Biophytis S.A.
Sorbonne University—BC 9, Bâtiment A 4ème étage
4 place Jussieu
75001 Paris, France
+33 1 44 27 23 00
(Address, Including Zip Code, and Telephone Number, Including Area Code, of Registrant's Principal Executive Offices)

Puglisi & Associates
850 Library Avenue, Suite 204
Newark, Delaware 19711
(302)738-6680
(Name, Address, Including Zip Code, and Telephone Number, Including Area Code, of Agent For Service)

Approximate date of commencement of proposed sale to the public:
As soon as practicable after the effective date of this Registration Statement.

If any of the securities being registered on this form are to be offered on a delayed or continuous basis pursuant to Rule 415 under the Securities Act of 1933, check the following box. o

If this Form is filed to register additional securities for an offering pursuant to Rule 462(b) under the Securities Act, check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering. o

If this Form is a post-effective amendment filed pursuant to Rule 462(c) under the Securities Act, check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering. o

If this Form is a post-effective amendment filed pursuant to Rule 462(d) under the Securities Act, check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering. o

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933.

If an emerging growth company that prepares its financial statements in accordance with U.S. GAAP, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards† provided pursuant to Section 7(a)(2)(B) of the Securities Act. o

The registrant hereby amends this registration statement on such date or dates as may be necessary to delay its effective date until the registrant shall file a further amendment which specifically states that this registration statement shall thereafter become effective in accordance with Section 8(a) of the Securities Act of 1933, as amended, or until the registration statement shall become effective on such date as the Securities and Exchange Commission acting pursuant to said Section 8(a), may determine.

The information in this prospectus is not complete and may be changed. We may not sell these securities until the registration statement filed with the Securities and Exchange Commission is effective. This prospectus is not an offer to sell these securities and is not soliciting an offer to buy these securities in any state where the offer or sale is not permitted.

(Including 8,750,000 Ordinary Shares in the form of American Depositary Shares)

We are offering an aggregate of 13,125,000 ordinary shares in a global offering.

We are offering 8,750,000 ordinary shares in the form of American Depositary Shares, or ADSs, primarily in the United States, but also in countries outside the United States including the European Union, referred to herein as the ADS offering. Each ADS represents the right to receive 10 ordinary shares. The ADSs may be evidenced by American Depositary Receipts, or ADRs.

We are concurrently offering 4,375,000 ordinary shares, primarily to qualified investors in the European Union and to investors in countries outside the United States, but also in the United States, referred to herein as the ordinary share offering.

This is our initial public offering of ADSs. Prior to this offering there has been no public market for the ADSs. We have applied to list the ADSs on the Nasdaq Capital Market under the symbol "BPTS." Our ordinary shares are listed on the Euronext Growth Paris under the symbol "ALBPS."

The offering price is expected to be between $7.00 and $9.00 per ADS, or between €0.62 and €0.80 per ordinary share. The final offering price per ADS in U.S. dollars and the corresponding offering price per ordinary share in euros will be determined through negotiations between us and H.C. Wainwright & Co., LLC, or Wainwright, as the representative of the several underwriters, and by reference to the prevailing market prices of our ordinary shares on the Euronext Growth Paris after taking into account market conditions and other factors. On July 8, 2019, the last reported sale price of our ordinary shares on the Euronext Growth Paris was €0.88 per ordinary share, corresponding to a price of $9.87 per ADS, assuming an exchange rate of €0.89 per U.S. dollar, the Banque de France exchange rate on July 8, 2019, and based on an assumed ratio of 10 ordinary shares for each ADS.

The closings of the ADS offering and the ordinary share offering, which are together referred to as the global offering, will occur simultaneously. The total number of ordinary shares and ADSs to be offered and sold in the ADS offering and the ordinary share offering is subject to reallocation between these offerings as permitted under applicable laws and regulations.

We are an "emerging growth company" as that term is used in the Jumpstart Our Business Startups Act of 2012 and, as such, have elected to comply with certain reduced public company reporting requirements for this prospectus and future filings.

Investing in the ADSs and ordinary shares involves risks. See "Risk Factors" beginning on page 13.

Neither the Securities and Exchange Commission nor any U.S. state or other securities commission has approved or disapproved of these securities or passed upon the adequacy or accuracy of this prospectus. Any representation to the contrary is a criminal offense.

Wainwright may also exercise its option to purchase up to an additional 1,968,750 ordinary shares (to be delivered in the form of an aggregate of 196,875 ADSs) from us in the global offering, at the public offering price, less underwriting discounts and commissions, within 30 days after the date of this prospectus. If Wainwright exercises this option in full, the total underwriting commissions payable by us will be € ($ ) and the total proceeds to us, before expenses, will be € ($ ), based on the Banque de France exchange rate on , 2019.

The underwriters expect to deliver the ADSs to purchasers in the ADS offering on or about , 2019 through the book-entry facilities of The Depository Trust Company. The underwriters expect to deliver the ordinary shares to purchasers in the ordinary share offering on or about , 2019 through the book-entry facilities of Euroclear France.

You should rely only on the information contained in this prospectus and any related free-writing prospectus that we authorize to be distributed to you. We and the underwriters have not authorized any person to provide you with information different from that contained in this prospectus or any related free-writing prospectus that we authorize to be distributed to you. This prospectus is not an offer to sell, nor is it seeking an offer to buy, these securities in any state or jurisdiction where the offer or sale is not permitted. The information in this prospectus speaks only as of the date of this prospectus unless the information specifically indicates that another date applies, regardless of the time of delivery of this prospectus or of any sale of the securities offered hereby.

For investors outside the United States: Neither we nor the underwriters have taken any action in any jurisdiction outside the United States to permit a public offering of the ADSs or the ordinary shares, or possession or distribution of this prospectus in that jurisdiction. Persons outside the United States who come into possession of this prospectus must inform themselves about and observe any restrictions as to this global offering and the distribution of the prospectus applicable to that jurisdiction.

We are incorporated in France, and a majority of our outstanding securities are owned by non-U.S. residents. Under the rules of the U.S. Securities and Exchange Commission, or SEC, we are currently eligible for treatment as a "foreign private issuer." As a foreign private issuer, we will not be required to file periodic reports and financial statements with the SEC as frequently or as promptly as domestic

registrants whose securities are registered under the Securities Exchange Act of 1934, as amended, or the Exchange Act.

The financial statements included in this prospectus are presented in euros. All references in this prospectus to "$," "US$," "U.S.$," "U.S. dollars," "dollars" and "USD" mean U.S. dollars and all references to "€" and "euros," mean euros, unless otherwise noted. Throughout this prospectus, references to ADSs mean ADSs or ordinary shares represented by ADSs, as the case may be.

Unless otherwise indicated, information contained in this prospectus concerning our industry and the markets in which we operate, including our general expectations and market position, market opportunity and market size estimates, is based on information from independent industry analysts, third-party sources and management estimates. Management estimates are derived from publicly available information released by independent industry analysts and third-party sources, as well as data from our internal research, and are based on assumptions made by us based on such data and our knowledge of such industry and market, which we believe to be reasonable. Although we are responsible for all of the disclosures contained in this prospectus, we have not independently verified any of the data from third-party sources, nor have we ascertained the underlying economic assumptions relied upon therein. In addition, while we believe the market opportunity information included in this prospectus is generally reliable and is based on reasonable assumptions, such data involves risks and uncertainties, including those discussed under the heading "Risk Factors."

This prospectus may contain references to our trademarks and to trademarks belonging to other entities. Solely for convenience, trademarks and trade names referred to in this prospectus, including logos, artwork and other visual displays, may appear without the ® or ^TM symbols, but such references are not intended to indicate, in any way, that we will not assert, to the fullest extent under applicable law, our rights or the rights of the applicable licensor to these trademarks and trade names. We do not intend our use or display of other companies' trade names or trademarks to imply a relationship with, or endorsement or sponsorship of us by, any other company.

PROSPECTUS SUMMARY

The following summary highlights information contained elsewhere in this prospectus and does not contain all of the information you should consider before investing in the ADSs and/or ordinary shares. You should read the entire prospectus carefully, including "Risk Factors" and our financial statements and the related notes appearing elsewhere in this prospectus. You should carefully consider, among other things, the matters discussed in the sections of this prospectus titled "Business," and "Management's Discussion and Analysis of Financial Condition and Results of Operations" before making an investment decision. Unless otherwise indicated, "Biophytis," "the company," "our company," "we," "us" and "our" refer to Biophytis S.A. and its consolidated subsidiary.

Overview

We are a clinical-stage biotechnology company focused on the development of therapeutics that slow the degenerative processes associated with aging and improve functional outcomes for patients suffering from age-related diseases. Our goal is to become a leader in the emerging field of aging science by delivering life-changing therapies to the growing number of patients in need. To accomplish this goal, we have assembled an experienced and skilled group of industry professionals, scientists, clinicians and key opinion leaders from leading industry and academic institutions from around the world.

The global population of people over the age of 60 is expected to double from approximately 962 million in 2017 to 2.1 billion by 2050, according to estimates from the United Nations' World Population Prospects: the 2017 Revision. Healthcare costs, including costs associated with treatments and long-term care for age-related diseases associated with this demographic shift, are expected to rise proportionally, as effective treatment solutions are currently lacking. We believe that developing treatments to slow disease progression and reduce the risk of severe disability associated with age-related diseases is of the utmost importance.

As we age, our natural ability to compensate for stress and remain functional, called biological resilience, degrades. The decline in biological resilience contributes to the acceleration of the degenerative processes and the impairment of functional performance, which, in turn, can lead to severe disability, reduced healthspan and ultimately death. Our therapeutic approach is aimed at targeting and activating key biological resilience pathways that can protect against and counteract the effects of the multiple biological and environmental stresses, including inflammatory, oxidative and metabolic stresses that lead to age-related diseases.

We are focusing our efforts to develop our lead drug candidate, Sarconeos (BIO101), an orally administered small molecule in development for the treatment of neuromuscular diseases. Sarconeos (BIO101) is a plant-derived pharmaceutical-grade purified 20-hydroxyecdysone. We have completed preclinical studies and a Phase 1 clinical trial in healthy human volunteers, which are necessary for pursuing further clinical development of Sarconeos (BIO101). Our early data indicates that Sarconeos (BIO101) stimulates biological resilience and muscle anabolism in cellular models, and preserves strength, mobility and respiratory capacity in animal models of certain neuromuscular diseases. While we are still in the early stages of development, we believe that these results support further investigation and clinical development of Sarconeos (BIO101) in patients with neuromuscular diseases.

The initial indication we are seeking approval for is sarcopenia, an age-related degeneration of skeletal muscle, which is characterized by a loss of muscle mass, strength and function in elderly people (adults 65 years of age and older) leading to mobility disability and increased risk of adverse health events and hospitalization, and potential death resulting from falls, fractures, and physical disability. We are currently testing the safety and efficacy of Sarconeos (BIO101) in an ongoing global, randomized, multicenter, double-blind, placebo-controlled Phase 2b clinical trial (SARA-INT) of 334 elderly patients

with sarcopenia at risk of mobility disability. There is currently no approved medication for sarcopenia, which is highly prevalent in the elderly with an estimated prevalence between six and 22 percent.

We are also developing Sarconeos (BIO101) for Duchenne muscular dystrophy, or DMD, a rare genetic neuromuscular disease in male children and young adults, which is characterized by accelerated degeneration of muscle and is responsible for a loss of mobility, respiratory failure and cardiomyopathy, leading to premature death. There is currently no cure and limited treatment options for DMD, which affects approximately one in 5,000 newborn boys (approximately 20,000 new cases annually worldwide). In 2018, we received orphan drug designation for Sarconeos (BIO101) in DMD from the U.S. Food and Drug Administration, or FDA, and the European Medicines Agency, or EMA.

Our second drug candidate, Macuneos (BIO201), is an orally administered small molecule in development for the treatment of diseases of the retina, or retinopathies. It is a plant-derived pharmaceutical-grade purified 9 cis-norbixin, or norbixin. We have completed preclinical cellular and animal studies of Macuneos (BIO201) for the treatment of retinopathies. While we are still in the early stages of development, we believe that the results from our preclinical studies support continued investigation into whether Macuneos (BIO201) may stimulate biological resilience and protect the retina against phototoxic damage that leads to vision loss. The initial indication we plan to seek approval for is dry age-related macular degeneration, or AMD, a common eye disorder among people over the age of 50 that affects central vision, impairing functions such as reading, driving, and facial recognition, and has a major impact on quality of life and the ability to live independently. There are currently no approved treatments for dry AMD, which, based on our estimates from publicly available information, affects approximately 145 million people worldwide and is expected to increase over time as the population ages.

We are also exploring Macuneos (BIO201) as a potential treatment for Stargardt disease, which shares many of the characteristics of AMD. Stargart disease is the most common form of inherited macular degeneration that typically develops in childhood and leads to vision loss and, in some cases, blindness.

Subject to our entering into commercialization agreements with one of our research collaborators in relation to two patent applications we recently filed, we will hold exclusive commercialization rights through licenses for each of our drug candidates. We currently plan to develop our drug candidates through clinical proof-of-concept, or PoC (typically Phase 2), and then seek licensing and/or partnership opportunities for further clinical development through regulatory approval and commercialization.

We have developed our lead drug candidate Sarconeos (BIO101), preclinical drug candidate Macuneos (BIO201), and a preclinical pipeline of life-cycle extension products, consisting of BIO103 and BIO203, through a drug discovery platform in collaboration with Sorbonne University in Paris, France based on work with medicinal plants. The platform is based on a reverse pharmacology approach that tests a collection of bioactive secondary metabolites along with chemical analogs that we have synthesized in phenotypic screens of various age-related diseases. Our long-term goal is to advance the field of aging science with the continued discovery and development of new drug candidates that treat age-related diseases by stimulating biological resilience pathways that are involved in the aging process and/or age-related diseases.

We have assembled an executive team of scientific, clinical, and business leaders with broad expertise in biotechnology and clinical drug development. Stanislas Veillet, our co-founder, Chairman and Chief Executive Officer, has held positions in the biotechnology, pharmaceutical and nutritional industries for the last 25 years. He holds a Ph.D. in genetics and has authored more than a dozen patents. Our other co-founder and Chief Scientific Officer, René Lafont, is a biochemist (Ecole Normale Supérieure), Professor Emeritus and former Dean of the Department of Life Sciences at Sorbonne University. He has authored over 170 scientific publications and a dozen patents and is also notably a Chevalier de l'Ordre des Palmes Académiques and a Laureate of the Karlson Foundation in

Germany. Dr. Samuel Agus, our Chief Medical Officer, holds a Doctor in Medicine, is a board-certified neurologist with academic training in biostatistics and bioinformatics, and has over 15 years of clinical development experience in the pharmaceutical industry.

Our Clinical Pipeline

We are developing a portfolio of programs targeting biological resilience pathways that slow the degenerative processes associated with aging and improve functional outcomes for patients suffering from age-related diseases. Our current pipeline of drug candidates is illustrated below.

Sarconeos (BIO101)

We are developing Sarconeos (BIO101) for the treatment of certain neuromuscular diseases, including sarcopenia and DMD. Both are diseases of muscular degeneration, but with different causes and pathophysiologies. However, similar key muscular processes are impaired in each of these diseases as well as other muscle wasting conditions, including metabolism, mitochondrial function, stem cell proliferation and loss of biological resilience, which are mediated through multiple signaling pathways. Early cellular and animal model data suggest that Sarconeos (BIO101) directly targets muscle tissue and cells, and improves several key muscle cell functions, including protein syntheses, regeneration and energy production that may have the potential to improve muscle function and preserve strength, mobility and respiratory capacity in various muscle wasting diseases.

Sarcopenia (the SARA clinical program)

We are currently testing the safety and efficacy of Sarconeos (BIO101) in an ongoing global, randomized, multicenter, double-blind, placebo-controlled Phase 2b clinical trial (SARA-INT) of 334 elderly patients with sarcopenia at risk of mobility disability. We enrolled the first patient in this trial in May 2018 and currently expect to complete enrollment in 2020. We completed a Phase 1 clinical trial (SARA-PK) of 54 healthy adult and elderly subjects in 2017 that allowed us to determine the two dosing levels (175 and 350 mg b.i.d.) for our ongoing SARA-INT trial. Based on results from our cellular and animal studies, we believe Sarconeos (BIO101) stimulates biological resilience and preserves muscle strength, function and mobility. While preclinical studies provide only limited data, particularly in diseases whose pathophysiology is not well understood, and may not be indicative of the likelihood of success of future trials, we believe that the results of our Phase 1 clinical trial and cellular and animal studies support continued research and clinical development of Sarconeos (BIO101) in sarcopenia.

If approved by regulatory authorities for commercial use, we believe there is a market potential for Sarconeos (BIO101) in sarcopenia, which is highly prevalent in the elderly with an estimated prevalence between six and 22 percent. There is currently no approved medication for sarcopenia. Based on our review of research in this area, we believe Sarconeos (BIO101) is currently the only drug candidate being tested in an interventional Phase 2 clinical trial for the treatment of sarcopenia. There is

currently no widely accepted standard of care for sarcopenia. Current non-medicinal treatment recommendations primarily focus on moderate physical activity, such as 30 minutes of walking per day or resistance-based (strength) training, as they exert effects on both the nervous and muscular systems that are critical to positive physiological and functional adaptations in older adults, and nutritional intervention. Other potential drug modalities that have been tested in the clinic for sarcopenia have yet to demonstrate effectiveness on clinically meaningful outcomes (strength and mobility) and/or safety in larger clinical trials, and/or have not progressed through the clinic. Based on our understanding and discussions with regulatory agencies, including the FDA and EMA, functional mobility endpoints must be achieved in order to obtain marketing approval for sarcopenia We believe that based on our potential mechanism-of-action and preclinical cellular and animal data that Sarconeos (BIO101) directly targets muscle tissue and cells and improves key muscle cell functions, and that it has the potential to achieve clinically relevant functional mobility endpoints necessary for marketing approval.

DMD (the MYODA clinical program)

Subject to regulatory approval of our protocol, we plan to test the safety and efficacy of Sarconeos (BIO101) in a global, multicentric, double-blind placebo-controlled clinical PoC trial (MYODA-INT) in approximately 48 patients with DMD utilizing a seamless clinical trial design with a primary endpoint defined as a composite score combining muscle strength, mobility, and respiratory outcomes, which is adapted to the stage of severity of the disease in each patient. We are preparing to submit an investigational new drug, or IND, application to the FDA and clinical trial applications to the applicable regulatory agencies in Europe in the second half of 2019 to initiate clinical development as early as 2020, subject to regulatory approval. We had pre-IND correspondence with the FDA in October 2018 and a scientific advisory meeting with the Committee for Medicinal Products for Human Use, or the CHMP, of the EMA in December 2018. In 2018, we received orphan drug designation from the FDA and EMA for Sarconeos (BIO101) in DMD.

We have observed a positive effect on muscle function, mobility, and respiratory capacity (a major disability in later stage DMD disease progression) in mdx mice models of DMD that were treated with Sarconeos (BIO101). While preclinical studies provide only limited data, particularly in diseases whose pathophysiology is not well understood, and may not be indicative of the likelihood of success of future trials, we believe that the results of our cellular and animal studies support continued research and clinical development of Sarconeos (BIO101) in DMD.

If approved by regulatory authorities for commercial use, we believe there is market potential for Sarconeos (BIO101) in DMD, which affects approximately one in 5,000 newborn boys (approximately 20,000 new cases annually worldwide). There is currently no cure for DMD and there are only limited treatment options that aim to control the symptoms and slow the disease progression. In many countries, corticosteroids are the standard drug therapy, however, corticosteroids typically only slow the progression of muscle weakness and delay the loss of ambulation by up to two years. They have also been associated with adverse side effects and are generally not suitable for long-term administration. There are two targeted therapies (i.e., therapies targeting a specific dystrophin mutation by exon skipping or with stop codons) available on the market (one in the United States and one in Europe). As these therapies each target a specific gene mutation, they can only address approximately 13% of the overall DMD patient population with those genetic mutations. We believe that Sarconeos (BIO101) directly targets muscle tissue and cells, increases key muscle cell functions that are impaired independent of the genetic mutation that causes the disease, and has the potential to be used complementarily with corticosteroids, current targeted therapies and other gene therapies under development. We also believe that because Sarconeos (BIO101) targets various impaired muscle tissues and cells relevant to muscle strength, mobility and respiratory function, it has the potential to be used in all stages of DMD progression, including both ambulatory and non-ambulatory patients.

Macuneos (BIO201)

Dry AMD (the MACA clinical program)

We plan to hold, in the second half of 2019, scientific advice meetings with the EMA and applicable regulatory agencies in Europe regarding our clinical development plan for Macuneos (BIO201) in dry AMD and, subject to regulatory review and approval of the protocol, commence a Phase 1 clinical trial (MACA-PK) in healthy volunteers. We expect the MACA-PK Phase 1 clinical trial will assess the safety, pharmacokinetics, or PK, and pharmacodynamics, or PD, of Macuneos (BIO201). We have completed chronic and acute animal toxicology studies to support IND and clinical trial applications. We have observed that Macuneos (BIO201) appears to protect the retina against phototoxic damage caused by A2E (a by-product of the visual pigment cycle) accumulation that leads to vision loss in several cellular and animal models of dry AMD and Stargardt disease.

If approved by regulatory authorities for commercial use, we believe that there is market potential for Macuneos (BIO201) in dry AMD. Therapeutic options for dry AMD have proven challenging with no currently approved therapies available that can slow or reverse the disease progression.

We intend to investigate whether Macuneos (BIO201) may also be an effective treatment for Stargardt disease, the most common form of inherited juvenile macular degeneration. The pathophysiology of Stargardt disease is similar to that of AMD, in that it may also be characterized by accelerated retinal degeneration.

Our Strategy

We are focused on the development of therapeutics that improve functional outcomes for patients suffering from age-related diseases. Our goal is to build Biophytis into a leading biotechnology company focused on targeting biological resilience pathways that slow the degenerative processes associated with age-related disease progression in order to improve the lives of patients that have limited or no treatment options. We currently plan to develop our drug candidates through clinical PoC (Phase 2) and then seek licensing and/or partnership opportunities for further clinical development through regulatory approval and commercialization. To achieve our goal, we are pursuing the following strategies:

•: Demonstrate clinical proof-of-concept (PoC) of Sarconeos (BIO101) in sarcopenia. Our resources and business efforts are primarily focused on advancing the clinical development of Sarconeos (BIO101) for the treatment of neuromuscular disorders, with an initial focus on sarcopenia. Our goal is to demonstrate clinical PoC (Phase 2) safety and efficacy of Sarconeos (BIO101) to treat sarcopenia in our ongoing SARA-INT Phase 2b clinical trial. Upon successful completion, we plan to pursue licensing and/or partnership opportunities to advance Sarconeos (BIO101) into a confirmatory or Phase 3 clinical trial necessary to secure marketing approval for commercial use. We believe this indication has significant value and that establishing clinical PoC may help attract partners for further clinical development and commercialization.
•: Initiate clinical development of Sarconeos (BIO101) in DMD. Our efforts are also focused on leveraging our knowledge and the development of Sarconeos (BIO101) in sarcopenia to commence and advance the development of Sarconeos (BIO101) for the treatment of DMD, independent of genetic mutation and across the disease spectrum. We are preparing to submit an IND application to the FDA and clinical trial applications to the applicable regulatory agencies in Europe in the second half of 2019 to initiate clinical development starting with the MYODA-INT clinical PoC stage (Phase 1/2) as early as 2020, subject to regulatory approval.
•: Advance the development of our second drug candidate, Macuneos (BIO201). We are also focused on continuing the preclinical development of our second drug candidate, Macuneos (BIO201), for the treatment of retinopathies, with an initial focus on dry AMD. We plan to hold, in the

second half of 2019, scientific advice meetings with the EMA and applicable regulatory agencies in Europe regarding our clinical development plan for Macuneos (BIO201) in dry AMD and, subject to regulatory review and approval of the protocol, commence a Phase 1 clinical trial (MACA-PK) in healthy volunteers.

•: Expand our presence in the United States to support co-development in Europe and the United States. We plan to continue the expansion of our company in the United States and Europe. In 2018, we opened offices in Cambridge, Massachusetts and New York, New York to support our growing clinical, regulatory, and operational efforts, and we hired a U.S.-based Chief Financial Officer and Chief Medical Officer. Our goal is to continue to build our clinical and regulatory operations to support clinical trials and obtain regulatory approval in both the United States and Europe. We plan to work with patient associations, regulatory agencies, government and third-party payors and other key constituencies in both regions.
•: Expand our pipeline and explore potential strategic partnerships and alliances to maximize the value of our development programs. We plan to continue to leverage our collaborations with leading scientific and academic institutions in order to pursue new INDs for our existing drug candidates, including Sarconeos (BIO101), BIO103, Macuneos (BIO201) and BIO203. We believe that our drug candidates may be applicable for additional age-related diseases. We plan to explore the commercial potential of our drug candidates after establishing clinical PoC through Phase 2.

Risks Associated with Our Business

Our business is subject to a number of risks of which you should be aware before making an investment decision. These risks are discussed more fully in the "Risk Factors" section of this prospectus immediately following this prospectus summary. These risks include, but are not limited to, the following:

•: We are a clinical-stage biotechnology company, with no products approved for commercial sale. We have incurred significant losses since inception and anticipate that we will continue to incur losses for the foreseeable future.
•: We will require substantial additional financing to achieve our goals and a failure to obtain this capital when needed on acceptable terms, or at all, could force us to delay, limit, reduce or terminate our drug development or other operations.
•: Our indebtedness could restrict our operations and make us more vulnerable to adverse economic conditions.
•: Our business is dependent on the successful development, regulatory approval, manufacture and commercialization of our drug candidates, each of which is in the early stages of development.
•: The denial or delay of regulatory approval for our drug candidates would preclude or delay the commercialization of our drug candidates and adversely impact our potential to generate revenue and/or raise financing, our business and our results of operations.
•: Clinical development is a lengthy and expensive process with an uncertain outcome, and results of earlier studies and trials, especially preclinical data and early phase clinical trial data, may not be predictive of future trial results.
•: We rely on third parties to provide the raw materials necessary for our drug candidates and to manufacture preclinical and clinical supplies of our drug candidates and we intend to rely on third parties to produce commercial supplies of any approved drug candidate. The loss of these suppliers or manufacturers, or their failure to comply with applicable regulatory requirements or

to provide us with sufficient quantities at acceptable quality levels or prices, or at all, would materially and adversely affect our business.

•: We rely on third parties in the conduct of all of our preclinical studies and clinical trials and intend to rely on third parties in the conduct of all of our future clinical trials. If these third parties do not successfully carry out their contractual duties, fail to comply with applicable regulatory requirements or meet expected deadlines, we may be unable to obtain regulatory approval for our drug candidates.
•: Our existing collaborations as well as additional collaboration arrangements that we may enter into in the future may not be successful, which could adversely affect our ability to develop and commercialize our drug candidates.
•: Our ability to compete may decline if we do not adequately protect our proprietary rights.
•: The requirements of being a U.S. public company may strain our resources, divert management's attention and affect our ability to attract and retain executive management and qualified board members.
•: There has been no market for the ADSs prior to the global offering and an active and liquid market for our securities may fail to develop, which could harm the market price of the ADSs.
•: The rights of shareholders in companies subject to French corporate law differ in material respects from the rights of shareholders of corporations incorporated in the United States.
•: As a foreign private issuer, we are exempt from a number of rules under the U.S. securities laws and are permitted to file less information with the SEC than a U.S. company. This may limit the information available to holders of ADSs and ordinary shares.
•: We are an "emerging growth company" under the JOBS Act and will be able to avail ourselves of reduced disclosure requirements applicable to emerging growth companies, which could make the ADSs less attractive to investors.

Corporate Information

We were incorporated as a société anonyme, or SA, on September 27, 2006. We are registered at the Paris Registre du Commerce et des Sociétés under the number 492 002 225. Our principal executive offices are located at Sorbonne University—BC 9, Bâtiment A 4ème étage, 4 place Jussieu 75001 Paris, France and our telephone number is +1 44 27 23 00. Our website address is www.biophytis.com. Our agent for service of process in the United States is Puglisi & Associates. The reference to our website is an inactive textual reference only and the information contained in, or that can be accessed through, our website is not a part of this prospectus.

Implications of Being an "Emerging Growth Company"

We qualify as an "emerging growth company," as defined in the Jumpstart our Business Startups Act of 2012, or the JOBS Act. An emerging growth company may take advantage of specified reduced reporting and regulatory requirements in contrast to those otherwise applicable generally to public companies. These provisions include:

•: the requirement to have only two years of audited financial statements and only two years of related Management's Discussion and Analysis of Financial Condition and Results of Operations disclosure; and
•: exemption from the auditor attestation requirement in the assessment of our internal control over financial reporting pursuant to Section 404 the Sarbanes-Oxley Act of 2002, or the Sarbanes-Oxley Act.

We may take advantage of these reduced reporting and other regulatory requirements for up to five years or such earlier time that we are no longer an emerging growth company. We would cease to be an emerging growth company if we have more than $1.07 billion in annual revenue, have more than $700 million in market value of our ordinary shares held by non-affiliates or issue more than $1.0 billion of non-convertible debt over a three-year period. In addition, the JOBS Act provides that an emerging growth company may delay adopting new or revised accounting standards until those standards apply to private companies. We have irrevocably elected not to avail ourselves of this delayed adoption of new or revised accounting standards and, therefore, we will be subject to the same new or revised accounting standards as public companies that are not emerging growth companies. If we choose to take advantage of any of these reduced reporting burdens, the information that we provide shareholders may be different than you might get from other public companies.

Implications of Being a Foreign Private Issuer

Upon consummation of the global offering, we will report under the Exchange Act as a non-U.S. company with foreign private issuer status. Even after we no longer qualify as an emerging growth company, as long as we qualify as a foreign private issuer under the Exchange Act, we will be exempt from certain provisions of the Exchange Act that are applicable to U.S. domestic public companies, including:

•: the sections of the Exchange Act regulating the solicitation of proxies, consents or authorizations in respect of a security registered under the Exchange Act;
•: the sections of the Exchange Act requiring insiders to file public reports of their stock ownership and trading activities and liability for insiders who profit from trades made in a short period of time; and
•: the rules under the Exchange Act requiring the filing with the SEC of quarterly reports on Form 10-Q containing unaudited financial and other specified information, or current reports on Form 8-K upon the occurrence of specified significant events.

We intend to take advantage of these exemptions as a foreign private issuer.

The Global Offering


Global offering		13,125,000 ordinary shares offered by us, consisting of ordinary shares in the form of ADSs offered in the ADS offering and ordinary shares offered in the ordinary share offering. The closings of the ADS offering and the ordinary share offering will occur simultaneously. The total number of ordinary shares and ADSs to be offered and sold in the ADS offering and ordinary share offering is subject to reallocation between these offerings as permitted under applicable laws and regulations.
ADS offering		875,000 ADSs, each representing 10 ordinary shares
Ordinary share offering		4,375,000 ordinary shares
Offering price		The offering price is expected to be between $7.00 and $9.00 per ADS, or between €0.62 and €0.80 per ordinary share. The final offering price per ADS in U.S. dollars and the corresponding offering price per ordinary share in euros will be determined by reference to the prevailing market prices of our ordinary shares on the Euronext Growth Paris after taking into account market conditions and other factors.
Ordinary shares (including ordinary shares in the form of ADSs) to be outstanding immediately after the global offering		26,588,413 ordinary shares (including ordinary shares in the form of ADSs), or 28,557,163 ordinary shares (including ordinary shares in the form of ADSs) if Wainwright exercises its option to purchase additional ADSs in full.
Option to purchase additional ADSs in the global offering		We have granted Wainwright an option, which is exercisable within 30 days from the date of this prospectus, to purchase up to an additional 1,968,750 ordinary shares (to be delivered in the form of an aggregate of 196,875 ADSs) from us at the public offering price, less the underwriting discounts and commissions.
The ADSs		Each ADS represents 10 ordinary shares, nominal value €0.20 per share. The ADSs may be evidenced by ADRs. Purchasers of ADSs in the ADS offering will have the rights of an ADS holder as provided in the deposit agreement among us, the depositary and all holders and beneficial owners of ADSs issued thereunder. To better understand the terms of the ADSs, you should carefully read the section in this prospectus titled "Description of American Depositary Shares." We also encourage purchasers of ADSs to read the deposit agreement, which is filed as an exhibit to the registration statement that includes this prospectus.
Depositary		The Bank of New York Mellon


Use of proceeds		We estimate that the net proceeds to us from the global offering will be approximately €6.8 million ($7.6 million), based on an assumed public offering price of $8.00 per ADS in the ADS offering, which is the midpoint of the price range set forth on the cover page of this prospectus, corresponding to €0.71 per ordinary share in the ordinary share offering (assuming an exchange rate of €0.89 per U.S. dollar), after deducting underwriting discounts and commissions and estimated offering expenses payable by us.
		We intend to use the net proceeds we receive from the global offering to advance our Phase 2b clinical trial (SARA-INT) of Sarconeos (BIO101) in sarcopenia, to continue our development of Sarconeos (BIO101) in DMD through submission of an IND application to the FDA and clinical trial applications to the applicable regulatory agencies in Europe, and to continue to build our preclinical research and development platform on retinopathies and for other new and on-going research and development activities, working capital and other general corporate purposes. See the section of this prospectus titled "Use of Proceeds."
Dividend policy		We do not expect to pay any dividends on ordinary shares or ADSs in the foreseeable future.
Risk factors		You should read the "Risk Factors" section of this prospectus for a discussion of factors to consider carefully before deciding to invest in the ADSs or ordinary shares.
Proposed Nasdaq trading symbol for the ADSs		"BPTS"
Euronext Growth Paris trading symbol for our ordinary shares		"ALBPS"

The number of our ordinary shares (including ordinary shares in the form of ADSs) that will be outstanding immediately following the completion of the global offering is based on 13,463,413 ordinary shares outstanding and zero ADSs outstanding as of March 31, 2019, and excludes:

•: 1,063,409 ordinary shares issuable upon the exercise of warrants issued to investors outstanding as of March 31, 2019, with a weighted-average exercise price of €3.59 per ordinary share; and
•: 998,500 ordinary shares issuable upon the exercise of warrants issued pursuant to equity incentive awards and outstanding as of March 31, 2019, with a weighted average exercise price of €6.35 per ordinary share, 125,000 of which expired on May 21, 2019 with a weighted average exercise price of €2.06 per ordinary share and 35,000 of which expired on June 30, 2019 with a weighted average exercise price of €7.53 per ordinary share.

