Inventiva(IVA) - 2024 Q4 - Annual Report

Key Information The company requires substantial additional funding, raising significant doubt about its ability to continue as a going concern - The company requires substantial additional funding, raising significant doubt about its ability to continue as a going concern[24][34] - The business heavily relies on lanifibranor's success, facing clinical, regulatory, and commercialization risks[25][68] - Complete reliance on third-party manufacturing and lack of internal sales capabilities pose significant commercialization risks[25][114][167] - Concentrated voting control among executives and major shareholders could influence corporate decisions and impede change of control[25][288] Risk Factors The company faces significant financial, operational, and product-specific risks, including substantial doubt about its ability to continue as a going concern Risks related to Financial Position and Need for Additional Capital - Substantial doubt exists about the company's ability to continue as a going concern, with €96.6 million cash as of December 31, 2024, sufficient only until mid-Q3 2025[34][35][36] - An additional €40 to €45 million is needed for the next 12 months, contingent on closing Structured Financing tranches and a $10 million CTTQ milestone payment[38][39] - The company has a history of significant losses, including a €184.2 million net loss in 2024, with no product sales revenue and no foreseeable profitability[50] - Future equity or convertible debt fundraising will dilute existing shareholders, as seen with recent dilutive financing including Royalty Certificates tied to future lanifibranor net sales[56][65] Risks Related to Product Development, Regulatory Approval and Commercialization - The company is heavily dependent on its sole clinical candidate, lanifibranor, with a February 2025 plan to exclusively focus on it and halt all pre-clinical research programs[68][46] - A treatment-related SUSAR of elevated aminotransferases in the NATiV3 trial in Q1 2024 led to a voluntary pause, potentially impacting regulatory assessment and approval[69][96][142] - Significant competition, notably Madrigal's FDA approval of Rezdiffra for MASH in March 2024, could impact trial recruitment, market acceptance, and lanifibranor's expedited designations[69][105][136] - Prioritizing lanifibranor development by suspending odiparcil and terminating pre-clinical programs (YAP-TEAD, NR4A1) increases single-asset risk[74][75] - Lanifibranor's market penetration, if approved, faces challenges due to the difficulty of non-invasive MASH diagnosis, as liver biopsy remains the standard for measuring improvement[145][146] Risks Related to Our Reliance on Third Parties - The company relies on development and commercialization partnerships with CTTQ (Greater China) and Hepalys (Japan/South Korea), which may not perform as expected or could be terminated[151][156][157] - Reliance on CROs for clinical trials, as evidenced by a 2023 delay with Avant Santé in Mexico, poses risks of development and regulatory approval delays[161][166] - Complete reliance on third-party CMOs for drug supplies means manufacturing issues, non-compliance, or supply disruptions could significantly impact development and marketing[167][168] - Dependence on single-source suppliers for lanifibranor components creates risks of supply interruption, delays, and challenges in finding alternative suppliers[176][177] Risks Related to Our Intellectual Property - Commercial success hinges on patent protection for product candidates, with risks of non-grant, challenge, invalidation, or circumvention by competitors[183][184] - Changes in patent law, including the Leahy-Smith Act and the new UPC system, create uncertainties that could weaken patent enforcement capabilities[193][196] - The company may not protect IP rights globally due to costs, and enforcement in some foreign countries may be weak or difficult[199][201] - Inadequate patent terms could lead to expiration before or shortly after commercialization, and while extensions are possible, they are not guaranteed[214] Risks Related to Our Organization, Structure and Operation - The 2025 Pipeline Prioritization Plan's 50% workforce reduction could lead to loss of key personnel, operational disruption, and