LICENCE AND CO-DEVELOPMENT AGREEMENT

265 Strand
London WC2R 1BH
Tel: +44 (0)20 7067 2000
Fax: +44 (0)20 7067 2222

BETWEEN:

EMERGENT EUROPE LIMITED, a company organised and existing under the laws of England (Company number 03270465) and having its registered office at 545 Eskdale Road, Winnersh Triangle, Wokingham, Berkshire, RG41 5TU (“Emergent”);

AND

SANOFI PASTEUR, S.A., a Société Anonyme organised and existing under the laws of France (Company registration number 349 505 370 Lyon) and having its registered head office at 2, avenue pont pasteur, Lyon 69007 France (“sanofi pasteur”).

WHEREAS:

IT IS AGREED as follows:

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“Affiliate” means any company or other business entity which controls, is controlled by, or is under common control with, either Emergent or sanofi pasteur (as the context requires). For the purpose of this definition, “control” means direct or indirect beneficial ownership of at least fifty percent (50%) of the voting share capital in such company or other business entity.

“Annual Budget” has the meaning set out in Clause 5.3.

“Annual Development Plan” means the detailed plan setting out the activities to be conducted by Emergent and sanofi pasteur in any Year (or such other period as the SC may decide) as part of the Development Programme.

“Antigen” means a distinct and uniquely identifiable protein (including glycoproteins and lipoproteins), peptide, polysaccharide, or protein-polysaccharide conjugate, capable of eliciting a specific immune response and reacting with the products of that response and in respect of which a Party has provided to the other complete details of (a) in the case of a protein, the amino acid sequence or (b) in the case of other molecules, the chemical structure of such molecule, in each case sufficient to identify such molecule. For the purpose of this Agreement in the case of: (i) a protein Antigen encoded by a given gene, any antigenic determinants or epitope containing portions of such protein, and all fragments, derivatives and variants of any such protein, shall all be deemed to be one Antigen; (ii) a polysaccharide Antigen from a given serogroup of Neisseria meningitidis or another bacterial pathogen, any antigenic determinants or epitope containing portions of such polysaccharide, and all fragments, derivatives and variants of any such polysaccharide, shall all be deemed to be one Antigen; and (iii) a protein-polysaccharide conjugate where each of the protein and polysaccharide components would individually meet the definition of Antigen as defined above and each component separately contributes to protection against Neisseria meningitidis serogroup B infections, such protein and polysaccharide components will each be deemed to be one Antigen (each of which will be deemed to be the same Antigen as the relevant protein or polysaccharide and any antigenic determinants, epitope containing portions, fragments, derivatives and variants of such protein or polysaccharide, as set out above) and such protein-polysaccharide conjugate will in such circumstances be considered two (2) Antigens.

“Applicable Law” means the applicable laws, rules and regulations (including any rules, regulations, guidelines or other requirements of national and international patent offices and of the Regulatory Authorities, including GMP, GLP and GCP) that may be in effect from time to time in the Territory, to the extent applicable.

“Business Day” means a day other than a Saturday or Sunday on which banking institutions in both Paris, France and London, England are open for business.

“Candidate Antigen” means any of the [**] candidate Antigens identified by Emergent prior to the Effective Date as more particularly described in Schedule 3.

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“Clinical Candidate” means any Candidate Antigen or other Programme Antigen selected by the SC for clinical Development in accordance with this Agreement and the Development Plan (and in particular the Outline Candidate Evaluation and Selection Plan). A Clinical Candidate is a Programme Antigen.

“Clinical Study” means any investigation in human subjects intended to discover or verify the clinical, pharmacological and/or other pharmacodynamic effects of any Antigen or Meningitis B Product, or to identify any adverse reactions to any Antigen or Meningitis B Product and/or to study absorption, distribution, metabolism and excretion of any Antigen or Meningitis B Product with the object of ascertaining its safety and/or efficacy. Clinical Study includes any Phase I Study, Phase II Study, Phase III Study, Phase IV Study or any other investigation in human subjects involving a Clinical Candidate or Product that a Regulatory Authority may require that either Party performs for inclusion in Regulatory Documentation or as a condition of a Regulatory Approval.

“Clinical Study Application” means an investigational new drug application filed with a Regulatory Authority for any Regulatory Approval required to supply or use a Clinical Candidate or Product for the purposes of a Clinical Study in a country or jurisdiction in the Territory.

“Co-Exclusive Antigen” has the meaning set out in Clause 5.12.5.

“Combination Product” means a product developed and administered as a single product pursuant to a single Marketing Authorisation that comprises a Unitary Product combined with another product that is not a Meningitis B Product and does not contain a Programme Antigen or an Additional Antigen. For the avoidance of doubt a Unitary Product will not constitute a Combination Product merely because it is packaged with another product and sold as one product or is sold as a “bundle” with one or more products.

“Commercialisation” or “Commercialise” means any and all lawful activities directed to the commercialisation of a Product (whether before or after Marketing Authorisation has been obtained), including marketing, manufacturing for commercial sale, promoting, detailing, distributing, offering to sell and selling a Product, importing a Product for sale, conducting additional human clinical studies with respect to an indication for which Marketing Authorisation has been obtained and interacting with Regulatory Authorities regarding the foregoing. When used as a

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“Commercialisation Plan” means the written plan for the Commercialisation of a Product in the Territory (including detailed strategy, budget and proposed timelines), as more particularly described in Clause 6.3 as may be amended or updated in accordance with Clause 6.3.

“Commercially Reasonable Efforts” means, with respect to the Development or Commercialisation of any Programme Antigen or Product, the level of efforts and resources customarily applied in the research-based pharmaceutical industry in the development of a product candidate or the commercialisation of a product of similar commercial potential at a similar stage in its lifecycle, taking into consideration its safety and efficacy, its cost to develop, the competitiveness of alternative products, its proprietary position, the likelihood of regulatory approval, its profitability (provided that in assessing such profitability sanofi pasteur shall not be entitled to take into account the royalties, milestones or other payments due or potentially due to Emergent with respect to such Programme Antigen or Product pursuant to this Agreement), and all other relevant factors.

“Competitive Product” means a Meningitis B Product or potential Meningitis B Product (in each case, other than a Product) Exploited by sanofi pasteur or any of its Affiliates or Sub-Licensees.

“Confidential Information” means either the Emergent Confidential Information or the sanofi pasteur Confidential Information, or both the Emergent Confidential Information and the sanofi pasteur Confidential Information, as the context requires.

“Control” means, with respect to any Antigen or other Materials, or Patent Rights, item of Know How, Regulatory Documentation, Trademark or other intellectual property right, possession of the right, whether directly or indirectly, and whether by ownership, licence or otherwise (other than pursuant to this Agreement), to grant access to such Antigen, other Materials or Regulatory Documentation or to assign, or grant a licence, sub-licence or other right to or under, such Patent Rights, Know How, Regulatory Documentation, Trademark or other intellectual property right as provided for herein, without violating the terms of any agreement with any Third Party or any other arrangement with any Third Party.

“Demonstration of Presence of SBAs” has the meaning set out in Clause 5.6.3.

“Development” and, with correlative meaning, “Develop”, means all activities related to preclinical research, discovery and testing, toxicology, process development, stability studies, formulation development, manufacturing scale-up, production of clinical product batches, development of quality assurance/quality control testing, clinical studies and regulatory affairs, including the conduct of Clinical Studies, for a Product in connection with obtaining Regulatory Approvals of such Product.

