(c)                                  the outcome of any element of the Programme in reality
differs from the assumptions at the Commencement Date as set out in section 4
of the Scope Statement,

 

the work carried out under the
Programme will require changes which may cause an increase in the payments set
out in Clause 3 below.  The PSC shall
have authority to execute Programme Amendment Orders having a value of up to
US$1,000,000 calculated at the US$/£ exchange rate current at the date of such
execution.  Above this threshold, the PSC
shall make recommendations relating to the execution of such Programme
Amendment Orders to the parties.

 

2.6                                 Technical Assistance. 
During the Programme, Avecia will provide assistance to Stressgen in
respect of Stressgen’s regulatory filing activities for HspE7 and the Process
as indicated in the Scope Statement and the QA Agreement, and after Completion,
Avecia will offer reasonable assistance to Stressgen with regard to the same,
subject to payment by Stressgen of Avecia’s reasonable expenses.

 

2.7                                 Delay Due to Avecia Default.  In the event that Avecia is not able to carry out any
manufacturing run identified to be GMP-compliant in the Scope Statement in
accordance

 

[*] =
Confidential Treatment Request(ed).

 

 

5

 

with
the Programme Timeline as a result of an Avecia Default, then the following
provisions shall apply:

 

(a)                                  Avecia shall notify Stressgen as soon as it believes
that it will not be able to carry out such GMP manufacturing run in accordance
with the then-current Programme Timeline.

 

(b)                                 If Stressgen still wishes Avecia to carry out such GMP
manufacturing run, Avecia shall use its best commercial endeavours to carry out
or complete such GMP manufacturing run as soon as reasonably practicable and at
no extra cost to Stressgen.

 

(c)                                  If Stressgen does not wish Avecia to carry out or
complete such GMP manufacturing run, Stressgen shall be entitled to terminate
this Agreement and the provisions of Clause 9.1(e) shall apply.

 

2.8                                 Delay Due to Stressgen Option.  Stressgen shall have an option to delay the
commencement of the initiation of any manufacturing run [* *] for a period of time up to [* *].  In the event
that Stressgen decides to exercise such option, the following provisions shall
apply:

 

(a)                                  Stressgen shall give written notice to Avecia of its
intention to delay the commencement of any such [* *] manufacturing run setting out the estimated length of
the delay.

 

(b)                                 Stressgen shall pay to Avecia the Cancellation Fee.

 

(c)                                  The parties shall meet to discuss availability of
Avecia’s manufacturing facility for the delayed [* *] manufacturing run and the amount payable by Stressgen
to Avecia in respect of such later commencement of such [* *] manufacturing run.

 

(d)                                 Avecia shall not be obliged to carry out the delayed [* *] manufacturing run until [* *], but will use reasonable efforts to reschedule the
availability of its facility and appropriate personnel.

 

2.9                                 Commercial Supply Terms.  At any time following the initiation of the first [* *] manufacturing run for API, at Stressgen’s request, the
parties will meet to negotiate in good faith the terms and conditions of a commercial
supply arrangement for the supply
of API by Avecia to Stressgen following the satisfactory completion of the
Programme.

 

3              Payments

 

3.1                                 Payment Schedule.

 

(a)                                  In consideration of Avecia carrying out the technical
consultancy research and development activities pursuant to the Programme,
Stressgen shall pay to Avecia such amounts, at such times as are specified in
the Scope Statement and payment schedule attached as Schedule 9 in respect thereof.

 

(b)                                 in consideration of Avecia carrying out the sale of
the API to Stressgen, Stessgen shall pay to Avecia such amounts, at such times
as are specified in the Scope Statement and payment schedule attached as Schedule 9 in respect thereof.

 

3.2                                 Excluded Items. 
The sums set out in Schedule 9
do not include:

 

[*] =
Confidential Treatment Request(ed).

 

6

 

(a)                                  any costs for [* *]; or

 

(b)                                 costs actually incurred by Avecia for [* *] involved
in the non GMP and GMP production; or

 

(c)                                  costs actually incurred by Avecia associated with [*
*].

 

Avecia shall obtain Stressgen’s
approval in writing prior to incurring such costs in Clause 3.2 (a).  Avecia shall obtain Stressgen’s approval in
writing prior to incurring such costs in Clause 3.2 (b) and (c) if such
costs are anticipated to exceed [* *]. 
If such approval is given, the provisions of Clause 3.3 will apply.

 

3.3                                 Further Consideration.  Avecia shall invoice Stressgen for a further amount for technical
consultancy research and development work to cover management, administration
and quality control activities.  This
amount shall equal the actual cost which Avecia incurs in respect of [* *] under
Clauses 3.2(b) and (c), plus the actual cost of [* *] under Clause 3.2(a) which will be [* *] and a
reasonable allocation of the actual cost of [* *] under Clause 3.2(a) that may be used [* *], plus
[* *].

 

3.4                                 Issue of Invoices. 
Avecia shall issue monthly invoices for authorized work completed during
such time period and for sums arising under Clause 3.3 as such sums fall due,
including with such invoices appropriate documentation for pass-through costs
described in Clause 3.2.  Stressgen
shall pay such sums within 30 days of the date of Stressgen’s receipt of the
relevant invoice.

 

3.5                                 Bank Account Details. 
All amounts payable to Avecia under this Agreement shall be paid in
Pounds Sterling, without deduction, by authenticated and value dated Swift telegraphic
transfer to:

 

[* *] Bank, London

SWIFT:  [* *]

Sort Code:             [* *]

Account No:         [* *]

Account:               Avecia Ltd

IBAN [* *].

 

3.6                                 Value Added Tax. 
All sums payable under this Agreement are stated exclusive of any VAT
which may be payable and which shall be for the account of Stressgen.  Subject to Clause 4.3(d), the parties
anticipate that supply of
technical consultancy and sale of API made by Avecia to Stressgen pursuant to
this Agreement [* *].  Avecia will use reasonable efforts to ensure that
such VAT treatment is afforded to supply of technical consultancy and sale of API made under
this Agreement, and to inform Stressgen of the VAT liability [* *] so that
Stressgen may obtain a United Kingdom VAT registration or take other
appropriate steps.

 

4                                         Delivery of API and Cell
Banks

 

4.1                                 Delivery of Material. 
Subject to Clauses 4.3 and 4.4, delivery of all material, including the
API and the Cell Banks, will be made EXW Avecia’s Billingham facility (Incoterms 2000).

 

4.2                                 Packing and Shipping. 
Avecia shall arrange for packing of any of the material to be delivered
under Clause 4.1 at Stressgen’s expense, shall comply with the QA Agreement in
packing the API, and shall meet all reasonable requirements of Stressgen in
packing the Cell Banks at such time as they are returned to Stressgen under the
provisions of the

 

[*] =
Confidential Treatment Request(ed).

 

7

 

[* *] agreement described in Clause 4.4.  Risk and title in respect of all material supplied to Stressgen
under this Agreement shall pass on delivery at Avecia’s Billingham facility,
except as otherwise provided herein. 
Subject to Clause 4.3, Stressgen agrees to export the API promptly from
the United Kingdom.

 

4.3                                 [* *] of the API. 
Avecia shall [* *] the API in accordance with the QA Agreement, subject
to written agreement on the terms of such [* *], including fees and liability
for such [* *], provided that:

 

(a)                                  [* *] shall be at Stressgen’s expense under [* *] to
be agreed in writing; and

 

(b)                                 [* *] shall be at Avecia’s risk, unless, despite [* *]
in accordance with the conditions agreed under Clause 4.3(a), the API [* *]
from its condition at the start of such [* *]; and

 

(c)                                  risk of loss in the API shall pass in the event of
delivery to Stressgen under Clause 4.1 but title will pass on the later of (i)
Avecia’s notification that the API has passed the quality assurance release
protocols set out in the QA Agreement or (ii) agreement between the parties
that Avecia will [* *] the API;

 

(d)                                 Stressgen recognises that [* *] of the API at Avecia
for a period of [* *] to Stressgen.

 

In the absence of agreement on
the terms of such [* *], Avecia shall not be obliged to [* *] the API and shall
deliver it to Stressgen subject to the provisions of Clauses 4.1 and 4.2.

 

4.4                                 [* *] of Cell Banks. 
On completion of the Programme, Avecia will [* *] the Cell Banks
pursuant to the [* *] terms substantially in the form attached as Schedule 10.

 

4.5                                 Process Specific
Equipment.  At Stressgen’s request, any
process specific equipment dedicated solely to the Programme under Clause 3.3
shall be sold to Stressgen for consideration of [* *] on Completion.

 

5              Intellectual Property

 

5.1                                 Ownership of Background Intellectual Property.  Nothing in this Agreement shall affect the
ownership by either party of its Background Intellectual Property.  In addition, Stressgen shall retain all
right, title and interest in and to the Cell Banks pursuant to the Material
Transfer Agreement.

 

5.2                                 Licence to Intellectual Property for the
Programme.  Stressgen grants to Avecia a
non-exclusive, royalty-free licence to use Stressgen’s Background Intellectual
Property and Stressgen’s New Intellectual Property whilst this Agreement
remains in force for the sole purpose of carrying out the Programme.

 

5.3                                 New Intellectual Property.  Each party shall promptly disclose to the other any New
Intellectual Property.  New Intellectual
Property shall be owned by:

 

(a)                                  Stressgen if it relates primarily to [* *]; and

 

(b)                                 Avecia if it relates to primarily to [* *].

 

[*] =
Confidential Treatment Request(ed).

 

8

 

5.4                                 New Intellectual Property - Not Clearly Within Scope
of Clauses 5.3 (a) or (b).  In respect
of New Intellectual Property not clearly falling within the scope of either of
Clauses 5.3 (a) or (b), such New Intellectual Property shall be jointly owned
by the parties unless the Project Steering Committee through negotiations in
good faith determines the ownership of such New Intellectual Property on the
basis that such New Intellectual Property shall be owned by the party whose
Background Intellectual Property is most directly related to the New
Intellectual Property. With regard
to any jointly owned New Intellectual Property, the parties shall jointly
determine whether to seek patent protection for such New Intellectual Property
and if both parties wish to seek patent protection, the parties shall jointly
and collaboratively prepare, file and maintain any patents and patent
applications, using mutually agreed attorneys, with expenses shared
equally.  Should either party elect not
to pay its share of expenses related to such preparation, filing, or
maintenance of any such patent or patent application, it will promptly notify
the other party in writing, and the other party shall have the right, but not
the obligation, to prepare, file or maintain such patent application or patent,
at its sole expense.  In that case, the
party electing not to pay its share of expenses related to such preparation,
filing, or maintenance of such patent or patent application shall promptly
assign, deliver, convey and transfer to the other party, its successors and
assigns, without reservation, all of its right, title and interests in, to and
under such New Intellectual Property. 
If the parties mutually agree that either or both party(ies) will use
its in-house attorneys to obtain or maintain any registered intellectual
property rights in respect of New Intellectual Property, neither the party(ies)
using its in-house attorneys (“the relevant party”) nor any of its employees,
servants or agents shall be liable for any damage or loss suffered by the other
party as a result of any mutually agreed action or inaction on the part of the
relevant party or its employees, servants or agents in the course of the
filing, prosecution or maintenance of any patent or patent application with
respect to such New Intellectual Property. 
Each party shall have the right to license and otherwise commercially
exploit jointly owned New Intellectual Property without the consent of the
other party, provided that Avecia shall not be entitled to exercise its rights
under jointly owned New Intellectual Property to make, use, sell, offer for
sale, import, keep and otherwise deal in any [* *] or license any third party to do so. 
Neither party shall owe the other party any consideration in respect of
licensing or commercial exploitation of jointly owned New Intellectual
Property.  Each party may assign or
transfer its share of jointly owned New Intellectual Property without the
consent of the other party, subject to the terms hereof.

 

5.5                                 Further Assistance. 
Each party shall, and shall ensure that its employees shall, at the
expense of the party owning the New Intellectual Property, perform all acts and
execute all instruments, including assignments, necessary to obtain and vest in
the owning party (as determined under Clauses 5.3 and 5.4) all rights, title
and interest in the New Intellectual Property together with all patents and
patent applications or otherwise for such New Intellectual Property.  All fees, costs and expenses connected with
the filing, prosecution and maintenance of a patent or other protection shall
be borne and paid by the party owning such Intellectual Property.  The responsibility and authority for filing,
prosecution and maintenance of a patent or other protection for jointly-owned
New Intellectual Property shall be determined by the Project Steering
Committee.

 

5.6                                 Provision of Technical Assistance
and Access to Avecia’s Background Intellectual Property.  If:

 

(a)                                  following Completion or following termination of this
Agreement for any reason, Stressgen or a Nominated Manufacturer requires
Avecia’s technical assistance; and/or

 

(b)                                 at any time while this Agreement is in effect,
Stressgen requires a licence under Avecia’s Background Intellectual Property;
and/or

 

[*] =
Confidential Treatment Request(ed).

 

9

 

(c)                                  following Completion or following termination of this
Agreement for any reason Stressgen or a Nominated Manufacturer requires a
licence under Avecia’s Background Intellectual Property,

 

to operate the Process, then
such assistance and/or access shall be provided to Stressgen or such Nominated
Manufacturer by Avecia subject to agreement of reasonable commercial terms
between Stressgen and Avecia.  Any such
negotiations shall be carried out between the parties in good faith.

 

5.7                                 Licence under New Intellectual
Property.

 

(a)                                  Stressgen hereby grants to Avecia a royalty-free,
irrevocable, perpetual, non-exclusive, world-wide licence, with power to
sublicense, under New Intellectual Property owned by Stressgen under Clauses
5.3(a) or 5.4 to make, use, sell, offer for sale, import, keep and
otherwise deal in products other than [* *].

 

(b)                                 Avecia hereby grants to Stressgen a royalty-free,
irrevocable, perpetual, world-wide licence, with power to sublicense, under New
Intellectual Property owned by Avecia under Clauses 5.3(b) or 5.4 for any
purpose.  Such licence shall be
exclusive to make, use, sell, offer for sale, import, keep and otherwise deal
in [* *]  and non-exclusive otherwise.

 

6              Warranties, Liability and Indemnity

 

6.1                                 General Warranty. 
Each party warrants to the other that:

 

(a)                                  it has the necessary right and authority to enter into
this Agreement and that to the best of its knowledge at the date of this
Agreement it is the rightful owner or licensee of all of its Background
Intellectual Property; and

 

(b)                                 to the best of its knowledge at the date of this
Agreement, the use of Background Intellectual Property made available by it to
the other party pursuant to this Agreement for the purposes set out in this
Agreement will not infringe the Intellectual Property of a Third Party.

 

6.2                                 Intellectual Property Indemnity.  Each party (“the First Party”) shall be liable for and indemnify the other (“the Second Party”) against any
liability, loss, claim, damage, proceedings and costs whatsoever arising out of any
actual or suspected infringement of any Third Party Intellectual Property (an “IP Infringement”) as a result of the
Second Party’s use in its performance of this Agreement of the Background
Intellectual Property provided by the First Party, provided that the Second
Party:

 

(a)                                  gives the First Party the sole conduct of the defence
to any claim or action in respect of the IP Infringement and does not at any
time admit liability or otherwise settle or compromise or attempt to settle or
compromise the said claim or action except upon the express instructions of the
First Party; and

 

(b)                                 acts in accordance with the reasonable instructions of
the First Party and gives the First Party such assistance as it shall
reasonably require in respect of the conduct of such defence.

 

Notwithstanding the foregoing
provisions of this Clause 6.2, the First Party’s liability to indemnify the
Second Party shall cease in respect of continuing use by the Second Party

 

[*] =
Confidential Treatment Request(ed).

 

10

 

of the Background Intellectual
Property which is the subject of the IP Infringement following either:

 

(i)                                     notification (which shall be given promptly) by the
First Party to the Second Party that the Background Intellectual Property
provided by the First Party is actually or is believed by the First Party to be
the subject of an IP Infringement; or

 

(ii)                                  the Second Party becoming aware that the Background
Intellectual Property provided by the First Party is the subject of an IP
Infringement.

 

6.3                                 Liability for the API

 

(a)                                  Avecia warrants to Stressgen that the API delivered to
Stressgen pursuant to this Agreement: 
(i) will [* *]; (ii) will [* *]; and (iii) will be
transferred free and clear of any liens or encumbrances of any kind to the
extent arising through or as a result of the acts or omissions of Avecia, its
Affiliates or their respective agents. 
Each shipment of API from Avecia to Stressgen shall contain such quality
control certificates as are necessary to show that the API is [* *] and was
manufactured [* *].

 

(b)                                 Avecia shall be liable to either (1) [* *], or (2) [*
*] lost, damaged, or destroyed API [* *],
unless in each case, despite [* *] in accordance with the conditions agreed
under Clause 4.3(a), the API [* *] from its condition at the start of such [*
*].

 

(c)                                  In the event that either party discovers [* *] at any
time following delivery, the discovering party shall notify the other party
promptly.  If [* *] causes the API to be
[* *], and if the discovery of the [* *] occurs within [* *] of Release of the API, the provisions of Clause 6.3(g)
shall apply.

 

(d)                                 Stressgen shall notify Avecia of any [* *] within [* *] of Release of a shipment of the API.  If Stressgen fails to so notify Avecia,
Stressgen will be deemed to have accepted the API in a satisfactory condition
and in all respects in accordance with [* *] for purposes of this Agreement,
subject to any subsequently discovered [* *].  
If Stressgen so notifies Avecia and Avecia accepts that the API is a [*
*], the provisions of Clause 6.3(g) shall apply.