harm to morale and future talent attraction[221][222][279] - High dependence on key management, including CEO Frédéric Cren and Deputy CEO/CSO Pierre Broqua, means their loss could harm the business[217] - Subject to data privacy laws (e.g., GDPR, CCPA), non-compliance or cybersecurity incidents, like a November 2021 email server vulnerability exploit, could result in significant fines, litigation, and reputational harm[232][233][260] - International operations expose the company to anti-corruption laws like FCPA and U.K. Bribery Act, with potential violations leading to significant penalties and reputational damage[227] Risks Related to Ownership of our Ordinary Shares and ADSs - The company's ADSs exhibit price volatility, ranging from $1.65 to $4.69 between January 1, 2024, and April 11, 2025[282] - Voting control is highly concentrated; as of March 1, 2025, CEO Frédéric Cren and Deputy CEO Pierre Broqua controlled approximately 18% of voting rights, while executives, directors, and major shareholders collectively owned approximately 76% of shares and voting rights[288][289] - As a foreign private issuer, the company adheres to French corporate governance, which differs from Nasdaq standards and may offer less shareholder protection regarding board independence, committee composition, and quorum requirements[309][310][311] - U.S. holders may face adverse tax consequences if the company is classified as a PFIC; while not believed to be a PFIC for 2024, this annual determination is not guaranteed for future years[320][322] Company Information Business Overview Inventiva is a clinical-stage biopharmaceutical company exclusively focused on developing lanifibranor for MASH, currently in a pivotal Phase 3 trial with results expected in H2 2026 - The company is a clinical-stage biopharmaceutical firm developing oral small molecule therapies for MASH and other diseases with significant unmet medical needs[327] - Lanifibranor, an orally-available pan-PPAR agonist, is the sole pan-PPAR agonist in clinical development for MASH[328] - The February 2025 '2025 Pipeline Prioritization Plan' focuses exclusively on lanifibranor, halting all pre-clinical research, including YAP-TEAD and NR4A1 programs[327][46] - The pivotal NATiV3 Phase 3 trial, initiated in September 2021, completed last patient randomization in April 2025 after a SUSAR-related pause, targeting topline results in H2 2026 and potential NDA submission in H1 2027[330][335][460] Pipeline Inventiva's pipeline is now exclusively focused on lanifibranor for MASH, following the suspension of odiparcil and termination of pre-clinical programs Inventiva's Clinical Pipeline | Product Candidate | Indication | Pre-clinical | Phase 1 | Phase 2 | Phase 3 | | :--- | :--- | :--- | :--- | :--- | :--- | | Lanifibranor | MASH | | | | NATiV3 (Ongoing) | | Odiparcil | MPS | | | Suspended | | | YAP-TEAD | Oncology | Terminated | | | | | NR4A1 | IPF | Terminated | | | | - The company suspended clinical efforts for odiparcil for MPS and has not yet found a suitable development partner[340] - The 2025 Pipeline Prioritization Plan halts all pre-clinical research, including YAP-TEAD and NR4A1 programs, to focus exclusively on lanifibranor[327][340] Competition The MASH therapeutic market is highly competitive, with recent FDA approval of Madrigal's Rezdiffra and several other late-stage competitors posing risks to Inventiva's market share - Madrigal received FDA approval for Rezdiffra for MASH with moderate to advanced liver fibrosis in March 2024, a significant competitive development[349] - Novo Nordisk reported positive Phase 3 results for semaglutide in NASH in November 2024, with a marketing authorization filing expected in 2025[350] - Other companies with MASH candidates in Phase 3 trials include Boehringer Ingelheim, Akero Therapeutics, and 89 Bio, with many others in earlier development stages[350] Intellectual Property Inventiva's success depends on its IP, with lanifibranor's portfolio including 6 U.S. patents and ~235 international patents/applications, extending protection to 2039-2041 - As of March 1, 2025, the lanifibranor portfolio comprises 6 issued U.S. patents and 9 U.S. applications (expiring 2026-2041), plus approximately 154 issued patents and 81 pending applications