Financial Performance - The company incurred losses of €31.2 million, €24.3 million, and €17.6 million ($19.5 million) for the years ended December 31, 2021, 2022, and 2023, respectively, primarily due to expenses related to preclinical and clinical programs [64]. - The company expects to continue incurring losses as it develops drug candidates and conducts clinical trials, with no revenue expected from product sales in the foreseeable future [74]. - The company has a history of significant losses since its inception in 2006, raising doubts about its ability to continue as a going concern [62]. - The company anticipates that its current capital resources will only fund planned operating expenses into the first quarter of 2025, indicating a need for additional financing [68]. - The company may need to seek additional funds through public or private equity offerings or debt financings due to changing operating plans and market conditions [68]. Financing and Capital Resources - As of December 31, 2023, the company had cash and cash equivalents of €5.6 million ($6.2 million) and drew down €4 million from its credit facility with ATLAS Special Opportunities LLC [67]. - The company signed a convertible bond financing agreement with ATLAS for up to €32 million, of which €12 million has been issued as of December 2023, with an outstanding debt of €1.45 million [90]. - The company entered into a financing agreement with Kreos Capital VI for up to €10 million, which includes €7.75 million in convertible bonds and €2.25 million in non-convertible bonds [91]. - The company has the capacity to issue two additional tranches of convertible bonds for a total amount of €8 million under the ATLAS agreement, expiring on June 14, 2024 [90]. - The company’s debt agreements impose restrictions that limit operational flexibility, including limitations on incurring additional indebtedness and asset sales [96]. Clinical Development and Drug Candidates - The company has no products approved or authorized for sale, with its lead drug candidate, BIO101 (20-hydroxyecdysone), currently in clinical development, and the second drug candidate, BIO201, still in preclinical development [109]. - The company plans to develop a pipeline of drug candidates targeting age-related diseases, necessitating prioritization of certain candidates and indications [80]. - The company is focused on obtaining necessary marketing approvals from regulatory authorities for its drug candidates [113]. - Future success will depend on the timely completion of clinical trials and the ability to secure additional capital [113]. Clinical Trials and Results - The SARA-PK Phase 1 clinical trial involved 54 healthy adult and elderly subjects, establishing safe dosing levels of 175 and 350 mg b.i.d. for the subsequent Phase 2b trial [122]. - No serious adverse events were reported during the single ascending dose phase of the clinical trial, indicating a favorable safety profile [123]. - The pharmacokinetic analysis showed a short half-life of 3 to 4 hours for BIO101, with steady state reached by the second day of administration [129]. - The company observed a dose-dependent effect on muscle growth and repair, as indicated by plasma Procollagen type III N-terminal peptide (PIIINP) levels [131]. - The SARA-INT Phase 2b study evaluated the safety and effectiveness of two doses of BIO101 (20-hydroxyecdysone) at 175 mg and 350 mg b.i.d. over 26 weeks against a placebo in elderly participants at risk of impaired mobility [189]. Impact of COVID-19 - The company has implemented measures to address disruptions caused by COVID-19, including social distancing and remote work policies, which have affected clinical trial operations [101]. - The company reported a significant impact on clinical trials due to the COVID-19 pandemic, affecting patient movement and healthcare services [166]. - The SARA-INT study involved 233 participants receiving BIO101 at doses of 175 or 350 mg b.i.d. for 6 to 9 months, but only 45% completed the study due to COVID-19 disruptions [135]. - The study was underpowered due to only 45% of participants completing the end-of-study assessments at the clinic [213]. Regulatory and Compliance Risks - The company is subject to various risks, including competition, regulatory scrutiny, and potential product liability lawsuits, which could adversely affect its business [29]. - Regulatory approval may be suspended or withdrawn if compliance with requirements is not maintained [164]. - Regulatory approvals for drug candidates may face delays or denials, impacting commercialization and revenue generation [168]. - The FDA requires compliance with regulations throughout the drug development process, and failure to do so may result in sanctions including license suspension or product recalls [190]. - Legislative changes in the U.S. and EU could impose additional requirements, increasing operating costs and affecting profitability [179]. Market and Economic Conditions - The company may face challenges in obtaining additional financing, which could delay or limit its product development and operations [72]. - The company’s ability to access capital may be negatively impacted by economic downturns resulting from health pandemics, which could affect liquidity and demand for future products [107]. - The cumulative effects of various factors could lead to unpredictability in the company’s annual operating results, making period-to-period comparisons less meaningful [87].

• Sarconeos (BIO101) showed a very good safety profile at the doses of 175 mg bid and of 350 mg bid with no Serious Adverse Events (AE) related to the product Rare, genetic neuromuscular disease in male children characterized by accelerated degeneration of muscles, responsible for loss of mobility, respiratory failure and cardiomyopathy, leading to premature death. 20 21 LIVE HEALTHIER LONGER Forward Looking Statements Change from baseline at M6 Gait speed Full Analysis Set Per-Protocol Population p = 0.008 ...