 

(e)                                  If Stressgen and Avecia dispute whether API is a [*
*], whether due to an [* *] or [* *], then the provisions of section 6 of the
QA Agreement shall apply.  The fees and
expenses of the independent QA expert referred to in section 6 of the QA
Agreement shall be borne [* *].  In the event that the independent QA expert
determines that the API is not a [* *], Stressgen will be deemed to have
accepted the API in a satisfactory condition and in all respects in accordance
with the [* *] for the purposes of this Agreement.  In the event that the independent QA expert determines that the
API is a [* *], provided that Stressgen notified Avecia of the [* *] within [* *] of Release or a [* *] in the API was discovered within
[* *] of Release, the provisions of Clause 6.3(g) shall
apply.

 

(f)                                    Stressgen shall not use any API in humans unless and
until it has been accepted.

 

(g)                                 In the circumstances described in Clause 6.3(c), (d)
or (e) related to an Avecia Default or Avecia’s failure to perform in
accordance with the QA Agreement, Avecia shall use reasonable commercial
efforts to either (1) [* *], or (2) manufacture [* *].  In addition, Avecia shall [* *] it incurs in
connection with the [* *],

 

[*] =
Confidential Treatment Request(ed).

 

11

 

provided that Avecia’s liability to [* *] Stressgen shall be limited to
a [* *] as appropriate.

 

(h)                                 If the API is [* *] and Clause 6.3(g) does not apply,
the parties shall meet to discuss availability of Avecia’s Advanced Biologics
Centre for [* *], or manufacture of [* *] and, subject to Clause 2.5,
agree on a revised period during such [* *] or manufacture of [* *] will take
place and the amount payable by Stressgen to Avecia in respect of such [* *].

 

(i)                                     Subject to and except to the extent of any
indemnification from Avecia pursuant to Clause 6.3(j) below, Stressgen
shall indemnify, defend and hold harmless Avecia against all claims, suits,
actions, demands, liabilities, expenses and/or losses (including reasonable
legal fees) (collectively, “Liabilities”)
brought or made by a Third Party against Avecia, its Affiliates, directors,
officers or employees, to the extent such Liabilities arise out of or result
from the [* *].

 

(j)                                     Subject to and except to the extent of any
indemnification from Stressgen pursuant to Clause 6.3(i) above and 6.4
below, Avecia shall indemnify, defend and hold harmless Stressgen against any
Liabilities brought or made by a Third Party against Stressgen, its Affiliates,
directors, officers or employees to the extent such Liabilities arise out of or
result from:  (i) [* *] under this
Agreement; (ii) [* *] provided to Avecia; (iii) Avecia’s failure to
ensure that the Programme is conducted in accordance with [* *]; or
(iv) Avecia’s [* *] or intentional misconduct.

 

6.4                                 Liability for the [* *].  Liability in respect of [* *], by or on behalf of Stressgen shall
rest solely on Stressgen, except to the extent that Avecia is required to indemnify Stressgen in
accordance with Clause 6.3 above or except to the extent that such
liability arises from a Third Party claim for property damage or personal
injury arising from Avecia’s failure to [* *] in accordance with [* *].  Stressgen shall indemnify Avecia against any
liability, loss, damages, costs, legal costs, professional and other expenses
whatsoever incurred or suffered by Avecia arising out of or in respect of [* *]
by or on behalf of Stressgen except to the extent that Avecia is required to
indemnify Stressgen in accordance with Clause 6.3 above or except to the extent
that such loss, damages, costs, legal costs, professional and other expenses
arise from a Third Party claim for property damage or personal injury arising
from Avecia’s failure to [* *].

 

6.5                                 Indemnification
Procedure.  In the event that either
party seeks indemnification under the terms of this Clause 6, it shall
inform the other party of the claim [* *] after it receives notice thereof,
shall permit the other party, [* *], to assume direction and control of the
defense of the claim, and shall co-operate as requested ([* *]), in the defense
of the claim.  The indemnifying party
shall not admit fault on the part of the indemnified party without its prior
written consent.

 

6.6                                 Limitation on Liability.  Except where [* *] described in Clauses 2.7(b), 6.3(b), 6.3(g) or
Section 4(b) of Schedule 10, but in each case subject to the provisions of
Clause 6.7, Avecia’s total
liability (whether for breach of contract, negligence, breach of statutory duty
and/or other tort, or otherwise) in connection with or as a result of the work carried
out under this Agreement shall be limited to [* *]. 
Notwithstanding the foregoing, the [* *] in respect of Avecia’s
obligation under Clause 6.3(j) to indemnify, defend and hold harmless Stressgen
against any Liabilities brought or made by a Third Party against Stressgen, its
Affiliates, directors, officers or employees to the extent such Liabilities
arise out of or result from [* *].

 

6.7                                 No Liability for Indirect Losses.  Except for violations of Clause 7 below
and amounts finally awarded for indemnification for Third Party liabilities
under Clause 6 above, neither

 

[*] =
Confidential Treatment Request(ed).

 

12

 

party shall be liable to the other for any indirect, consequential or
special loss, loss of profits or damage suffered by the other howsoever
arising.

 

6.8                                 Insurance. 
Each party shall secure and maintain in full force and effect during the
term of this Agreement policies of insurance providing coverage for
(a) Workmen’s Compensation or Employer’s Liability, (b) General
Liability or Public and Products Liability, and
(c) Automobile Liability or Motor Liability having policy limits, deductibles and other terms
appropriate to the conduct of that party’s business.  Evidence of such insurance in the form of a broker’s
letter will be made
available for examination upon request of the other party.

 

6.9                                 Representation, Warranty
and Covenants Regarding Debarment. 
Avecia represents and warrants that neither it, its employees, nor any
other person retained by it to perform the Programme pursuant to this
Agreement, (i) is under investigation by the FDA for debarment action or is
presently debarred pursuant to the Generic Drug Enforcement Act of 1992, as
amended (21 U.S.C. §301 et seq), or (ii) has a disqualification hearing pending
or has been disqualified by the FDA pursuant to 21 CFR Section 312.70 or its
successor provisions.  In addition,
Avecia represents and warrants that it has not engaged in any conduct or
activity which could lead to any of the above mentioned disqualification or
debarment actions. If during the term of this Agreement Avecia or any person
employed or retained by it to perform the Programme (i) comes under
investigation by FDA for debarment action or disqualification, (ii) is debarred
or disqualified, or (iii) engages in any conduct or activity which could lead
to any of the above mentioned disqualification or debarment actions, Avecia
shall immediately notify Stressgen of such event and address the issue as
mutually agreed by the Parties, such address to include immediate removal of
any such debarred or disqualified person from performance of Programme
activities.  At the reasonable request
of Stressgen, Avecia will provide a certification to the effect of this Clause
6.9 to support Stressgen’s submissions to applicable regulatory authorities,
including the FDA.

 

7                                         Confidentiality

 

7.1                                 Maintenance of Confidentiality.  In consideration of the Disclosing Party
disclosing the Confidential Information to the Receiving Party, the Receiving
Party hereby undertakes to maintain confidential all such Confidential Information
and it will accordingly not directly or indirectly use any of the Confidential
Information in whole or in part save for the purposes envisaged in this
Agreement or disclose any of the Confidential Information to any Third Party
other than under and in accordance with the terms of Clauses 7.4, 7.5 or 7.6.

 

7.2                                 Exceptions. 
The foregoing restrictions on the Receiving Party shall not apply to any
Confidential Information which:

 

(a)                                  the Receiving Party can prove was already in its
possession and at its free disposal before the disclosure hereunder to it;

 

(b)                                 is hereafter disclosed to, purchased or otherwise
legally acquired by the Receiving Party by or from a Third Party who has not
derived it directly or indirectly from the Disclosing Party under an obligation
of confidentiality;

 

(c)                                  is or becomes available to the public whether in
printed publications or otherwise through no act or default on the part of the
Receiving Party; or

 

[*] =
Confidential Treatment Request(ed).

 

13

 

(d)                                 the Receiving Party can prove to the reasonable
satisfaction of the Disclosing Party has been developed independently of the
Programme by the Receiving Party without reference to any of the Confidential
Information disclosed by the Disclosing Party.

 

7.3                                 Exercise of Reasonable Precautions.  In order to secure the obligations set out
in this Clause 7 the Receiving Party agrees to exercise every reasonable
precaution to prevent and restrain the unauthorised disclosure and use of information
subject to confidentiality, including restricting access to such information to
such of its employees as are bound to keep such information confidential and
need to have such access for the purpose of this Agreement.

 

7.4                                 Disclosure to Nominated Manufacturer.  Stressgen shall not be entitled to reveal
Confidential Information of Avecia to a Nominated Manufacturer unless Stressgen
either:

 

(a)                                  makes such disclosure under confidentiality
obligations no less restrictive than those contained in this Clause 7; or

 

(b)                                 procures the entry of such the Nominated Manufacturer
into a confidentiality agreement with Avecia directly.

 

7.5                                 Disclosure to Affiliates.  Either party may disclose Confidential Information to or via an
Affiliate, provided that the party making any such disclosure shall, prior to
such disclosure, ensure each Affiliate to which Confidential Information is to
be disclosed is made aware of the obligations contained in this Agreement and
agrees to be subject to confidentiality obligations no less onerous than those
contained in this Agreement.  Any
breaches of the obligations of confidentiality contained in this agreement by
such Affiliate shall be treated as a breach of such obligations by the party
making the disclosure to the Affiliate.

 

7.6                                 Disclosure to Courts or by Law or Other Rules.  Nothing in this Clause 7 shall preclude
disclosure of any Confidential Information required by any court entitled by
law to disclosure of the same, or which is required by applicable law, rule or
regulation to be disclosed, provided that the Receiving Party promptly notifies
the Disclosing Party when such requirement to disclose has arisen, to enable
the Disclosing Party to seek an appropriate protective order and to make known
to the said court or governmental authority the proprietary nature of the
Confidential Information and to make any applicable claim of confidentiality in
respect thereof.  The Receiving Party
agrees to co-operate in any appropriate action which the Disclosing Party may
decide to take.  If the Receiving Party
is advised to make a disclosure in accordance with this Clause 7.6 it shall
only make a disclosure to the extent to which it is obliged.

 

7.7                                 Survival of Obligations.  The provisions of this Clause 7 shall survive termination or
expiry of this Agreement and shall continue for a period of [* *] from the date
of that termination or expiry.

 

7.8                                 Continuation of the Confidentiality Agreement.  The parties shall remain bound by the
obligations in the Confidentiality Agreement, but in the event of any conflict
between the terms of the Confidentiality Agreement and the terms of this
Agreement, the Agreement shall prevail.

 

[*] =
Confidential Treatment Request(ed).

 

14

 

8                                         Duration and Termination

 

8.1                                 Duration.  This
Agreement shall be deemed to have commenced on the Commencement Date and shall
continue until Completion unless terminated in accordance with the provisions
of Clause 8.2.

 

8.2                                 Termination. 
Subject to Clause 9, this Agreement may be terminated in the following ways:

 

(a)                                  by mutual agreement at any time prior to Completion in
the event that both parties agree that [* *];

 

(b)                                 by either party at any time by giving written notice
to the other;

 

(c)                                  by either party forthwith if the other is in breach of
this Agreement and does not rectify such breach within 30 days of receipt of
written notice from the first party requiring rectification of the breach,
provided that it is intended that the parties will discuss any alleged breach
and its remediation as soon as it is known; or

 

(d)                                 by either party forthwith upon written notice if the
other has a liquidator, receiver, manager receiver or administrator appointed,
or ceases to continue trading or is unable to pay debts as defined in Section
227 of the Insolvency Act 1986 (England and Wales) or the equivalent occurs in
any jurisdiction in which the other is resident or carried on business.

 

9                                         Consequences of Termination

 

9.1                                 Consequences. 
In the event of termination under Clause 8.2 above:

 

(a)                                  If the termination is by mutual agreement pursuant to
Clause 8.2(a), then:

 

(i)                                     Stressgen shall pay to Avecia all sums payable for
work completed up to the date of termination but not yet paid, but shall not be
liable for any amounts for any work identified in the Scope Statement, but not
yet initiated; and

 

(ii)                                  Avecia shall assist Stressgen with the transfer of the
Process and all technical information generated during the course of the
Programme to a Third Party designated by Stressgen, at Stressgen’s option and
cost.

 

(b)                                 if Stressgen terminates on notice under Clause 8.2(b),
Stressgen shall pay to Avecia:

 

(i)                                     all sums payable for work completed up to the date of
termination but not yet paid, but shall not be liable for any amounts for any
work identified in the Scope Statement, but not yet initiated;

 

(ii)                                  all reasonable costs incurred by Avecia relating to
the wind-down of the Programme after termination which could not be cancelled
or reasonably avoided; and

 

(iii)                               the Cancellation Fee.

 

(c)                                  if Avecia terminates on notice under Clause 8.2(b),
then:

 

[*] =
Confidential Treatment Request(ed).

 

15

 

(i)                                     Stressgen shall pay to Avecia all sums payable for work
completed up to the date of termination but not yet paid, but shall not be
liable for any amounts for any work identified in the Scope Statement, but not
yet initiated; and

 

(ii)                                  Avecia shall [* *] at the
time of Avecia’s termination.

 

(d)                                 if Avecia terminates for Stressgen’s unremedied breach
or insolvency under Clauses 8.2(c) or (d), then Stressgen shall pay to Avecia:

 

(i)                                     all sums payable for work completed up to the date of
termination but not yet paid, but shall not be liable for any amounts for any
work identified in the Scope Statement, but not yet initiated;

 

(ii)                                  all reasonable costs incurred by Avecia relating to
the wind-down of the Programme after termination which could not be cancelled
or reasonably avoided; and

 

(iii)                               the Cancellation Fee.

 

(e)                                  if Stressgen terminates for delay due to an Avecia
Default under Clause 2.7(c) or for Avecia’s unremedied breach or insolvency
under Clauses 8.2(c) or (d), then:

 

(i)                                     Stressgen shall pay to Avecia all sums payable for
work completed up to the date of termination but not yet paid, but shall not be
liable for any amounts for any work identified in the Scope Statement, but not
yet initiated;

 

(ii)                                  Avecia shall refund to Stressgen any monies paid to
Avecia, less an agreed sum in respect of work done by Avecia and not affected
by the breach, and in the absence of agreement upon such sum the provisions of
Clause 19 shall apply; and

 

(iii)                               Avecia shall [* *]  at the time of Avecia’s termination.

 

9.2                                 Acquired Rights. 
Termination or expiry of this Agreement, for whatever reason, shall not
prejudice the acquired rights of either party, including the right to payment for the
Programme pursuant to Clause 3 (subject to Clause 9.1).

 

9.3                                 Survival.  The
provisions of Clauses 3, 5, 6, 7, 9, 10, 11, 13 - 17 and 19 shall survive the
termination or expiry of this Agreement.

 

10                                  Independent Contractor

 

Nothing
in this Agreement shall create, or be deemed to create, a partnership or the
relationship of principal and agent or employer and employee between the
parties.  Each party agrees to perform
under this Agreement solely as an independent contractor.

 

11                                  Entire Agreement

 

This
Agreement, including the Schedules attached hereto, together with the
Confidentiality Agreement and the Material Transfer Agreement, contains the
entire agreement between the

 

[*] =
Confidential Treatment Request(ed).

 

16

 

parties
and supersedes any previous agreements relating to the Programme and any
understandings between the parties with respect thereto.

 

12                                  Announcements And Publicity

 

Stressgen
and Avecia will jointly discuss and agree in writing on any statement to the
public regarding this Agreement or their business relationship, unless
disclosure is otherwise required by law, regulation or any listing or trading
agreement concerning such parties’ publicly traded securities, as determined in
good faith by the releasing party.  When
a party elects to make a public statement relating to the other party, the
releasing party will give the other party at least five (5) days notice so it
can agree on such statement, except in the event more immediate disclosure is
required pursuant to the securities requirements set forth above, in which case
the releasing party will give the other party as much notice as is practicable.

 

13                                  Assignment and
Subcontracting

 

13.1                           This
Agreement shall be binding upon and inure to the benefit of the parties hereto
and their respective legal successors but shall not otherwise be assignable by
either party, without the prior written consent of the other party, which
consent shall not be unreasonably withheld, provided that either party may
assign this Agreement without consent by notice in writing to the other party
to a purchaser of the whole or part of the business to which this Agreement
relates.

 

13.2                           Avecia shall be
entitled to subcontract certain analytical work under the Programme, subject to
inclusion in such subcontract of confidentiality and intellectual property
provisions no less onerous than those contained herein and provided that Avecia
shall be liable for any acts or omissions of any subcontractor as if such acts
or omissions were Avecia’s own.

 

14                                  Variation

 

No
variation or amendment of this Agreement shall bind either party unless made in
writing in the English language and agreed to in writing by duly authorised
officers of both parties.

 

15                                  Illegality

 

If any
provision of this Agreement is agreed by the parties to be illegal, void or
unenforceable under any law that is applicable hereto or if any court of competent
jurisdiction in a final decision so determines, this Agreement shall continue
in force save that such provision shall be deemed to be excised herefrom with
effect from the date of such agreement or decision or such earlier date as the
parties may agree.

 

16                                  Waiver

 

A
failure by either party hereto to exercise or enforce any rights conferred upon
it by this Agreement shall not be deemed to be a waiver of any such rights or
operate so as to bar the exercise or enforcement thereof at any subsequent time
or times.

 

[*] =
Confidential Treatment Request(ed).

 

17

 

17                                  Notices and Communications

 

17.1                           Formal Notices. 
Any formal notice required or permitted under this Agreement shall be in
writing which may take the form of a letter or facsimile and shall be sent
by prepaid post, facsimile, or hand delivery (including messenger
service).  The addresses for any such
notice or other communication shall be those stated on the first page of this
Agreement.

 

17.2                           Other Communications. 
In addition to the methods set out in Clause 17.1, any other
communications between the parties may be made by telephone or by email.

