2012 REFERENCE DOCUMENT INCLUDING THE COMPANY’S ANNUAL FINANCIAL REPORT AND MANAGEMENT REPORT

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(1)This is a free translation into English of Adocia reference document issued in the French language for informational purposes only. A French société anonyme (corporation) with €619,787.60 in share capital Registered office: 115 Avenue Lacassagne, 69003 Lyon Lyon Trade and Companies Registry no. 487 647 737. 2012 REFERENCE DOCUMENT INCLUDING THE COMPANY’S ANNUAL FINANCIAL REPORT. Pursuant to the General Regulation of the French financial markets authority (Autorité des Marchés Financiers – “AMF”), in particular Article 212-13 thereof, the AMF filed this reference document on April 25, 2013 under number R13-017. This document may be used in support of a financial transaction only if it is supplemented by an offering circular approved by the AMF. This reference document was prepared by the issuer, and its signatories are liable for its content. In accordance with Article L. 621-8-1-I of the French Monetary and Financial Code, this reference document was filed after the AMF verified that the document is complete and comprehensible and that the information it contains is coherent. This does not imply that the AMF has verified the accounting and financial information presented. Copies of this reference document are available free of charge from the company at 115 Avenue Lacassagne, 69003 Lyon. In addition, an electronic version is available on the company’s website (www.adocia.com) and the AMF website (www.amf-france.org).. WorldReginfo - 7d0e69d2-ec19-4b72-a70d-226286e85924. AND MANAGEMENT REPORT.

(2) TABLE OF CONTENTS 1.. PERSONS RESPONSIBLE FOR THE REFERENCE DOCUMENT ................................... 7. 1.1 1.2 1.3. Person responsible for the reference document ............................................................................. 7 Responsibility statement ................................................................................................................ 7 Person responsible for financial information ................................................................................. 7. 2.. STATUTORY AUDITORS ........................................................................................................ 8. 2.1 2.2 2.3. Principal statutory auditors ............................................................................................................ 8 Alternate statutory auditors ........................................................................................................... 8 Certificate of fees paid to statutory auditors .................................................................................. 9. 3.. SELECTED FINANCIAL INFORMATION.......................................................................... 10. 4.. RISKS FACTORS ..................................................................................................................... 12. Cross reference to 2013 English Reference document pp. 14 to 28 5.. INFORMATION ABOUT THE COMPANY ......................................................................... 13. 5.1 History and evolution of the company......................................................................................... 13 Cross reference to 2013 English Reference document pp. 29 to 30 5.2 Investments .................................................................................................................................. 13 6.. OVERVIEW OF ACTIVITIES ............................................................................................... 14. Cross reference to 2013 English Reference document pp. 31 to 94 7.. ORGANIZATIONAL CHARTS .............................................................................................. 15. 7.1 7.2. Organization of the company ...................................................................................................... 15 Subsidiaries, branches and secondary establishments ................................................................. 15. 8.. REAL ESTATE, FACTORIES AND EQUIPEMENT .......................................................... 16. 9.. REVIEW OF THE COMPANY’S RESULTS AND FINANCIAL POSITION .................. 17. 9.1 9.2. Overview ..................................................................................................................................... 17 Comparison of the last three fiscal years ..................................................................................... 17. 10.. CASH AND CASH EQUITY.................................................................................................... 22. 10.1 10.2 10.3 10.4 10.5. Information on the company’s equity, liquidities and sources of financing ................................ 22 Cash flows ................................................................................................................................... 24 Information on borrowing terms and funding structure............................................................... 25 Restrictions on the use of equity.................................................................................................. 25 Future sources of financing required ........................................................................................... 25. 11.. INVENTIONS, PATENTS, LICENSES, TRADEMARKS AND DOMAIN NAMES ........ 26. 11.1 Innovation policy ......................................................................................................................... 26 11.2 Patents and patent applications .................................................................................................... 26 11.3 Contracts covering cooperation, research and licences granted by or to the company ............... 35. 1. WorldReginfo - 7d0e69d2-ec19-4b72-a70d-226286e85924. Cross reference to 2013 English Reference document pp. 96 to 100.

(3) 11.4 Trademarks, trademark applications and domain names ............................................................. 35 12.. TRENDS ..................................................................................................................................... 37. 13.. PROFIT FORECASTS OR ESTIMATES .............................................................................. 39. 14.. ADMINISTRATIVE, MANAGEMENT, SUPERVISORY AND EXECUTIVE MANAGEMENT BODIES ....................................................................................................... 40. Cross reference to 2013 English Reference document pp. 130 to 135 15.. COMPENSATION AND BENEFITS ...................................................................................... 41. 15.1 Compensation of corporate officers............................................................................................. 41 15.2 Amounts that the company has provisioned for payment of pensions, retirement allowances and other benefits to corporate officers ....................................................................................... 44 15.3 Bonus shares, stock warrants and stock options granted to corporate officers............................ 44 15.4 Summary of transactions by managers and the persons referred to in Article L. 621-18-2 of the French Monetary and Financial Code (Code monétaire et financier) in the company’s shares during the past fiscal year ................................................................................................. 44 16.. FUNCTIONING OF SUPERVISORY AND MANAGEMENT BODIES ........................... 45. Cross reference to 2013 English Reference document pp. 141 to 146 17.. EMPLOYEES ............................................................................................................................ 46. 18.. MAJOR SHAREHOLDERS .................................................................................................... 52. 18.1 18.2 18.3 18.4 18.5 18.6 18.7. Change in the company's capital structure since December 31, 2010 on an undiluted basis ...... 52 Distribution of capital and voting rights as of December 31, 2012 on a fully diluted basis........ 52 Major shareholders not represented on the board of directors..................................................... 53 Voting rights of major shareholders ............................................................................................ 53 Control of the company ............................................................................................................... 54 Agreements that can lead to a change in control ......................................................................... 54 Pledges of the company's shares .................................................................................................. 54. 19.. RELATED-PARTY TRANSACTIONS .................................................................................. 55. 19.1 Intra-group agreement ................................................................................................................. 55 19.2 Related-party transactions ........................................................................................................... 55 19.3 Statutory auditors' report on regulated agreements made for the fiscal year ended December 31, 2012 ....................................................................................................................................... 55 20.. FINANCIAL INFORMATION ................................................................................................ 59. 20.1 Consolidated financial statements prepared under IFRS for the fiscal years ended December 31, 2010 and December 31, 2011 and individual financial statements prepared under IFRS. 2. WorldReginfo - 7d0e69d2-ec19-4b72-a70d-226286e85924. 17.1 Human Resources ........................................................................................................................ 46 17.2 Financial instruments conferring equity rights in the company granted to the top ten employees who are not corporate officers ................................................................................... 48 17.3 Equity interests and stock options held by corporate officers ..................................................... 49 17.4 Equity interests held by employees ............................................................................................. 49 17.5 Profit-sharing and equity interest contracts ................................................................................. 49 17.6 Employment information required by Article R. 225-105-1 of the French Commercial Code ... 50.

