PROSPECTUS SUMMARY

         This summary highlights selected information about us contained elsewhere in this prospectus. This summary does not contain all of the information that you should consider in making your investment decision. Before investing in the ADSs, you should read this entire prospectus carefully, including the sections entitled "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" and our consolidated financial statements and related notes, for a more complete understanding of our business and this offering.

         Except as otherwise required by the context, references to "TiGenix," "Company," "we," "us" and "our" are to TiGenix and its subsidiaries.

        We are an advanced biopharmaceutical company focused on developing and commercializing novel therapeutics from our proprietary technology platforms of allogeneic, or donor-derived, stem cells. We have completed, and received positive data in, a single pivotal Phase III trial in Europe and Israel of our most advanced product candidate Cx601, a first-in-class injectable allogeneic stem cell therapy indicated for the treatment of complex perianal fistulas in patients suffering from Crohn's disease. A complex perianal fistula consists of abnormal tracts between the rectum and the exterior surroundings of the anus, and is commonly associated with Crohn's disease. It is a serious clinical condition affecting the anal sphincter and is potentially associated with a perianal abscess. Cx601 has been granted orphan designation by the European Medicines Agency, or EMA, in recognition of its potential application for the treatment of anal fistulas, which affect approximately 120,000 adult patients in the United States and Europe and for which existing treatment options are inadequate. The EMA grants orphan designation to medicinal products for indications that affect no more than five out of 10,000 people in the European Union. The benefits of orphan designation include a streamlined process for obtaining relevant regulatory approvals and up to ten years of exclusivity in the European market.

        Cx601 is our lead product candidate based on our platform of expanded adipose, or fat tissue, derived stem cells, known as eASCs. In the randomized, double-blind Phase III study, Cx601 met the primary endpoint of combined remission of complex perianal fistulas at twenty four weeks.

        Based on the data from our pivotal Phase III trial in Europe, we plan to submit a marketing authorization application to the EMA in the first quarter of 2016 and anticipate launching the approved product in Europe during the second half of 2017. We also intend to initiate a pivotal Phase III trial for Cx601 for the treatment of complex perianal fistulas in the United States by the first quarter of 2017 and have begun the technology transfer process to Lonza, a U.S.-based contract manufacturing organization. Based on discussions with the U.S. Food and Drug Administration, or FDA, we believe that the U.S. Phase III trial, if successful, could, together with the European Phase III data, serve as supportive evidence for filing a biologics license application, or BLA, for regulatory approval with the FDA. We have already reached an agreement with the FDA through a special protocol assessment, or SPA, procedure for our proposed protocol. The agreed primary endpoint for the U.S. Phase III trial is the same as the one for the European Phase III trial. We intend to apply for fast track designation from the FDA, which would facilitate and expedite development and review of our U.S. Phase III trial. Fast track designation by the FDA is granted to drugs that treat serious conditions and fill an unmet medical need. It results in earlier and more frequent communication with the FDA during the drug development and review process.

        Our eASC-based platform has generated other product candidates, including Cx611, for which we have completed a European Phase I trial in severe sepsis. We are currently preparing to initiate a Phase II clinical trial in severe sepsis in Europe by the end of 2015.

        On July 31, 2015, we acquired Coretherapix, a Spanish biopharmaceutical company focused on developing cost-effective regenerative therapeutics to stimulate the endogenous repair capacity of the heart and mitigate the negative effects of myocardial infarction, or a heart attack. Coretherapix has

 

developed an allogeneic platform of expanded cardiac stem cells, or CSCs, and its lead product candidate, AlloCSC-01, employs allogeneic CSCs as a potential treatment for acute ischemic heart disease. We are sponsoring a European Phase I/II trial to evaluate the safety and efficacy of the intracoronary infusion of AlloCSC-01 in patients with acute myocardial infarction. We expect to receive six-month interim exploratory data during the second half of 2016, and final results will be available during the first half of 2017. We are also developing AlloCSC-02, the second product candidate from the CSC-based platform, which is in a preclinical proof of concept stage for a chronic cardiac indication.

        We also developed and commercialized ChondroCelect, the first cell-based medicinal product to receive marketing authorization from the EMA, which is indicated for cartilage repair in the knee.