 

17.3                           Change of Address. 
Any party may, at any time by written notice to the other parties, change
the address or the facsimile numbers to which notices or other communications
shall be sent.  All notices and other communications shall have
been duly given or made (i) when delivered by hand (including by messenger
service) upon delivery or (ii) when delivered by post upon delivery or (iii)
when faxed upon receipt of a legible copy by recipient and production of a
satisfactory transmission report by sender confirming transmission of the fax
in full to the appropriate number by the fax machine which sent the fax.

 

18                                  Force Majeure

 

Neither
party shall be liable to the other party in any manner whatsoever for any
failure or delay in performing its obligations under this Agreement if and to
the extent, and for the duration, that such is due to Force Majeure.  Without prejudice to Clause 8, any said
failure or delay shall not give either party the right to terminate this
Agreement except, and to the extent that such Force Majeure continues for a
period exceeding [* *].  Termination as
a result of Force Majeure shall take effect as if the Agreement had been
terminated by mutual agreement under Clause 8.2(a).  Stressgen shall not be entitled to relief under this Clause 18
for any delay or failure in performing any of its payment obligations under
this Agreement, or in the event of failure of HspE7 in clinical trials or
failure of HspE7 to gain regulatory approval.

 

19                                  Law and Jurisdiction

 

19.1                           Governing Law. 
This Agreement is governed by and shall be construed and interpreted in
accordance with the laws of the State of Delaware.  Any proceedings between the parties shall be conducted in the English
language.

 

19.2                           Reference to Parties’ Senior Representatives.  Prior to any dispute, difference or
disagreement concerning this Agreement proceeding to litigation to arbitration
or through the courts the parties shall seek to resolve the matter within
thirty days by referring it to the Senior Vice-President, Avecia Biotechnology
and the CEO of Stressgen.

 

19.3                           Arbitration. 
Any matter or dispute arising out of or in connection with this
Agreement which is not able to be resolved pursuant to Clause 19.2 shall be finally settled by
commercial arbitration to be held in the State of Delaware.  In appointing arbitrators, the parties shall
consider the appointment of an arbitrator or arbitrators capable of making
decisions on the technical aspects of the Programme.

 

19.4                           Interim Steps. 
Neither of the parties shall be deemed to be precluded from taking such
interim formal steps as may be considered necessary to protect such party’s
position while the procedures referred to in Clauses 19.2 and 19.3 are pursued.

 

[*] =
Confidential Treatment Request(ed).

 

18

 

19.5                           Other Proceedings. 
In the event that the matter or dispute remains unresolved by such
commercial arbitration within thirty days of commencement of such procedure,
then the parties shall be at liberty to take such other proceedings (as defined
below) as they think fit.

 

19.6                           Jurisdiction. 
Except as provided for in Clauses 19.2, 19.3 and 19.4, in relation to
any legal action or proceedings to enforce this Agreement or arising out of in
connection with this Agreement (“proceedings”) each of the parties irrevocably submits
to the exclusive jurisdiction of the Courts of Delaware.

 

[*] =
Confidential Treatment Request(ed).

 

19

 

IN
WITNESS WHEREOF, the authorised representatives of the parties have executed
this Agreement on the date written at the top of this Agreement.

 

For and
on behalf of AVECIA LIMITED

 

 

	
  Signature

  	
  /s/
  Kevin Cox

  	
   

  
	
   

  	
   

  
	
   

  	
   

  
	
  Name

  	
  Kevin
  Cox

  
	
   

  	
   

  
	
   

  	
   

  
	
  Position

  	
  Vice
  President

  

 

 

For and
on behalf of STRESSGEN DEVELOPMENT
CORPORATION

 

 

	
  Signature

  	
  /s/
  Mary Ellen Borque

  	
   

  
	
   

  	
   

  
	
   

  	
   

  
	
  Name

  	
  Mary
  Ellen Borque

  
	
   

  	
   

  
	
   

  	
   

  
	
  Position

  	
  Assistant
  Secretary

  

 

[*] =
Confidential Treatment Request(ed).

 

20

 

Schedule 1

 

Material Transfer Agreement

 

Copy Agreement Attached (4 pages)

 

[*] =
Confidential Treatment Request(ed).

 

21

 

Certain confidential information contained in
this document, marked by brackets, has been omitted and filed separately with
the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
Amended.

 

MATERIAL TRANSFER AGREEMENT

 

THIS MATERIAL TRANSFER AGREEMENT (this
“Agreement”) dated as of January 9, 2004 (the “Effective Date”), is entered
into between Stressgen Biotechnologies, Inc. (“Stressgen”), having a principal
place of business at 10241 Wateridge Circle, Suite C200, San Diego, California
92121 and Avecia Limited, acting through its Avecia Biotechnology (“Avecia”)
(the “Recipient”), having a place of business at business of Hexagon House,
Blackley, Manchester, M9 8ZS, England. 
The parties agree as follows:

 

1.             Stressgen
shall provide the Recipient with the materials described on Exhibit A
and certain information regarding such materials and their use (together with
all progeny, derivatives and parts thereof, collectively, the “Materials”)
solely for the use by the Recipient for the development and manufacturing on
behalf of Stressgen of HspE7 (a recombinant DNA-derived fusion protein
containing (a) a human papilloma virus (HPV) type-16 E7 antigen, antigenic
fragment or conjugate thereof and (b) a bacterial stress protein, including
without limitation, a bacterial stress protein derived from the [* *] heat
shock protein of Mycobacterium bovis var. BCG (Hsp65), where such bacterial
stress protein is [* *] the E7 protein of the HPV type 16), but not for sale,
license or other commercial exploitation of either the Materials or any
progeny, products, cell lines, materials, organisms, derivatives or other
manifestations thereof which are produced or derived by Recipient.

 

2.             The
Recipient hereby acknowledges that, as between Stressgen and the Recipient,
Stressgen is the sole owner or licensee of the Materials.  The Recipient shall use the Materials, and
any information and other materials directly or indirectly derived therefrom,
solely for the limited purpose of performing agreed product development
services on behalf of Stressgen.  The
Recipient shall not use the Materials, or any information or other materials
directly or indirectly derived therefrom, for any other purpose.  The Recipient shall not (and shall not
attempt or purport to) file or prosecute in any country any patent application
which claims or uses or purports to claim or use the Materials or their use,
without the prior express written consent of Stressgen.  THE RECIPIENT UNDERSTANDS THAT MATERIALS ARE
PROVIDED SOLELY FOR CERTAIN RESEARCH USE ONLY AND HAVE NOT BEEN APPROVED FOR
HUMAN USE.  THE RECIPIENT SHALL NOT
ADMINISTER THE MATERIALS TO HUMANS IN ANY MANNER OR FORM.

 

3.             The
Recipient shall not transfer the Materials, or any information or other
materials directly or indirectly derived therefrom, to any third party without
the prior express written consent of Stressgen.  The Recipient shall limit transfer and disclosure of the Materials,
and any information or other materials directly or indirectly derived
therefrom, on a need to know basis, as reasonably necessary, to its directors,
officers and employees who are bound by written agreements with the Recipient
to hold in confidence and not to make use of the Materials, and such
information and other materials, for any purpose other than those permitted by
this Agreement.  The Recipient shall
notify Stressgen promptly upon discovery of any unauthorized use or disclosure
thereof.  Promptly after the request of
Stressgen, the Recipient promptly shall return all remaining Materials to
Stressgen.

 

[*]
= CONFIDENTIAL TREATMENT REQUEST(ED).

 

1

 

4.             If
the Recipient’s use of the Materials results in any invention, discovery or
derivative cell bank that is derived directly or indirectly from the Materials,
such invention or discovery shall be owned solely by Stressgen.  The Recipient shall promptly disclose each
such invention or discovery to Stressgen. 
The Recipient hereby assigns to Stressgen all right, title and interest
in all such inventions and discoveries and all intellectual property rights
therein. The Recipient shall not (and shall not attempt or purport to) file or
prosecute in any country any patent application which claims or uses or
purports to claim or use any invention or discovery that is derived directly or
indirectly from the Materials or their use, without the prior express written
consent of Stressgen.

 

5.             The
Recipient hereby acknowledges that the Materials are experimental in nature and
that it is provided “AS IS.”  STRESSGEN
MAKES NO REPRESENTATIONS OR WARRANTIES, EXPRESS OR IMPLIED, WITH RESPECT TO THE
MATERIALS OR THE USE THEREOF.  STRESSGEN
DISCLAIMS ALL IMPLIED WARRANTIES, INCLUDING WITHOUT LIMITATION ANY WARRANTY OF
MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE OR NONINFRINGEMENT.

 

6.             The
Recipient shall comply with all laws and governmental rules, regulations and
guidelines which are applicable to the Materials or the use thereof, including
biosafety procedures, and with any safety precautions accompanying the
Materials.

 

7.             This
Agreement shall not be construed to grant any license or other rights to the
Recipient in any patent rights or other intellectual property rights of
Stressgen.

 

8.             This
Agreement shall be binding upon and inure to the benefit of the parties hereto
and their respective legal successors but shall not otherwise be assignable by
either party, without the prior written consent of the other party, which
consent shall not be unreasonably withheld, provided that either party may
assign this Agreement without consent by notice in writing to the other party
to a purchaser of the whole or part of the business to which this Agreement
relates.

 

9.             This
Agreement and the Confidentiality Agreement between Stressgen Biotechnologies
Corporation (the parent of Stressgen) and the Recipient dated July 18, 2002
represent the entire agreement between the parties regarding the subject matter
hereof and shall supersede all previous communications, representations,
understandings and agreements, whether oral or written, by or between the
parties with respect to the subject matter hereof.  The Recipient acknowledges that the Materials constitute
Confidential Information under the Confidentiality Agreement.

 

10.           No
change, modification, extension, termination or waiver of this Agreement, or
any of the provisions herein contained, shall be valid unless made in writing
and signed by duly authorized representatives of the parties.

 

11.           This
Agreement shall be governed by and construed in accordance with the laws of the
State of Delaware, without regard to the conflicts of law principles thereof.

 

[*]
= CONFIDENTIAL TREATMENT REQUEST(ED).

 

2

 

IN WITNESS WHEREOF, the parties have entered
into this Agreement as of the date first written above.

 

	
   

  	
  STRESSGEN BIOTECHNOLOGIES, INC.

  
	
   

  	
   

  
	
   

  	
  By:

  	
  /s/ Marvin Siegel

  	
   

  
	
   

  	
   

  	
   

  
	
   

  	
  Title:

  	
  Executive V.P. Research & Development

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  1/12/04

  	
   

  
	
   

  	
   

  
	
   

  	
   

  
	
   

  	
  AVECIA LIMITED

  
	
   

  	
   

  
	
   

  	
  By:

  	
  /s/ S.C. Taylor

  	
   

  
	
   

  	
   

  	
   

  
	
   

  	
  Title:

  	
  Business General Manager

  	
   

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  9 January 2004

  	
   

  

 

[*]
= CONFIDENTIAL TREATMENT REQUEST(ED).

 

3

 

EXHIBIT A

 

Materials

 

Master Cell Bank vials for SGN-00101 (HspE7)

 

Working Cell Bank vials for SGN-00101 (HspE7)

 

Vials of SGN-00101 Drug Product produced by “Process A” (For research
purpose only – not for human use).

 

Vials of SGN-00101 Drug Product produced by “Process B” (For research
purpose only – not for human use).

 

Samples of SGN-00101 Drug Substance produced by “Process A” (For
research purpose only – not for human use).

 

Samples of SGN-00101 Drug Substance produced by “Process B”  (For research purpose only – not for human
use).

 

Samples of SGN-00101 Drug Substance produced by “Roche Process” (For
research purpose only – not for human use).

 

Samples of fermentation cell pastes containing SGN-00101 (For research
purpose only – not for human use).

 

Vials of [* *] cells

 

Anti HspE7 antisera

 

Anti-Hsp65 antisera

 

Anti-E7 antisera

 

[*]
= CONFIDENTIAL TREATMENT REQUEST(ED).

 

4

 

Schedule 2

 

The Cancellation Fee

 

The
Cancellation Fee shall be as follows:

 

(i)                                     If
Stressgen gives notice of its intention to cancel or delay the GMP manufacture
of API [* *] before the date specified in the Programme Timeline, Stressgen
shall pay to Avecia [* *].

 

(ii)                                  If Stressgen gives notice of its intention to cancel or delay the GMP
manufacture of API [* *] before the date specified in the Programme Timeline, Stressgen
shall pay to Avecia an amount determined by reference to the table below:

 

	
  Period of notice

  	
   

  	
  [* *] fee payable for GMP manufacture for the

  relevant year set out in Schedule 9

  
	
  Less than [* *] but more than [* *]

  	
   

  	
  [* *]

  
	
  Less than [* *] but more than [* *]

  	
   

  	
  [* *]

  
	
  Less than [* *] but more than [* *]

  	
   

  	
  [* *]

  
	
  Less than [* *] but more than [* *]

  	
   

  	
  [* *]

  
	
  Less than [* *] but more than [* *]

  	
   

  	
  [* *]

  
	
  Less than [* *]

  	
   

  	
  [* *]

  

 

If
Stressgen gives notice of its intention to cancel or delay the GMP manufacture
of API due to take place [* *] at any time prior to [* *], then the
Cancellation Fee payable in respect of such delayed GMP manufacture shall be [*
*].

 

Avecia
shall [* *] but for the termination of the Agreement by Stressgen under Clause
9.1(b) or Avecia under Clauses 9.1(c) or (d), or exercise of Stressgen’s option to delay the commencement of
the initiation of [* *] in the Scope Statement pursuant to Clause
2.8.  Avecia shall [* *] up to [*
*].  In this context, [* *] but shall
not mean [* *] work.

 

[*]
= CONFIDENTIAL TREATMENT REQUEST(ED).

 

 

Schedule 3

 

Programme Amendment Order

 

	
  (1)           Project
  Title & Number

  	
  (2)           Date
  Project Started

  	
  (3)           P.A.O.
  Number

  
	
   

  	
   

  	
   

  
	
  (4)           Reason
  for P.A.O.

   

   

   

  
	
  (5)           Amendment
  required and new milestones

   

   

   

  
	
  (6)           Impact
  on price, time frame, resources

   

   

   

  
	
  (7)           Amended
  payment schedule (if required)

   

   

   

  
	
  Authorisation

   

   

   

  
	
   

  	
   

  	
   

  	
   

  
	
  for
  Avecia

  	
  for
  customer

  
						

 

[*]
= CONFIDENTIAL TREATMENT REQUEST(ED).

 

 

Schedule 4

 

Programme
Management Plan

 

     Program Management
Plan for the Process Development, Validation and cGMP manufacture of Drug
substance    (HspE7)intended for Pivotal Clinical Studies and
Launched Drug Product.

 

Avecia and
Stressgen will jointly develop and maintain a Program Management Plan.  The plan will include the composition and
responsibilities of a Steering committee, Program management team and a
technical project team.

 

This document
outlines the process by which this program will be managed.

 

Project Steering Team

 

Composition: Will consist of members from Avecia and from
Stressgen.

 

Frequency: Meets monthly or as required, making use of
teleconf or videoconf facilities as appropriate.

 

Responsibilities:

 

•                  Resolve issues that cannot be
resolved by the program management team

•                  Authorize completion of milestones

 

Program Management Team

 

Composition: Avecia team consisting of representatives of
all the major functions involved in the delivery of the overall program,
Program Man, Process Development, Quality Assurance, Quality Control,
Manufacturing Technology, Manufacturing operations, Supply Chain (when
appropriate), Commercial and Finance.

 

Frequency:  Meets
weekly or as appropriate.

 

Outputs:

 

•                  Minutes

•                  Actions lists

•                  Program Risk Registers

•                  Updated Project plans and progress
data.

•                  Monthly status update

 

Responsibilities:

 

•                  Manages the overall shape and
delivery of the program

•                  Co-ordinates the activities of the
various contributing individuals and functions.

•                  Informs customer and steering team as
to progress and issues.

 

[*]
= CONFIDENTIAL TREATMENT REQUEST(ED).

 

 

Technical Project Team

 

Composition: Team of technical scientists with particular
skills in the area of fermentation, down stream processing and analytical
development.

 

Frequency:  Meets
fortnightly

 

Outputs:

 

•                  Minutes

•                  Data summaries

•                  Technical plans and reports

•                  Sample registers.

 

Responsibilities:

 

•                  Detailed planning of technical
program

•                  Delivery of technical program

•                  Supervision and overview of project
tasks and technical program

 

 

Responsible
Persons

 

The following
tables list the responsible individuals and their roles within Stressgen and
within Avecia. These nominated individuals may be changed in the light of
changing circumstances. In this eventuality details of the new contact persons
will be provided to the other party.

 

Stressgen
Representatives

 

	
  Name

  	
   

  	
  Function

  	
   

  	
  Role

  	
   

  	
  Phone

  	
   

  	
  e-mail

  
	
  [* *]

  	
   

  	
  Executive Sponsor

  	
   

  	
  Approvals

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  
	
  [* *]

  	
   

  	
  Project Leader

  	
   

  	
  Tech. Expert

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  
	
  [* *]

  	
   

  	
  Quality Leader

  	
   

  	
  QA

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  
	
  [* *]

  	
   

  	
  Project Manager

  	
   

  	
  Communication and contracts

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  
	
  [* *]

  	
   

  	
  Controller

  	
   

  	
  Invoicing

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  
	
  [* *]

  	
   

  	
  Biological testing

  	
   

  	
  Biological testing

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  

 

[*]
= CONFIDENTIAL TREATMENT REQUEST(ED).