“Development Activities” means the activities of the Parties relating to the Development of Programme Antigens and Products as set out in the Development Plan or any Annual Development Plan.

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“Development Programme” has the meaning set out in Clause 2.1.

“Early Development Phase” means the period from the Effective Date until the Transition Date.

“Effective Date” means 1 April 2006.

“Emergent Activities” means the Development Activities allocated to Emergent in the Development Plan or any Annual Development Plan.

“Emergent Combined Improvements” means any patentable improvement, enhancement or modification, which is made, developed or conceived by employees or consultants of Emergent, solely or jointly with Third Parties, in the conduct of the Development Programme, that relates to any subject matter that is covered both by Emergent Independent Patent Rights and sanofi pasteur Independent Patent Rights, such that the Exploitation of such improvement, enhancement or modification without consent would infringe both Emergent Independent Patent Rights and sanofi pasteur Independent Patent Rights.

“Emergent Confidential Information” means Emergent Independent Know How, non-patented Emergent Programme Technology and trade secrets and any other confidential information relating to the business affairs or finances of Emergent or its Affiliates.

“Emergent Expenses” means (i) costs or expenditures incurred by Emergent (or for its account by an Affiliate) in connection with the engagement of any Third Party to conduct work in connection with Emergent Activities; and (ii) any capital expenditures incurred by Emergent (or for its account by an Affiliate of Emergent) in connection with the Development Programme; and (iii) any other costs or expenses incurred by Emergent (or for its account by an Affiliate of Emergent), in each case as provided for in an Annual Budget and without any mark-up.

“Emergent Independent Know How” means all Know How that (i) as of the Effective Date is in the Control of Emergent, (ii) Emergent is free to disclose to a Third Party and (iii) is necessary or reasonably useful to the Development Programme or to the Exploitation of a Product.

“Emergent Independent Patent Rights” means those Patent Rights Controlled by Emergent as of the Effective Date that are set out in Schedule 5.

“Emergent Independent Technology” means Emergent Independent Patent Rights and Emergent Independent Know How.

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“Emergent Programme Patent Rights” means the Patent Rights Controlled by Emergent that claim or otherwise cover Emergent Programme Technology.

“Emergent Programme Technology” means any Technology made, developed or conceived by employees or consultants of Emergent, alone or jointly with Third Parties, in the conduct of the Development Programme other than Emergent Combined Improvements.

“Emergent Project Leader” means the Project Leader appointed by Emergent pursuant to Clause 2.2.

“Emergent Technology” means the Emergent Independent Technology and the Emergent Programme Technology.

“European Union” or “EU” means the countries of the European Union as constituted from time to time during the term of this Agreement.

“Exploit” means to make, have made, import, use, sell, or offer for sale, including to discover, research, develop, register, modify, enhance, improve, manufacture, have manufactured, hold/keep (whether for disposal or otherwise), formulate, optimise, have used, export, transport, distribute, promote, market or have sold or otherwise dispose or offer to dispose of, a product or process and “Exploitation” means the act of Exploiting a product or process.

“FDA” means the United States Food and Drug Administration and any successor agency or authority thereto.

“Field” means the prophylactic immunisation of human populations to prevent Neisseria meningitidis infections.

“First Commercial Sale” means the first commercial sale by or on behalf of sanofi pasteur, its Affiliates or Sub-Licensees of a Product in each country of the Territory after Marketing Authorisation has been granted by the appropriate Regulatory Authority in that country.

“First Year” means the period commencing on the Effective Date and ending on 31 December 2006.

“FTE” means a Full Time Equivalent of one thousand, five hundred and eighty nine (1,589) hours of work per year (based on a thirty-five (35) hour working week and standard vacations and holidays), devoted to or in support of the Emergent Activities that is carried out by employees, contract personnel or consultants of Emergent as recorded on Activity Forms.

“FTE Cost” means, for any period, the FTE Rate multiplied by the applicable number of FTEs in such period. The FTE Cost shall be denominated in pounds sterling (£).

“FTE Rate” means an amount reflecting the average annual gross salary, social charges and benefits (including for notice periods in compliance with applicable

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“GAAP” means in relation to Emergent, United Kingdom, and in relation to sanofi pasteur, French, generally accepted accounting principles consistently applied, or such other generally accepted accounting principles, consistently applied, as may be applicable to the relevant Party or Third Party at the relevant time.

“GCP” means the then-current standards for Clinical Studies involving pharmaceuticals as are required by the Regulatory Authorities in Europe, the United States and Japan and other organisations and governmental agencies in countries in which any Product is intended to be sold or tested, to the extent such standards are not less stringent than ICH Topic E6: Good Clinical Practice Consolidated Guideline.

“GLP” means the then-current standards for laboratory activities for pharmaceuticals, as are required by the Regulatory Authorities of Europe, the United States and Japan, including 21 C.F.R. part 58 and EC Directives 87/18/EEC, 88/320/EEC and 1999/11/EC, in each case, as amended from time to time and any relevant international standards or principles such as those adopted by the Organisation for Economic Co-operation and Development.

“GMP” means the then-current standards for good manufacturing practices as are required by the Regulatory Authorities in Europe, the United States and Japan and other organisations and governmental agencies in countries in which any Product is intended to be manufactured or sold, to the extent such standards are not less stringent than standards of good manufacturing practice in Europe, the United States and Japan.

“ICH” means the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use.

“Inclusion Criteria” means the criteria set out in Schedule 8 for the inclusion of an Antigen into a Meningitis B Product.

“Indicative Cost Schedule” means the indicative FTE Costs and Emergent Expenses set out in Schedule 2.

“Joint Patent Rights” means the Patent Rights that claim or otherwise cover Joint Technology.

“Joint Project Team” or “JPT” means the committee of Emergent and sanofi pasteur representatives established in accordance with Clause 4.1.

“Joint Technology” means any and all Technology conceived, discovered, developed or otherwise made jointly by or on behalf of Emergent (or its Affiliates or, to the extent permitted by their agreements therewith, their respective licensees and sub-licensees), on the one hand, and sanofi pasteur (or its Affiliates or, to the extent permitted by their agreements therewith, their respective licensees and sub-licensees)

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“Know How” means unpatented technical and other information which is not known to the public, including information comprising or relating to concepts, discoveries, data, designs, formulae, ideas, experience, inventions, improvements, methods, models, assays, research plans, procedures, designs or experiments and tests and results of experimentation and testing, including results of research or development, together with processes, including manufacturing processes, specifications, techniques, chemical, pharmacological, toxicological, clinical, analytical and quality control data, trial data, case report forms, data analyses, reports or summaries and information contained in submissions to and information from ethical committees and regulatory authorities. The fact that an item is known to the public shall not be taken to exclude the possibility that a compilation including the item, or a development related to the item, is (or remains) not known to the public.

“Late Development Phase” means the period commencing on the Transition Date and continuing for so long as any Product is in Development including, if applicable, any period(s) during which the Development Programme is continuing pursuant to Clause 5.9.

“Later Stage Clinical Development Plan” means the plan set out in Appendix 3 to the Development Plan.

“Liabilities” has the meaning set out in Clause 13.1.