        Our eASC-based product candidates are manufactured at our facility in Madrid that has been approved by the Spanish Medicines and Medical Devices Agency as being compliant with current Good Manufacturing Practices, or cGMP, requirements, which are the standards prescribed by regulatory agencies that control and license the manufacture and supply of pharmaceutical products, such as eASCs. Through our expansion process, we can generate up to 2,400 doses of Cx601 from cells extracted from a single healthy donor. We believe we already have the capacity to scale up the production of our eASC-based products on a late-stage clinical as well as commercial scale. Our CSC-based product candidates are manufactured in Spain by 3P Biopharmaceuticals, a sub-contractor, which has been approved by the Spanish Medicines and Medical Devices Agency as being compliant with cGMP requirements, based on a manufacturing process developed by Coretherapix.

        We have retained the worldwide rights for all of our product candidates. As of September 30, 2015, we owned or co-owned twenty-seven patent families and had more than one hundred granted patents in more than twenty jurisdictions, including the United States, with expiration dates starting from 2020 for a patent relating to ChondroCelect.

Product and Product Candidates

        Our therapeutic approach is to focus on the use of living cells, rather than conventional drugs, for the treatment of inflammatory and autoimmune diseases, through our eASC-based platform, and heart disease, through our CSC-based platform. Our pipeline of stem cell programs is based on validated platforms of allogeneic stem cells. Our eASCs are extracted and cultured from fat tissue sourced from healthy consenting adult donors for clinical studies focused on the treatment of autoimmune and inflammatory diseases. Our CSCs are sourced from a small amount of myocardial tissue that would typically be discarded during a routine valvular replacement operation.

 

        The following chart summarizes our product candidates and our marketed product in Europe:

Cx601

        Cx601, our lead product candidate, is a potential first-in-class local injectable allogeneic stem cell therapy that has completed a pivotal Phase III trial in Europe and Israel for the treatment of complex perianal fistulas in patients suffering from Crohn's disease. We have observed compelling clinical results that suggest that Cx601 has clinical utility in treating perianal fistulas in a single treatment with increased efficacy and a more favorable adverse events profile than currently available therapies in Europe and the United States, with patients having a 44.3% greater probability of achieving combined remission than placebo patients. Based on the results of our pivotal Phase III trial, we plan to submit a marketing authorization application to the EMA the first quarter of 2016 and launch the product in Europe during the second half of 2017. Moreover, Cx601 enjoys significant benefits due to its designation as an orphan drug by the EMA.

        We have also had a meeting with the FDA to discuss the adequacy of our clinical and non-clinical data to support an investigational new drug, or IND, application for a U.S.-based Phase III trial. We received positive feedback regarding our pivotal European Phase III trial design for supporting a BLA and have reached an agreement with the FDA through an SPA procedure for our proposed protocol for a Phase III trial in the United States. In addition, we intend to apply to the FDA for fast track designation. We expect to submit an IND application to the FDA by the end of 2016 and to initiate a Phase III trial in the United States by the first quarter of 2017.

Cx611

        Cx611, our second eASC-based product candidate, is a potential first-in-class intravenous injectable allogeneic stem cell therapy intended for the treatment of severe sepsis. We believe that Cx611, if approved for severe sepsis, would be an add-on therapy that has the potential to reduce mortality, which is estimated at up to 20% to 50% for patients suffering from severe sepsis. Following positive

 

data from a European Phase I trial, we are planning to advance Cx611 in severe sepsis in a Phase II trial in Europe.

Cx621

        We have explored the intra-lymphatic administration of allogeneic eASCs with Cx621 and generated positive safety and feasibility information in a Phase I trial in Europe. This different route of administration has the potential to enable applications in autoimmune diseases.

AlloCSC-01

        AlloCSC-01, our lead CSC-based product candidate, is a suspension of allogeneic CSCs administered into the coronary artery of the patient. We are currently in the second stage of a two-stage Phase I/II trial in Europe to evaluate the safety and efficacy of the intracoronary infusion of AlloCSC-01 in patients with acute myocardial infarction. We expect to receive interim exploratory data during the second half of 2016 and final results during the first half of 2017. We believe that AlloCSC-01 has the potential to limit the extent of tissue damage caused by myocardial infarction and delay the onset, or reduce the severity of, congestive heart failure.

AlloCSC-02

        We are also developing AlloCSC-02, the second product candidate from our CSC-based platform, which is in a preclinical proof of concept stage for a chronic cardiac indication.

ChondroCelect

        ChondroCelect, our commercial product, was the first cell-based product approved in Europe, and received centralized marketing authorization in October 2009 as an advanced therapy medicinal product. During the first six months of 2014, we discontinued our operations in connection with ChondroCelect, through the combination of the sale of our manufacturing subsidiary to PharmaCell and the entry into an agreement with Swedish Orphan Biovitrium, or Sobi, for the exclusive marketing and distribution rights with respect to ChondroCelect within the European Union (except for Finland), as well as several other countries, including the Middle East and North Africa. We continue to generate revenues from the sale of ChondroCelect in the form of royalty payments from Sobi and revenues generated by Finnish Red Cross Blood Service.

