10q10k10q10k.net

What changed in DBV Technologies S.A.'s 10-K — 2022 vs 2023

vs

Paragraph-level year-over-year comparison of DBV Technologies S.A.'s 2022 and 2023 10-K annual filings, covering the Business, Risk Factors, Legal Proceedings, Cybersecurity, MD&A and Market Risk sections. Every new, removed and edited paragraph is highlighted side-by-side so you can see exactly what management changed in the 2023 report.

+653 added−620 removedSource: 10-K (2024-03-07) vs 10-K (2023-03-02)

Top changes in DBV Technologies S.A.'s 2023 10-K

653 paragraphs added · 620 removed · 508 edited across 6 sections

Item 1. Business

Business — how the company describes what it does

192 edited+72 added−32 removed257 unchanged
Biggest changeClinically, peanut allergy is characterized by rapid onset of symptoms which are triggered by the release of mediators from mast cells and basophils and typically involves one or more target organs. Presentation and 1 Table of Contents severity of allergic reactions are unpredictable and may vary from mild to severe (anaphylaxis) within populations and within individuals over time.
Biggest changePresentation and severity of allergic reactions are unpredictable and may vary from mild to severe (anaphylaxis) within populations and within individuals over time. In the case of peanut allergy, all individuals are therefore considered at risk for severe allergic reactions, irrespective of their past history.
Viaskin Milk Our second product candidate, Viaskin Milk, is in development for the treatment of cow’s milk protein allergy, (IgE-mediated) or CMPA, in children two to 17 years of age, and received fast track designation from the FDA in September 2016.
Viaskin Milk Our second product candidate, Viaskin Milk, is in development for the treatment of cow’s milk protein allergy, (IgE-mediated) or CMPA, in children two to 17 years of age, and received fast track designation from the FDA in 17 September 2016.
U.S. Patent Term Restoration and Marketing Exclusivity Depending upon the timing, duration, and specifics of the FDA approval of our product candidates, some of our U.S. patents may be eligible for limited patent term extension under the Drug Price Competition and Patent Term Restoration Act of 1984, commonly referred to as the Hatch-Waxman Amendments.
U.S. Patent Term Extension and Marketing Exclusivity Depending upon the timing, duration, and specifics of the FDA approval of our product candidates, some of our U.S. patents may be eligible for limited patent term extension under the Drug Price Competition and Patent Term Restoration Act of 1984, commonly referred to as the Hatch-Waxman Amendments.
The results of pre-clinical studies and clinical trials are then submitted to the FDA as part of a BLA, along with proposed labeling for the product and information about the manufacturing process and facilities that will be used to ensure product quality, results of analytical testing conducted on the chemistry of the product candidate, and other relevant information.
The results of pre-clinical studies and clinical trials are then submitted to the FDA as part of a BLA, along with proposed labeling for the product candidate and information about the manufacturing process and facilities that will be used to ensure product quality, results of analytical testing conducted on the chemistry of the product candidate, and other relevant information.
To support marketing approval, the data submitted must be sufficient in quality and quantity to establish the safety and efficacy of the investigational product to the satisfaction of the FDA. FDA approval of a BLA must be obtained before a biologic may be marketed in the United States.
To support marketing approval, the data submitted must be sufficient in quality and quantity to establish the safety and efficacy of the investigational product to the satisfaction of the FDA. FDA approval of a BLA must be obtained before a biologic product may be marketed in the United States.
Our Viaskin product candidates are combination products comprising a device for delivery of a biologic. Under the FDCA, the FDA is charged with assigning a center with primary jurisdiction, or a lead center, for review of a combination product.
Our Viaskin product candidates are combination products comprising a device for delivery of a biologic product. Under the FDCA, the FDA is charged with assigning a center with primary jurisdiction, or a lead center, for review of a combination product.
In the EU, clinical trials are governed by the Clinical Trials Regulation (EU) No 536/2014, or CTR, which entered into application on January 31, 2022, repealing and replacing the Clinical Trials Directive 2001/20, or CTD.
In the EU, clinical trials are governed by the Clinical Trials Regulation (EU) No 536/2014, or CTR, which entered into application on January 31, 2022, repealing and replacing the Clinical Trials Directive 2001/20, or 31 CTD.
This assessment is then submitted to the competent authorities of all the concerned Member States in which the trial is to be conducted for their review. Part II is assessed separately by the competent authorities and Ethics Committees in each concerned EU Member State.
This assessment is then submitted to the competent authorities of all the concerned EU Member States in which the trial is to be conducted for their review. Part II is assessed separately by the competent authorities and Ethics Committees in each concerned EU Member State.
Each concerned Member State will issue a single decision on the authorization of the clinical trial including input from the national competent authority and Ethics Committee. Individual EU Member States, therefore, retain the power to authorize the conduct of clinical trials in their territory.
Each concerned EU Member State will issue a single decision on the authorization of the clinical trial including input from the national competent authority and Ethics Committee. Individual EU Member States, therefore, retain the power to authorize the conduct of clinical trials in their territory.
The PIP sets out the timing and measures proposed to generate data to support a pediatric indication of the medicinal product for which MA is being sought.
The PIP sets out the timing and measures proposed to generate data to support a pediatric indication of the medicinal product for which the MA is being sought.
Moreover, the government may assert that a claim including items or services resulting from a violation of the federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the federal civil False Claims Act; • federal civil and criminal false claims laws, including the federal civil False Claims Act, which impose penalties and provide for civil whistleblower or qui tam actions, and civil monetary penalty laws, which prohibit, among other things, knowingly presenting, or causing to be presented, claims for payment from Medicare, Medicaid, or other third-party payors that are false or fraudulent, or making a false statement or record material to payment of a false claim or avoiding, decreasing, or concealing an obligation to pay money to the federal government, including for example, providing inaccurate billing or coding information to customers or promoting a product off-label; • HIPAA, which created additional federal criminal statutes that prohibit knowingly and willfully executing or attempting to execute a scheme to defraud any healthcare benefit program, knowingly and willfully falsifying, concealing or covering up a material fact or making false statements relating to healthcare matters, knowingly and willfully embezzling or stealing from a healthcare benefit program, or willfully obstructing a criminal investigation of a healthcare offense.
Moreover, the government may assert that a claim including items or services resulting from a violation of the federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the federal civil False Claims Act; • federal civil and criminal false claims laws, including the federal civil False Claims Act, which impose penalties and provide for civil whistleblower or qui tam actions, and civil monetary penalty laws, which prohibit, among other things, knowingly presenting, or causing to be presented, claims for 40 payment from Medicare, Medicaid, or other third-party payors that are false or fraudulent, or making a false statement or record material to payment of a false claim or avoiding, decreasing, or concealing an obligation to pay money to the federal government, including for example, providing inaccurate billing or coding information to customers or promoting a product off-label; • HIPAA, which created additional federal criminal statutes that prohibit knowingly and willfully executing or attempting to execute a scheme to defraud any healthcare benefit program, knowingly and willfully falsifying, concealing or covering up a material fact or making false statements relating to healthcare matters, knowingly and willfully embezzling or stealing from a healthcare benefit program, or willfully obstructing a criminal investigation of a healthcare offense.
Similar to the federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it to have committed a violation; • the federal Physician Payments Sunshine Act, enacted as part of the ACA, which requires applicable manufacturers of covered drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program, with specific exceptions, to track and annually report to CMS payments and other transfers of value provided to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), other healthcare professionals (such as physician assistants and nurse practitioners), and teaching hospitals and information regarding certain ownership and investment interests held by physicians or their immediate family members; • HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, or HITECH, and its implementing regulations, which imposes certain requirements on covered entities and their business associates, and their covered subcontractors, relating to the privacy, security and transmission of individually identifiable health information; and • state, local and foreign law equivalents of each of the above federal laws, such as state anti- kickback and false claims laws which may apply to items or services reimbursed by any third- party payor, including commercial insurers; state and local marketing and/or transparency laws applicable to manufacturers that may be broader in scope than the federal requirements; state laws that require biopharmaceutical companies to comply with the biopharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government; state and local laws that require licensure or registration by pharmaceutical sales representatives; state laws that require disclosure of information related to drug pricing; and state and foreign laws governing the privacy and security of health information in certain circumstances, many of which differ from each other in significant ways and may not have the same effect as HIPAA, thus complicating compliance efforts.