“Major Market Country” means each country in the European Union, the United States, Japan, Australia, Canada, China, New Zealand, Norway, Russia, Singapore, Hong Kong, India and South Korea.

“Marketing Authorisation” means a Biologics License Application (as defined in the United States Federal Food Drug and Cosmetic Act (as amended from time to time) and the regulations promulgated thereunder), and any corresponding Regulatory Approval necessary to import, market, transfer, supply or sell a product in any country, but not including pricing and reimbursement approvals.

“Materials” means biological and chemical materials including Antigens, screens, cell lines, cells, vectors, nucleic acids and reagents, and any progeny or derivatives thereof.

“Meningitis B Product” means a product or potential product for the prophylactic immunisation of human populations to prevent Neisseria meningitidis serogroup B infections (whether or not such product confers protection against any other meningococcal serogroup infection).

“Net Sales” means the gross invoice price of Products sold by sanofi pasteur, its Affiliates and Sub-Licensees to the first Third Party less, to the extent specifically allocable to the Product and actually incurred or allowed and if not already deducted in the amount invoiced:

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Any of the deductions listed above that involves a payment by sanofi pasteur, its Affiliates or its Sub-Licensees, as the case may be, shall be taken as a deduction in the Quarter in which the payment is accrued by such entity. For purposes of determining Net Sales, any Product shall be deemed to be sold when invoiced. For purposes of calculating Net Sales, sales between or among sanofi pasteur, its Affiliates, and its Sub-Licensees shall be excluded from the computation of Net Sales, but sales by sanofi pasteur, its Affiliates or its Sub-Licensees to Third Parties (other than its Sub-Licensees) shall be included in the computation of Net Sales. If, in any country, any Product is sold or otherwise disposed of for any consideration other than an exclusively monetary consideration on bona fide arm’s length terms, such Product shall be deemed to have been sold exclusively for money at the average sales price during the applicable Quarter generally achieved for such Product in the country in which such sale or other disposition occurs or if there is no average sales price in that country, the average sales price in comparable countries.

Adjusted Combination Net Sales. In the event that a Product is sold in any country in any Quarter in the form of a Combination Product, Net Sales of such Combination Product shall be adjusted to represent the contribution of each product to the value of the Combination Product by multiplying actual Net Sales of such Combination Product in such country in such Quarter calculated as set out above by the fraction A/(A+B) (such adjusted amount the “Adjusted Combination Net Sales”) where A and B are determined as follows:

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Minimum royalties payable to Emergent on a Combination Product in any country: If the Product is sold as a Combination Product, the royalty payable to Emergent on sales of the Combination Product in the relevant country in the applicable Quarter shall be the higher of:

Bundled products: If, in any country, a Product and one or more products capable of separate sales are “bundled” and sold without separate pricing for each product within the bundle, Net Sales per unit of such Product shall be deemed to be the average sales price at which that Product has been sold unbundled in such country during the applicable Quarter.

“Outline Candidate Evaluation and Selection Plan” means the plan for the screening, selection and progression of Programme Antigens prior to clinical Development as set out in Appendix 1 to the Development Plan.

“Outline Commercialisation Plan” means the Outline Commercialisation Plan set out in Schedule 4.

“Party” means either Emergent or sanofi pasteur and “Parties” means Emergent and sanofi pasteur.

“Patent Rights” means any and all (a) patents, (b) pending patent applications, including all provisional applications, continuations, continuations-in-part, divisions,

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“Phase I Product and Clinical Development Plan” means the plan set out as Appendix 2 to the Development Plan.

“Phase I Study” means a Clinical Study in any country that is intended to initially evaluate the safety or pharmacological effect of an Antigen or Meningitis B Product in subjects or that would otherwise satisfy requirements of 21 C.F.R. 312.21(a), or its equivalent outside the United States.

“Phase II Study” means a Clinical Study in any country that is intended to initially evaluate the effectiveness of an Antigen or Meningitis B Product for a particular indication or indications in patients with the disease or indication under study or that would otherwise satisfy requirements of 21 C.F.R. 312.21(b), or its equivalent outside the United States.

“Phase III Study” means a pivotal Clinical Study, the principal purpose of which is to establish safety and efficacy in patients with the disease or indication under study as required in 21 C.F.R. 312.21(c), or similar clinical studies prescribed by the Regulatory Authorities in a country other than the United States whether or not such study is a traditional Phase III Study.

“Phase IV Study” means a Clinical Study that is required or requested by a Regulatory Authority as a condition of or in connection with obtaining or maintaining a Regulatory Approval (whether commenced either prior to or after receipt of such Regulatory Approval).

“Pre-Clinical Study” means any investigation in animals or in vitro intended to discover or verify the pharmacological or other pharmacodynamic effects of any Programme Antigen or Product, or to study absorption, distribution, metabolism and excretion of any Programme Antigen or Product with the object of ascertaining its safety.

“Primary Inclusion Criteria” means the criteria set out in Schedule 8 Part I for the progress of Antigens into Phase II Studies.

“Product” means a vaccine or potential vaccine containing one or more Programme Antigens. Unitary Products and Combination Products are Products.

“Product Trademark” has the meaning set out in Clause 6.5.

“Programme Antigen” means any Candidate Antigen, including any Antigen derived from a Candidate Antigen by either Party, or any other Antigen (other than a Terminated Antigen or a Repatriated Antigen) claimed or otherwise covered by Emergent Patent Rights or Joint Patent Rights.

“Project Leader” has the meaning set out in Clause 2.2.

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“Regulatory Approval” means any and all approvals (including any applicable supplements, amendments, pre- and post-approvals, governmental price and reimbursement approvals and approvals of applications for regulatory exclusivity), licences, registrations, or authorisations of any federal, national, multinational, international, state, provincial or local regulatory agency, department, bureau, commission, council or other governmental entity necessary for the manufacture, distribution or other transfer of possession, use, holding, storage, import, export, transport, promotion, marketing, supply or sale of a product in a country or jurisdiction in the Territory, or the use of a product or Antigen in any Pre-Clinical Study or Clinical Study. For clarity, a compendia listing shall not be deemed to be a Regulatory Approval.

“Regulatory Authority” means the FDA or any counterpart of the FDA outside the United States, or other national, supra-national, regional, state or local regulatory agency, department, bureau, commission, council or other governmental entity with authority over the distribution, importation, exportation, manufacture, production, use, storage, transport, pre-clinical or clinical testing or sale of a Meningitis B Product or Antigen.

“Regulatory Documentation” means all applications, registrations, governmental licences, authorisations and approvals (including all Regulatory Approvals), all correspondence submitted to or received from Regulatory Authorities and all supporting documents and all clinical studies and tests, relating to a Programme Antigen or Product, and all data contained in any of the foregoing.

“Repatriated Antigen” means a Programme Antigen repatriated to Emergent in accordance with Clause 5.12.3(f). An Antigen shall cease to be a Programme Antigen on becoming a Repatriated Antigen.

“Royalty Burden” has the meaning set out in Clause 7.4.1.

“sanofi pasteur Antigen” means an Antigen Controlled by sanofi pasteur that is not either a Third Party Antigen or a Programme Antigen.

“sanofi pasteur Confidential Information” means sanofi pasteur Independent Know How, unpatented sanofi pasteur Programme Technology and trade secrets and any other confidential information relating to the business affairs or finances of sanofi pasteur or an Affiliate.