(4) for the fiscal year ended December 31, 2012 .............................................................................. 59 20.2 Statutory auditors' reports on the individual financial statements prepared under IFRS for the fiscal year ended December 31, 2012 .................................................................................... 90 20.3 Individual financial statements prepared under French GAAP for the fiscal years ended December 31, 2010, December 31, 2011, and December 31, 2012 ............................................ 93 20.4 Statutory auditors' report on the individual financial statements prepared for the fiscal year ended December 31, 2012 ......................................................................................................... 109 20.5 Five-year financial summary ..................................................................................................... 112 20.6 Dividend payout policy ............................................................................................................. 112 20.6.1 Dividends paid over the last three years.................................................................................... 112 20.6.2 Dividend payout policy ............................................................................................................. 112 20.7 Legal and arbitration proceedings ............................................................................................. 112 20.8 Significant change in the financial or trading position .............................................................. 113 21.. ADDITIONAL INFORMATION .......................................................................................... 113. Cross reference to 2013 English Reference document pp. 214 to 230 22.. MAJOR AGREEMENTS ....................................................................................................... 113. Cross reference to 2013 English Reference document pp. 231 to 236 23.. INFORMATION FROM THIRD PARTIES, EXPERTS' STATEMENTS AND DECLARATIONS OF INTERESTS ..................................................................................... 113. Cross reference to 2013 English Reference document pp. 237 ........................................................... 113 24.. DOCUMENTS AVAILABLE TO THE PUBLIC ................................................................ 113. Cross reference to 2013 English Reference document pp. 238 25.. INFORMATION REGARDING EQUITY INTERESTS.................................................... 113. Cross reference to 2013 English Reference document pp. 239 26.. GLOSSARY ............................................................................................................................. 113. APPENDIX I - Chairman's report on internal control.................................................................. 114 APPENDIX II - Statutory auditors' report on the Chairman's report ........................................ 124. 3. WorldReginfo - 7d0e69d2-ec19-4b72-a70d-226286e85924. Cross reference to 2013 English Reference document pp. 240 to 243 ................................................ 113.

(5) CROSS-REFERENCE TABLE The cross-reference table below will facilitate locating in this reference document: -. the information contained in the annual financial report (Article L. 451-1-2 of the French Monetary and Financial Code and Article 222-3 of the AMF’s General Regulation); and - the information contained in the annual management report (Article L. 225-100 et seq. of the French Commercial Code). Annual financial report Reference document 1. Responsibility statement See section 1.2 2. Corporate annual financial statements - French GAAP See section 20.3 3. Corporate annual financial statements - IFRS See section 20.1 4. Management report See index below 5. Chairman’s report on internal control See appendix I 6. Annual information document See section 5.1.6 7. Information on statutory auditors’ fees See section 2.3 8. Statutory auditors’ report on the annual financial statements prepared See section 20.2 and 20.4 under French GAAP and IFRS 9. Statutory auditors’ report on the chairman’s report See appendix II. 10. Executive management of the company 11. Information on corporate officers 12. Acquisition of significant equity interests in, or control of, companies headquartered in France; disposals of such equity interests 13. Activities of subsidiaries and controlled entities 14. Information on shareholder structure and treasury shares – Share redemption programs 15. Changes during the fiscal year to the company’s shareholder structure 16. Changes in the share price – Risk of price changes 17. Summary of transactions in the company’s securities during the past fiscal year by persons referred to in Article L. 621-18-2 of the French Monetary and Financial Code 18. Information required by Article L. 225-100-3 of the French Commercial Code 19. Employment and environmental information 20. Table showing the company’s results over the last five fiscal years 21. Authorizations to effect capital increases. 4. Reference document See chapters 6 and 9 See chapters 9 and 10 See section9.2.2 See section 6 See chapter 4 See chapters6 and 11 See chapters 6 and 12 See section 20.8 See chapter 17 See chapters 14 and 15 See chapters 14 and 15 See chapters 7 and 25 See chapters 7 and 25 See sections 18.1, 18.2 and 21.1.4 See sections 18.1, 18.2 and 21.1.8 See sections 4.6.5 and 21.1.8 See chapter15.4. See section 16.6 See sections 8.3 and 8.4 and chapter 17 See section 20.5 See section 21.1.6. WorldReginfo - 7d0e69d2-ec19-4b72-a70d-226286e85924. Annual management report 1. Position and business of the company during the past fiscal year 2. Review of financial statements and results – Appropriation of income – Information on dividends distributed – Non-tax deductible expenses 3. Information on supplier payment terms 4. Progress made and difficulties encountered 5. Major risks and uncertainties faced by the company / Use of financial instruments by the company 6. Research and development activities 7. Foreseeable changes and outlook 8. Significant events since the fiscal year-end 9. Equity interests held by employees.

(6) Notice In this reference document, the terms “Adocia” and the “company” refer to Adocia, a French sociétéanonyme (corporation) whose registered office is located at 115 Avenue Lacassagne, 69003 Lyon, France, and which is registered with the Lyon Trade and Companies Registry under number 487 647 737. This reference document presents or incorporates by reference the audited financial statements of the company and its subsidiaries for the fiscal years ended December 31, 2010, December 31, 2011 and December 31, 2012. The IFRS financial statements for the year ended December 31, 2012 are in section 20.1 of this reference document. The report of the statutory auditors relative to the parent company financial statements prepared under IFRS for the year ended December 31, 2012 is in section 20.2 of this document. This reference document presents or incorporates by reference the audited financial statements of the company prepared under French GAAP for the years ended December 31, 2011 and December 31, 2012. The annual financial statements for the year ended December 31, 2012 are in section 20.3 of this reference document. The report of the statutory auditors relative to the annual financial statements for the year ended December 31, 2012 is in section 20.4. A glossary containing the definitions of certain technical terms used in this reference document, as well as an index of abbreviations used, can be found in Chapter 26. Terms indicated by an asterisk (*) are defined in the glossary. Disclaimer Market and competition information This reference document contains, in particular in Chapter 6 “Overview of Activities”, information about the company’s markets and competitive position. This information is taken inter alia from studies conducted by external sources. Publicly available information that the company deems reliable has not been verified by independent experts, and the company cannot guarantee that a third party using different methods to collect, analyze or calculate data on these markets would obtain the same results.. This reference document contains information on the company’s outlook and development priorities. At times, this information is identified by the use of the future or conditional tense or forward-looking words such as “consider”, “plan”, “think”, “have as an objective”, “expect”, “intend”, “should”, “aspire to”, “estimate”, “believe”, “wish”, “could” or, where applicable, the negative form of these terms, or any variation thereof or similar terminology. This information is not historical data and should not be viewed as a guarantee that the facts and events described will occur. This information is based on data, assumptions and estimates that the company deems reasonable. It is subject to change or amendment due to uncertainties associated with inter alia the economic, financial, competitive and regulatory environment. This information is provided in the various sections of this reference document and includes particulars about the company’s intentions, estimates and objectives with respect to inter alia the market in which it operates and its strategy, growth, results, financial position, cash position and forecasts. The forward-looking information in this reference document is provided only as of the filing date of this reference document. The company operates in a constantly changing competitive environment. Therefore, it cannot anticipate all risks, uncertainties and other factors that may affect its business, the potential impact thereof on its business, or the extent to which the occurrence of a risk or combination of risks could have significantly different results from those implied in any forward-looking information. Lastly, it should be kept in mind that none of this forward-looking information is a guarantee of actual results.. 5. WorldReginfo - 7d0e69d2-ec19-4b72-a70d-226286e85924. Forward-looking information.

(7) Risk factors. 6. WorldReginfo - 7d0e69d2-ec19-4b72-a70d-226286e85924. Investors are advised to carefully review the risk factors described in Chapter 4 “Risk Factors” of this reference document before making any investment decision. The occurrence of any or all of these risks may have a material adverse impact on the company’s business, financial position, income and outlook. Furthermore, other risks of which the company is not aware or that it does not deem significant as of the filing date of this reference document may also have a material adverse impact..