Financial Position - As of December 31, 2022, the company had cash and cash equivalents of €11.1 million ($11.8 million) to support its operations[41]. - The company has incurred significant losses since inception and anticipates continued losses for the foreseeable future[40]. - The company expects its existing capital resources will be sufficient to fund planned operating expenses for the next 12 months[198]. - The company may need to seek additional funds sooner than planned due to various unknown factors[198]. - As of December 31, 2022, the company had 238,297,642 ordinary shares outstanding[175]. - The company is classified as an emerging growth company[180]. Drug Development and Regulatory Challenges - The company plans to develop a pipeline of drug candidates targeting age-related diseases, focusing resources on specific diseases and pathways[44]. - The company has no products approved for sale, with its lead drug candidate Sarconeos (BIO101) in clinical development and Macuneos (BIO201) in preclinical development[73]. - The company may face challenges in obtaining regulatory approvals, which are critical for commercialization[64]. - The company is not permitted to market investigational drug candidates in the EU, the United States, or other countries until receiving requisite regulatory approvals[77]. - A small percentage of biotechnology and pharmaceutical products in development successfully complete regulatory approval processes and are commercialized[78]. - Clinical development is lengthy and expensive, with uncertain outcomes; earlier study results may not predict future trial results[79]. - The company may experience delays in obtaining regulatory approval, recruiting suitable patients, and accessing trial sites due to COVID-19 restrictions[82]. - The company may face challenges in demonstrating the safety and efficacy of drug candidates, which could lead to marketing approval delays or restrictions[85]. - The company may incur unplanned costs and may not obtain marketing approval for broader indications or patient populations as intended[99]. - Regulatory authorities may impose additional restrictions or withdraw approvals if undesirable side effects are identified, which could significantly impact revenue[122]. - The contract manufacturer must comply with strict regulatory requirements, and any failure to do so could significantly impact the ability to develop and market drug candidates[140]. - The company may need to secure alternative sources of commercial supply to meet anticipated market demand, which could involve significant challenges and additional regulatory approvals[142]. - The company does not currently have the ability to independently conduct GLP-compliant preclinical studies or GCP-compliant clinical trials, relying on third parties for these activities[143]. - The company faces significant risks related to health pandemics, which could disrupt business operations and delay clinical programs[161]. - Regulatory authorities may experience increased workloads, potentially prolonging review timelines for drug applications and impacting commercialization schedules[152]. - The company may experience delays in obtaining necessary regulatory authorizations for clinical programs, affecting the timeline for initiating studies and trials[166]. Supply Chain and Manufacturing Risks - The company relies on third parties for raw materials and clinical trials, which may impact its operations[32]. - The company relies on a single supplier for the plant material required for Sarconeos (BIO101) and has not established a long-term supply agreement, which poses a risk to clinical trials and future commercialization[111]. - Macuneos (BIO201) relies on a single supplier for the plant material required for its clinical program, with no long-term supply agreement in place, which poses a risk to future clinical trials and commercialization[139]. - The company has not entered into a long-term manufacturing agreement with its contract manufacturing partner, Patheon, which could affect the ability to produce drug candidates for commercialization[127]. - The company is evaluating alternative methods for producing 20-hydroxyecdysone to optimize the supply chain for Sarconeos (BIO101) in anticipation of commercial needs[126]. - The company is evaluating alternative methods for producing norbixin to optimize the supply chain for projected commercial needs[139]. Competition and Market Dynamics - The commercial success of drug candidates will depend significantly on physician and patient adoption, influenced by factors such as safety, efficacy, and competitive pricing[123]. - The company faces competition from larger pharmaceutical and biotechnology firms with greater resources, which may inhibit market penetration efforts[133]. - Competition in the biotechnology and pharmaceutical industries is intense, with numerous companies developing similar healthcare products, which could hinder market penetration[144]. - The company must navigate public misperceptions regarding its therapies, particularly those related to "anti-aging," which could hinder adoption and market success[110]. Financing and Debt Obligations - The company signed a convertible bond financing agreement of €24 million with ATLAS to support the development of Sarconeos (BIO101)[226]. - All convertible bonds related to the ATLAS contract have been converted as of December 31, 2022[226]. - Company signed a new convertible bond financing agreement with ATLAS for €32 million, issuing two tranches totaling €10 million as of December 2022[227]. - Kreos Capital financing agreement provides up to €10 million, including €7.75 million in convertible bonds and €2.25 million in non-convertible bonds[228]. - Non-convertible bonds from Kreos bear a 10% annual interest rate, repayable in 36 monthly installments starting April 2022[228]. - Convertible bonds from Kreos have a 9.5% annual interest rate, with repayment or conversion required by March 31, 2025[228]. - Company issued 2,218,293 warrants to Kreos, allowing the purchase of new ordinary shares at €0.56 per share over seven years[228]. - Potential inability to make required payments may necessitate refinancing, asset sales, or delays in capital expenditures[229]. - Existing debt agreements may restrict refinancing options, potentially leading to higher interest rates and more onerous covenants[229]. - Failure to meet debt obligations could adversely affect the company's financial condition and operations[229]. - Changes in credit and capital markets may increase financing costs and restrict access to liquidity[229]. - Inability to generate sufficient cash flow could materially impact the company's ability to satisfy debt obligations[229].