“sanofi pasteur Independent Know How” means all Know How which either at the Effective Date or subsequently during the Term is in the Control of sanofi pasteur or its Affiliates (other than any Know How that constitutes unpatented Joint Technology or unpatented sanofi pasteur Programme Technology) and which sanofi pasteur is free to disclose to a Third Party which is necessary or reasonably useful to the Development Programme or to the Exploitation of a Product.

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“sanofi pasteur Independent Technology” means sanofi pasteur Independent Patent Rights and sanofi pasteur Independent Know How.

“sanofi pasteur In-Licence” means any licence deemed to be a sanofi pasteur In-Licence pursuant to Clause 5.8.1.

“sanofi pasteur Patent Rights” means the sanofi pasteur Independent Patent Rights and the sanofi pasteur Programme Patent Rights.

“sanofi pasteur Programme Patent Rights” means the Patent Rights Controlled by sanofi pasteur that claim or otherwise cover sanofi pasteur Programme Technology.

“sanofi pasteur Programme Technology” means any Technology made, developed or conceived by employees or consultants of sanofi pasteur, alone or jointly with Third Parties, in the conduct of the Development Programme.

“sanofi pasteur Project Leader” means the Project Leader appointed by sanofi pasteur pursuant to Clause 2.2.

“sanofi pasteur Technology” means the sanofi pasteur Independent Technology and the sanofi pasteur Programme Technology.

“SBA” means a serum bactericidal antibody, i.e., an antibody or antibodies which, in the presence of an exogenous source of complement, has the ability to kill Neisseria meningitidis bacteria. For clarity, the source of the complement used in the SBA assay shall be appropriate to the serum being measured, for example, for human sera, a human complement source obtained from a donor without bactericidal activity against the test strain shall be utilised.

“SBA Activity” means measurement of SBA titres in serum.

“Selection Criteria” means the technical selection criteria set out in the Outline Candidate Evaluation and Selection Plan and included in Appendix 1 to the Development Plan for the selection of Candidate Antigens to progress into Phase I Studies.

“Senior Officer” has the meaning set out in Clause 3.5.1.

“Serious Adverse Event” means an Adverse Event that at any dose: (a) results in death, (b) puts the patient at risk of death at the time of the event or occurrence, (c) requires inpatient hospitalisation or prolongation of existing hospitalisation, (d) results in persistent or significant disability or incapacity, (e) is a congenital anomaly/birth defect or (f) based upon reasonable medical scientific judgment, places a patient in jeopardy or may require intervention to prevent any of the events or occurrences

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“Steering Committee” or “SC” means the committee of Emergent and sanofi pasteur representatives established in accordance with Clause 3.1.

“Sub-Licensee” means a person (other than an Affiliate of sanofi pasteur) that is authorised by sanofi pasteur (with the express prior written consent of Emergent) to manufacture and sell a Product in the Field in the Territory (including any Third Party acting in collaboration with sanofi pasteur or its Affiliates). For clarity, a Sub-Licensee shall not include a Third Party to whom sanofi pasteur sells bulk Product together with a right to fill/finish, label, market and distribute such Product, provided that sanofi pasteur is not entitled to any additional consideration upon the Exploitation of such Product.

“Technology” means inventions, discoveries, improvements, trade secrets and proprietary methods, whether or not patentable, including Know How.

“Term” means the term of this Agreement, which term shall be the period commencing on the Effective Date and ending either on the date on which the final obligation of sanofi pasteur to make royalty payments under Clause 7.3 expires or, if earlier, the date on which this Agreement is terminated in accordance with Clause 14.2.

“Terminated Antigen” means the Antigens listed on Schedule 11 and each Programme Antigen determined by the SC to be a Terminated Antigen in accordance with Clause 5.15. An Antigen shall cease to be a Programme Antigen on becoming a Terminated Antigen.

“Territory” means all countries of the world.

“Third Party” means any corporation, unincorporated organisation, person or other legal entity other than Emergent or sanofi pasteur or their respective Affiliates.

“Third Party Antigen” means any Antigen Controlled by sanofi pasteur the Exploitation of which as a constituent of any Unitary Product would, but for a sanofi pasteur In-Licence infringe the Patent Rights of a Third Party.

“Trademark” means any corporate name, trade name, trade dress, service mark, logos and trademarks (whether or not registered) and all applications for, and registrations of, and all renewals, extensions or modifications to, and any goodwill associated with, any of the foregoing in the Territory.

“Transition Date” means the date on which all Pre-Clinical Studies and Phase I Studies involving a Programme Antigen and described in any Development Plan or Annual Development Plan have been completed or, if later, the date on which all Transition Plans in effect at such date are fully implemented to the satisfaction of the Parties.

“Transition Plan” has the meaning set out in Clause 5.5.1.

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“Valid Claim” means a claim of (i) an issued and unexpired patent, (ii) a patent the term of which has been extended pursuant to an extension of term or equivalent right anywhere in the world, (iii) a patent listed in a supplementary protection certificate or equivalent instrument anywhere in the world, (iv) a pending patent application providing that such application has been pending for no longer than ten (10) years, in each case which has not been withdrawn, cancelled, abandoned, disclaimed, revoked or held unpatentable, invalid or unenforceable by final decision of a court or other governmental agency of competent jurisdiction, which decision is unappealable or unappealed within the time allowed for appeal.

“Year” means the First Year and thereafter each successive period of twelve (12) months ending on the last day of December.

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Number of Programme Antigens and Additional Antigens in a Unitary Product

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Number of Programme Antigens and Additional Antigens in a Unitary Product

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For the avoidance of doubt, the Parties acknowledge that whether or not it is commercially reasonable to launch a Unitary Product before a Combination Product in any market will depend on market conditions at the relevant time and that consequently a failure by sanofi pasteur to launch a Unitary Product prior to a Combination Product in any country is not in itself sufficient to demonstrate that sanofi pasteur has failed to use Commercially Reasonable Efforts in accordance with Clause 6.2.

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For the avoidance of doubt, nothing in this Clause 14.3.1 is intended nor shall it operate to (i) grant any rights to Emergent under the sanofi pasteur Independent Technology; (ii) grant any rights to sanofi pasteur under the Emergent Technology; (iii) restrict sanofi pasteur’s rights with respect to the sanofi pasteur Technology or the Joint Technology; or (iv) restrict Emergent’s rights with respect to the Emergent Technology or the Joint Technology.

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(a) Clause 14.3.1 other than sub-clauses 14.3.1(a), (b) and (c) shall apply; and

(b) without prejudice to Emergent’s rights pursuant to Clause 14.3.7, Emergent shall have a non-exclusive, fully paid-up, royalty free licence under sanofi pasteur’s interest in the Joint Technology to Exploit any Programme Antigens, Terminated Antigens, Repatriated Antigens or Product anywhere in the world with the right to grant sub-licences for the Exploitation of such Programme Antigens, Terminated Antigens and Repatriated Antigens.

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provided that if the Notice is delivered by hand or transmitted by facsimile and such delivery or transmission occurs after 4.00 pm on a Business Day or on a day other than a Business Day, service will be deemed to occur at 9.00 am on the next following Business Day (such times and dates being local time at the address of the recipient).