(8) 1.. PERSONS RESPONSIBLE FOR THE REFERENCE DOCUMENT. 1.1. Person responsible for the reference document. Mr. Gérard Soula, Chairman and Chief Executive Officer. 1.2. Responsibility statement. “I hereby certify, after having taken all reasonable measures to this effect, that to my knowledge the information contained in this reference document is accurate and contains no omissions likely to affect its import. I hereby certify that, to my knowledge, the financial statements have been prepared in accordance with applicable accounting standards and give a true and fair view of the company’s assets and liabilities, financial position and income, and that the information cross-referenced from the management report gives a true and fair view of the company’s business trends, income and financial position, as well as a description of the main risks and uncertainties it faces. I have obtained a letter from the statutory auditors certifying completion of their work in which they state that they have verified the information in this reference document relating to the company’s financial position and financial statements, and that they have read the reference document in its entirety. The statutory auditors issued reports, without comments, on the annual financial statements for the fiscal year ended December 31, 2012. The reports are provided in chapters 20.2 and 20.4. Executed in Lyon, on April 25, 2013 Gérard Soula Chairman and Chief Executive Officer. Person responsible for financial information. Ms. ValérieDanaguezian Chief Financial Officer Address: 115 Avenue Lacassagne, 69003 Lyon Telephone: +33 (0) 4 72 61 06 10 Fax: +33 (0) 4 72 36 39 67 Email ; contactinvestisseurs@adocia.com. 7. WorldReginfo - 7d0e69d2-ec19-4b72-a70d-226286e85924. 1.3.

(9) 2.. STATUTORY AUDITORS. 2.1. Principal statutory auditors. Odicéo represented by Mr. Sylvain Boccon-Gibod 115 Boulevard Stalingrad, 69100 Villeurbanne member of the Lyon regional statutory auditors’ association Appointed by a decision adopted by the sole shareholder on July 31, 2006 until the general shareholders’ meeting convened to vote on the financial statements for the fiscal year ended December 31, 2011. This term of office was renewed by the general shareholders’ meeting held on June 15, 2012 for a period of six fiscal years, which will expire at the conclusion of the ordinary general shareholders’ meeting convened to vote on the financial statements for the fiscal year ending December 31, 2017. Ernst & Young etAutres represented by Mr. Sylvain Lauria, a partner 41 Rue Ybry, 92200 Neuilly-sur-Seine member of the Versailles regional statutory auditors’ association Appointed by the combined general shareholders’ meeting held on October 24, 2011 for a period of six fiscal years, which will expire at the conclusion of the ordinary general shareholders’ meeting convened to vote on the financial statements for the fiscal year ending December 31, 2016.. 2.2. Alternate statutory auditors. Appointed by a decision adopted by the sole shareholder on July 31, 2006 until the general shareholders’ meeting convened to vote on the financial statements for the fiscal year ended December 31, 2011. This term of office was renewed by the general shareholders’ meeting held on June 15, 2012 for a period of six fiscal years, which will expire at the conclusion of the ordinary general shareholders’ meeting convened to vote on the financial statements for the fiscal year ending December 31, 2017. Auditex Tour Ernst & Young, Faubourg de l’Arche, 92037 La Défense Cedex, member of the Versailles regional statutory auditors’ association Appointed by the combined general shareholders’ meeting held on October 24, 2011 for a period of six fiscal years, which will expire at the conclusion of the ordinary general shareholders’ meeting convened to vote on the financial statements for the fiscal year ending December 31, 2016. During the period covered by the historical financial information, no statutory auditor has resigned or been removed from office.. 8. WorldReginfo - 7d0e69d2-ec19-4b72-a70d-226286e85924. Mr. Pierre Grafmeyer 115 Boulevard Stalingrad, 69100 Villeurbanne member of the Lyon regional statutory auditors’ association.

(10) 2.3. Certificate of fees paid to statutory auditors. The table below shows the statutory auditors’ fees that the company has paid during the last three years: Ernst & Young. (€ thousands) 2012. 2011. 23. 48. 23. 48. 23. 48. Odicéo 2010. 2012. 2011. 2010. 23. 63. 0. 23. 63. 15. 0. 23. 63. 15. Audit services * statutory auditor services, certification, review of individual and consolidated financial statements. 15. * other services and due diligence directly related to the statutory audit assignment Subtotal Other services * tax * others Subtotal. TOTAL. 9. WorldReginfo - 7d0e69d2-ec19-4b72-a70d-226286e85924. The amounts above do not include VAT..

(11) 3.. SELECTED FINANCIAL INFORMATION. The selected financial information presented in this Chapter 3 is taken from the company’s financial statements for the fiscal years ended December 31, 2010, December 31, 2011 and December 31, 2012, which were prepared in accordance with IFRS and are shown in section 20.1 of this reference document. This financial information should be read in conjunction with (i) the review of the company’s income and financial position presented in Chapter 9 of this reference document and (ii) the review of the company’s cash position and equity presented in Chapter 10 of this reference document. Selected financial information for the fiscal years ended December 31, 2010, December 31, 2011 and December 31, 2012 (IFRS) Selected financial information taken from the income statement: FY 2012 (12 months). (IFRS - € thousands). FY 2011 (12 months). (*). FY 2010 (12 months). Revenue from licenses Research and cooperation agreements Sales (a) Research tax credit Project and other financing Other revenue (b). 2 104. 180. 73. 577. 3 241. 2 236. 2 036. Operating revenue (a)+(b). 7 236. 3 787. 2 147. Research and development expenses. (11 784). (8 568). (5 927). General and administrative expenses. (1 522). (1 294). (857). (13 306). (9 862). (6 784). (6 070). (6 074). (4 637). FINANCIAL INCOME. 75. (64). (94). NET INCOME / (loss). (5 995). (6 454). (4 731). Operating expenses OPERATING INCOME / (loss). 79. 1 892. 1 472. 3 995. 1 551. 111 111. 3 061. 2 163. 1 459. 10. WorldReginfo - 7d0e69d2-ec19-4b72-a70d-226286e85924. (*) including €1,905 linked to the partial recognition of the up-front payment of $10 million (€7.6 million) received from Eli Lilly..

(12) Selected financial information taken from the balance sheet:. (IFRS - € thousands) NON-CURRENT ASSETS. FY 2012 (12 months). FY 2011 (12 months). FY 2010 (12 months). 1 281. 564. 706. 555. 378. 475. of which: laboratory equipment of which: other fixed tangible assets. 384. 179. 161. CURRENT ASSETS. 35 345. 17 072. 14 357. of which: cash and cash equivalents. 30 462. 5 905. 12 024. TOTAL ASSETS. 36 627. 17 636. 15 063. EQUITY. 23 028. 4 330. 10 687. 2 244. 1 957. 2 431. NON-CURRENT LIABILITIES of which: long-term financial debts. 2 046. 1 823. 2 083. CURRENT LIABILITIES. 11 354. 11 350. 1 946. TOTAL LIABILITIES. 36 627. 17 636. 15 063. FY 2012 (12 months). FY 2011 (12 months). FY 2010 (12 months) (4 956). (IFRS - € thousands) Net cash flow generated by the business Net cash flow in connection with investment transactions Net cash flow in connection with financing transactions. 919. (6 217). (1 774). (155). (137). 25 413. 252. 4 418. CHANGES IN NET CASH. 24 558. (6 119). (674). 5 905. 12 024. 12 698. 30 462. 5 905. 12 024. Cash and cash equivalents at the start of the year Cash and cash equivalents at year-end. 11. WorldReginfo - 7d0e69d2-ec19-4b72-a70d-226286e85924. Selected financial information taken from the cash flow statement:.

(13) RISKS FACTORS Cross reference to 2013 English Reference document pp. 14 to 28. 12. WorldReginfo - 7d0e69d2-ec19-4b72-a70d-226286e85924. 4..