Compliance and Market Status - Biophytis has regained compliance with the Nasdaq Global Select Market minimum bid price requirement, with the closing bid price of its American Depositary Shares at $1.00 or greater for the last 10 consecutive business days from March 30, 2023 to April 13, 2023[7]. - The notification from Nasdaq was received on April 14, 2022, indicating the company's compliance status[6]. Product Development and Clinical Trials - The company is developing Sarconeos (BIO101) as a treatment for sarcopenia, currently in a Phase 2 clinical trial in the United States and Europe[2]. - Sarconeos (BIO101) has shown positive results in a Phase 2-3 study for severe COVID-19 patients, with results released in Q1 2023[2]. - A pediatric formulation of Sarconeos (BIO101) is being developed for the treatment of Duchenne Muscular Dystrophy (DMD)[2]. Company Focus and Operations - Biophytis is focused on therapeutics aimed at slowing degenerative processes associated with aging and improving functional outcomes for patients with age-related diseases[2]. - The company is based in Paris, France, and Cambridge, Massachusetts, with its ordinary shares listed on Euronext Growth and ADSs on Nasdaq Capital Market[2]. Forward-Looking Statements - The company considers its forward-looking statements to be based on reasonable assumptions, but acknowledges various risks and uncertainties that could affect actual outcomes[8]. - Biophytis has no obligation to publicly update or review any forward-looking statements except as required by law[8]. Investor Relations - The company’s contact for investor relations is Philippe Rousseau, CFO, available via email for inquiries[10].

Company Overview - Biophytis is focused on developing therapeutics to slow degenerative processes associated with aging, including treatments for severe respiratory failure in COVID-19 patients[5]. - The company is based in Paris, France, and Cambridge, Massachusetts[5]. - The company’s ordinary shares are listed on Euronext Growth (Ticker: ALBPS) and ADSs on Nasdaq Capital Market (Ticker: BPTS)[5]. Drug Development - The leading drug candidate, Sarconeos (BIO101), is in a Phase 2 clinical trial for sarcopenia in the U.S. and Europe, with positive results from a Phase 2-3 study (COVA) for severe COVID-19 patients released in Q1 2023[5]. - A pediatric formulation of Sarconeos (BIO101) is being developed for the treatment of Duchenne Muscular Dystrophy (DMD)[5]. Corporate Governance - The company held an Extraordinary General Meeting on March 30, 2023, which was adjourned due to insufficient quorum; a second call is scheduled for April 17, 2023[3][4]. - The quorum required for the Extraordinary General Meeting on the first call was 25%[3]. Financial Information - The company has not provided specific financial performance metrics or guidance in the current release[7]. - Forward-looking statements in the press release are subject to various risks and uncertainties, and actual outcomes may differ materially[7]. Investor Relations - Contact information for investor relations is provided, including CFO Philippe Rousseau[8].