Similar to the federal Anti- Kickback Statute, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it to have committed a violation; • the federal Physician Payments Sunshine Act, enacted as part of the ACA, which requires applicable manufacturers of covered drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program, with specific exceptions, to track and annually report to CMS payments and other transfers of value provided to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), other healthcare professionals (such as physician assistants and nurse practitioners), and teaching hospitals and information regarding certain ownership and investment interests held by physicians or their immediate family members; • federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, or HITECH, and its implementing regulations, which imposes certain requirements on covered entities and their business associates, and their covered subcontractors, relating to the privacy, security and transmission of individually identifiable health information; and • state, local and foreign law equivalents of each of the above federal laws, such as state anti-kickback and false claims laws which may apply to items or services reimbursed by any third-party payor, including commercial insurers; state and local marketing and/or transparency laws applicable to manufacturers that may be broader in scope than the federal requirements; state laws that require biopharmaceutical companies to comply with the biopharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government; state and local laws that require licensure or registration by pharmaceutical sales representatives; state laws that require disclosure of information related to drug pricing; and state and foreign laws governing the privacy and security of health information in certain circumstances, many of which differ from each other in significant ways and may not have the same effect as HIPAA, thus complicating compliance efforts.
If our operations are found to be in violation of any of these laws or any other governmental regulations that may apply to us, we may be subject to significant administrative, civil, and/or criminal penalties, damages, fines, disgorgement, individual imprisonment, exclusion from government funded healthcare programs, such as Medicare and Medicaid, or comparable foreign programs, integrity obligations, contractual damages, reputational harm, diminished profits and future earnings, and the curtailment or restructuring of our operations.
If our operations are found to be in violation of any of these laws or any other governmental regulations that may apply to us, we may be subject to significant administrative, civil, and/or criminal penalties, damages, fines, disgorgement, individual imprisonment, exclusion from government funded healthcare programs, such as Medicare and Medicaid, or comparable foreign programs, integrity obligations, contractual damages, reputational harm, diminished profits and future earnings, and the curtailment or 41 restructuring of our operations.
Differentiating competitive factors in the pharmaceutical industry include product efficacy and safety; quality and breadth of an organization’s technology; skill of an organization’s employees and its ability to recruit and retain key employees; timing and scope of regulatory approvals; government reimbursement rates for, and the average selling price of, products; the availability of raw materials and qualified manufacturing capacity; manufacturing and distribution costs; intellectual property and patent rights and their protection; and sales and marketing capabilities.
Differentiating competitive factors in the pharmaceutical industry include product efficacy and safety; quality and breadth of an 22 organization’s technology; skill of an organization’s employees and its ability to recruit and retain key employees; timing and scope of regulatory approvals; government reimbursement rates for, and the average selling price of, products; the availability of raw materials and qualified manufacturing capacity; manufacturing and distribution costs; intellectual property and patent rights and their protection; and sales and marketing capabilities.
To support the application, the MA holder must provide the EMA or the competent authority with a consolidated version of the eCTD (Common Technical Document) providing up-to-date data concerning the quality, safety and efficacy of the product, including all variations introduced since the MA was granted, at least nine months before the MA ceases to be valid.
To support the application, the MA holder must provide the EMA or the competent authority with a consolidated version of the eCTD (Common Technical Document) providing up-to-date data concerning the quality, safety and efficacy of the product, including all variations introduced 33 since the MA was granted, at least nine months before the MA ceases to be valid.
We were incorporated as a société par actions simplifiée (S.A.S.) under the laws of the French Republic on March 29, 2002 for a period of 99 years and subsequently converted on March 13, 2003 into a société anonyme . We are registered at the Nanterre Commerce and Companies Register under the number 441 772 522.
We were incorporated as a société par actions simplifiée (S.A.S.) under the laws of the French Republic on March 29, 2002 for a period of 99 years and subsequently converted on March 13, 2003 into a société anonyme . We are registered at the Nanterre Commerce 42 and Companies Register under the number 441 772 522.
The FDA may refer applications for novel drug product candidates or drug product candidates which present difficult questions of safety or efficacy to an advisory committee, typically a panel that includes clinicians and other experts, for review, evaluation and a recommendation as to whether the application should be approved and under what conditions.
The FDA may refer applications for novel drug product candidates or drug product candidates which present difficult questions of safety or efficacy to an advisory committee, typically a panel that includes clinicians and other experts, for review, evaluation and a recommendation as to 26 whether the application should be approved and under what conditions.
The FDA will not approve the product unless it determines that the manufacturing processes and facilities are in compliance with cGMP requirements and adequate to assure consistent production of the product within required specifications. In addition, before approving a BLA, the FDA may also audit data from clinical trials to ensure compliance with GCP requirements.
The FDA will not approve the product candidate unless it determines that the manufacturing processes and facilities are in compliance with cGMP requirements and are adequate to assure consistent production of the product candidate within required specifications. In addition, before approving a BLA, the FDA may also audit data from clinical trials to ensure compliance with GCP requirements.
The Joint Select Committee on Deficit Reduction was tasked with recommending to Congress proposals in spending reductions. Because they did not achieve a targeted deficit reduction of at least $1.2 trillion for fiscal years 2012 through 2021, it triggered the legislation’s automatic reduction to several government programs.
The Joint Select Committee on Deficit Reduction was tasked with recommending to Congress proposals in spending reductions. Because they did not achieve a targeted deficit reduction of at least 38 $1.2 trillion for fiscal years 2012 through 2021, it triggered the legislation’s automatic reduction to several government programs.
Sales of our products will depend, in part, on the extent to which our products, once approved, will be covered and reimbursed by third-party payors, such as government health programs, commercial insurance and managed healthcare organizations. These third-party payors are increasingly reducing reimbursements for medical products and services.
Sales of our products will depend, in part, on the extent to 37 which our products, once approved, will be covered and reimbursed by third-party payors, such as government health programs, commercial insurance and managed healthcare organizations. These third-party payors are increasingly reducing reimbursements for medical products and services.
Clinical trials are conducted under protocols detailing, among other things, the objectives of the clinical trial, dosing procedures, subject selection and exclusion criteria, and the parameters to be used to monitor subject safety and assess efficacy. Each protocol, and any subsequent amendments to the protocol, must be submitted to the FDA as part of the IND.
Clinical trials are conducted under protocols detailing, among other things, the objectives of the clinical trial, dosing procedures, subject selection and exclusion criteria, and the parameters to be used to monitor subject safety and assess efficacy. Each protocol, and any subsequent amendments to such protocol, must be submitted to the FDA as part of the IND.
The BLA is a request for approval to market the biologic for one or more specified indications and must contain proof of safety, purity, potency and efficacy, which is demonstrated by extensive pre-clinical and clinical testing. The application includes both negative or ambiguous results of pre-clinical and clinical trials and positive findings.
The BLA is a request for approval to market a biologic product for one or more specified indications and must contain proof of safety, purity, potency and efficacy, which is demonstrated by extensive pre-clinical and clinical testing. The application includes both negative or ambiguous results of pre-clinical and clinical trials and positive findings.
In such a case, the IND sponsor and the FDA must resolve any outstanding concerns before the clinical trial can begin. The FDA may also impose clinical holds on a product candidate at any time before or during clinical trials due to safety concerns or non-compliance.
In such a case, the IND sponsor and the FDA must resolve any outstanding concerns before the clinical trial can begin. The FDA may also impose clinical holds on a product candidate at any time before or during clinical trials due to safety concerns or regulatory non-compliance.
We believe that with improved knowledge about the evolution of immunological biomarkers and epigenetic modulation, we may be able to determine the level of patient response earlier during treatment, ensure follow-up and measure tolerance maintained once treatment is completed.
We believe that with improved knowledge about the evolution of immunological biomarkers and epigenetic modulation, we may be able to determine the level of patient response earlier during treatment, ensure follow-up and measure tolerance 18 maintained once treatment is completed.