(14) 5.. INFORMATION ABOUT THE COMPANY. 5.1. History and evolution of the company Cross reference to 2013 English Reference document pp. 29 to 30. 5.2. Investments. 5.2.1 Major investments The company’s major investments over the last three fiscal years were primarily for purchases of laboratory, IT and office equipment (see note 3.3 of the notes to the company’s financial statements prepared in accordance with IFRS, in Paragraph 20.1 of this reference document). FY 2012 (12 months). (IFRS - € thousands) Intangible assets Property, plant and equipment Long-term investments. FY 2011 (12 months). 16. 11. 3. 722. 238. 133. 329. TOTAL. FY 2010 (12 months). 1 067. 1 249. 137. 5.2.2 Major current and future investments. 13. WorldReginfo - 7d0e69d2-ec19-4b72-a70d-226286e85924. No significant investment is currently in progress. At this time, the company does not plan to make any major investments in the coming years and intends to maintain its current investment policy. At this stage, the company’s management bodies have not made any firm commitments in this respect..

(15) OVERVIEW OF ACTIVITIES Cross reference to 2013 English Reference document pp. 31 to 94. 14. WorldReginfo - 7d0e69d2-ec19-4b72-a70d-226286e85924. 6..

(16) 7.. ORGANIZATIONAL CHARTS. 7.1. Organization of the company. As of the filing date of this reference document, the company does not have any subsidiaries.. 7.2. Subsidiaries, branches and secondary establishments. 15. WorldReginfo - 7d0e69d2-ec19-4b72-a70d-226286e85924. None.

(17) REAL ESTATE, FACTORIES AND EQUIPEMENT Cross reference to 2013 English Reference document pp. 96 to 100. 16. WorldReginfo - 7d0e69d2-ec19-4b72-a70d-226286e85924. 8..

(18) 9.. REVIEW OF THE COMPANY’S RESULTS AND FINANCIAL POSITION. Readers are invited to read this analysis of the company’s financial position and results in conjunction with the company’s financial statements prepared in accordance with IFRS for the fiscal years ended December 31, 2010, December 31, 2011 and December 31, 2012. Readers may also review the notes to the financial statements presented in Chapter 20 "Financial information" of this reference document, and all other financial information included herein.. 9.1. Overview. The company’s financial statements have been prepared in accordance with the standards and interpretations published by the International Accounting Standards Board (IASB) and adopted by the European Union as of the date the financial statements were prepared. These financial statements for the year ended December 31, 2012 were approved by the company’s board of directors at its meeting held on March 15, 2013. Adocia, which was created in 2005, has designed and developed a unique and versatile technological platform, called BioChaperone, which enables development of innovative therapeutic protein formulations in the field of regenerative medicine and treatment of chronic pathologies. The outcome of this research and the commercial development of the results obtained is a long-term project. The company’s financial statements show primarily research and development expenses, which, for the most part, have been financed by capital increases, OSEO reimbursable advances and grants, and the research tax credit. However, in 2009, the company recorded its first revenues when it concluded research and cooperation agreements. At the end of 2011, a major license agreement was signed with the Eli Lilly group, which indicated potential revenues in excess of €166 million. Since the company’s creation, it has raised over €27 million through capital increases subscribed, in particular, by the company’s founders, Messrs. Gérard, Olivier and Rémi Soula, and institutional investors (IdInvest, Amundi, Viveris, BioAm, SHAM and InnoBio). In 2012, the company was listed on the NYSE Euronext regulated market in Paris and raised over €27.4 million (net of transaction expenses).. Comparison of the last three fiscal years. 9.2.1 Net income items Operating income Until 2011 the company had been financed mostly by equity, OSEO grants and the research tax credit, but by the end of 2011 it recorded its first license revenues.. (normes IFRS en milliers d'euros). FY 2012 FY 2011 FY 2010 (12 months) (12 months) (12 months). Income from licenses Research and cooperation agreements Revenue (a) Grants, public financing and research tax Operating income (a)+(b). 17. 2 104. 79. 1 892. 1 472. 111. 3 995. 1 551. 111. 3 241. 2 236. 2 036. 7 236. 3 787. 2 147. WorldReginfo - 7d0e69d2-ec19-4b72-a70d-226286e85924. 9.2.

(19) Operating income amounted to €2,147 thousand in 2010, €3,787 thousand in 2011 and €7,236 thousand in 2012. This significant growth between 2011 and 2012 is mainly due to the increase in revenues following the signing, in late December 2011, of a license agreement with the pharmaceutical group Eli Lilly for the development of a fast acting insulin analog formulation. As provided in this agreement, the upfront payment of $10 million (€7.6 million), to be recognized over the expected duration of the clinical development program, was partially recognized in 2012 (€1.9 million) under license revenue. In addition, the research agreements relating to this partnership and the continuation of the collaboration on monoclonal antibodies totaled €1,892 thousand in 2012. Other income recognized in 2010, 2011 and 2012 mainly corresponds to grants and the research tax credit , which provides a tax credit to companies heavily investing in R&D activities (eligible expenses include wages and salaries, consumables, outsourcing costs with approved organizations and intellectual property costs). In 2012, the Company received a new reimbursable advance of €800,000 to continue the development of its HinsBet fast acting human insulin project. Grants in the amount of €166,873 were recognized under IFRS, reflecting the Company’s interest expense savings with respect to the zero interest rate reimbursable advance granted by OSEO for this project. The amounts recognized under the research tax credit were: €1,453,296 in 2010, €2,162,885 in 2011 and €3,060,543 in 2012. The Company also benefited from apprenticeship tax credits of €5,472 in 2010, €7,328 in 2011 and €8,128 in 2012. Operating expenses The Company incurred the following operating expenses due to the nature of its business:. Purchases used in operations Payroll expense External expenses Taxes and contributions Depreciation, amortization and provisions Other current operating revenue and expenses Operating expenses. FY 2011 (12 months). FY 2010 (12 months). 834. 434. 341. 4 934. 4 047. 3 130. 7 050. 5 169. 3 192. 69. 62. 21. 419. 151. 101. 13 306. 9 862. 6 784. During fiscal 2012, operating expenses rose by 35% (€13,306 thousand in 2012, compared with €9,862 thousand in 2011), primarily as a result of: -. an increase of over 36.4% in external expenses, which consist primarily of pre-clinical and clinical study costs (€3,100 thousand and €86 thousand, respectively), outsourcing costs (€1,450 thousand), administrative and scientific professional fees (€91 thousand), rents (€370 thousand, including rental expenses) and patent attorney fees (€655 thousand). External expenses accounted for 53% of operating expenses for the year ended December 31, 2012, compared with 52.4% a year earlier; and. -. a rise in payroll expenses by nearly 22%, reflecting mainly the increase in FTEs (full-time equivalent), which climbed from 55.9 in 2011 to 66.6 in 2012.. 18. WorldReginfo - 7d0e69d2-ec19-4b72-a70d-226286e85924. FY 2012 (12 months). (IFRS - € thousands).