PART I [Key Information](index=8&type=section&id=Item%203.%20Key%20Information) The company faces significant risks due to its limited operating history, financial needs, and reliance on successful drug development and regulatory approvals [Risk Factors](index=8&type=section&id=D.%20Risk%20Factors) - The company is a clinical-stage biotechnology firm with no approved products, a history of **significant losses**, and requires **substantial additional financing**[28](index=28&type=chunk)[64](index=64&type=chunk) - Business operations and clinical trials face material adverse effects from health pandemics like COVID-19, potentially causing supply chain disruptions, clinical program delays, and increased costs[57](index=57&type=chunk)[58](index=58&type=chunk) - The company's business is highly dependent on the successful development, regulatory approval, and commercialization of its drug candidates, primarily **Sarconeos (BIO101)**[97](index=97&type=chunk)[98](index=98&type=chunk)[99](index=99&type=chunk) - A **material weakness** in internal control over financial reporting was identified as of December 31, 2021, due to incorrect IFRS 9 application for convertible notes' fair value assessment[390](index=390&type=chunk)[391](index=391&type=chunk) Historical Financial Losses | Year Ended December 31 | Net Loss (€ million) | Net Loss ($ million) | | :--- | :--- | :--- | | 2019 | 18.9 | N/A | | 2020 | 25.5 | N/A | | 2021 | 31.2 | 35.4 | [Information on the Company](index=94&type=section&id=Item%204.%20Information%20on%20the%20Company) Biophytis is a clinical-stage biotech developing therapeutics for age-related diseases, with lead candidates Sarconeos (BIO101) and Macuneos (BIO201), relying on outsourcing and partnerships [History and Development of the Company](index=94&type=section&id=A.%20History%20and%20Development%20of%20the%20Company) Capital and R&D Expenditures (€ thousands) | Expense Type | 2019 | 2020 | 2021 | | :--- | :--- | :--- | :--- | | Capital Expenditures | 642 | 484 | 844 | | R&D Costs | 9,089 | 9,921 | 19,213 | - Capital expenditures primarily involved acquiring patent rights from the CEO and rights of use for the company's French headquarters[401](index=401&type=chunk) - The company anticipates **significant capital expenditures and R&D costs** as it advances clinical development of Sarconeos (BIO101) and Macuneos (BIO201)[401](index=401&type=chunk) [Business Overview](index=96&type=section&id=B.%20Business%20Overview) - Biophytis develops therapeutics to slow age-related degenerative processes, targeting sarcopenia, AMD, DMD, and severe COVID-19 respiratory failure[405](index=405&type=chunk) - The lead drug candidate, **Sarconeos (BIO101)**, is an orally administered small molecule for neuromuscular diseases, while **Macuneos (BIO201)** targets retinopathies[410](index=410&type=chunk)[414](index=414&type=chunk) - The company's strategy involves demonstrating drug efficacy through clinical trials, obtaining regulatory authorizations, and seeking licensing or partnership opportunities for commercialization[421](index=421&type=chunk) - Biophytis outsources drug candidate manufacturing for preclinical and clinical trials to third-party CDMOs, such as Patheon/ThermoFisher Scientific[578](index=578&type=chunk)[581](index=581&type=chunk) - The company's patent portfolio comprises **15 patent families**, with **48 co-owned issued patents** and **48 co-owned pending applications**, jointly held with academic institutions like Sorbonne University[594](index=594&type=chunk)[597](index=597&type=chunk) [Operating and Financial Review and Prospects](index=162&type=section&id=Item%205.%20Operating%20and%20Financial%20Review%20and%20Prospects) The company reports no revenue, continued losses, significant R&D expense increases, and a material weakness in internal controls, but has sufficient cash and credit for the next 12 months [Operating Results](index=167&type=section&id=A.%20Operating%20Results) Consolidated Operations Summary (€ thousands) | Metric | 2020 | 2021 | Change (%) | | :--- | :--- | :--- | :--- | | Research and Development Expenses, Net | (9,921) | (19,665) | 98.2% | | General and Administrative Expenses | (4,021) | (7,150) | 77.8% | | Operating Loss | (13,942) | (26,815) | 92.3% | | Net Financial Expense | (11,575) | (4,432) | -61.7% | | Net Loss | (25,517) | (31,247) | 22.4% | - The **98.2% increase in R&D expenses** in 2021 was primarily due to the COVA Phase 2-3 study and the SARA-INT Phase 2 study finalization[775](index=775&type=chunk) - General and administrative expenses rose in 2021 due to staff reinforcement for Business Development and SOX compliance, and costs from being a U.S. public company since February 2021[778](index=778&type=chunk)[779](index=779&type=chunk) - Net financial expense **decreased significantly** in 2021, primarily due to a smaller negative change in the fair value of convertible notes[782](index=782&type=chunk) [Liquidity and Capital Resources](index=180&type=section&id=B.%20Liquidity%20and%20Capital%20Resources) - As of December 31, 2021, the company held **€23.9 million in cash and cash equivalents**[843](index=843&type=chunk)[851](index=851&type=chunk) - Operations have been primarily financed through capital increases, convertible debt instruments (ATLAS and Kreos), non-convertible bonds, and proceeds from its Euronext Growth and U.S. IPOs[844](index=844&type=chunk) - The company expects existing capital resources, including a **€32 million credit facility with ATLAS**, will fund operations for at least the next 12 months[852](index=852&type=chunk) Consolidated Cash Flows (€ thousands) | Cash Flow Activity | 2019 | 2020 | 2021 | | :--- | :--- | :--- | :--- | | Operating Activities | (15,051) | (9,743) | (23,795) | | Investing Activities | (278) | (12,713) | 12,160 | | Financing Activities | 7,278 | 21,953 | 29,715 | | Net Change in Cash | (8,069) | (490) | 18,079 | [Directors, Senior Management and Employees](index=193&type=section&id=Item%206.