Unless otherwise indicated, all information contained in this prospectus assumes no exercise of Wainwright's option to purchase up to an additional 1,968,750 ordinary shares (to be delivered in the form of an aggregate of 196,875 ADSs) from us in the global offering.

Summary Consolidated Financial Data

The following tables summarize our consolidated financial data for the periods and as of the dates indicated below. We derived the summary statement of consolidated operations data for the years ended December 31, 2017 and 2018 from our audited consolidated financial statements included elsewhere in this prospectus. Our audited consolidated financial statements have been prepared in accordance with International Financial Reporting Standards, or IFRS, as issued by the International Accounting Standards Board, or IASB. The following summary statement of consolidated operations data for the three months ended March 31, 2018 and 2019 and statement of consolidated financial position data as of March 31, 2019 have been derived from our unaudited interim condensed consolidated financial statements as of March 31, 2019 and for the three months ended March 31, 2018 and 2019 included elsewhere in this prospectus. The unaudited interim condensed consolidated financial statements as of March 31, 2019 and for the three months ended March 31, 2018 and 2019 were prepared in accordance with IAS 34, Interim Financial Reporting, the standard of the IFRS applicable to interim financial statements.

Our historical results are not necessarily indicative of the results that may be expected in the future. You should read these data together with our consolidated financial statements and related notes beginning on page F-1, as well as the sections of this prospectus titled "Selected Financial and Other Data" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" and the other financial information included elsewhere in this prospectus.

	Year Ended December 31,						Three Months Ended March 31,

	2017			2018			2018			2019
	€			€			€			€			U.S. $(1)
	(in thousands, except share and per share data)
Statement of Consolidated Operations Data:
Operating expenses:
Research and development, net		7,043			9,513			2,017			2,289			2,570
General and administrative expenses		2,865			4,348			865			1,211			1,360
Total operating expenses		9,908			13,861			2,882			3,500			3,930
Operating loss		(9,908	)		(13,861	)		(2,882	)		(3,500	)		(3,930	)
Financial expenses		(3,293	)		(215	)		(26	)		(276	)		(310	)
Financial income		37			17			4			49			55
Change in fair value of financial instruments		1,756			—			—			—			—
Financial loss		(1,500	)		(198	)		(22	)		(227	)		(255	)
Net loss before taxes		(11,408	)		(14,059	)		(2,904	)		(3,727	)		(4,185	)
Income tax benefit		—			72			—			—			—

Net loss		(11,408	)		(13,987	)		(2,904	)		(3,727	)		(4,185	)



Earnings (losses) per share(2)
Basic		(1.24	)		(1.04	)		(0.22	)		(0.28	)		(0.31	)
Diluted		(1.24	)		(1.04	)		(0.22	)		(0.28	)		(0.31	)
Weighted average number of ordinary shares outstanding used for computing Basic		9,188,179			13,463,413			13,463,413			13,463,413			13,463,413
Weighted-average number of ordinary shares outstanding used for computing Diluted		9,188,179			13,463,413			13,463,413			13,463,413			13,463,413

(1): Translated solely for convenience into dollars at an exchange rate of €1.00 = US$1.1228, the noon buying rate of the Federal Reserve Bank of New York on March 29, 2019.
(2): See Note 2.22 to our audited consolidated financial statements and Note 15 to our unaudited interim condensed consolidated financial statements for further details on the calculation of basic and diluted loss per ordinary share.

	As of March 31, 2019

	Actual						As Adjusted(1)(2)
	€			US$(3)			€			US$(3)
	(in thousands)
Statement of Consolidated Financial Position Data:
Cash and cash equivalents		11,152			12,521			17,933			20,112
Total assets		19,446			21,834			26,227			29,424
Non-controlling interests		(31	)		(35	)		(31	)		(35	)
Total shareholders' equity		2,383			2,676			9,164			10,221
Total non-current liabilities		7,688			8,632			7,688			8,632
Total current liabilities		9,375			10,526			9,375			10,526

(1): As adjusted basis gives effect to the issuance and sale of 13,125,000 ordinary shares (including 8,750,000 ordinary shares in the form of ADSs) in the global offering at an assumed offering price of $8.00 per ADS in the ADS offering, which is the midpoint of the price range set forth on the cover page of this prospectus, corresponding to €0.71 per ordinary share in the ordinary share offering (assuming an exchange rate of €0.89 per U.S. dollar), after deducting estimated underwriting discounts and commissions and estimated offering expenses payable by us and the application of net proceeds from the global offering described under "Use of Proceeds."
(2): Each €0.89 ($1.00) increase or decrease in the assumed offering price of $8.00 per ADS in the ADS offering which is the midpoint of the price range set forth on the cover page of this prospectus, corresponding to €0.71 per ordinary share in the ordinary share offering (assuming an exchange rate of €0.89 per U.S. dollar), would increase or decrease each of as adjusted cash and cash equivalents, total assets and total shareholders' equity by €1.1 million ($1.2 million), assuming that the number of ordinary shares offered by us (including ordinary shares in the form of ADSs), as set forth on the cover page of this prospectus, remains the same and after deducting underwriting commissions and estimated offering expenses payable by us and applying the net proceeds from the global offering. Subject to applicable law, we may also increase or decrease the number of ordinary shares (including ordinary shares in the form of ADSs) we are offering in the global offering. Each increase or decrease of 1,000,000 ordinary shares (including ordinary shares in the form of ADSs) offered by us would increase or decrease each of as adjusted cash and cash equivalents, total assets and total shareholders' equity by €0.7 million ($0.7 million), assuming that the assumed offering price per ordinary share remains the same, and after deducting estimated underwriting commissions and offering expenses payable by us and applying the net proceeds from the global offering.
: The as adjusted information discussed above is illustrative only and will be adjusted based on the actual public offering price, the actual number of ordinary shares and ADSs offered by us, and other terms of the global offering determined at pricing.
(3): Translated solely for convenience into dollars at an exchange rate of €1.00 = US$1.1228, the noon buying rate of the Federal Reserve Bank of New York on March 29, 2019 except as it relates to the impact of the assumed proceeds, which are translated into U.S. dollars at an exchange rate of €1.00 = US$1.1215, the exchange rate of the Banque de France on July 8, 2019.

Investing in our ordinary shares (including ordinary shares in the form of ADSs) involves a high degree of risk. You should carefully consider the risks and uncertainties described below, together with all of the other information in this prospectus, including our consolidated financial statements and related notes, before deciding whether to purchase our securities. If any of the following risks are realized, our business, financial condition, operating results and prospects could be materially and adversely affected. In that event, the market price of our securities could decline, and you could lose part or all of your investment.

Risks Related to Our Limited Operating History, Financial Condition, and Capital Requirements

We are a clinical-stage biotechnology company with no products approved for commercial sale. We have incurred significant losses since our inception and anticipate that we will continue to incur losses for the foreseeable future.

Biotechnology product development is a highly speculative undertaking because it entails substantial upfront capital expenditures and significant risk that any potential drug candidate will not demonstrate adequate effectiveness in the targeted indication or an acceptable safety profile, gain regulatory approval or become commercially viable. We have incurred significant losses since our inception in 2006, and we anticipate that we will continue to incur losses for the foreseeable future, which, together with our limited operating history, may make it difficult to assess our future viability.

We incurred losses of €11.4 million, €14.0 million and €3.7 million for the years ended December 31, 2017 and 2018 and the three months ended March 31, 2019, respectively. As of March 31, 2019, we had an accumulated deficit of €43.4 million. Substantially all of our losses have resulted from expenses incurred in connection with our preclinical and clinical programs and other research and development activities and from general and administrative costs associated with our operations. We expect to continue to incur losses for the foreseeable future, and we anticipate these losses will increase as we continue to develop our drug candidates, conduct clinical trials and pursue research and development activities. Even if we achieve profitability in the future, we may not be able to sustain profitability in subsequent periods. Our prior losses, combined with expected future losses, have had and will continue to have an adverse effect on our shareholders' equity and working capital.

We will require substantial additional financing to achieve our goals, and a failure to obtain this capital when needed on acceptable terms, or at all, could force us to delay, limit, reduce or terminate our product development or other operations.

Since our inception, we have invested a significant portion of our efforts and financial resources on our preclinical studies and clinical trials and other research and development activities. We believe that we will continue to expend substantial resources for the foreseeable future in connection with the preclinical and clinical development of our current drug candidates and the discovery and development of any other drug candidates we may choose to pursue. These expenditures will include costs associated with conducting preclinical studies and clinical trials and obtaining regulatory approvals, and any expenses associated with commercializing, marketing and selling products approved for sale that we elect to commercialize ourselves. In addition, other unanticipated costs may arise. Because the outcome of any preclinical study or clinical trial is highly uncertain, we cannot reasonably estimate the actual amounts necessary to successfully complete the development of our current drug candidates or any future drug candidates we may choose to pursue.

We estimate that the net proceeds from the global offering will be approximately €6.8 million ($7.6 million), based on an assumed public offering price of $8.00 per ADS in the ADS offering, which is the midpoint of the price range set forth on the cover page of this prospectus, corresponding to €0.71 per ordinary share in the ordinary share offering (assuming an exchange rate of €0.89 per U.S. dollar), and after deducting the underwriting discounts and commissions and estimated offering

expenses payable by us. As of March 31, 2019, we had capital resources consisting of cash, cash equivalents, and marketable securities of €11.2 million. We expect our existing capital resources, including our ability to draw down on our credit facility with Bracknor Fund Limited, or Bracknor Fund (as described in further detail in the section of this prospectus titled "Management's Discussion and Analysis of Financial Condition and Results of Operations"), together with the proceeds from the global offering, will be enough to fund our planned operating expenses for the next 12 months. However, our current operating plans may change as a result of many factors currently unknown to us, and we may need to seek additional funds even sooner than planned, through public or private equity or debt financings or other sources, such as strategic collaborations. In addition, we may seek additional capital due to favorable market conditions or strategic considerations even if we believe we have sufficient funds for our current or future operating plans.

Additional funds may not be available when we need them, on terms that are acceptable to us, or at all. If adequate funds are not available to us on a timely basis on terms acceptable to us, we may be required to:

We do not expect to realize revenue from sales of products or royalties from licensed products in the foreseeable future, if at all, and unless and until our drug candidates are clinically tested, approved for commercialization and successfully marketed. To date, we have primarily financed our operations through the sale of debt and equity securities, as well as public aid for innovation and reimbursement of the French research tax credit, described elsewhere in this prospectus. We will need to seek additional funding in the future and currently intend to do so through collaborations, public or private equity offerings or debt financings, credit or loan facilities, public funding, or a combination of one or more of these funding sources. Our ability to raise additional funds will depend on financial, economic and other factors, many of which are beyond our control. Additional funds may not be available to us on acceptable terms or at all. If we enter into arrangements with collaborators or others, we may be required to relinquish rights to some of our drug candidates that we would otherwise pursue on our own. If we raise additional funds by issuing equity securities, our shareholders will suffer dilution and the terms of any financing may adversely affect the rights of our shareholders. In addition, as a condition to providing additional funds to us, future investors may demand, and may be granted, rights superior to those of existing shareholders. Debt financing, if available, is likely to involve restrictive covenants limiting our flexibility in conducting future business activities, and, in the event of insolvency, debt holders would be repaid before holders of our equity securities received any distribution of our corporate assets.

We have benefited from certain reimbursable financial advances and non-reimbursable subsidiaries from the French government that if terminated or reduced may restrict our ability to successfully develop, manufacture and commercialize our drug candidates.

We have benefited from certain reimbursable advances and non-reimbursable subsidies from the French government and intend to continue to seek advances and/or subsidies from these agencies in the future in order to accelerate the development of our drug candidates. There is no assurance that these benefits will continue to be available to us in the future. If such benefits and programs were to be terminated or reduced, it could have an adverse effect on our business, operating results and financial condition and could deprive us of financial resources necessary for research and development of our drug candidates. Furthermore, in the event that we do not comply with the contractual conditions of the subsidies, we may be required to reimburse the French government for these payments and could be liable for any damages incurred by such agencies resulting from the breach of contract.

Due to the significant resources required for the development of our drug candidates, we must prioritize development of certain drug candidates and/or certain disease indications. We may expend our limited resources on candidates or indications that do not yield a successful product and fail to capitalize on drug candidates or indications that may be more profitable or for which there is a greater likelihood of success.

We plan to develop a pipeline of drug candidates to treat age-related diseases and diseases whose progression and symptoms are similar to those associated with aging. Due to the significant resources required for the development of drug candidates, we must focus our attention and resources on specific diseases and disease pathways and decide which drug candidates to pursue and the amount of resources to allocate to each.

Our decisions concerning the allocation of research, development, collaboration, management and financial resources toward particular drug candidates or therapeutic areas may not lead to the development of any viable commercial product and may divert resources away from better

opportunities. Similarly, any decision to delay, terminate or collaborate with third parties in respect of certain programs may subsequently prove to be suboptimal and could cause us to miss valuable opportunities. If we make incorrect determinations regarding the viability or market potential of any of our programs or drug candidates or misread trends in the aging or healthspan, or biotechnolgy industry, our business, financial condition and results of operations could be materially adversely affected. As a result, we may fail to capitalize on viable commercial products or profitable market opportunities, be required to forego or delay pursuit of opportunities with other drug candidates or other diseases and disease pathways that may later prove to have greater commercial potential than those we choose to pursue, or relinquish valuable rights to such drug candidates through collaboration, licensing or other royalty arrangements in cases in which it would have been advantageous for us to invest additional resources to retain development and commercialization rights.

Our operating results may fluctuate significantly, which makes our future operating results difficult to predict.

Our operating results may fluctuate significantly, which makes it difficult for us to predict our future operating results. These fluctuations may occur due to a variety of factors, many of which are outside of our control and may be difficult to predict, including:

The cumulative effects of these factors could result in large fluctuations and unpredictability in our annual operating results. As a result, comparing our operating results on a period-to-period basis may not be meaningful. Investors should not rely on our past results as an indication of our future performance.

This variability and unpredictability could also result in our failing to meet the expectations of industry or financial analysts or investors for any period. If our revenue or operating results fall below the expectations of analysts or investors or below any forecasts we may provide to the market, or if the forecasts we provide to the market are below the expectations of analysts or investors, the price of our

ordinary shares and ADSs could decline substantially. Such a stock price decline could occur even when we have met any previously publicly stated revenue or earnings guidance we may provide.

Our indebtedness could restrict our operations and make us more vulnerable to adverse economic conditions.

On September 10, 2018, we entered into a Venture Loan Agreement and Bonds Issue Agreement with Kreos Capital V (UK) Ltd., or Kreos, which provides for up to €10 million in financing to us. Pursuant to the terms of the agreements, Kreos agreed to subscribe for up to €10 million in non-convertible bonds, to be issued by us in up to four tranches of €2.5 million each. The first two tranches were issued in September 2018, a third tranche was issued in December 2018, and the final tranche was issued on March 1, 2019. Each tranche bears a 10% annual interest rate and must be repaid in 36 monthly installments, with monthly payments of €320,004 commencing in April 2019. In connection with the first tranche, we issued a warrant to Kreos giving them the right to purchase 442,477 new ordinary shares at an exercise price of €2.67 per share over a 7-year period from the issue date.

If we are unable to make the required payments, we may need to refinance all or a portion of our indebtedness, sell assets, delay capital expenditures or seek additional equity. The terms of our existing or future debt agreements may also restrict us from affecting any of these alternatives. Any refinancing of our debt could be at higher interest rates and may require us to comply with more onerous covenants, which could further restrict our business operations. Further, changes in the credit and capital markets, including market disruptions and interest rate fluctuations, may increase the cost of financing, make it more difficult to obtain favorable terms, or restrict our access to these sources of future liquidity. In addition, any failure to make scheduled payments of interest and principal on our outstanding indebtedness would likely result in a reduction of our credit rating, which could harm our ability to incur additional indebtedness on commercially reasonable terms or at all. Our inability to generate sufficient cash flow to satisfy our debt service obligations, or to refinance or restructure our obligations on commercially reasonable terms or at all, could have a material adverse effect on our business, financial condition and results of operations, as well as on our ability to satisfy our obligations in respect of our indebtedness.

Pursuant to the terms of the agreements, we have the right, at any time but with no less than 30 days prior notice to Kreos, to prepay or purchase the bonds, exclusively in full. The prepayment will be equal to (i) the principal amount outstanding, plus (ii) the sum of all interest repayments which would have been paid throughout the remainder of the term of the relevant tranche discounted by 10% per annum.

Our debt agreements contain restrictions that limit our flexibility in operating our business.

Our Venture Loan Agreement and Bonds Issue Agreement with Kreos and our convertible notes agreement with Bracknor Fund impose certain operating and financial restrictions. These covenants may limit our ability and the ability of our subsidiaries, under certain circumstances, to, among other things:

These agreements also contain certain customary affirmative covenants and events of default, including a change of control.

As a result of the covenants and restrictions contained in our existing debt agreements, we are limited in how we conduct our business, and we may be unable to raise additional debt to compete

effectively or to take advantage of new business opportunities. The terms of any future indebtedness we may incur could include more restrictive covenants. We cannot guarantee that we will be able to maintain compliance with these covenants in the future and, if we fail to do so, that we will be able to obtain waivers from Kreos and/or amend the covenants.

Our failure to comply with the restrictive covenants described above as well as others contained in our future debt instruments from time to time could result in an event of default, which, if not cured or waived, could result in our being required to repay these borrowings before their maturity dates. In addition, any event of default or declaration of acceleration under one debt instrument could also result in an event of default under one or more of our other debt instruments. If we are unable to repay, refinance or restructure our indebtedness under our secured debt, the holders of such debt could proceed against the collateral securing that indebtedness. If we are forced to refinance these borrowings on less favorable terms or if we are unable to repay, refinance or restructure such indebtedness, our financial condition and results of operations could be adversely affected.

Our business is dependent on the successful development, regulatory approval, manufacture and commercialization of our drug candidates, both of which are in the early stages of development.

We have no products approved for sale. Our lead drug candidate, Sarconeos (BIO101), is in the early stages of clinical development and our second drug candidate, Macuneos (BIO201) is still in preclinical phase. Our life-cycle extension drug candidates, BIO103 and BIO203, are still in the preclinical phase. To secure marketing approval, we will need to meet endpoints satisfactory to the FDA and EMA in larger confirmatory clinical trials. The success of our business, including our ability to finance our company and generate any revenue in the future, will primarily depend on the successful development, regulatory approval and commercialization of drug candidates. However, given our early stage of development, it may be many years, if we succeed at all, before we have demonstrated the safety and efficacy of a drug candidate sufficient to warrant approval for commercialization.

In the future, we may also become dependent on other drug candidates that we may develop or acquire. The clinical and commercial success of our current drug candidates and any future drug candidates will depend on a number of factors, including the following:

These factors, many of which are beyond our control, could cause us to experience significant delays or an inability to obtain regulatory approvals or commercialize or license our drug candidates. Even if regulatory approvals are obtained, we may never be able to successfully commercialize or license any of our drug candidates. Accordingly, we cannot provide assurances that we will be able to generate sufficient revenue through the sale of our drug candidates or any future drug candidates we may develop to continue our business or achieve profitability.

We may not be able to obtain regulatory approval for our drug candidates under applicable regulatory requirements. The denial or delay of any such approval would preclude or delay the commercialization of our drug candidates and adversely impact our potential to generate revenue and/or raise financing, our business and our results of operations.

To gain approval to market our drug candidates, we must provide the FDA, EMA and other foreign regulatory authorities with clinical data that adequately demonstrate the safety and efficacy of the drug candidate for the intended indication applied for in the applicable regulatory filing. Product development is a long, expensive and uncertain processes, and delay or failure can occur at any stage of any of our clinical development programs. A number of companies in the biotechnology and pharmaceutical industries have suffered significant setbacks in clinical trials, even after promising data in preclinical studies or earlier phase clinical trials. These setbacks have been caused by, among other

things, new preclinical findings made while clinical trials were underway and safety or efficacy observations made in clinical trials, including previously unreported adverse events. Success in preclinical testing and early phase clinical trials does not ensure that later phase clinical trials will be successful, and the results of clinical trials conducted by other parties may not be indicative of the results in trials we may conduct.

The research, testing, manufacturing, labeling, approval, sale, marketing and distribution of drug and biologic products are subject to extensive regulation by the FDA, EMA and other foreign regulatory authorities, and such regulations differ from country to country. We are not permitted to market our investigational drug candidates in the European Union, the United States or any other country until they receive the requisite approval from the applicable regulatory authorities of such jurisdictions.

The FDA, EMA or any foreign regulatory bodies can delay, limit or deny approval of our drug candidates for many reasons, including:

Of the large number of biotechnology and pharmaceutical products in development, only a small percentage successfully complete the applicable regulatory approval processes and are commercialized.

Even if we eventually complete clinical testing and receive approval from the FDA, EMA or applicable foreign agencies for any of our drug candidates, the applicable agency may grant approval contingent on the performance of costly additional clinical trials, which may be required after approval. The FDA, EMA or the applicable foreign regulatory agency also may approve our drug candidates for a more limited indication or a narrower patient population than we originally requested, and the applicable agency, may not approve our drug candidates with the labeling that we believe is necessary or desirable for the successful commercialization of such drug candidates.

Any delay in obtaining, or inability to obtain, applicable regulatory approval would delay or prevent commercialization of our drug candidates and would materially adversely impact our business and prospects.

Clinical development is a lengthy and expensive process with an uncertain outcome, and results of earlier studies and trials may not be predictive of future trial results.

Clinical testing is expensive and can take many years to complete, and its outcome is inherently uncertain. Failure or delay can occur at any time during the different phases, or stages, of the clinical trial process. Success in preclinical studies and early clinical trials does not ensure that later clinical

trials will be successful. A number of companies in the biotechnology, biopharmaceutical and pharmaceutical industries have suffered significant setbacks in clinical trials, even after positive results in earlier preclinical studies or earlier phase clinical trials. These setbacks have been caused by, among other things, new preclinical findings made while clinical trials were underway and safety or efficacy observations made in clinical trials, including previously unreported adverse events. The results of our preclinical studies or in vivo and in vitro studies provide very limited data in diseases whose physiopathology is not well understood and may not be predictive of the results of study outcomes in human clinical trials. Drug candidates in later stages of clinical trials may fail to show the desired pharmacological properties or safety and efficacy traits despite having progressed through preclinical studies and early phase clinical trials. Notwithstanding any promising results in earlier studies, we cannot be certain that we will not face setbacks and receive less promising results in later studies. Even if we are able to initiate and complete clinical trials, the safety and efficacy data may not be sufficient to obtain regulatory approval for our drug candidates.

We may experience delays in obtaining the necessary regulatory authorization to initiate our planned MYODA clinical program of Sarconeos (BIO101) and/or our planned MACA clinical trial program for Macuneos (BIO201), completing our SARA-INT Phase 2b clinical trial of Sarconeos (BIO101), and initiating other planned studies and trials. Additionally, we cannot be certain that studies or trials for our drug candidates will begin on time, not require redesign, enroll an adequate number of subjects on time or be completed on schedule, if at all. Clinical trials can be delayed or terminated for a variety of reasons, including delays or failures related to:

We may experience numerous adverse or unforeseen events during, or as a result of, preclinical studies and clinical trials that could delay or prevent our ability to receive marketing approval or commercialize our drug candidates, including:

If we are required to conduct additional clinical trials or other testing of our drug candidates beyond those that we currently contemplate, if we are unable to successfully complete clinical trials of our drug candidates or other testing, if the results of these trials or tests are not positive or are only moderately positive or if there are safety concerns, we may:

We could also encounter delays if a clinical trial is suspended or terminated by us, by the IRBs of the institutions in which such trials are being conducted, by the Data Safety Monitoring Board, or DSMB, for such trial or by the FDA, EMA or other regulatory authorities. Such authorities may suspend or terminate a clinical trial due to a number of factors, including failure to conduct the clinical trial in accordance with regulatory requirements or our clinical protocols, inspection of the clinical trial operations or trial site by the FDA, EMA or other regulatory authorities resulting in the imposition of a clinical hold, unforeseen safety issues or adverse side effects, failure to demonstrate a benefit from using a drug, changes in governmental regulations or administrative actions or lack of adequate funding to continue the clinical trial.

Further, conducting clinical trials in foreign countries presents additional risks that may delay completion of our clinical trials. These risks include the failure of enrolled patients in foreign countries to adhere to clinical protocol as a result of differences in healthcare services or cultural customs, managing additional administrative burdens associated with foreign regulatory schemes, as well as political and economic risks relevant to such foreign countries.

Principal investigators for our clinical trials may serve as scientific advisors or consultants to us from time to time and may receive cash or equity compensation in connection with such services. If these relationships and any related compensation result in perceived or actual conflicts of interest, or a regulatory authority concludes that the financial relationship may have affected the interpretation of the trial, the integrity of the data generated at the applicable clinical trial site may be questioned and the utility of the clinical trial itself may be jeopardized, which could result in the delay or rejection of the marketing application we submit. Any such delay or rejection could prevent or delay us from commercializing our current or future drug candidates.

If we experience delays in the completion, or termination, of any preclinical study or clinical trial of our drug candidates, the commercial prospects of our drug candidates may be harmed, and our ability to generate revenues from any of these drug candidates will be delayed or not realized at all. In addition, any delays in completing our clinical trials may increase our costs, slow down our drug candidate development and approval process and jeopardize our ability to commercialize our products and generate revenues. Any of these occurrences may significantly harm our business, financial condition and prospects. In addition, many of the factors that cause, or lead to, a delay in the commencement or completion of clinical trials may also ultimately lead to the denial of regulatory approval of our drug candidates. If one or more of our drug candidates prove to be ineffective, unsafe or commercially unviable, our entire platform and pipeline would have little, if any, value, which would have a material and adverse effect on our business, financial condition, results of operations and prospects.

If we encounter difficulties enrolling patients in our clinical trials, our clinical development activities could be delayed or otherwise adversely affected.

The timely completion of clinical trials in accordance with their protocols depends on, among other things, our ability to enroll a sufficient number of patients who remain in the study until its conclusion. We may experience difficulties in patient enrollment in our clinical trials for a variety of reasons. The enrollment of patients depends on many factors, including:

In addition, our clinical trials may compete with other clinical trials for drug candidates that are in the same therapeutic areas as our drug candidates, and this competition will reduce the number and types of patients available to us, because some patients who might have opted to enroll in our trials may instead opt to enroll in a trial being conducted by one of our competitors. Since the number of qualified clinical investigators is limited, we may conduct some of our clinical trials at the same clinical trial sites that some of our competitors use, which will reduce the number of patients who are available for our clinical trials in such clinical trial site.

Delays in patient enrollment may result in increased costs or may affect the timing or outcome of the planned clinical trials, which could prevent completion of these trials and adversely affect our ability to advance the development of our drug candidates.

Our drug candidates may cause undesirable side effects or have other properties that could delay or prevent their regulatory approval, limit the commercial profile of an approved label, or result in significant negative consequences following marketing approval, if any.

Undesirable side effects caused by our drug candidates could cause us or regulatory authorities to interrupt, delay or halt clinical trials and could result in a more restrictive label or the delay or denial of regulatory approval by the FDA, EMA or comparable foreign regulatory authorities.

If unacceptable side effects arise in the development of our drug candidates, we, the FDA, EMA, the IRBs at the institutions in which our studies are conducted, or the DSMB could suspend or terminate our clinical trials or the FDA, EMA or comparable foreign regulatory authorities could order us to cease clinical trials or deny approval of our drug candidates for any or all targeted indications. Treatment-related side effects could also affect patient recruitment or the ability of enrolled patients to complete any of our clinical trials or result in potential product liability claims. In addition, these side effects may not be appropriately recognized or managed by the treating medical staff. Failure to recognize or manage the potential side effects of our drug candidates could result in patient injury. Any of these occurrences may harm our business, financial condition and prospects significantly.

If our drug candidates are used in combination with other drugs or treatments, they may interact negatively with those other drugs or treatments. We plan to conduct studies in order to assess the risks of interactions of our drug candidates with other drugs and treatments taken together. However, there can be no guarantee that our drug candidates will not interact negatively with other drugs or treatments not covered by our studies or that such interactions will not be revealed until after the products have been commercialized. These interactions could have adverse, unacceptable or undetected side effects, or could reduce or destroy the effectiveness of the our drug candidates, which could diminish the commercial potential of our drug candidates, slow their development and consequently, have a material adverse effect on our business, financial condition and prospects.

Even if we successfully advance any of our drug candidates into and through clinical trials, such trials will likely only include a limited number of subjects and limited duration of exposure to our drug candidates. As a result, we cannot be assured that adverse effects of our drug candidates will not be uncovered when a significantly larger number of patients are exposed to the drug candidate. Further, any clinical trials may not be sufficient to determine the effect and safety consequences of taking our drug candidates over a multi-year period.

If any of our drug candidates receives marketing approval, and we or others later identify undesirable side effects caused by such products, a number of potentially significant negative consequences could result, including:

Any of the foregoing events could prevent us from achieving or maintaining market acceptance of the particular drug candidate, if approved, and result in the loss of significant revenues to us, which would materially and adversely affect our results of operations and business. In addition, if one or more of our drug candidates prove to be unsafe, our entire platform and pipeline could be affected, which would have a material and adverse effect on our business, financial condition, results of operations and prospects.

Even if our current drug candidates or any future drug candidates obtain regulatory approval, they may fail to achieve the broad degree of physician and patient adoption and use necessary for commercial success.

Even if one or more of our drug candidates receives the necessary regulatory approvals, the commercial success of any of our current or future drug candidates will depend significantly on the broad adoption and use of the resulting product by physicians and patients for approved indications. Our drug candidates may not be commercially successful. For a variety of reasons, including among other things, competitive factors, pricing or physician preference, reimbursement by insurers, the degree and rate of physician and patient adoption of our current or future drug candidates, if approved, will depend on a number of factors, including:

We cannot assure you that our current or future drug candidates, if approved, will achieve broad market acceptance among physicians and patients. Any failure by our drug candidates that obtain regulatory approval to achieve market acceptance or commercial success would adversely affect our results of operations.

We rely on third parties to provide the raw materials necessary for our drug candidates and to manufacture preclinical and clinical supplies of our drug candidates and we intend to rely on third parties to produce commercial supplies of any approved drug candidate. The loss of these suppliers or manufacturers, or their failure to comply with applicable regulatory requirements or to provide us with sufficient quantities at acceptable quality levels or prices, or at all, would materially and adversely affect our business.

We do not have nor do we plan to build or acquire the infrastructure or capability internally to source the raw materials necessary to produce our drug candidates and/or to manufacture our drug candidates on a preclinical, clinical or commercial scale.

Sarconeos (BIO101) is a pharmaceutical-grade purification of 20-hydroxyecdysone, which is derived from the Stemmacantha carthamoides Willd, a plant cultivated in China and used for medicinal purposes in traditional Chinese medicine. There are a limited number of growers of this plant and suppliers of the plant material and we must account for the lead time required to grow sufficient quantities of the plant to meet our needs. At this time we rely on one supplier for the plant quantities we require for our clinical trials. We have not entered into a long-term supply agreement with this supplier. We have already obtained a GMP batch of Sarconeos (BIO101) for our ongoing SARA-INT Phase 2b clinical trial and we believe we can secure sufficient quantities for our SARA and MYODA clinical programs through our current supply chain up to regulatory approval and/or marketing authorization. If our current supplier is unable to provide sufficient quantities of the plant to produce Sarconeos (BIO101) for future clinical trials, our ability to obtain regulatory approval for Sarconeos (BIO101) would be affected. If we receive regulatory approval, we will likely need substantial quantities of plants to produce Sarconeos (BIO101) for commercial development. If our current supplier is unable to provide sufficient quantities of the plant to produce Sarconeos (BIO101) and if we are unable to find an alternative source, our ability to commercialize Sarconeos (BIO101) would be impaired. In order to address this issue, we are evaluating alternative methods for producing 20-hydroxyecdysone in order to optimize the supply chain to support our projected commercial needs.

Macuneos (BIO201) is a pharmaceutical-grade purification of norbixin, which is derived from seeds of Bixa orellana L., a plant traditionally used for medicinal purposes in the Amazon and currently used for producing a food color in many countries. Although this plant is more widely available, there are a limited number of suppliers of the plant material that could meet our requirement for quality. At this time we rely on one supplier for the plant quantities we will require for our MACA clinical program. We have not entered into a long-term supply agreement with this supplier. If our current supplier is unable to provide sufficient supply to produce Macuneos (BIO201) for future clinical trials, our ability to obtain regulatory approval Macuneos (BIO201) would be affected. If we receive regulatory approval, we will likely need substantial quantities of plants to produce Macuneos (BIO201) for commercial development. If our current supplier is unable to provide sufficient quantities of the plant to produce Macuneos (BIO201) and if we are unable to find an alternative source, our ability to commercialize Macuneos (BIO201) would be impaired. In order to address this issue, we are evaluating alternative

methods for producing norbixin in order to optimize the supply chain to support our projected commercial needs.

Our contract manufacturing partner for both Sarconeos (BIO101) and Macuneos (BIO201) is Patheon, a part of Thermo Fisher Scientific, located in Germany. We have not entered into a long-term contract manufacturing agreement with Patheon or any other contract manufacturer.

The facilities used by our contract manufacturer to manufacture our drug candidates are subject to various regulatory requirements and may be subject to the inspection of the FDA, EMA or other regulatory authorities. We do not control the manufacturing process of, and are completely dependent on, our contract manufacturing partner for compliance with the regulatory requirements, known as cGMPs. If our contract manufacturer cannot successfully manufacture material that conforms to our specifications and the strict regulatory requirements of the FDA, EMA or comparable regulatory authorities in foreign jurisdictions, we may not be able to rely on their manufacturing facilities for the manufacture of our drug candidates. In addition, we have limited control over the ability of our contract manufacturer to maintain adequate quality control, quality assurance and qualified personnel. If the FDA, EMA or a comparable foreign regulatory authority finds these facilities inadequate for the manufacture of our drug candidates or if such facilities are subject to enforcement action in the future or are otherwise inadequate, we may need to find alternative manufacturing facilities, which would significantly impact our ability to develop, obtain regulatory approval for or market our drug candidates. Any significant delay in, or quality control problems with respect to, the supply of a drug candidate, or the raw material components thereof, for an ongoing study or trial could considerably delay completion of our preclinical studies or future clinical trials, product testing and potential regulatory approval of our drug candidates.