On February 1, 2018, we entered to a Master API Supply Agreement with Sanofi which sets forth the terms and conditions governing the manufacture and supply of peanut, milk and egg API to be used in our Viaskin product candidates.
On February 1, 2018, we entered into a Master API Supply Agreement with Sanofi which sets forth the terms and conditions governing the manufacture and supply of peanut, milk and egg API to be used in our Viaskin product candidates.
Low discontinuations due to adverse events were observed, with two children discontinuing the trial due to treatment- related TEAEs during PEOPLE. Exploratory analyses suggest Viaskin Peanut may offer sustained effect even after a period without treatment.
Low discontinuations due to adverse events were observed, with two children discontinuing the trial due to treatment- related TEAEs during PEOPLE. 10 Exploratory analyses suggest Viaskin Peanut may offer sustained effect even after a period without treatment.
The decision to withdraw was based on the view of CHMP that the data available to date from a single pivotal clinical trial were not sufficient to preclude a Major Objection at Day 180 in the review cycle.
The decision to withdraw was 6 based on the view of CHMP that the data available to date from a single pivotal clinical trial were not sufficient to preclude a Major Objection at Day 180 in the review cycle.
Although general requirements for advertising and promotion of medicinal products are established under EU legislation, the details are governed by regulations in individual EU Member States and can differ from one country to another.
Although general requirements for advertising and promotion of medicinal products are established under EU legislation, the details are governed by 35 regulations in individual EU Member States and can differ from one country to another.
A Complete Response Letter indicates that the review cycle of the application is complete and the application will not be approved in its present form. A Complete Response Letter usually describes all of the specific deficiencies in the BLA identified by the FDA.
A Complete Response Letter indicates that the review cycle of the application is complete and the application will not be approved in its present form. A Complete Response Letter usually describes the specific deficiencies in the BLA identified by the FDA.
The PDCO can grant a deferral of the obligation to implement some or all of the measures provided in the PIP until there are sufficient data to demonstrate the efficacy and safety of the product in adults.
The PDCO can grant a deferral of the obligation to implement some or all of the measures provided in the PIP until 34 there are sufficient data to demonstrate the efficacy and safety of the product in adults.
A treatment responder was defined as either a subject with a baseline ED ≤10 mg who reached an ED ≥300 mg of peanut protein at month 12, or a subject with a baseline ED >10 mg who reached an ED ≥1,000 mg of peanut protein at month 12.
A treatment responder was defined as either a subject with a baseline ED ≤10 mg who reached an ED ≥300 mg of peanut protein at month 12, or a subject with a baseline ED >10 mg and ≤300 mg who reached an ED ≥1,000 mg of peanut protein at month 12.
As a condition of approval, the FDA may require that a sponsor of a drug or biological product receiving accelerated approval perform adequate and well-controlled post-marketing clinical trials.
As a condition of approval, the FDA may require that a sponsor of a 28 drug or biological product receiving accelerated approval perform adequate and well-controlled post-marketing clinical trials.
Phase 3 clinical trials generally involve large numbers of patients at multiple sites, in multiple countries (from several hundred to several thousand subjects) and are designed to provide the data necessary to demonstrate the efficacy of the product for its intended use, its safety in use, and to establish the overall benefit/risk relationship of the product and provide an adequate basis for product approval.
Phase 3 clinical trials generally involve large numbers of subjects at multiple sites, in multiple countries (from several hundred to several thousand subjects) and are designed to provide the data necessary to demonstrate the efficacy of the product candidate for its intended use, its safety in use, and to establish the overall benefit/risk relationship of the product candidate and provide an adequate basis for product approval.
If any such changes were to be imposed, they could adversely affect the operation of our business. European Union Drug Development In the European Union, our future product candidates may also be subject to extensive regulatory requirements. Approval from the competent authorities of EU Member States must be obtained before commencing clinical trials.
If any such changes were to be imposed, they could adversely affect the operation of our business. European Union Drug Development In the European Union, or the EU, product candidates may also be subject to extensive regulatory requirements. Approval from the competent authorities of EU Member States must be obtained before commencing clinical trials.
Specifically, under regulations issued by the FDA, a combination product may be: • a product comprised of two or more regulated components that are physically, chemically, or otherwise combined or mixed and produced as a single entity; • two or more separate products packaged together in a single package or as a unit and comprised of drug and device products; • a drug, device, or biological product packaged separately that according to its investigational plan or proposed labeling is intended for use only with an approved individually specified drug, device or biological where both are required to achieve the intended use, indication, or effect and where upon 24 Table of Contents approval of the proposed product the labeling of the approved product would need to be changed, e.g., to reflect a change in intended use, dosage form, strength, route of administration, or significant change in dose; or • any investigational drug, device, or biological packaged separately that according to its proposed labeling is for use only with another individually specified investigational drug, device, or biological product where both are required to achieve the intended use, indication, or effect.
Specifically, under regulations issued by the FDA, a combination product may be: • a product comprised of two or more regulated components that are physically, chemically, or otherwise combined or mixed and produced as a single entity; 27 • two or more separate products packaged together in a single package or as a unit and comprised of drug and device products; • a drug, device, or biological product packaged separately that according to its investigational plan or proposed labeling is intended for use only with an approved individually specified drug, device or biological where both are required to achieve the intended use, indication, or effect and where upon approval of the proposed product the labeling of the approved product would need to be changed, e.g., to reflect a change in intended use, dosage form, strength, route of administration, or significant change in dose; or • any investigational drug, device, or biological packaged separately that according to its proposed labeling is for use only with another individually specified investigational drug, device, or biological product where both are required to achieve the intended use, indication, or effect.
As no DBPCFCs were required, the primary endpoint of the clinical trial is safety as measured by adverse events, treatment-emergent adverse events and serious adverse events after six months of blinded treatment. Secondary endpoints included evolution of peanut-specific serological markers over time, including IgE, IgG and skin prick test wheal.
As no DBPCFCs were required, the primary endpoint of the clinical trial was safety as measured by adverse events, treatment-emergent adverse events and serious adverse events after six months of blinded treatment. Secondary endpoints included evolution of peanut-specific serological markers over time, including IgE, IgG and skin prick test wheal.
A harmonized procedure for the assessment of applications for clinical trials has been introduced and is divided into two parts. Part I assessment is led by the competent authorities of a reference Member State selected by the trial sponsor and relates to clinical trial aspects that are considered to be scientifically harmonized across EU Member States.
A harmonized procedure for the assessment of applications for clinical trials has been introduced and is divided into two parts. Part I assessment is led by the competent authorities of a reporting EU Member State selected by the trial sponsor and relates to clinical trial aspects that are considered to be scientifically harmonized across EU Member States.
This includes aggregate reductions to Medicare payments to providers of up to 2% per fiscal year, which went into effect in April 2013 and, due to subsequent legislative amendments, including the Infrastructure Investment and Jobs Act, will stay in effect until 2031,unless additional Congressional action is taken.
This includes aggregate reductions to Medicare payments to providers of up to 2% per fiscal year, which went into effect in April 2013 and, due to subsequent legislative amendments, including the Infrastructure Investment and Jobs Act, will stay in effect until 2032,unless additional Congressional action is taken.
We defined initiation as the submission of the trial protocol to selected study sites for subsequent Institutional Review Board (IRB)/Ethics Committee (EC) approval. On September 21, 2022, we announced we had received feedback from the FDA in the form of a partial clinical hold on VITESSE.
We defined initiation as the submission of the trial protocol to selected study sites for subsequent Institutional Review Board (IRB) approval and Ethics Committee (EC) opinion. On September 21, 2022, we announced we had received feedback from the FDA in the form of a partial clinical hold on VITESSE.
In November 2014, we initiated a multi-center, double-blind, placebo-controlled, randomized Phase 1/2 dose-finding trial to study the safety and efficacy of Viaskin Milk in 198 patients with Immunoglobulin E, or IgE, mediated CMPA, which we refer to as the Milk Efficacy and Safety, or MILES, trial.