%20Directors,%20Senior%20Management%20and%20Employees) This section details the company's leadership, including executive officers and directors, their compensation, board structure, and the 26-person workforce primarily in R&D [Directors and Senior Management](index=193&type=section&id=A.%20Directors%20and%20Senior%20Management) - The company's leadership includes **Stanislas Veillet as Chairman and CEO**, **Philippe Rousseau as CFO**, and other key officers across business, science, clinical operations, and medical affairs[931](index=931&type=chunk) - The Board of Directors comprises **five members**, including the Chairman & CEO[944](index=944&type=chunk) [Compensation](index=197&type=section&id=B.%20Compensation) - Aggregate compensation paid to executive officers and directors for the year ended December 31, 2021, totaled **€5.0 million**[947](index=947&type=chunk) CEO Compensation for FY 2021 (€) | Nature of Compensation | Amount Paid or Earned | | :--- | :--- | | Fixed remuneration | 250,000 | | Variable annual remuneration | 75,000 | | Benefits in kind | 25,329 | | **Total** | **350,329** | - As of February 28, 2022, the company had outstanding founders' and share warrants for **6,832,358 ordinary shares** at a weighted average exercise price of **€0.59 per share**[968](index=968&type=chunk) [Board Practices](index=203&type=section&id=C.%20Board%20Practices) - The board of directors currently consists of **five members**, each elected for three-year terms[980](index=980&type=chunk)[981](index=981&type=chunk) - All directors, except CEO Stanislas Veillet and Jean Mariani, are deemed independent under Nasdaq rules[986](index=986&type=chunk) - The board has established an Audit Committee and a Compensation and Governance Committee, both serving advisory roles under French law[988](index=988&type=chunk)[989](index=989&type=chunk) [Employees](index=207&type=section&id=D.%20Employees) - As of December 31, 2021, the company had **26 full-time employees**, with **20 in research and development** and **6 in general and administrative roles**[1003](index=1003&type=chunk) [Major Shareholders and Related Party Transactions](index=207&type=section&id=Item%207.%20Major%20Shareholders%20and%20Related%20Party%20Transactions) This section details ownership structure, with directors and executive officers holding 3.7% of shares, and outlines key related party transactions including an IP agreement with the CEO and intercompany agreements [Major Shareholders](index=207&type=section&id=A.%20Major%20Shareholders) Beneficial Ownership as of February 28, 2022 | Owner | Number of Ordinary Shares | Percentage | | :--- | :--- | :--- | | Stanislas Veillet (CEO) | 3,142,534 | 2.2% | | All directors and executive officers as a group (10 persons) | 5,134,152 | 3.7% | - As of February 28, 2022, no beneficial owners held more than **5% of the company's outstanding ordinary shares**[1005](index=1005&type=chunk) [Related Party Transactions](index=210&type=section&id=B.%20Related%20Party%20Transactions) - The company has an IP agreement with CEO Stanislas Veillet, entitling him to lump sum payments and a **6.5% royalty** on related product income, capped at **€2.1 million per platform**[1020](index=1020&type=chunk)[1021](index=1021&type=chunk) - In 2021, **€270 thousand** was paid to the CEO under the intellectual property agreement[1024](index=1024&type=chunk) - The company maintains intercompany agreements for cash advances and services with its U.S. and Brazilian subsidiaries[1025](index=1025&type=chunk)[1029](index=1029&type=chunk) [Financial Information](index=214&type=section&id=Item%208.%20Financial%20Information) This section presents consolidated financial statements and details legal proceedings, including an AMF fine for disclosure delays and a contractual dispute with NEGMA - The company was involved in a legal dispute with NEGMA, resulting in a March 2021 court order to pay **€910 thousand** and deliver **7 million shares**, which the company complied with but has appealed[1045](index=1045&type=chunk)[1047](index=1047&type=chunk) - The French securities regulator (AMF) fined the company **€100,000** and its CEO **€20,000** for delayed disclosure of clinical trial timelines, a decision confirmed in December 2020[1044](index=1044&type=chunk) - The company has never paid cash dividends and does not anticipate doing so, intending to retain all earnings for business operations and expansion[1051](index=1051&type=chunk) [Additional Information](index=217&type=section&id=Item%2010.%20Additional%20Information) This section provides supplementary information on securities, contracts, and tax considerations, including French foreign exchange regulations and U.S. and French income tax implications for ADS holders - The company believes it was likely not a Passive Foreign Investment Company (PFIC) for 2021, but offers no assurance for current or future years[383](index=383&type=chunk)[1088](index=1088&type=chunk) - Under the U.S.