internationally[353][356] - The odiparcil portfolio includes 2 issued U.S. patents expiring October 2034 and approximately 84 patents in other jurisdictions[353][358] - A new patent granted in Japan in July 2024 extends lanifibranor's protection for cirrhosis patients until at least November 2039[347][922] Manufacturing Inventiva relies entirely on CMOs for drug candidate production under cGMP, requiring scale-up or alternative suppliers for future commercial demand - The company relies on CMOs to produce drug candidates for clinical trials in accordance with cGMP regulations[360] - Meeting future regulatory and commercial needs requires CMOs to increase production scale or securing alternate suppliers[361] Government Regulation and Approval The company's products are subject to extensive, costly regulatory approval processes by authorities like the FDA and EMA, with lanifibranor holding Fast Track and Breakthrough Therapy designations - Drug development and approval are governed by the FDA in the U.S. and EMA in the E.U., requiring extensive pre-clinical and clinical data for safety and efficacy[363][405] - Lanifibranor has received Fast Track and Breakthrough Therapy Designations from the FDA, potentially expediting its development and review process[70][390] - The company is subject to healthcare reform measures like the U.S. Inflation Reduction Act (IRA), which could impact drug pricing and reimbursement via negotiation and inflation rebates[400][402] - In France, the company is subject to strict rules on disclosures of payments to healthcare professionals and anti-gift provisions, with significant penalties for non-compliance[426][427] Operating and Financial Review and Prospects Operating Results In 2024, revenue decreased to €9.2 million and R&D expenses fell by 17%, but net loss widened to €184.2 million due to a significant financial loss from derivative instruments Comparison of Operating Results (in thousands of €) | | Year ended Dec 31, 2023 | Year ended Dec 31, 2024 | % Change | | :--- | :--- | :--- | :--- | | Revenues | 17,477 | 9,198 | -47.4% | | Research and Development Expenses | 110,012 | 90,880 | -17.4% | | General and Administrative Expenses | 13,837 | 15,839 | +14.5% | | Operating Loss | (102,709) | (97,558) | -5.0% | | Net Financial (Expense)/Income | (5,095) | (86,029) | -1588.5% | | Net Loss | (110,426) | (184,212) | +66.8% | - Revenue for 2024 was €9.2 million from a CTTQ milestone payment, down from €17.5 million in 2023 which included CTTQ and Hepalys payments[463][484][485] - R&D expenses decreased primarily due to a €19.6 million reduction in pre-clinical and clinical trial costs, largely from the temporary pause in NATiV3 patient recruitment[489] - The €86.0 million net financial loss in 2024 was primarily due to a €73.4 million loss on fair value variation of derivative instruments from the second tranche of Structured Financing[496] Liquidity and Capital Resources Cash increased to €96.6 million in 2024 due to financing, but substantial doubt about going concern remains, with future liquidity dependent on closing the second Structured Financing tranche Cash and Cash Equivalents (in millions of €) | As of December 31, | 2022 | 2023 | 2024 | | :--- | :--- | :--- | :--- | | Cash and cash equivalents | 86.8 | 26.9 | 96.6 | Summary of Cash Flows (in thousands of €) | | Year ended Dec 31, 2023 | Year ended Dec 31, 2024 | | :--- | :--- | :--- | | Net cash used in operating activities | (81,614) | (85,928) | | Net cash provided by (used in) investing activities | (7,731) | 8,745 | | Net cash provided by financing activities | 29,081 | 145,592 | - In 2024, the company secured significant funding via a multi-tranche Structured Financing of up to €348 million, with initial tranches providing aggregate gross proceeds of €115.5 million (€94.1 million + €21.4 million)[507][521] - Current cash is insufficient for the next 12 months' operating needs, raising substantial doubt about going concern; an additional €40-45 million is required[531][532] - Future funding depends on closing the second Structured Financing tranche (approx. €116 million) and a $10 million CTTQ milestone, extending cash runway to end of Q3 2026[533][534] Material Cash Requirements As of December 31, 2024, total contractual obligations were €374.2 million, primarily €290.7 million in CRO/CMO purchase obligations for the NATiV3 trial Material Contractual Obligations as of December 31, 2024 (in thousands of €) | Obligation Type | 2025 | Thereafter | Total | | :--- | :--- | :--- | :--- | | Bank borrowings and other loans | 3,349 | 46,325 | 49,674 | | Royalty Certificates | — | 29,207 | 29,207 | | Lease liabilities | 2,520 | 2,135 | 4,654 | | Purchase obligations (CRO/CMO) | 128,468 | 162,187 | 290,655 | | Total | 134,336 | 239,853 | 374,190 | - The most significant commitment is €291 million for the NATiV3 clinical trial with CROs and CMOs, with payments extending to 2029[529] Directors, Senior Management, and Employees Directors and Senior Management The company's leadership includes CEO Frédéric Cren and Deputy CEO Pierre Broqua, with a December 2024 board restructuring appointing Mark Pruzanski as Chairman - The executive team is led by co-founders Frédéric Cren (CEO) and Pierre Broqua (Deputy CEO & CSO)[541][548][549] - In December 2024, Mark Pruzanski was appointed Chairman and Srinivas Akkaraju a director, as part of the Structured Financing agreement[557][558][565] Compensation Aggregate compensation for executives and directors was €3.5 million in 2024, including significant equity awards and various incentive plans to attract and retain talent - Aggregate compensation for executive officers and directors for the year ended December 31, 2024, was €3.5 million[566] 2024 Compensation for Top Executive Officers (€) | Name | Position | Salary | Bonus | Equity Awards | Total | | :--- | :--- | :--- | :--- | :--- | :--- | | Frédéric Cren | CEO & Director | 311,116 | 148,690 | 263,861 | 760,229 | | Pierre Broqua | Deputy CEO & CSO | 249,717 | 102,487 | 263,861 | 632,587 | - In 2024, the company had nineteen share-based compensation plans in force, including various warrants (BSA, BSPCE), free shares (AGA), and stock options (SO)[583] - Significant new equity grants in December 2024 included 800,000 free shares each to the CEO and Deputy CEO, and 12,898,116 stock options to Chairman Mark Pruzanski[609][610][614] Board Practices The eight-member Board of Directors follows French corporate governance, differing from Nasdaq rules, and operates with Audit, Compensation and Appointments, and Corporate Social Responsibility committees - The Board of Directors consists of eight members and follows French corporate governance practices instead of certain Nasdaq standards[617][626] - The Board has an Audit Committee, a Compensation and Appointments Committee, and a Corporate Social Responsibility Committee; the Audit Committee has two members, utilizing a foreign private issuer exemption[630][633] - The Board of Directors met 17 times in 2024, achieving an attendance rate over 88%[639] Employees As of December 31, 2024, Inventiva had 118 employees, with a planned 50% workforce reduction in Q2 2025 as part of its strategic shift Employee Headcount by Year | As of December 31, | 2022 | 2023 | 2024 | | :--- | :--- | :--- | :--- | | Total Employees | 113 | 123 | 118 | | R&D | 89 | 96 | 89 | | G&A / Other | 24 | 27 | 29 | - The 2025 Pipeline Prioritization Plan includes an approximate 50% workforce reduction, expected to be implemented in Q2 2025[645] Major Shareholders and Related Party Transactions Major Shareholders As of March 1, 2025, company ownership is concentrated among institutional investors and management, with several holding over 5% beneficial ownership Beneficial Ownership of Major Shareholders (as of March 1, 2025) | Shareholder | Percentage of Shares Beneficially Owned | | :--- | :--- | | BVF Partners L.P. | 8.9% | | Invus Public Equities | 8.8% | | New Enterprise Associates | 8.7% | | Sofinnova Crossover I SLP | 7.0% | | Yiheng Capital Management, L.P. | 6.6% | | Andera Partners | 6.4% | | Frédéric Cren (CEO) | 6.1% | | Perceptive Advisors | 5.8% | | Qatar Holding LLC | 5.4% | | Eventide | 5.3% | | All directors and executive officers as a group | 15.6% | Related Party Transactions In 2024, the company engaged in significant related-party transactions, including issuing €20.1 million in Royalty Certificates and a multi-tranche Structured Financing with major shareholders - On July 17, 2024, the company issued €20.1 million in 2024 Royalty Certificates to related parties including Samsara