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Emergent Europe Limited
545 Eskdale Road,
Winnersh Triangle,
Wokingham,
Berkshire, RG41 5TU
England

Fax no. 44 (0) 118 9443301

Attention: President, Emergent Europe Limited

With copy to:

Emergent Biosolutions, Inc
300 Professional Drive
Gaithersburg, MD 20879
USA

Fax no: 1 301 944 0173

Attention: General Counsel

If to sanofi pasteur:

Sanofi Pasteur S.A.
2, avenue pont pasteur
Lyon 69007 France

Fax no. 33 4 3737 7061
Attention: General Counsel

With copy to: Vice President, Corporate Development

Sanofi Pasteur SA
1541 avenue Marcel Mérieux
Marcy l’Etoile, 69280 France

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         IN WITNESS WHEREOF, the Parties have caused this Agreement to be executed by their duly authorised representatives.

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Appendix 1

Outline Candidate Evaluation and Selection Plan

1. Introduction

This appendix is intended to serve as supporting documentation to the main body of the Agreement. It has been compiled on the basis of a number of face to face interactions and represents the parties shared view of the work-plan required to fully evaluate the Candidate Antigens and to select Candidate Antigens for clinical development. The plan will be subject to change as agreed by the Steering Committee (SC), but it is recognised that the plan will require both parties to commit resources (personnel and equipment) that cannot be redeployed easily.

Sanofi pasteur and Emergent propose to enter a collaboration to develop a Meningitis B vaccine based on one or more of the potential [**] Candidate Antigens that Emergent has identified. These Candidate Antigens were identified as virulence genes encoding probable surface located proteins in a signature–tagged mutagenesis (STM) screen, or as surface located or secreted proteins in a leaderless PhoA functional screen. The Candidate Antigens are described and claimed in the Emergent owned patent applications [**] and [**] and related national filings and divisionals (as listed in Schedule 5 under Emergent Independent Patent Rights).

The starting point of the Co-Development Programme is to evaluate the pool of approximately [**] Candidate Antigens as potential meningitis vaccine candidates. An effective vaccine providing broad coverage against multiple menB strains or even potentially against multiple meningitis serogroups may contain multiple antigens ([**] antigens). In order to select Candidate Antigens or Programme Antigens for clinical development the Parties have agreed the Outline Candidate Evaluation and Selection plan detailed within this Appendix. This plan describes the main tasks to be performed and the Party or Parties responsible for performing each task. This plan may be refined periodically as necessary upon the agreement of the SC. In the following plan the evaluation and selection steps apply equally to Programme Antigens as to Candidate Antigens, however only the term Candidate Antigen is used for simplicity.

The aim of the candidate evaluation process is to comprehensively evaluate the pool of Candidate Antigens and to ensure that a suitable preclinical data package (with emphasis on functional assays and conservation) is generated on each of the Candidate Antigens in a systematic and objective manner to enable selection of individual Candidate Antigens for clinical development within an appropriate timeframe. However, if promising Candidate Antigens are

The selection criteria for selecting Candidate Antigens for clinical development are to be finalised and agreed by the SC, but will be based on the selection criteria listed below.

2. Prioritisation of Candidate Antigens for Pre-Clinical Screening

Given the large number of potential Candidate Antigens [**], the Candidate Antigens will first be evaluated on the basis of [**] and [**] to enable a prioritised Candidate Antigen list to be compiled.

2.1 [**] (Task Responsibility; Emergent and sanofi pasteur)

Emergent has performed some initial screens for [**]. Sanofi pasteur has also performed [**].

[**] Candidate Antigens have been identified that have potentially significant [**] and which may require further [**].

Sanofi pasteur has strong [**] capabilities, particularly in the areas of [**]. It is proposed that sanofi pasteur lead the [**] analysis of these Candidate Antigens.

If the [**], then a decision will be taken on whether the [**]. The collaboration will then consider the use of these [**] proteins. Candidate Antigens that [**] will be excluded.

Sanofi pasteur and Emergent will agree on the patentability and freedom to operate position for each Candidate Antigen or Programme Antigen. It is envisaged that the [**] will be key to and underpin the product development and that additional Intellectual Property [**] is likely to be generated during the collaboration which will provide further patent protection for any collaboration Product.

2.3 [**] (Task Responsibility; Emergent and sanofi pasteur)

Emergent and sanofi pasteur have performed a number of [**] screens to rank the Candidate Antigens (see below). Sanofi pasteur and Emergent have agreed to a prioritised list of Candidate Antigens [**].

2.3.1. [**] (Task Responsibility; Emergent)

An [**] screen has been performed to determine the level of [**]. Candidate Antigens have been ranked in the following order;

2.3.2. [**] (Task Responsibility; Emergent and sanofi pasteur)

Candidate Antigens have been updated for [**] using [**] Candidate Antigens have been predicted to be [**]. The work plan below is focused on these [**] candidates. [**] of remaining Candidate Antigens will be experimentally confirmed at a later stage.

The Candidate Antigens clearly predicted to be [**] have been prioritised, followed by those with [**].

2.3.3. Literature search (Task Responsibility; Emergent)

The literature search for each Candidate Antigen will be updated. Candidate Antigens known to be [**] have been identified [**].

[**] Candidate Antigens will be evaluated for [**]. Expressed Candidate Antigen proteins will be used to [**].
Of those [**] prioritized Candidate Antigens, [**]

3.1 Candidate Antigen [**] (Task Responsibility; Emergent)

The high degree of [**] seen within the [**] of the Candidate Antigens [**] suggests that the Candidate Antigens are likely to be [**].

[**] screening of each Candidate Antigen will be performed initially for approximately [**]. This involves using [**]. These would first be checked [**], but would be underwritten by [**]. This approach should pick up Candidate Antigens that have [**] and will be used as a criterion to exclude Candidate Antigens from further progress on the basis of [**]. However, even if [**] is poor, this data may be valuable in later decisions on [**].

It is likely that many if not all Candidate Antigen will pass this [**] screen and that a significant number of Candidate Antigens will require extended [**] screening against a [**] at a later point in the Co-Development Programme, particularly if selected as a Clinical Candidate.

It is likely that [**] of Candidate Antigens will prove to be a significant rate-limiting step within the pre-clinical screening programme. The approach taken will be to [**]. Less emphasis will be applied in producing a [**] for a given Candidate Antigen at this initial evaluation stage, with the emphasis on producing [**] as quickly as possible for [**] evaluation.

[**]. Emergent propose to use the [**] that should be suitable for down-stream process (DSP) development. [**] Candidate Antigens may not be at suitable levels or be deemed as unsuitable for further process development and alternate [**] may be considered.

Given that many of the Candidate Antigens are predicted to be [**] proteins, it is likely that they will be [**] that contain highly pure Candidate Antigen [**]. This can be advantageous for [**]. However, the [**]. Once in a [**] state the protein is [**]. The aim of the [**] step is to obtain protein in a [**] form suitable for [**]. Emergent proposes to assess the success of the [**] using [**]. The [**] protein should [**].

Particular attention will be given to protein [**], as maintaining [**] may be important in generating [**], particularly in the case of [**]. A [**] screen will be performed to assess a range of [**]. As [**] assays are not available, it is proposed that the [**] of the protein [**] will be defined as the [**]. The success of [**] will initially be assessed by [**]. Samples which show [**] will then be further analysed by [**].