In November 2014, we initiated a multi-center, double-blind, placebo-controlled, randomized Phase 1/2 dose-finding trial to study the safety and efficacy of Viaskin Milk in 198 subjects with Immunoglobulin E, or IgE, mediated CMPA, which we refer to as the Milk Efficacy and Safety, or MILES, trial.
In order to secure coverage and reimbursement for any product candidate that might be approved for sale, we may need to conduct expensive pharmacoeconomic studies in order to demonstrate the medical necessity and cost- effectiveness of the product candidate, in addition to the costs required to obtain FDA or other comparable regulatory approvals.
In order to secure coverage and reimbursement for any product candidate that might be approved for sale, sponsors may need to conduct expensive pharmacoeconomic studies in order to demonstrate the medical necessity and cost- effectiveness of the product candidate, in addition to the costs required to obtain FDA or other comparable regulatory approvals.
In addition, as in the United States, medicinal products can only be marketed if a marketing authorization from the competent regulatory authorities has been obtained. Clinical Trials in the EU Similar to the United States, the various phases of pre-clinical and clinical research in the European Union are subject to significant regulatory controls.
In addition, as in the United States, medicinal products can only be marketed if a marketing authorization from the competent regulatory authorities has been obtained. Clinical Trials in the EU Similar to the United States, the various phases of pre-clinical and clinical research in the EU are subject to significant regulatory controls.
In September 2018, we announced that the independent data safety and monitoring board, or DSMB, completed its review of Part A of EPITOPE and recommended that the dose of Viaskin Peanut 250 µg be evaluated in Part B. On October 26, 2018, we announced that the first patient was enrolled in Part B of EPITOPE.
In September 2018, we announced that the independent data safety and monitoring board, or DSMB, completed its review of Part A of EPITOPE and recommended that the dose of Viaskin Peanut 250 µg be evaluated in Part B. On October 26, 2018, we announced that the first subject was enrolled in Part B of EPITOPE.
In the future, we may apply for restoration of patent term for our currently owned or licensed patents to add patent life beyond its current expiration date, depending on the expected length of the clinical trials and other factors involved in the filing of the relevant BLA.
In the future, we may apply for extension of patent term for our currently owned or licensed patents to add patent life beyond its current expiration date, depending on the expected length of the clinical trials and other factors involved in the filing of the relevant BLA.
The FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions. The FDA will likely re-analyze the clinical trial data, which could result in extensive discussions between the FDA and us during the review process.
The FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions. The FDA will likely re-analyze the clinical trial data, which could result in extensive discussions between the FDA and the sponsor during the review process.
Enrollment of Part B of EPITOPE was complete in first quarter of 2021. In June 2022, we announced positive topline results from Part B of EPITOPE, which enrolled 362 subjects ages 1 to 3 years, of which 244 and 118 were in the active and placebo arms, respectively.
Enrollment of Part B of EPITOPE was completed in the first quarter of 2021. In June 2022, we announced positive topline results from Part B of EPITOPE, which enrolled 362 subjects ages 1 to 3 years, of which 244 and 118 were in the active and placebo arms, respectively.
The Hatch-Waxman Amendments permit a patent restoration term of up to five years as compensation for patent term lost during product development and the FDA regulatory review process. However, patent term restoration cannot extend the remaining term of a patent beyond a total of 14 years from the product’s approval date.
The Hatch-Waxman Amendments permit a patent extension of up to five years as compensation for patent term lost during product development and the FDA regulatory review process. However, patent term extension cannot extend the remaining term of a patent beyond a total of 14 years from the product’s approval date.
Data exclusivity, if granted, prevents regulatory authorities in the EU from referencing the innovator’s data to assess a generic application or biosimilar application for eight years from the date of authorization of the innovative product, after which a generic or biosimilar MAA can be submitted, and the innovator’s data may be referenced.
Data exclusivity prevents regulatory authorities in the EU from referencing the innovator’s data to assess a generic application or biosimilar application for eight years from the date of authorization of the innovative product, after which a generic or biosimilar MAA can be submitted, and the innovator’s data may be referenced.
This does not include a supplement for the biological product or a subsequent application by the same sponsor or manufacturer of the biological product (or licensor, predecessor in interest, or other related entity) for a change that results in a new indication, route of administration, dosing schedule, dosage form, delivery system, delivery 18 Table of Contents device, or strength, unless that change is a modification to the structure of the biological product and such modification changes its safety, purity, or potency.
This does not include a supplement for the biological product or a subsequent application by the same sponsor or manufacturer of the biological product (or licensor, predecessor in interest, or other related entity) for a change that results in a new indication, route of administration, dosing schedule, dosage form, delivery system, delivery device, or strength, unless that change is a modification to the structure of the biological product and such modification changes its safety, purity, or potency.
On June 26, 2020, we announced that in Part A, patients in both treatment arms showed consistent treatment effect after 12 months of therapy, as assessed by a double-blind placebo-controlled food challenge and biomarker results.
On June 26, 2020, we announced that in Part A, subjects in both treatment arms showed consistent treatment effect after 12 months of therapy, as assessed by a double-blind placebo-controlled food challenge and biomarker results.
Pursuant to Regulation (EC) No 726/2004, the centralized procedure is compulsory for specific products, including for (i) medicinal products derived from biotechnological processes, (ii) products designated as orphan medicinal products, (iii) advanced therapy medicinal products, or ATMPs, and (iv) products with a new active substance indicated for the treatment of HIV/AIDS, cancer, neurodegenerative diseases, diabetes, auto immune and other immune dysfunctions and viral diseases.
Pursuant to Regulation (EC) No 726/2004, the centralized procedure is compulsory for specific products, including for (i) medicinal products derived from biotechnological processes, (ii) products designated as orphan medicinal products, (iii) ATMPs, and (iv) products with a new active substance indicated for the treatment of HIV/AIDS, cancer, neurodegenerative diseases, diabetes, auto immune and other immune dysfunctions and viral diseases.
After the initial blinded six-month period, 97.5% of patients in both the placebo and active arms opted into an open-label portion of the study, which continued monitoring patients for a total of 36 months of active treatment.
After the initial blinded six-month period, 97.5% of subjects in both the placebo and active arms opted into an open-label portion of the study, which continued monitoring subjects for a total of 36 months of active treatment.
“First licensure” typically means the initial date the particular product at issue was licensed in the United States.
“First 21 licensure” typically means the initial date the particular product at issue was licensed in the United States.
Once the MA is obtained in all EU Member States and 31 Table of Contents study results are included in the product information, even when negative, the product is eligible for a six-month extension to the Supplementary Protection Certificate, or SPC, if any is in effect at the time of authorization or, in the case of orphan medicinal products, a two-year extension of orphan market exclusivity.
Once the MA is obtained in all EU Member States and study results are included in the product information, even when negative, the product is eligible for a six-month extension to the Supplementary Protection Certificate, or SPC, if any is in effect at the time of authorization or, in the case of orphan medicinal products, a two-year extension of orphan market exclusivity.
The most commonly reported adverse events were skin reactions localized to the administration site, the majority of which were mild to moderate in nature. 12 Table of Contents Fifty-five subjects (22.5%) in the Viaskin Peanut arm experienced an application site reaction that was assessed as severe by an investigator compared with 10 subjects (8.5%) in the placebo arm.
The most commonly reported adverse events were skin reactions localized to the administration site, the majority of which were mild to moderate in nature. Fifty-five subjects (22.5%) in the Viaskin Peanut arm experienced an application site reaction that was assessed as severe by an investigator compared with 10 subjects (8.5%) in the placebo arm.
Additionally, some clinical trials are overseen by an independent group of qualified experts organized by the clinical trial sponsor, known as a data safety monitoring board or committee. This group provides 22 Table of Contents authorization for whether or not a trial may move forward at designated intervals based on access to certain data from the trial.
Additionally, some clinical trials are overseen by an independent group of qualified experts organized by the clinical trial sponsor, known as a data safety monitoring board or committee. This group provides authorization for whether or not a trial may move forward at designated intervals based on access to certain data from the trial.
A favorable safety and tolerability profile was observed with Viaskin Peanut. Treatment adherence was high (98.5%), and similar discontinuation rates between treatment groups were reported, with 89.9% of patients completing the trial.