(20) Depreciation, amortization & provisions grew by €268 thousand (€419 thousand in 2012, compared with €151 thousand in 2011), primarily due to the acquisition of fittings, equipment and laboratory tooling to equip additional laboratory space. Net financial income/expense The company had net financial expenses for the fiscal years 2010 and 2011 (€94 thousand and €64 thousand respectively). In 2012, it recorded net financial income (€75 thousand), consisting mainly of income from the investment of surplus cash balances and foreign exchange translation adjustments (the recognition of unrealized translation gains). Interest on OSEO reimbursable advances amounted to €99 thousand in 2012 (compared with €108 thousand in 2011). Taxable profit/loss In the last three fiscal years, Adocia recorded losses and therefore incurred no income tax expense. As of December 31, 2012, the company had a tax loss carryforward of €37,057 thousand (of which €13,110 thousand with respect to fiscal year 2012, €0 with respect to fiscal year 2011 thanks to tax credits, and €5,986 thousand for fiscal year 2010). This amount can be carried forward indefinitely. Because the company is unable to determine with sufficient certainty when it will be able to offset its accumulated losses, it has not recognized any related deferred tax assets. Losses for fiscal years 2010, 2011 and 2012 Adocia recorded losses in each of the past three years (€4,731 thousand in 2010, €6,454 thousand in 2011 and €5,995 thousand in 2012). Proposed allocation of 2012 loss - Payment of dividends It is proposed that the loss for the fiscal year ended December 31, 2012 in the amount of €5,994,544 be allocated to accumulated losses. The company paid no dividend for the last three fiscal years. Non-tax-deductible expenses. 9.2.2 Statement of financial position items Total assets amounted to €15,063 thousand as of December 31, 2010, €17,636 thousand as of December 31, 2011, and €36,626 thousand as of December 31, 2012. Non-current assets Non-current assets totaled €706 thousand as of December 2010, €564 thousand as of December 31, 2011, and €1,281 thousand as of December 31, 2012. They include intangible assets, property, plant and equipment and financial assets. In 2012, the rise in non-current assets is mainly due to a €177 thousand increase in laboratory tooling, a €204 thousand rise in other property, plant and equipment and a €329 thousand hike in financial assets (mainly from cash on the liquidity contract signed with BIL Finance in March 2012).. 19. WorldReginfo - 7d0e69d2-ec19-4b72-a70d-226286e85924. Pursuant to Article 223 quater of the French Tax Code, non-tax-deductible expenditures on luxuries or charges within the meaning of Article 39-4 of the Code amounted to €19,384 for the year ended December 31, 2012..

(21) Current assets Current assets totaled €14,357 thousand as of December 31, 2010, €17,072 thousand as of December 31, 2011 and €35,345 thousand as of December 31, 2012. They are comprised essentially of “cash and cash equivalents”, “research tax credit” and “VAT receivables”. Cash and cash equivalents increased from €5,905 thousand as of December 31, 2011 to €30,462 thousand as of December 31, 2012, due to the company’s listing on the NYSE Euronext regulated market in Paris, pursuant to which it increased its capital by €27,362 thousand (excluding transaction costs). Because the company has not had taxable profits, the research tax credits are systematically collected in the fiscal year following the fiscal year in which they are recognized: -. 2009 research tax credit: €1.460 thousand was reimbursed in 2010. -. 2010 research tax credit: €1,453 thousand was reimbursed on May 17, 2011. -. 2011 research tax credit: €1,848 thousand was reimbursed on October 1, 2012. VAT receivables were €275 thousand as of December 31, 2010, €392 thousand as of December 31, 2011, and €822 thousand as of December 31, 2010. Shareholders' equity Net changes in equity are, to a large extent, explained by the losses recognized in fiscal years 2010, 2011 and 2012, which were offset by capital increases. Number of shares 12/31/2009. Profit/loss for the period Capital increase Share-based payments Other comprehensive income Capital increase expenses. Capital. Additional Reserves paid-in and profit capital. 399 014. 399. 20 290. 45 527. 46. 3 755. -9 185 -4 731 119. -6. Other 12/31/2010. Profit/loss for the period Capital increase Share-based payments Other comprehensive income Capital increase expenses. 444 541. 445. 24 039. 13 300. 1. -1. -13 797 -6 454 96. Other 12/31/2011. Profit/loss for the period Capital increase Share-based payments Other comprehensive income Capital increase expenses. 4 000 869 4 458 710. 446. 24 038. 1 723 066 16 100. 172 2. 27 190 (2). 59. 619. (2 030) (698) 48 498. (26 090). Other 12/31/2012. 6 197 876. 20. (20 154) (5 995). Group total equity 11 504 -4 731 3 800 119 0 -6 0 10 687 -6 454 0 96 0 0 0 4 329 (5 995) 27 362 59 0 (2 030) (698) 23 028. WorldReginfo - 7d0e69d2-ec19-4b72-a70d-226286e85924. CHANGES IN EQUITY (in € thousands).

(22) Non-current liabilities Non-current liabilities are comprised of two items: “long-term financial debt” and “long-term provisions”. Non-current liabilities at the end of fiscal years 2010, 2011 and 2012 totaled €2,431 thousand, €1,957 thousand and €2,444 thousand, respectively. The “long-term financial debts” item corresponds to reimbursable advances made by OSEO. These are measured at amortized cost under IFRS and amounted to €2,083 thousand as of end-2010, €2,431 thousand as of end-2011 and €2,441 thousand as of end-2012 (see Note 3.10 of the notes to the company’s financial statements in Section 20.1 of this reference document). Long-term provisions consist primarily of provisions for retirement benefits, which rose from €117 thousand as of end-2011 to €198 thousand as of end-2012.. Current liabilities Current liabilities totaled €1,946 thousand as of December 31, 2010, €11,350 thousand as of December 31, 2011, and €11,354 thousand as of December 31, 2012. They are comprised of trade payables (€1,230 thousand as of end-2010, €2,972 thousand as of end-2011 and €3,824 thousand as of end-2012), and other current liabilities, mainly taxes and social security contributions (€644 thousand as of end-2010, €1,294 thousand as of end 2011 and €1,463 thousand as of end 2012).. Information on supplier payment terms Pursuant to Article L. 441-6-1 of the French Commercial Code, the company’s trade payables break down by maturity as follows:. Cash payment Payment in 30 days Payment in 45 days Payment in 60 days other term payment Litigation Suppliers, invoices pending. Fiscal year 2012. Fiscal year 2011. Fiscal year 2010. 870. 304. 238. 803. 145. 99. 219. 2. 47. 1. 4. (*). 110. (*) SACVL mediation. 21. 142. 194. 118. 1 748. 916. 743. WorldReginfo - 7d0e69d2-ec19-4b72-a70d-226286e85924. Supplier category (in € thousands).

(23) 10.. CASH AND CASH EQUITY. 10.1 Information on the company’s equity, liquidities and sources of financing As of December 31, 2012, cash and cash equivalents amounted to €30,462 thousand (compared with €5,905 thousand as of 31 December 2011 and €12,024 thousand as of 31 December 2010). Equity financing The company received a total of about €55 million in the form of capital increases between its creation and the filing date of this reference document, of which €27.4 million was received in fiscal year 2012: - €11,999,999.97 was raised in a first round of equity financing carried out in October 2007 and supplemented in December 2007; - €9,023,548.80 was raised in connection with a capital increase carried out on November 2, 2009; - €4,976,665.44 was raised in connection with various exercises of stock warrants in fiscal years 2009 and 2010; and - €27,362,288.08 was raised from the company’s stock exchange listing in February 2012, which was carried out by an initial public offering in France and an institutional placement in France and certain other European countries, which, in each case, concerned new shares. Debt financing As of the filing date of this reference document, the company has been granted non-interest bearing reimbursable assistance for its research from OSEO, for a total amount of €3,470,000: a) €2,250,000 granted on March 12, 2007 for the development of a new system of local and controlled release of growth factors for bone regeneration; this reimbursable advance was received in full, in four installments: €450,000 on March 15, 2007, €450,000 on November 26, 2007, €900,000 on July 15, 2008, and €450,000 on February 15, 2010. If the program is successful, the company agreed to reimburse €2,250,000 to OSEO in the manner specified below:. -. €300,000 by March 31, 2012, €400,000 by March 31, 2013, €450,000 by March 31, 2014, €500,000 by March 31, 2015, and €600,000 by March 31, 2016.. In the event of license transfers or product marketing, the company agreed to pay to OSEO by March 31 of each year, with effect from January 1, 2010: -. 49.51% of the revenue, excluding tax, from the sale or transfer of licenses, patents, or know-how, received during the previous calendar year if such sales or transfers cover all or part of the results of the assisted program; and 49.51% of the revenue, excluding tax, generated by the marketing (including the sale to a third party) or the use by the company for its own purposes of prototypes, pilot runs or mock-ups made under the assisted program.. 22. WorldReginfo - 7d0e69d2-ec19-4b72-a70d-226286e85924. The company agreed to reimburse the full amount advanced by OSEO, according to the following schedule:.