BioCapital, BVF Partners, New Enterprise Associates, Sofinnova, and Yiheng[668][727] - In October 2024, the company entered a Structured Financing agreement for up to €348 million with investors including related parties like BVF Partners, New Enterprise Associates, and Samsara BioCapital[672][728] - On December 11, 2024, an agreement with Deputy CEO Pierre Broqua governed the transfer of his know-how and inventions since January 1, 2023, with potential milestone payments up to €335,000[666][667] Additional Information Material Contracts Key material contracts include lanifibranor licensing agreements with CTTQ and Hepalys, and financing agreements like Royalty Certificates and the multi-tranche Structured Financing - The CTTQ license agreement for Greater China was amended in October 2024, tying up to $30 million in milestone payments to financing and NATiV3 results, while reducing future sales royalties to low single digits[703][710] - An exclusive licensing agreement with Hepalys Pharma covers lanifibranor development and commercialization in Japan and South Korea, including a $10 million upfront payment and up to $231 million in potential milestones plus tiered royalties[713][717] - The company issued 2024 Royalty Certificates, entitling holders to 3% of future lanifibranor net sales in the US, EU, or UK for 14 years[669][727] - The company entered a multi-tranche Structured Financing agreement for up to €348 million, with initial tranches closing in October and December 2024[672][728] Taxation This section outlines U.S. and French tax considerations for U.S. ADS holders, focusing on the potential PFIC classification risk and French withholding taxes on dividends - There is a risk of the company being classified as a Passive Foreign Investment Company (PFIC) for U.S. federal income tax purposes, leading to adverse tax consequences for U.S. holders[320][735] - Based on 2024 estimates, the company believes it was likely not a PFIC; however, this annual determination is not assured for any future year[322][738] - Dividends to non-resident U.S. holders are generally subject to French withholding tax, potentially reduced to 15% (or 5% for certain corporate holders) under the U.S.-France tax treaty[769][770] - Capital gains from ADS sales by U.S. holders are generally not subject to French tax, provided the holder has not held over 25% of the company's dividend rights in the preceding five years[763][764] Quantitative and Qualitative Disclosures About Market Risk The company faces significant liquidity, foreign currency, and derivatives risks, with substantial doubt about its going concern ability without additional financing - The company faces significant liquidity risk, with material uncertainty casting substantial doubt on its going concern ability, as current cash is sufficient only until mid-Q3 2025[799][800] - The company is exposed to foreign currency exchange risk, with 31.5% of its €96.6 million cash in U.S. dollars as of December 31, 2024; a 5% exchange rate increase would negatively impact by €1.4 million[791][792][793] - The company faces fair value measurement risk from derivative instruments (EIB warrants, Structured Financing options); a one-percentage point volatility change would impact their fair value by €0.8 million (€0.1 million for EIB warrants, €0.7 million for structured financing options)[795] - Credit risk is low, primarily from cash with financial institutions and receivables from major collaboration partners like CTTQ and Hepalys[796] Controls, Procedures and Cybersecurity Controls and Procedures Management concluded that disclosure controls and internal controls over financial reporting were effective as of December 31, 2024, with no auditor attestation due to emerging growth company status - Management concluded that as of December 31, 2024, the company's disclosure controls and procedures were effective at a reasonable assurance level[823] - Management concluded that the company's internal control over financial reporting was effective as of December 31, 2024, based on the 2013 COSO Framework[825] - The annual report does not include an attestation report from the registered public accounting firm on internal controls, as the company is an emerging growth company[826] Cybersecurity The company manages cybersecurity