If any of our drug candidates is approved by the FDA, EMA and/or comparable foreign regulatory authorities and we choose to independently commercialize such drug candidate, we will need to engage manufacturers for the commercial supply of such drug candidates. However, we may be unable to enter into any such agreement or do so on commercially reasonable terms, which could have a material adverse impact upon our business. Moreover, if there is a disruption to one or more of our third-party manufacturers' or suppliers' relevant operations, or if we are unable to enter into arrangements for the commercial supply of our drug candidates, we will have no other means of producing our drug candidates until they restore the affected facilities or we or they procure alternative manufacturing facilities or sources of supply. Our ability to progress our preclinical and clinical programs could be materially and adversely impacted if any of the third party suppliers upon which we rely were to experience a significant business challenge, disruption or failure due to issues such as financial difficulties or bankruptcy, issues relating to other customers such as regulatory or quality compliance issues, or other financial, legal, regulatory or reputational issues. Additionally, any damage to or destruction of our third-party manufacturers' or suppliers' facilities or equipment may significantly impair our ability to manufacture our drug candidates on a timely basis.

In addition, to manufacture our drug candidates in the quantities that we believe would be required to meet anticipated market demand, our third-party manufacturers would likely need to increase manufacturing capacity and, in some cases, we could be required to secure alternative sources of commercial supply, which could involve significant challenges and could require additional regulatory approvals. In addition, the development of commercial-scale manufacturing capabilities could require us and our third-party manufacturers to invest substantial additional funds and hire and retain the technical personnel who have the necessary manufacturing experience. Neither we nor our third-party manufacturers may successfully complete any required increase to existing manufacturing capacity in a timely manner, or at all. If our manufacturers or we are unable to purchase the raw materials necessary for the manufacture of our drug candidates on acceptable terms, at sufficient quality levels, or in adequate quantities, if at all, the commercial launch of our drug candidates or any future drug

candidates would be delayed or there would be a shortage in supply, which would impair our ability to generate revenues from the sale of such drug candidates, if approved.

We rely on third parties in the conduct of all of our preclinical studies and clinical trials and intend to rely on third parties in the conduct of all of our future clinical trials. If these third parties do not successfully carry out their contractual duties, fail to comply with applicable regulatory requirements or meet expected deadlines, we may be unable to obtain regulatory approval for our drug candidates.

We currently do not have the ability to independently conduct preclinical studies that comply with the regulatory requirements known as good laboratory practice, or GLP, requirements. We also do not currently have the ability to independently conduct any clinical trials. The FDA, EMA and regulatory authorities in other jurisdictions require us to comply with regulations and standards, commonly referred to as good clinical practice, or GCP, requirements for conducting, monitoring, recording and reporting the results of clinical trials, in order to ensure that the data and results are scientifically credible and accurate and that the trial subjects are adequately informed of the potential risks of participating in clinical trials. We rely on medical institutions, clinical investigators, contract laboratories and other third parties, such as CROs, to conduct GLP-compliant preclinical studies and GCP-compliant clinical trials on our drug candidates properly and on time. While we have agreements governing their activities, we control only certain aspects of their activities and have limited influence over their actual performance. The third parties with whom we contract for execution of our GLP-compliant preclinical studies and our GCP-compliant clinical studies play a significant role in the conduct of these studies and trials and the subsequent collection and analysis of data. These third parties are not our employees and, except for restrictions imposed by our contracts with such third parties, we have limited ability to control the amount or timing of resources that they devote to our programs. Although we rely on these third parties to conduct our GLP-compliant preclinical studies and GCP-compliant clinical trials, we remain responsible for ensuring that each of our GLP preclinical studies and clinical trials is conducted in accordance with its investigational plan and protocol and applicable laws and regulations, and our reliance on the CROs does not relieve us of our regulatory responsibilities.

Many of the third parties with whom we contract may also have relationships with other commercial entities, including our competitors, for whom they may also be conducting clinical trials or other drug development activities that could harm our competitive position. If the third parties conducting our preclinical studies or our clinical trials do not adequately perform their contractual duties or obligations, experience significant business challenges, disruptions or failures, do not meet expected deadlines, terminate their agreements with us or need to be replaced, or if the quality or accuracy of the data they obtain is compromised due to their failure to adhere to our protocols or to GCPs, or for any other reason, we may need to enter into new arrangements with alternative third parties. This could be difficult, costly or impossible, and our preclinical studies or clinical trials may need to be extended, delayed, terminated or repeated. As a result we may not be able to obtain regulatory approval in a timely fashion, or at all, for the applicable drug candidate, our financial results and the commercial prospects for our drug candidates would be harmed, our costs could increase, and our ability to generate revenues could be delayed.

We face significant competition in an environment of rapid technological and scientific change, and our drug candidates, if approved, will face significant competition and our failure to effectively compete may prevent us from achieving significant market penetration. A number of our competitors have significantly greater resources than we do and we may not be able to successfully compete.

The biotechnology and pharmaceutical industries in particular are characterized by rapidly advancing technologies, intense competition and a strong emphasis on developing proprietary therapeutics. Numerous companies are engaged in the development, patenting, manufacturing and

marketing of healthcare products competitive with those that we are developing. We face competition from a number of sources, such as pharmaceutical companies, generic drug companies, biotechnology companies and academic and research institutions, many of which have greater financial resources, marketing capabilities, sales forces, manufacturing capabilities, research and development capabilities, clinical trial expertise, intellectual property portfolios, experience in obtaining patents and regulatory approvals for drug candidates and other resources than we do. Some of the companies that offer competing products also have a broad range of other product offerings, large direct sales forces and long-term customer relationships with our target physicians, which could inhibit our market penetration efforts. Mergers and acquisitions in the biotechnology and pharmaceutical industry may result in even more resources being concentrated among a smaller number of our competitors. Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies. These competitors also compete with us in recruiting and retaining qualified scientific and management personnel and establishing clinical trial sites and patient registration for clinical trials, as well as in acquiring technologies complementary to, or necessary for, our programs. In addition, certain of our drug candidates, if approved, may compete with other products that treat age-related diseases, including over-the-counter, or OTC, treatments, for a share of some patients' discretionary budgets and for physicians' attention within their clinical practices.

We are aware of other companies seeking to develop treatments to prevent or treat aging-related diseases through various biological pathways. For sarcopenia, we believe that we will compete with several pharmaceutical companies that are developing various technology modalities, including myostatin inhibitors and selective androgen receptor modulators, or SARMs, in similar therapeutic areas. Such competitors include, but are not limited to Cytokinetics in collaboration with Astellas, Eli Lilly, Novartis, Pfizer, and Sanofi in collaboration with Regeneron. For DMD, we believe that we will compete with PTC Therapeutics and Sarepta Therapeutics and a number of other companies that are developing drugs to treat this disease, including BioMarin Pharmaceuticals, Capricor Therapeutics, Catabasis Pharmaceuticals, FibroGen, Intalfarmaco, Pfizer, Roche, Sarepta Therapeutics, Solid Biosciences, Summit Therapeutics andWave Life Sciences. For dry AMD, we believe that we will compete with a number of companies that are developing drugs to treat this disease including Allegro Ophthalmics, Apellis Pharmaceuticals, Astellas, Hemera Biosciences, Ionis Pharmaceuticals, Ophthotech Corporation, Roche and Stealth Biotherapeutics.

Certain alternative treatments offered by competitors may be available at lower prices and may offer greater efficacy or better safety profiles. Furthermore, currently approved products could be discovered to have application for treatment of age-related diseases generally, which could give such products significant regulatory and market timing advantages over any of our drug candidates. Our competitors also may obtain FDA, EMA or other regulatory approval for their products more rapidly than we may obtain approval for ours and may obtain orphan product exclusivity from the FDA or EMA for indications our drug candidates are targeting, which could result in our competitors establishing a strong market position before we are able to enter the market. Newly developed systemic or non-systemic treatments that replace existing therapies that are currently only utilized in patients suffering from severe disease may also have lessened side effects or reduced prices compared to current therapies, which make them more attractive for patients suffering from mild to moderate disease. Even if a generic product or an OTC product is less effective than our drug candidates, a less effective generic or OTC product may be more quickly adopted by physicians and patients than our competing drug candidates based upon cost or convenience. For additional information regarding our competition, see the section of this prospectus captioned "Business—Competition."

Government restrictions on pricing and reimbursement, as well as other healthcare payor cost-containment initiatives, may negatively impact our ability to generate revenues and become profitable even if we obtain regulatory approval to market a product.

Our ability to commercialize any products successfully also will depend in part on the extent to which coverage and adequate reimbursement for these products and related treatments will be available from government health administration authorities, private health insurers and other organizations. Government authorities and other third-party payors, such as private health insurers and health maintenance organizations, determine which medications they will cover and establish reimbursement levels. Assuming we obtain coverage for a given product by a third-party payor, the resulting reimbursement payment rates may not be adequate or may require co-payments that patients find unacceptably high. Patients who are prescribed medications for the treatment of their conditions, and their prescribing physicians, generally rely on third-party payors to reimburse all or part of the costs associated with their prescription drugs. Patients are unlikely to use our products unless coverage is provided and reimbursement is adequate to cover all or a significant portion of the cost of our products. Therefore, coverage and adequate reimbursement is critical to new product acceptance. Coverage decisions may depend upon clinical and economic standards that disfavor new drug products when more established or lower cost therapeutic alternatives are already available or subsequently become available.

Government authorities and other third-party payors are developing increasingly sophisticated methods of controlling healthcare costs, such as by limiting coverage and the amount of reimbursement for particular medications. Increasingly, third-party payors are requiring that drug companies provide them with predetermined discounts from list prices as a condition of coverage, are using restrictive formularies and preferred drug lists to leverage greater discounts in competitive classes, and are challenging the prices charged for medical products.

In the United States, federal programs impose penalties on drug manufacturers in the form of mandatory additional rebates and/or discounts if commercial prices increase at a rate greater than the Consumer Price Index-Urban, and these rebates and/or discounts, which can be substantial, may impact our ability to raise commercial prices. Further, no uniform policy requirement for coverage and reimbursement for drug products exists among third-party payors in the United States. Therefore, coverage and reimbursement for drug products can differ significantly from payor to payor. As a result, the coverage determination process is often a time-consuming and costly process that will require us to provide scientific and clinical support for the use of our products to each payor separately, with no assurance that coverage and adequate reimbursement will be applied consistently or obtained in the first instance.

In the European Union, coverage and reimbursement possibilities for drug products differ from one Member State to another. Each Member State has the ability to set the prices and restrict the range of medicinal products for which their national health insurance systems provide reimbursement. Factors contributing to price changes between Member States depend on different regulatory approaches and instruments used by each Member State to govern the supply and demand of medicinal products. For example, in France, a pharmaceutical company may freely set a price of a drug after obtaining the National MA. However, in order for the product to be reimbursed under the French Social Security scheme, the pharmaceutical company must follow a specific process and submit an application to the French High Authority for Health (HAS). The opinion issued by the HAS is then transmitted to the French Economic Committee for Health Products (CEPS)—with which the pharmaceutical company has to negotiate the price of the product. The final decision on reimbursement is issued by the French Minister of Health and can be revised afterwards depending on the cost/benefit balance of the medicinal product over time. Other EU countries may adopt a system of direct or indirect controls on the profitability of the company placing the medicinal product on the

market. In view of these differences from one Member State to another, there is still a risk that some EU countries do not allow favorable reimbursements and pricing arrangements.

The continuing efforts of governments, insurance companies, managed care organizations and other payors of healthcare costs to contain or reduce costs of healthcare may negatively affect our commercialization prospects, including:

We cannot be sure that coverage and reimbursement will be available for any potential drug candidate that we may commercialize and, if reimbursement is available, what the level of reimbursement will be. Coverage and reimbursement may impact the demand for, or the price of, any drug candidate for which we obtain marketing approval. If coverage and reimbursement are not available or reimbursement is available only to limited levels, we may not successfully commercialize any drug candidate for which we obtain marketing approval.

In the event we elect to commercialize any of our drug candidates that receive regulatory approval, we will need to establish sales capabilities on our own or through third parties. If we are unsuccessful in our efforts, we may not be able to market and sell our drug candidates effectively in the United States, European Union and/or other foreign jurisdictions, if approved, or generate product revenue.

We currently do not have a marketing or sales organization. In order to commercialize our drug candidates in the United States and foreign jurisdictions, we would need to establish marketing, sales, distribution, managerial and other non-technical capabilities or make arrangements with third parties to perform these services, and we may not be successful in doing so. If any of our drug candidates receive regulatory approval and we elect to independently commercialize such drug candidates, we would expect to establish a sales organization with technical expertise and supporting distribution capabilities to commercialize each such drug candidate, which would be expensive and time consuming. We have no prior experience in the marketing, sale and distribution of pharmaceutical products and there are significant risks involved in building and managing a sales organization, including our ability to hire, retain, and incentivize qualified individuals, generate sufficient sales leads, provide adequate training to sales and marketing personnel, and effectively manage a geographically dispersed sales and marketing team. Any failure or delay in the development of our internal sales, marketing and distribution capabilities would adversely impact the commercialization of these products. Alternatively, we may choose to collaborate with third parties that have direct sales forces and established distribution systems, either to augment our own sales force and distribution systems or in lieu of our own sales force and distribution systems. If we are unable to enter into such arrangements on acceptable terms or at all, we may not be able to successfully commercialize our drug candidates. If we are not successful in commercializing our drug candidates or any future drug candidates, either on our own or through arrangements with one or more third parties, and are not otherwise able to license these products to third parties, we may not be able to generate any future product revenue and we would incur significant additional losses.

We will need to increase the size of our organization, and we may experience difficulties in managing growth.

As of the date of this prospectus, we had 24 full-time employees, 19 of whom were engaged in research and development activities and five of whom were engaged in general and administrative activities. Additionally, we have two part-time employees who are engaged in research and development activities. We will need to continue to expand our managerial, operational, finance and other resources

in order to manage our operations and clinical trials, continue our development activities and commercialize our drug candidates or any future drug candidates. Our management and personnel, systems and facilities currently in place may not be adequate to support this future growth. Our need to effectively execute our growth strategy requires that we:

If we fail to attract and retain senior management and key scientific personnel, we may be unable to successfully develop our drug candidates or any future drug candidates, conduct our clinical trials and commercialize our current or any future drug candidates.

We are dependent upon the services of key members of senior management and the loss of any of these individuals could harm our business. On June 7, 2019, we announced that Mr. Montigny, our Chief Operating Officer, who oversaw our financial operations as principal financial officer and principal accounting officer, has resigned from the Company. Mr. Schneiderman, who has served as Chief Financial Officer for Biophytis, Inc., our wholly-owned U.S. subsidiary, has expanded his role to include the financial operations for Biophytis S.A. as Chief Financial Officer for the Company. Mr. Montigny will remain with us until July 24, 2019 in order to ensure a smooth transition. This change, or the loss of services of any of our other key executive officers or other members of our senior management team, may be disruptive to, or cause uncertainty in, our business and could have a negative impact on our ability to manage and grow our business effectively. Such disruption could have a material adverse impact on our financial performance, financial condition, and the market price of our ordinary shares.

Our success also depends on our ability to continue to attract, retain and motivate highly qualified clinical and scientific personnel. Competition for qualified personnel in the biotechnology and pharmaceuticals field is intense due to the limited number of individuals who possess the skills and experience required by our industry. We will need to hire additional personnel as we expand our clinical development and if we initiate commercial activities. We may not be able to attract and retain quality personnel on acceptable terms, or at all. In addition, to the extent we hire personnel from competitors, we may be subject to allegations that they have been improperly solicited or that they have divulged proprietary or other confidential information, or that their former employers own their research output.

If product liability lawsuits are brought against us, we may incur substantial liabilities and may be required to limit commercialization of our current or future drug candidates.

We face an inherent risk of product liability as a result of the clinical testing of our drug candidates and will face an even greater risk if we commercialize any products. For example, we may be sued if any product we develop allegedly causes injury or is found to be otherwise unsuitable during product testing, manufacturing, marketing or sale. Any such product liability claims may include allegations of defects in manufacturing, defects in design, a failure to warn of dangers inherent in the product, negligence, strict liability, and a breach of warranty. Claims could also be asserted under state consumer protection acts. If we cannot successfully defend ourselves against product liability claims, we

may incur substantial liabilities or be required to limit commercialization of our drug candidates. Even a successful defense would require significant financial and management resources. Regardless of the merits or eventual outcome, liability claims may result in:

Our inability to obtain and maintain sufficient product liability insurance at an acceptable cost and scope of coverage to protect against potential product liability claims could prevent or inhibit the commercialization of our current or any future drug candidates we develop. We currently carry product liability insurance covering our clinical trials. Although we maintain such insurance, any claim that may be brought against us could result in a court judgment or settlement in an amount that is not covered, in whole or in part, by our insurance or that is in excess of the limits of our insurance coverage. Our insurance policies also have various exclusions and deductibles, and we may be subject to a product liability claim for which we have no coverage. We will have to pay any amounts awarded by a court or negotiated in a settlement that exceed our coverage limitations or that are not covered by our insurance, and we may not have, or be able to obtain, sufficient funds to pay such amounts. Moreover, in the future, we may not be able to maintain insurance coverage at a reasonable cost or in sufficient amounts to protect us against losses. If and when we obtain approval for marketing any of our drug candidates, we intend to expand our insurance coverage to include the sale of such drug candidate; however, we may be unable to obtain this liability insurance on commercially reasonable terms or at all.

Our existing collaborations as well as additional collaboration arrangements that we may enter into in the future may not be successful, which could adversely affect our ability to develop and commercialize our drug candidates.

We utilize external collaborations and currently maintain several active early-stage research and discovery focused collaborations. We may seek to partner with pharmaceutical laboratories to conduct clinical trials of our drug candidates. We may also seek additional collaboration arrangements for the commercialization, or potentially for the development, of certain of our drug candidates depending on the merits of retaining commercialization rights for ourselves as compared to entering into collaboration arrangements. To the extent that we decide to enter into additional collaboration agreements in the future, we may face significant competition in seeking appropriate collaborators. Moreover, collaboration arrangements are complex and time-consuming to negotiate, document, implement and maintain and challenging to manage. We may not be successful in our efforts to prudently manage our existing collaborations or to enter new ones should we choose to do so. The terms of new collaborations or other arrangements that we may establish may not be favorable to us.

The success of our collaboration arrangements will depend heavily on the efforts and activities of our collaborators. Collaborations are subject to numerous risks, which may include risks that:

Significant disruptions of information technology systems or breaches of data security could materially adversely affect our business, results of operations and financial condition.

We collect and maintain information in digital form that is necessary to conduct our business, and we are increasingly dependent on information technology systems and infrastructure to operate our business. In the ordinary course of our business, we collect, store and transmit large amounts of confidential information, including intellectual property, proprietary business information and personal

information. It is critical that we do so in a secure manner to maintain the confidentiality and integrity of such confidential information. We have established physical, electronic and organizational measures to safeguard and secure our systems to prevent a data compromise, and rely on commercially available systems, software, tools, and monitoring to provide security for our information technology systems and the processing, transmission and storage of digital information. We have also outsourced elements of our information technology infrastructure, and as a result a number of third-party vendors may or could have access to our confidential information. Our internal information technology systems and infrastructure, and those of our current and any future collaborators, contractors and consultants and other third parties on which we rely, are vulnerable to damage from computer viruses, malware, natural disasters, terrorism, war, telecommunication and electrical failures, cyber-attacks or cyber-intrusions over the Internet, attachments to emails, persons inside our organization, or persons with access to systems inside our organization.

The risk of a security breach or disruption, particularly through cyber-attacks or cyber-intrusion, including by computer hackers, foreign governments and cyber-terrorists, has generally increased as the number, intensity and sophistication of attempted attacks and intrusions from around the world have increased. In addition, the prevalent use of mobile devices that access confidential information increases the risk of data security breaches, which could lead to the loss of confidential information or other intellectual property. The costs to us to mitigate network security problems, bugs, viruses, worms, malicious software programs and security vulnerabilities could be significant, and while we have implemented security measures to protect our data security and information technology systems, our efforts to address these problems may not be successful, and these problems could result in unexpected interruptions, delays, cessation of service and other harm to our business and our competitive position. If such an event were to occur and cause interruptions in our operations, it could result in a material disruption of our product development programs. For example, the loss of clinical trial data from completed or ongoing or planned clinical trials could result in delays in our regulatory approval efforts and significantly increase our costs to recover or reproduce the data. Moreover, if a computer security breach affects our systems or results in the unauthorized release of personally identifiable information, our reputation could be materially damaged.

In addition, such a breach may require notification to governmental agencies, the media or individuals pursuant to various federal and state privacy and security laws, if applicable, including the Health Insurance Portability and Accountability Act of 1996, as amended by the Health Information Technology for Clinical Health Act of 2009, and its implementing rules and regulations, as well as regulations promulgated by the Federal Trade Commission and state breach notification laws.

Under the EU regulation and notably the General Data Protection Regulation, or GDPR, No. 2016/679, which entered into force on May 25, 2018 and is applicable personal data that we process in relation to our presence in the EU, the offering of products or services to individuals in the EU or the monitoring of the behavior of individuals in the EU, we have also a legal responsibility to report personal data breaches to the competent supervisory authority. The EU data protection regulation includes a broad definition and a short deadline for the notification of personal data breaches, which may be difficult to implement in practice and requires that we implement robust internal processes. Under this regulation, we have to report personal data breaches to the competent supervisory authority within 72 hours of the time we become aware of a breach "unless the personal data breach is unlikely to result in a risk to the right and freedoms of natural persons" (Article 33 of the GDPR). In addition, the GDPR requires that we communicate the breach to the Data Subject if the breach is "likely to result in a high risk to the rights and freedoms of natural persons" (Article 34 of the GDPR). In order to fulfil these requirements, we have to implement specific internal processes to be followed in case of a personal data breach, which will allow us to (a) contain and recover the breach, (b) assess the risk to the data subjects, (c) notify, and possibly communicate the breach to the data subjects, (d) investigate

and respond to the breach. The performance of these processes imply substantial costs in resources and time.

Moreover, as we may rely on third parties that will also process as processor the data for which we are a data controller—for example, in the context of the manufacturing of our drug candidates or for the conduct of clinical trials, we must contractually ensure that strict security measures, as well as appropriate obligations including an obligation to report in due delay any security incident are implemented, in order to allow us fulfilling our own regulatory requirements.

We would also be exposed to a risk of loss or litigation and potential liability for any security breach on personal data for which we are data controller. The costs of above-mentioned processes together with legal penalties, possible compensation for damages and any resulting lawsuits arising from a breach may be extensive and may have a negative impact on reputation and materially adversely affect our business, results of operations and financial condition.

Our employees and independent contractors, including principal investigators, consultants, commercial collaborators, service providers and other vendors may engage in misconduct or other improper activities, including noncompliance with regulatory standards and requirements, which could have an adverse effect on our results of operations.

We are exposed to the risk that our employees and independent contractors, including principal investigators, consultants, any future commercial collaborators, service providers and other vendors may engage in misconduct or other illegal activity. Misconduct by these parties could include intentional, reckless and/or negligent conduct or other unauthorized activities that violate the laws and regulations of the FDA, EMA and other similar regulatory bodies, including those laws that require the reporting of true, complete and accurate information to such regulatory bodies; manufacturing standards; healthcare fraud and abuse, data privacy laws and other similar laws; or laws that require the true, complete and accurate reporting of financial information or data. Activities subject to these laws also involve the improper use or misrepresentation of information obtained in the course of clinical trials, the creation of fraudulent data in our preclinical studies or clinical trials, or illegal misappropriation of product, which could result in regulatory sanctions and cause serious harm to our reputation. It is not always possible to identify and deter misconduct by employees and other third parties, and the precautions we take to detect and prevent this activity may not be effective in controlling unknown or unmanaged risks or losses or in protecting us from governmental investigations or other actions or lawsuits stemming from a failure to be in compliance with such laws or regulations. In addition, we are subject to the risk that a person or government could allege such fraud or other misconduct, even if none occurred. If any such actions are instituted against us, and we are not successful in defending ourselves or asserting our rights, those actions could have a significant impact on our business and financial results, including, without limitation, the imposition of significant civil, criminal and administrative penalties, damages, monetary fines, disgorgements, possible exclusion from participation in governmental healthcare programs, individual imprisonment, other sanctions, contractual damages, reputational harm, diminished profits and future earnings and curtailment of our operations, any of which could adversely affect our ability to operate our business and our results of operations.

Our business involves the use of hazardous materials and we and our third-party manufacturers and suppliers must comply with environmental laws and regulations, which can be expensive and restrict how we do business.

Our research and development activities and our third-party manufacturers' and suppliers' activities involve the controlled storage, use and disposal of hazardous materials owned by us, including the components of our product and drug candidates and other hazardous compounds. We and any third-party manufacturers and suppliers we engage are subject to numerous federal, state and local environmental, health and safety laws, regulations and permitting requirements, including those

governing laboratory procedures; the generation, handling, use, storage, treatment, and disposal of hazardous and regulated materials and wastes; the emission and discharge of hazardous materials into the ground, air and water; and employee health and safety. Our operations involve the use of hazardous and flammable materials, including chemicals and biological materials. Our operations also produce hazardous waste. In some cases, these hazardous materials and various wastes resulting from their use are stored at our and our manufacturers' facilities pending their use and disposal. We generally contract with third parties for the disposal of these materials and wastes. We cannot eliminate the risk of contamination, which could cause an interruption of our commercialization efforts, research and development efforts and business operations, environmental damage resulting in costly clean-up and liabilities under applicable laws and regulations governing the use, storage, handling and disposal of these materials and specified waste products.

Although we believe that the safety procedures utilized by our third-party manufacturers for handling and disposing of these materials generally comply with the standards prescribed by these laws and regulations, we cannot guarantee that this is the case or eliminate the risk of accidental contamination or injury from these materials. Under certain environmental laws, we could be held responsible for costs relating to any contamination at our current or past facilities and at third-party facilities. In such an event, we may be held liable for any resulting damages and such liability could exceed our resources and state or federal or other applicable authorities may curtail our use of certain materials and/or interrupt our business operations. Furthermore, environmental laws and regulations are complex, change frequently and have tended to become more stringent. We cannot predict the impact of such changes and cannot be certain of our future compliance.

Compliance with applicable environmental laws and regulations may be expensive, and current or future environmental laws and regulations may impair our research, product development and manufacturing efforts. In addition, we cannot entirely eliminate the risk of accidental injury or contamination from these materials or wastes. Although we maintain workers' compensation insurance to cover us for costs and expenses we may incur due to injuries to our employees resulting from the use of hazardous materials, this insurance may not provide adequate coverage against potential liabilities. We do not carry specific biological or hazardous waste insurance coverage, and our property, casualty, and general liability insurance policies specifically exclude coverage for damages and fines arising from biological or hazardous waste exposure or contamination. Accordingly, in the event of contamination or injury, we could be held liable for damages or be penalized with fines in an amount exceeding our resources, and our clinical trials or regulatory approvals could be suspended, which could have a material adverse effect on our business, results of operations and financial condition.

Our Ability To Compete May Decline If We Do Not Adequately Protect Our Proprietary Rights.

Our success depends on obtaining and maintaining proprietary rights to our drug candidates for the treatment of age-related diseases, as well as successfully defending these rights against third-party challenges. We will only be able to protect our drug candidates, and their uses from unauthorized use by third parties to the extent that valid and enforceable patents, or effectively protected trade secrets, cover them. Our ability to obtain patent protection for our drug candidates is uncertain due to a number of factors, including:

Even if we have or obtain patents covering our drug candidates or compositions, we may still be barred from making, using and selling our drug candidates or technologies because of the patent rights of others. Others may have filed, and in the future may file, patent applications covering compositions or products that are similar or identical to ours. There are many issued U.S. and foreign patents relating to chemical compounds and therapeutic products, and some of these relate to compounds we intend to commercialize. Numerous U.S. and foreign issued patents and pending patent applications owned by others exist in the allergy treatment field in which we are developing products. These could materially affect our ability to develop our drug candidates or sell our products if approved. Because patent applications can take many years to issue, there may be currently pending applications unknown to us that may later result in issued patents that our drug candidates or compositions may infringe. These patent applications may have priority over patent applications filed by us.

Obtaining and maintaining a patent portfolio entails significant expense and resources. Part of the expense includes periodic maintenance fees, renewal fees, annuity fees, various other governmental fees on patents and/or applications due in several stages over the lifetime of patents and/or applications, as well as the cost associated with complying with numerous procedural provisions during the patent application process. We may or may not choose to pursue or maintain protection for particular inventions. In addition, there are situations in which failure to make certain payments or noncompliance with certain requirements in the patent process can result in abandonment or lapse of a patent or patent application, resulting in partial or complete loss of patent rights in the relevant jurisdiction. If we choose to forgo patent protection or allow a patent application or patent to lapse purposefully or inadvertently, our competitive position could suffer.

In addition, it is unclear at this time what Brexit's impact will have on our intellectual property rights and the process for obtaining and defending such rights. It is possible that certain intellectual property rights, such as trademarks, granted by the EU will cease being enforceable in the UK absent special arrangements to the contrary. With regard to existing patent rights, the effect of Brexit should be minimal considering enforceable patent rights are specific to the UK, whether arising out of the European Patent Office or directly through the UK patent office.

Legal actions to enforce our proprietary rights (including patents and trademarks) can be expensive and may involve the diversion of significant management time. In addition, these legal actions could be unsuccessful and could also result in the invalidation of our patents or trademarks or a finding that they are unenforceable. We may or may not choose to pursue litigation or other actions against those that have infringed on our patents or trademarks, or used them without authorization,

due to the associated expense and time commitment of monitoring these activities. If we fail to protect or to enforce our intellectual property rights successfully, our competitive position could suffer, which could harm our results of operations.

Biotechnology Patents And Patent Applications Involve Highly Complex Legal And Factual Questions, Which, If Determined Adversely To Us, Could Negatively Impact Our Patent Position.

The patent positions of biotechnology companies can be highly uncertain and involve complex legal and factual questions. The interpretation and breadth of claims allowed in some patents covering biotechnology compositions may be uncertain and difficult to determine, and are often affected materially by the facts and circumstances that pertain to the patented compositions and the related patent claims. The standards of the United States Patent and Trademark Office, or USPTO, are sometimes uncertain and could change in the future. Consequently, the issuance and scope of patents cannot be predicted with certainty. Patents, if issued, may be challenged, invalidated or circumvented. U.S. patents and patent applications may also be subject to interference proceedings, and U.S. patents may be subject to reexamination proceedings, post-grant review and/or inter partes review in the USPTO. Foreign patents may be subject also to opposition or comparable proceedings in the corresponding foreign patent office, which could result in either loss of the patent or denial of the patent application or loss or reduction in the scope of one or more of the claims of the patent or patent application. In addition, such interference, reexamination, post-grant review, inter partes review and opposition proceedings may be costly. Accordingly, rights under any issued patents may not provide us with sufficient protection against competitive products or processes.

In addition, changes in or different interpretations of patent laws in the United States and foreign countries may permit others to use our discoveries or to develop and commercialize our technology and products without providing any compensation to us, or may limit the number of patents or claims we can obtain. The laws of some countries do not protect intellectual property rights to the same extent as U.S. laws and those countries may lack adequate rules and procedures for defending our intellectual property rights. This may also result in having the same invention covering differing claims in different countries and provide a different scope of protection in foreign countries.

If we fail to obtain and maintain patent protection and trade secret protection of our drug candidates, we could lose our competitive advantage and competition we face would increase, reducing any potential revenues and adversely affecting our ability to attain or maintain profitability.

From time to time, the United States Supreme Court, or the Supreme Court, other federal courts, the United States Congress, the USPTO or similar foreign authorities may change the standards of patentability and any such changes could have a negative impact on our business.

In addition, the Leahy-Smith America Invents Act, or the America Invents Act, which was signed into law in 2011, includes a number of significant changes to U.S. patent law. These changes include a transition from a "first-to-invent" system to a "first-to-file" system, changes to the way issued patents are challenged, and changes to the way patent applications are disputed during the examination process. These changes may favor larger and more established companies that have greater resources to devote to patent application filing and prosecution. The USPTO has developed new and untested regulations and procedures to govern the full implementation of the America Invents Act, and many of the substantive changes to patent law associated with the America Invents Act, and, in particular, the first-to-file provisions, became effective on March 16, 2013. Substantive changes to patent law associated with the America Invents Act may affect our ability to obtain patents, and if obtained, to enforce or defend them. Accordingly, it is not clear what, if any, impact the America Invents Act will have on the cost of prosecuting our patent applications, our ability to obtain patents based on our

discoveries and our ability to enforce or defend any patents that may issue from our patent applications, all of which could have a material adverse effect on our business.

If We Are Unable To Protect The Confidentiality Of Our Trade Secrets, Our Business And Competitive Position Would Be Harmed.

In addition to patent protection, because we operate in the highly technical field of development of therapies, we rely in part on trade secret protection in order to protect our proprietary technology and processes. However, trade secrets are difficult to protect. We expect to enter into confidentiality and intellectual property assignment agreements with our employees, consultants, outside scientific collaborators, sponsored researchers, and other advisors. These agreements generally require that the other party keep confidential and not disclose to third parties all confidential information developed by the party or made known to the party by us during the course of the party's relationship with us. These agreements also generally provide that inventions conceived by the party in the course of rendering services to us will be our exclusive property. However, these agreements may not be honored and may not effectively assign intellectual property rights to us.

In addition to contractual measures, we try to protect the confidential nature of our proprietary information using physical and technological security measures. Such measures may not, for example, in the case of misappropriation of a trade secret by an employee or third party with authorized access, provide adequate protection for our proprietary information. Our security measures may not prevent an employee or consultant from misappropriating our trade secrets and providing them to a competitor, and recourse we take against such misconduct may not provide an adequate remedy to protect our interests fully. Enforcing a claim that a party illegally disclosed or misappropriated a trade secret can be difficult, expensive, and time-consuming, and the outcome is unpredictable. In addition, courts outside the United States may be less willing to protect trade secrets. Trade secrets may be independently developed by others in a manner that could prevent legal recourse by us. If any of our confidential or proprietary information, such as our trade secrets, were to be disclosed or misappropriated, or if any such information was independently developed by a competitor, our competitive position could be harmed.