Technology Platform

        Our development programs are based on our proprietary allogeneic stem cell-based technology platforms and focus on the treatment of both inflammatory and autoimmune diseases and the chronic and acute settings of heart disease. The cells target different pathways than conventional drugs and may be effective in patients who fail to respond to such drugs, or in indications for which there is currently no available treatment. We believe our platforms offer significant market opportunities based on the following distinguishing factors:

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Our use of allogeneic adult stem cells. This has the potential to enable efficient production of large batches of cells, does not require any biopsy or tissue procurement from the patient and results in the immediate and consistent availability of cells when required for treatment.



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Our expertise in optimizing the delivery of stem cells as required by different indications through both local and systemic routes of administration.



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Our use of eASCs extracted from human adipose tissue sourced from healthy donors. We believe that this type of cell may offer significant advantages over other mesenchymal cell types,

 

such as stem cells sourced from bone marrow, for the treatment of inflammatory and autoimmune diseases.

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Our use of human-derived cardiac tissue that would typically be discarded during a routine valvular replacement operation. We believe that CSCs extracted from this tissue play a role in the regulation of the regeneration process in the infarcted heart upon their administration.



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The mechanism of action of our eASC-based product candidates, which utilizes two main biological pathways that underlie the efficacy of stem cells generally in disease treatment: (i) their anti-inflammatory properties and (ii) their secretion of repair and growth promoting molecules. In clinical studies, our eASCs have exhibited broad immunomodulatory properties, including the regulation of immune cells such as B lymphocytes, T lymphocytes, natural killer cells, monocytes or macrophages and neutrophils.



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The mechanism of action of our CSC-based product candidates, which we believe relies on three potential biological pathways: (i) cardioprotection of damaged tissue, (ii) modulation of the immune response to reduce scarring and ameliorate the effects of chronic inflammation and (iii) promotion of the regeneration of new myocardial tissue.

Strategy

        Key elements of our strategy to provide innovative and safe treatment options for a broad range of inflammatory and autoimmune diseases and to leverage our cell-therapy experience by expanding into other treatment areas, such as cardiology indications, with our recent acquisition of Coretherapix, are as follows:

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Advance the clinical development of Cx601 for the treatment of complex perianal fistulas in patients with Crohn's disease and secure regulatory approval in Europe and the United States.



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Achieve global commercialization of Cx601, leveraging our experience in bringing ChondroCelect to market.



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Advance our product candidates Cx611, AlloCSC-01 and AlloCSC-02 in the United States and the rest of the world.



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Discover, develop and commercialize first-in-class novel therapeutics for areas of high unmet medical need by leveraging our proprietary allogeneic stem cell-based technology platforms and our experience in bringing stem-cell based products to market.



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Strengthen our competitive position by leveraging our experienced management team and reinforcing key opinion leader support.

Summary Risk Factors

        An investment in the ADSs involves a high degree of risk. You should consider carefully the risks discussed below and under the heading " Risk Factors " beginning on page 17 of this prospectus before purchasing the ADSs. If any of these risks actually occurs, our business, financial condition or results of operations would likely be materially adversely affected. In such case, the trading price of our ADSs would likely decline, and you may lose all or part of your investment.

        These risks include the following:

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We may experience delays or failure in the preclinical and clinical development of our product candidates.



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Regulatory approval of our product candidates may be delayed, not obtained or not maintained, and we may be affected by future changes to any pharmaceutical legislation or guidelines.

 

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We may need substantial additional funding, which may not be available on acceptable terms when required, if at all.



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We have an accumulated deficit of 97.6 million euros as of June 30, 2015, and our net losses and significant cash used in operating activities have raised substantial doubt regarding our ability to continue as a going concern.



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The Coretherapix acquisition could cause disruptions in our business or the business of Coretherapix, which could have a material adverse effect on the business prospects and financial results of the combined company.



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We may not be able to protect our proprietary technology adequately or enforce any rights related thereto.



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We rely or may rely on third parties for certain of our research, clinical trials, technology, supplies, manufacturing and sales and marketing, and a failure of service by such parties could adversely affect our business and reputation.