(24) In these cases, payments will be applied in priority and in proportion to the final installment due to OSEO Innovation, as detailed in the schedule above and, if applicable, to the penultimate installment. In the event of technical or commercial failure (even partial) of the program, given the nature of the work performed under the Osteoporosis project, Adocia agreed to reimburse to OSEO a lump sum of €700,000 as follows: -. €300,000 by March 31, 2012, and €400,000 by March 31, 2013.. Upon non-compliance with the company’s obligations, OSEO is entitled to demand the full payment of the advance. Under the terms of the contract, an amount of €700,000 was payable by March 31, 2013, regardless of the outcome of the program (unknown as of the date of this reference document). In this respect, the company paid the first installment in the amount of €300,000 in 2012 and a second amount of €400,000 on April 1, 2013. The balance of the advance (€1,550,000) becomes payable only upon the technical and/or commercial success (approved by OSEO) of the project under financing. b)- €420,000 granted on July 20, 2010 to develop a fast acting human insulin formulation under a Phase I clinical study. This amount was received in full: €84,000 on July 26, 2010, €84,000 on August 18, 2010, €168,000 on April 4, 2011, and €84,000 on November 16, 2011. The results of this project contributed to the signing of a license agreement with the Eli Lilly group in December 2011. Accordingly, on June 19, 2012, the Company paid off the full amount of the advance received (€420,000), as stipulated in the contract in the event of commercial success. c)- €800,000 granted on April 25, 2012 for the continuation of the fast acting human insulin project. As the terms for obtaining this assistance were met in March 2012, the company received the full amount on April 30, 2012.. -. €32,500 by March 31, 2017, €32,500 by June 30, 2017, €32,500 by September 30, 2017, €32,500 by December 31, 2017, and €37,500 by March 31, 2018, €37,500 by June 30, 2018, €37,500 by September 30, 2018, €37,500 by December 31, 2018, and €50,000 by March 31, 2019, €50,000 by June 30, 2019, €50,000 by September 30, 2019, €50,000 by December 31, 2019, and €80,000 by March 31, 2020, €80,000 by June 30, 2020, €80,000 by September 30, 2020, €80,000 by December 31, 2020.. In the event of license transfers or product marketing, the company agreed to pay to OSEO by March 31 of each year, with effect from January 1, 2014:. 23. WorldReginfo - 7d0e69d2-ec19-4b72-a70d-226286e85924. If the program is successful, the company agreed to reimburse the full amount advanced by OSEO, according to the following schedule:.

(25) -. 44.82% of the revenue, excluding tax, from the sale or transfer of licenses, patents, or know-how, received during the previous calendar year if such sales or transfers cover all or part of the results of the assisted program; and 44.82% of the revenue, excluding tax, generated by the marketing (including the sale to a third party) or the use by the company for its own purposes of prototypes, pilot runs or mock-ups made under the assisted program.. In these cases, payments will be applied in priority and in proportion to the final installment due to OSEO Innovation, as detailed in the schedule above and, if applicable, to the penultimate installment. In the event of technical or commercial failure (even partial) of the program, given the nature of the work performed under the Fast acting human insulin project, Adocia agreed to reimburse to OSEO a lump sum of €280,000 as follows: -. €32,500 by March 31, 2017, €32,500 by June 30, 2017, €32,500 by September 30, 2017, €32,500 by December 31, 2017, and €37,500 by March 31, 2018, €37,500 by June 30, 2018, €37,500 by September 30, 2018, €37,500 by December 31, 2018.. Upon non-compliance with the company’s obligations, OSEO is entitled to demand the full payment of the advance. Off-statement of financial position commitments As of the date of this reference document, the company had only one off-statement of financial position commitment (as described in Note 6.1 of the notes to the company’s financial statements included in Section 20.1 of this reference document), in connection with the lease of its premises.. (IFRS - € thousands). FY 2012 (12 months). FY 2011 (12 months). FY 2010 (12 months) (4 956). Net cash flow generated by the business Net cash flow in connection with investment transactions Net cash flow in connection with financing transactions. 919. (6 217). (1 774). (155). (137). 25 413. 252. 4 418. CHANGES IN NET CASH. 24 558. (6 119). (674). Cash and cash equivalents at the start of the year Cash and cash equivalents at year-end. 5 905. 12 024. 12 698. 30 462. 5 905. 12 024. 10.2.1 Cash flows from operating activities Net cash used in operating activities for the years amounted to €4,956 thousand for the year ended December 31, 2010 and €6,217 thousand for the year ended December 31, 2011. In 2012, cash inflows generated by operations exceeded cash outflows used, resulting in net cash of €919 thousand.. 24. WorldReginfo - 7d0e69d2-ec19-4b72-a70d-226286e85924. 10.2 Cash flows.

(26) This decrease in operating cash requirements is explained by the fall in working capital requirements, mostly due to a drop in trade receivables, as the upfront payment of $10 million relating to the license agreement signed with Eli Lilly was received in January 2012.. 10.2.2 Cash flows from investments Net cash used investing activities increased by €1,603 thousand. This is explained by the signing of a €1,000 thousand liquidity contract with BIL in March 2012 and the acquisition of equipment and fittings for the outfitting of additional laboratory space.. 10.2.3 Cash flows from financing transactions As mentioned above, Adocia successfully completed its listing on the NYSE Euronext regulated market in Paris, pursuant to which it raised €25,332 thousand. The company received OSEO reimbursable assistance (see Section 10.1 “Information on the company’s equity, liquidities and sources of financing” in this reference document) in 2010, 2011 and 2012. In 2011, it received the balance of the reimbursable advance (granted for a total amount of €420 thousand) on the human insulin research project. This advance was fully paid off on June 30, 2012. Adocia also received a new €800 thousand reimbursable advance to continue the development of its HinsBet fast acting human insulin project. Lastly, the company paid the first installment (€300 thousand) of a €2,250 thousand reimbursable advance that enabled the company to develop its project for a new system of local and controlled release of growth factors for bone regeneration.. 10.3 Information on borrowing terms and funding structure See Notes 3.10 and 3.11 of the notes to the company’s financial statements prepared in accordance with IFRS in Section 20.1 of this reference document.. 10.4 Restrictions on the use of equity. 10.5 Future sources of financing required As of December 31, 2012, the company’s cash and cash equivalents totaled €30.5 million. Adocia’s financing requirements for future years is strongly dependent on (i) the progress of the product licensed to Eli Lilly (which may generate installment payments by Eli Lilly), (ii) its ability to enter into new agreements for other products under development, and (iii) the development of the company’s project portfolio, which could have a material impact on research and development expenditures. Nevertheless, the company deems that it has the resources necessary to finance its operating expenses for at least the next 18 months.. 25. WorldReginfo - 7d0e69d2-ec19-4b72-a70d-226286e85924. None..