We Will Not Seek To Protect Our Intellectual Property Rights In All Jurisdictions Throughout The World And We May Not Be Able To Adequately Enforce Our Intellectual Property Rights Even In The Jurisdictions Where We Seek Protection.

Filing, prosecuting and defending patents on our drug candidates and our trademarks in all countries and jurisdictions throughout the world would be prohibitively expensive, and our intellectual property rights in some countries outside the United States could be less extensive than those in the United States, assuming that rights are obtained in the United States. In addition, the laws of some foreign countries do not protect intellectual property rights to the same extent as federal and state laws in the United States. Consequently, we may not be able to prevent third parties from practicing our inventions or using our trademarks in all countries outside the United States, or from selling or importing products made using our inventions or commercialized under identical or similar trademarks in and into the United States or other jurisdictions. The statutory deadlines for pursuing patent and trademark protection in individual foreign jurisdictions are based on the priority dates of each of our patent and trademark applications.

Competitors may use our technologies or trademarks in jurisdictions where we do not pursue and obtain patent or trademark protection to develop their own products and further, may export otherwise infringing products to territories where we have patent or trademark protection, but enforcement is not as strong as that in the United States. These products may compete with our products and our patents or other intellectual property rights may not be effective or sufficient to prevent them from competing. Even if we pursue and obtain issued patents and trademarks in particular jurisdictions, our patent

claims or other intellectual property rights may not be effective or sufficient to prevent third parties from so competing.

The laws of some foreign countries do not protect intellectual property rights to the same extent as the laws of the United States. Many companies have encountered significant problems in protecting and defending intellectual property rights in certain foreign jurisdictions. The legal systems of some countries, particularly developing countries, do not favor the enforcement of patents and other intellectual property protection, especially those relating to biopharmaceuticals or biotechnologies. This could make it difficult for us to stop the infringement of our patents, if obtained, or the misappropriation of our other intellectual property rights. For example, many foreign countries have compulsory licensing laws under which a patent owner must grant licenses to third parties. In addition, many countries limit the enforceability of patents against third parties, including government agencies or government contractors. In these countries, patents may provide limited or no benefit. Patent protection must ultimately be sought on a country-by-country basis, which is an expensive and time-consuming process with uncertain outcomes. Accordingly, we may choose not to seek patent protection in certain countries, and we will not have the benefit of patent protection in such countries.

Proceedings to enforce our patent or other intellectual property rights in foreign jurisdictions could result in substantial costs and divert our efforts and attention from other aspects of our business, could put our patents or other intellectual property at risk of being invalidated or interpreted narrowly, could put our patent or trademark applications at risk of not issuing and could provoke third parties to assert claims against us. We may not prevail in any lawsuits that we initiate and the damages or other remedies awarded, if any, may not be commercially meaningful. In addition, changes in the law and legal decisions by courts in the United States and foreign countries may affect our ability to obtain adequate protection for our technology and the enforcement of intellectual property. Accordingly, our efforts to enforce our intellectual property rights around the world may be inadequate to obtain a significant commercial advantage from the intellectual property that we develop or license.

Third Parties May Assert Ownership Or Commercial Rights To Inventions We Develop.

Third parties may in the future make claims challenging the inventorship or ownership of our intellectual property. We have written agreements with collaborators that provide for the ownership of intellectual property arising from our collaborations. These agreements provide that we must negotiate certain commercial rights with collaborators with respect to joint inventions or inventions made by our collaborators that arise from the results of the collaboration. In some instances, there may not be adequate written provisions to address clearly the resolution of intellectual property rights that may arise from a collaboration. If we cannot successfully negotiate sufficient ownership and commercial rights to the inventions that result from our use of a third-party collaborator's materials where required, or if disputes otherwise arise with respect to the intellectual property developed with the use of a collaborator's samples, we may be limited in our ability to capitalize on the market potential of these inventions. In addition, we may face claims by third parties that our agreements with employees, contractors, or consultants obligating them to assign intellectual property to us are ineffective, or in conflict with prior or competing contractual obligations of assignment, which could result in ownership disputes regarding intellectual property we have developed or will develop and interfere with our ability to capture the commercial value of such inventions. Litigation may be necessary to resolve an ownership dispute, and if we are not successful, we may be precluded from using certain intellectual property, or may lose our exclusive rights in that intellectual property. Either outcome could have an adverse impact on our business.

Our Chief Executive Officer, who is a corporate officer (mandataire social) but not an employee of the Company under French law, is involved in our research and development activities. He has contributed to research results for which we have submitted patent applications in which he is listed as a co-inventor and other inventions that we expect may give rise to patent applications in the future for

which we expect he will be included as a co-inventor. Under French intellectual property law, inventors who are employees of a company have legal rights that are typically circumscribed in France by a combination of French labor law and contractual arrangements. Because Mr. Veillet is our CEO, and not an employee, we have entered into an assignment agreement with him, pursuant to which he will be entitled to certain payments as consideration for his prior and future contributions to our research projects and inventions. See "Intellectual Property Agreement with Stanislas Veillet" in the "Business" section of this prospectus for additional information.

Third Parties May Assert That Our Employees Or Consultants Have Wrongfully Used Or Disclosed Confidential Information Or Misappropriated Trade Secrets.

We employ individuals who were previously employed at universities or other biotechnology companies, including our competitors or potential competitors. Although we try to ensure that our employees and consultants do not use the proprietary information or know-how of others in their work for us, we may be subject to claims that we or our employees, consultants or independent contractors have inadvertently or otherwise used or disclosed intellectual property, including trade secrets or other proprietary information, of a former employer or other third parties. Litigation may be necessary to defend against these claims. If we fail in defending any such claims, in addition to paying monetary damages, we may lose valuable intellectual property rights or personnel. Even if we are successful in defending against such claims, litigation could result in substantial costs and be a distraction to management and other employees.

A Dispute Concerning The Infringement Or Misappropriation Of Our Proprietary Rights Or The Proprietary Rights Of Others Could Be Time-Consuming And Costly, And An Unfavorable Outcome Could Harm Our Business.

There is significant litigation in the biotechnology industry regarding patent and other intellectual property rights. While we are not currently subject to any pending intellectual property litigation, and are not aware of any such threatened litigation, we may be exposed to future litigation by third parties based on claims that our drug candidates, technologies or activities infringe the intellectual property rights of others. If our development activities are found to infringe any such patents, we may have to pay significant damages or seek licenses to such patents. A patentee could prevent us from using the patented drugs or compositions. We may need to resort to litigation to enforce a patent issued to us, to protect our trade secrets, or to determine the scope and validity of third-party proprietary rights. From time to time, we may hire scientific personnel or consultants formerly employed by other companies involved in one or more areas similar to the activities conducted by us. Either we or these individuals may be subject to allegations of trade secret misappropriation or other similar claims as a result of prior affiliations. If we become involved in litigation, it could consume a substantial portion of our managerial and financial resources, regardless of whether we win or lose. We may not be able to afford the costs of litigation. Any adverse ruling or perception of an adverse ruling in defending ourselves against these claims could have a material adverse impact on our cash position and the price of the ADSs. Any legal action against us or our collaborators could lead to:

We May Infringe The Intellectual Property Rights Of Others, Which May Prevent Or Delay Our Product Development Efforts And Stop Us From Commercializing Or Increase The Costs Of Commercializing Our Drug Candidates, If Approved.

Our success will depend in part on our ability to operate without infringing the intellectual property and proprietary rights of third parties. We cannot assure you that our business, products and methods do not or will not infringe the patents or other intellectual property rights of third parties.

The biotechnology industry is characterized by extensive litigation regarding patents and other intellectual property rights. Other parties may allege that our drug candidates or the use of our technologies infringes patent claims or other intellectual property rights held by them or that we are employing their proprietary technology without authorization. Patent and other types of intellectual property litigation can involve complex factual and legal questions, and their outcome is uncertain. Any claim relating to intellectual property infringement that is successfully asserted against us may require us to pay substantial damages, including treble damages and attorney's fees if we are found to be willfully infringing another party's patents, for past use of the asserted intellectual property and royalties and other consideration going forward if we are forced to take a license. In addition, if any such claim were successfully asserted against us and we could not obtain such a license, we may be forced to stop or delay developing, manufacturing, selling or otherwise commercializing products.

Even if we are successful in these proceedings, we may incur substantial costs and divert management time and attention in pursuing these proceedings, which could have a material adverse effect on us. If we are unable to avoid infringing the patent rights of others, we may be required to seek a license, defend an infringement action or challenge the validity of the patents in court, or redesign our products. Patent litigation is costly and time consuming. We may not have sufficient resources to bring these actions to a successful conclusion. In addition, intellectual property litigation or claims could force us to do one or more of the following:

Any of these risks coming to fruition could have a material adverse effect on our business, results of operations, financial condition and prospects.

Issued Patents Covering Our Drug Candidates Could Be Found Invalid Or Unenforceable If Challenged In Court.

If we or one of our licensing partners initiated legal proceedings against a third party to enforce a patent covering our drug candidate, the defendant could counterclaim that the patent covering our drug candidate is invalid and/or unenforceable. In patent litigation in the United States, defendant counterclaims alleging invalidity and/or unenforceability are commonplace. Grounds for a validity challenge include alleged failures to meet any of several statutory requirements, including lack of novelty, obviousness or non-enablement. Grounds for unenforceability assertions include allegations that someone connected with prosecution of the patent withheld relevant information from the USPTO, or made a misleading statement, during prosecution. Third parties may also raise similar

claims before administrative bodies in the United States or abroad, even outside the context of litigation. Such mechanisms include re-examination, post grant review and equivalent proceedings in foreign jurisdictions, e.g., opposition proceedings. Such proceedings could result in revocation or amendment of our patents in such a way that they no longer cover our drug candidates or competitive products. The outcome following legal assertions of invalidity and unenforceability is unpredictable. With respect to validity, for example, we cannot be certain that there is no invalidating prior art, of which we and the patent examiner were unaware during prosecution. If a defendant were to prevail on a legal assertion of invalidity and/or unenforceability, we would lose at least part, and perhaps all, of the patent protection on our drug candidates. Such a loss of patent protection would have a material adverse impact on our business.

Even if we obtain regulatory approval for a drug candidate, our products will remain subject to regulatory scrutiny.

If our drug candidates are approved, they will be subject to ongoing regulatory requirements for manufacturing, labeling, packaging, storage, advertising, promotion, sampling, record-keeping, conduct of post-marketing studies, and submission of safety, efficacy, and other post-market information, including both federal and state requirements in the United States and requirements of comparable foreign regulatory authorities.

Manufacturers and manufacturers' facilities are required to comply with extensive FDA, EMA and comparable foreign regulatory authority requirements, including ensuring that quality control and manufacturing procedures conform to cGMP regulations. As such, we and our contract manufacturers will be subject to continual review and inspections to assess compliance with cGMP and adherence to commitments made in any approved marketing application. Inspections by regulatory authorities and the potential need for subsequent corrective actions may require additional investment or changes to our manufacturing or suppliers' manufacturing facilities, and may cause delays, interruptions, or complete stoppage of the manufacturing process. Accordingly, we and others with whom we work must continue to expend time, money, and effort in all areas of regulatory compliance, including manufacturing, production, and quality control.

Given that we expect to have a global supply chain, our supply chain may also be affected by the FDA's enforcement activity at the U.S. border, such as import detentions or refusals. Despite our investment in regulatory compliance, the FDA may raise issues with our regulatory compliance, and suppliers outside of our direct control may also fail to adhere to the FDA's regulatory requirements, in which case our supply chain and business plans may be interrupted. Further import detentions or holds may also occur while the FDA attempts to verify the imported products' compliance with the law. Such detentions or holds may affect our supply chain and business plans.

We will have to comply with requirements concerning advertising and promotion for our products. Promotional communications with respect to prescription drugs and biologics are subject to a variety of legal and regulatory restrictions and must be consistent with the information in the product's approved label. As such, we may not promote our products for indications or uses for which they do not have approval. The holder of an approved application must submit new or supplemental applications and obtain approval for certain changes to the approved product, product labeling, or manufacturing process. We could also be asked to conduct post-marketing clinical trials to verify the safety and efficacy of our products in general or in specific patient subsets. An unsuccessful post-marketing study or failure to complete such a study could result in the withdrawal of marketing approval. In addition, under European regulation, certain of our drug candidates could be added to the list of drugs subject to additional monitoring. Such list concerns drugs for which there is no experience due to their recent marketing or a lack of data on their long-term use. This classification would lead to additional

requirements regarding post-marketing surveillance measures of our products, which may require more resources on our end.

If a regulatory agency discovers previously unknown problems with a product, such as adverse events of unanticipated severity or frequency, or problems with the facility where the product is manufactured, or disagrees with the promotion, marketing or labeling of a product, such regulatory agency may impose restrictions on that product or us, including requiring withdrawal of the product from the market. If we fail to comply with applicable regulatory requirements, a regulatory agency or enforcement authority may, among other things:

Any government investigation of alleged violations of law could require us to expend significant time and resources in response, and could generate negative publicity. Any failure to comply with ongoing regulatory requirements may significantly and adversely affect our ability to commercialize and generate revenue from our products. If regulatory sanctions are applied or if regulatory approval is withdrawn, the value of our company and our operating results will be adversely affected.

Moreover, the policies of the FDA, EMA and of other regulatory authorities may change and additional government regulations may be enacted that could prevent, limit or delay regulatory approval of our drug candidates. We cannot predict the likelihood, nature or extent of government regulation that may arise from future legislation or administrative or executive action, in Europe, the United States or elsewhere. For example, the new European regulation on clinical trials on medicinal products for human use published in the Official Journal of the European Union on May 27, 2014 will soon come into force upon the implementation of the European portal and database and could impact the administrative procedure that we will have to follow in order to obtain regulatory approval for our drug candidates. Depending on the date of our application for clinical trial authorization, we could be required to adapt quickly to the new requirements and procedures resulting from this new regulation, in particular regarding the new required deadlines that will require us to be reactive in the event of additional requests from the authorities. We are also anticipating further guidance from national regulators of each Member State (such as ANSM for France) as those are involved in the process.

In addition, certain policies of the Trump administration in the United States may impact our business and industry. Namely, the Trump administration has taken several executive actions, including the issuance of a number of Executive Orders, that could impose significant burdens on, or otherwise materially delay, the FDA's ability to engage in routine oversight activities such as implementing statutes through rulemaking, issuance of guidance, and review and approval of marketing applications. It is difficult to predict how these orders will be implemented, and the extent to which they will impact the FDA's ability to exercise its regulatory authority. If these executive actions impose restrictions on

the FDA's ability to engage in oversight and implementation activities in the normal course, our business may be negatively impacted. In addition, if we are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies, or if we are not able to maintain regulatory compliance, we may lose any marketing approval that we may have obtained and we may not achieve or sustain profitability.

If any of our drug candidates obtain regulatory approval, additional competitors could enter the market with generic versions of such drugs, which may result in a material decline in sales of affected products.

Under the Drug Price Competition and Patent Term Restoration Act of 1984, or the Hatch-Waxman Act, a pharmaceutical manufacturer may file an abbreviated new drug application, or ANDA, seeking approval of a generic version of an approved, small molecule innovator product. Under the Hatch-Waxman Act, a manufacturer may also submit a new drug application, or NDA, under section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act, or FDCA, that references the FDA's prior approval of the innovator product. A 505(b)(2) NDA product may be for a new or improved version of the original innovator product. The Hatch-Waxman Act also provides for certain periods of regulatory exclusivity, which preclude FDA approval (or in some circumstances, FDA filing and review) of an ANDA or 505(b)(2) NDA. In addition to the benefits of regulatory exclusivity, an innovator NDA holder may have patents claiming the active ingredient, product formulation or an approved use of the drug, which would be listed with the product in the FDA publication, "Approved Drug Products with Therapeutic Equivalence Evaluations," known as the Orange Book. If there are patents listed in the Orange Book for a product, a generic or 505(b)(2) applicant that seeks to market its product before expiration of the patents must include in their applications what is known as a "Paragraph IV" certification, challenging the validity or enforceability of, or claiming non-infringement of, the listed patent or patents. Notice of the certification must be given to the patent owner and NDA holder and if, within 45 days of receiving notice, either the patent owner or NDA holder sues for patent infringement, approval of the ANDA or 505(b)(2) NDA is stayed for up to 30 months.

Accordingly, if any of our drug candidates are approved, competitors could file ANDAs for generic versions of our drug candidates or 505(b)(2) NDAs that reference our small molecule drug products. If there are patents listed for our drug candidates in the Orange Book, those ANDAs and 505(b)(2) NDAs would be required to include a certification as to each listed patent indicating whether the ANDA applicant does or does not intend to challenge the patent. We cannot predict which, if any, patents in our current portfolio or patents we may obtain in the future will be eligible for listing in the Orange Book, how any generic competitor would address such patents, whether we would sue on any such patents, or the outcome of any such suit.

We may not be successful in securing or maintaining proprietary patent protection for products and technologies we develop or license. Moreover, if any of our owned or in-licensed patents that are listed in the Orange Book are successfully challenged by way of a Paragraph IV certification and subsequent litigation, the affected product could immediately face generic competition and its sales would likely decline rapidly and materially.

We may seek orphan drug designation for certain future drug candidates, but we may be unable to obtain such designations or to maintain the benefits associated with orphan drug designation, including market exclusivity, which may cause our revenue, if any, to be reduced.

We may pursue orphan drug designation for certain of our future drug candidates. In the European Union, the EMA's Committee for Orphan Medicinal Products, or COMP, grants orphan drug designation to promote the development of products that are intended for the diagnosis, prevention, or treatment of a life-threatening or chronically debilitating condition affecting not more than five in 10,000 persons in the European Union. Additionally, designation is granted for products intended for the diagnosis, prevention, or treatment of a life-threatening, seriously debilitating or serious and

chronic condition when, without incentives, it is unlikely that sales of the drug in the European Union would be sufficient to justify the necessary investment in developing the drug or biological product or where there is no satisfactory method of diagnosis, prevention, or treatment, or, if such a method exists, the medicine must be of significant benefit to those affected by the condition. Under the Orphan Drug Act, the FDA may designate a drug or biologic product as an orphan drug if it is intended to treat a rare disease or condition, defined as a patient population of fewer than 200,000 in the United States, or a patient population greater than 200,000 in the United States where there is no reasonable expectation that the cost of developing the drug will be recovered from sales in the United States.

In the European Union, orphan drug designation entitles a party to financial incentives such as reduction of fees or fee waivers and ten years of market exclusivity following drug or biological product approval. This period may be reduced to six years if the orphan drug designation criteria are no longer met, including where it is shown that the product is sufficiently profitable not to justify maintenance of market exclusivity. In the United States, orphan drug designation entitles a party to financial incentives such as opportunities for grant funding towards clinical trial costs, tax advantages, and application fee waivers. In addition, if a product receives the first FDA approval for the indication for which it has orphan designation, the product is entitled to orphan drug exclusivity, which means the FDA may not approve any other application to market the same drug for the same indication for a period of seven years, except in limited circumstances, such as a showing of clinical superiority over the product with orphan exclusivity or where the manufacturer is unable to assure sufficient product quantity for the orphan patient population.

Even if we obtain orphan drug designation, we may not be the first to obtain marketing approval for any particular orphan indication due to the uncertainties associated with developing pharmaceutical products. Further, even if we obtain orphan drug exclusivity for a drug candidate, that exclusivity may not effectively protect the product from competition because different drugs with different active moieties can be approved for the same condition. Orphan drug designations are not in any way indicative of a drug's likelihood of receiving the final marketing authorization from FDA. The FDA does not evaluate a drug candidate's safety and effectiveness using the same standard as it would when reviewing a drug candidate's safety and effectiveness prior to granting final marketing approvals. The FDA may grant orphan drug designations to multiple drugs intended for the same indication. Even after an orphan drug is approved, the EMA or FDA can subsequently approve the same drug with the same active moiety for the same condition if the EMA or FDA concludes that the later drug is clinically superior in that it is safer, more effective, or makes a major contribution to patient care. Orphan drug designation neither shortens the development time or regulatory review time of a drug or biologic nor gives the drug or biologic any advantage in the regulatory review or approval process.

Enacted and future healthcare legislation may increase the difficulty and cost for us to obtain marketing approval of and commercialize our drug candidates and may affect the prices we may set.

In the United States, the EU and other jurisdictions, there have been, and we expect there will continue to be, a number of legislative and regulatory changes and proposed changes to the healthcare system that could affect our future results of operations. In particular, there have been and continue to be a number of initiatives at the U.S. federal and state levels that seek to reduce healthcare costs and improve the quality of healthcare. For example, in March 2010, the Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act, or collectively the Affordable Care Act, was enacted, which substantially changed the way healthcare is financed by both governmental and private insurers. Among the provisions of the Affordable Care Act, those of greatest importance to the pharmaceutical and biotechnology industries include the following:

Since its enactment, there have been judicial and Congressional challenges to certain aspects of the Affordable Care Act, and we expect there will be additional challenges and amendments to the Affordable Care Act in the future. The current presidential administration and Congress will likely continue to seek to modify, repeal, or otherwise invalidate all, or certain provisions of, the Affordable Care Act. It is uncertain the extent to which any such changes may impact our business or financial condition.

In addition, other legislative changes have been proposed and adopted in the United States since the Affordable Care Act was enacted. In August 2011, the Budget Control Act of 2011, among other things, led to aggregate reductions of Medicare payments to providers of 2% per fiscal year. These reductions went into effect in April 2013 and, due to subsequent legislative amendments to the statute, will remain in effect through 2025 unless additional action is taken by Congress. In January 2013, the American Taxpayer Relief Act of 2012 was signed into law, which, among other things, further reduced Medicare payments to several types of providers, including hospitals, imaging centers and cancer treatment centers, and increased the statute of limitations period for the government to recover overpayments to providers from three to five years.

Individual states in the United States have also become increasingly aggressive in passing legislation and implementing regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing. Legally-mandated price controls on payment amounts by third-party payors or other restrictions could harm our business, results of operations, financial condition and prospects. In addition, regional healthcare authorities and individual hospitals are increasingly using bidding procedures to determine what pharmaceutical products and which suppliers will be included in their prescription drug and other healthcare programs. This could reduce the ultimate demand for our drug candidates or put pressure on our product pricing. Moreover, payment methodologies may be subject to changes in healthcare legislation and regulatory initiatives. For example, CMS may develop new payment and delivery models, such as bundled payment models. In addition, recently there has been heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed products.

In the EU, similar political, economic and regulatory developments may affect our ability to profitably commercialize our drug candidates, if approved. In addition to continuing pressure on prices and cost containment measures, legislative developments at the EU or member state level may result in significant additional requirements or obstacles that may increase our operating costs. The delivery of healthcare in the EU, including the establishment and operation of health services and the pricing and reimbursement of medicines, is almost exclusively a matter for national, rather than EU, law and policy. National governments and health service providers have different priorities and approaches to the delivery of health care and the pricing and reimbursement of products in that context. In general, however, the healthcare budgetary constraints in most EU member states have resulted in restrictions on the pricing and reimbursement of medicines by relevant health service providers. Generally, pricing negotiations with governmental authorities can take many months after the receipt of regulatory approval and product launch. In some EU Member States, such as in France, we may be required to conduct a clinical trial that compares the cost-effectiveness of our products candidates with available therapies in order to obtain favorable reimbursement for the indications sought or pricing approval. Should reimbursement for our drug candidates be unavailable in any country in which we seek reimbursement, or be limited or subject to additional clinical trials, or should pricing be set at unsatisfactory levels, then this might have an impact on our operating results. Coupled with ever-increasing EU and national regulatory burdens on those wishing to develop and market products, this could prevent or delay marketing approval of our drug candidates, restrict or regulate post-approval activities and affect our ability to commercialize our drug candidates, if approved. In markets outside of the United States and EU, reimbursement and healthcare payment systems vary significantly by country, and many countries have instituted price ceilings on specific products and therapies.

We cannot predict the likelihood, nature or extent of government regulation that may arise from future legislation or administrative action in the United States, the EU or any other jurisdiction. If we or any third parties we may engage are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies, or if we or such third parties are not able to maintain regulatory compliance, our drug candidates may lose any regulatory approval that may have been obtained and we may not achieve or sustain profitability.

Our business operations and current and future relationships with investigators, healthcare professionals, consultants, third-party payors, patient organizations and customers will be subject to applicable healthcare regulatory laws, which could expose us to penalties.

Our business operations and current and future arrangements with investigators, healthcare professionals, consultants, third-party payors, patient organizations and customers, may expose us to

broadly applicable fraud and abuse and other healthcare laws and regulations. These laws may constrain the business or financial arrangements and relationships through which we conduct our operations, including how we research, market, sell and distribute our drug candidates, if approved. Such laws include:

Ensuring that our internal operations and future business arrangements with third parties comply with applicable healthcare laws and regulations will involve substantial costs. It is possible that governmental authorities will conclude that our business practices do not comply with current or future statutes, regulations, agency guidance or case law involving applicable fraud and abuse or other healthcare laws and regulations. If our operations are found to be in violation of any of the laws described above or any other governmental laws and regulations that may apply to us, we may be subject to significant penalties, including civil, criminal and administrative penalties, damages, fines, exclusion from government-funded healthcare programs, such as Medicare and Medicaid or similar programs in other countries or jurisdictions, disgorgement, individual imprisonment, contractual damages, reputational harm, diminished profits and the curtailment or restructuring of our operations. Further, defending against any such actions can be costly, time-consuming and may require significant personnel resources. Therefore, even if we are successful in defending against any such actions that may be brought against us, our business may be impaired.

In addition, considering that our activity involves the processing of EU personal data, our business activities are also subject to GDPR and other national data protection laws with respect to this EU data, which implies that we must implement significant and continuous efforts to comply with these data protection regulations. The GDPR has allowed EU Member States to introduce additional requirements for the processing of health data. This means the Company must comply with both EU as well as national laws in order to conduct the Company's activities as regards patient data. In particular, our GDPR compliance's business involves the precise identification of our data processing operations and the risks incurred, the implementation of an organization of our internal processes and the establishment of a documentation relating to our compliance. Our GDPR compliance also means being very aware to the fulfilment of our third-party contractors's obligations and their own GPDR compliance, which requires us to impose strict contractual provisions to our third-party contractors as processors. Moreover, the transfer of data from the EU to our U.S. entities or others U.S. companies must be subject to a valid legal mechanism for the lawful transfer of data, which may have to require some of our third-party contractors who process personal data to take additional privacy and security measures. Non-compliance could cause us to incur potential disruption and expense related to our business processes. Any violations of these laws and regulations could also result in substantial penalties and could materially damage our reputation.

We are subject to U.S. and foreign anti-corruption and anti-money laundering laws with respect to our operations and non-compliance with such laws can subject us to criminal and/or civil liability and harm our business.

We are subject to the U.S. Foreign Corrupt Practices Act of 1977, as amended, or the FCPA, the U.S. domestic bribery statute contained in 18 U.S.C. § 201, the U.S. Travel Act, the USA PATRIOT Act, and possibly other state and national anti-bribery and anti-money laundering laws in countries in which we conduct activities. Anti-corruption laws are interpreted broadly and prohibit companies and their employees, agents, third-party intermediaries, joint venture partners and collaborators from authorizing, promising, offering, or providing, directly or indirectly, improper payments or benefits to recipients in the public or private sector. We engage third-party investigators, CROs, and other consultants to design and perform preclinical studies of our drug candidates, and will do the same for any clinical trials. Also, once a drug candidate has been approved and commercialized, we may engage third-party intermediaries to promote and sell our products abroad and/or to obtain necessary permits, licenses, and other regulatory approvals. We or our third-party intermediaries may have direct or indirect interactions with officials and employees of government agencies or state-owned or affiliated entities. We can be held liable for the corrupt or other illegal activities of these third-party intermediaries, our employees, representatives, contractors, collaborators, partners, and agents, even if we do not explicitly authorize or have actual knowledge of such activities.

Noncompliance with anti-corruption and anti-money laundering laws could subject us to whistleblower complaints, investigations, sanctions, settlements, prosecution, other enforcement actions, disgorgement of rofits, significant fines, damages, other civil and criminal penalties or injunctions, suspension and/or debarment from contracting with certain persons, the loss of export privileges, reputational harm, adverse media coverage, and other collateral consequences. If any subpoenas, investigations, or other enforcement actions are launched, or governmental or other sanctions are imposed, or if we do not prevail in any possible civil or criminal litigation, our business, results of operations and financial condition could be materially harmed. In addition, responding to any action will likely result in a materially significant diversion of management's attention and resources and significant defense and compliance costs and other professional fees. In certain cases, enforcement authorities may even cause us to appoint an independent compliance monitor which can result in added costs and administrative burdens.

Our failure to maintain certain tax benefits applicable to French technology companies may adversely affect our results of operations.

As a French biotechnology company, we have benefited from certain tax advantages, including, for example, the research tax credit (Crédit d'Impôt Recherche), or CIR. The CIR is a French tax credit aimed at stimulating research and development. The CIR can be offset against French corporate income tax due and the portion in excess (if any) may be refunded at the end of a three fiscal-year period (or, sooner, for smaller companies such as ours). The CIR is calculated based on our claimed amount of eligible research and development expenditures in France and represented €2.5 million and €3.1 million as of December 31, 2017 and 2018, respectively. The French tax authority with the assistance of the Research and Technology Ministry may audit each research and development program in respect of which a CIR benefit has been claimed and assess whether such program qualifies in its view for the CIR benefit. The French tax authorities may challenge our eligibility to, or our calculation of certain tax reductions and/or deductions in respect of our research and development activities and, should the French tax authorities be successful, we may be liable for additional corporate income tax, and penalties and interest related thereto, or we may not obtain the refunds for which we have applied, which could have a significant impact on our results of operations and future cash flows. Furthermore, if the French Parliament decides to eliminate, or reduce the scope or the rate of, the CIR benefit, either of which it could decide to do at any time, our results of operations could be adversely affected.

Recent U.S. tax legislation and future changes to applicable U.S. tax laws and regulations may have an adverse effect on our business, financial condition and results of operations.

Changes in laws and policy relating to taxes may have an adverse effect on our business, financial condition and results of operations. For example, the U.S. government recently enacted significant tax reform, and certain provisions of the new law may adversely affect us. Changes include, but are not limited to, a federal corporate tax rate decrease to 21% for tax years beginning after December 31, 2017, a reduction to the maximum deduction allowed for net operating losses generated in tax years after December 31, 2017, eliminating carrybacks of net operating losses, and providing for indefinite carryforwards for losses generated in tax years after December 31, 2017. The legislation is unclear in many respects and could be subject to potential amendments and technical corrections, and will be subject to interpretations and implementing regulations by the Treasury and Internal Revenue Service, or IRS, any of which could mitigate or increase certain adverse effects of the legislation. In addition, it is unclear how these U.S. federal income tax changes will affect state and local taxation. Generally, future changes in applicable U.S. tax laws and regulations, or their interpretation and application could have an adverse effect on our business, financial conditions and results of operations.

Risks Related to the Global Offering, Ownership of our Ordinary Shares and the ADSs and Our Status as a Non-U.S. Company with Foreign Private Issuer Status

The requirements of being a U.S. public company may strain our resources, divert management's attention and affect our ability to attract and retain executive management and qualified board members.

As a U.S. public company following the global offering, we will incur legal, accounting, and other expenses that we did not previously incur. We will be subject to the Exchange Act, including the reporting requirements thereunder, the Sarbanes-Oxley Act, the Dodd-Frank Wall Street Reform and Consumer Protection Act, the Nasdaq listing requirements and other applicable securities rules and regulations. Compliance with these rules and regulations will increase our legal and financial compliance costs, make some activities more difficult, time-consuming or costly and increase demand on our systems and resources, particularly after we are no longer an "emerging growth company" and/or a foreign private issuer. For example, for so long as we remain a foreign private issuer, we will not be required to file with the SEC quarterly reports with respect to our business and results of operations, which are required to be made by domestic issuers pursuant to the Exchange Act.

Pursuant to Section 404 of the Sarbanes-Oxley Act, or Section 404, we will be required to furnish a report by our management on our internal control over financial reporting, including an attestation report on internal control over financial reporting issued by our independent registered public accounting firm. However, while we remain an emerging growth company, we will not be required to include this attestation report on internal control over financial reporting issued by our independent registered public accounting firm. When our independent registered public accounting firm is required to undertake an assessment of our internal control over financial reporting, the cost of complying with Section 404 will significantly increase and management's attention may be diverted from other business concerns, which could adversely affect our business and results of operations. We may need to hire more employees in the future or engage outside consultants to comply with these requirements, which will further increase our cost and expense. If we fail to implement the requirements of Section 404 in the required timeframe, we may be subject to sanctions or investigations by regulatory authorities, including the SEC and the Nasdaq. Furthermore, if we are unable to conclude that our internal control over financial reporting is effective, we could lose investor confidence in the accuracy and completeness of our financial reports, the market price of the ADSs and our ordinary shares could decline, and we could be subject to sanctions or investigations by regulatory authorities. Failure to implement or maintain effective internal control systems required of public companies could also restrict our future access to the capital markets.

In addition, enhanced legal and regulatory regimes and heightened standards relating to corporate governance and disclosure for public companies result in increased legal and financial compliance costs and make some activities more time consuming. Further, being a U.S. public company and a French public company will have an impact on disclosure of information and require compliance with two sets of applicable rules. This could result in uncertainty regarding compliance matters and higher costs necessitated by legal analysis of dual legal regimes, ongoing revisions to disclosure and adherence to heightened governance practices.

There has been no public market for the ADSs prior to the global offering, and an active market may not develop in which investors can resell the ADSs.

Prior to the global offering, there has been no public market for the ADSs. We cannot predict the extent to which an active trading market for the ADSs will develop or be sustained after the global offering, or how the development of such a market might affect the market price for the ADSs. The initial public offering price of the ADSs in the global offering has been agreed upon between us and the underwriters based on a number of factors, including the trading price of our ordinary shares on the Euronext Growth Paris as of the date of this prospectus, as well as certain market conditions in

effect at the time of the global offering, which may not be indicative of the price at which the ADSs will trade following completion of the global offering. Investors may not be able to sell their ADSs at or above the initial public offering price. In addition, investors may not be able to successfully withdraw the underlying ordinary shares of the ADSs for the reasons discussed under the risk factor titled "You may not be able to withdraw the underlying ordinary shares of the ADSs" described below. In connection with any withdrawal of any of our ordinary shares represented by ADSs, the ADSs will be surrendered to the depositary. Unless additional ADSs are issued, the effect of such transactions will be to reduce the number of outstanding ADSs and, if a significant number of transactions are effected, to reduce the liquidity of the ADSs. See "Description of American Depositary Shares."