A favorable safety and tolerability profile was observed with Viaskin Peanut. Treatment adherence was high (98.5%), and similar discontinuation rates between treatment groups were reported, with 89.9% of subjects completing the trial.
The CTR also 28 Table of Contents establishes a single set of documents to be prepared and submitted for the application including, among other things, a copy of the trial protocol and an investigational medicinal product dossier containing information about the manufacture and quality of the medicinal product under investigation, as well as simplified reporting procedures for clinical trial sponsors.
The CTR also establishes a single set of documents to be prepared and submitted for the application including, among other things, a copy of the trial protocol and an investigational medicinal product dossier containing information about the manufacture and quality of the medicinal product under investigation, as well as simplified reporting procedures for clinical trial sponsors.
In experimental models, EPIT induced a population of regulatory T cells, or Tregs, with specific properties that resulted in suppression of allergic 2 Table of Contents symptoms and protection against further sensitizations. EPIT-induced epigenetic modifications favored a Treg- mediated immune response and a downregulated Th2 response and may play a role in the sustainability of effect.
In experimental models, EPIT induced a population of regulatory T cells, or Tregs, with specific properties that resulted in suppression of allergic. symptoms and protection against further sensitizations. EPIT-induced epigenetic modifications favored a Treg-mediated immune response and a downregulated Th2 response and may play a role in the sustainability of effect.
Additional legislative proposals to reform healthcare and government insurance programs, along with the trend toward managed healthcare in the United States, could influence the purchase of medicines and reduce demand 35 Table of Contents and prices for our products, if approved. This could harm our or our collaborators’ ability to market any products and generate revenues.
Additional legislative proposals to reform healthcare and government insurance programs, along with the trend toward managed healthcare in the United States, could influence the purchase of medicines and reduce demand and prices for our products, if approved. This could harm our or our collaborators’ ability to market any products and generate revenues.
EPITOPE is a two-part, pivotal Phase 3 clinical trial assessing the safety and efficacy of Viaskin Peanut 250 µg for the treatment of peanut-allergic toddlers one to three years of age.
EPITOPE is a two-part, pivotal Phase 3 clinical trial assessing the safety and efficacy of Viaskin Peanut for the treatment of peanut-allergic toddlers one to three years of age.
There is no assurance that the FDA will ultimately approve a product for marketing in the United States and we may encounter significant difficulties or costs during the review process.
There is no assurance that the FDA will ultimately approve a product for marketing in the United States and a sponsor may encounter significant difficulties or costs during the review process.
The GDPR applies to any company established in the EEA and to companies established outside the EEA that process personal data in connection with the offering of goods or services to data subjects in the EU or the monitoring of the behavior of data subjects in the European Union.
The GDPR applies to any company established in the EEA and to companies established outside the EEA that process personal data in connection with the offering of goods or services to data subjects in the EU or the monitoring of the behavior of data subjects in the EU.
At the 2016 EAACI meeting in Vienna, Austria, we presented initial findings from some of these collaborations, which suggest that proprietary biomarker modeling may be used to help monitor patient responses to Viaskin Peanut. Additional research is being performed to further strengthen the results of these early findings.
At the 2016 EAACI meeting in Vienna, Austria, we presented initial findings from some of these collaborations, which suggest that proprietary biomarker modeling may be used to help monitor patient responses to Viaskin Peanut. Additional research is planned to further strengthen the results of these early findings.
Detailed results were published in The Journal of the American Medical Association in February 2019. 7 Table of Contents With respect to CRD, a key secondary endpoint which measures threshold reactivity during the DBPCFC, we observed that at month 12, patients treated with Viaskin Peanut 250 µg and placebo reached a mean CRD of 906 mg (median 444 mg) and 361 mg (median 144 mg) of peanut protein, respectively.
Detailed results were published in The Journal of the American Medical Association (JAMA) in February 2019. 7 With respect to CRD, a key secondary endpoint which measures threshold reactivity during the DBPCFC, we observed that at month 12, patients treated with Viaskin Peanut 250 µg or placebo reached a mean CRD of 906 mg (median 444 mg) and 361 mg (median 144 mg) of peanut protein, respectively.
A Member State may approve a specific price for the medicinal product or it may instead adopt a system of direct or indirect controls on the profitability of the company placing the medicinal product on the market.
An EU Member State may approve a specific price for the medicinal product or it may instead adopt a system of direct or indirect controls on the profitability of the company placing the medicinal product on the market.
Part A subjects were not included in Part B and the efficacy analyses from Part A were not statistically powered to demonstrate superiority of either dose versus placebo. These results validate the ongoing investigation of the 250 µg dose in this age group, which is the dose being studied in Part B of the study.
Part A subjects were not included in Part B and the efficacy analyses from Part A were not statistically powered to demonstrate superiority of either dose versus placebo. These results validate the ongoing investigation of the 250 µg dose in this age group, which is the dose that was studied in Part B of the study.
Moreover, the GDPR grants data subjects the right to claim compensation for damages resulting from infringement of the GDPR. Following the United Kingdom’s withdrawal and the expiration of the transition period, from January 31, 2020, companies doing business in the EU and the UK will be obliged to comply with both the GDPR and the UK GDPR.
Moreover, the GDPR grants data subjects the right to claim compensation for damages resulting from infringement of the GDPR. Following the UK’s withdrawal and the expiration of the transition period, from January 31, 2020, companies doing business in the EU and the UK will be obliged to comply with both the GDPR and the UK GDPR.
No imbalance in SAEs was observed in the trial, with three cases in three patients in the active arm (1.0%) and two cases in two patients in the placebo arm (2.0%). One case in one patient in the active arm was qualified by the investigator as moderate anaphylaxis probably related to treatment. The patient responded to standard outpatient therapy.
No imbalance in SAEs was observed in the trial, with three cases in three patients in the active arm (1.0%) and two cases in two subjects in the placebo arm (2.0%). One case in one subject in the active arm was qualified by the investigator as moderate anaphylaxis probably related to treatment. The subject responded to standard outpatient therapy.
In the six-month blinded period, the discontinuation rate was 2.5%, with a 1.0% dropout related to adverse events. The mean patient compliance was above 95%.
In the six-month blinded period, the discontinuation rate was 2.5%, with a 1.0% dropout related to adverse events. The mean participant compliance was above 95%.
Any authorization which is not followed by the actual placing of the 30 Table of Contents medicinal product on the EU market (for a centralized MA) or on the market of the authorizing EU Member State within three years after authorization ceases to be valid (the so-called sunset clause).
Any authorization which is not followed by the actual placing of the medicinal product on the EU market (for a centralized MA) or on the market of the authorizing EU Member State within three years after authorization ceases to be valid (the so-called sunset clause).
Any agency or judicial enforcement action could have a material adverse effect on us. Our product candidates must be approved by the FDA through the Biologics License Application, or BLA, process before they may be legally marketed in the United States.
Any agency or judicial enforcement action could have a material adverse effect on us. Our product candidates must be approved by the FDA through the BLA process before they may be legally marketed in the United States.
The intent standard under the federal Anti-Kickback Statute was amended by the ACA to a stricter standard such that a person or entity no longer needs to have actual knowledge of the statute or specific intent to 36 Table of Contents violate it in order to have committed a violation.
The intent standard under the federal Anti-Kickback Statute was amended by the ACA to a stricter standard such that a person or entity no longer needs to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation.
Outside the United States, interactions between pharmaceutical companies and health care professionals are also governed by strict laws, such as national anti-bribery laws of EU Member States, national sunshine rules and regulations, industry self-regulation codes of conduct and physicians’ codes of professional conduct.
Outside the United States, interactions between pharmaceutical companies and healthcare professionals are also governed by strict laws, such as national anti-bribery laws of EU Member States, national sunshine rules and regulations, industry self-regulation codes of conduct and physicians’ codes of professional conduct.