Emergent propose to [**] only once [**] is demonstrated.

Candidate Antigen proteins that are successfully [**]. This ensures that the material is sufficiently [**] to allow material to be [**].

3.3. [**] (Task Responsibility; Emergent)

[**] assays depend on the ability of [**]. Different [**], and in particular, different [**] vary [**]. Therefore they can be expected to vary in [**]. Overall, there is not a clear [**] among [**], although in most systems, [**] has lowest activity in terms of [**] regimen that induces [**] would give the best chances of [**]. Therefore [**] are selected for pre-clinical studies, as the priority should be [**] will thus initially be selected on the basis of [**], rather than whether or not [**].

Accordingly Emergent proposes to use the [**] may be included at a later stage with Candidate Antigens firstly selected with [**].

[**] will only be performed if time and resource permits, priority will be given to performance of the [**] assays.

3.4 Pre-clinical [**] evaluation (Task Responsibility; Emergent and sanofi pasteur)

Pre-clinical [**] testing will be used to establish which Candidate Antigens will be selected for further clinical development. Selection can be based upon [**]

[**] used in the pre-clinical assays may be very important for each antigen and [**] in some or all of the pre-clinical assays. [**] will be evaluated, first under [**] and alternate [**].

3.5 [**] (Task Responsibility; Emergent)

[**] will be used to measure if [**] the Candidate Antigens [**]. Furthermore, a number of [**] will be evaluated to demonstrate [**]. Alternatively, [**] may be used to [**].

3.6 [**] (Task Responsibility; Emergent and sanofi pasteur)

A reliable and well-understood [**] is a key functional activity test for each Candidate Antigen as this assay is currently the [**]. Both Emergent and sanofi pasteur will perform [**]. Candidates that meet the [**] selection criteria set by the SC, will be considered by the SC for entry into clinical development.

A candidate that does not demonstrate [**], or in another agreed [**] assay [**], is unlikely to be taken forward into clinical development.

3.7 [**] assays (Task Responsibility; Emergent or sanofi pasteur),

Assays that utilise [**] will be used as an alternative [**] measure [**]. Both [**] assays provide [**] measurement, although these assays can be [**]. However, the assay may be more sensitive than the [**]. Positive activity in either assay format is valuable, however

3.8 [**] (Task Responsibility; sanofi pasteur)

[**] can give valuable characterisation data on individual Candidate Antigens. Demonstration of [**] for a Candidate Antigen is valuable as [**]. The parties intend that only Candidate Antigens that fail to generate [**] but are positive in pre-clinical [**] assays [**], should be further evaluated for the [**]. Further [**] work may be performed once a Candidate Antigen has been selected for clinical development.

A flow chart of the proposed Candidate Evaluation and Selection Plan is shown below.

[**]

The table below summarises the main tasks and responsible parties for the Candidate Evaluation and Selection Plan.

Table 1. Task responsibilities for the Candidate Evaluation and Selection Plan

5. Project Management and Resources Required (Task Responsibility; Joint)

5.1 Project Timelines

The current project work-plan to evaluate the [**] Candidate Antigens will be completed within approximately [**] with the proposed level of resource below. A Gantt chart outlining the main tasks and associated timelines follows.
[**]

5.2 Emergent Resource Required

In order to resource the programme adequately, Emergent will need to dedicate the necessary number of skilled Full Time Equivalents (FTEs) to the project. Whilst it is recognised that the work-plan may be modified by the SC, the following represents Emergent’s best estimate of the Emergent resource that will be required to execute the work-plan illustrated in the Gantt chart above. Resource levels assume a [**]. The proposed resource levels do not include any contingency resource [**]

Year 1

Year 2

5.3 [**]

At the present time, based on current rates, this is estimated as being approximately [**].

5.4 Capital Expenditure Equipment

At this point it is anticipated that the following capital expenditure equipment will be required to meet the projected needs of the project work-plan. Any further
capital expenditure required will be discussed and agreed at the Joint Project Team level and approved as necessary by the SC. This equipment remains the property of [**].

6. Selection of Candidate Antigens for clinical development
(Emergent and sanofi pasteur)

Following completion of the pre-clinical evaluation of the Candidate Antigens a final ranking of the Candidate Antigens will be performed to facilitate selection of the best Candidate Antigens for clinical development.

Candidate Antigens will only be selected for clinical development by the SC if they pass certain criteria, currently anticipated to include the following;

[**]

These criteria will be defined and agreed by the SC in advance of any Candidate Antigen selection for clinical development.

Assuming all of the above criteria are met for more than one Candidate Antigen, each criterion ranking, together with the ability to develop a scalable commercial process will be used to prioritise the Candidate Antigens for entry into full-scale development and ultimately clinical development.

At the SC’s discretion, there is also the option to [**] into the clinic ahead of completing the evaluation of all Candidate Antigens, if the Candidate Antigens meet the agreed pre-clinical selection criteria.

The Parties envisage that [**] Candidate Antigens will be selected for clinical development, with the final vaccine comprising [**].

[**]

Appendix 2

Early Development Phase

Phase I Product and Clinical Development Plan

This appendix is intended to serve as supporting documentation to the main body of the agreement.

It is recognised that it is difficult to plan precisely the further one goes out from the commencement of the project. In this regard it is acknowledged that the following plan may change, subject to approval by the Steering Committee (SC). However the material below represents an overview of the work that will be required to take one protein through from selection for clinical development to the end of Phase I.

Specifically, this plan highlights the work that will be required to take one protein from the point at which it becomes a Clinical Candidate in the evaluation and selection phase to the point at which the data from a Phase I will have been analysed and reported.

It is recognised that there may need to be a Transition Plan to attain smooth and efficient handover of pilot scale processes and associated data to Sanofi after completion of Phase I trials.

If more than one Clinical Candidate were to be chosen for clinical development then the plan will need to be modified appropriately to take account of the extra resource (and potential synergies) required by such a decision.

Following the selection of Clinical Candidates(s) for clinical development, the Steering Committee will finalise and agree the details of a Phase I Product and Clinical Development Plan for each selected antigen including the main activities to be performed, allocation of responsibilities, an appropriate level of product compliance, the resource requirements (financial, FTEs, contractors, hardware and reagents) and expected timelines. The general principles and the anticipated major components of the plan are listed below.

General Principles

Emergent will be responsible for manufacture of Phase I clinical material, for interactions with regulatory bodies relating to Phase I, and for conducting/managing Phase I clinical trials.

The components of a Phase I Product and Clinical Development Plan will include the following;

An outline description of the anticipated tasks is given below.

1. Further Preclinical Characterisation (Task responsibility; Emergent and Sanofi)

The intention of the pre-clinical screening and evaluation process is to select candidates that are suitable for development as a vaccine against N. meningitidis serogroup B within an appropriate timeframe. When a Clinical Candidate moves from pre-clinical screening into clinical development further pre-clinical characterisation will be performed. Whilst the additional pre-clinical work required is likely to be Clinical Candidate specific, further [**] studies may be performed, [**].

Following selection of a Clinical Candidate for clinical development, one of the first steps will be to demonstrate that the [**] profile for the Clinical Candidate remains consistent following [**]. For this purpose the Clinical Candidate [**] Clinical Candidate protein will then be [**].