(27) 11. INVENTIONS, PATENTS, LICENSES, TRADEMARKS AND DOMAIN NAMES 11.1 Innovation policy The company’s mission is to create and develop inventions that are subsequently licensed. These inventions concern innovative therapeutic treatments based on combinations of its proprietary BioChaperone® technology and therapeutic proteins approved in Europe and the United States. New inventions based on combinations of these therapeutic proteins with small proprietary or non-proprietary molecules have also been made within the last few months. Since it was founded, Adocia has created inventions in several therapeutic domains, such as the healing of chronic wounds and the treatment of diabetes with insulin therapy. The company’s innovation policy consists of all measures the company takes in this area. The company’s innovative mission guides the recruitment of management employees and technicians, the training of employees, and its work methods. Furthermore, the inventions that Adocia develops are cross-disciplinary and cover various scientific, chemical, physicochemical, analytical and biological fields. To meet this challenge, teams of experts have been formed in each discipline. The various teams are coordinated during regular working meetings held for each project. In addition, every two weeks, each management-level scientist presents a briefing on scientific advances, in the form of a bimonthly report. Mr. Gérard Soula has significant research and innovation management experience, with over 30 years’ experience in this field. Mr. Olivier Soula, R&D Director, has 10 years of experience in R&D management, first with Flamel Technologies and then with Adocia.. Furthermore, Mr. Gérard Soula has assigned to the company, without any financial consideration, all of the rights he holds to date in his inventions within the company’s field of business. Assignment agreements are signed whenever required by a country’s law (in particular the USA and Canada). Furthermore, Mr. Gérard Soula has undertaken to assign to the company, also without any financial consideration, all new intellectual property rights within the company’s field of business that he may hold in the future during the time he continues to be an officer of the company.. 11.2 Patents and patent applications 11.2.1 Industrial property protection policy The success of the company depends at least in part on its capacity to protect its inventions, primarily by obtaining and renewing patents in Europe and the rest of the world. An active policy is continuing to protect products under clinical development (offensive strategy) and also to protect alternative solutions (defensive strategy). Patent applications are qualified as (i) protection of core business, (ii) protection of alternative solutions and (iii) defensive applications. Priority applications are filed in France and the United States: priority applications are filed simultaneously in France and the United, as a provisional patent application in France. The purpose of. 26. WorldReginfo - 7d0e69d2-ec19-4b72-a70d-226286e85924. Adocia has set up a compensation policy to incite inventions in order to promote innovation within the company. An in-house memorandum explains the conditions under which employees who develop inventions are entitled to the additional compensation prescribed by the French Industrial Property Code: it is a flat fee fixed when a patent is filed, followed by a variable progressive compensation proportional to sales generated by the relevant invention..

(28) the provisional application is to commence the American procedure as rapidly as possible. This procedure will change as a result of new American regulations since 16 March 2013. The patent portfolio is analyzed periodically and applications for inventions no longer under development and that cannot be transferred are abandoned in order to control costs. An invention declaration form has been created to describe the invention in question and designate the inventor(s), mentioning their respective contributions. The company's patents deposited or in the course of being deposited are the property of the company because their inventors are employees, except for Mr. Gérard Soula for whom all rights to his inventions (i) have been ceded to the company as stipulated in the accord signed by the principal shareholders of the company on December 15, 2009, which stated that the said accord shall be null and void when stocks are traded on the NYSE Euronext in Paris on February 20, 2012 and (ii) since that date, are ceded to the company in compliance with a contract for the transfer of intellectual property rights between the company and Mr. Gérard Soula. In the case of company employees, each labor contract contains a clause covering inventions and so all inventions legally belong to the company as stipulated in article L.611-7 of the Intellectual Property Code. In addition, transfer agreements are systematically signed for each invention. At the present time, 25 inventions have been protected by patent application deposits for 25 distinct families. Adocia's portfolio therefore contains almost 200 patents and patent applications belonging to the company, most of which are still being examined by patent authorities.. 11.2.2 Type and coverage of patents and held by the company The core of the company's patent portfolio involves patents and patent applications protecting BioChaperone® polymers and small organic molecules that can interact with therapeutic proteins/peptides to improve their properties. The following table lists the patents and patent applications in the name of Adocia that protect families of polymers or of small organic molecules (table updated in early March 2013).. F03. 09/26/2006. F13. 10/06/2008. F29. 12/23/2009. F30. 11/19/2010. F32. 10/05/2011. F35. 09/30/2011. F41. 09/08/2012. F43. 11/13/2012. Dextran functionalized by hydrophobic amino acids Polysaccharides with functional carboxyl groups substituted with a derivative of a hydrophobic alcohol Anionic polysaccharides functionalized by a derivative of a hydrophobic acid Polysaccharides with functional carboxyl groups substituted with hydrophobic derivative with a spacer at least trivalent Polysaccharides whose degree of substitution can be modulated Functionalized oligosaccharides Dextrans with functional carboxyl groups and one hydrophobic moiety at the reducing end of the chain Substituted anionic compounds composed of a skeleton on a small number of sugar units. *The priority date of a patent is the date of the first application in France and/or the United States (or via PCT for family 39). Patents are granted for 20 years from their application date (the date when national, European or international applications were deposited, with the stipulation that European and international patent applications must be deposited within 12 months of the priority patent application), provided that when products are registered (a Marketing Authorization is granted) patents may receive a maximum extension of their protection from 6 months to a maximum of 5 years, depending on the case.. 27. WorldReginfo - 7d0e69d2-ec19-4b72-a70d-226286e85924. Patents protecting polymers and small organic molecules Priority Family  Title * F02 04/07/2006 Bi-functional polysaccharides.

(29) The second aspect of the company's portfolio concerns patents and patent applications protecting complexes formed between BioChaperone® polymers and proteins of interest. These molecular complexes can be demonstrated using a variety of methods. The formation of complexes improves the useful properties of the protein. Patents and patent applications in the name of Adocia protecting families of complexes are listed in the following table (table updated in early March 2013): Patents protecting complexes Family Priority* Title F01. 09/26/2005. F05. 07/27/2007. F12. 09/26/2008. Amphiphilic-PDGF polymer complex Complex between an amphiphilic polymer and an osteogenic protein belonging to the family of BMPs Complex composed of a polysaccharide and an HBP. F27. 19/11/2009. Polysaccharide/BMP complexes soluble at physiological pH. Finally, patents and patent applications protecting formulations of BioChaperone® polymers or small molecules with therapeutic proteins or complexes are the third aspect of Adocia's portfolio. In addition, all products under clinical development are covered by patents/patent applications.. F18. 07/31/2009. New form of administration of complexes of osteogenic proteins. F21. 03/27/2009. F23. 14/04/2008. F33. 08/10/2011. F37. 01/09/2012. F39. 09/18/2012. F40. 08/10/2012. F42. 09/10/2012. F44. 11/14/2012. F45. 11/02/2011. F46. 02/12/2013. F47. 02/12/2013. Formulation of fast acting recombinant human insulin Estrogenic composition comprising a growth factor/amphiphilic polymer complex, a soluble cationic salt and an organic support Solution for injection at pH 7 comprising at least one basal insulin whose pI is between 5.8 and 8.5 Solution for injection at pH 7 comprising at least one basal insulin whose pI is between 5.8 and 8.5 and a substituted co-polyamino acid Stable pharmaceutical composition containing an aqueous solution of an antibody derived from a therapeutically active protein Process for lowering the viscosity of solutions of proteins at high concentrations Aqueous solution of a protein at high concentration with reduced viscosity Formulation of fast acting insulin comprising a substituted anionic compound Formulation of fast acting insulin comprising an oligosaccharide Solution for injection at pH 7 comprising at least one basal insulin whose pI is between 5.8 and 8.5 and a carboxylated anionic compound and hydrophobic moieties Solution for injection at pH 7 comprising at least one basal insulin whose pI is between 5.8 and 8.5 and an anionic polymer rendered hydrophobic. ‡‡‡‡‡‡‡*. The priority date of a patent is the date of the first application in France and/or the United States (or via PCT for family 39). Patents are granted for 20 years from their application date (the date when national, European or international applications were deposited, with the stipulation that European and international patent applications must be deposited within 12 months of the priority patent application), provided that when products are registered (a Marketing Authorization is granted) patents may receive a maximum extension of their protection from 6 months to a maximum of 5 years, depending on the case.. 28. WorldReginfo - 7d0e69d2-ec19-4b72-a70d-226286e85924. Patents and patent applications in the name of Adocia protecting families of formulations are listed in the following table (table updated in early March 2013): Patents protecting formulations ‡‡‡‡‡‡‡ Priority Family * Title.