-France Tax Treaty, dividends to eligible U.S. holders are generally subject to a reduced French withholding tax rate of **15%** (or **5%** for certain corporate holders)[1118](index=1118&type=chunk)[1120](index=1120&type=chunk) - Capital gains from ADS sales by U.S. holders are generally not subject to French tax, provided the holder has not held more than **25% of dividend rights** in the preceding five years[1115](index=1115&type=chunk) [Quantitative and Qualitative Disclosures About Market Risk](index=232&type=section&id=Item%2011.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) The company faces market, credit, and significant liquidity risks, with equity risk from convertible notes and a need for substantial future funding due to negative operating cash flows - The company's primary financial risks include market, credit, and liquidity risk, with an overall risk management program focused on capital preservation[1135](index=1135&type=chunk) - Liquidity risk is a key concern due to significant R&D expenses and **negative operating cash flows of €23.8 million in 2021**, necessitating substantial future funding for drug development[1144](index=1144&type=chunk)[1145](index=1145&type=chunk) - Equity risk arises from financing agreements involving convertible notes (with Atlas and Kreos) whose value is linked to the company's share price[1141](index=1141&type=chunk) PART II [Material Modifications to the Rights of Security Holders and Use of Proceeds](index=238&type=section&id=Item%2014.%20Material%20Modifications%20to%20the%20Rights%20of%20Security%20Holders%20and%20Use%20of%20Proceeds) The company completed its U.S. IPO in February 2021, issuing 1,200,000 ADSs for **€16.58 million** gross proceeds, with all net proceeds used as described in the prospectus U.S. Initial Public Offering (February 2021) | Metric | Amount (€ million) | Amount ($ million) | | :--- | :--- | :--- | | Gross Proceeds | 16.58 | 20.1 | | Underwriting Discounts & Expenses | 3.1 | 3.8 | | Net Proceeds | 13.49 | 16.35 | - All net proceeds from the U.S. IPO were used as described in the final prospectus, with no payments to directors, officers, or affiliates[1168](index=1168&type=chunk) [Controls and Procedures](index=238&type=section&id=Item%2015.%20Controls%20and%20Procedures) Management concluded disclosure controls were ineffective as of December 31, 2021, due to a material weakness in IFRS 9 application for convertible notes, with a remediation plan underway - Management concluded that disclosure controls and procedures were **not effective** as of December 31, 2021[1169](index=1169&type=chunk) - A **material weakness** in internal control over financial reporting was identified due to incorrect IFRS 9 application for convertible notes' fair value assessment, stemming from a lack of formalized policies and technical expertise[1174](index=1174&type=chunk)[1175](index=1175&type=chunk) - Management is implementing a remediation plan including policy updates, improved documentation review, systematic accounting treatment reviews, and additional staff training[1177](index=1177&type=chunk)[1178](index=1178&type=chunk)[1179](index=1179&type=chunk) - As an emerging growth company, the annual report does not include an attestation report from the independent registered public accounting firm regarding internal control over financial reporting[1183](index=1183&type=chunk) [Other Information](index=241&type=section&id=Item%2016.%20Other%20Information) This section covers governance, identifying Nadine Coulm as the audit committee financial expert, detailing the Code of Conduct, Ernst & Young fees, and the company's adherence to French corporate governance practices as a foreign private issuer - The Board of Directors has determined that **Nadine Coulm** is an "audit committee financial expert"[1186](index=1186&type=chunk) - The company has adopted a Code of Business Conduct and Ethics, available on its website[1187](index=1187&type=chunk) Principal Accountant Fees (€ thousands) | Fee Type | 2020 | 2021 | | :--- | :--- | :--- | | Audit Fees | 428 | 332 | | Audit-Related Fees | — | — | | Tax Fees | — | — | | Other Fees | — | — | | **Total** | **428** | **332** | - As a foreign private issuer, the company follows French corporate governance practices instead of Nasdaq standards, including different requirements for board independence and shareholder meeting quorums[1199](index=1199&type=chunk)[1201](index=1201&type=chunk) PART III [Financial Statements](index=245&type=section&id=Item%2017.%20Financial%20Statements) The IFRS consolidated financial statements for 2019-2021, audited by Ernst & Young, show a **net loss of €31.2 million** in 2021 and increased assets and equity, prepared on a going concern basis [Statements of Consolidated Financial Position](index=255&type=section&id=Statements%20of%20Consolidated%20Financial%20Position) Consolidated Financial Position (€ thousands) | Metric | Dec 31, 2020 | Dec 31, 2021 | | :--- | :--- | :--- | | **Total Assets** | **27,210** | **36,262** | | Total Non-Current Assets | 3,200 | 4,571 | | Total Current Assets | 24,010 | 31,691 | | **Total Liabilities** | **24,942** | **30,557** | | Total Non-Current Liabilities | 2,021 | 7,414 | | Total Current Liabilities | 22,921 | 23,143 | | **Total Shareholders' Equity** | **2,268** | **5,705** | [Statements of Consolidated Operations](index=256&type=section&id=Statements%20of%20Consolidated%20Operations) Consolidated Operations (€ thousands) | Metric | 2019 | 2020 | 2021 | | :--- | :--- | :--- | :--- | | Research and Development Expenses, Net | (9,089) | (9,921) | (19,665) | | General and Administrative Expenses | (6,593) | (4,021) | (7,150) | | Operating Loss | (15,682) | (13,942) | (26,815) | | Net Financial Expense | (3,344) | (11,575) | (4,432) | | **Net Loss** | **(18,946)** | **(25,517)** | **(31,247)** | Loss Per Share (€/share) | Metric | 2019 | 2020 | 2021 | | :--- | :--- | :--- | :--- | | Basic Loss Per Share | (1.12) | (0.43) | (0.26) | | Diluted Loss Per Share | (1.12) | (0.43) | (0.26) | [Statements of Consolidated Cash Flows](index=259&type=section&id=Statements%20of%20Consolidated%20Cash%20Flows) Consolidated Cash Flows (€ thousands) | Cash Flow Activity | 2019 | 2020 | 2021 | | :--- | :--- | :--- | :--- | | Net Cash Used in Operating Activities | (15,051) | (9,743) | (23,795) | | Net Cash (Used in) Provided by Investing Activities | (278) | (12,713) | 12,160 | | Net Cash Provided by Financing Activities | 7,278 | 21,953 | 29,715 | | **Net Increase (Decrease) in Cash** | **(8,069)** | **(490)** | **18,079** |