Co-Ownership Agreement AP-HP and Université de Paris-Descartes In December 2008, we entered into an assignment, development and co-ownership agreement with AP-HP and Université Paris-Descartes, or UPD (which through a merger and a name change became Université Paris Cité), by which we agreed to terms of co-ownership with AP-HP and Université Paris Cité of certain U.S. and foreign patents and patent applications, referred to herein as the shared patents.
Co-Ownership Agreement AP-HP and Université Paris Cité (formerly known as Université de Paris-Descartes) In December 2008, we entered into an assignment, development and co-ownership agreement with AP-HP and Université Paris-Descartes, which through a merger and a name change became Université Paris Cité, by which we agreed to terms of co-ownership with AP-HP and Université Paris Cité of certain U.S. and foreign patents and patent applications, referred to herein as the shared patents.
An additional post-hoc analysis showed that 53.1% of patients treated with Viaskin Peanut increased their baseline ED from 100 mg or less to 300 mg or more, compared to 19% in the placebo group.
An additional post-hoc analysis showed that 53.1% of subjects treated with Viaskin Peanut increased their baseline ED from 100 mg or less to 300 mg or 8 more, compared to 19% in the placebo group.
In August 2017, we announced the completion of enrollment of the PEOPLE trial, with 298 (92%) patients who completed PEPITES enrolling in this follow-up trial.
In August 2017, we announced the completion of enrollment of the PEOPLE trial, with 298 (92%) subjects who completed PEPITES enrolling in this follow-up trial.
Following the completion of PEPITES, all patients were eligible to enroll in PEOPLE ( Open-Label Follow-Up Study of the PEPITES Study to Evaluate the Long-term Efficacy and Safety of Viaskin Peanut ), a long-term, open-label extension trial of Peanut 250 µg in children.
Following the completion of PEPITES, all eligible subjects were invited to enroll in PEOPLE ( Open-Label Follow-Up Study of the PEPITES Study to Evaluate the Long-term Efficacy and Safety of Viaskin Peanut ), a long-term, open-label extension trial of Peanut 250 µg in children.
Once a BLA has been accepted for filing, which occurs, if at all, sixty days after the BLA’s submission, the FDA’s goal is to review BLAs within ten months of the filing date for standard review or six months of the filing date for priority review, if the application is for a product intended for a serious or life-threatening condition and the product, if approved, would provide a significant improvement in safety or effectiveness.
Once a BLA has been accepted for filing, which occurs, if at all, sixty days after the BLA’s submission, the FDA’s goal is to review such BLA within ten months of the filing date for standard review or six months of the filing date for priority review (if granted by the FDA), if the application is for a product intended for a serious or life-threatening condition and the product, if approved, would provide a significant improvement in safety or effectiveness.
An MA may be granted only to an applicant established in the EU. 29 Table of Contents The centralized procedure provides for the grant of a single MA by the European Commission that is valid for all EU Member States.
An MA may be granted only to an applicant established in the EU. The centralized procedure provides for the grant of a single MA by the European Commission that is valid for all EU Member States.

… 216 more changes not shown on this page.

Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

241 edited+46 added−27 removed428 unchanged
Biggest changeOur business could be adversely affected by economic downturns, inflation, increases in interest rates, natural disasters, public health crises such as the COVID-19 pandemic, political crises, geopolitical events, such as the crisis in Ukraine, or other macroeconomic conditions, which have in the past and may in the future negatively impact our business and financial performance.
Biggest changeIn this case securities cannot be sold in such an offering at a price that is more than a 15% discount to (i) the last closing price of the Company’s shares on the regulated market Euronext Paris prior to the date on which the issue price is set, (ii) the volume-weighted average price of the share of the Company on the regulated market of Euronext Paris over a period determined by the Board of Directors of between one to five consecutive trading days chosen from the last thirty trading days prior to the date on which the issue price is set. 46 Our business could be adversely affected by economic downturns, inflation, increases in interest rates, natural disasters, public health crises such as the COVID-19 pandemic, political crises, geopolitical events, such as the crisis in Ukraine and the Israel-Hamas war, or other macroeconomic conditions, which have in the past and may in the future negatively impact our business and financial performance.
Moreover, because our business is almost entirely dependent upon Viaskin technology, any such setback in our pursuit of regulatory approval would have a material adverse effect on our business and prospects.
Moreover, because our business is almost entirely dependent upon our Viaskin technology, any such setback in our pursuit of regulatory approval would have a material adverse effect on our business and prospects.
Manufacturers of of products with which we contract are required to operate in accordance with FDA-mandated current good manufacturing practices, or cGMPs, or comparable GMP requirements in foreign countries.
Manufacturers of products with which we contract are required to operate in accordance with FDA-mandated current good manufacturing practices, or cGMPs, or comparable GMP requirements in foreign countries.
The results of this or future ICER report or any similar recommendations or guidelines may affect our reputation, and any recommendations or guidelines that result in decreased use or reimbursement of Viaskin Peanut, if approved, could have a material adverse effect on our results of operations and financial condition.
The results of this or any future ICER report or any similar recommendations or guidelines may affect our reputation, and any recommendations or guidelines that result in decreased use or reimbursement of Viaskin Peanut, if approved, could have a material adverse effect on our results of operations and financial condition.
In addition, these legal actions could be unsuccessful and could also result in the invalidation of our patents or a finding that they are unenforceable.
In addition, these legal actions could be unsuccessful and could also result in the invalidation of our patents and/or a finding that they are unenforceable.
Once a product is approved for sale and commercialized, the likelihood of product liability lawsuits increases. Criminal or civil proceedings might be filed against us by patients, the regulatory authorities, biopharmaceutical companies and any other third party using or marketing our products.
Once a product is approved for sale and commercialized, the likelihood of product liability lawsuits increases. Criminal or civil proceedings might be filed against us by patients, regulatory authorities, other biopharmaceutical companies and any other third party using or marketing our products.
In addition, if we are held liable in any of these lawsuits, we may incur substantial liabilities and may be forced to limit or forgo further commercialization of the affected products. We may incur significant costs from class action litigation.
In addition, if we are held liable in any of these lawsuits, we may incur substantial liabilities and we may be forced to limit or forgo further commercialization of the affected products. We may incur significant costs from class action litigation.
Furthermore, companies may face private litigation related to processing of personal data brought by classes of data subjects or consumer protection organizations authorized at law to represent their interests.
Furthermore, companies may face private litigation related to processing of personal data brought by data subjects, classes of data subjects or consumer protection organizations authorized at law to represent their interests.
In addition, we may unable to obtain the financing for these acquisitions under favorable conditions, and could be led to finance these acquisitions using cash that could be allocated to other purposes in the context of existing operations.
In addition, we may be unable to obtain the financing for these acquisitions under favorable conditions, and could be led to finance these acquisitions using cash that could be allocated to other purposes in the context of existing operations.
Before we can commercialize of Viaskin Peanut, if approved, and any of our other product candidates in North America, we will need to implement and improve our managerial, operational and financial systems, expand our facilities and continue to recruit and train additional qualified personnel.
Before we can commercialize Viaskin Peanut, if approved, and any of our other product candidates in North America, we will need to implement and improve our managerial, operational and financial systems, expand our facilities and continue to recruit and train additional qualified personnel.
It is possible that some of these parties will have interests that are different from, or in addition to, your interests as a shareholder. We are a “smaller reporting company,” and the reduced disclosure requirements applicable to smaller reporting companies may make our ADSs less attractive to investors.
It is possible that some of these parties will have interests that are different from, or are in addition to, your interests as a shareholder. We are a “smaller reporting company,” and the reduced disclosure requirements applicable to smaller reporting companies may make our ADSs less attractive to investors.
Furthermore, if we fail to comply with applicable FDA and other regulatory requirements at any stage during this regulatory process, we may encounter or be subject to: • issuance of warning letters, show cause notices or untitled letters describing alleged violations, which may be publicly available; • diminishment of any competitive advantages that such product candidates may have or attain; • suspension, delays or termination in clinical trials or commercialization; • delays or refusal by the FDA or similar foreign regulatory authorities to review pending applications for regulatory approval or supplements to approved applications; • voluntary or mandatory product recalls or seizures; • refusal to permit the import or export of medicinal products or intermediary chemicals; • suspension, restrictions or additional requirements on operations, including of manufacturing or revocation of necessary licenses; • withdrawals, variations or suspensions of regulatory approvals; and • fines, civil penalties, and criminal prosecutions.