Company Information

        TiGenix was incorporated in Belgium on February 21, 2000 as a company with limited liability under Belgian corporate law. Our principal executive and registered offices are located at Romeinse straat 12, box 2, 3001 Leuven, Belgium. Our telephone number is +32 (16) 39 60 60. We are registered with the Register of Legal Entities (Leuven) under the enterprise number 0471.340.123. Our internet website is www.tigenix.com. The information contained on, or accessible through, our website is not incorporated by reference into this prospectus and should not be considered a part of this prospectus.

        Our agent for service of process in the United States is CT Corporation System, whose registered offices are located at 111 Eighth Avenue, 13th Floor, New York, NY 10011. Their telephone number is +1 (212) 894-8800.

        For additional information regarding our Company organizational history, see " History and Organizational Structure ."

Recent Developments

        On July 31, 2015, we completed the acquisition of Coretherapix, a Spanish biopharmaceutical company in the cardiology field, through a contribution agreement with Genetrix for an upfront payment of 1.2 million euros in cash and 7.7 million new shares issued in connection with the acquisition, as a result of which Genetrix became one of our principal shareholders. Genetrix is also entitled to receive contingent payments linked to certain milestones in terms of product development and net sales of products based on the Coretherapix pipeline.

        On August 24, 2015, we announced that Cx601, our lead product candidate, met the primary endpoint of its pivotal Phase III clinical trial conducted in eight participating countries (Spain, Italy, Austria, Belgium, Germany, France, the Netherlands and Israel) in Crohn's disease patients with complex perianal fistulas.

        On November 27 and December 3, 2015, we raised a total of 8.7 million euros through a private placement of 9,106,180 new shares.

Implications of Being an Emerging Growth Company and a Foreign Private Issuer

        As a company with less than $1.0 billion in revenue during its fiscal year, we qualify as an "emerging growth company" as defined in Section 2(a) of the Securities Act of 1933, as amended, as modified by the Jumpstart our Business Startups Act of 2012, or the JOBS Act. As such, we are eligible

 

to take advantage of specified reduced reporting requirements and are relieved of certain other significant requirements that are otherwise generally applicable to public companies. As an emerging growth company:

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We are permitted to present only two years of audited consolidated financial statements and only two years of related Management's Discussion and Analysis of Financial Condition and Results of Operations in the registration statement of which this prospectus forms a part.



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We are exempt from the requirement to obtain an attestation and report from our auditors on the assessment of our internal control over financial reporting pursuant to Section 404(b) of the Sarbanes-Oxley Act of 2002.



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We are permitted to provide less extensive disclosure about our executive compensation arrangements.

        We expect to remain an "emerging growth company" for up to five years, or until any one of the following occurs:

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The last day of the first fiscal year in which our annual gross revenue exceeds $1 billion.



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The date on which we become a "large accelerated filer" as defined in Rule 12b-2 under the Securities Exchange Act of 1934, as amended, which would occur if the market value of our common equity held by non-affiliates exceeds $700 million as of the last business day of our most recently completed second fiscal quarter and we have been publicly reporting for at least twelve months.



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The date on which we have issued more than $1.0 billion in non-convertible debt during the preceding three-year period.

        We may choose to take advantage of some but not all of these reduced burdens. We have taken advantage of reduced reporting requirements in this prospectus. Accordingly, the information contained herein may be different from the information you receive from our competitors that are public companies, or other public companies in which you have made an investment.

        Further, as a foreign private issuer, we are not subject to the same requirements that are imposed upon U.S. domestic issuers by the Securities and Exchange Commission, or the SEC. Under the Exchange Act, we will be subject to reporting obligations that, in certain respects, are less detailed and less frequent than those of U.S. domestic reporting companies. For example, we will not be required to issue quarterly reports, proxy statements that comply with the requirements applicable to U.S. domestic reporting companies, or individual executive compensation information that is as detailed as that required of U.S. domestic reporting companies. We will also have four months after the end of each fiscal year to file our annual reports with the SEC and will not be required to file current reports as frequently or promptly as U.S. domestic reporting companies. We will also present financial statements pursuant to International Financial Reporting Standards, or IFRS, instead of pursuant to U.S. generally accepted accounting principles, or U.S. GAAP. Furthermore, although the members of our management and supervisory boards will be required to notify the Belgian Financial Markets and Services Authority of certain transactions they may undertake, including with respect to our ordinary shares, our officers, directors and principal shareholders will be exempt from the requirements to report transactions in our equity securities and from the short-swing profit liability provisions contained in Section 16 of the Exchange Act. These exemptions and leniencies will reduce the frequency and scope of information and protections available to you in comparison to those applicable to a U.S. domestic reporting companies. We intend to take advantage of the exemptions available to us as a foreign private issuer after we no longer qualify as an emerging growth company.