Financial Performance and Capital Resources - The company incurred losses of €14.0 million, €17.8 million, and €17.1 million ($20.9 million) for the years ended December 31, 2018, 2019, and 2020 respectively[83]. - As of December 31, 2020, the company had capital resources of €18.7 million ($22.9 million) and received approximately €13.49 million ($16.35 million) in net proceeds from its U.S. initial public offering[86]. - The company anticipates that losses will continue to increase as it develops drug candidates and conducts clinical trials[83]. - The company expects existing capital resources will be sufficient to fund planned operating expenses for the next 12 months, but may need to seek additional funds sooner due to various factors[87]. - Future capital requirements will depend on the scope and costs of research and development, regulatory approvals, and commercialization activities[88]. - The company has a history of losses and requires substantial additional financing to achieve its goals[84]. Regulatory and Clinical Development Risks - The ongoing COVID-19 pandemic has adversely affected the company's operations and may impact future clinical trials and supply chain[75]. - The company is in the early stages of development and faces risks related to obtaining regulatory approval for drug candidates[36]. - The company relies on third parties for raw materials and conducting preclinical studies and clinical trials, which poses additional risks[41]. - The company has incurred significant expenses related to preclinical and clinical programs, impacting its financial condition[83]. - The company has no products approved for sale, with its lead drug candidate Sarconeos (BIO101) in clinical development and Macuneos (BIO201) in preclinical phase[111]. - The company may face challenges in meeting the expectations of analysts or investors, which could lead to a decline in stock price[100]. - The company faces significant delays in obtaining regulatory approvals for its drug candidates due to various factors, including the impact of COVID-19 on clinical trials and regulatory processes[114]. - The company is experiencing challenges in recruiting and retaining principal investigators and site staff for clinical trials, which may adversely affect clinical trial operations[113]. - The FDA and EMA may delay, limit, or deny approval of drug candidates for reasons such as safety and efficacy concerns, disagreements on trial protocols, or insufficient data from modified studies[119]. - The company may incur unplanned costs and delays in obtaining marketing approval if additional clinical trials or testing are required beyond current plans[129]. - The ongoing COVID-19 pandemic has led to limitations in clinical trial operations, including patient enrollment and data collection, which could impact the acceptability of data for regulatory review[128]. - The company is subject to extensive regulations by the FDA, EMA, and other foreign authorities, which differ by country and can significantly affect the ability to market investigational drug candidates[116]. - The company may face challenges in demonstrating that the clinical benefits of drug candidates outweigh any safety risks, which is critical for regulatory approval[119]. - The potential for approval policies or regulations to change significantly could render the company's clinical data insufficient for approval[119]. - The company is at risk of delays in clinical trials due to factors such as disagreements with regulatory authorities, recruitment challenges, and compliance with trial protocols[125]. - The company acknowledges that success in preclinical studies does not guarantee success in later-phase clinical trials, highlighting the uncertainty in drug development[123]. - Patient enrollment in clinical trials may face delays due to various factors, including eligibility criteria and proximity to trial sites, potentially impacting trial completion and costs[136]. - Competition for patient enrollment from other clinical trials in the same therapeutic areas may reduce the number and types of patients available for the company's trials[137]. - Undesirable side effects from drug candidates could lead to regulatory delays or prevent approval, affecting the commercial profile of the products[139]. Supply Chain and Manufacturing Risks - The company relies on a single supplier for the plant material required for Sarconeos (BIO101) and Macuneos (BIO201), which poses risks to production and regulatory approval if supply is disrupted[154][156]. - The contract manufacturing partner, Patheon, is critical for compliance with regulatory requirements, and any issues with their facilities could significantly impact the company's ability to develop and