 

 

Avecia Representatives

 

	
  Name

  	
   

  	
  Function

  	
   

  	
  Role

  	
   

  	
  Phone

  	
   

  	
  e-mail

  
	
  [* *]

  	
   

  	
  General Manager

  	
   

  	
  Approvals

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  
	
  [* *]

  	
   

  	
  R&D Manager

  	
   

  	
  Technical review

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  
	
  [* *]

  	
   

  	
  Quality

  	
   

  	
  Quality Compliance

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  [* *]

  	
   

  	
  R&D

  	
   

  	
  Tech Project Leader

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  
	
  [* *]

  	
   

  	
  Program Manager

  	
   

  	
  Planning, communication

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  
	
  [* *]

  	
   

  	
  QA

  	
   

  	
  QA compliance

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  
	
  [* *]

  	
   

  	
  QC

  	
   

  	
  Product testing and protocols

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  
	
  [* *]

  	
   

  	
  Analytical Development

  	
   

  	
  Analytical methods.

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  
	
  [* *]

  	
   

  	
  MTG

  	
   

  	
  Tech transfer to plant

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  
	
  [* *]

  	
   

  	
  Operations

  	
   

  	
  CGMP Manufacture of product

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  
	
  [* *]

  	
   

  	
  Finance

  	
   

  	
  Finance control and invoicing

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  
	
  [* *]

  	
   

  	
  Commercial

  	
   

  	
  Account Manager

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  

 

[*]
= CONFIDENTIAL TREATMENT REQUEST(ED).

 

 

SCHEDULE 5

 

PROGRAMME TIMELINE

 

	
  Scope

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  6

  	
   

  	
  Tech Transfer

  	
   

  	
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  7

  	
   

  	
  Feasibility

  	
   

  	
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  8

  	
   

  	
  [* *] development

  	
   

  	
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  8.3.2.4

  	
   

  	
  [* *] HspE7

  [* *]

  	
   

  	
  [*]

  	
   

  	
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  8.5.2.5.

  	
   

  	
  [* *] report comparing HspE7 with

  [* *]

  	
   

  	
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  9.1

  	
   

  	
  GMP pre-production

  	
   

  	
  [*]

  	
   

  	
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  9.2

  	
   

  	
  GMP fermentation production

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  	
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  9.2.2.8

  	
   

  	
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  9.3

  	
   

  	
  API batches — Pivotal Clinical supply

  	
   

  	
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  9.4

  	
   

  	
  GMP Drug substance characterization report

  	
   

  	
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  10.1

  	
   

  	
  Validation Master Plan

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [*]

  	
   

  	
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  10.1.2.1

  	
   

  	
  Laboratory Performance Characterisation study

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  	
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  10.2

  	
   

  	
  Analytical Method Validation

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [*]

  	
   

  	
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  10.3

  	
   

  	
  API Validation Batch Pre-production

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  	
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  10.4/10.5

  	
   

  	
  Fermentation and API Validation Batches

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  	
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  10.5.2.5

  	
   

  	
  Fermentation/ API Validation batches release

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [*]

  	
   

  	
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  10.5.2.3

  	
   

  	
  Validation reports

  	
   

  	
   

  	
   

  	
   

  	
   

  	
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  11.1

  	
   

  	
  IND amendment

  	
   

  	
   

  	
   

  	
   

  	
   

  	
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[*]
– CONFIDENTIAL TREATMENT REQUEST(ED).

 

 

	
  11.3

  	
   

  	
  Mock audits

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [*]

  	
   

  	
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  11.4

  	
   

  	
  Pre-Approval Inspection Support

  	
   

  	
   

  	
   

  	
   

  	
   

  	
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[*]
= CONFIDENTIAL TREATMENT REQUEST(ED).

 

 

	
   

  	
  Schedule 6

  	
   

  
	
   

  	
   

  	
   

  
	
  [Stressgen logo]

  	
  Stressgen

  BIOTECHNOLOGIES

  	
  PO#

  PAD0071

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  This
  number must appear on all packages invoices & correspondence

  
	
   

  	
   

  	
   

  
	
  SUPPLIER
  NAME AND ADDRESS:

  

  Avecia Limited

  PO Box 43

  Hexagon House

  Blackley, Manchester M9 972

  England

  Fax #: [* *]

  Phone #: [* *]

  Acct #:  302 477-8275

  Vendor #: 302-477-8102

  	
  SHIP
  TO:

  

  Stressgen Biotechnologies Inc.

  409 2nd Avenue Suite 201

  Collegeville, PA  19426

  Attn:  PO# PAD0071

  Phone:  [* *]  Fax: [* *]

  INVOICE
  TO:

  Stressgen Biotechnologies Inc.

  10241 Wateridge Circle Suite C200

  San Diego, CA 92121

  Attn:  PO# PAD0071

  Phone:  (858) 202-4900  Fax: [* *]

  	
  For Internal
  Use Only:

  Name of employee submitting PO:

  [* *]

  
	
  To
  be invoiced:

  	
  o

  
	
  Cheque
  required:

  	
  o

  
	
  • Return to User

  	
  o

  
	
  • Mail with application

  	
  o

  
	
  • Fed Ex             

  	
  o

  
	
  • by Purchasing Dept

  	
  o

  
	
  • by User

  	
  o

  
	
   

  
	
   

  

 

COMMENTS

 

	
  DATE
  ORDERED

  	
   

  	
  DATE
  REQUIRED

  	
   

  	
  ESTIMATED
  ARRIVAL DATE

  	
   

  	
  TAX
  I.D. NO.

  	
   

  	
  TERMS

  
	
  December
  18, 2003

  	
   

  	
  ASAP

  	
   

  	
   

  	
   

  	
  124387457

  	
   

  	
  —

  
	
  SHIPPED
  VIA:

  	
   

  	
  CURRENCY:  USD

  	
   

  	
  PPD.   ̈

  	
   

  	
  COLL.   ̈

  
	
  ACCT CODE

  	
   

  	
  USER

  	
   

  	
  QTY

  	
   

  	
  CAT#

  	
   

  	
  DESCRIPTION

  	
   

  	
  UNIT PRICE

  	
   

  	
  AMOUNT

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  420-5640

  	
   

  	
  LBOUK

  	
   

  	
  1

  	
   

  	
  Manufacturing

  	
   

  	
  1.  Avecia Limited (“Avecia”) and Stressgen
  Biotechnologies Inc. (“Stressgen”) agree to negotiate in good faith for an
  agreement to cover certain work to be carried out by Avecia on behalf of
  Stressgen, with the aim of executing such agreement by 23rd January 2004.

  	
   

  	
  $

  	
  [*
  *]

  	
   

  	
  $

  	
  [*
  *]

  
	
  —

  	
   

  	
  —

  	
   

  	
  —

  	
   

  	
  —

  	
   

  	
  2.
  Certain work (set out below) will be commenced prior to execution of the
  equipment following acceptance of this purchase order:

  	
   

  	
  —

  	
   

  	
  $

  	
  —

  
	
  —

  	
   

  	
  —

  	
   

  	
  —

  	
   

  	
  —

  	
   

  	
  (i)
  Transfer of information and materials to allow the project to start.  This will include proceeds and safety
  details, available standards, reagents and assay methodology.

  	
   

  	
  —

  	
   

  	
  $

  	
  —

  
	
  —

  	
   

  	
  —

  	
   

  	
  —

  	
   

  	
  —

  	
   

  	
  (ii)
  Agreed definition of the process to be operated to demonstrate Avecia [* *]

  	
   

  	
  —

  	
   

  	
  $

  	
  —

  
	
  —

  	
   

  	
  —

  	
   

  	
  —

  	
   

  	
  —

  	
   

  	
  (iii)
  Establish as a minimum, a priority list of assays at Avecia and establish
  other assays as time permits.

  	
   

  	
  —

  	
   

  	
  $

  	
  —

  
	
  —

  	
   

  	
  —

  	
   

  	
  —

  	
   

  	
  —

  	
   

  	
  (iv)
  Operation of the agreed process at laboratory scale and assay for the product
  to establish activity.

  	
   

  	
  —

  	
   

  	
  $

  	
  —

  
	
  —

  	
   

  	
  —

  	
   

  	
  —

  	
   

  	
  —

  	
   

  	
  In
  consideration for Avecia carrying out the technical consultancy work detailed
  above, Stressgen shall pay to Avecia on acceptance of this purchase order the
  sum of US$[* *], being an amount equal to the technology transfer fee.

  	
   

  	
  —

  	
   

  	
  $

  	
  —

  
	
  —

  	
   

  	
  —

  	
   

  	
  —

  	
   

  	
  —

  	
   

  	
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  $

  	
  —

  
	
  —

  	
   

  	
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  —

  	
   

  	
  —

  	
   

  	
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  $

  	
  —

  
	 
	
  CONDITIONS OF PURCHASE ORDER. 
  THIS 

  	
   

  	
   

  	
   

  	
  SUB TOTAL

  	
   

  	
  $

  	
  [* *]

  
	 
	
  ORDER IS SUBJECT TO ALL OF THE TERMS 

  	
   

  	
   

  	
   

  	
  SHIPPING

  	
   

  	
  $

  	
  0.00

  
	 
	
  AND CONDITIONS STATED ON BOTH PAGES 

  	
   

  	
   

  	
   

  	
  DUTIES/TAXES

  	
   

  	
  $

  	
  0.00

  
	 
	
  OF THIS ORDER FORM.  IF ANY
  TERMS 

  	
   

  	
   

  	
   

  	
  Sales Tax

  	
   

  	
   

  	
   

  
	 
	
  CONTAINED IN SUPPLIER’S ACCEPTANCE OF THIS ORDER OR THE SUPPLIER’S
  INVOICES ARE AT VARIANCE WITH THE TERMS OF THIS ORDER, THIS ORDER SHALL
  GOVERN NO ORAL AGREEMENT OR OTHER UNDERSTANDING SHALL IN ANY WAY MODIFY OR
  CHANGE THE TERMS OF THIS ORDER UNLESS AGREED TO IN 

  	
   

  	
  /s/ D.L.
  Korpolinski

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	 
	
  WRITING AND SIGNED BY STRESSGEN

  	
   

  	
  AUTHORIZED BY

  	
   

  	
  TOTAL

  	
   

  	
  $

  	
  [* *]

  
																	

 

 

[*]
= CONFIDENTIAL TREATMENT REQUEST(ED).

 

 

Certain confidential information contained in
this document, marked by brackets, has been omitted and filed separately with
the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
Amended.

 

Schedule 7

 

QUALITY
AGREEMENT

 

 

Avecia Biotechnology

Biologics Business

Billingham

UK

 

And

 

Stressgen Development Corporation

 

 

	
  Approved by:-

  	
  Approved by:-

  
	
   

  	
   

  
	
   

  	
   

  
	
  /s/ H. Holden

  	
   

  	
  /s/ K. Neurohr

  	
   

  
	
  H. Holden

  	
  K. Neurohr

  
	
  Vice President

  	
  Head of Quality and Regulatory Affairs

  
	
  Regulatory Affairs and Compliance

  	
  Avecia Biologics Business

  
	
  Stressgen Biotechnologies Inc

  	
  19 January 2004

  
	
  19 January 2004

  	
   

  
				

 

 

[*]
= CONFIDENTIAL TREATMENT REQUEST(ED).

 

 

Index

 

	
  1.

  	
   

  	
  Quality Agreement

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  2.

  	
   

  	
  Manufacturing cGMP Compliance

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  3.

  	
   

  	
  Quality Control

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  4.

  	
   

  	
  Stability

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  5.

  	
   

  	
  Quality Assurance

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  6.

  	
   

  	
  Dispute Resolution

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  7.

  	
   

  	
  Validation

  	
   

  

 

	
  Appendix I

  	
  -

  	
  Responsibilities

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  Appendix II

  	
  -

  	
  List of Contacts

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  Appendix III

  	
  -

  	
  Glossary of Terms

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  Appendix IV

  	
  -

  	
  List of Jointly Approved Documents

  	
   

  

 

[*]
= CONFIDENTIAL TREATMENT REQUEST(ED).

 

1

 

1.                                     Quality Agreement

 

1.1                                 Purpose

 

1.1.1                        This agreement
defines the roles and responsibilities for both Avecia and Stressgen QA

1.1.2
                     This agreement
also defines how Avecia Quality Unit and Stressgen  Quality Unit will interact with each other over Quality related
issues

1.1.3
                     This agreement
shall be incorporated with and constitute a part of the  Biological Service Agreement (BSA) between the two companies.

1.1.4                        This Quality
Agreement between Stressgen and Avecia defines Quality Responsibilities as they
are related to the manufacturing of the Stressgen Active Pharmaceutical Ingredient
(API) in accordance with the terms of the BSA to be entered into between the
two parties.  It is the intention of the
parties that the Quality Agreement is read in conjunction with the BSA.

 

1.2                               Duration of Agreement

 

1.2.1                      The agreement will be effective
as of the Effective Dates of the BSA and will expire with the termination of
the BSA.

 

1.3
                             Product

 

1.3.1                      Avecia will manufacture a [*
*] Biologic API in accordance with cGMP regulations.

 

1.4                               Regulatory Compliance

 

1.4.1                    Avecia will manufacture the API in compliance
with [* *].

 

1.4.2                      Avecia will manufacture the
API’s in compliance with [* *].

 

2.                                     Manufacturing cGMP
Compliance

 

2.1
                             Materials

 

2.1.1                     Avecia will use raw
materials, packaging and labelling components that are acceptable to Stressgen
QA and sampled, tested via validated methods and stored in accordance with
Avecia documentation and procedures.

 

2.1.2                     Avecia QC and Stressgen QA
will jointly approve the key tests to be performed for incoming raw materials
packaging and labelling.

 

2.1.3                       Avecia is responsible for
ensuring that all materials procured by Avecia for use in the API are in
compliance with pre-determined specifications. 
Raw materials are given an expiration date upon the satisfactory completion
of all initial tests.  Avecia will hold
the relevant Certificates of Analysis for the materials.

 

[*]
= CONFIDENTIAL TREATMENT REQUEST(ED).

 

2

 

2.1.4                       Avecia QA will inform
Stressgen QA of any non-conforming raw materials within [* *].

 

2.1.5        Avecia
will only purchase raw materials from Avecia approved suppliers.

 

2.2
                             Documentation

 

2.2.1                       Avecia will prepare the
necessary documentation for each lot of API in its standard format as evidence
that the API was manufactured in compliance with current GMP.

 

2.2.2                       Avecia will retain batch
documentation for at least [* *] after the expiry date of the batch or for [*
*] after the distribution of the batch whichever is the longer.  Avecia will give advanced warning of [* *]
to Stressgen QA prior to destruction.

 

2.2.3                     Avecia will store the API
under conditions approved by Stressgen QA. 
Avecia will hold records of storage conditions according to the Avecia
Standard Procedure.

 

2.2.4                     Avecia and Stressgen QA will
agree storage conditions, containers and delivery configuration.  Avecia is responsible for packaging, and
labelling; Avecia will co-operate with Stressgen QA for transit arrangements.

 

2.2.5                       Delivery of API -  Stressgen QA will authorise Avecia to
deliver upon submission of a Stressgen QA delivery request form.  Only released, finished API will be
delivered by Avecia to a location designated by Stressgen QA.  The same applies to any samples requested by
Stressgen QA.  Delivery records etc will
be documented in a Dispatch Batch Record.

 

2.2.6                       Avecia will deliver samples
upon the submission of a Stressgen QA sample request form and Avecia will
co-operate with Stressgen QA for transit arrangements.

 

2.2.7        Avecia
will upon request deliver samples ahead of QA batch release.

 

3.                                     Quality Control

 

3.1                               The testing activities for
the API that are to be performed by Avecia QC will be in accordance with the
specifications defined in the QC Document. 
Avecia QA/QC and Stressgen QA will jointly approve both test methods and
specifications.  Stressgen is responsible
for the specification from safety or regulatory suitability perspectives and
Avecia is responsible for the specification from a technical feasibility
perspective.  Avecia will not sub
contract any testing without prior approval to Stressgen QA.  All sub contractors analytical laboratories
will be audited by Avecia.

 

3.2                                 Avecia will notify Stressgen
QA of any investigations and OOS results related to the in process testing and
final testing of the API within [* *].

 

3.3                               Avecia QC will retain sufficient
samples of raw materials and the API from each batch to permit at least [* *]
specification analysis excluding [* *].

 

[*]
= CONFIDENTIAL TREATMENT REQUEST(ED).

 

3

 

3.4                                 Avecia QC will retain
samples for at least [* *] after the expiration date of the last lot of drug
product containing the API.  Stressgen
QA will inform Avecia of this date and give advanced warning of expiration of
[* *].

 

3.5                                 Avecia QA/QC and Stressgen
QA will (if required) agree an abbreviated Certificate of Analysis to allow
delivery.  These key tests will cover
Identity, Purity and Safety.

 

3.6                                 Avecia QC will produce a
Certificate of Analysis for each batch of API confirming that the API has been
tested via validated methods in accordance with the Specification in the
jointly approved QC document.

 

4.                                     Stability

 

4.1                                 Avecia QA/QC and Stressgen
QA, where appropriate, are jointly responsible to ensure that a routine
stability monitoring programme is implemented.

 

4.2                                 Avecia will provide
Stressgen QA with stability samples within [* *] of the manufacture.

 

5.                                     Quality Assurance

 

5.1                                 Documentation

 

5.1.1                      Avecia QA are responsible
for ensuring creation of the Stressgen API specific manufacturing master
documentation.  Avecia QA and Stressgen
QA will approve the batch documentation before commencement of manufacturing.

 

5.1.2                      Avecia QA will approve
Standard Procedures required for the manufacture of the API.

 

5.1.3                      Avecia QA will inform
Stressgen QA of any critical/major deviations generated during the manufacture
of each batch of API within [* *].

 

5.1.4                      Avecia QA will inform
Stressgen QA of any critical/major changes to the master batch records, bills
of materials specification and equipment.