Furthermore, if we fail to comply with applicable FDA and other regulatory requirements at any stage during this regulatory process, we may encounter or be subject to: • issuance of warning letters, show cause notices or untitled letters describing alleged violations, which may be publicly available; • diminishment of any competitive advantages that such product candidates may have or attain; • suspension, delays or termination in clinical trials or commercialization; • delays or refusal by the FDA or similar foreign regulatory authorities to review pending applications for regulatory approval or supplements to approved applications; • voluntary or mandatory product recalls or seizures; • refusal to permit the import or export of medicinal products or intermediary chemicals; • suspension, restrictions or additional requirements on operations, including of manufacturing or revocation of necessary licenses; 55 • withdrawals, variations or suspensions of regulatory approvals; and • fines, civil penalties, and criminal prosecutions.
The impact to Ukraine as well as actions taken by other countries, including new and stricter sanctions imposed by Canada, the United Kingdom, the European Union, the United States and other countries and companies and organizations against officials, individuals, regions, and industries in Russia and Ukraine, and actions taken by Russia in response to such sanctions, and responses of countries and political bodies to such sanctions, tensions, and military actions and the potential for more widespread conflict, have resulted in supply chain disruptions, and resulting increases in inflation, financial market volatility and capital markets disruption, potentially increasing in magnitude, and such effects on the global economy and financial markets could affect our business, operations, operating results and financial condition as well as the price of our common stock and our ability to raise additional capital when needed on acceptable terms.
The impact to Ukraine as well as actions taken by other countries, including new and stricter sanctions imposed by Canada, the United Kingdom, the European Union, the United States and other countries and companies and organizations against officials, individuals, regions, and industries in Russia and Ukraine, and actions taken by Russia in response to such sanctions, and responses of countries and 47 political bodies to such sanctions, tensions, and military actions and the potential for more widespread conflict, have resulted in supply chain disruptions, and resulting increases in inflation, financial market volatility and capital markets disruption, potentially increasing in magnitude, and such effects on the global economy and financial markets could affect our business, operations, operating results and financial condition as well as the price of our common stock and our ability to raise additional capital when needed on acceptable terms.
Further, if our Viaskin patch product candidates receive regulatory approval and we or others identify undesirable side effects caused by the products (or any other similar products) after the approval, a number of potentially significant negative consequences could result, including: • regulatory authorities may withdraw or limit their approval of the products; • regulatory authorities may require the addition of labeling statements, such as a “boxed” warning or a contraindication; • we may be required to change the way the products are distributed or administered, conduct additional clinical trials or change the labeling of the products; • we may decide to remove the products from the marketplace; • we could be sued and held liable for injury caused to individuals exposed to or taking our products; and • our reputation may suffer.
Further, if our Viaskin patch product candidates receive regulatory approval and we or others identify undesirable side effects caused by the products (or any 68 other similar products) after approval, a number of potentially significant negative consequences could result, including: • regulatory authorities may withdraw or limit their approval of the products; • regulatory authorities may require the addition of labeling statements, such as a “boxed” warning or a contraindication; • we may be required to change the way the products are distributed or administered, conduct additional clinical trials or change the labeling of the products; • we may decide to remove the products from the marketplace; • we could be sued and held liable for injury caused to individuals exposed to or taking our products; and • our reputation may suffer.
In particular, such filings are required in connection with investments exceeding €15,000,000 that lead to the acquisition of at least 10% of our share capital or voting rights or cross such 10% threshold; • under French law, certain investments in a French company relating to certain strategic industries by individuals or entities not established in a Member State of the EU are subject to prior authorization of the Ministry of Economy; • the owner of 90% of the share capital and voting rights of a public company listed on a regulated market in an EEA country, including from the main French Stock Exchange, has the right to force out minority shareholders following a tender offer made to all shareholders; 87 Table of Contents • a merger (i.e., in a French law context, a share for share exchange following which our company would be dissolved into the acquiring entity and our shareholders would become shareholders of the acquiring entity) of our company into a company incorporated in the European Union would require the approval of our board of directors as well as a two-thirds majority of the votes held by the shareholders present, represented by proxy or voting by mail at the relevant meeting; • under French law, a cash merger is treated as a share purchase and would require the consent of each participating shareholder; • our shareholders have granted and may grant in the future our board of directors’ broad authorizations to increase our share capital or to issue additional ordinary shares or other securities (for example, warrants) to our shareholders, the public or qualified investors, including as a possible defense following the launching of a tender offer for our shares; • our shareholders have preferential subscription rights on a pro rata basis on the issuance by us of any additional securities for cash or a set-off of cash debts, which rights may only be waived by the extraordinary general meeting (by a two-thirds majority vote) of our shareholders or on an individual basis by each shareholder; • our board of directors has the right to appoint directors to fill a vacancy created by the resignation or death of a director, subject to the approval by the shareholders of such appointment at the next shareholders’ meeting, which prevents shareholders from having the sole right to fill vacancies on our board of directors; • our board of directors can only be convened by our chairman or our managing director, if any, or, when no board meeting has been held for more than two consecutive months, by directors representing at least one-third of the total number of directors; • our board of directors meetings can only be regularly held if at least half of the directors attend either physically or by way of videoconference or teleconference enabling the directors’ identification and ensuring their effective participation in the board’s decisions; however, this mode of participation (by way of videoconference or teleconference) does not apply to the adoption of decisions taken for the closing of the accounts for the fiscal year, including the consolidated financial statements; • our shares are nominative or bearer, if the legislation so permits, according to the shareholder’s choice.
In particular, such filings are required in connection with investments exceeding €15,000,000 that lead to the acquisition of at least 10% of our share capital or voting rights or cross such 10% threshold; • under French law, certain investments in a French company relating to certain strategic industries by individuals or entities not established in a Member State of the EU are subject to prior authorization of the Ministry of Economy; • the owner of 90% of the share capital and voting rights of a public company listed on a regulated market in an EEA country, including from the main French Stock Exchange, has the right to force out minority shareholders following a tender offer made to all shareholders; • a merger (i.e., in a French law context, a share for share exchange following which our company would be dissolved into the acquiring entity and our shareholders would become shareholders of the acquiring entity) of our company into a company incorporated in the European Union would require the approval of our board of directors as well as a two-thirds majority of the votes held by the shareholders present, represented by proxy or voting by mail at the relevant meeting; • under French law, a cash merger is treated as a share purchase and would require the consent of each participating shareholder; • our shareholders have granted and may grant in the future our board of directors’ broad authorizations to increase our share capital or to issue additional ordinary shares or other securities (for example, warrants) to our shareholders, the public or qualified investors, including as a possible defense following the launching of a tender offer for our shares; • our shareholders have preferential subscription rights on a pro rata basis on the issuance by us of any additional securities for cash or a set-off of cash debts, which rights may only be waived by the extraordinary general meeting (by a two-thirds majority vote) of our shareholders or on an individual basis by each shareholder; • our board of directors has the right to appoint directors to fill a vacancy created by the resignation or death of a director, subject to the approval by the shareholders of such appointment at the next shareholders’ meeting, which prevents shareholders from having the sole right to fill vacancies on our board of directors; • our board of directors can only be convened by our chairman or our managing director, if any, or, when no board meeting has been held for more than two consecutive months, by directors representing at least one-third of the total number of directors; • our board of directors meetings can only be regularly held if at least half of the directors attend either physically or by way of videoconference or teleconference enabling the directors’ identification and ensuring their effective participation in the board’s decisions; however, this mode of participation (by way of videoconference or teleconference) does not apply to the adoption of decisions taken for the closing of the accounts for the fiscal year, including the consolidated financial statements; • our shares are nominative or bearer, if the legislation so permits, according to the shareholder’s choice.