The market price of our equity securities may be volatile, and purchasers of the ADSs or ordinary shares could incur substantial losses.

The market price for the ADSs and ordinary shares may be volatile. The stock market in general and the market for biotechnology companies in particular have experienced extreme volatility that has often been unrelated to the operating performance of particular companies. As a result of this volatility, investors may not be able to sell the ADSs or ordinary shares at or above the price originally paid for the security. The market price for our securities may be influenced by many factors, including:

These and other market and industry factors may cause the market price and demand for our securities to fluctuate substantially, regardless of our actual operating performance, which may limit or prevent investors from readily selling the ADSs and ordinary shares and may otherwise negatively affect the liquidity of the trading market for the ADSs and ordinary shares.

We may be exposed to significant foreign exchange risk. Exchange rate fluctuations may adversely affect the foreign currency value of the ADSs.

We incur portions of our expenses and may in the future derive revenues in currencies other than the euro, in particular, the U.S. dollar. As a result, we are exposed to foreign currency exchange risk as our results of operations and cash flows are subject to fluctuations in foreign currency exchange rates. We currently do not engage in hedging transactions to protect against uncertainty in future exchange rates between particular foreign currencies and the euro. Therefore, for example, an increase in the value of the euro against the U.S. dollar could be expected to have a negative impact on our revenue and earnings growth as U.S. dollar revenue and earnings, if any, would be translated into euros at a reduced value. We cannot predict the impact of foreign currency fluctuations, and foreign currency fluctuations in the future may adversely affect our financial condition, results of operations and cash flows. The ADSs will be quoted in U.S. dollars on the Nasdaq Capital Market and our ordinary shares are trading in euros on the Euronext Growth Paris. Our financial statements are prepared in euros. Fluctuations in the exchange rate between euros and the U.S. dollar will affect, among other matters, the U.S. dollar value and the euro value of our ordinary shares and ADSs.

If we do not achieve our projected development and commercialization goals in the timeframes we announce and expect, our business will be harmed and the price of our securities could decline as a result.

We sometimes estimate for planning purposes the timing of the accomplishment of various scientific, clinical, regulatory and other product development objectives. These milestones may include our expectations regarding the commencement or completion of scientific studies, clinical trials, the submission of regulatory filings, or commercialization objectives. From time to time, we may publicly announce the expected timing of some of these milestones, such as the completion of an ongoing clinical trial, the initiation of other clinical programs, receipt of marketing approval, or a commercial launch of a product. The achievement of many of these milestones may be outside of our control. All of these milestones are based on a variety of assumptions which may cause the timing of achievement of the milestones to vary considerably from our estimates, including:

If we fail to achieve announced milestones in the timeframes we expect, the commercialization of our drug candidates may be delayed, our business and results of operations may be harmed, and the trading price of our securities may decline as a result.

After the completion of the global offering, we may be at an increased risk of securities class action litigation.

Historically, securities class action litigation has often been brought against a company following a decline in the market price of its securities. This risk is especially relevant for us because biotechnology and biopharmaceutical companies have experienced significant share price volatility in recent years. If we were to be sued, it could result in substantial costs and a diversion of management's attention and resources, which could harm our business.

We have broad discretion in the use of the net proceeds from the global offering and may use them in ways with which you do not agree and in ways that may not increase the value of your investment.

Our management will have broad discretion in the application of the net proceeds that we receive from the global offering. We may spend or invest these proceeds in a way with which our shareholders and ADS holders disagree. The failure by our management to apply these funds effectively could harm our business and financial condition. Pending their use, we may invest the net proceeds from the global offering in a manner that does not produce income or that loses value. These investments may not yield a favorable return to our investors.

If securities or industry analysts do not publish research or publish inaccurate or unfavorable research about our business, the price of our ordinary shares and ADSs and their trading volume could decline.

The trading market for the ADSs and ordinary shares depends in part on the research and reports that securities or industry analysts publish about us or our business. If no or few securities or industry analysts cover our company, the trading price for the ADSs and ordinary shares would be negatively impacted. If one or more of the analysts who covers us downgrades our equity securities or publishes incorrect or unfavorable research about our business, the price of our securities would likely decline. If one or more of these analysts ceases coverage of our company or fails to publish reports on us regularly, or downgrades our securities, demand for our securities could decrease, which could cause the price of the ADSs and ordinary shares or their trading volume to decline.

We do not currently intend to pay dividends on the ADSs or ordinary shares and, consequently, your ability to achieve a return on your investment will depend on appreciation in the price of the ADSs and ordinary shares. In addition, French law may limit the amount of dividends we are able to distribute.

We have never declared or paid any cash dividends on our ordinary shares and do not currently intend to do so for the foreseeable future. We currently intend to invest our future earnings, if any, to fund our growth. Therefore, you are not likely to receive any dividends on the ADSs or ordinary shares for the foreseeable future and the success of an investment in these securities will depend upon any future appreciation in their value. Consequently, investors may need to sell all or part of their holdings of ADSs or ordinary shares after price appreciation, which may never occur, as the only way to realize any future gains on their investment. There is no guarantee that the ADSs or ordinary shares will appreciate in value or even maintain the price at which investors have purchased them. Investors seeking cash dividends should not purchase the ADSs or ordinary shares.

Further, under French law, the determination of whether we have been sufficiently profitable to pay dividends is made on the basis of our statutory financial statements prepared and presented in accordance with accounting standards applicable in France. Please see the section of this prospectus titled "Description of Share Capital—Key Provisions of Our Articles of Incorporation and Articles of Association—Rights, Preferences and Restrictions Attaching to Ordinary Shares" for further details on

the limitations on our ability to declare and pay dividends imposed by Article 34 of our By-laws and "Material United States Federal Income Tax and French Considerations" the taxes that may be imposed on you if we elect to pay a dividend. Therefore, we may be more restricted in our ability to declare dividends than companies not based in France.

In addition, exchange rate fluctuations may affect the amount of euros that we are able to distribute, and the amount in U.S. dollars that our shareholders receive upon the payment of cash dividends or other distributions we declare and pay in euros, if any. These factors could harm the value of the ADSs, and, in turn, the U.S. dollar proceeds that holders receive from the sale of the ADSs.

If you purchase ADSs or ordinary shares in the global offering, you will experience substantial and immediate dilution.

If you purchase ADSs or ordinary shares in the global offering, you will experience substantial and immediate dilution of $4.93 per ADS and €0.44 per ordinary share in net tangible book value as of March 31, 2019, after giving effect to the global offering at the assumed offering price of $8.00 per ADS in the ADS offering, which is the midpoint of the price range set forth on the cover page of this prospectus, corresponding to €0.71 per ordinary share in the ordinary share offering (assuming an exchange rate of €0.89 per U.S. dollar), because the price that you pay will be substantially greater than the net tangible book value per ADS or ordinary share that you acquire. You will experience additional dilution upon exercise of any outstanding warrants to purchase ordinary shares or if we otherwise issue additional ADSs or ordinary shares below the offering price. For a further description of the dilution that you will experience immediately after the global offering, see the section of this prospectus titled "Dilution."

Future sales, or the possibility of future sales, of a substantial number of the ADSs or ordinary shares could adversely affect the price of the ADSs and ordinary shares.

Future sales of a substantial number of the ADSs or ordinary shares, or the perception that such sales will occur, could cause a decline in the market price of the ADSs and/or ordinary shares. Based upon the number of shares outstanding as of March 31, 2019, after giving effect to the closing of the global offering, we will have 26,588,413 ordinary shares outstanding (including ordinary shares in the form of ADSs), assuming Wainwright does not exercise its option to purchase up to an additional 1,968,750 ordinary shares (to be delivered in the form of an aggregate of 196,875 ADSs) from us in the global offering. ADSs and ordinary shares sold in the global offering may be resold in the public market immediately without restriction, unless purchased by our affiliates. If ADS or ordinary share holders sell substantial amounts of ADSs and/or ordinary shares in the public market, or the market perceives that such sales may occur, the market price of the ADSs and ordinary shares and our ability to raise capital through an issuance of equity securities in the future could be adversely affected.

Approximately 6.0% of our ordinary shares outstanding after the global offering will be subject to lock-up agreements described in the "Underwriting" section of this prospectus. If, after the expiration of such lock-up agreements, these shareholders sell substantial amounts of our ordinary shares in the public market, or the market perceives that such sales may occur, the market price of our ordinary shares and the ADSs could be adversely affected.

The rights of shareholders in companies subject to French corporate law differ in material respects from the rights of shareholders of corporations incorporated in the United States.

We are a French company with limited liability. Our corporate affairs are governed by our bylaws and by the laws governing companies incorporated in France. The rights of shareholders and the responsibilities of members of our board of directors are in many ways different from the rights and obligations of shareholders in companies governed by the laws of U.S. jurisdictions. For example, in the

performance of its duties, our board of directors is required by French law to consider the interests of our company, rather than solely our shareholders and/or creditors. It is possible that some of these parties will have interests that are different from, or in addition to, your interests as a holder of ADSs.

U.S. investors may have difficulty enforcing civil liabilities against our company and directors and senior management and the experts named in this prospectus.

Certain members of our board of directors and senior management and certain experts named in this prospectus are non-residents of the United States, and all or a substantial portion of our assets and the assets of such persons are located outside the United States. As a result, it may not be possible to serve process on such persons or us in the United States or to enforce judgments obtained in U.S. courts against them or us based on civil liability provisions of the securities laws of the United States. Additionally, it may be difficult to assert U.S. securities law claims in actions originally instituted outside of the United States. Foreign courts may refuse to hear a U.S. securities law claim because foreign courts may not be the most appropriate forums in which to bring such a claim. Even if a foreign court agrees to hear a claim, it may determine that the law of the jurisdiction in which the foreign court resides, and not U.S. law, is applicable to the claim. Further, if U.S. law is found to be applicable, the content of applicable U.S. law must be proved as a fact, which can be a time-consuming and costly process, and certain matters of procedure would still be governed by the law of the jurisdiction in which the foreign court resides. In particular, there is some doubt as to whether French courts would recognize and enforce certain civil liabilities under U.S. securities laws in original actions or judgments of U.S. courts based upon these civil liability provisions. In addition, awards of punitive damages in actions brought in the United States or elsewhere may be unenforceable in France. An award for monetary damages under the U.S. securities laws would be considered punitive if it does not seek to compensate the claimant for loss or damage suffered but is intended to punish the defendant. French law provides that a shareholder, or a group of shareholders, may initiate a legal action to seek indemnification from the directors of a corporation in the corporation's interest if it fails to bring such legal action itself. If so, any damages awarded by the court are paid to the corporation and any legal fees relating to such action may be borne by the relevant shareholder or the group of shareholders.

The enforceability of any judgment in France will depend on the particular facts of the case as well as the laws and treaties in effect at the time. The United States and France do not currently have a treaty providing for recognition and enforcement of judgments (other than arbitration awards) in civil and commercial matters. See the section of this prospectus titled "Enforcement of Civil Liabilities."

ADSs holders may not be entitled to a jury trial with respect to claims arising under the deposit agreement, which could result in less favorable outcomes to the plaintiff(s) in any such action.

The deposit agreement governing the ADSs representing our ordinary shares provides that, to the fullest extent permitted by law, ADS holders waive the right to a jury trial of any claim they may have against us or the depositary arising out of or relating to our shares, the ADSs or the deposit agreement, including any claim under the U.S. federal securities laws.

If we or the depositary opposed a jury trial demand based on the waiver, the court would determine whether the waiver was enforceable based on the facts and circumstances of that case in accordance with the applicable state and federal law. To our knowledge, the enforceability of a contractual pre-dispute jury trial waiver in connection with claims arising under the federal securities laws has not been finally adjudicated by the United States Supreme Court. However, we believe that a contractual pre-dispute jury trial waiver provision is generally enforceable, including under the laws of the State of New York, which govern the deposit agreement, by a federal or state court in the City of New York, which has non-exclusive jurisdiction over matters arising under the deposit agreement. In determining whether to enforce a contractual pre-dispute jury trial waiver provision, courts will generally consider whether a party knowingly, intelligently and voluntarily waived the right to a jury

trial. We believe that this is the case with respect to the deposit agreement and the ADSs. In addition, New York courts will not enforce a jury trial waiver provision in order to bar a viable setoff or counterclaim sounding in fraud or one which is based upon a creditor's negligence in failing to liquidate collateral upon a guarantor's demand, or in the case of an intentional tort claim (as opposed to a contract dispute), none of which we believe are applicable in the case of the deposit agreement or the ADSs. It is advisable that you consult legal counsel regarding the jury waiver provision before entering into the deposit agreement.

If you or any other holders or beneficial owners of ADSs bring a claim against us or the depositary in connection with matters arising under the deposit agreement or the ADSs, including claims under federal securities laws, you or such other holder or beneficial owner may not be entitled to a jury trial with respect to such claims, which may have the effect of limiting and discouraging lawsuits against us and/or the depositary. If a lawsuit is brought against us and/or the depositary under the deposit agreement, it may be heard only by a judge or justice of the applicable trial court, which would be conducted according to different civil procedures and may result in different outcomes than a trial by jury would have had, including results that could be less favorable to the plaintiff(s) in any such action.

Nevertheless, if this jury trial waiver provision is not permitted by applicable law, an action could proceed under the terms of the deposit agreement with a jury trial. No condition, stipulation or provision of the deposit agreement or ADSs serves as a waiver by any holder or beneficial owner of ADSs or by us or the depositary of compliance with any substantive provision of the U.S. federal securities laws and the rules and regulations promulgated thereunder. By agreeing to the jury trial waiver provision in the deposit agreement, investors will not be deemed to have waived our compliance with or the depositary's compliance with the federal securities laws and the rules and regulations promulgated thereunder.

Our Articles of Association and By-laws and French corporate law contain provisions that may delay or discourage a takeover attempt.

Provisions contained in our Articles of Association and/or French corporate law could make it more difficult for a third party to acquire us, even if doing so might be beneficial to our shareholders. In addition, provisions of our bylaws impose various procedural and other requirements, which could make it more difficult for shareholders to effect certain corporate actions. These provisions include the following:

You may not be able to exercise your right to vote the ordinary shares underlying your ADSs.

Holders of ADSs may exercise voting rights with respect to the ordinary shares represented by the ADSs only in accordance with the provisions of the deposit agreement. The deposit agreement provides that, upon receipt of notice of any meeting of holders of our ordinary shares, the depositary will fix a record date for the determination of ADS holders who shall be entitled to give instructions for the exercise of voting rights. Upon timely receipt of notice from us, if we so request, the depositary shall distribute to the holders as of the record date (1) the notice of the meeting or solicitation of consent or

proxy sent by us and (2) a statement as to the manner in which instructions may be given by the holders.

Purchasers of ADSs may instruct the depositary of the ADSs to vote the ordinary shares underlying their ADSs. Otherwise, purchasers of ADSs will not be able to exercise voting rights unless they withdraw the ordinary shares underlying the ADSs they hold. However, a holder of ADSs may not know about the meeting far enough in advance to withdraw those ordinary shares. If we ask for a holder of ADSs' instructions, the depositary, upon timely notice from us, will distribute notice of the upcoming vote and arrange to deliver our voting materials to him or her. We cannot guarantee to any holder of ADSs that he or she will receive the voting materials in time to ensure that he or she can instruct the depositary to vote his or her ordinary shares or to withdraw his or her ordinary shares so that he or she can vote them. If the depositary does not receive timely voting instructions from a holder of ADSs, it may give a proxy to a person designated by us to vote the ordinary shares underlying his or her ADSs. In addition, the depositary and its agents are not responsible for failing to carry out voting instructions or for the manner of carrying out voting instructions. This means that a holder of ADSs may not be able to exercise his or her right to vote, and there may be nothing he or she can do if the ordinary shares underlying the ADSs are not voted as he or she requested.

A holder of ADSs will not be treated as one of our shareholders and will not have direct shareholder rights. French law governs our shareholder rights. The depositary will be the holder of the ordinary shares underlying ADSs held by purchasers of ADSs in the global offering. Purchasers of ADSs will have ADS holder rights. The deposit agreement among us, the depositary and purchasers of ADSs in the global offering, as an ADS holder, and all other persons directly and indirectly holding ADSs, sets out ADS holder rights, as well as the rights and obligations of the depositary.

The right as a holder of ADSs to participate in any future preferential subscription rights or to elect to receive dividends in shares may be limited, which may cause dilution to the holdings of purchasers of ADSs in the global offering.

According to French law, if we issue additional securities for cash, current shareholders will have preferential subscription rights for these securities on a pro rata basis unless they waive those rights at an extraordinary meeting of our shareholders (by a two-thirds majority vote) or individually by each shareholder. However, ADS holders in the United States will not be entitled to exercise or sell such rights unless we register the rights and the securities to which the rights relate under the Securities Act or an exemption from the registration requirements is available. In addition, the deposit agreement provides that the depositary will not make rights available to purchasers of ADSs unless the distribution to ADS holders of both the rights and any related securities are either registered under the Securities Act or exempted from registration under the Securities Act. Further, if we offer holders of our ordinary shares the option to receive dividends in either cash or shares, under the deposit agreement the depositary may require satisfactory assurances from us that extending the offer to holders of ADSs does not require registration of any securities under the Securities Act before making the option available to holders of ADSs. We are under no obligation to file a registration statement with respect to any such rights or securities or to endeavor to cause such a registration statement to be declared effective. Moreover, we may not be able to establish an exemption from registration under the Securities Act. Accordingly, ADS holders may be unable to participate in our rights offerings or to elect to receive dividends in shares and may experience dilution in their holdings. In addition, if the depositary is unable to sell rights that are not exercised or not distributed or if the sale is not lawful or reasonably practicable, it will allow the rights to lapse, in which case you will receive no value for these rights.

Purchasers of ADSs may be subject to limitations on the transfer of their ADSs and the withdrawal of the underlying ordinary shares.

ADSs, which may be evidenced by ADRs, are transferable on the books of the depositary. However, the depositary may close its books at any time or from time to time when it deems expedient in connection with the performance of its duties. The depositary may refuse to deliver, transfer or register transfers of ADSs generally when our books or the books of the depositary are closed, or at any time if we or the depositary think it is advisable to do so because of any requirement of law, government or governmental body, or under any provision of the deposit agreement, or for any other reason subject to a holder of ADSs' right to cancel his or her ADSs and withdraw the underlying ordinary shares. Temporary delays in the cancellation of ADSs and withdrawal of the underlying ordinary shares may arise because the depositary has closed its transfer books or we have closed our transfer books, the transfer of ordinary shares is blocked to permit voting at a shareholders' meeting or we are paying a dividend on our ordinary shares. In addition, a holder of ADSs may not be able to cancel his or her ADSs and withdraw the underlying ordinary shares when he or she owes money for fees, taxes and similar charges and when it is necessary to prohibit withdrawals in order to comply with any laws or governmental regulations that apply to ADSs or to the withdrawal of ordinary shares or other deposited securities. See the section of this prospectus titled "Description of American Depositary Shares."

As a foreign private issuer, we are exempt from a number of rules under the U.S. securities laws and are permitted to file less information with the SEC than a U.S. company. This may limit the information available to holders of ADSs.

We are a foreign private issuer, as defined in the SEC's rules and regulations and, consequently, we are not subject to all of the disclosure requirements applicable to public companies organized within the United States. For example, we are exempt from certain rules under the Exchange Act that regulate disclosure obligations and procedural requirements related to the solicitation of proxies, consents or authorizations applicable to a security registered under the Exchange Act, including the U.S. proxy rules under Section 14 of the Exchange Act. In addition, our officers and directors are exempt from the reporting and "short-swing" profit recovery provisions of Section 16 of the Exchange Act and related rules with respect to their purchases and sales of our securities. Moreover, while we currently make annual and semi-annual filings with respect to our listing on Euronext Paris and expect to file financial reports on an annual and semi-annual basis, we will not be required to file periodic reports and financial statements with the SEC as frequently or as promptly as U.S. public companies and will not be required to file quarterly reports on Form 10-Q or current reports on Form 8-K under the Exchange Act. Accordingly, there will be less publicly available information concerning our company than there would be if we were not a foreign private issuer.

As a foreign private issuer, we are permitted and we expect to follow certain home country practices in relation to corporate governance matters that differ significantly from Nasdaq's corporate governance standards. These practices may afford less protection to shareholders than they would enjoy if we complied fully with the corporate governance standards of Nasdaq.

As a foreign private issuer listed on the Nasdaq Capital Market, we will be subject to Nasdaq's corporate governance standards. However, Nasdaq rules provide that foreign private issuers are permitted to follow home country corporate governance practices in lieu of Nasdaq's corporate governance standards as long as notification is provided to Nasdaq of the intention to take advantage of such exemptions. We intend to rely on exemptions for foreign private issuers and follow French corporate governance practices in lieu of Nasdaq's corporate governance standards, to the extent possible. Certain corporate governance practices in France, which is our home country, may differ significantly from Nasdaq corporate governance standards. For example, as a French company, neither

the corporate laws of France nor our bylaws require a majority of our directors to be independent and we can include non-independent directors as members of our remuneration committee, and our independent directors are not required to hold regularly scheduled meetings at which only independent directors are present.

We are also exempt from provisions set forth in Nasdaq rules which require an issuer to provide in its bylaws for a generally applicable quorum, and that such quorum may not be less than one-third of the outstanding voting stock. Consistent with French law, our bylaws provide that a quorum requires the presence of shareholders having at least (1) 20% of the shares entitled to vote in the case of an ordinary shareholders' general meeting or at an extraordinary shareholders' general meeting where shareholders are voting on a capital increase by capitalization of reserves, profits or share premium, or (2) 25% of the shares entitled to vote in the case of any other extraordinary shareholders' general meeting.

As a foreign private issuer, we are required to comply with certain Nasdaq rules and Rule 10A-3 of the Exchange Act, relating to audit committee composition and responsibilities. Under French law, the audit committee may only have an advisory role and appointment of our statutory auditors, in particular, must be decided by the shareholders at our annual meeting.

Therefore, our shareholders may be afforded less protection than they otherwise would have under Nasdaq's corporate governance standards applicable to U.S. domestic issuers.

We may lose our foreign private issuer status in the future, which could result in significant additional cost and expense.

While we currently qualify as a foreign private issuer, the determination of foreign private issuer status is made annually on the last business day of an issuer's most recently completed second fiscal quarter and, accordingly, the next determination will be made with respect to us on June 30, 2019. In the future, we would lose our foreign private issuer status if we fail to meet the requirements necessary to maintain our foreign private issuer status as of the relevant determination date. We will remain a foreign private issuer until such time that more than 50% of our outstanding voting securities are held by U.S. residents and any of the following three circumstances applies: (i) the majority of our executive officers or directors are U.S. citizens or residents; (ii) more than 50% of our assets are located in the United States; or (iii) our business is administered principally in the United States.

The regulatory and compliance costs to us under U.S. securities laws as a U.S. domestic issuer may be significantly more than costs we incur as a foreign private issuer. If we are not a foreign private issuer, we will be required to file periodic reports and registration statements on U.S. domestic issuer forms with the SEC, which are more detailed and extensive in certain respects than the forms available to a foreign private issuer. We would be required under current SEC rules to prepare our financial statements in accordance with U.S. GAAP, rather than IFRS, and modify certain of our policies to comply with corporate governance practices associated with U.S. domestic issuers. Such conversion of our financial statements to U.S. GAAP would involve significant time and cost. In addition, we may lose our ability to rely upon exemptions from certain corporate governance requirements on U.S. stock exchanges that are available to foreign private issuers such as the ones described herein and exemptions from procedural requirements related to the solicitation of proxies.

We are an "emerging growth company" under the JOBS Act and will be able to avail ourselves of reduced disclosure requirements applicable to emerging growth companies, which could make the ADSs less attractive to investors.

We are an "emerging growth company," as defined in the U.S. Jumpstart Our Business Startups Act of 2012, or the JOBS Act, and we intend to take advantage of certain exemptions from various reporting requirements that are applicable to other public companies that are not "emerging growth

companies," including not being required to comply with the auditor attestation requirements of Section 404(b) of the Sarbanes-Oxley Act of 2002, or the Sarbanes-Oxley Act, and exemptions from the requirements of holding a nonbinding advisory vote on executive compensation and shareholder approval of any golden parachute payments not previously approved. In addition, Section 107 of the JOBS Act also provides that an emerging growth company can take advantage of the extended transition period provided in Section 7(a)(2)(B) of the U.S. Securities Act of 1933, as amended, or the Securities Act, for complying with new or revised accounting standards. We will not take advantage of the extended transition period provided under Section 7(a)(2)(B) of the Securities Act for complying with new or revised accounting standards. Since IFRS makes no distinction between public and private companies for purposes of compliance with new or revised accounting standards, the requirements for our compliance as a private company and as a public company are the same.

We cannot predict if investors will find the ADSs less attractive because we may rely on these exemptions. If some investors find the ADSs less attractive as a result, there may be a less active trading market for the ADSs and the price of the ADSs may be more volatile. We may take advantage of these reporting exemptions until we are no longer an emerging growth company. We will remain an emerging growth company until the earliest of (i) the last day of the fiscal year in which we have total annual gross revenue of $1.07 billion or more; (ii) the last day of our fiscal year following the fifth anniversary of the date of the completion of the global offering; (iii) the date on which we have issued more than $1.0 billion in nonconvertible debt during the previous three years; and (iv) the date on which we are deemed to be a large accelerated filer under the rules of the SEC.

U.S. holders of ADSs may suffer adverse tax consequences if we are characterized as a passive foreign investment company.

Generally, if, for any taxable year, at least 75% of our gross income is passive income, or at least 50% of the value of our assets is attributable to assets that produce passive income or are held for the production of passive income, including cash, we would be characterized as a passive foreign investment company, or PFIC, for U.S. federal income tax purposes. For purposes of these tests, passive income includes dividends, interest, and gains from the sale or exchange of investment property and rents and royalties other than rents and royalties which are received from unrelated parties in connection with the active conduct of a trade or business. If we are characterized as a PFIC, U.S. holders of the ADSs may suffer adverse tax consequences, including having gains realized on the sale of the ADSs treated as ordinary income, rather than capital gain, the loss of the preferential rate applicable to dividends received on the ADSs by individuals who are U.S. holders, and having interest charges apply to certain distributions by us and the proceeds of sales of the ADSs. See "Material United States Federal Income and French Tax Considerations—Material U.S. Federal Income Tax Considerations—Passive Foreign Investment Company Considerations."

Our status as a PFIC will depend on the composition of our income (including whether we receive certain non-refundable grants or subsidies and whether such amounts and reimbursements of certain refundable research tax credits will constitute gross income for purposes of the PFIC income test) and the composition and value of our assets, which may be determined in large part by reference to the market value of the ADSs and our ordinary shares, which may be volatile, from time to time. Our status may also depend, in part, on how quickly we utilize the cash proceeds from the global offering in our business. Based on the current composition of our gross income and assets and on reasonable assumptions and projections, we believe that it is more likely than not that we would not have been considered a PFIC for our taxable year ending December 31, 2018; however, there can be no assurance that we will or will not be considered a PFIC for any taxable year.

We must maintain effective internal control over financial reporting, and if we are unable to do so, the accuracy and timeliness of our financial reporting may be adversely affected, which could hurt our business, lessen investor confidence and depress the market price of our securities.

We must maintain effective internal control over financial reporting in order to accurately and timely report our results of operations and financial condition. In addition, as a public company listed in the United States, the Sarbanes-Oxley Act will require, among other things, that we assess the effectiveness of our internal control over financial reporting at the end of each fiscal year. We anticipate being first required to issue management's annual report on internal control over financial reporting, pursuant to Section 404 of the Sarbanes-Oxley Act, in connection with issuing our consolidated financial statements as of and for the year ending December 31, 2020 and the filing of our second annual report with the SEC.

The rules governing the standards that must be met for our management to assess our internal control over financial reporting pursuant to Section 404 of the Sarbanes-Oxley Act are complex and require significant documentation, testing and possible remediation. These stringent standards require that our audit committee be advised and regularly updated on management's review of internal control over financial reporting. We are in the process of designing, implementing, and testing the internal control over financial reporting required to comply with this obligation. This process is time-consuming, costly, and complicated. In addition, our independent registered public accounting firm will be required to attest to the effectiveness of our internal controls over financial reporting beginning with our annual report following the date on which we are no longer an "emerging growth company," which may be up to five fiscal years following the date of the global offering.

As noted elsewhere in this prospectus, Mr. Montigny, our Chief Operating Officer, who oversaw our financial operations as principal financial officer and principal accounting officer, has resigned from the Company. Mr. Schneiderman, who has served as Chief Financial Officer for Biophytis, Inc., our wholly-owned U.S. subsidiary, has expanded his role to include the financial operations for Biophytis S.A. as Chief Financial Officer for the Company. Mr. Montigny will remain with us until July 24, 2019 in order to ensure a smooth transition. While we will strive to reduce any negative impact of this change in management, the transition could result in disruptions to our operations, and could impact the effectiveness of our disclosure controls and procedures and our internal control over financial reporting. In addition, our management may not be able to effectively and timely implement controls and procedures that adequately respond to the increased regulatory compliance and reporting requirements that will be applicable to us as a public company listed in the United States. If we fail to staff our accounting and finance function adequately or maintain internal control over financial reporting adequate to meet the demands that will be placed upon us as a public company listed in the United States, our business and reputation may be harmed and the price of our ordinary shares and ADSs may decline. Furthermore, investor perceptions of us may be adversely affected, which could cause a decline in the market price of our securities.

This prospectus contains forward-looking statements that involve substantial risks and uncertainties. The forward-looking statements are contained principally in the sections of this prospectus titled "Prospectus Summary," "Risk Factors," "Management's Discussion and Analysis of Financial Condition and Results of Operations" and "Business." All statements, other than statements of historical facts, contained in this prospectus, including statements regarding our future results of operations and financial position, business strategy, prospective products, product approvals, research and development costs, timing and likelihood of success, plans and objectives of management for future operations, and future results of current and anticipated products, are forward-looking statements. These statements relate to future events or to our future financial performance and involve known and unknown risks, uncertainties and other factors which may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. The words "anticipate," "assume," "believe," "contemplate," "continue," "could," "estimate," "expect," "goal," "intend," "may," "might," "objective," "plan," "potential," "predict," "project," "positioned," "seek," "should," "target," "will," "would," or the negative of these terms or other similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These forward-looking statements are based on current expectations, estimates, forecasts and projections about our business and the industry in which we operate and management's beliefs and assumptions, are not guarantees of future performance or development and involve known and unknown risks, uncertainties and other factors. These forward-looking statements include statements regarding:

Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements we make. As a result, any or all of our forward-looking statements in this prospectus may turn out to be inaccurate. We have included important factors in the cautionary statements included in this prospectus, particularly in the section of this prospectus titled "Risk Factors," that we believe could cause actual results or events to differ materially from the forward-looking statements that we make. We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. Moreover, we operate in a highly competitive and rapidly changing environment in which new risks often emerge. It is not possible for our management to predict all risks, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements we may make. Our forward-looking statements do not reflect the potential impact of any future acquisitions, mergers, dispositions, joint ventures or investments we may make.

You should read this prospectus and the documents that we reference in this prospectus and have filed as exhibits to the registration statement of which this prospectus is a part completely and with the understanding that our actual future results may be materially different from what we expect. The forward-looking statements contained in this prospectus are made as of the date of this prospectus, and we do not assume any obligation to update any forward-looking statements except as required by applicable law.

We estimate that we will receive net proceeds from the global offering of approximately €6.8 million ($7.6 million), assuming a public offering price of $8.00 per ADS in the ADS offering, which is the midpoint of the price range set forth on the cover page of this prospectus, corresponding to €0.71 per ordinary share in the ordinary share offering (assuming an exchange rate of €0.89 per U.S. dollar), after deducting underwriting discounts and commissions and estimated offering expenses payable by us, and assuming no exercise of the underwriters' option to purchase an additional 1,968,750 ordinary shares (to be delivered in the form of an aggregate of 196,875 ADSs) from us in the global offering. If the underwriters exercise in full their option to purchase up to an additional 1,968,750 ordinary shares (to be delivered in the form of an aggregate of 196,875 ADSs), we estimate that we will receive net proceeds of approximately €8.1 million ($9.1 million), assuming a public offering price of $8.00 per ADS in the ADS offering, which is the midpoint of the price range set forth on the cover page of this prospectus, corresponding to €0.71 per ordinary share in the ordinary share offering (assuming an exchange rate of €0.89 per U.S. dollar), after deducting underwriting discounts and commissions and estimated offering expenses payable by us.

Each €0.89 ($1.00) increase or decrease in the assumed offering price of $8.00 per ADS in the ADS offering which is the midpoint of the price range set forth on the cover page of this prospectus, corresponding to €0.71 per ordinary share in the ordinary share offering (assuming an exchange rate of €0.89 per U.S. dollar), would increase or decrease our net proceeds by €1.1 million ($1.2 million), assuming that the number of ordinary shares offered by us (including ordinary shares in the form of ADSs), as set forth on the cover page of this prospectus, remains the same and after deducting underwriting commissions and estimated offering expenses payable by us. Subject to applicable law, we may also increase or decrease the number of ordinary shares (including ordinary shares in the form of ADSs) we are offering in the global offering. Each increase or decrease of 1,000,000 ordinary shares (including ordinary shares in the form of ADSs) offered by us would increase or decrease our net proceeds by €0.7 million ($0.7 million), assuming that the assumed offering price per ordinary share remains the same, and after deducting estimated underwriting commissions and estimated offering expenses payable by us.

The actual net proceeds payable to us will be adjusted based on the actual number of ordinary shares (including ordinary shares in the form of ADSs) offered by us in the global offering, the actual offering price of the ADSs and ordinary shares and other terms of the global offering determined at pricing.