 

5.2                                 Batch Disposition

 

5.2.1                        For each batch of API Avecia
QA will provide to Stressgen QA copies of the release, executed batch record,
Certificate of Analysis, Certificate of Conformance, any deviation/change
control reports, and copies of supporting Analytical Raw Data.

 

5.2.2                      Avecia QA is responsible for
ensuring that the API has been manufactured according to the Specifications,
Procedures and Master Batch Records and cGMP.

 

5.2.3                      The release of the API for
delivery to Stressgen is the responsibility of Avecia QA.

 

[*]
= CONFIDENTIAL TREATMENT REQUEST(ED).

 

4

 

5.2.4                      It is the responsibility of
Avecia QA Manager in conjunction with Stressgen QA to review and decide on the
disposition of potentially Non Conforming Materials.

 

5.2.5                      Avecia QA will carry out a
Product Quality Review at the end of each campaign of manufacture and indicate
the findings to Stressgen QA in a summary report.

 

5.3                                 Reprocess/Rework

 

5.3.1                      Avecia QA will not
internally authorise any rework/reprocessing without written prior approval
from Stressgen QA.

 

5.4                                 Internal Audits

 

5.4.1                      Avecia QA will carry out
routine internal audits for GMP compliance according to approved schedules
developed as part of the Avecia Quality System.  Avecia QA will inform Stressgen QA of any major observations that
may impact the Stressgen Process.

 

5.5                                 Audits by the Customer

 

5.5.1                      Avecia will allow one audit
for a maximum of two representatives from Stressgen QA to have access for a
maximum of [* *] to Avecia’s facilities associated with the manufacturing and
testing of Stressgen QA API.  Avecia
require [* *] prior notice of a Stressgen QA audit.

 

5.5.2                       Avecia will permit Stressgen
QA to conduct audits to address significant API Quality or Safety issues as
discovered through API failures or complaints related to Avecia manufacturing
of the API.  Avecia will require prior
notice of [* *] from Stressgen QA.

 

5.5.3                       Avecia will provide
Stressgen with a response to audit observations with [* *] after an audit.  Avecia will provide Stressgen with a plan
for resolution of audit findings within [* *] after the audit.  The plan shall be mutually agreed by both
parties.  Avecia will provide [* *]
updates to Stressgen on the status of the other observations until they are
resolved.

 

5.6                                 Customer Technical Support

 

Avecia
and Stressgen will jointly agree the availability on site of Stressgen
Technical Support and Quality Personnel. 
Stressgen Personnel (1) will be allowed by exception access to clean
rooms for a major quality and/or process issue.

 

5.7                                 Regulatory Actions

 

5.7.1                      Avecia QA will provide
Stressgen QA information and support for any Stressgen QA regulatory submission
(eg CMC) upon request. Stressgen QA will supply Avecia with copies of the
submitted information.

 

[*]
= CONFIDENTIAL TREATMENT REQUEST(ED).

 

5

 

5.7.2                      Stressgen QA will inform
Avecia QA of any pertinent changes in the CMC section of its regulatory
document.

 

5.7.3                      Avecia QA will inform
Stressgen QA of any change that may impact Stressgen QA regulatory submissions.
Stressgen QA will provide written prior approval of the change within [* *].

 

5.7.4                      Avecia QA will provide
Stressgen QA of advanced notice of any FDA/MHRA regulatory Inspection.

 

5.7.5                      Avecia will notify Stressgen
within [* *] of the notification of an inspection or within [* *] of an
unannounced arrival of a health authority investigator, of any inspections or
actions by regulatory agencies or other enforcement bodies which could
potentially impact Stressgen API

 

5.7.6                      Avecia QA will inform
Stressgen of any observations (from a Regulatory Inspection) that may affect
the Stressgen Process.

 

5.7.7                      PAI Activities: Avecia will
cooperate with Stressgen in preparing for pre-approval inspections (PAI) by
health authorities.  This includes PAI
preparation and mock PAI.  Stressgen
will perform mock PAI.  Avecia will take
the lead during PAI by health authorities and Stressgen will be on site to
provide support.

 

6.                                     Dispute Resolution

 

In
the event that a dispute arises between Avecia and Stressgen QA relating to
conformity of a batch of API with cGMP or with the specifications defined in
the Commercial Contract, such dispute shall be resolved in the following
manner.  The parties’ Quality Units
shall promptly discuss the dispute in good faith to attempt to reach agreement
on whether there has been a non-conformity in the batch of API and, if so, what
course of action shall be taken to address it. 
In the event that the parties’ Quality Units fail to reach such agreement,
the matter shall be referred to an independent expert nominated by agreement of
the parties and both parties will abide by the decision of the independent QA
expert. Such referral shall be solely for the purpose of establishing whether
or not there is any non-conformity in the batch of API.  The decision of such independent expert
shall be binding upon the parties.

 

7.                                     Validation

 

Avecia
and Stressgen QA will jointly agree the Validation Master Plan.

 

7.1                                 Equipment Computer Facility
and Utility Qualification

 

7.1.1                       Avecia is responsible for
ensuring that equipment, computer, facility, utility and support system for the
manufacture of Stressgen API are qualified according to regulatory
requirements.

 

[*]
= CONFIDENTIAL TREATMENT REQUEST(ED).

 

6

 

7.2                                 Laboratory Qualification

 

7.2.1                       Avecia is responsible for
ensuring that all QC laboratories are in compliance with cGMP’s and are
qualified in all of the methodology associated with Stressgen API.

 

7.2.2                       Avecia and Stressgen QA will
agree responsibility for Validation Methodology.  Validation methodology will be developed in compliance with ICH
Q2A test on Validation of Analytical Procedures and ICH Q2B Validation of
Analytical Procedures.  If Stressgen QA
provide Avecia with validated method then Avecia will only need to verify the
methods.

 

7.3                                 Cleaning
Verification/Validation

 

7.3.1                      Avecia is responsible for
ensuring that adequate cleaning verification of product contact parts used in
the manufacture of Stressgen QA API is carried out between batches of different
products to prevent cross-contamination.

 

7.3.2                       Stressgen QA will provide
information (solubility, toxicity, dose etc.) to establish cleaning limits.

 

7.4                                 Process Validation

 

Avecia and Stressgen QA will agree the Process
Validation Strategy.

 

7.4.1                       When required, Avecia is
responsible for ensuring that the manufacturing process is validated.  The validation should ensure that the
process is capable of consistently achieving the API acceptance specification.
Avecia will provide adequate resources to execute process validations as per
mutually approved protocols.

 

[*]
= CONFIDENTIAL TREATMENT REQUEST(ED).

 

7

 

Appendix I  -  Responsibilities

 

	
  Responsibility

  	
   

  	
  Avecia

  	
   

  	
  Stressgen
  QA

  	
   

  
	
  Master Batch Record Approval

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  
	
  Formula

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  
	
  Production Method

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  
	
  Scale-up Procedure

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  
	
  Validation Procedures

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  
	
  Stability Programme

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  
	
  Raw Material Selection/Review

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  
	
  Documentation for TSE risk

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  
	
  Specific Product Information (safety,
  transport etc)

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  
	
  Product Delivery

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  
	
  API Storage

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  
	
  API Specification – Technical Feasibility

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  
	
  API Specification – Safety and Regulatory

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  
	
  Method of Analysis

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  
	
  Method of Analysis Validation

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  
	
  Analysis + Release

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  
	
  Storage of API QC Samples

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  
	
  Stability Programme

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  
	
  Manufacture of API

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  
	
  Batch Number Assignment

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  
	
  Expiry Date Assignment

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  
	
  Manufacturing Documentation

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  
	
  In Process Controls

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  
	
  Expiry Date Assignment

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  
	
  Audit of API Manufacturer

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  
	
  Deviation Management

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  
	
  Change Management

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  
	
  Retention of Records

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  
	
  Validation Master Plan Approval

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  
	
  API Release to Stressgen QA

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  
	
  Stressgen QA API Release to Fill Finish

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  

 

[*]
= CONFIDENTIAL TREATMENT REQUEST(ED).

 

8

 

Appendix II - List of
Contacts

 

	
  Area of Responsibility

  	
   

  	
  AVECIA

  Main Fax:

  [* *]

  	
   

  	
  Stressgen
  QA

  Main Fax:

  	
   

  
	
  QA

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  
	
  QC

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  
	
  Regulatory Manager

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  

 

[*]
= CONFIDENTIAL TREATMENT REQUEST(ED).

 

9

 

Appendix
III - Glossary of Terms

 

Critical
Deviation

 

A
departure from an approved instruction or established standard that will have a
direct impact on product quality.

 

Major
Deviation

A
departure from an approved instruction or established standard that has a
potential to impact on product quality.

 

Validation
Master Plan

A
high level document to summarise the key elements of the validation programme
for a Customer Project.

 

Master
Batch Record

A
manufacturing instruction jointly approved by Avecia QA and Stressgen QA.

 

Quality

 

Safety,
identity, purity, strength and potency requirements for API.

 

[*]
= CONFIDENTIAL TREATMENT REQUEST(ED).

 

10

 

Appendix IV - List of Jointly Approved Documents

 

Quality
Agreement

 

Master
Batch Records

 

Quality
Control Document

 

Quality
Control Test Methods

 

Process
Description

 

Validation
Master Plan

 

[*]
= CONFIDENTIAL TREATMENT REQUEST(ED).

 

11

 

Schedule 8

 

Scope Statement

 

[*]
= CONFIDENTIAL TREATMENT REQUEST(ED).

 

 

Certain confidential information contained in
this document, marked by brackets, has been omitted and filed separately with
the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
Amended.

 

CONFIDENTIAL

 

Schedule 8

 

Scope Statement

 

 

Scope Statement
for Process Development, Validation and cGMP Manufacturing of Drug Substance

intended for use in Pivotal Clinical Studies and Marketed Drug Product.

 

 

	
  STRESSGEN:

  	
  Stressgen Biotechnologies, Inc.

  
	
   

  	
  409 2nd Avenue, Suite 201

  
	
   

  	
  Collegeville, PA 19426-2655

  

 

 

Date:
  January 23, 2004

 

[*] = Confidential Treatment Request(ed).

 

1

 

Table of Contents

 

	
  1

  	
  PURPOSE

  	
   

  
	
  2

  	
  PROGRAM
  DEFINITIONS

  	
   

  
	
  3

  	
  ACRONYMS

  	
   

  
	
  4

  	
  SCOPE CONSTRAINTS AND
  ASSUMPTIONS

  	
   

  
	
  5

  	
  STRESSGEN’S
  RESPONSIBILITIES

  	
   

  
	
  6

  	
  TECHNOLOGY TRANSFER STAGE

  	
   

  
	
  6.1

  	
  Fermentation Process
  Transfer

  	
   

  
	
  6.2

  	
  Downstream Process Transfer

  	
   

  
	
  6.3

  	
  Formulation Process
  Transfer

  	
   

  
	
  6.4

  	
  Analytical Methods Transfer

  	
   

  
	
  6.5

  	
  Technology Transfer Report

  	
   

  
	
  7

  	
  [* *] STUDY
  STAGE

  	
   

  
	
  7.1

  	
  [* *]
  Study

  	
   

  
	
  7.2

  	
  [* *]
  Study

  	
   

  
	
  7.3

  	
  [* *]
  Study

  	
   

  
	
  7.4

  	
  [* *]
  Study

  	
   

  
	
  7.5

  	
  [* *]
  Study

  	
   

  
	
  7.6

  	
  Feasibility Report
  and Development Authorization

  	
   

  
	
  8

  	
  [* *] STAGE

  	
   

  
	
  8.1

  	
  [* *]

  	
   

  
	
  8.2

  	
  Cell Paste [* *]

  	
   

  
	
  8.3

  	
  [* *]

  	
   

  
	
  8.4

  	
  API Formulation
  [* *]

  	
   

  
	
  8.5

  	
  [* *]

  	
   

  
	
  8.6

  	
  Report and Process
  Description

  	
   

  
	
  9

  	
  API
  Production: Pivotal Clinical Trial Supply

  	
   

  
	
  9.1

  	
  GMP Pre-production
  Deliverables

  	
   

  
	
  9.2

  	
  GMP Fermentation Production

  	
   

  
	
  9.3

  	
  API Batches:
  Pivotal Clinical Trial Supply

  	
   

  
	
  9.4

  	
  GMP
  Drug Substance Characterization Report (IND)

  	
   

  
	
  10

  	
  Validation
  Stage

  	
   

  
	
  10.1

  	
  Validation Master Plan

  	
   

  
	
  10.2

  	
  Analytical Method
  Validation

  	
   

  
	
  10.3

  	
  API Validation
  Batch Pre-production

  	
   

  
	
  10.4

  	
  Fermentation
  Validation Batch Manufacturing

  	
   

  
	
  10.5

  	
  API Validation Batches

  	
   

  
	
  11

  	
  Regulatory
  Support

  	
   

  
	
  11.1

  	
  IND [* *] CMC Process)

  	
   

  
	
  11.2

  	
  Marketing Applications

  	
   

  
	
  11.3

  	
  Mock Audits

  	
   

  
	
  11.4

  	
  Pre-Approval Inspection
  Support

  	
   

  
	
  12

  	
  Program
  Management

  	
   

  
				

 

[*] = Confidential Treatment Request(ed).

 

2

 

1      PURPOSE

 

This Scope Statement is
incorporated into the Biological Service Agreement dated January 23, 2004
by and between Stressgen and Avecia (for the purposes of this Scope Statement,
the “BSA”).  This Scope Statement is based on Avecia’s
Proposal 2346.04 and describes in further detail the services and deliverables
to be performed and provided by Avecia for the development of commercial
process, cGMP manufacture of phase III clinical supply of the API, validation
of the process at scale and ancillary activities necessary to support a BLA
filing with the FDA.  If any item in
this Scope Statement is inconsistent with the BSA, the terms of this Scope
Statement will control, but only with respect to the services to be performed
under this Scope Statement.  All
capitalized terms used and not expressly defined in this Scope Statement will
have the meanings given to them in the Agreement.  No Changes to this Scope Statement will be effective unless made
in writing pursuant to a mutually agreed Programme Amendment Order (as defined
in the BSA) signed by both parties.

 

The work will be conducted on a
time and materials basis in [* *] distinct stages.  The initial stage was commenced under Stressgen PO# PAD0071 dated
December 19, 2003.  Stressgen must [* *]
prior to any further billable work by Avecia. 
Planning for each stage will be [* *] overseen by the Project Team.

 

2      PROGRAM DEFINITIONS

 

The definitions listed below reflect terms
used in this document.

 

	
  API

  	
   

  	
  See
  “Drug Substance”

  
	
  Avecia

  	
   

  	
  Avecia Limited, acting through
  its Avecia Biotechnology business of Hexagon House, Blackley, Manchester, M9
  8ZS, England.

  
	
  Batch

  	
   

  	
  Output from the fermentation
  or Purification activities (e.g., Drug Substance Batch). The working volumes
  of the fermenters [* *].

  
	
  BSA

  	
   

  	
  The Biological Service
  Agreement between Stressgen and Avecia dated January 23, 2004, setting
  forth the terms and conditions governing the conduct of the Programme.

  
	
  Cell Paste:

  	
   

  	
  Bulk recovered cells from the
  production fermenter.

  
	
  cGMP:

  	
   

  	
  Current
  Good Manufacturing Practice as described in: Guidance for Industry Q7A Good
  Manufacturing Practice Guidance for Active Pharmaceutical Ingredients, and 21
  Code of Federal Regulations, Parts 210 and 211.

  
	
  Common
  Technical Document

  	
   

  	
  Common
  Technical Document as defined by ICH guidelines.

  
	
  [*
  *]

  	
   

  	
  [*
  *]

  
	
  Development
  Run:

  	
   

  	
  A
  non-GMP run at manufacturing scale intended to show that the process and
  resulting bulk meets all specifications.

  
	
  Drug
  Product:

  	
   

  	
  The
  dosage form in the final immediate packaging intended for clinical use or
  commercial sale.

  
	
  Drug
  Substance:

  	
   

  	
  Any
  substance or mixture of substances intended to be used in the manufacture of
  a drug (medicinal) product and that, when used in the production of a drug,
  becomes an active ingredient of the Drug Product.  Such substances are intended to furnish pharmacological
  activity or other direct effect in the diagnosis, cure, mitigation,
  treatment, or prevention of disease or to affect the structure and function
  of the body. In this document, Drug Substance refers to HspE7 manufactured in
  compliance with cGMP and ready for processing into Drug Product.

  

 

[*] = Confidential Treatment Request(ed).

 

3

 

	
  Fermentation

  	
   

  	
  All unit operations involved
  in the fermentation step of the process.

  
	
  Formulation
  Process

  	
   

  	
  All
  unit operations involved in final processing of HspE7 and filling it into the
  bulk containers.

  
	
  HspE7

  	
   

  	
  Stressgen’s
  target protein molecule (SGN-00101). Also used to refer to material or
  samples not made under cGMP (i.e., not Drug Substance).

  
	
  Interim
  Reference Standard

  	
   

  	
  Reference
  Standard qualified from HspE7 taken from a Development Batch.

  
	
  Lot

  	
   

  	
  Output from finish/fill
  activities (e.g., Drug Product Lot).

  
	
  MiniPrep

  	
   

  	
  Bench-scale purification of
  material for [* *]  testing.

  
	
  Process A

  	
   

  	
  The original downstream
  process as described [* *].

  
	
  Process B

  	
   

  	
  A redeveloped downstream
  process that [* *]

  
	
  Process
  Consumables:

  	
   

  	
  Materials
  used as an aid in the manufacture of an intermediate or Drug Substance that
  do not themselves participate in a chemical or biological reaction.  For example: resins, raw materials,
  filters, membranes, disposable analytical test kits, disposable bags.