The [**] assays used to demonstrate [**] in the preclinical selection screen will then be repeated for [**]. Depending on the [**] assay selected, these assays may be performed at both Emergent and Sanofi. The corresponding [**] will be repeated alongside the [**] as a positive control. This will confirm that the [**]. However, if the [**] fails to demonstrate [**] activity, this may indicate a technical problem, which will

As further Clinical Candidates move into clinical development, detailed pre-clinical studies will be performed to support [**] that would support the clinical development strategy

2. Product Development (Task responsibility; Emergent)

[**] characterisation will be performed on the [**].

2.1 [**] and Selection

Emergent will [**] and select the [**] in-house. The criteria for selection are:

If a [**] meets all of these criteria, a [**] will be manufactured in-house. This [**] will be progressed into development. No animal-derived materials will be used in the [**] in-house or at Contract Manufacturing Organisations (CMOs).

2.2 [**]

The [**] will be transferred to the selected Contract Manufacturing Organisation (CMO) and will be tested to ensure that it is pure and free from adventitious agents before being accepted into the CMO facility. The [**] will be manufactured from the [**]. This manufacture will be performed by [**]. Phase I clinical supplies will be manufactured directly from the [**]. It is anticipated that the [**] will be manufactured following successful completion of Phase I.

2.3 Process Development and Manufacturing Strategy

[**] purification processes suitable for transfer to a CMO will be developed in-house and will immediately focus on deriving both a commercially and regulatory acceptable process. Emergent will systematically screen each process step to find the optimal process conditions e.g. [**]

The selected skeleton process will be refined and scaled up at a CMO so that it is suitable for the manufacture of clinical trials material. Emergent will provide the necessary support to the CMO to ensure that a suitable manufacturing process is developed in a timely manner. Emergent will manage the transfer of

2.3.1 Development of Processes

2.3.1.1 Early Process Development

The purpose of early process development, undertaken in the laboratories of Emergent, is to determine a skeleton process that will be transferred to a CMO for refinement and scale-up.

2.3.1.2 Upstream Development

[**] will be determined, [**] for the Clinical Candidate performed. The [**] will be determined. [**] will be performed.

2.3.1.3 Downstream Development

In the case that the protein is [**], then scouting of [**] will be performed. Where the protein is [**], then [**] will be performed and optimised. [**] will be evaluated [**] and the data analysed using [**] analysis, [**]. Scouting of the [**], where possible. No animal components will be used in the manufacturing process for any of the candidates.

This small-scale material will likely be used to begin performing the primary pharmacodynamic studies and analytical method development and formulation studies. Additionally, degradation and stability studies will begin at once to assess the degradation profile of the material and selection of suitable methods to perform longer-term stability studies.

This material may form an early reference preparation for use in various analytical and pre-clinical assays.

2.4 Process Transfer, Scale Up and Consistency Runs

Once the small-scale process is transferred to the CMO, it will be refined/optimised [**]. Finally the process will be performed several times to ensure reasonable process robustness and consistency as part of process understanding studies. Material from this stage may also be used for ongoing pre-clinical work in addition to the continued development of In-Process Control (IPC) and Drug Substance (DS) assays.

2.5 Manufacturing Scale Batch

After successful completion of consistency runs at small scale, the process will be operated at the pilot manufacturing scale under non-GMP conditions to verify

2.6 Toxicology Batch

The toxicology batch will be produced at the same scale as the clinical batch [**], will be released to specification and will be used primarily for toxicology studies. It will also undergo analytical characterisation suitable for incorporation within a Clinical Trial Application (CTA). Stability studies will also be performed on the material and it may also be used as a reference preparation for use as reference controls and standards in assays.

2.7 Clinical Batch (GMP)

The clinical batch will be produced to GMP and released for use in a clinical study. Again, this batch will undergo product characterisation and stability testing.

2.7.1 Method Development

Analytical methods for IPC, DS and Drug Product (DP) will be developed and qualified prior to initiation of Phase I clinical trials. Methods will be developed in-house or contracted to a CMO depending on the complexity or nature of the assay. This will initially be performed on early process material once available. Qualification of assays will be performed upon large-scale process derived material. Assays will be transferred to the QC laboratory of the CMO or nominated sub-contractor, as appropriate, where QC release testing of cGMP lots will be undertaken.

At the current time, it is anticipated that the DP formulation will be based on [**] will be evaluated [**]. Conditions for the optimum [**] will be determined and these initial experiments will be carried out using protein prepared from the in-house skeleton process. Once material manufactured at the CMO is available, formulation experiments will be repeated using the knowledge gained from the initial formulation development work using the early material from the skeleton process.

The formulation process will then be transferred to a secondary manufacturer for the manufacture of transfer, toxicology and clinical batches of DP.

2.9 Stability of Product

Stability studies will be performed on both DS and DP. Tests used will be shown to be stability indicating and will selectively be used throughout the stability assessment. [**] will be used to predict a suitable shelf life for the product.

2.10 Product Characterisation

Preliminary product characterisation will be performed upon the active pharmaceutical ingredient (API). This will assess [**] of the product, potentially using state of the art techniques indicated in ICH guidelines, e.g. [**].

2.11 Generation of a Pre-Clinical package for a Clinical Trial Application [**]

2.11.1 Primary Pharmacodynamic Studies

Data obtained from the pre-clinical screening of the candidate will be detailed in this section of the application, including [**]. Dosing studies in animals will help to determine [**]. These studies will also support the formulation studies as described above.

2.11.1.1 [**] Studies

[**] will be assessed. [**] will be evaluated in an appropriate [**]. The [**] will then be assessed by [**].

2.11.1.2 [**] Studies

2.11.2 Secondary Pharmacodynamic Studies

2.11.2.1 Screening of [**]

[**] will be assessed in a [**]. Furthermore, [**].

2.11.3 Toxicology Studies

Repeat dose toxicology and local tolerance will be performed [**]. Studies will be reflective of the clinical dosing regimen.

2.12 GMP Manufacturing

The Parties intend that GMP manufacturing will be performed by the same CMO that is carrying out the process development work for an individual protein candidate.

2.12.1 Transfer of Process from Development to GMP

Emergent will oversee the transfer of the process from the in-house development group to the GMP group at the chosen CMO. GMP operators from the CMO will be trained on the details of the process by Emergent. Emergent will approve the GMP batch records prior to commencement of manufacturing.

2.12.2 Manufacturing

The CMO will produce a transfer batch (non-GMP) at full (pilot) scale, one GMP-like toxicology/stability batch and one GMP clinical batch of Drug Substance. The final process developed by the CMO will yield [**].

3. Phase I Clinical and Regulatory Plan (Task responsibility; Emergent)

3.1 General Principles

It is anticipated that Clinical Candidate(s) selected for clinical development will have demonstrated the ability to [**]. However, Clinical Candidates may have demonstrated [**]. The objective of the Phase I studies will be to determine safety and immunogenicity (serum antibody levels) of Clinical Candidates. However, it is important for ease of clinical development that [**] antibodies generated by the Clinical Candidate(s) demonstrate [**].

The Parties intend that the Phase I safety and immunogenicity studies will be undertaken by Emergent in the UK, under Clinical Trial Applications (CTA). This is considered to be the [**]. The Phase I studies will be Emergent sponsored studies and each study will require its own CTA. In support of each CTA, each Clinical Candidate will require its own Investigational Medicinal Product Dossier (IMPD), as each Clinical Candidate will be classified as a different product.