We currently expect to use the net proceeds from the global offering as follows:

We expect our existing capital resources, together with the proceeds from the global offering, will fund our planned operating expenses for at least the next 12 months. However, we will need additional funds to advance our drug candidates beyond the intended uses described above. We currently plan to develop our drug candidates through clinical PoC and seek licensing and/or partnership opportunities for regulatory approval and commercialization. Until then, we may satisfy our future cash needs

through public or private equity or debt financings, government or other third-party funding, or a combination of these approaches.

This expected use of the net proceeds from the global offering represents our intentions based upon our current plans and business conditions. As of the date of this prospectus, we cannot predict with certainty all of the particular uses for the net proceeds to be received upon the completion of the global offering or the amounts that we will actually spend on the uses set forth above. The amounts and timing of our actual expenditures and the extent of clinical development may vary significantly depending on numerous factors, including the progress of our development efforts, the status of and results from preclinical studies and any ongoing clinical trial or any clinical trial we may commence in the future, as well as any collaborations that we may enter into with third parties for our drug candidates and any unforeseen cash needs. As a result, our future financing needs remain uncertain and our management will retain broad discretion over the allocation of the net proceeds from the global offering.

Pending our use of the net proceeds from the global offering, we intend to invest the net proceeds in a variety of capital preservation investments, including short-term, investment-grade, interest-bearing instruments.

We have never declared or paid any cash dividends on our ordinary shares. We do not anticipate paying cash dividends on our equity securities in the foreseeable future and intend to retain all available funds and any future earnings for use in the operation and expansion of our business.

Subject to the requirements of French law and our by-laws, dividends may only be distributed from our distributable profits, plus any amounts held in our reserves other than those reserves that are specifically required by law. See the section of this prospectus titled "Description of Share Capital—Key Provisions of Our By-laws and French Law Affecting our Ordinary Shares—Rights, Preferences and Restrictions Attaching to Ordinary Shares" for further details on the limitations on our ability to declare and pay dividends. Dividend distributions, if any, will be made in euros and converted into U.S. dollars with respect to the ADSs, as provided in the deposit agreement.

The following table sets forth our cash and cash equivalents and capitalization as of March 31, 2019 on:

Our capitalization following the global offering will be adjusted based on the actual offering price and offer terms of the global offering determined at pricing, including the amount by which actual offering expenses are higher or lower than estimated. You should read this table together with our audited consolidated financial statements and related notes beginning on page F-1, as well as the sections of this prospectus titled "Use of Proceeds," "Selected Financial and Other Data," "Management's Discussion and Analysis of Financial Condition and Results of Operations" and the other financial information included elsewhere in this prospectus.

As Adjusted(1)	As of March 31, 2019

	(in thousands)
Cash and cash equivalents	€	11,152		€	17,933



Non-current financial liabilities		7,519			7,519

Current financial liabilities		3,034			3,034
Shareholders' equity
Ordinary shares, €0.20 nominal value: 13,463,413 shares issued and outstanding, actual; 26,588,413 shares issued and outstanding, as adjusted		2,693			5,318
Premiums related to the share capital		43,379			47,535
Treasury shares		(116	)		(116	)
Foreign currency translation adjustment		(113	)		(113	)
Accumulated deficit—attributable to our shareholders		(39,702	)		(39,702	)
Net loss—attributable to our shareholders		(3,727	)		(3,727	)
Non-controlling interests		(31	)		(31	)

Total shareholders' equity		2,383			9,164

Total capitalization	€	12,936		€	19,717

The as adjusted information discussed above is illustrative only and will change based on the actual offering price, the actual number of ordinary shares offered by us (including ordinary shares in the form of ADSs), and other terms of the global offering determined at pricing.

If you invest in the ADSs or ordinary shares, your interest will be diluted to the extent of the difference between the offering price per ADS or ordinary share paid by purchasers in the global offering and our as adjusted net tangible book value per ADS or ordinary share after completion of the global offering.

Our net tangible book value as of March 31, 2019 was €504 thousand ($566 thousand), corresponding to a net tangible book value of €0.04 per ordinary share (equivalent to $0.42 per ADS). Net tangible book value per ordinary share represents the amount of our total assets less our total liabilities, excluding goodwill and other intangible assets, divided by the total number of our ordinary shares outstanding as of March 31, 2019.

After giving effect to the sale by us of a total of 13,125,000 ordinary shares in the global offering, consisting of 8,750,000 ordinary shares in the form of ADSs at an assumed initial public offering price of $8.00 per ADS in the ADS offering, which is the midpoint of the price range on the cover page of this prospectus, and 4,375,000 ordinary shares at an assumed offering price of €0.71 per ordinary share in the ordinary share offering (assuming the July 8, 2019 exchange rate of €0.89 per U.S. dollar), and after deducting the estimated underwriting discounts and commissions and estimated expenses payable by us, and the application of the estimated net proceeds from the global offering as described under "Use of Proceeds," our as adjusted net tangible book value as of March 31, 2019 would have been €7.3 million ($8.2 million), representing an as adjusted net tangible book value of €0.27 per ordinary share and $3.07 per ADS. This represents an immediate increase in net tangible book value of €0.23 per ordinary share (equal to $2.65 per ADS) to existing shareholders and an immediate dilution of €0.44 per ordinary share and $4.93 per ADS to new investors purchasing ordinary shares or ADSs in the global offering. Dilution per ordinary share or ADS to new investors is determined by subtracting the as adjusted net tangible book value per ADS or ordinary share after the global offering from the assumed initial public offering price per ADS or the assumed offering price per ordinary share, as applicable, paid by new investors.

The following table illustrates this dilution to new investors purchasing ADSs or ordinary shares in the global offering.

The dilution information discussed above is illustrative only and will change based on the actual offering price and other terms of the global offering determined at pricing.

If the underwriters exercise in full their option to purchase an additional 1,968,750 ordinary shares (to be delivered in the form of an aggregate of 196,875 ADSs), our as adjusted net tangible book value after the global offering would be €0.30 per ordinary share and $3.37 per ADS, representing a further immediate increase in as adjusted net tangible book value of €0.03 per ordinary share and $0.30 per ADS to existing shareholders and the dilution to new investors participating in the global offering

would be €0.41 per ordinary share and $4.63 per ADS, based on the assumed initial public offering price of $8.00 per ADS in the ADS offering, which is the midpoint of the price range set forth on the cover page of this prospectus, corresponding to €0.71 per ordinary share in the ordinary share offering (assuming an exchange rate of €0.89 per U.S. dollar).

Each €0.89 ($1.00) increase or decrease in the assumed offering price of $8.00 per ADS in the ADS offering, which is the midpoint of the price range set forth on the cover page of this prospectus, corresponding to €0.71 per ordinary share in the ordinary share offering (assuming an exchange rate of €0.89 per U.S. dollar), would further increase or decrease the as adjusted net tangible book value after the global offering by €0.04 per ordinary share and $0.45 per ADS and the dilution to new investors in the global offering by €0.04 per ordinary share and $0.45 per ADS, assuming that the number of ordinary shares (including ordinary shares in the form of ADSs) offered by us in the global offering, as set forth on the cover page of this prospectus, remains the same and after deducting the estimated underwriting discounts and commissions and estimated offering expenses payable by us, and the application of the estimated net proceeds from the global offering as described under "Use of Proceeds."

An increase or decrease of 1,000,000 in the number of ordinary shares (including ordinary shares in the form of ADSs) offered by us in the global offering, as set forth on the cover page of this prospectus, would further increase or decrease the as adjusted net tangible book value after the global offering by €0.02 per ordinary share and $0.16 per ADS and decrease (increase) the dilution to new investors participating in the global offering by €0.02 per ordinary share and $0.16 per ADS, assuming no change in the assumed initial public offering price per ADS or in the assumed offering price per ordinary share and after deducting the estimated underwriting discounts and commissions and estimated offering expenses payable by us, and the application of the estimated net proceeds from the global offering as described under "Use of Proceeds."

The following table summarizes, as of March 31, 2019, on the as adjusted basis described above, the number of ordinary shares purchased from us (including ordinary shares in the form of ADSs), the total consideration paid to us and the average price per ordinary share and per ADS paid by existing shareholders and by new investors purchasing ordinary shares or ADSs in the global offering. The table below and the two paragraphs that follow the table are based on an assumed initial public offering price of $8.00 per ADS in the ADS offering, which is the midpoint of the price range set forth on the cover page of this prospectus, corresponding to €0.71 per ordinary share in the ordinary share offering (assuming an exchange rate of €0.89 per U.S. dollar), before deducting the estimated underwriting discounts and commissions and estimated offering expenses payable by us, and the application of the estimated net proceeds from the global offering as described under "Use of Proceeds," and reflect the Banque de France exchange rate on July 8, 2019:

the form of ADSs) offered by us in the global offering, as set forth on the cover page of this prospectus, remains the same. An increase or decrease of 1,000,000 in the number of ordinary shares (including ordinary shares in the form of ADSs) offered by us, as set forth on the cover page of this prospectus, would increase or decrease the total consideration paid by new investors by €0.7 million ($0.7 million), assuming no change in the assumed initial public offering price per ADS or in the assumed offering price per ordinary share.

The information described above is illustrative only and will change based on the actual offering price, the actual number of ordinary shares offered by us (including ordinary shares in the form of ADSs) and other terms of the global offering determined at pricing.

If the underwriters exercise in full their option to purchase up to an additional 1,968,750 ordinary shares (to be delivered in the form of an aggregate of 196,875 ADSs), the following will occur:

The tables and calculations above are based on the number of ordinary shares (including ordinary shares in the form of ADSs) that will be outstanding after the global offering, which is based on 13,463,413 ordinary shares outstanding as of March 31, 2019 and excludes:

To the extent that warrants are exercised or we issue additional ADSs or ordinary shares in the future, there will be further dilution to investors participating in the global offering. In addition, we may choose to raise additional capital because of market conditions or strategic considerations, even if we believe that we have sufficient funds for our current or future operating plans. If we raise additional capital through the sale of equity or convertible debt securities, the issuance of these securities could result in further dilution to our shareholders.

The following tables summarize our consolidated financial data for the periods and as of the dates indicated below. We derived the selected statement of consolidated operations data for the years ended December 31, 2017 and 2018 and statement of consolidated financial position data from our audited consolidated financial statements included elsewhere in this prospectus. Our audited consolidated financial statements have been prepared in accordance with IFRS, as issued by the IASB. The following summary statement of consolidated operations data for the three months ended March 31, 2018 and 2019 and statement of consolidated financial position data as of March 31, 2019 have been derived from our unaudited interim condensed consolidated financial statements as of March 31, 2019 and for the three months ended March 31, 2018 and 2019 included elsewhere in this prospectus. The unaudited interim condensed consolidated financial statements as of March 31, 2019 and for the three months ended March 31, 2018 and 2019 were prepared in accordance with IAS 34, Interim Financial Reporting, the standard of the IFRS applicable to interim financial statements.

	Year Ended December 31,						Three Months Ended March 31,

	2017			2018			2018			2019
	€			€			€			€			U.S. $(1)
	(in thousands, except share and per share data)
Statement of Consolidated Operations Data:
Operating expenses:
Research and development, net		7,043			9,513			2,017			2,289			2,570
General and administrative expenses		2,865			4,348			865			1,211			1,360
Total operating expenses		9,908			13,861			2,882			3,500			3,930
Operating loss		(9,908	)		(13,861	)		(2,882	)		(3,500	)		(3,930	)
Financial expenses		(3,293	)		(215	)		(26	)		(276	)		(310	)
Financial income		37			17			4			49			55
Change in fair value of financial instruments		1,756			—			—			—			—
Financial loss		(1,500	)		(198	)		(22	)		(227	)		(255	)
Net loss before taxes		(11,408	)		(14,059	)		(2,904	)		(3,727	)		(4,185	)
Income tax benefit		—			72			—			—			—

Net loss		(11,408	)		(13,987	)		(2,904	)		(3,727	)		(4,185	)



Earnings (losses) per share(2)
Basic		(1.24	)		(1.04	)		(0.22	)		(0.28	)		(0.31	)
Diluted		(1.24	)		(1.04	)		(0.22	)		(0.28	)		(0.31	)
Weighted average number of ordinary shares outstanding used for computing Basic		9,188,179			13,463,413			13,463,413			13,463,413			13,463,413
Weighted-average number of ordinary shares outstanding used for computing Diluted		9,188,179			13,463,413			13,463,413			13,463,413			13,463,413

MANAGEMENT'S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND
RESULTS OF OPERATIONS

You should read the following discussion of our financial condition and results of operations in conjunction with our consolidated financial statements and the notes included elsewhere in this prospectus. The following discussion contains forward-looking statements that involve certain risks and uncertainties. Our actual results could differ materially from those discussed in these statements. Factors that could cause or contribute to these differences include those discussed below and elsewhere in this prospectus, particularly under the "Risk Factors" and "Special Note Regarding Forward-Looking Statements" sections.

Our therapeutic approach is aimed at targeting and activating key biological resilience pathways that can protect against and counteract the effects of the multiple biological and environmental stresses, including inflammatory, oxidative and metabolic stresses that lead to age-related diseases. Our lead drug candidate, Sarconeos (BIO101), is in development for the treatment of neuromuscular diseases, including sarcopenia and DMD. Our second drug candidate, Macuneos (BIO201), is in development for the treatment of retinopathies, including dry AMD and Stargardt disease.

We are currently testing the safety and efficacy of Sarconeos (BIO101) in an ongoing global, randomized, multicenter, double-blind, placebo-controlled Phase 2b clinical trial (SARA-INT) of 334 elderly patients with sarcopenia at risk for mobility disability. We are also developing Sarconeos (BIO101) for DMD and are preparing to submit an IND application to the FDA and clinical trial applications to the applicable regulatory agencies in Europe in the second half of 2019 to initiate clinical development as early as 2020, subject to regulatory approval. We plan to hold, in the second half of 2019, scientific advice meetings with the EMA and applicable regulatory agencies in Europe regarding our clinical development plan for Macuneos (BIO201) in dry AMD and, subject to regulatory review and approval of the protocol, commence a Phase 1 clinical trial (MACA-PK) in healthy volunteers.

Subject to our entering into commercialization agreements with one of our research collaborators in relation to two patent applications we recently filed, we will hold exclusive commercialization rights, through licenses for each of our drug candidates. We currently plan to develop our drug candidates through clinical PoC (typically Phase 2), and then seek licensing and/or partnership opportunities for further clinical development through regulatory approval and commercialization.

The following discussion sets forth certain components of our statements of operations as well as factors that impact those items.

To date we have not generated any revenues from product sales and we do not expect to recognize any revenue from the sale of products, even if approved, in the near term. Our ability to generate revenue in the future will depend almost entirely on our ability to successfully develop, obtain regulatory approval for and then commercialize our drug candidates.

Our research and development expenses consist primarily of costs incurred in connection with the development of our drug candidates, including:

To date, we have expensed all research and development costs as incurred, as we do not currently meet the conditions to capitalize expenditures on drug development activities, as provided in IAS 38 Intangible Assets.

Clinical development expenses for our drug candidates are a significant component of our current research and development expenses as we advance our drug candidates into and through clinical trials. Drug candidates in later stage clinical development generally have higher research and development costs than those in earlier stages of development, primarily due to increased size and duration of the clinical trials. We recognize costs for each grant project, preclinical study or clinical trial that we conduct based on our evaluation of the progress to completion, using information and data provided to us by our research and development vendors and clinical sites.

We expect our research and development expenses to increase for the foreseeable future as we progress our drug candidates into and through clinical trials. Furthermore, to the extent we undertake to commercialize any drug candidates approved for any indication for sale, our expenses will likely increase even more. The process of conducting the necessary clinical research to obtain regulatory approval of a drug candidate is costly and time consuming. We will require additional funding, beyond any proceeds raised in the global offering, to fund our continuing operations. The probability that any of our drug candidates receives regulatory approval and eventually is able to generate revenue depends on a variety of factors, including the quality of our drug candidates, early clinical data, investment in our clinical program and further clinical validation, competition, manufacturing capability and commercial viability. We may never succeed in obtaining regulatory approval for any of our drug candidates. As a result of these uncertainties, we are unable to determine the duration and completion costs of our research and development projects or if, when and to what extent we will generate revenue from the commercialization and sale of any of our drug candidates, if approved.

General and administrative expenses include personnel costs, costs for outside professional services and other allocated expenses. Personnel costs consist of salaries, bonuses, benefits, travel and share-based compensation. Outside professional services consist of legal, accounting and audit services, commercial evaluation and strategy services, and other consulting services. We expect general and administrative expenses to increase in the near future with the expansion of our staff and management team to include new personnel responsible for finance, legal, information technology and later, sales and business development functions. We also expect to incur additional general and administrative costs as a result of operating as a U.S. public company, including expenses related to compliance with the

rules and regulations of the SEC and those of any national securities exchange on which our securities are traded, additional insurance expense, investor relations activities and other administrative and professional services. We also expect to incur additional expenses related to in-licenses, acquisitions or similar transactions that we may pursue as part of our strategy, including legal, accounting and audit services and other consulting fees.

Net financial income (expense) include amortized cost of the reimbursable advances, convertible notes and non-convertible bonds, fair value adjustments on financial instruments and other financial income and expense. We expect to incur additional financial expenses related to financing agreements or similar transactions that we may enter into to finance the development of the Company.

Our audited and unaudited consolidated financial statements have been prepared in accordance with IFRS, as issued by the IASB. Some of the accounting methods and policies used in preparing our financial statements under IFRS are based on complex and subjective assessments by our management or on estimates based on past experience and assumptions deemed realistic and reasonable based on the circumstances. The actual value of our assets, liabilities and shareholders' equity and of our losses could differ from the value derived from these estimates if conditions change and these changes have an impact on the assumptions adopted. We believe that the most significant management judgments and assumptions in the preparation of our financial statements are described below. See Note 2.2 to our audited consolidated financial statements as of December 31, 2017 and 2018 and for each of the two years in the period ended December 31, 2017 and 2018.

The fair value measurement of share-based payments is based on the Black-Scholes option valuation model, which makes assumptions about complex and subjective variables. These variables notably include the value of the Company's shares, the expected volatility of the share price over the lifetime of the instrument, and the present and future behavior of holders of those instruments. There is a high inherent risk of subjectivity when using an option valuation model to measure the fair value of share-based payments in accordance with IFRS 2 Share-based Payment.

During the year ended December 31, 2017, we issued notes convertible into ordinary shares and/or redeemable for cash with warrants attached.

During the year ended December 31, 2018, we issued non-convertible bonds with attached warrants.

During the three-month period ended March 31, 2019, we issued non-convertible bonds.

In accordance with IAS 39 Financial Instruments (in 2017) and IFRS 9 Financial Instruments (in 2018), we measured the fair value of the equity instrument based on the Black-Scholes option valuation model, which makes assumptions about complex and subjective variables. These variables notably include the value of our shares, the expected volatility of the share price over the lifetime of the instrument, and the present and future behavior of holders of those instruments. There is a high inherent risk of subjectivity when using an option valuation model to measure the fair value of financial instruments and equity instruments in accordance with IAS 32 Financial Instruments: presentation, IAS 39 Financial Instruments (in 2017) and IFRS 9 Financial Instruments (in 2018 and in 2019).

The determination of the amount of deferred tax assets which can be recognized requires management to make estimates on both the period in which tax losses carried forward will be realizable, and the level of future taxable income.

As of December 31, 2017 and 2018, no deferred tax asset has been recognized in the Company's financial statements except as a result of the expected taxable income to be derived from deferred tax liabilities.

As an "emerging growth company" under the JOBS Act, we can take advantage of an extended transition period for complying with new or revised accounting standards. This allows an "emerging growth company" to delay the adoption of certain accounting standards until those standards would otherwise apply to private companies. We will not take advantage of the extended transition period provided under Section 7(a)(2)(B) of the Securities Act of 1933, as amended for complying with new or revised accounting standards. Since IFRS makes no distinction between public and private companies for purposes of compliance with new or revised accounting standards, the requirements for our compliance as a private company and as a public company are the same.

We are in the process of evaluating the benefits of relying on other exemptions and reduced reporting requirements under the JOBS Act. Subject to certain conditions, as an "emerging growth company," we intend to rely on certain of these exemptions including, without limitation, the exemptions from providing an auditor's attestation report on our system of internal controls over financial reporting pursuant to Section 404(b) of the Sarbanes-Oxley Act. We will remain an "emerging growth company" until the earliest of: (1) the last day of the fiscal year in which we have total annual gross revenues of $1.07 billion or more; (2) the last day of the fiscal year following the fifth anniversary of the date of the completion of this global offering; (3) the date on which we have issued more than $1 billion in non-convertible debt during the previous three years; and (4) the date on which we are deemed to be a large accelerated filer under the rules of the SEC.

The following table sets forth our results of operations for the three-month periods ended March 31, 2018 and 2019.

(Amounts in thousands of euros)

Revenue	—		—
Costs of sales	—		—

Gross margin	—		—

Research and development, net	(2,017	)	(2,289	)
General and administrative expenses	(865	)	(1,211	)

Operating loss	(2,882	)	(3,500	)

Financial expenses	(26	)	(276	)
Financial income	4		49
Change in fair value of financial instruments	—		—

Net financial expense	(22	)	(227	)

Loss before taxes	(2,904	)	(3,727	)

Income taxes	—		—

Net loss	(2,904	)	(3,727	)

Research and development expenses may be summarized as follows for the three-month periods ended March 31, 2018 and 2019.

Research and development expenses primarily relate to activities in connection with conducting clinical trials and non-clinical studies of the Company's drug candidates for the treatment of age-related diseases.

The increase of €0.3 million in personnel expenses is primarily related to the hiring of employees in the United States to support the Company's increased clinical and regulatory activities for Sarconeos (BIO101) in the Company's SARA clinical program.

The increase of €0.2 million in purchases and external expenses is primarily related to the Company's clinical trials and research costs. These expenses consisted primarily of the cost of Contract Research Organization (CROs) in conducting clinical trials and non-clinical regulatory studies.

We have benefited from the Research Tax Credit (CIR) since our incorporation. The CIR amounted to €599 thousand and €859 thousand for the three-month periods ended March 31, 2018 and 2019, respectively. The increase of €0.3 million in CIR is primarily related to increased research expenses eligible for the CIR.

General and Administrative expenses may be summarized as follows for the three-month periods ended March 31, 2018 and 2019.

Personnel expenses, including share-based payments, for general management and administrative staff increased by €0.4 million due to the reorganization and reinforcement of our administrative and finance function, and the subsequent increase in personnel from four people to eight people, including the hiring of a financial controller in France and a Chief Financial Officer by our U.S. subsidiary.

Other purchases and external expenses consisted primarily of administrative expenses associated with being a public listed company in France, accounting and audit fees, and legal fees.

Net financial expense may be summarized as follows for the three-month periods ended March 31, 2018 and 2019.

Net financial expense were €(22) thousand and €(227) thousand for the three-month periods ended March 31, 2018 and 2019, respectively.

On March 1, 2019, the fourth tranche of non-convertible bonds was issued to Kreos for total gross proceeds of €2.5 million. In accordance with IFRS 9 Financial instruments, the non-convertible debt component is measured according to the amortized cost method. The amount of the amortized cost adjustment and interest for all four tranches of the non-convertible bonds, including the three tranches issued in the latter part of 2018, was €268 thousand in the three-month period ended March 31, 2019.

No income tax expenses were charged in the three-month periods ended March 31, 2018 and 2019.

The following table sets forth our results of operations for the years ended December 31, 2017 and 2018.

(Amounts in thousands of euros)

Revenue	—		—
Costs of sales	—		—

Gross margin	—		—

Research and development, net	(7,043	)	(9,513	)
General and administrative expenses	(2,865	)	(4,348	)

Operating loss	(9,908	)	(13,861	)

Financial expenses	(3,293	)	(215	)
Financial income	37		17
Change in fair value of financial instruments	1,756		—

Net financial expense	(1,500	)	(198	)

Loss before taxes	(11,408	)	(14,059	)

Income taxes	—		72

Net loss	(11,408	)	(13,987	)

Research and development expenses may be summarized as follows for the years ended December 31, 2017 and 2018.

Personnel costs, including stock-based payments for engineers and research personnel, were €2,104 thousand and €2,962 thousand for the years ended December 31, 2017 and 2018, respectively. The increase in personnel expenses is mainly related to the hiring of employees to support our increased clinical and regulatory activities for Sarconeos (BIO101) through our SARA and MYODA programs. Research and development personnel consisted of 16 people as of December 31, 2017 and 23 people as of December 31, 2018.

Purchases and external expenses related to our research activity were €7,312 thousand and €9,539 thousand for the years ended December 31, 2017 and 2018, respectively. The increase of €2,227 thousand in purchases and external expenses is mainly related to our clinical trials and research costs, which are summarized by program as follows:

These expenses consisted primarily of the cost of CROs in conducting clinical trials and non-clinical regulatory studies of our drug candidates.

We have benefited from the Research Tax Credit (CIR) since our incorporation. The CIR amounted to €2,545 thousand and €3,133 thousand for the years ended December 31, 2017 and 2018, respectively. The 2017 CIR was reimbursed in 2018.

General and Administrative expenses may be summarized as follows for the years ended December 31, 2017 and 2018.

Personnel costs, including share-based payments, for general management and administrative staff were €1,257 thousand and €1,804 thousand for the years ended December 31, 2017 and 2018, respectively, due to the hiring of a financial controller in France, and a Chief Financial Officer by our U.S. subsidiary.

Other purchases and external expenses were €1,576 thousand and €2,428 thousand for the years ended December 31, 2017 and 2018, respectively. These expenses consisted primarily of administrative expenses associated with being a public listed company, accounting and audit fees, and legal fees.

The overall increase in general and administrative expenses for the year ended December 31, 2018, is primarily due to increased administrative expenses and our expansion in the United States, including opening offices in Cambridge, Massachusetts and hiring staff.

Net financial expense may be summarized as follows for the years ended December 31, 2017 and 2018.

Net financial expense were €(1,500) thousand and €(198) thousand for the years ended December 31, 2017 and 2018, respectively.

On April 3, 2017, the Company signed a convertible notes agreement with Bracknor Fund (as described in further detail below). On May 15, 2017, we issued the first tranche of 300 convertible notes to Bracknor Fund in exchange for €3 million plus 30 convertible notes, as a commitment fee, in exchange for €300 thousand pursuant to the terms of the convertible notes agreement. On July 7, 2017, we issued a second tranche of 300 convertible notes to Bracknor Fund in exchange for €3 million.

In accordance with IAS 39 Financial Instruments, the convertible debt component was measured according to the amortized cost method. The conversion option was classified in financial instruments and measured at the fair value with recognition of the changes in fair value in the statement of consolidated operations. All convertible notes were converted in 2017, which resulted in the elimination of the financial instrument and reclassification of the debt to equity upon share issuance with the net impact of the conversion using the nominal value of the debt being reflected in "financial interest and amortized cost of the convertible notes and non-convertible bonds" in the table above.

On September 10, 2018, the Company signed a venture loan agreement and bonds issue agreement with Kreos (as described in further detail below). The first and second tranches of non-convertible bonds were issued to Kreos on September 10, 2018. The third tranche of non-convertible bonds was issued to Kreos on December 17, 2018, for total gross proceeds to us of €7.5 million.

In accordance with IFRS 9 Financial instruments, the non-convertible debt component is measured according to the amortized cost method.

In 2018, a deferred tax asset has been recognized through the consolidated statement of operations to offset the deferred tax liability related to the equity component of the non-convertible bonds recorded in equity. Management expects that losses on ordinary activities will continue to be offset by unrecognized tax losses.

As of December 31, 2018 and March 31, 2019, we had cash and cash equivalents of €14,406 thousand and €11,152 thousand, respectively. Cash in excess of immediate requirements is invested in accordance with our investment policy, primarily with a view to liquidity and capital

preservation. Currently, our funds are held in bank accounts and fixed bank deposits primarily in France.

Our operations have been financed primarily by capital contributions from our founders, capital increases carried out between 2006 and 2018 and net proceeds from the initial public offering of our ordinary shares on the Euronext Growth Market in France in 2015. Our primary uses of capital are, and we expect will continue to be, third-party expenses associated with the planning and conduct of preclinical studies and clinical trials, costs of process development services and manufacturing of our drug candidates, and compensation-related expenses.

We do not expect to generate significant revenue from product sales unless and until we out-license one or more drug candidates or we obtain regulatory approval for and commercialize our current or any future drug candidates, either directly or through others. We anticipate that we will continue to generate losses for the foreseeable future, and we expect our losses to increase as we continue the development of and seek regulatory approvals for our drug candidates and begin to commercialize any approved products.

We are subject to numerous risks applicable to the development of new products, and we may encounter unforeseen expenses, difficulties, complications, delays and other unknown factors that may harm our business. Upon the closing of the global offering, we expect to incur additional costs associated with operating as a public company in the United States and we anticipate that we will need substantial additional funding in connection with our continuing operations.

Our future funding requirements will depend on many factors, including the following:

Our ability to achieve and maintain profitability will depend upon the successful development, regulatory approval and commercialization of our drug candidates and achieving a level of revenues adequate to support our cost structure. We may never achieve profitability, and unless and until we do, we will continue to need to raise additional capital. If we need to raise additional capital to fund our operations and complete our ongoing and planned clinical trials, funding may not be available to us on acceptable terms, or at all.

We plan to continue to fund our operations and capital funding needs through a combination of equity offerings, debt financings and collaborations. The sale of additional equity would result in additional dilution to our shareholders. The incurrence of debt financing would result in debt service obligations and the instruments governing such debt could provide for operating and financing covenants that would restrict our operations. If we are not able to secure adequate additional funding, we may be forced to make reductions in spending, extend payment terms with suppliers, sell assets

where possible or suspend or curtail planned programs. In addition, lack of funding would limit any strategic initiatives to in-license or acquire additional drug candidates or programs.

We expect that our existing capital resources, including our ability to draw down on our credit facility with Bracknor Fund, together with the proceeds from the global offering, will be sufficient to fund our current operations for the next 12 months. However, this estimate is based on assumptions that may prove to be wrong, and we could use our capital resources sooner than we currently expect. In any event, we will need additional funding to pursue preclinical and clinical activities, obtain regulatory approval for, and commercialize our drug candidates.

Net cash used in operating activities were €8,727 thousand and €12,057 for the years ended December 31, 2017 and 2018, respectively. The increase in net cash used mainly related to costs incurred in completing our SARA-PK study and launching our SARA-OBS and SARA-INT trials, as well as the acceleration of non-clinical studies in our MYODA and MACA programs.

During the three-month periods ended March 31, net cash used in operating activities increased from €3,745 thousand in 2018 to €5,030 thousand in 2019, primarily reflecting the increase in research and development expenses and general and administrative expenses.

Net cash used in investing activities was €122 thousand and €104 thousand for the years ended December 31, 2017 and 2018, respectively, consisting mainly of the purchase and lease of research laboratory equipment.

During the three-month periods ended March 31, net cash used in investing activities was €6 thousand and €13 thousand for 2018 and 2019, respectively.

Net cash provided by financing activities were €25,643 thousand and €6,771 thousand for the years ended December 31, 2017 and 2018, respectively.

We issued an aggregate of 4,812,431 ordinary shares in three capital increases that occurred in April and October 2017 for total proceeds to us of €21,741 thousand. In relation to these equity transactions, we incurred costs of €2,043 thousand.

In May and July 2017, we issued two tranches of convertible notes for €3,000 thousand each. The convertible notes issued in 2017 were fully converted as of December 31, 2017, resulting in the issuance of an aggregate 2,412,481 ordinary shares.

Between September and December 2018, we issued three tranches of non-convertible bonds to Kreos for €2,500 thousand each for total gross proceeds to us of €7,500 thousand. A guarantee deposit of €240 thousand was withheld by Kreos from the proceeds received by us. The amount withheld will be deducted from the last installment to be repaid by us. In relation to these debt issuances, we incurred costs of €305 thousand. We also received net proceeds of €329 thousand from conditional advances in 2018 compared to net repayments of €34 thousand in 2017, and we paid interest of €135 thousand in 2018.

In the three-month period ended March 31, 2019, net cash provided by financing activities was €1,839 thousand.

On March 1, 2019, we issued one tranche of non-convertible bonds to Kreos for €2,500 thousand. A guarantee deposit of €80 thousand was withheld by Kreos from the proceeds received by us. The amount withheld will be deducted from the last installment to be repaid by us. In relation to these debt issuances, we incurred costs of €50 thousand. Offsetting this amount, we made repayments of conditional advances for €123 thousand, payments of interest for €208 thousand and certain equity transaction costs for €158 thousand along with lease payments for €47 thousand.

We have benefited from the CIR since our incorporation. The CIR is usually payable by the government in the year following its recognition when there is no taxable net income to be offset if certain business size criteria are met. The CIR for 2015 and 2016 were reimbursed in 2017 for €2,054 thousand, and the CIR for 2017 was reimbursed in 2018 for €2,545 thousand. The CIR for 2018 was €3,133 thousand and is expected to be reimbursed in 2019. The CIR for 2019 (including the CIR computed for the three-month period ended March 31, 2019) is expected to be reimbursed in 2020.

A reimbursable advance was granted to us by BPI France on August 7, 2008. This was a non-interest-bearing reimbursable advance of €230 thousand for the clinical development of an extract of quinoa active on metabolic syndrome. Following the successful completion of the project and the extension of the repayment terms granted by BPI France (formerly OSEO), this advance was repaid by means of quarterly payments made between March 31, 2016 and December 31, 2018. As of December 31, 2018, this conditional advance has been fully satisfied by the Company.

A reimbursable advance was granted to us by BPI France on February 4, 2015. This was a non-interest-bearing reimbursable advance of €260 thousand for the "in vitro, in vivo, and pharmacokinetic characterization of a candidate drug." Following the successful completion of the project and the extension of the repayment terms granted by BPI France, this advance is being repaid by means of quarterly payments made between June 30, 2017 and March 31, 2022.

A reimbursable advance was granted to us by BPI France on November 28, 2016. This is a non-interest-bearing reimbursable advance of €1,100 thousand for the production of clinical batches, in the preclinical regulatory phase and clinical Phase 1 of BIO101, for the treatment of sarcopenic obesity. The agreement with BPI France provides that the advance would be paid to us in two tranches, with the first of €600 thousand paid at the signing date of the agreement, and the second of €500 thousand to be paid at the end of the program. We received €500 thousand during the year ended December 31, 2018 related to the second tranche. Following the successful completion of the project, this advance is being repaid by means of quarterly payments made between December 31, 2018 and September 30, 2023.