  
	
  Program:

  	
   

  	
  The services performed by
  Avecia under this Agreement.

  
	
  Purification:

  	
   

  	
  All unit operations involved
  in the purification of the Drug Substance.

  
	
  Recovery:

  	
   

  	
  All unit operations which
  yield Cell Paste from the fermentation broth.

  
	
  Reference Standard

  	
   

  	
  A substance that has been
  shown by an extensive set of analytical tests to be authentic material that
  should be of high purity.  This
  standard can be (1) [* *]; (2) [* *]; (3) [* *] or (4) [* *].

  
	
  Research Batch:

  	
   

  	
  A non-cGMP run intended to execute
  the series of unit operations at reduced scale, in the specified order, to
  demonstrate [* *] in its entirety.

  
	
  Scope Statement:

  	
   

  	
  This schedule to the BSA,
  which represents the statement of work by Avecia for the Programme and
  specifies the design, information desired, estimated duration of the
  Programme and all other matters pertinent to the conduct and completion of
  the Programme.  The Scope Statement
  will be used to define the [* *] for the Programme.

  
	
  Stressgen:

  	
   

  	
  Stressgen Biotechnologies,
  Inc.: Contract and Program Management performed at the offices located at 409
  2nd Avenue, Suite 201Collegeville, PA 19426-2655

  
	
  [* *]

  	
   

  	
  Assay used to determine [* *]
   of API.

  
	
  Up Stream Process:

  	
   

  	
  Up Stream Processing
  operations to include seed fermentation through Cell Paste recovery

  
	
  Validation Master Plan:

  	
   

  	
  The outline of activities
  relating to the validation aspects of a manufacturing process.

  
	
  Work Breakdown Structure

  	
   

  	
  A hierarchical organization of
  deliverables due from a project. Forms the outline of the Scope Statement and
  Statement of Work. Addition of durations and dependences to the work elements
  leads to a project schedule (usually depicted as a Gantt chart).

  

 

[*] = Confidential Treatment Request(ed).

 

4

 

3      ACRONYMS

 

	
  BSA

  	
  Biological Services Agreement

  
	
  C of A

  	
  Certificate of Analysis

  
	
  C of C

  	
  Certificate of Compliance

  
	
  CMC

  	
  Chemistry, Manufacturing and
  Controls

  
	
  EOP

  	
  End Of Production

  
	
  ETP

  	
  Engineering Test Plan

  
	
  FDA 

  	
  Food and Drug Administration

  
	
  GMP

  	
  Good Manufacturing Practices

  
	
  [* *]

  	
  [* *] 

  
	
  ICH 

  	
  International Committee on
  Harmonization

  
	
  IPC

  	
  In-Process Control

  
	
  MCB

  	
  Master Cell Bank

  
	
  MWCB

  	
  Manufacturing Working Cell
  Bank

  
	
  PTP

  	
  Process Transfer Package

  
	
  QA

  	
  Quality Assurance

  
	
  QC

  	
  Quality Control

  
	
  [* *]

  	
  [* *]

  
	
  SOP

  	
  Standard Operating Procedure

  
	
  STM

  	
  Standard Test Method

  
	
  USP

  	
  United States Pharmacopoeia

  
	
  WBS

  	
  Work Breakdown Structure

  

 

[*] = Confidential Treatment Request(ed).

 

5

 

4        SCOPE CONSTRAINTS AND ASSUMPTIONS

 

The following constraints define the limits of the
Program’s scope. The deliverables must fall within these constraints;
conversely, work outside these constraints would require a scope change
approval mutually agreed upon by the parties.

1)              Process Consumables used in
manufacturing must meet [* *] regulatory standards, where applicable and
materials are available.

2)              Avecia will select only
Process Consumables for which [* *], where possible.

3)              Drug Product testing will
be [* *].

4)              All work outputs (e.g. reports
on the Program, and cGMP documentation) will be prepared using Avecia’s
standard format(s)  unless
otherwise specified in the Scope Statement. Avecia will supply all
documentation in electronic format compatible with regulatory guidelines on
submissions, where possible.

5)              The final process design
will be suitable for a commercial supply of Drug Substance at a batch size of
[* *].

6)              The minimum number of
successful validation batches to meet [* *] requirements is stipulated to be [*
*].

7)              Third parties contracted by
Avecia or Stressgen must not adversely impact the timeline.

8)              Existing assays that will
be transferred to Avecia can be modified, if necessary, but no totally new
assays will be developed, unless otherwise specified in this Scope Statement.

9)              All specifications for IPC
and release [* *]. Stressgen is responsible for the appropriateness of any
specification from [* *], Avecia will be responsible for the appropriateness of
any specification from [* *].

10)        The following assumptions
have been used by Avecia in preparing the Proposal and estimating costs:

10.1   [* *]development:

10.1.1                  The process flow sheet [*
*] for the technology transfer, feasibility and development activities;

10.1.2                  The above flow sheet will
give figures for [* *];

10.1.3                  Product from [* *]
specifications;

10.1.4                  The feasibility study will
indicate that the variables that require optimization are [* *] the required
specification value by [* *];

10.1.5                  If [* *] for product
manufacture;

10.1.6                  If [* *] is acceptable to
[* *] and they [* *] will [* *];

10.1.7                  The potential for a method
[* *] within the current scope of the program;

10.1.8                  [* *] API formulation [*
*].

10.2                        Manufacture

10.2.1                  Processing [* *] would be
expected to deliver [* *] product

10.2.2                  [* *] delivers product that
meets [* *] for the product

10.2.3                  The overall process takes
[* *]and involves [* *] major unit operations or as defined in 10.1.1

10.2.4                  Avecia will manufacture [*
*]  batches during the validation stage.

 

5      STRESSGEN’S RESPONSIBILITIES

 

This section lists the information and materials
that will be provided by Stressgen as applicable to facilitate the Program
(“Stressgen Deliverables”) and Stressgen’s responsibilities under the Program.

 

[*] = Confidential Treatment Request(ed).

 

6

 

1)              Provide diligent and timely
direction on the overall program strategy and objectives, and will fully
collaborate on the scientific, technical, and managerial aspects of the
program.

2)              Support and
cooperate with the execution of the Program and shall not knowingly engage in
any act or omission, which may reasonably be expected to prevent or delay the
successful execution of the Program.

3)              Provide timely review and
approval of all documents from Avecia such as: batch records, client-specific
STMs, bill of materials and other applicable documentation.  Turn around time from Stressgen will be [*
*].

4)              Facilitate support from [*
*] to coordinate final [* *].

5)              Supply appropriate material
for [* *].

6)              Provide [* *] by Avecia.

7)              Provide [* *] that could be
used [* *] at Avecia’s discretion, [* *].

8)              Submission of regulatory
filings.

9)              Development and manufacture
of Drug Product, and any associated activities requiring work by Avecia [* *].

10)         Author the non-CMC
submissions for IND and BLA.

11)        Comply with Avecia’s SOP
regarding visitor conduct while at Avecia’s site.

 

6      TECHNOLOGY TRANSFER STAGE

 

6.1  Fermentation Process Transfer

 

6.1.1  Objective

 

Pursuant to Stressgen PO# PAD0071 dated December
19, 2003, Stressgen will transfer information about and samples from [* *] to
[* *]. Stressgen and Avecia will agree to a [* *] that Avecia will perform to
demonstrate capability. Avecia will produce [* *] for further processing and
analysis, and report results to Stressgen.

 

6.1.2       Stressgen Input

6.1.2.1        Fermentation process description

6.1.2.2        Fermentation batch record

6.1.2.3        [* *] report

6.1.2.4        [* *] vials

6.1.2.5        [* *] stability and characterization
reports

6.1.2.6        [* *] method

6.1.2.7        Samples of [* *]

 

6.1.3       Avecia Deliverables

6.1.3.1        [* *] report, including Avecia analysis
of previous work:

•                  Master and executed batch records

•                  [* *] reports ([* *], etc.)

•                  [* *]

•                  [* *] report

•                  [* *] report

•                  [* *] reports

 

[*] = Confidential Treatment Request(ed).

 

7

 

•                  Draft [* *]

 

6.1.3.2        Established cell banks

6.1.3.2.1  [* *] Storage
protocols and records

6.1.3.2.2  [* *] safety report,
if required.

 

6.1.3.3        [* *]

6.1.3.4        Plan for [* *] activities during [* *]
stage.

 

6.2  Downstream Process Transfer

 

6.2.1       Objective

 

Stressgen will transfer information about and
samples from [* *]. Stressgen and Avecia will agree to [* *] that Avecia will
perform to demonstrate capability. Avecia will produce [* *] HspE7 at [* *],
plus another [* *], for analysis, and report results to Stressgen.

 

6.2.2       Stressgen Input

•                  [* *]
Description

•                  [* *] Batch
Records

•                  [* *]
Development Report including updated info for [* *]

•                  Samples of
HspE7 and process intermediates.

•                  Cell Paste
used previously to produce acceptable HspE7 batches for comparison

 

6.2.3       Avecia Deliverables

6.2.3.1        [* *] report,
including Avecia analysis of previous work:

•                  Master and executed batch records

•                  [* *]

•                  [* *]

6.2.3.2        [* *] API [* *]

6.2.3.3        Analysis of [* *] API

6.2.3.4        Plan for [* *] during [* *] stage

 

6.3  Formulation Process Transfer

 

6.3.1       Objective

 

Stressgen will transfer information about and
samples from [* *] to facilitate [* *]. Avecia will review this information and
provide [* *].

 

6.3.2       Stressgen Input

•                  Report on [*
*].

•                  [* *] report.

•                  Container
closure system descriptions for bulk Drug Substance and Drug Product.

•                  Data on
stability of Drug Substance and Drug Product.

 

[*] = Confidential Treatment Request(ed).

 

8

 

•                  Samples of
Drug Substance and Drug Product

 

6.3.3       Avecia Deliverables

6.3.3.1        [* *] transfer report, including Avecia
review of previous work:

•                  API Container closure system suitability

•                  API Stability data and stability program
design

•                  [* *] API formulation process

 

6.3.3.2        Plan for [* *] work during [* *] stage
(in conjunction with Stressgen [* *])

6.3.3.3        Formulated [* *] API batches

 

6.4  Analytical Methods Transfer

 

6.4.1       Objective

 

Stressgen
will transfer information about [* *] to facilitate Avecia’s ability to [* *].
Avecia will review this information, provide [* *]. Stressgen and Avecia will
agree to [* *].

 

6.4.2       Stressgen Input

6.4.2.1        List of [* *]

6.4.2.2        List of [* *]

6.4.2.3        List of [* *] specifications

6.4.2.4        Test methods for above

6.4.2.5        List of [* *]

6.4.2.6        List of assays to be performed during
transfer stage

6.4.2.7        [* *] Methods and related assays, [* *]

 

6.4.3       Avecia Deliverables

6.4.3.1        [* *] transfer report; including
analysis of:

•      [* *] assays

•      Assays requiring [* *]

•      [* *] developed

•      Avecia’s [* *] development

6.4.3.2        Plan for analytical work [* *]

 

6.5  Technology Transfer Report

 

6.5.1       Objective

 

Avecia to summarize the individual unit
operations reviews listed above and report readiness to proceed to feasibility
stage.

 

6.5.2       Avecia Deliverables

•      Meeting minutes, action items, and
completed transfer summary report

 

[*] = Confidential Treatment Request(ed).

 

9

 

7  [* *] STUDY
STAGE

 

7.1       [*
*] Study

 

7.1.1       Objective

 

To screen the [* *] during the transfer stage to
identify [* *] for commercial manufacture, recommend [* *], and plan the [* *]
activities.

 

7.1.2       Avecia Deliverables

 

7.1.2.1       Experiments to:

•      [* *]

•      [* *]

•      [* *] extract

•      [* *] stability [* *]

7.1.2.2        [* *] report,
including plan for [* *] work during [* *] stage.

 

7.2  [* *] Study

 

7.2.1       Objective

 

To screen [* *]  design(s)
[* *]  for commercial manufacture, recommend [* *],
and plan the [* *]  activities.

 

7.2.2       Avecia Deliverables

7.2.2.1        Experiments to:

•      Characterize [* *]

•      Determine [* *] — Cell Paste storage data

•      Evaluate [* *]  vs.
[* *] phase

•      Characterize [* *] scales and steps

•      Determine [* *] strategy

7.2.2.2        [* *] report,
including plan for [* *] stage.

 

7.3  [* *] Study

 

7.3.1       Objective

 

To screen [* *]  for
commercial manufacture, recommend [* *], and plan the [* *]  activities.

 

7.3.2       Avecia Deliverables

7.3.2.1        Experiments to
investigate:

•      Initial [* *]

•      [* *]

•      [* *]

•      [* *] HspE7

•      [* *]

•      Final overall HspE7 [* *]

•      [* *]

 

[*] = Confidential Treatment Request(ed).

 

10

 

7.3.2.2        [* *] report,
including plan for [* *] during [* *] stage.

 

7.4  [* *] Study

 

7.4.1       Objective

 

To screen API [* *]  to
identify [* *]  commercial
manufacture, recommend [* *], and plan the [* *]  activities.
This work will be done [* *]  ,
to the extent possible, will recommend an API formulation [* *]  Drug Product; however, [* *]  the
final API formulation will be Avecia’s responsibility.

 

7.4.2       Avecia Deliverables

7.4.2.1        Experiments to:

•      [* *]

•      [* *]

•      [* *] of HspE7

•      [* *]  of
the formulated API

7.4.2.2        [* *] report
including plans for [* *] work during [* *] stage.

 

7.5  [* *] Study

 

7.5.1       Objective

 

To screen [* *], select and qualify [* *] purposes,
and plan the [* *]  stage activities.

 

7.5.2       Avecia Deliverables

7.5.2.1        Experiments to:

•      [* *]  methods [* *]

•      [* *] assays as required, e.g.,

•      [* *] need

•      [* *]

•      Review [* *] for entire process

•      [* *] batch release and stability assays

 

7.5.2.2        [* *] report,
including objectives for further [* *].

 

7.6  [* *]
Report and Development Authorization

 

7.6.1       Objective

 

Avecia to summarize [* *]  reports listed above, and report readiness
to proceed.

 

7.6.2       Stressgen Input

•      Review of [* *]

•      Approval to [* *]  stage

 

[*] = Confidential Treatment Request(ed).

 

11

 

7.6.3       Avecia Deliverables

7.6.3.1        Summary [* *]
Report, including [* *]  plans and goals
for [* *] stage.

 

8  [*
*] STAGE

 

Upon Stressgen’s approval to proceed with [* *],
Avecia will execute the [* *]  from
the [* *]  stage in order to develop [* *]. Avecia will
parallel track its work to the extent possible, and will resource the work
adequately to allow [* *], particularly on [* *]. This stage will [* *]  the final [* *]  for the pivotal
clinical trial supply and commercial manufacture, and produce pilot batches at
scale.

 

8.1       [* *]

 

8.1.1       [* *] Objectives

 

Avecia will execute the [* *]  approved during the [* *]  stage
to [* *]  process for future commercial scale, and
produce pilot batches of Cell Paste. 
Criteria for completion of development include [* *]  process:

 

•      [* *]

•      Produces at least [* *]HspE7 batches (not for clinical use)

•      Generates HspE7 with [* *].

 

8.1.2       [* *]  Deliverables

8.1.2.1        [* *] report

8.1.2.2        Draft [* *] records
and any [* *] control automation code

8.1.2.3        [* *] acceptable
HspE7 Cell Paste batches at the [* *] 
scale

8.1.2.4        Cell Paste samples
for testing

8.1.2.5        Cell
characterization analysis

8.1.2.6        Draft [* *] batch
records

8.1.2.7        Draft sample
testing plan

8.1.2.8        Draft GMP transfer
package for the [* *] process

 

8.2  Cell Paste
[* *]

 

8.2.1       [* *] Objectives

 

Avecia will execute the [* *]   approved during the [* *]  stage to [* *]  for future
commercial scale, and produce pilot batches of Cell Paste.  Criteria for completion of development
include evidence that the [* *]:

 

•      [* *]

•      Produces acceptable Cell
Paste batches at the scales tested in section 8.1.2  (not
for clinical use)

 

8.2.2       [* *] Deliverables

8.2.2.1        Draft [* *] batch
records, including [* *] for Cell Paste

8.2.2.2        Cell Paste samples
for testing

 

[*] = Confidential Treatment Request(ed).

 

12

 

8.2.2.3        Draft sample
testing plan

8.2.2.4        Draft GMP transfer
package for the [* *] process

 

8.3  [* *]

 

8.3.1       Objective

 

Avecia will execute the [* *]  approved during the [* *]  the
downstream purification process for future commercial scale, and produce pilot
batches of API. Avecia will [* *], demonstrating process robustness and reproducibility

 

Specific objectives are that the process [* *]  HspE7 with:

 

•      [* *] material.

•      [* *]

•      [* *] as determined by [* *].

•      [* *] similar to the [* *]  reference material, as measured by the [* *]  bioassay.

•      Overall quality that allows
for release of an Interim Reference Standard batch that can be qualified for
release of the Drug Substance for pivotal clinical trial supplies.

 

8.3.2       Avecia Deliverables

8.3.2.1        Updated Technical
Summary Report

8.3.2.2        [* *]

8.3.2.3        HspE7 samples for
testing

8.3.2.4        [* *] acceptable
batches of HspE7 at [* *]

8.3.2.5        Draft batch records

8.3.2.6        Draft sample test
plan.

 

8.4  API
Formulation [* *]

 

8.4.1       Formulation [* *]
Objectives

 

Avecia will [* *]  bulk
Drug Substance formulation that [* *]  a
commercial manufacturing process. 
Avecia will collaborate with the [* *] to ensure compatibility of the [*
*]  with the [* *]  to
the extent possible, but responsibility for the [* *] for the API lies with
Avecia.