risks through processes led by the CIO, overseen by the audit committee, and integrated into its enterprise risk management program - The company's cybersecurity risk management is led by the Chief Information Officer and integrated into the overall enterprise risk management program[844][847] - The Board of Directors' audit committee oversees cybersecurity risks, receiving reports from the CFO and Head of Internal Control[851][854] - The company utilizes third-party service providers, including professional services firms and cybersecurity consultants, to assist in managing cybersecurity risks[848] Financial Information Report of Independent Registered Public Accounting Firm KPMG S.A. issued a fair opinion on the consolidated financial statements, highlighting a material uncertainty regarding the company's ability to continue as a going concern - The auditor's report includes a "Going Concern" paragraph, citing operating losses and negative cash flows as substantial doubt about the company's ability to continue as a going concern[866] Consolidated Financial Statements Consolidated financial statements show a net loss of €184.2 million in 2024, with total assets at €119.0 million and liabilities at €225.6 million, resulting in negative shareholders' equity Consolidated Statement of Financial Position (in thousands of €) | | As of Dec 31, 2023 | As of Dec 31, 2024 | | :--- | :--- | :--- | | Total Assets | 69,561 | 118,967 | | Total Liabilities | 101,592 | 225,614 | | Total Shareholders' Equity | (32,032) | (106,647) | Consolidated Statement of Income (Loss) (in thousands of €) | | Year ended Dec 31, 2023 | Year ended Dec 31, 2024 | | :--- | :--- | :--- | | Revenues | 17,477 | 9,198 | | Operating Loss | (102,709) | (97,558) | | Net Loss for the period | (110,426) | (184,212) | Notes to the Consolidated Financial Statements Notes detail accounting policies and financial results, covering 2024 significant events, going concern uncertainty, revenue recognition, and complex financial debt and derivative accounting Significant Events of 2024 - Drew down the final €25 million Tranche B from the EIB Finance Contract in January 2024[905] - Reported a treatment-related SUSAR in the NATiV3 trial in Q1 2024, leading to a temporary pause and protocol amendments[907] - Issued €20.1 million of 2024 Royalty Certificates in July 2024[917] - Amended the CTTQ license agreement in October 2024 to tie milestones to financing and clinical data, subsequently receiving a $10 million payment[923] - Announced and closed the first tranches of a Structured Financing for up to €348 million in October and December 2024[924] Going Concern - The company's financial statements were prepared on a going concern basis, but management notes a material uncertainty that may cast significant doubt on this ability[1104][1108] - Current cash of €96.6 million (as of Dec 31, 2024) is estimated to fund operations only until mid-Q3 2025[1102][1103] - An additional €40 to €45 million in cash is required for the next 12 months, with continued operations dependent on proceeds from the second Structured Financing tranche and a CTTQ milestone payment[1104][1105] Financial Debt and Derivatives - Total financial debt increased to €181.3 million in 2024 from €54.1 million in 2023, largely due to new financing and derivative instrument accounting[1192] - Derivative liabilities of €97.7 million were recognized as of Dec 31, 2024, including €24.3 million for EIB warrants and €73.4 million for Structured Financing call options[1192][1226] - Royalty Certificate liabilities increased to €29.2 million at year-end 2024, following the issuance of the 2024 series[1240][1241] Revenue Recognition - 2024 revenue of €9.2 million was recognized from a milestone payment under the amended CTTQ License Agreement, following the successful first phase of Structured Financing[1270][1279] - In 2023, the company recognized €12.7 million in revenue from the Hepalys License Agreement, including a $10 million upfront payment and $3.6 million fair value of the option to acquire Hepalys shares[954][1292] - The CTTQ agreement has three distinct performance obligations: Transfer of Know-How, Development Services, and Transfer of Manufacturing Technology, with the upfront payment allocated across them[1272][1275]