On June 3, 2019, we entered into a collaboration agreement with the French Muscular Dystrophy Association (AFM-Telethon), pursuant to which AFM-Telethon has provided funding of €400,000 to us. This is a non-interest bearing reimbursable advance of €400,000 for certain preclinical studies and preparations for our MYODA program. Under the terms of the agreement, subject to regulatory approval to conduct the MYODA clinical trial in Europe and conclusive results from the collaboration, we will submit to AFM-Telethon a new research project for further collaboration on the clinical development of Sarconeos (BIO101) in DMD. If funding for the new research project is approved by AFM-Telethon, we will negotiate in good faith the terms of a new collaboration agreement with AFM-Telethon. If entered into, the new collaboration agreement will grant certain rights to AFM-Telethon that may, in the event we later decide to abandon or not pursue the development of Sarconeos (BIO101), entitle AFM-Telethon to continue the development and/or commercialization of Sarconeos (BIO101) and/or any pharmaceutical product derived from Sarconeos (BIO101) for the purpose of guaranteeing the access of such products to DMD patients. The advance will be repaid upon our obtaining authorization to commence a Phase 3 clinical trial of Sarconeos (BIO101) for the treatment of DMD. In addition, we will be required to repay the advance if we are unable to come to an agreement with AFM-Telethon on further funding of our MYODA clinical program or we materially breach the agreement and AFM-Telethon requests reimbursement.

We signed a loan agreement with BPI France (formerly OSEO) on November 4, 2008 for the partial financing of an innovation program in the amount of €150 thousand. This loan was repaid in quarterly installments of €7.5 thousand until August 31, 2018 (term of the loan). This equity loan has been fully satisfied by the Company.

In April 2017, we established a credit facility with Bracknor Fund providing for up to €15 million in financing to us. Pursuant to the terms of the credit facility agreement, in consideration for this debt commitment, we issued 1,500 convertible note warrants to Bracknor Fund with a nominal value of €10 thousand each. Each convertible note warrant may be exercised, at our option, for an exercise price of €10 thousand, for one non-interest-bearing note convertible into (i) new shares of Biophytis or (ii) cash. Upon exercise of the convertible note warrants, each convertible note issued will be accompanied by that number of share subscription warrants that would entitle us to receive proceeds upon their exercise for a total amount equal to 25% of the nominal amount of the convertible notes to which such warrants were attached. We have the right, but not the obligation, to instruct Bracknor Fund to exercise the convertible note warrants in tranches of 300 in accordance with a schedule provided for in the agreement. The credit facility has a term of 36 months.

The 300 convertible notes issued on May 15, 2017 and 300 convertible notes issued on July 7, 2017 have been converted into an aggregate of 2,412,481 ordinary shares. The Company may require Bracknor Fund to exercise the remaining 900 convertible note warrants under the terms of credit facility, which would provide for up to an additional €9 million to us.

In September 2018, we entered into a venture loan agreement and bonds issue agreement with Kreos providing for up to €10 million in financing to us. Pursuant to the terms of the agreements, Kreos agreed to subscribe for up to €10 million in non-convertible bonds, to be issued by us in up to four tranches of €2.5 million each, with a warrant to purchase 442,477 ordinary shares attached to the first tranche. As required under the terms of the agreements, we pledged a security interest in the Company's assets for the profit of Kreos. We also granted a security interest in the business as a going concern, including a portion of our patents, to Kreos.

Each tranche of non-convertible bonds bears a 10% annual interest rate and must be repaid in 36 monthly installments of €320,004 per month commencing in April 2019. The first and second tranches were issued to Kreos on September 10, 2018. The third tranche was issued to Kreos on December 17, 2018. The final tranche was issued on March 1, 2019.

In connection with the first tranche, we issued 442,477 warrants to Kreos giving them the right to purchase 442,477 new ordinary shares at an exercise price of €2.67 per share over a 7-year period from the issue date.

The following table discloses aggregate information about material contractual obligations and periods in which payments were due as of December 31, 2018. Future events could cause actual payments to differ from these estimates.

The following table discloses the commitments given as part of these agreements:

Agreements for the exploitation of industrial property		Commitments given

SARCOB commercialization agreement—SATT Lutech Agreement of 1 January 2016		This agreement covers the family S IV patents covered by the consortium agreement and the family S I patents and family S II and S III patents. The contractual structure of the consideration payable by us is as follows: firstly, in the year after the first marketing of a product and in any event at the latest, from 2023 onwards, we will pay a guaranteed annual minimum amount of €40 thousand, which will be deducted from the amount of royalties effectively due annually. With regard to the direct exploitation, the agreement provides for an annual royalty for a figure based on the net sales of products, distinguishing between sales of nutraceutical and medicinal products. With regards to indirect exploitation, the agreement provides for annual double-digit royalties based on income received from licensees, distinguishing (i) between the sales of nutraceutical products (double-digit royalties) and drug products (two or one-digit royalties) and (ii) the product development phase (Phase 1, 2 or 3) at the time of the conclusion of the licensing agreement.
MACULIA commercialization agreement—SATT Lutech Agreement of 1 January 2016		The contractual structure of the consideration payable by us is as follows: firstly, in the year following the first marketing of a nutraceutical product and in any event no later than in 2020, we will pay an annual guaranteed minimum amount of €15 thousand. In the same way, we will pay a guaranteed minimum amount of €50 thousand in the event of marketing of a drug product and in any event no later than from 2026. These amounts will be deducted from the amount of royalties effectively due annually. For direct exploitation, the agreement also provides for an annual royalty of a figure based on net sales of products, distinguishing between sales of nutraceutical and medicinal drugs. For indirect exploitation, it also provides for annual double-digit royalties based on income received from licensees, distinguishing (i) between the sales of nutraceuticals (double-digit royalties) and drug products (one or two-digit royalties) and (ii) the product development phase of these products (Phase 1, 2 or 3) at the time of conclusion of the licensing agreement.

We do not have variable interests in variable interest entities or any off-balance sheet arrangements as defined under the SEC rules, such as relationships with unconsolidated entities or financial partnerships, which are often referred to as structured finance or special purpose entities, established for the purpose of facilitating financing transactions that are not required to be reflected on our balance sheets.

For our Quantitative and Qualitative Disclosures about Market Risk, see (1) Note 21 "Management and assessment of financial risks" to our audited consolidated financial statements as of

and for the two years ended December 31, 2017 and 2018, and (2) Note 18 "Management and assessment of financial risks" to our unaudited condensed consolidated financial statements as of March 31, 2019 and for the three-month periods ended March 31, 2018 and 2019, which appear elsewhere in this prospectus.

For a discussion of the new standards and interpretations adopted and not yet adopted by us, see Note 2 "Accounting principles, rules and methods" to (1) our audited consolidated financial statements as of December 31, 2017 and 2018 and for each of the two years in the period ended December 31, 2017 and 2018 and (2) our unaudited condensed consolidated financial statements as of March 31, 2019 and for the three-month periods ended March 31, 2018 and 2019, which appear elsewhere in this prospectus.

A number of degenerative diseases associated with aging have been characterized in the last century, including sarcopenia and AMD. The pathophysiology of these and many other age-related diseases is not yet well understood, and effective treatment solutions are lacking. The global population of people over the age of 60 is expected to double from approximately 962 million in 2017 to 2.1 billion by 2050, according to estimates from the United Nations' World Population Prospects: the 2017 Revision. We believe that the need for effective therapeutics for age-related diseases will continue to grow throughout the 21^st century. In addition, healthcare costs, including costs associated with treatments and long-term care for age-related diseases associated with this demographic shift, are expected to rise proportionally, as effective treatment solutions are currently lacking. We believe that developing treatments to slow disease progression and reduce the risk of severe disability associated with age-related diseases is of the utmost importance.

As we age, our physical, visual and cognitive performances gradually decline due, in part, to the accumulation of multiple biological and environmental stresses to which we are exposed during our lifetime. The functional decline can be much faster in some individuals as a consequence of, among other things, the degenerative processes affecting specific cells, tissues and organs. Through evolution, cells, tissues and organisms have developed natural means or pathways to counteract and balance the effects of the many stresses they face. This natural ability to compensate for stress and remain functional, called biological resilience, degrades over time. The decline in biological resilience contributes to the acceleration of these degenerative processes and the impairment of functional performance, which, in turn, can lead to severe disability, reduced healthspan and ultimately death. Our therapeutic approach is aimed at targeting and activating key biological resilience pathways that can protect against and counteract the effects of the multiple biological and environmental stresses, including inflammatory, oxidative and metabolic stresses that lead to age-related diseases.

We are focusing our efforts to develop our lead drug candidate, Sarconeos (BIO101), an orally administered small molecule in development for the treatment of neuromuscular diseases. Sarconeos (BIO101) is a plant-derived pharmaceutical-grade purified 20-hydroxyecdysone. We have completed preclinical studies, including chronic toxicology and safety pharmacology studies, and a Phase 1 clinical trial in healthy human volunteers, which are necessary for pursuing further clinical development of Sarconeos (BIO101). Our early data indicates that Sarconeos (BIO101) stimulates biological resilience and muscle anabolism in cellular models, and preserves strength, mobility and respiratory capacity in animal models of certain neuromuscular diseases. While we are still in the early stages of development, we believe that these results support further investigation and clinical development of Sarconeos (BIO101) in patients with neuromuscular diseases.

The initial indication we are seeking approval for is sarcopenia, an age-related degeneration of skeletal muscle, which is characterized by a loss of muscle mass, strength and function in elderly people (adults 65 years of age and older) leading to reduced mobility, or mobility disability, and increased risk of adverse health events and potential death resulting from falls, fractures, and physical disability. There is currently no approved medication for sarcopenia, which is highly prevalent in the elderly with an estimated prevalence between six and 22 percent. We are currently testing the safety and efficacy of

Sarconeos (BIO101) in an ongoing global, randomized, multicenter, double-blind, placebo-controlled Phase 2b clinical trial (SARA-INT) of 334 elderly patients with sarcopenia at risk of mobility disability. The first patient in the SARA-INT Phase 2b clinical trial was enrolled in May 2018 and we expect to complete enrollment in 2020.

We are also developing Sarconeos (BIO101) for DMD, a rare genetic neuromuscular disease in male children and young adults, which is characterized by accelerated degeneration of muscle and is responsible for a loss of mobility, respiratory failure and cardiomyopathy, leading to premature death. There is currently no cure and limited treatment options for DMD, which affects approximately one in 5,000 newborn boys (approximately 20,000 new cases annually worldwide). In 2018, we received orphan drug designation for Sarconeos (BIO101) in DMD from the FDA and the EMA. We are preparing to submit an IND application to the FDA and clinical trial applications to the applicable regulatory agencies in Europe in the second half of 2019 to initiate clinical development of an oral pediatric formulation of Sarconeos (BIO101) for DMD through our MYODA clinical program, which could start as early as 2020, subject to regulatory approval of our study plan, clinical trial design, and study endpoints. Subject to regulatory approval of our protocol, we intend to use a 'seamless' clinical trial design (a seamless clinical trial combines and allows patients to participate in one or more phases) with a primary endpoint defined as a composite score combining muscle strength, mobility, and respiratory outcomes, which is adapted to the stage of severity of the disease in each patient, which has been discussed with the FDA through pre-IND correspondence and with the EMA in scientific advice meetings in 2018.

Our second drug candidate, Macuneos (BIO201), is an orally administered small molecule in development for the treatment of retinopathies. It is a plant-derived pharmaceutical-grade purified norbixin. We have completed preclinical cellular and animal studies of Macuneos (BIO201) for the treatment of certain retinopathies. While we are still in the early stages of development, we believe that the results from our preclinical studies support continued investigation into whether Macuneos (BIO201) may stimulate biological resilience and protect the retina against phototoxic damage that leads to vision loss. The initial indication we plan to seek approval for is dry AMD, a common eye disorder among people over the age of 50 that affects central vision, impairing functions such as reading, driving, and facial recognition, and has a major impact on quality of life and the ability to live independently. There are currently no approved treatments for dry AMD, which, based on our estimates from publicly available information, affects approximately 145 million people worldwide and is expected to increase over time as the population ages. We plan to hold, in the second half of 2019, scientific advice meetings with the EMA and applicable regulatory agencies in Europe regarding our clinical development plan for Macuneos (BIO201) in dry AMD, and subject to regulatory review and approval of the protocol, commence a Phase 1 clinical trial (MACA-PK) in healthy volunteers.

We are also exploring Macuneos (BIO201) as a potential treatment for Stargardt disease, which shares many of the characteristics of dry AMD. Stargardt disease is the most common form of inherited macular degeneration that typically develops in childhood and leads to vision loss and, in some cases, blindness. We plan to explore clinical development of Macuneos (BIO201) for Stargardt disease following our MACA-PK Phase 1 clinical trial.

Subject to our entering into commercialization agreements with the Centre National de la Recherche Scientifique (CNRS), one of our research collaborators, in relation to two patent applications we recently filed, which are described below as patent families S8 and S9, we hold exclusive commercialization rights through licenses for each of our drug candidates. We currently plan to develop our drug candidates through clinical PoC (typically Phase 2), and then seek licensing and/or partnership opportunities for further clinical development through regulatory approval and commercialization.

We have developed our lead clinical drug candidate Sarconeos (BIO101), preclinical drug candidate Macuneos (BIO201), and a preclinical pipeline of life-cycle extension products, consisting of BIO103 and BIO203, through a drug discovery platform in collaboration with Sorbonne University in Paris, France based on work with medicinal plants. Plants are major sources of small molecules, called secondary metabolites, which are produced as a defense mechanism to various environmental stresses, including attack from predatory and pathogenic species (e.g., insects, bacteria and fungi). Our drug discovery platform is based on a reverse pharmacology approach that tests a collection of bioactive secondary metabolites along with chemical analogs that we have synthesized in phenotypic screens of various age-related diseases. Our long-term goal is to advance the field of aging science with the continued discovery and development of new drug candidates that treat age-related diseases by stimulating biological resilience pathways that are involved in the aging process and/or age-related diseases.

We have assembled an executive team of scientific, clinical, and business leaders with broad expertise in biotechnology and clinical drug development. Stanislas Veillet, our co-founder, Chairman and Chief Executive Officer, has held numerous positions in the biotechnology, pharmaceutical and nutritional industries for the last 25 years. He holds a Ph.D. in genetics and has authored more than a dozen patents. Our other co-founder and Chief Scientific Officer, René Lafont, is a biochemist (Ecole Normale Supérieure), Professor Emeritus and former Dean of the Department of Life Sciences at Sorbonne University. He has authored over 170 scientific publications and a dozen patents and is also notably a Chevalier de l'Ordre des Palmes Académiques and a Laureate of the Karlson Foundation in Germany. Dr. Samuel Agus, our Chief Medical Officer, holds a Doctor in Medicine, is a board-certified neurologist with academic training in biostatistics and bioinformatics, and has over 15 years of clinical development experience in the pharmaceutical industry.

We are developing Sarconeos (BIO101) for the treatment of certain neuromuscular diseases, including sarcopenia and DMD. Both are diseases of muscular degeneration, but with different complex causes and pathophysiologies (i.e., age-related versus genetic). However, similar key muscular processes are impaired in each of these diseases as well as other muscle wasting conditions, including metabolism, mitochondrial function, stem cell proliferation and loss of biological resilience, which are mediated through multiple signaling pathways. Early cellular and animal model data suggest that Sarconeos (BIO101) directly targets muscle tissue and cells, and improves several key muscle cell functions, including protein syntheses, regeneration and energy production that may have the potential to improve

muscle function and preserve strength, mobility and respiratory capacity in various muscle wasting diseases.

Sarcopenia is an age-related degeneration of skeletal muscle. It is a major cause of mobility disability in the elderly, characterized by a loss of muscle mass, strength, balance and the ability to stand and/or walk, resulting in a loss of independence, increased risk of adverse health events and hospitalization, and potential death resulting from falls, fractures, and physical disability. We have observed activity of Sarconeos (BIO101) on cellular function and muscle performance in several cellular and animal models of various age-related and muscular wasting conditions. We also completed a Phase 1 clinical trial (SARA-PK) of 54 healthy adult and elderly subjects in 2017 that allowed us to determine the two dosing levels (175 and 350 mg b.i.d.) for our ongoing SARA-INT trial. We are currently testing the safety and efficacy of Sarconeos (BIO101) in an ongoing global, randomized, multicenter, double-blind, placebo-controlled Phase 2b clinical trial (SARA-INT) of 334 elderly patients with sarcopenia at risk of mobility disability. We enrolled the first patient in the SARA-INT Phase 2b clinical trial in May 2018 and currently expect to complete enrollment in 2020.

If approved by regulatory authorities for commercial use, we believe there is market potential for Sarconeos (BIO101) in sarcopenia, which is highly prevalent in the elderly with an estimated prevalence between six and 22 percent. There is currently no approved medication for sarcopenia and no therapeutic agents are currently being tested in confirmatory or Phase 3 clinical trials. Based on our review of research in this area, we believe Sarconeos (BIO101) is currently the only drug candidate being tested in an interventional Phase 2 clinical trial for the treatment of sarcopenia. There is currently no widely accepted standard of care for sarcopenia. Current non-medicinal treatment recommendations primarily focus on moderate physical activity, such as 30 minutes of walking per day or resistance-based (strength) training, as they exert effects on both the nervous and muscular systems that are critical to positive physiological and functional adaptations in older adults, and nutritional intervention. Other potential drug modalities that have been tested in the clinic for sarcopenia, have yet to demonstrate effectiveness on clinically meaningful outcomes (strength and mobility) and/or safety in larger clinical trials and/or have not progressed through the clinic. Based on our understanding and discussions with regulatory agencies, including the FDA and EMA, functional mobility endpoints must be achieved in order to obtain marketing approval for sarcopenia. We believe that based on our potential mechanism-of-action and preclinical cellular and animal model data that Sarconeos (BIO101) directly targets muscle tissue and cells, and improves key muscle cell functions, and has the potential to achieve clinically relevant functional mobility endpoints necessary for marketing approval.

DMD is rare neuromuscular genetic disease in male children and young adults, which is characterized by accelerated degeneration of muscle and is responsible for a loss of mobility, respiratory failure and cardiomyopathy, leading to premature death. It is the most common form of muscular dystrophy in children. DMD is caused by mutations in the dystrophin gene that result in the absence or very low levels of functional dystrophin, a cytoskeletal protein that protects muscle cells. We have observed a positive effect on muscle function, mobility, and respiratory capacity (a major disability in later stage DMD disease progression) in mdx mice models of DMD that were treated with Sarconeos (BIO101). In 2018, we received orphan drug designation from the FDA and EMA for Sarconeos (BIO101) in DMD. We are preparing to submit an IND application to the FDA and clinical trial applications to the applicable regulatory agencies in Europe in the second half of 2019 to initiate clinical development through our MYODA clinical program, utilizing a 'seamless' clinical trial design with a primary endpoint defined as a composite score combining muscle strength, mobility, and respiratory outcomes, which is adapted to the stage of severity of the disease in each patient, as early

as 2020, subject to regulatory approval of our study plan and clinical trial design, and study endpoints. Based on recommendations provided by the FDA in pre-IND correspondence received in October 2018 and a scientific advisory meeting with the CHMP of the EMA held in December 2018, we intend to initiate a global, multicentric, double-blind placebo-controlled MYODA clinical PoC trial (Phase 1/2) as early as 2020 in approximately 48 patients with DMD to test the safety and efficacy of Sarconeos (BIO101), subject to regulatory approvals of our protocol.

If approved by regulatory authorities for commercial use, we believe there is market potential for Sarconeos (BIO101) in DMD, which affects approximately one in 5,000 newborn boys, or approximately 20,000 new cases annually worldwide, based on our estimates from publicly available information. There is currently no cure for DMD and there are only limited treatment options that aim to control the symptoms and slow the disease progression. In many countries, corticosteroids are the standard drug therapy, however corticosteroids typically only slow the progression of muscle weakness and delay the loss of ambulation by up to two years. They have also been associated with adverse side effects and are generally not suitable for long-term administration. There are two targeted therapies (i.e., therapies targeting a specific dystrophin mutation by exon skipping or with stop codons) available on the market (one in the United States and one in Europe). As these therapies each target a specific gene mutation, they can only address the approximately 13% of the overall DMD patient population with those genetic mutations. We believe that Sarconeos (BIO101) directly targets muscle tissue and cells, increases key muscle cell functions that are impaired independent of the genetic mutation that causes the disease, and has the potential to be used complementarily with corticosteroids, current targeted therapies and other gene therapies under development. We also believe that because Sarconeos (BIO101) targets various impaired muscle tissues and cells relevant to muscle strength, mobility and respiratory function, it has the potential to be used in all stages of DMD progression, including both ambulatory and non-ambulatory patients.

AMD is an age-related degeneration of the macula, the central part of the retina. It is one of the leading causes of irreversible vision loss and blindness in people over the age of 50 worldwide, according to the BrightFocus Foundation's Age-Related Macular Degeneration: Facts & Figures Fact Sheet. Approximately 85 to 90% of AMD patients suffer from the dry (atrophic) form, called dry AMD, according to estimates provided by the American Macular Degeneration Foundation. Based on our estimates from publicly available information, we believe that dry AMD affects approximately 145 million people worldwide and is expected to increase over time as the population ages. Dry AMD affects central vision and impairs many functions affecting quality of life and independent living such as reading, driving, and facial recognition. The prevalence of dry AMD increases significantly with advancing age.

We have observed that Macuneos (BIO201) appears to protect the retina against phototoxic damage caused by A2E (a by-product of the visual pigment cycle) accumulation that leads to vision loss in several cellular and animal models of dry AMD and Stargardt disease. We have completed chronic and acute animal toxicology studies to support IND and clinical trial applications. We plan to hold, in the second half of 2019, scientific advice meetings with the EMA and applicable regulatory agencies in Europe regarding our clinical development plan for Macuneos (BIO201) in dry AMD and, subject to regulatory review and approval of the protocol, commence a Phase 1 clinical trial (MACA-PK) in healthy volunteers. We expect the MACA-PK Phase 1 clinical trial will assess the safety, PK and PD of Macuneos (BIO201).

We are focused on the development of therapeutics that improve functional outcomes for patients suffering from age-related diseases. Our goal is to build Biophytis into a leading biotechnology company focused on targeting biological resilience pathways that slow the degenerative processes associated with age-related disease progression in order to improve the lives of millions of patients that have limited or no treatment options. We currently plan to develop our drug candidates through clinical PoC (Phase 2) and then seek licensing and/or partnership opportunities for further clinical development through regulatory approval and commercialization. To achieve our goal, we are pursuing the following strategies:

Our lead drug candidate, Sarconeos (BIO101), is an orally administered small molecule in development for the treatment of neuromuscular diseases. We have completed preclinical studies and plan to pursue further clinical development of Sarconeos (BIO101) for the treatment of neuromuscular diseases. While preclinical studies provide limited data, based on results from our cellular and animal studies, we believe Sarconeos (BIO101) stimulates biological resilience through activation of the MAS receptor, which may preserve muscle strength, function and mobility in various age-related and muscular wasting conditions. The initial indication we are seeking approval for is sarcopenia, an age-related degeneration of skeletal muscle, which is characterized by a loss of muscle mass, strength, function and mobility disability, and increased risk of adverse health events and potential death resulting from falls, fractures, and physical disability. There is currently no approved medication for sarcopenia, which is highly prevalent in the elderly with an estimated prevalence between six and 22 percent. We are also developing Sarconeos (BIO101) for DMD, the most common form of muscular dystrophy in children leading to early mortality.

In collaboration with Sorbonne University in Paris, France, we began our drug discovery efforts with a class of plant secondary metabolites called phytoecdysteroids, which are produced by plants to protect them against insect attack. Phytoecdysteroids are analogs of the insect molting hormones ecdysone, which protects the plants by acting as endocrine disrupters and/or feeding deterrent. Phytoecdysteroids are found in various medicinal plants throughout the world and are used in traditional medicines as tonics or anti-diabetics.

We utilized a reverse pharmacology approach starting with phenotypic screens of a collection of phytoecdysteroids that had been gathered for over 30 years by scientists from Sorbonne University, along with chemical analogs that we have synthesized for their ability to stimulate protein synthesis in muscle cells. We selected 20-hydroxyecdysone for clinical development based on its safety profile, pharmacological activity and potential in maintaining key muscle functions, including mobility, strength and mass. This compound was tested under different stresses, including metabolic stress (high fat dieting or diabetic models), age-related stress (sarcopenia and disuse models), and genetic-related stress (DMD models). Next, we identified its molecular target(s) and a potential mechanism of action.

Our preclinical studies demonstrate that Sarconeos (BIO101) activates the MAS receptor in muscle cells, a key component of the renin-angiotensin system, or RAS. The RAS is a fundamental endocrine system that is known to control fluid balance and blood pressure, playing a key role in cardio-vascular function. It is involved in the regulation of smooth, cardiac and skeletal muscle metabolism, and plays a key role in muscle function and mobility in disease states. It is made up of two different arms that counter-regulate each other: (i) angiotensin II, or Ang II, through the AT-1 receptor, and

(ii) angiotensin 1-7, through the MAS receptor. Ang II blood concentration has been shown to be increased with aging and in various muscle wasting conditions, such as sarcopenia and cachexia. Angiotensin 1-7 opposes the numerous actions of Ang II, including the harmful effects associated with muscle degeneration.

We believe Sarconeos (BIO101), through the activation of the MAS receptor, triggers three key downstream signaling pathways: (i) the P13K/AKT/mTOR pathway, or the AKT pathway, which is known to be responsible for increasing protein synthesis, which we believe is a key factor for preserving muscle mass and increasing muscle strength under muscle wasting conditions (ii) the MAPK/P38/JNK pathway, or the MAPK pathway, which is known to be involved in stem cell proliferation and differentiation, which we believe is a key factor for improving muscle regeneration, and (iii) the AMPK/ACC pathway, or the AMPK pathway, which is known to be involved in stimulating energy production, which we believe may be a key factor for increasing muscle strength and improved endurance. We have demonstrated that Sarconeos (BIO101) activates major signaling pathways such as the AKT pathway, MAPK pathway and potentially the AMPK pathway in C2C12 myotubes and human muscle cells through western blot analysis. The AKT pathway, MAPK pathway and AMPK pathway have all been shown to be impaired in muscle wasting conditions.

We have also observed in preclinical studies that activation of the MAS receptor by Sarconeos (BIO101) shares many common properties with angiotensin 1-7 at the cellular level. However, Sarconeos (BIO101) did not show an effect on blood pressure or heart rate when compared to enalapril, an angiotensin-converting enzyme (ACE) inhibitor, in classical rat models of hypertension (high blood pressure). Hypertension and cardiac issues affect a majority of people over 60 years of age. ACE inhibitors, which decrease the production of Ang II, and Ang II receptor blockers, or ARBs, are widely prescribed for controlling hypertension, heart failure and preventing strokes. ACE inhibitors and ARBs may also be prescribed to treat cardiomyopathy in patients with DMD. We believe that this could be an important feature of Sarconeos (BIO101), which may allow for dual administration in patients that are also prescribed ACE inhibitors or ARBs. Sarcopenic patients on ACE inhibitors or ARBs are not excluded from the SARA-INT Phase 2b clinical trial.

The potential mechanism-of-action through activation of the MAS receptor is illustrated in the diagram below:

Our preclinical data in C2C12 cell lines and human cell models suggests that Sarconeos (BIO101) enlarges myotubes, the main structural units of muscle, warranting continued research. We believe that this is important for limiting muscle mass loss and increasing muscle strength under muscle wasting conditions. As depicted below, results from an in vitro study demonstrate that human myotubes are larger in muscle cells treated with Sarconeos (BIO101) as compared to untreated control cells.

We believe Sarconeos (BIO101) directly targets muscle tissue and cells, and improves several key muscle cell functions, including protein synthesis, regeneration and energy production through key signaling pathways that are impaired in muscle wasting conditions, regardless of the disease stage, state of disease progression or severity, and may have the potential to improve muscle function and preserve strength, mobility and respiratory capacity in various neuromuscular diseases, independent of cause (i.e., age-related or genetic) and pathophysiology.

Sarcopenia was first defined in 1989 and officially classified as a disease in 2016 based on the establishment of a code from the World Health Organization (WHO)'s International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM), used by physicians, researchers and health systems. There is currently no widely accepted standard of care for sarcopenia, however current non-medicinal treatment recommendations primarily focus on moderate physical activity, such as 30 minutes of walking per day or resistance-based (strength) training, as they exert effects on both the nervous and muscular systems that are critical to positive physiological and functional adaptations in older adults, and nutritional intervention. According to the International Clinical Practice Guidelines for Sarcopenia (ICFSR): Screening, Diagnosis and Management (Dent et al., J Nutr Health Aging. 2018;22(10):1148-1161) there is moderate certainty of evidence for the beneficial effects of physical therapy in treating patients with sarcopenia as most of the evidence for physical activity comes from studies of non-sarcopenic older adults or those with mild-moderate sarcopenia and large anecdotal effects. The efficacy of more structured physical activity programs along with certain supplementation (i.e. dietary protein intake and/ or nutrients) for the treatment of sarcopenia is being assessed in various studies, including the SPRINTT trial. However, no consensus on nutritional intervention currently exists.

Over the past two decades, other potential drug modalities have been tested in the clinic for sarcopenia, mainly myostatin inhibitors. However these treatments have yet to demonstrate effectiveness on clinically meaningful outcomes (strength and mobility) and/or safety in larger clinical trials. Based on our review of publicly available information, we believe that Sarconeos (BIO101) is the only drug candidate currently being tested in late-stage Phase 2 or Phase 3 clinical trials for sarcopenia. Based on our understanding and discussions with regulatory agencies, including the FDA and EMA, functional mobility endpoints must be achieved in order to obtain marketing approval in sarcopenia. We believe that, based on our potential mechanism-of-action and early and preclinical results, Sarconeos (BIO101) has the potential to achieve clinically relevant functional mobility endpoints necessary for marketing approval.

Our ongoing Phase 2 clinical trial is comprised of two parts: (i) an observational study (SARA-OBS) and (ii) an interventional trial (SARA-INT). The objective of the SARA-OBS study is to characterize, pre-recruit and confirm the optimal patient population for the SARA-INT Phase 2b clinical trial. Patients in the SARA-OBS study are eligible for inclusion in the SARA-INT Phase 2b clinical trial, but will need to be rescreened and reconsented prior to inclusion in the SARA-INT Phase 2b clinical trial. The SARA-INT Phase 2b clinical trial will assess the safety and efficacy of two dose levels of Sarconeos (BIO101) administered orally for 26 weeks versus a placebo in 334 elderly patients with sarcopenia at risk of mobility disability.

The SARA-INT Phase 2b clinical trial has been designed as a continuation of the SARA-OBS study, and both studies share similar governance, inclusion criteria, primary and secondary endpoints, and data management system. Both trials are being run by ICON Clinical Research under the supervision of Professor Roger Fielding at Tufts University, who serves as the principal investigator.

Beginning in February 2017, the SARA-OBS study followed 218 participants with sarcopenia across 11 clinical centers in the United States and Europe (France, Italy and Belgium) over six months. We completed enrollment in our SARA-OBS study in October 2018 and completed the study in April 2019. We enrolled the first patient in the SARA-INT Phase 2b clinical trial in May 2018. We currently have 15 open centers in the United States and Belgium and plan to expand into additional centers in the United States, Europe and potentially other countries. The regulatory agencies in France (the National Agency for the Safety of Medicines and Health Products or ANSM)) and Italy (the Italian Medicines Agency or AIFA) have each requested additional information prior to granting authorization to commence the SARA-INT Phase 2b clinical trial in their countries. While we did not anticipate gathering such information at our current stage of clinical development, we are complying with the requests and plan to submit clinical trial application supplements with the requested information in 2019 to each of the applicable regulatory agencies in an effort to commence recruitment of patients in the SARA-INT Phase 2b clinical trial in those countries.

We currently expect to complete enrollment for the SARA-INT Phase 2b clinical trial in 2020. Inclusion criteria of the SARA Phase 2 clinical trials are based on a Short Performance Physical

Battery (SPPB) score £8 out of 12 (as an index of loss of motor function) and the Foundation for the National Institutes of Health guidelines, which are summarized in the table below:

The primary endpoint of the study is gait-speed over the 400-meter walk test (400MWT), which represents a measure of the participant's mobility function. The key secondary endpoints are: (i) the chair-stand test, which is one of the mobility criteria that make up the SPPB test, (ii) the analysis of responders in the 400MWT, which are defined as those who improve more than 0.1 m/sec compared to baseline, and (iii) patient reported outcomes (PROs) as evaluated by the Short-form Health-survey (SF-36), including the Physical Function domain (PF-10) of the questionnaire.

Objectives and Study Design. The SARA-OBS study aims to characterize sarcopenia in patients over the age of 65 at risk of mobility disability. The mobility and physical performance of these participants, including body composition, are evaluated over a six-month period. This observational phase includes two main visits, one at the inclusion and one at the end of the study, supplemented by a telephone interview at three months to determine whether participants are complaining of a poor physical condition. The SARA-OBS study was designed and structured as a pre-selection for the SARA-INT Phase 2b clinical trial. Participants may consent to enroll in the SARA-INT Phase 2b clinical trial at the end of the observation period but will need to be rescreened and reconsented prior to inclusion.

Initial Results. Baseline characteristics of the 218 participants were presented in December 2018 at the Society on Sarcopenia, Cachexia and Wasting Disorders, or SCWD, conference in Maastricht, Netherlands and are summarized in the table below. We believe these characteristics are consistent with other clinical trials of sarcopenia patients, including the SPRINTT and LIFE trials.