 

Specific objectives are that the bulk formulation
process:

 

•      [* *]

•      Be stable at [* *]

•      Has components that [* *]assays

•      [* *] Drug Product formulation that can be
lyophilized

•      Generates samples that
Stressgen can use for lyophilization [* *]

 

[*] = Confidential Treatment Request(ed).

 

13

 

8.4.2       API Formulation [* *]
Deliverables

8.4.2.1        [* *] samples (less
than [* *]) for testing ([* *], etc.)

8.4.2.2        Report on API [* *]
formulation process [* *].

8.4.2.3        API Formulation
material [* *]

8.4.2.4        API Stability report
([* *])

8.4.2.5        API Container
closure system specifications for bulk Drug Substance.

8.4.2.6        Report evaluating
stability of Drug Substance to [* *]

8.4.2.7        Draft API
formulation records

 

8.5  [* *]

 

8.5.1       [* *] Objectives

 

[* *]  methods
for

 

•      [* *] testing,

•      demonstration of [* *],

•      Batch release,

•      Characterization of HspE7,

•      Stability studies, including
[* *] stability indicating
assays from forced degradation and/or accelerated studies.

 

8.5.2       [* *] Deliverables

 

[* *] listed in the following table, which is
indicative and will be reviewed during [* *].

 

	
  Assay

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  Safety

  	
   

  	
  Purity

  	
   

  	
  Identity

  	
   

  	
  Stability

  	
   

  	
  Strength

  	
   

  	
  IPC

  	
   

  	
  [* *]

  
	
  [* *]

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  
	
  [* *]

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  
	
  [* *]

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  
	
  [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  
	
  [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
  [* *]

  	
   

  	
  X

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  
	
  [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  
	
  [* *]

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  
	
  [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  
	
  [* *]

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  
	
  [* *]

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
  [* *]

  
	
  [* *]

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
  [* *]

  
	
  [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
  [* *]

  
	
  [* *]

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  
	
  [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  
	
  [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  
	
  [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  

 

[*] = Confidential Treatment Request(ed).

 

14

 

	
  [* *]

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  
	
  [* *]

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  
	
  [* *]

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  
	
  [* *]

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  
	
  [* *]

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  
	
  [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  
	
  [* *]

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  

 

* if necessary

 

8.5.2.1        Assays requiring
special attention

•      [* *] assay for Cell Paste strength, identity, and
stability

•      [* *], or a summary report
documenting the work done and data produced and [* *]. The report will include
data generated from [* *] testing.

•      At least [* *] assays for [* *]

•      A [* *] assay, or a summary report documenting the
work done and data produced and the reasons [* *].  The report will include the data generated from [* *]  results using [* *] standard
commercial kit methods, and estimates of [* *]  by other methods.

 

8.5.2.2        [* *] report,
including reports on any assays that were [* *]  is available

8.5.2.3        Draft [* *]

8.5.2.4        [* *] Reference
Standard qualification report

8.5.2.5        Characterization
report comparing HspE7 [* *]

8.5.2.6        Pilot stability
study protocols and initiated studies

8.5.2.7        Pilot stability
study interim data report

8.5.2.8        Draft stability
protocols for Drug Substance

8.5.2.9        HspE7 batch
released with a Certificate of Fill for fill/finish processing and
qualification as the [* *] Reference Standard for release of pivotal clinical
trial supplies (could be part of 8.3.2.4)

 

8.6       [*
*] Report and Process Description

 

8.6.1       Objective

 

Avecia to summarize the individual reports
listed above, and document the rationale for the overall process design.

 

8.6.2       Stressgen Input

•      Review of individual development reports

 

8.6.3       Stressgen Deliverable

•      Approval to proceed to Phase III GMP
campaign

 

[*] = Confidential Treatment Request(ed).

 

15

 

8.6.4       Avecia Deliverables

8.6.4.1        Development Report

8.6.4.2        API Process
Description.

 

9  API Production: Pivotal Clinical Trial
Supply

 

Upon Stressgen’s approval of the successful
completion of the [* *] stage, Avecia will manufacture, and release API for
processing into Drug Product for use in pivotal clinical trials.

 

9.1       GMP Pre-production Deliverables

 

9.1.1       GMP Pre-Production
Objectives

 

Avecia will complete a detailed study of the
readiness of the process to fit into the cGMP facilities and the suitability of
the available equipment and utilities for the process design. Required
alterations to [* *] will be identified and implemented in advance of the
campaign so that the [* *] is not delayed.

 

9.1.2       GMP Pre-Production
Deliverables

9.1.2.1        Released raw
materials

9.1.2.2        Approved equipment
list, utilities and automation codes

9.1.2.3        Approved batch
records

9.1.2.4        Approved ETP

9.1.2.5        Approved STM

9.1.2.6        Approved PTP for
the fermentation process, through Cell Paste recovery

9.1.2.7        Approved PTP for
Purification and Formulation Processes, including final formulation

9.1.2.8        Approved Stability
Protocols for Cell Paste and Drug Substance

9.1.2.9        Updated development
reports (as needed)

9.1.2.10      Approved GMP Campaign
Plan

 

9.2       GMP Fermentation Production

 

9.2.1       Fermentation
Production Objectives

 

Produce at least [* *]  of
Cell Paste at the [* *]   scale for use in the manufacture
of Drug Substance at the [* *]  scale
for use in pivotal clinical trials. Produce [* *]  of
Cell Paste at the [* *]  scale to confirm
the process [* *].

 

[*] = Confidential Treatment Request(ed).

 

16

 

9.2.2       Deliverables

 

9.2.2.1     Updated technical summary reports from the Cell Paste
production.

9.2.2.2     Executed and reviewed batch documentation.

9.2.2.3     cGMP Cell Paste for subsequent Drug
Substance batches, suitable for pivotal clinical trials.

9.2.2.4     Cell Paste stability studies initiated

9.2.2.5     Cleaning summary report.

9.2.2.6     EOP testing

•      Approved Protocol

•      Execute EOP sampling.

•      Approved EOP report

 

9.2.2.7     [* *]  HspE7 Cell Paste
batches at the [* *]  scale

9.2.2.8     Purification of [* *]
equivalent fermentation scale aliquot of cell paste from a [* *] fermentation
under non-GMP conditions.

 

9.3       API Batches: Pivotal Clinical Trial
Supply

 

9.3.1       Objective

Produce [* *]  scale
batches of API for processing into Drug Product for pivotal clinical trials.

 

9.3.2       Deliverables

9.3.2.1        Updated technical
summary reports from the API production.

9.3.2.2        Executed and
reviewed batch records.

9.3.2.3        At least [* *]
successful engineering batches at the [* *] scale

9.3.2.4        [* *] batches at
the [* *] scale of cGMP Drug Substance

9.3.2.5        [* *] for the Drug
Substance batches.

9.3.2.6        Drug Substance
stability studies initiated.

9.3.2.7        Cleaning summary
report.

 

9.4       GMP Drug Substance Characterization
Report (IND)

 

9.4.1       Characterization
Objective

Avecia will characterize the [* *]
and [* *] and [* *] cGMP clinical batches to support Stressgen
IND Amendment filing.

 

[*] = Confidential Treatment Request(ed).

 

17

 

9.4.2       Characterization
Deliverables

9.4.2.1        Characterization
protocol

9.4.2.2        Characterization
Summary report

9.4.2.3        Reference Standard
qualification protocol

9.4.2.4        Reference Standard
qualification report

9.4.2.5        Qualified reference
standard.

 

10  Validation
Stage

 

10.1     Validation Master Plan

 

10.1.1                     Objective

Determine the acceptable operating ranges for the
process and Drug Substance specifications, to provide assurance that the Drug
Substance manufacturing process and testing methods will reliably and
reproducibly perform their intended purpose in the manufacture of a commercial
Drug Product.

 

10.1.2                     Deliverables

10.1.2.1      Laboratory
Performance Characterization Study

10.1.2.2      Draft VMP

10.1.2.3      Draft Protocols for
process validation.

10.1.2.4      Draft protocols for
cleaning method validation

10.1.2.5      Draft ETP (as
needed)

 

10.2     Analytical Method Validation

 

10.2.1                     Analytical
Method Validation Objectives

 

Avecia will generate data demonstrating the:

 

•      Complete [* *] HspE7 related [* *].

•      Limits of [* *].

•      Completion of method
validation for [* *] tests
prior to validation batch manufacturing.

 

10.2.2                     Deliverables

10.2.2.1      Validation Summary

 

Report for each method identified in the table
below, which is indicative and will be reviewed during development:

 

	
  Assay

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  Safety

  	
   

  	
  Purity

  	
   

  	
  Identity

  	
   

  	
  Stability

  	
   

  	
  Strength

  	
   

  	
  IPC

  	
   

  	
  [* *]

  
	
  [* *]

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  
	
  [* *]

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  
	
  [* *]

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  

 

[*] = Confidential Treatment Request(ed).

 

18

 

	
  [* *]

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  
	
  [* *]

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  [* *]

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  
	
  [* *]

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  
	
  [* *]

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  [* *]

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  
	
  [* *]

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
  X

  	
   

  	
  X

  
	
  [* *]

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
  X

  
	
  [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
  X

  
	
  [* *]

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  
	
  [* *]

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  X

  

 

10.3     API Validation Batch Pre-production

 

10.3.1                     Objective

 

Prepare Avecia facilities and process
documentation for validation batch manufacturing.

 

10.3.2                     Deliverables

10.3.2.1 Updated Process documentation

10.3.2.2 Approved PQ batch validation protocols

10.3.2.3 Approved cleaning validation protocols

 

10.4     Fermentation Validation Batch Manufacturing

 

10.4.1                     Objective

 

Produce [* *]   batches of Cell Paste to support process validation.

 

10.4.2                     Deliverables

10.4.2.1      [* *] batches to
support [* *] filing (scales to be determined)

10.4.2.2      Executed Protocols.

10.4.2.3      Process validation
reports from fermentation and Cell Paste recovery.

10.4.2.4      Cleaning validation
reports.

10.4.2.5      Executed and
reviewed batch records.

10.4.2.6      Cell Paste stored
for future manufacturing [* *]

10.4.2.7      Cell Paste on
stability

 

10.5     API Validation Batches

 

10.5.1                     Objective

Produce [* *]  batches of Drug Substance process
validation.

 

[*] = Confidential Treatment Request(ed).

 

19

 

10.5.2                     Deliverables

10.5.2.1      [* *] to support [*
*] filing
(design scale)

10.5.2.2      Executed Protocols.

10.5.2.3      Process validation
reports from the Downstream Process.

10.5.2.4      Cleaning validation
reports.

10.5.2.5      Executed and
reviewed batch records.

10.5.2.6      Drug Substance
stored [* *]

10.5.2.7      Drug Substance from
all [* *] batches on stability.

10.5.2.8      [* *] for the Drug
Substances.

10.5.2.9      Characterization
report on API from validation batches: comparison to each other and pivotal [*
*] batch

 

11  Regulatory Support

 

11.1     IND [* *] CMC Process)

 

11.1.1                     Regulatory
Support Objective

 

Support Stressgen’s regulatory filing by assembling
data, documentation and information from work performed at Avecia into the CMC
section of an IND [* *] process in preparation for pivotal clinical trials.

 

11.1.2                     Stressgen’s
Input

11.1.2.1      Regulatory strategy

11.1.2.2      Editorial
supervision of CMC section

11.1.2.3      Submission of IND [*
*]

 

11.1.3                     Avecia
Deliverables

11.1.3.1      Copies of data and
documents as requed for regulatory submission support.

11.1.3.2      Characterization
report (from section 8.5.2.5)

11.1.3.3      Completed, [* *] for
IND [* *], formatted in Word or PDF.

 

11.2     Marketing Applications

 

11.2.1                     Objective

 

Provide Stressgen with the written CMC section to
support BLA filing in [* *], in accordance with the [* *].

 

[*] = Confidential Treatment Request(ed).

 

20

 

11.2.2                     Stressgen’s
Input

11.2.2.1      Regulatory strategy

11.2.2.2      Editorial
supervision of CMC section

11.2.2.3      Submission of
marketing applications to [* *]

 

11.2.3                     Avecia
Deliverables

11.2.3.1      QA’d CMC section
formatted in Word or PDF, ready for BLA filing in [* *].

11.2.3.2      Supporting documents
for CMC section

 

11.3     Mock Audits

 

11.3.1                     Objective

 

Support [* *]  mock Pre-Approval Inspection audits, [* *].

 

11.3.2     Deliverables

11.3.2.1      Audit Observation
report and any associated corrective actions for each mock audit.

11.3.2.2      Other objects to be
determined

 

11.4     Pre-Approval Inspection Support

 

11.4.1     Objective

 

Support Stressgen readiness for inspections
from [* *]  regulatory
authorities in anticipation of Drug Product approval.

 

11.4.2     Deliverables

11.4.2.1      To be determined.

 

12  Program Management

 

12.1.1     Objective

 

Stressgen and Avecia will jointly develop and
maintain a Project Management Plan. The plan will include the composition and
responsibilities of a Steering Committee, a Project Team, and the communication
plan and change control process for the project.

 

12.1.2     Deliverables

 

12.1.2.1      Scope Statement

•      This document, supported by detailed work
plans  for each unit operation. Modified by means of
approved Programme Amendment Orders only. Updated monthly.

 

12.1.2.2      Programme Cost
Schedule

•      The estimated Programme budget, organized
according to the [* *]. Updated monthly.

 

12.1.2.3      Programme Timeline

•      Timeline of events, [* *]. Updated
monthly.

 

[*] = Confidential Treatment Request(ed).

 

21

 

12.1.2.4      Project team minutes
and other documentation

12.1.2.5      Monthly project
status report:

•      Project metrics

•      Milestone status (current and
next quarter)

•      Current activities update and
[* *]

•      Meeting calendar

•      Current and incipient risk
events and mitigation plans

•      Issues log

•      Change requests and change
control log.

 

[*] = Confidential Treatment Request(ed).

 

22

 

Schedule 9

 

Programme Budget and Payment Schedule

 

See Attached (2 pages)

 

[*] = Confidential Treatment Request(ed).

 

 

	
  ID

  	
   

  	
  Invoice
  Trigger

  Scope Reference

  	
   

  	
  Task Name

  	
   

  	
  Total
  £’000

  	
   

  
	
  1

  	
   

  	
  6

  	
   

  	
  Technology
  transfer

  	
   

  	
  [*
  *]

  	
   

  
	
  2

  	
   

  	
  7

  	
   

  	
  Feasibility
  study 

  	
   

  	
  [*
  *]

  	
   

  
	
  3

  	
   

  	
  8
  except below

  	
   

  	
  [*
  *] development 

  	
   

  	
  [*
  *]

  	
   

  
	
  4

  	
   

  	
  8.3.2.4

  	
   

  	
  [*
  *] batches HspE7 at [* *] scale

  	
   

  	
  [*
  *]

  	
   

  
	
  5

  	
   

  	
  8.5.2.5

  	
   

  	
  Characteristion
  report comparing HspE7 with [* *]

  	
   

  	
  [*
  *]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
  API production Pivotal Clinical trial supply

  	
   

  	
   

  	
   

  
	
  6

  	
  [**]

  	
   

  	
   

  	
  GMP
  pre-payment

  	
   

  	
  [*
  *]

  	
   

  
	
  7

  	
   

  	
  9.1

  	
   

  	
  GMP
  Pre- production deliverables

  	
   

  	
  [*
  *]

  	
   

  
	
  8

  	
  [**]

  	
  9.2

  	
   

  	
  GMP
  Fermentation Production 

  	
   

  	
  [*
  *]

  	
   

  
	
  9

  	
   

  	
  9.2.2.8

  	
   

  	
  Non-GMP
  purification from [* *]

  	
   

  	
  [*
  *]

  	
   

  
	
  10

  	
  [**]

  	
  9.3

  	
   

  	
  API
  batches - Pivotal clinical trial supply - Release

  	
   

  	
  [*
  *]

  	
   

  
	
  11

  	
   

  	
   

  	
   

  	
  API
  batches - Receipt of shipment instruction for final delivery

  	
   

  	
  [*
  *]

  	
   

  
	
  12

  	
   

  	
  9.4

  	
   

  	
  Drug
  substance characterisation report

  	
   

  	
  [*
  *]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
  Validation Stage

  	
   

  	
   

  	
   

  
	
  13

  	
   

  	
  10.1

  	
   

  	
  Validation
  Master Plan

  	
   

  	
  [*
  *]

  	
   

  
	
  14

  	
   

  	
  10.1.2.1

  	
   

  	
  Laboratory
  Performance Characterisation Study

  	
   

  	
  [*
  *]

  	
   

  
	
  15

  	
   

  	
  10.2

  	
   

  	
  Analytical
  Method Validation

  	
   

  	
  [*
  *]

  	
   

  
	
  16

  	
  [**]

  	
   

  	
   

  	
  GMP
  pre-payment

  	
   

  	
  [*
  *]

  	
   

  
	
  17

  	
  [**]

  	
  10.5.2.1
  by batch

  	
   

  	
  Fermentation/API
  validation batches

  	
   

  	
  [*
  *]

  	
   

  
	
  18

  	
   

  	
   

  	
   

  	
  1

  	
   

  	
   

  	
   

  
	
  19

  	
   

  	
   

  	
   

  	
  2

  	
   

  	
   

  	
   

  
	
  20

  	
   

  	
   

  	
   

  	
  3

  	
   

  	
   

  	
   

  
	
  21

  	
   

  	
   

  	
   

  	
  4

  	
   

  	
   

  	
   

  
	
  22

  	
   

  	
   

  	
   

  	
  5

  	
   

  	
   

  	
   

  
	
  23

  	
  [**]