Each [**] studied is also likely to require its own IMPD as it is potentially classified as a separate product. [**].

An outline of the likely Phase I clinical development path is provided below. Detailed clinical development plans will be compiled following further discussion between the Parties and agreed by the SC ahead of selection of candidate antigens for clinical development. [**]. In addition, the preferred optimal study design needs to be decided on the basis of a number of factors and it is not possible to be definitive about the final study design at this stage of development.

3.2 Phase I Clinical Studies

3.2.1 Objectives

The key objective for the Phase I studies will be to demonstrate for individual Clinical Candidates [**] that a range of doses can be administered, that the Clinical Candidates have an acceptable safety profile and induce a potentially protective immune response [**] against [**].

3.2.2 Previous Study

Emergent have already undertaken a Phase I study in healthy volunteers [**]. However, the design of the [**] study can however be used to assist the design of future Phase I studies.

3.2.3 Design of Study

Phase I studies are exploratory and are usually performed in small groups of twenty (20) to forty (40) adults to assess the safety of the product and to detect the expected immune response [**]. Phase I studies might also be extended to the final target population [**]. The following general design is proposed at present. Each Phase I study will investigate a number of different dose levels (normally up to 4 dose levels) of Clinical Candidates [**]

It is proposed that [**] dose levels will be included to establish a no effect/minimal effect dose group and to investigate if there is a dose response.

Safety will be of primary importance. For this reason dose escalation will be done [**] with the lowest dose group dosed first and safety reviewed prior to the second dose group receiving their first dose. Following an appropriate safety review the third [**] will receive their first dose and if appropriately safe the final [**] will receive their first dose. Hence, the dosing of each subsequent [**] will occur approximately [**] days after dosing the preceding [**]. Subjects will receive their second dose [**] days after the first dose and their third dose [**] months after the first dose. Eligibility for administration of the second and third doses to individual volunteers will depend on the safety profile in the individual subjects following the first and second doses and will only be administered if a subject tolerates the first/second injection. Safety reviews will be conducted after each [**] receives their second and third dose to determine if it is appropriate to administer the second/third doses to the next [**].

3.2.4 Immunological and Safety Endpoints

Immunological endpoints will be [**]. The [**] will be evaluated [**] will also be evaluated. Emergent will be responsible for ensuring suitable clinical assays exist that have been qualified and may be performed within Emergents’s clinical assay laboratory or at a suitable contractor that is skilled in the testing of clinical samples that possess suitable experience in the techniques proposed.

Safety endpoints will be adverse events, incidence of flu-like illnesses (myalgia, fever, muscle/joint aches, general malaise and headache), serious adverse events and injection site reactions assessed by the modified Draize score.

The costs of a Phase I study are estimated in section 4.3. These are Emergents’ best estimates of potential costs, at this stage, based on previous Phase I trial experience. The budget for Phase I studies will be agreed by the SC on an annual basis, or at the appropriate time during development. The estimates in section 4.3 includes the contract fees for a Phase I unit to run the study along with the project management fees, monitoring costs and performing immunological analysis of clinical samples. Each study will run for approximately a total of [**] in clinic [**].

If more than one Clinical Candidate becomes available for clinical evaluation at any time [**].

3.2.6 [**] Phase I Studies

The final vaccine formulation may contain [**] Clinical Candidate to provide an effective immune response against [**]. Therefore there may need to be a need to study [**]. Broadly, there are [**] potential strategies for a Phase I clinical programme investigating the safety and immunogenicity [**] and these are outlined below. Emergent’s proposed approach to Phase I clinical evaluation is the [**] approach, however these plans are for indicative purposes only, until the number of Clinical Candidates for evaluation and the timing of availability of GMP manufactured material is known.

3.2.6.1 [**] Approach (Emergent Proposed Approach)

A Phase I clinical trial will be performed as outlined above, to evaluate the first Clinical Candidate available for clinical evaluation. Assuming that the protein in the study has an acceptable safety profile, [**] and a second suitable protein is available to move into clinical research a second Phase I study will be planned that investigates a [**].

The second study in the series will utilise [**]. In this way information on the safety and immunogenicity [**] will be determined and [**].

Hence, [**] groups could be involved [**]. The duration of the [**] study will depend on how many groups are dosed, but could be up to [**] weeks in clinic if there are [**] dose groups and [**] dose levels of each product.

When a third protein is available the next study will investigate [**] doses of Clinical Candidate 3 [**].

The advantage of this approach over screening all proteins [**] is that the safety and efficacy [**] are potentially looked at much earlier. [**] as soon as Clinical Candidates become available and this approach is thought to be the quickest route through the Phase I clinical research.

The limitation of this design is that the timings of when [**] become available is unknown. Also, prior to starting a study where a [**] is to be used all materials for the study will need to have been manufactured. At this time it will not be known if the new protein [**].

3.2.6.2 Alternative Approaches

Alternative strategies for clinical evaluation [**] include a direct [**] approach where [**] are selected for clinical studies based on preclinical data. The [**] will then be tested in human subjects directly in a study as outlined above. The dose groups will be made up of [**]. The study will be conducted under a

The main advantage of this approach is that it could reduce the number of early clinical trials to be conducted (potentially to one Phase I clinical study) and thus provide a rapid development path. However, there is a potential risk that a [**]. A further risk of this approach is that a safety issue [**] could prevent further development of potential safe and effective vaccine [**]. It may also be more difficult to evaluate [**]. The Clinical Candidates will also have to be available [**] for preclinical [**] testing, which could delay early clinical proof of concept if a promising Clinical Candidate is identified early in the selection process.

[**] Phase I studies of Clinical Candidates may also be performed. The safety and immunogenicity of all the Clinical Candidates is then established [**]. This is the most protracted route of clinical development and requires extensive resources, particularly if multiple Phase I studies are to be performed [**].

3.2.6.3 Selection of Phase I Approach

The choice of which approach to take to Phase I development may not be ideally determined at present, however it seems probable that the proposed series approach will be the most expedient.

4. Project Management and Resources Required; (Task Responsibility; Joint)

4.1 Project Timelines

The parties recognise that it is important to try to perform the clinical studies in as timely a manner as possible, without compromising the quality or integrity of the programme. As such this plan will be subject to periodic review by the SC and Joint Project Team. It is anticipated that the timeline for the Phase I clinical development of a single Clinical Candidate (with the proposed level of Emergent resource below) will be approximately [**].

These estimates are based upon Emergent’s past experience of Phase I clinical development of protein vaccine candidates. While the intention is to use a contract manufacturer for manufacture of GMP clinical material and a contract clinical trial unit for the performance of the clinical trial, Emergent staff will closely manage and interact with these contract organisations. The selection of appropriate contract organisations will be agreed at the SC.

[**]

4.2 Emergent Resource Requirement

In order to resource the programme adequately, Emergent will need to dedicate the necessary number of skilled Full Time Equivalents (FTEs) to the project. Whilst it is recognised that the work-plan may be modified by the SC, the following represents Emergent’s best estimate of the Emergent resource that will be required to execute the work-plan for the Phase I clinical development of a single Clinical Candidate.

Year 1