Objectives and Endpoints. The objectives and endpoints of the study are summarized below:


		Objectives:				• Evaluate the safety and effectiveness of two doses, 175 and 350 mg b.i.d. (twice daily) of Sarconeos (BIO101) administered orally with a meal for 26 weeks against a placebo in participants over 65 at risk of impaired mobility; and
						• Measure treatment effect on improvement of physical function and on decrease of risk of mobility disability after six-month treatment.
		Primary Endpoint:				• The change from baseline in the time it takes to complete 400MWT. A minimum clinically significant benefit is set at 0.05 meter per second in the mean difference between groups.
		Key Secondary Endpoints:				• Change from baseline in the time it takes to rise from a chair, which is one of the mobility criteria that make up the SPPB test;
						• 400MWT responder analysis;
						• Change from baseline and responder analysis on standard patient reported outcome (PRO), including:
						o Short-form Health-survey (SF-36); and
						o Physical Function domain (PF-10) of the SF-36 questionnaire.
		Other Secondary, Tertiary and Exploratory Endpoints:				• Change from baseline 6-minute walk test;
						• Change from baseline in ALM measured by DEXA body composition;
						• Change in baseline in the total score of the SPPB test;
						• Change from baseline in muscle strength of the upper and lower limbs (handgrip/knee extension);
						• Change from baseline on the stair-power-climbing-test;
						• Change from baseline in the sarcopenia quality-of-life (SarQOL) questionnaire;
						• The rate of success in completing the 400MWT; and
						• Plasma parameters including safety markers, biomarkers of the RAS (renin, aldosterone), inflammation (IL-6, CRP and hsCRP), and muscle metabolism (PIIINP, myoglobin, creatine kinase MM and creatine kinase MB).

These subpopulations represent sarcopenia patients that are at a significantly high-risk for deterioration and adverse outcomes. A treatment benefit in these populations will be of significant importance, to prevent further deterioration and reduce the risk for poor outcomes.

Prospective participants will be screened for a period of up to eight weeks prior to inclusion in the trial. The interventional phase is comprised of an inclusion visit (D0) where baseline measurements will be taken on the first day and dosing will start the following day (D1), a one-month safety visit (M1), a three-month follow-up visit (M3) with safety and reduced measurements in connection with the primary endpoint, a five-month telephone interview (M5), and a final six-month visit (M6) with safety and full measurements. Participants that exhibit poor physical function or deterioration of their physical function may be asked to bring the date of their next planned visit forward or go directly to the end-of-study visit.

In addition, we will conduct a population PK sub-study (SARA-POP-PK) to evaluate PK values after one month, three months and six months of administration in a subgroup of participants at certain European centers. This sub-study will allow us to determine the levels of exposure of participants during the various visits while evaluating the occurrence of adverse events related to the doses administered.

Clinical Centers. A total of 334 elderly patients with sarcopenia at risk of mobility disability will be recruited in multiple clinical investigation centers. Currently 15 clinical sites have been opened out of 22 that will be recruiting participants for the SARA-INT Phase 2b clinical trial in the United States and Belgium. We are in the process of opening additional clinical sites in the United States, Belgium and potentially other countries in order to complete patient recruitment in 2020. We plan to submit clinical trial application supplements to commence the SARA-INT Phase 2b clinical trial in France and Italy in 2019.

We conducted a dose-escalating Phase 1 clinical trial (SARA-PK) to evaluate the safety, PK and PD effects of Sarconeos (BIO101) in 54 healthy adult and elderly subjects. Based on the results of the SARA-PK Phase 1 clinical trial, we have chosen 175 and 350 mg b.i.d. (twice daily) as the safe, active dosing levels for the SARA-INT Phase 2b clinical trial.

Single Ascending Dose. In the single ascending dose, or SAD, phase, subjects were dosed once with Sarconeos (BIO101) at a range between 100 to 1,400 mg or placebo. No abnormal clinical vital signs were reported as treatment emergent adverse events, or TEAE. All TEAEs were mild in severity and were resolved by the end of the study. No serious adverse events, or SAEs, were reported in the SAD phase.

Multiple Ascending Dose. The multiple ascending dose, or MAD, phase was conducted with three selected doses of Sarconeos (BIO101) that were orally administered to 30 patients in total broken into three groups of older adults between 65 and 85 years over 14 days. Each group consisted of eight active and two placebo per dose.

No abnormal clinical vital signs were reported as TEAE. The most common were headache, nausea, with one participant reporting an event of food poisoning at the follow-up visit and dizziness postural (vertigo) and are described in the table below. All were mild or moderate and were resolved by the end of the study. No SAEs associated with Sarconeos (BIO101) were reported in the MAD phase.

PK analysis showed a short half-life between 3 to 4 hours and that the steady state was reached from the second day of administration in the MAD phase. No accumulation of Sarconeos (BIO101) was observed at 350 mg q.d. in the MAD phase (accumulation ratio of 1.14); however, a small accumulation was observed at 350 and 450 mg b.i.d. in the MAD phase (accumulation ratio of 1.31). We determined the optimal dosing of 175 and 350 mg b.i.d. from a PK modeling study.

We also evaluated the effects of Sarconeos (BIO101) on PD markers. Results showed a tendency towards a decreased plasma level in muscle catabolism markers (myoglobin, creatine kinase) and in markers of the RAS (aldosterone and renin). This is consistent with the proposed mechanism-of-action of Sarconeos (BIO101) and is coherent with the activity of Sarconeos (BIO101) on the RAS.

As shown in the graphs below, Sarconeos (BIO101) treatment over 14 days showed (i) a dose dependant effect on muscle growth and repair, as measured by Procollagen type III N-terminal peptide (PIIINP), a common marker of muscle growth, repair and fibrosis, and (ii) a dose dependant negative correlation of muscle wasting, as measured by myoglobin, a common marker of muscle catabolism.

Effect of Sarconeos (BIO101) treatment for 14 days on the evolution of PD markers related to muscle anabolism (PIIINP) and to muscle catabolism (myoglobin)

Results from the SARA-PK Phase 1 clinical trial were released in April 2017 in an oral presentation at the International Conference on Frailty & Sarcopenia Research, in Barcelona, Spain. The results confirmed the dosing levels (175 and 350 mg b.i.d.) for the ongoing SARA-INT Phase 2b clinical trial.

We have conducted numerous in vivo experiments in C57Bl/6J mouse models to assess the activity of Sarconeos (BIO101) within the context of aging, specifically studying a high fat diet and immobilization. Key in vivo results are summarized below.

Beneficial effect on mobility in mice. We administered Sarconeos (BIO101) at 50 mg/kg/day or a placebo control to "old" mice (22 months old at the beginning of the study) that were fed a high-fat diet over 14 weeks. The mice were exercised on a treadmill and maximum running velocity (Vmax) was recorded after 14 weeks of treatment. Untreated "adult" mice (12 months old at the beginning of the study) were also fed a high-fat diet and exercised similarly to determine a positive control velocity. As shown in the graph below, "old" control mice had a Vmax that was approximately 21% less than "adult" control mice (p<0.001) demonstrating the effects of aging. Further, results showed that "old" mice treated with Sarconeos (BIO101) demonstrated a significant improvement in Vmax as compared

to "old" control mice (p<0.01), compensating almost completely for the loss of mobility due to aging. These results were presented in December 2016 at the SCWD conference in Berlin, Germany.

Effect of chronic Sarconeos (BIO101) treatment over 14 weeks on maximum running velocity in old mice.

Preservation of muscle strength after immobilization in mice. To model muscle wasting associated with impaired mobility, we immobilized young mice (13 weeks old) and began administering either Sarconeos (BIO101) at 50 mg/kg/day or a placebo control (vehicle). After 14 days, we removed the immobilization and continued administration of Sarconeos (BIO101) for an additional 14 days. The absolute strength of hindlimb muscle was recorded at various times over the 28-day period. As shown in the graph below, mice treated with Sarconeos (BIO101) demonstrated a preservation of muscle strength while immobilized compared to vehicle control. We believe these results support continued research to investigate whether Sarconeos (BIO101) could be an effective treatment to preserve muscle function under conditions of disuse or immobility.

Effect of chronic Sarconeos (BIO101) treatment over 28 days on maximal absolute strength in hindlimb-immobilized mice.

Sarcopenia is a major cause of mobility disability in the elderly, resulting in a loss of independence, increased risk of adverse health events and hospitalization, and ultimately death. Sarcopenia is highly prevalent in adults greater than 65 years of age with an estimated prevalence between six and 22 percent. It poses a major public health issue and is steadily increasing as the global population ages. If approved by regulatory authorities for commercial use, we believe there is a market potential for Sarconeos (BIO101) in sarcopenia, as there is currently no approved medication for Sarcopenia and an unmet medical need for therapeutic treatments.

Over the past two decades, other companies have launched multiple clinical development programs to treat sarcopenia, primarily with drug candidates falling in one of two classes: (i) myostatin inhibitors and (ii) SARMs. Myostatin inhibitors, which primarily aim to increase muscle mass by blocking myostatin (myostatin acts as an essential negative regulator of muscle bulk), have been found to increase muscle mass in early clinical trials. However, they have yet to demonstrate effectiveness on clinically meaningful mobility outcomes (strength and mobility) or safety in larger clinical trials and/or have not progressed through the clinic. Both steroidal and non-steroidal SARMs have been tested as therapeutic agents for several medical conditions, including muscle-wasting diseases, but none have progressed through clinical development mainly due to safety concerns. Based on our review of publicly available information, currently, neither myostatin inhibitors or SARMs are being tested in late-stage clinical trials for sarcopenia. Based on our review of research in this area, we believe Sarconeos (BIO101) is currently the only drug candidate being tested in an interventional Phase 2 clinical trial for the treatment of sarcopenia and has the potential to improve the vital functional outcomes of mobility disability necessary for regulatory approval.

DMD is a rare, genetic neuromuscular disease in male children and young adults, which is characterized by accelerated degeneration of muscles and is responsible for a loss of mobility, respiratory failure and cardiomyopathy, leading to premature death. It is the most common form of muscular dystrophy in children, affecting approximately one in 5,000 newborn boys (approximately 20,000 new cases annually worldwide). DMD is caused by mutations in the dystrophin gene that result in the absence or very low levels of functional dystrophin, a cytoskeletal protein that protects muscle cells.

The absence of dystrophin in muscle severely weakens the structural and membrane stability of the muscle fibers. During normal muscle contraction and stretching the muscle fibers become damaged and eventually undergo necrosis (i.e., cell death). In order to compensate for the increased necrosis, muscle tissue regeneration is accelerated. This process soon becomes exhausted and muscle degeneration accelerates as muscle fibers are replaced by fat and connective tissue (fibrosis), resulting in the loss of muscle strength and mobility. DMD evolves according to a very well understood progression with symptoms that are similar to those associated with accelerated aging across all stages. DMD progression can be summarized as follows:

We believe there continues to be an unmet medical need in DMD. We are preparing to submit an IND application to the FDA and clinical trial applications to the applicable regulatory agencies in Europe in the second half of 2019 to advance an oral pediatric formulation of Sarconeos (BIO101) for DMD into the clinic through our MYODA clinical program, utilizing a seamless clinical trial design

with a primary endpoint defined as a composite score combining muscle strength, mobility, and respiratory outcomes, which is adapted to the stage of severity of the disease in each patient as early as 2020, subject to regulatory approval.

We have weight-adjusted the dose range of Sarconeos (BIO101) that we aim to test in the pediatric patient population based on modeling of data from animal studies and the SARA-PK Phase 1 trial in healthy adult and elderly participants. The low end of the dose range is driven by efficacy studies and the upper end of the dose range is driven by safety margins (toxicology and Phase 1). At the low end of the dose range, differences caused by the variance in animal models (i.e., specie, age and size) could affect efficacy between animals and humans (both adults and children). At the high end of the dose range, differences in body composition, absorption and metabolism between the age and patient segments could affect safety margins and tolerability. We do not have actual experimental safety PK, PD or efficacy data from clinical testing in a pediatric patient population comprised of developing children (2-12 years), adolescents (12-16 years) or young adults. The seamless MYODA clinical trial aims to test a range of doses in a dose escalating manner to address these potential differences in safety and efficacy.

We have designed our MYODA clinical program to specifically address the following known challenges in DMD clinical development:

We received feedback from the CHMP in December 2018 on our trial design concepts and will continue to work in concert with the relevant regulatory agencies. Subject to regulatory approval, we expect that our MYODA clinical trial will encompass all three phases of clinical development (Phase 1 to Phase 3) made up of two distinct stages: (i) a clinical PoC stage (MYODA-INT), followed by (ii) a confirmatory stage, both of which will be global, multicentric, double-blind, placebo-controlled clinical trials that will be run under one seamless design. However, the design described below may change following discussions with various regulatory agencies.

To address the issue of variability due to targeting a broad range of disease states (i.e., ambulatory to non-ambulatory), the primary endpoint will be a composite score combining muscle strength, mobility, and respiratory outcomes, which is adapted to the stage of severity of the disease in each patient. We believe Sarconeos (BIO101) directly targets muscle tissue and cells, and increases several key muscle cell functions that are impaired in individuals to varying degrees. A key factor will be designing clinical endpoints to measure the functional benefit to the individual, which will be dependent on the individual. We believe, therefore, that the challenge in designing the clinical endpoints will be more about finding the best measure of benefit and not about the particular disease and its state, assuming the regulatory agencies accept our study plan and clinical trial designs.

Our study design and clinical trial protocols are subject to regulatory approval and will be submitted to regulatory agencies for review. We plan to work with the agencies to finalize the protocols. Additional challenges and risks remain with our innovative clinical trial program, including:

We have conducted various in vivo experiments in mdx mice, a commonly used model of DMD. The results from these mdx mice studies are consistent with the results on cellular activity and functional outcomes from both in vitro and in vivo studies of Sarconeos (BIO101) in sarcopenia. We believe these results provide additional support for our belief that Sarconeos (BIO101) has the potential for improving mobility and muscle strength. In addition, we believe these results suggest that Sarconeos (BIO101) may increase respiratory function and decrease fibrosis. Key in vivo results in DMD are summarized below.

Improved respiratory function in mice. The loss of respiratory function is a major health issue for later-stage, non-ambulatory patients with DMD. Recent results have shown that chronic (eight weeks) daily administration of 50/mg/kg of Sarconeos (BIO101) ameliorates the time-dependent degradation of respiratory function observed in C57BL10-mdx mice as compared to C57BL10 control mice. This

protective effect on respiratory function is not only associated with breathing parameters as suggested by enhanced pause (PenH) measurements, but also by an improvement of deep airway structure of the respiratory system shown by FlexiVent experiments, which are a common measurement for in vivo lung function. PenH (enhance pause) is calculated as follows: (PIP/PEP) × Pause, where PIP is the maximum change in chamber pressure during inspiration, PEP is the maximum change in chamber pressure during expiration, and Pause equals (TE-TR)/TE, where TE is expiratory time and TR is relaxation time. As shown in the three graphs below, C57BL10-mdx mice treated with Sarconeos (BIO101) exhibited improved respiratory function as measured by resistance, elastance and PenH of the lung. These results were presented in March 2019 at the annual international congress of Myology in Bordeaux, France.

Effect of chronic Sarconeos (BIO101) treatment on resistance, elastance and airway reactivity (PenH).

Improved mobility and muscle strength in mice. We studied the effect of chronic oral administration of 50 mg/kg/day of Sarconeos (BIO101) on mobility and strength over eight weeks in C57BL10-mdx mice. Mobility was measured by running distance and strength was measured by maximum absolute strength (force) in the four-limb grip-test test. Results show that Sarconeos (BIO101) treatment improved mobility in certain animal models, as C57BL10-mdx mice treated with Sarconeos (BIO101) ran 2.4x farther than untreated control C57BL10-mdx mice. Results show that Sarconeos (BIO101) treatment improved muscle strength in animal models, as C57BL10-mdx mice treated with Sarconeos (BIO101) showed an approximate 14% improvement in strength as compared to untreated control C57BL10-mdx mice.

Effect of Sarconeos (BIO101) on mobility (running distance) and muscle strength (four-limb grip-test force).

These in vivo results on muscle functionality (mobility and strength) in mice are consistent with cellular and molecular changes observed in our previous preclinical studies, including (i) improved energy metabolism (mitochondrial respiration and spare respiratory capacity), (ii) improved myoblast differentiation, and (iii) confirmed activation of the AKT Pathway and MAPK Pathway involved in anabolism and regeneration, respectively, both known for being impaired in DMD muscle. These results were presented in October 2018 at the WMS conference in Mendoza, Argentina.

Improved lesional profile in mice. We have observed that Sarconeos (BIO101) treatment may improve the histological (muscular lesion) profile of muscle in mice, consistent with the improvements in physical performance and muscle function (mobility and strength), as mentioned above. We performed histopathological analysis of muscle from C57BL10-control mice, C57BL10-mdx mice and C57BL10-mdx mice treated with Sarconeos (BIO101). Muscle from C57BL10-mdx mice exhibited anisocytosis (atrophy of muscle fibers), as well as chronic inflammation associated with fibrosis as compared to healthy muscle from control mice. Observations of muscle from C57BL10-mdx treated mice showed that chronic administration of Sarconeos (BIO101) decreased anisocytosis and inflammation as compared to muscle from C57BL10-mdx mice. These results were presented in October 2017 at the WMS conference held in Saint Malo, France.

We believe that there is market potential for Sarconeos (BIO101) in DMD, if approved by regulatory authorities for commercial use. DMD is the most common form of genetic muscular dystrophy in children, affecting approximately one in 5,000 newborn boys, and resulting in premature death. In many countries, corticosteroids are the standard drug therapy. However, corticosteroids typically only slow the progression of muscle weakness and delay the loss of ambulation by up to two years. They have also been associated with adverse side effects and are generally not suitable for long-term administration.

DMD is caused by mutations in the dystrophin gene that result in the absence of very low levels of functional dystrophin, a cytoskeletal protein that protects muscle cells. Other therapeutic approaches aim to restore the expression of the dystrophin gene and thus restore protein function through exon-skipping. Currently, there are two marketed targeted treatments that can address approximate 13% of the overall DMD patient population with those genetic mutations.

In addition to these targeted therapies, gene therapies that are under development aim to introduce a gene coding for a truncated dystrophin protein that could limit immune reactions. These therapies typically suffer from low transfection rates resulting in low levels of dystrophin expression and potential severe immune reactions. This leaves room for combinations of genetic treatments with other disease modifying agents, regardless of the mutation. Additional approaches in development include: immune modulators, anti-fibrotic agents and agents that enhance muscle mass and function. We believe that Sarconeos (BIO101) directly targets muscle tissue and cells, increases key muscle cell functions that are impaired independent of the genetic mutation that causes the disease, and has the potential to be used complementarily with corticosteroids, current targeted therapies and other gene therapies under development. We also believe that because Sarconeos (BIO101) targets various impaired muscle tissues and cells relevant to muscle strength, mobility and respiratory function, and has the potential to be used in all stages of DMD progression, including both ambulatory and non-ambulatory patients.

Our second drug candidate, Macuneos (BIO201), is an orally administered small molecule in development for the treatment of retinopathies. The initial indication we plan to seek approval for is dry AMD, followed by Stargardt disease.

Utilizing our expertise in functional screens and assays, we expanded our drug discovery efforts to other age-related diseases, with a focus on retinopathies. Using cellular models developed with the Institute of Vision at Sorbonne University in Paris, we screened a variety of carotenoids and flavonoids for their ability to protect retinal pigment epithelium, or RPE, cells against the photo-oxidative stress induced by blue light in the presence of A2E, a phototoxic byproduct of the visual pigment cycle. We selected norbixin (an apo-carotenoid) for clinical development based on its pharmacological properties and safety profile in animal models of AMD and Stargardt disease. Next, we identified its molecular target(s) and identified a potential mechanism of action.

Results from our preclinical studies support continued research to investigate whether Macuneos (BIO201) may protect RPE cells against the photo-oxidative stress induced by blue light in the presence of A2E through non-canonical activation (of the transrepressive activity) of peroxisome proliferator-activated receptors, or PPARs. PPARs are nuclear receptors that have two types of activities: (i) a canonical activity, which primarily regulates carbohydrate and lipid metabolism in regenerative tissues only, and (ii) a non-canonical activity, which inhibits inflammatory processes in neuronal tissues, such as the brain or retina. Based on the result from our preclinical studies, we believe that Macuneos (BIO201) potentially counteracts the phototoxic effects of A2E by selective activation of the non-canonical pathway of PPARa and PPARb/d responsible for the anti-oxidative, anti-inflammatory and anti-apoptotic activity observed in the retina. We believe this is in contrast with most PPAR ligands that mainly exhibit canonical activity and are typically associated with known side effects.

The potential mechanism-of-action through non-canonoical activation of the transrepressive activity of PPARs is illustrated in the diagram on the below:

AMD is one of the leading causes of irreversible vision loss and blindness in the people over the age of 50 worldwide, according to the BrightFocus Foundation's Age-Related Macular Degeneration: Facts & Figures Fact Sheet. AMD affects the central part of the retina, known as the macula, which is responsible for central vision and its sharpness. There are two types of AMD:

Approximately 85 to 90% of patients with AMD suffer from dry AMD. We believe that photo-oxidative and inflammatory stresses induced by the accumulation of A2E in RPE cells are the main factors responsible for the degenerative process of the retina in diseases such as AMD. We believe the biggest opportunity in treating dry AMD is preventing advancement into the later stages, GA or wet AMD, where vision loss is severe and can lead to visual disability.

We have conducted chronic and acute rodent and non-rodent toxicology studies that we believe will be sufficient to support our IND and clinical trial applications for our MACA clinical development program. We plan to hold, in the second half of 2019, scientific advice meetings with the EMA and applicable regulatory agencies in Europe regarding our clinical development plan for Macuneos (BIO201) in dry AMD and, subject to regulatory approval, commence a Phase 1 clinical trial (MACA-PK) in healthy volunteers to assess the safety, PK and PD of Macuneos (BIO201).

In collaboration with the Institute of Vision, we used models of primary porcine RPE cell cultures to test the effect of Macuneos (BIO201). We believe this model best preserves functional defense mechanisms against photo-oxidative stress and better represents functioning human RPE cells as compared to existing stable cell lines. We exposed these RPE cells to blue light in the presence of A2E in order to explore the protective effect of Macuneos (BIO201) on RPE cell death.

Increased cell survival. Our preclinical data suggest that Macuneos (BIO201) may protect RPE cells from cell death, in a dose-dependent manner, against the photo-oxidative stress induced by blue light in the presence of A2E. These results were presented in 2016 at the annual meeting of the Association for Research in Vision and Ophthalmology, or ARVO, in Seattle, Washington, and published in PLoSONE (Fontaine et al; 2016).

We have observed that Macuneos (BIO201) protects the retina after both oral and intra-vitreal administration in various animal models of AMD and Stargardt disease. The results from the studies,

which are summarized below, were presented in 2016 at the annual meeting of the ARVO in Seattle, Washington.

Preservation of visual function in mice. We studied mice in which two genes encoding the proteins involved in the visual pigment cycle (the Abca4 transporter and the retinol dehydrogenase Rdh8) were absent. These animals, called Abca4^[ib]-/[ib]- Rdh8^[ib]-/-mice, accumulated A2E in their eyes and showed an early loss of electroretinogram amplitude. Our preclinical data suggest that chronic oral administration of Macuneos (BIO201) for three and six months may be effective in protecting the retina, as measured by electroretinography. This is a commonly used way to measure retinal function by looking at the electric signal transport from the retina to the brain. As shown in the figure below, Macuneos (BIO201) treated mice showed a less degraded electroretinogram as compared to the untreated control mice, meaning the treated mice have slower visual function loss. The six month results were presented in 2018 at the annual meeting of the ARVO in Honolulu, Hawaii.

Effects of chronic oral administration of Macuneos (BIO201) on ERG Amplitude in Abca4-/- Rdh8-/-mice.

Reduced A2E Accumulation in mice. We studied the effect of Macuneos (BIO201) treatment on the accumulation of A2E in the retina of Abca4^[ib]-/[ib]- Rdh8^[ib]-/-mice. We began a three-month dosing regimen starting on mice that were 2 months of age. We observed that there was significant accumulation of A2E in vehicle Abca4^[ib]-/[ib]- Rdh8^[ib]-/-mice treated with placebo over three months as compared to control wild type mice at the beginning of the study, confirming a dysfunction of the visual cycle. Results demonstrated that chronic oral administration of Macuneos (BIO201) reduced A2E accumulation in the retina in treated Abca4^[ib]-/[ib]- Rdh8^[ib]-/-mice by approximately 45% as compared to vehicle control mice, which we believe is a key factor for maintaining visual function.

Effects of chronic oral administration of Macuneos (BIO201) on A2E accumulation in Abca4^[ib]-/[ib]- Rdh8^[ib]-/-mice.

Dose-dependent protection of retina integrity in rats. In the classical blue light damage (BLD) rat model using normal albino rats, we observed that intra-peritoneal administration of Macuneos (BIO201) protected the retina in a dose-dependent manner, as measured by the number of remaining layers of photoreceptors. We demonstrated that there was an approximate 90% increase in the number of photoreceptors layers following the maximum dose of 100 mM of Macuneos (BIO201) as compared to the vehicle control. The results were published in PLoSONE (Fontaine et al.; 2016).

Number of layers of photoreceptors in the blue light rat model after intraperitoneal injection of Macuneos (BIO201).

Based on this body of work, we believe that Macuneos (BIO201) may have significant clinical potential for the treatment of retinopathies, including dry AMD and Stargardt disease, and warrants continued investigation.

We believe that there is market potential for Macuneos (BIO201) in dry AMD, if approved by regulatory authorities for commercial use. AMD is one of the leading causes of irreversible vision loss and blindness in people over the age of 50 worldwide, and its prevalence increases with advancing age. Based on our review of publicly available data, there is currently no approved medication for dry AMD, which represents between 85 to 90% of all AMD cases according to the American Macular Degeneration Foundation, and, based on our estimates from publicly available information, affects approximately 145 million people worldwide, and is expected to increase over time as the population ages.

There are a number of companies currently developing treatments for dry AMD, including anti-complement or neuroprotective agents that may treat or alter the progression of the disease. We believe the market for AMD will remain fragmented and will include stand-alone and combination treatments for all stages of the disease. We will continue to study Macuneos (BIO201) to determine its clinical safety and effectiveness, and to explore the feasibility of oral administration, and different modes of action.

Our preclinical pipeline currently consists of Macuneos (BIO201), as well as BIO103 and BIO203, which are chemically synthesized life-cycle extension products for Sarconeos (BIO101) and Macuneos (BIO201), respectively. We are testing these preclinical drug candidates in multiple age-related diseases, including rare and orphan disease indications whose disease progression and symptoms are similar to those associated with accelerated aging. We plan to continue to identify new drug candidates through our drug discovery platform based on our functional assays and reverse pharmacology approach.

The biotechnology and pharmaceutical industry is characterized by rapidly advancing technologies, intense competition and a strong emphasis on proprietary products. While we believe that our expertise in age-related diseases, scientific knowledge and intellectual property portfolio provide us with competitive advantages, we face potential competition from many different sources, including major pharmaceutical, specialty pharmaceutical and biotechnology companies, academic institutions, governmental agencies and public and private research institutions. Not only must we compete with other companies that are focused on neuromuscular diseases and retinopathies, but any drug candidates that we successfully develop and commercialize will compete with existing therapies and new therapies that may become available in the future.

Many of our competitors may have significantly greater financial resources and expertise in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approvals and marketing approved products than we do. These competitors also compete with us in recruiting and retaining qualified scientific and management personnel and establishing clinical trial sites and patient registration for clinical trials, as well as in acquiring technologies complementary to, or necessary for, our programs. Mergers and acquisitions in the pharmaceutical, biotechnology and diagnostic industries may result in even more resources being concentrated among a smaller number of our competitors. Smaller or early stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies.

The key competitive factors affecting the success of all of our drug candidates, if approved, are likely to be their efficacy, safety, tolerability, convenience, price and the availability of reimbursement from government and other third-party payors. Our commercial opportunity could be reduced or eliminated if our competitors develop and commercialize products that are safer, more effective, have fewer or less severe side effects, are more convenient or are less expensive than any products that we may develop. Our competitors also may obtain FDA, EMA or other regulatory approval for their products more rapidly than we may obtain approval for ours, which could result in our competitors establishing a strong market position before we are able to enter the market.

For our drug candidates, the main competitors for each target indication include:

Title of each class of securities to be registered	Proposed maximum aggregate offering price(1)	Amount of registration fee




Ordinary shares, €0.20 nominal value per share(2)(3)(4)	$12,075,000	$1,464(5)

	Per Ordinary Share	Per ADS	Total




Public Offering Price	€	$	$

Underwriting Discounts and Commissions(1)	€	$	$

Proceeds to us, before expenses	€	$	$

		Page

PROSPECTUS SUMMARY		1
RISK FACTORS		13
SPECIAL NOTE REGARDING FORWARD-LOOKING STATEMENTS		67
USE OF PROCEEDS		69
DIVIDEND POLICY		71
CAPITALIZATION		72
DILUTION		74
SELECTED FINANCIAL AND OTHER DATA		77
MANAGEMENT'S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITIONS AND RESULTS OF OPERATIONS		79
BUSINESS		95
MANAGEMENT		144
RELATED PARTY TRANSACTIONS		157
PRINCIPAL SHAREHOLDERS		160
DESCRIPTION OF SHARE CAPITAL AND ARTICLES OF ASSOCIATION		162
LIMITATIONS AFFECTING SHAREHOLDERS OF A FRENCH COMPANY		185
DESCRIPTION OF AMERICAN DEPOSITARY SHARES		187
SHARES AND ADSs ELIGIBLE FOR FUTURE SALE		195
MATERIAL UNITED STATES FEDERAL INCOME TAX AND FRENCH TAX CONSIDERATIONS		198
ENFORCEMENT OF CIVIL LIABILITIES		208
UNDERWRITING		209
EXPENSES OF THE GLOBAL OFFERING		220
LEGAL MATTERS		221
EXPERTS		221
WHERE YOU CAN FIND MORE INFORMATION		221
INDEX TO THE FINANCIAL STATEMENTS		F-1

	Ordinary shares purchased(1)					Total consideration

	Ordinary shares purchased(1)					Total consideration					Average price per ordinary share		Average price per ADS
	Number		Percent			Amount		Percent			Average price per ordinary share		Average price per ADS
Existing shareholders		13,463,413		50.6	%	€	50,735,000		84	%	€	3.77
New investors		13,125,000		49.4			9,362,461		16			0.71	$	8.00

Total		26,588,413		100	%	€	60,097,461		100	%

(Amounts in thousands of euros)

Personnel expenses	(666	)	(977	)
Purchases and external expenses	(1,904	)	(2,122	)
Other	(46	)	(50	)

Research and development expenses	(2,616	)	(3,148	)

Research tax credit	599		859
Subsidies	—		—

Research tax credit and Subsidies	599		859

Research and development, net	(2,017	)	(2,289	)


France (State or Other Jurisdiction of Incorporation or Organization)		2834 (Primary Standard Industrial Classification Code Number)		Not Applicable (I.R.S. Employer Identification Number)


Copies to:
Aron Izower Reed Smith LLP 599 Lexington Avenue, 26nd Floor New York, NY 10022 +1 (212) 521-5400		Linda Hesse Jones Day 2 rue Saint-Florentin 75001 Paris France +33 1 56 59 39 39

	As of March 31, 2019

	Per Ordinary Share				Per ADS
Assumed offering price			€	0.71			$	8.00
Historical net tangible book value per ordinary share or ADS as of March 31, 2019	€	0.04			$	0.42
Increase in net tangible book value per ordinary share or ADS attributable to new investors participating in the global offering		0.23				2.65

As adjusted net tangible book value per ordinary share or ADS after the global offering		0.27				3.07
Dilution in as adjusted net tangible book value per ordinary share or ADS to new investors participating in the global offering			€	0.44			$	4.93

(Amounts in thousands of euros)

Personnel costs	(326	)	(701	)
Purchases and external expenses	(531	)	(572	)
Other	(8	)	62

General and administrative expenses	(865	)	(1,211	)

(Amounts in thousands of euros)

Other financial expenses	(10	)	(8	)
Financial interest and amortized cost of the non-convertible bonds	—		(268	)
Other financial income	4		1
Foreign exchange gains (losses)	(16	)	48

Net financial expense	(22	)	(227	)

(Amounts in thousands of euros)

Personnel expenses	(2,104	)	(2,962	)
Purchases and external expenses	(7,312	)	(9,539	)
Other	(177	)	(190	)

Research and development expenses	(9,593	)	(12,691	)

Research tax credit	2,545		3,133
Subsidies	5		45

Research tax credit and Subsidies	2,550		3,178

Research and development, net	(7,043	)	(9,513	)

(Amounts in thousands of euros)

Personnel costs	(1,257	)	(1,804	)
Purchases and external expenses	(1,576	)	(2,428	)
Other	(32	)	(116	)

General and administrative expenses	(2,865	)	(4,348	)

(Amounts in thousands of euros)

Other financial expenses	(118	)	(38	)
Financial interest and amortized cost of the convertible notes and non-convertible bonds	(3,145	)	(189	)
Change in fair value of financial instruments	1,756		—
Other financial income	7		10
Foreign exchange gains (losses)	0		19

Net financial expense	(1,500	)	(198	)

(Amounts in thousands of euros)

Non-convertible bonds(a)	8,828	2,348	5,760	720		—
Conditional advances	1,295	327	564	404		—
Bank overdrafts	16	16	—	—		—
Finance leases(b)	46	46	—	—		—
Operating lease obligations(b)	215	215	—	—		—
Licence agreements(c)	45	—	45	(b	)	(b	)

Total	10,445	2,952	6,369	1,124		(b	)

Inclusion Criteria		Cutpoints

Age:		³ 65 years
SPPB score(1):		£ 8
DEXA body composition results for men(2):		ALM/BMI(3) index <0.789 or an absolute ALM index <19.75
DEXA body composition results for women(2):		ALM/BMI index <0.512 or an absolute ALM index <15.02
Physical activity(4):		30 minutes of exercise per day


Age:		79.29
BMI:		29.3
SPPB:		6.12
Gait speed:		<0.8 m/s
6-minute walk test:		295.14 meters

Dose	No. of treated subjects with TEAE (Type of TEAE)	No. of placebo subjects with TEAE

350 mg q.d. (once daily)	2 subjects (mainly wound and pain in extremity).	3 subjects (mainly musculoskeletal and connective tissues (back pain, spasms and stiffness) and nervous system (dizziness and headache)).
350 mg b.i.d. (twice daily)	7 subjects (mainly gastrointestinal (constipation, diarrhea and bloating), and musculoskeletal and connective tissue (back pain, spasms and stiffness)).
450 mg b.i.d. (twice daily)	8 subjects (mainly gastrointestinal (constipation, diarrhea and bloating), musculoskeletal and connective tissues (back pain, spasms and stiffness) and nervous system (dizziness and headache)).