  	
  10.5.2.5

  	
   

  	
  Fermentation/API
  validation  -  Release 

  	
   

  	
  [*
  *]

  	
   

  
	
  24

  	
   

  	
   

  	
   

  	
  API
  validation  -  Receipt of shipment instruction for final
  delivery

  	
   

  	
  [*
  *]

  	
   

  
	
  25

  	
   

  	
  10.5.2.2
  by batcf

  	
   

  	
  Execution
  of Validation Plan 

  	
   

  	
  [*
  *]

  	
   

  
	
  26

  	
   

  	
  10.5.2.3

  	
   

  	
  Validation
  reports

  	
   

  	
  [*
  *]

  	
   

  
	
  27

  	
   

  	
  11.1

  	
   

  	
  CMC
  section 

  	
   

  	
  [*
  *]

  	
   

  
	
  28

  	
   

  	
  11.3

  	
   

  	
  Mock
  PAI [* *]

  	
   

  	
  [*
  *]

  	
   

  
	
  29

  	
   

  	
  11.4

  	
   

  	
  PAI
  [* *]

  	
   

  	
  [*
  *]

  	
   

  
	
  30

  	
   

  	
   

  	
   

  	
  Raw
  materials (total estimate) 

  	
   

  	
  TBA

  	
   

  
	
  31

  	
   

  	
   

  	
   

  	
  Stability program (to be defined)

  	
   

  	
  Split
  tba  

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
  Total Budget

  	
   

  	
  [* *]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
  GMP Manufacture [* *]

  	
   

  	
   

  	
   

  
	
  6

  	
   

  	
   

  	
   

  	
  GMP
  pre-payment

  	
   

  	
  [*
  *]

  	
   

  
	
  8

  	
   

  	
  9.2

  	
   

  	
  GMP
  Fermentation Production 

  	
   

  	
  [*
  *]

  	
   

  
	
  10

  	
   

  	
  9.3

  	
   

  	
  API
  batches - Pivotal clinical trial supply - Release

  	
   

  	
  [*
  *]

  	
   

  
	
  11

  	
   

  	
   

  	
   

  	
  API
  batches - Receipt of shipment instruction for final delivery

  	
   

  	
  [*
  *]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
  GMP Manufacture [* *]

  	
   

  	
   

  	
   

  
	
  16

  	
   

  	
   

  	
   

  	
  GMP
  pre-payment

  	
   

  	
  [*
  *]

  	
   

  
	
  17

  	
   

  	
  10.5.2.1
  by batch

  	
   

  	
  Fermentation/API
  validation batches

  	
   

  	
  [*
  *]

  	
   

  
	
  23

  	
   

  	
  10.5.2.5

  	
   

  	
  Fermentation/API
  validation  -  Release 

  	
   

  	
  [*
  *]

  	
   

  
	
  24

  	
   

  	
   

  	
   

  	
  API
  validation  -  Receipt of shipment instruction for final
  delivery

  	
   

  	
  [*
  *]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
  Total
  consideration for sale of API

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
  Total consideration for technical consultancy
  research and development activities 

  	
   

  	
  [*
  *]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
  Total
  Budget Estimate

  	
   

  	
  [*
  *]

  	
   

  

 

 

	
  Budgeted Cost of Work Scheduled

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  BASELINE-REV 1.0  Oct 31, 2003

  	
   

  	
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  16

  	
   

  	
  17

  	
   

  	
  18

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
  Invoice Trigger

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  ID

  	
   

  	
  Scope Reference

  	
   

  	
  Task Name

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  1

  	
   

  	
   

  	
  6

  	
   

  	
  Technology transfer

  	
   

  	
  [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  2

  	
   

  	
   

  	
  7

  	
   

  	
  Feasibility study

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  3

  	
   

  	
   

  	
  8 except below

  	
   

  	
  [* *] development

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  4

  	
   

  	
   

  	
  8.3.2.4

  	
   

  	
  [* *] batches HspE7 at [* *] scale

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  5

  	
   

  	
   

  	
  8.5.2.5

  	
   

  	
  Characteristion report comparing HspE7 with
  [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
  API production Pivotal
  Clinical trial supply

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  6

  	
  [* *]

  	
   

  	
   

  	
   

  	
  GMP pre-payment

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  7

  	
   

  	
   

  	
  9.1

  	
   

  	
  GMP Pre- production deliverables

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  8

  	
  [* *]

  	
   

  	
  9.2

  	
   

  	
  GMP Fermentation Production

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  9

  	
   

  	
   

  	
  9.2.2.8

  	
   

  	
  Non-GMP purification from [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  10

  	
  [* *]

  	
   

  	
  9.3

  	
   

  	
  API batches - Pivotal clinical trial supply
  - Release

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  11

  	
   

  	
   

  	
   

  	
   

  	
  API batches - Receipt of shipment
  instruction for final delivery

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  12

  	
   

  	
   

  	
  9.4

  	
   

  	
  Drug substance characterisation report

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
  Validation Stage

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  13

  	
   

  	
   

  	
  10.1

  	
   

  	
  Validation Master Plan

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  14

  	
   

  	
   

  	
  10.1.2.1

  	
   

  	
  Laboratory Performance Characterisation
  Study

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  15

  	
   

  	
   

  	
  10.2

  	
   

  	
  Analytical Method Validation

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  16

  	
  [* *]

  	
   

  	
   

  	
   

  	
  GMP pre-payment

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  17

  	
  [* *]

  	
   

  	
  10.5.2.1 by batch

  	
   

  	
  Fermentation/API validation batches

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  18

  	
   

  	
   

  	
   

  	
   

  	
  1

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  19

  	
   

  	
   

  	
   

  	
   

  	
  2

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  20

  	
   

  	
   

  	
   

  	
   

  	
  3

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  21

  	
   

  	
   

  	
   

  	
   

  	
  4

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  22

  	
   

  	
   

  	
   

  	
   

  	
  5

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  23

  	
  [* *]

  	
   

  	
  10.5.2.5

  	
   

  	
  Fermentation/API validation  -  Release

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  24

  	
   

  	
   

  	
   

  	
   

  	
  API validation  -  Receipt of shipment
  instruction for final delivery

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  25

  	
   

  	
   

  	
  10.5.2.2 by batcf

  	
   

  	
  Execution of Validation Plan

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  26

  	
   

  	
   

  	
  10.5.2.3

  	
   

  	
  Validation reports

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  27

  	
   

  	
   

  	
  11.1

  	
   

  	
  CMC section

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  28

  	
   

  	
   

  	
  11.3

  	
   

  	
  Mock PAI [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  29

  	
   

  	
   

  	
  11.4

  	
   

  	
  PAI [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  30

  	
   

  	
   

  	
   

  	
   

  	
  Raw materials (total estimate)

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  31

  	
   

  	
   

  	
   

  	
   

  	
  Stability program (to be
  defined)

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
  Total Budget

  	
   

  	
  [* *]

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
  Cumulative Budget

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
  CANCELLATION

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
  Prepaid

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
  Additional

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  1[* *]

  	
   

  	
  1[* *]

  	
   

  	
  [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
  Cancellation

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
  Invoice Trigger

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  ID

  	
   

  	
  Scope Reference

  	
   

  	
  Task Name

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  Total

  	
   

  
	
  1

  	
   

  	
   

  	
  6

  	
   

  	
  Technology transfer

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  
	
  2

  	
   

  	
   

  	
  7

  	
   

  	
  Feasibility study

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  
	
  3

  	
   

  	
   

  	
  8 except below

  	
   

  	
  Process development

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  
	
  4

  	
   

  	
   

  	
  8.3.2.4

  	
   

  	
  [* *] batches HspE7 at [* *] scale

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  
	
  5

  	
   

  	
   

  	
  8.5.2.5

  	
   

  	
  Characteristion report comparing HspE7 with
  [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
  API production Pivotal
  Clinical trial supply

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  6

  	
  [* *]

  	
   

  	
   

  	
   

  	
  GMP pre-payment

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  
	
  7

  	
   

  	
   

  	
  9.1

  	
   

  	
  GMP Pre- production deliverables

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  
	
  8

  	
  [* *]

  	
   

  	
  9.2

  	
   

  	
  GMP Fermentation Production

  	
   

  	
  [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  
	
  9

  	
   

  	
   

  	
  9.2.2.8

  	
   

  	
  Non-GMP purification from [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  
	
  10

  	
  [* *]

  	
   

  	
  9.3

  	
   

  	
  API batches - Pivotal clinical trial supply
  - Release

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  
	
  11

  	
   

  	
   

  	
   

  	
   

  	
  API batches - Receipt of shipment
  instruction for final delivery

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  
	
  12

  	
   

  	
   

  	
  9.4

  	
   

  	
  Drug substance characterisation report

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
  Validation Stage

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  13

  	
   

  	
   

  	
  10.1

  	
   

  	
  Validation Master Plan

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  
	
  14

  	
   

  	
   

  	
  10.1.2.1

  	
   

  	
  Laboratory Performance Characterisation
  Study

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  
	
  15

  	
   

  	
   

  	
  10.2

  	
   

  	
  Analytical Method Validation

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  
	
  16

  	
  [* *]

  	
   

  	
   

  	
   

  	
  GMP pre-payment

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  
	
  17

  	
  [* *]

  	
   

  	
  10.5.2.1 by batch

  	
   

  	
  Fermentation/API validation batches

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  18

  	
   

  	
   

  	
   

  	
   

  	
  1

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  
	
  19

  	
   

  	
   

  	
   

  	
   

  	
  2

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  
	
  20

  	
   

  	
   

  	
   

  	
   

  	
  3

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  
	
  21

  	
   

  	
   

  	
   

  	
   

  	
  4

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  
	
  22

  	
   

  	
   

  	
   

  	
   

  	
  5

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  
	
  23

  	
  [* *]

  	
   

  	
  10.5.2.5

  	
   

  	
  Fermentation/API validation  - 
  Release

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  
	
  24

  	
   

  	
   

  	
   

  	
   

  	
  PI validation  -  Receipt of shipment
  instruction for final delivery

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  
	
  25

  	
   

  	
   

  	
  10.5.2.2 by batcf

  	
   

  	
  Execution of Validation Plan

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  
	
  26

  	
   

  	
   

  	
  10.5.2.3

  	
   

  	
  Validation reports

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  
	
  27

  	
   

  	
   

  	
  11.1

  	
   

  	
  CMC section

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  
	
  28

  	
   

  	
   

  	
  11.3

  	
   

  	
  Mock PAI [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  
	
  29

  	
   

  	
   

  	
  11.4

  	
   

  	
  PAI ([* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  
	
  30

  	
   

  	
   

  	
   

  	
   

  	
  Raw materials (total estimate)

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  31

  	
   

  	
   

  	
   

  	
   

  	
  Stability program (to be
  defined)

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
  Total Budget

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
  Cumulative Budget

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
  CANCELLATION

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
  Prepaid

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
  Additional

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  1[* *]

  	
   

  	
  [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
  Cancellation

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
  [* *]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  

 

 

Schedule 10

 

[* *] Terms

 

1.                                       [* *] Services.  Avecia shall provide [* *] of (a) the master cell bank
and the working cell bank provided by Stressgen to Avecia pursuant to the
Material Transfer Agreement dated January 9, 2004, (b) any additional working
cell banks produced by Avecia during the term of the Agreement and, if agreed,
(c) the API (collectively, the “Materials”). 
Avecia shall not [*
*] the Materials from the address set forth above without the express
written consent of Stressgen.  While
Avecia is [* *] the Materials
hereunder, Stressgen may visit, view or audit Avecia’s records or [* *] systems at any time during
normal business hours.

 

2.                                       Scope of
Custody.  Notwithstanding the [* *] of the Materials by Avecia,
Avecia acknowledges and agrees that it does not have, and shall not acquire or
claim, any title or ownership interest in the Materials by virtue of this
Agreement.   This Agreement shall not be
construed to grant any license or other rights to the Recipient in any patent
rights or other intellectual property rights of Stressgen.

 

3.                                       Term
of Services.  Avecia shall provide the [* *] services hereunder from
the time contemplated in the BSA until the later of (a) [* *] or (b) one year
after the acceptance by [* *] of Stressgen’s application to market HspE7,
unless Stressgen terminates this Agreement in agreement prior to such date by
providing written instructions as to the [* *] of the Materials. 
In the event Avecia wishes to terminate this Agreement, Avecia must
provide Stressgen with [* *] written notice to provide Stressgen with a
reasonable opportunity to [*
*] for the Materials. 
Notwithstanding the foregoing, Avecia may terminate this Agreement on 30
days written notice to Stressgen in the event of non-payment of invoices
pursuant to Clause 4.  The fee for [* *] services not rendered
for a full calendar year will be prorated monthly.  Stressgen will be billed for the cost of return or destruction of
the Materials.

 

4.                                       Risk, Insurance
and Title.

 

(a)                                  In the event of failure by Avecia to [* *] the
Materials under agreed conditions, Avecia shall [* *].

 

(b)                                 The obligation to insure the Materials against any
risks other than those attributable to the fault of Avecia, shall rest with
Stressgen.

 

(c)                                  Title in Materials not owned by Stressgen under the
terms of the Material Transfer Agreement will pass to Stressgen on Avecia’s
Release of the API.

 

5.                                       Payment.  Avecia shall submit annual invoices to
Stressgen for technical consultancy services to cover management, administration and quality
control activities.  The cost of
such technical consultancy services for the year 2004 shall equal the cost of
items set out in the table below:

 

[*] = Confidential Treatment Request(ed).

 

 

	
  CELL [* *]

  	
   

  	
  PRICE

  
	
  [* *] Biological
  Materials in [* *]:

  	
   

  	
  Market rate to be agreed

  
	
  [* *] for a single year or any portion thereof.
  Each additional [* *] group or any portion thereof.

  	
   

  	
  Market rate to be agreed

  
	
   

  	
   

  	
   

  
	
  [* *] fees
  per request: (Limited to [* *] or less)

  	
   

  	
  Market rate to be agreed

  
	
   

  	
   

  	
   

  
	
  Includes [* *]; Letter of [* *] required at time of
  request

  	
   

  	
   

  
	
   

  	
   

  	
   

  
	
  Inventory fees per request:

  	
   

  	
   

  
	
   

  	
   

  	
   

  
	
  Inventory reconciliation can be performed
  upon request.  Hourly fee applied

  	
   

  	
   

  
	
   

  	
   

  	
   

  
	
  [* *] fees
  per [* *] (Includes
  [* *]):

  	
   

  	
   

  
	
  Europe

  	
   

  	
  Market rate to be agreed

  
	
  US Locations

  	
   

  	
  Market rate to be agreed

  

 

No later than 1st
November in each year, the parties shall meet to agree pricing for technical
consultancy services for the following year, taking into consideration any
documented increases in the Avecia’s costs for providing such services.  If the parties are unable to reach agreement
on pricing by 30th November in any year, the price shall be
increased by reference to:

National Statistics - Monthly
Digest of Statistics (ISSN 0308-6666)

Section 18.11 Prices and Wages
Average Earnings Index - all employee jobs (not seasonally adjusted) -
excluding bonuses Industry Sector - Chemicals and man-made fibres.

 

Stressgen
shall pay invoices in accordance with the provisions of the Agreement.

 

[*] = Confidential Treatment Request(ed).Exhibit
10.1

 

ARRAY
BIOPHARMA INC.

 

AMENDMENT
TO

EMPLOYEE
STOCK PURCHASE PLAN

(as
amended and restated September 12, 2002)

 

The Array BioPharma Inc. Employee Stock Purchase Plan
(as amended and restated September 12, 2002) (the “Plan”) is hereby amended as
set forth below:

 

1.                                       The
first sentence of Section 8, “Rights to Purchase Common Stock; Purchase Price.”
is hereby amended and restated to read as follows:

 

“Rights to purchase shares of Common Stock will be
deemed granted to participating employees as of the first trading day of each
Offering Period for a number of shares equal to $25,000 divided by 85% of the
fair market value of the Common Stock on the first day of the Offering Period.”

 

2.                                       A
new first sentence is added to the end of Section 8, “Rights to Purchase Common
Stock; Purchase Price.” to read as follows:

 

“On the first day of each Purchase Period that: (i) is
not also the start of a new Offering Period and (ii) occurs in the same
calendar year as an earlier Purchase Period, each participating employee’s
right to purchase shares of Common Stock granted under this Section 8 shall be
reduced by the number of shares of Common Stock purchased on behalf of such
participating employee in the immediately preceding Purchase Period.”

 

3.                                       Section
14, “Changes in Elections to Purchase.” is hereby amended by the addition of a
new subsection (c) to read as follows:

 

“(c) 
Notwithstanding subsection 14(b) above, any participating employee may
increase (subject to the maximum limitation on purchases under the Plan
provided for in Section 9 and any additional limitations imposed by section 423
of the Code) or decrease his or her payroll deduction, to take effect on the
first day of the next Purchase Period, by delivering to the Company a new form
regarding election to participate in the Plan under Section 5 above.  The Company may impose reasonable
administrative restrictions on the frequency of changes in payroll deductions,
required advance notice for changes in payroll deductions and on the minimum
amount of payroll deductions.”

 

4.                                       The
Plan shall otherwise be unchanged by this Amendment.

 

This Amendment to the Plan was duly adopted and
approved by the Board of Directors of the Corporation at a meeting held on
April 29, 2004.

 

 

	
   

  	
   

  	
  /s/ R.
  Michael Carruthers

  	
   

  
	
   

  	
   

  	
  R. Michael Carruthers, CFO

Source: [{"source": "alea-institute/alea-institute/kl3m-data-edgar-agreements/train-00065-of-00352.parquet"}, [{"source": "alea-institute/alea-institute/kl3m-data-edgar-agreements/train-00065-of-00352.parquet"}]]