market drug candidates[158]. - The company has not entered into long-term supply agreements with its suppliers, which could affect the ability to secure necessary materials for clinical trials and commercial production[152][157]. - Regulatory authorities may impose additional restrictions or require risk evaluation strategies if undesirable side effects are identified post-approval, impacting market acceptance and revenue[145][146]. - The commercial success of drug candidates will depend on physician and patient adoption, influenced by factors such as safety, efficacy, and reimbursement availability[148][149]. - The company is evaluating alternative methods for producing key ingredients to optimize the supply chain and support projected commercial needs[154][156]. - Any disruption in third-party manufacturing or supply chains could materially impact the company's ability to progress preclinical and clinical programs[159]. - The company relies on third-party manufacturers for drug candidate production, which may require significant capacity increases and regulatory approvals[160]. Human Resources and Organizational Challenges - The company currently has 25 full-time employees, with 20 engaged in research and development activities[184]. - The company lacks a marketing or sales organization, which is critical for the commercialization of drug candidates[182]. - There are significant risks associated with building a sales organization, including hiring and retaining qualified personnel[182]. - The company may need to collaborate with third parties for sales and distribution, which could impact commercialization success[182]. - The company faces intense competition for qualified personnel in the biotechnology and pharmaceuticals field[187]. Legal and Compliance Risks - Product liability lawsuits could result in substantial liabilities and limit commercialization efforts[188]. - The company currently carries product liability insurance for clinical trials, but coverage may not be sufficient for future claims[192]. - Significant disruptions in information technology systems could adversely affect business operations and financial condition[198]. - The company must comply with GDPR regulations regarding data protection and breach notifications, which involve substantial costs[202]. - Misconduct by employees or contractors could adversely affect the company's results of operations[207]. - The company faces risks related to employee misconduct and regulatory compliance, which could lead to significant penalties and reputational harm[208]. - Compliance with environmental laws and regulations is costly and may restrict the company's business operations[209]. - The company is subject to numerous environmental, health, and safety laws, which could impact its research and development efforts[210]. - The company cannot eliminate the risk of contamination from hazardous materials, which could disrupt operations and lead to costly liabilities[211]. - The company may be held liable for contamination costs at its facilities, which could exceed its resources[211]. - The company does not carry specific biological or hazardous waste insurance, increasing its financial risk in case of contamination[213]. Intellectual Property Risks - The company's ability to protect its proprietary rights is uncertain, impacting its competitive position in the market[214]. - Legal actions to enforce intellectual property rights can be expensive and may divert management resources[219]. - The patent positions of biotechnology companies are complex and uncertain, which could negatively affect the company's patent rights[221]. - Ongoing patent opposition proceedings could lead to the cancellation of key patents, impacting the company's competitive edge[221].

Company Overview - Biophytis is a clinical-stage biotechnology company focused on developing therapeutics to slow degenerative processes associated with aging and improve outcomes for patients with age-related diseases, including severe respiratory failure due to COVID-19[5]. - The company is based in Paris, France, and Cambridge, Massachusetts, and aims to improve functional outcomes for patients suffering from age-related diseases[5]. - Biophytis' common shares are listed on Euronext Growth Paris (Ticker: ALBPS) and American Depositary Shares (ADSs) are listed on Nasdaq Capital Market (Ticker: BPTS)[5]. Drug Development - The leading drug candidate, Sarconeos (BIO101), is in a Phase 2 clinical trial for sarcopenia in the US and Europe, and is also being studied in a Phase 2-3 clinical trial for severe respiratory manifestations of COVID-19 in Europe, Latin America, and the US[5]. - A pediatric formulation of Sarconeos (BIO101) is being developed for the treatment of Duchenne Muscular Dystrophy (DMD)[5]. Annual General Meeting (AGM) - The Annual General Meeting (AGM) will be held on April 26, 2021, at 5:00 p.m. CET, behind closed doors due to COVID-19 restrictions[1][2]. - Shareholders are encouraged to vote in advance via mail, proxy, or the secure online platform VOTACCESS, with deadlines set for April 23 and April 25[4]. - The company has made available all legally required documents for shareholders' votes on its website[1]. - The notice of meeting was published in the French official legal bulletin, including information on how to vote at the AGM[3]. Forward-Looking Statements - The press release contains forward-looking statements that are subject to various risks and uncertainties, including those described in filings with the U.S. Securities and Exchange Commission[6].