(30) Adocia is currently active in four therapeutic domains: - wound healing, in particular for the treatment of diabetic foot ulcers: Adocia polymers enable a notable improvement in treatments with PDGF-BB. BioChaperone®-PDGF-BB has been the subject of a phase II clinical trial and a phase III trial will be conducted; -. treatment of diabetes with: o fast acting insulins administered before each meal. BioChaperone® polymers and small organic molecules reduce the time to onset of action of these fast acting insulins, whether human insulin or fast acting insulin analogs and o the combination of the best slow acting insulin, insulin glargine, with a fast acting insulin;. -. therapeutic treatments with monoclonal antibodies; and. -. kidney failure with a growth factor belonging to the family of BMPs.. The proteins used in these programs have been the subject of patents deposited by third parties. Some of these proteins are in the public domain whereas others are still covered by valid patents. The protection status of proteins is detailed in the description of each program (see below). For proteins still protected by a patent, no product resulting from the company's program can be marketed by a third party other than the holder of the said patent before the protein enters the public domain. The following diagrams show the different levels of patent protection implemented by Adocia around each of its flagship research programs. 11.2.2.1 Program for wound healing of chronic lesions. F03. Patents for complexes. The aim of this program is to develop treatments to improve wound healing of chronic lesions such as diabetic foot ulcers. The therapeutic compositions under development include: - a BioChaperone polymer® covered by the scope of patents and patent applications of family 03 of the company; -. a skin regeneration protein, PDGF-BB.. The polymer provides the protein with exceptional properties resulting from the formation of a complex: stability of the protein at room temperature for at least 3 months, resistance to enzymes in the wound and increased biological activity. The compositions resulting from this program are covered by a double patent protection, i.e. families F03 (patents for polymers) and F01 (patents for complexes). United States and European patents have also been granted for family F01 of complexes, in particular protecting the lead complex of the program under development. Since it concerns protein PDGF-BB, a product patented by a third party, most patents involving this. 29. WorldReginfo - 7d0e69d2-ec19-4b72-a70d-226286e85924. Patents for polymers. F01.

(31) protein have been in the public domain since 2010. 11.2.2.2 Program of treatment of diabetes with insulin. 11.2.2.2.1. Fast acting insulin. F21. F43. F44 F45. Patents for polymers and small organic molecules. Patents for formulations. The aim of this program is to develop formulations containing fast acting recombinant human insulin or its analogs. These formulations use special BioChaperone® polymers covered by the scope of patents and patent applications of family F03 of the company, that form complexes with recombinant insulin or its analogs to accelerate passage of insulin into the blood, thereby significantly reducing the time to onset of action. The formulations resulting from this program are covered by a double protection from the company's patent applications for polymers and small organic molecules (families F03, F35 and F43) and patent applications for formulations (families F21, F44 and F45). Human insulin is now in the public domain. There are three fast acting analogs on the market: - Humalog® (insulin lispro), patented by Eli Lilly, that entered the public domain in 2013; -. NovoLog® (insulin aspart), patented by Novo Nordisk, that entered the public domain in 2014;. -. Apidra® (insulin glulisine), patented by Sanofi that will enter the public domain in 2017. Combination of a slow acting insulin with a fast acting insulin. F33 F37 F46. F43. F47. Patents for polymers or small Patents for formulations organic molecules. The aim of this program is to develop insulin formulations for the combined administration of a fast acting prandial insulin and the most efficient basal insulin, insulin glargine, as a single injection of the product. Until the present, this type of combination was not possible because the products had to be formulated at different pH values. The use of the formulations proposed by Adocia resolves this issue of compatibility and thereby enables diabetic patients to reduce the number of daily insulin injections. These formulations are covered by a double protection from patent applications:. 30. WorldReginfo - 7d0e69d2-ec19-4b72-a70d-226286e85924. 11.2.2.2.2.

(32) -. for polymers (families F13 and F30) of the company, that now make it possible to mix insulin glargine with commercial prandial insulins;. -. for formulations (families F33, F37, F46 and F47) of the company. Families F37, F46 and F47 were filed for defensive protection.. A United States patent has been granted for family F13 of products, in particular for the protection of the principal product of the program under development. Insulin glargine is currently the subject of a patent held by Sanofi. Most patents and their extensions will expire in 2015. They are fast acting insulins and so the patent expiration dates are listed in the "fast acting insulin" part (see below). 11.2.2.3 Program of formulations of monoclonal antibodies. F42. Patents for formulations The aim of this program is to develop stable pharmaceutical compositions of monoclonal antibodies (mAb) in solution at high concentrations. The compositions proposed by the company involve special BioChaperone® polymers and small organic molecules enabling highly concentrated solutions of monoclonal antibodies to be prepared, while maintaining physical and chemical stability. The compositions created with this program are covered by double protection from polymer patent applications families F13, F26 and F30) and patent for formulations (families F39, F40 and F42) of the company). Most monoclonal antibodies are proprietary proteins still protected by third party patents. 11.2.2.4 Program for systemic applications. F13. Patents for polymers. Patents for complexes. The aim of this program is to develop pharmaceutical formulations containing a growth factor of the family of BMPs for systemic applications, in particular kidney regeneration. This BMP family growth factor is a key protein for the repair of these tissues. The formulations proposed by the company comprise special polymers that form a complex with this protein, improving its solubility at physiological pH and its stability. The formulations resulting from this program are doubly protected by the company's patents of families F30 (patents for polymers) and F27 (patents for complexes). This protein of the family of BMPs has been patented by a third party and most of the patents protecting it as a product will expire in 2015. 11.2.2.5 Bone regeneration. 31. WorldReginfo - 7d0e69d2-ec19-4b72-a70d-226286e85924. F27.

(33) F13. F5. F18. F27. Patents for polymers. Patents for complexes. F23. Patents for formulations. The aim of this program is to develop pharmaceutical formulations containing a growth factor from the family of BMPs, in particular intended for regeneration of bone tissues in vivo. The formulations proposed by the company involve special BioChaperone® polymers that form complexes with the growth factor of the family of BMPs: they improve its solubility at physiological pH and its stability. The formulations resulting from this program are covered by a triple patent protection of families F13 (patents for polymers), F27 (patents for complexes) and F23 (patents for formulations) of the company. This growth factor belonging to the family of BMPs has been patented by a third party and most of the patent protecting the product expired in 2012.. 11.2.3 Patents currently in use At the present time, no patent is used to protect products.. 11.2.4 Geographic coverage. -. Strategy 2 for alternative solutions: United States, Europe, Canada, China, Japan, India, Australia and Israel;. -. Strategy 3 for the core of the business: United States, Europe, Canada, China, Japan, India, Australia, Israel, Mexico, Brazil, Russia, South Africa, Singapore and South Korea.. These predetermined strategies are decision-making tools enabling the company to be reactive depending on results obtained and contacts made with partners, and also enable budget control when starting the national phase. The following table lists the countries in which the company's inventions are protected by a patent/patent application. "X": patent application deposited, "D": patent delivered (obtained), "w": patent application withdrawn or abandoned and "V*": European patent delivered and validated in France, Belgium, Luxemburg, Austria, Germany, Greece, Turkey, Spain, Portugal, Switzerland, Lichtenstein, Italy, United Kingdom, Ireland, Denmark, Finland, Sweden, Iceland, Holland, Poland, Hungary, Romania and the Czech Republic. 32. WorldReginfo - 7d0e69d2-ec19-4b72-a70d-226286e85924. Patent coverages are examined with respect to the importance of inventions and three predetermined strategies have been implemented by the company involving the choice of countries in which the national phase of PCT applications are in force (no later than 30 months after depositing the priority application). These three predetermined strategies are: - Strategy 1 for defensive applications: United States and Europe;.