Even if we contract with collaborators that successfully complete clinical trials for one or more of our product candidates, those candidates may not be commercialized for other reasons, including: • failing to receive regulatory approval to market them as drugs; • being subject to proprietary rights held by others; • failing to obtain approval from regulatory authorities on the manufacturing of our products; • being difficult or expensive to manufacture on a commercial scale; • having adverse side effects that make their use less desirable; • failing to compete effectively with products or treatments commercialized by competitors; or • failing to show long-term risk/benefit ratio of our products.
Even if we contract with collaborators that successfully complete clinical trials for one or more of our product candidates, those candidates may not be commercialized for other reasons, including: • failing to receive regulatory approval to market them as drugs; • being subject to proprietary rights held by others; • failing to obtain approval from regulatory authorities on the manufacturing of our products; • being difficult or expensive to manufacture on a commercial scale; 61 • having adverse side effects that make their use less desirable; • failing to compete effectively with products or treatments commercialized by competitors; or • failing to show long-term risk/benefit ratio of our products.
Any legal action against us or our collaborators could lead to: • payment of damages, potentially treble damages, if we are found to have willfully infringed a party’s patent rights; • injunctive or other equitable relief that may effectively block our ability to further develop, commercialize, and sell products; or • us or our collaborators having to enter into license arrangements that may not be available on commercially acceptable terms, if at all, all of which could have a material adverse impact on our cash position and business and financial condition.
Any legal action against us or our collaborators could lead to: • payment of damages, potentially treble damages, if we are found to have willfully infringed a party’s patent rights; 79 • injunctive or other equitable relief that may effectively block our ability to further develop, commercialize, and sell products; or • us or our collaborators having to enter into license arrangements that may not be available on commercially acceptable terms, if at all, all of which could have a material adverse impact on our cash position and business and financial condition.
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, transferable during a period starting two days prior to the opening of the subscription period or, if that day is not a trading day, the preceding trading day; and ending two days prior to the closing of the subscription period or, of that day is not a trading day, the preceding trading day, unless they waive those rights at an extraordinary meeting of our shareholders (by a two-thirds majority vote) or individually by each shareholder.
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, transferable during a period starting two days prior to 94 the opening of the subscription period or, if that day is not a trading day, the preceding trading day; and ending two days prior to the closing of the subscription period or, of that day is not a trading day, the preceding trading day, unless they waive those rights at an extraordinary meeting of our shareholders (by a two-thirds majority vote) or individually by each shareholder.
Even if Sanofi is able to meet our commercialization needs or if we are able to establish agreements with other third-party manufacturers, reliance on third-party manufacturers entails additional risks, including: • reliance on the third party for regulatory compliance and quality assurance; • the possible breach of the manufacturing agreement by the third party; • the possible misappropriation of our proprietary information, including our trade secrets and know- how; and • the possible termination or non-renewal of the agreement by the third party at a time that is costly or inconvenient for us.
Even if Sanofi is able to meet our commercialization needs or if we are able to establish agreements with other third-party manufacturers, reliance on third-party manufacturers entails additional risks, including: • reliance on the third party for regulatory compliance and quality assurance; • the possible breach of the manufacturing agreement by the third party; 59 • the possible misappropriation of our proprietary information, including our trade secrets and know- how; and • the possible termination or non-renewal of the agreement by the third party at a time that is costly or inconvenient for us.
It is also possible that Brexit may negatively affect our ability to attract and retain employees, particularly those from the EU. We are subject to healthcare laws and regulations, which could expose us to criminal sanctions, civil penalties, integrity obligations, exclusion from government healthcare programs, individual imprisonment, contractual damages, reputational harm and diminished profits and future earnings, among other consequences.
It is also possible that Brexit may negatively affect our ability to attract and retain employees, particularly those from the EU. 70 We are subject to healthcare laws and regulations, which could expose us to criminal sanctions, civil penalties, integrity obligations, exclusion from government healthcare programs, individual imprisonment, contractual damages, reputational harm and diminished profits and future earnings, among other consequences.
With regard to biopharmaceutical products, among other things, the ACA expanded and increased industry rebates for drugs covered under Medicaid programs and made changes to the coverage requirements under the Medicare prescription drug benefit. However, there have been executive, judicial and Congressional challenges to certain aspects of the ACA. For example, on June 17, 2021 the U.S.
With regard to biopharmaceutical products, among other things, the ACA expanded and increased industry rebates for drugs covered under Medicaid programs and made changes to the coverage requirements under the Medicare prescription drug benefit. However, there have been executive, judicial and Congressional 65 challenges to certain aspects of the ACA. For example, on June 17, 2021 the U.S.
The FDA and comparable foreign regulatory authorities impose stringent restrictions on manufacturers’ communications regarding off-label use and if we, or our collaborators, market any of our product candidates for which we, or they, receive regulatory approval for treatment other than their approved indications, we, or they, may be subject to warnings or enforcement action for off-label marketing.
The FDA and 57 comparable foreign regulatory authorities impose stringent restrictions on manufacturers’ communications regarding off-label use and if we, or our collaborators, market any of our product candidates for which we, or they, receive regulatory approval for treatment other than their approved indications, we, or they, may be subject to warnings or enforcement action for off-label marketing.
Even if the medical community accepts a product as safe and efficacious for its indicated use, prescribers may choose to restrict the use of the product if we or any collaborator is unable to demonstrate that, based on experience, clinical data, side-effect profiles and other factors, our product is preferable to any existing drugs or treatments.
Even if the medical community accepts a product as safe and efficacious for its indicated use, prescribers may choose to restrict the use of the product if we are,or any collaborator is, unable to demonstrate that, based on experience, clinical data, side-effect profiles and other factors, our product is preferable to any existing drugs or treatments.
Similar to the federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it to have committed a violation. • HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, or HITECH, and its implementing regulations, which impose certain requirements on covered entities and their business associates, and their covered subcontractors, including mandatory contractual terms, with respect to safeguarding the privacy, security and transmission of individually identifiable health information. 66 Table of Contents • The federal transparency requirements under the Physician Payments Sunshine Act, enacted as part of the ACA, that require applicable manufacturers of covered drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid, or the Children’s Health Insurance Program, with specific exceptions, to track and annually report to CMS payments and other transfers of value provided to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), other healthcare professionals (such as physician assistants and nurse practitioners), and teaching hospitals and certain ownership and investment interests held by physicians or their immediate family members in the applicable manufacturer, and disclosure of such information will be made by CMS on a publicly available website. • Analogous state, local or foreign laws and regulations, such as state anti-kickback and false claims laws, which may apply to items or services reimbursed by any third-party payor, including commercial insurers; state and local marketing and/or transparency laws applicable to manufacturers that may be broader in scope than the federal requirements, state laws that require biopharmaceutical companies to comply with the biopharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government, state and local laws that require licensure or registration of pharmaceutical sales representatives; state laws that require disclosure of information related to drug pricing; and state and foreign laws governing the privacy and security of health information in certain circumstances, many of which differ from each other in significant ways and may not have the same effect as HIPAA.
Similar to the federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it to have committed a violation. • HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, or HITECH, and its implementing regulations, which impose certain requirements on covered entities and their business associates, and their covered subcontractors, including mandatory contractual terms, with respect to safeguarding the privacy, security and transmission of individually identifiable health information. • The federal transparency requirements under the Physician Payments Sunshine Act, enacted as part of the ACA, that require applicable manufacturers of covered drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid, or the Children’s Health Insurance Program, with specific exceptions, to track and annually report to CMS payments and other transfers of value provided to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), other healthcare professionals (such as physician assistants and nurse practitioners), and teaching hospitals and certain ownership and investment interests held by physicians or their immediate family members in the applicable manufacturer, and disclosure of such information will be made by CMS on a publicly available website. 71 • Analogous state, local or foreign laws and regulations, such as state anti-kickback and false claims laws, which may apply to items or services reimbursed by any third-party payor, including commercial insurers; state and local marketing and/or transparency laws applicable to manufacturers that may be broader in scope than the federal requirements, state laws that require biopharmaceutical companies to comply with the biopharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government, state and local laws that require licensure or registration of pharmaceutical sales representatives; state laws that require disclosure of information related to drug pricing; and state and foreign laws governing the privacy and security of health information in certain circumstances, many of which differ from each other in significant ways and may not have the same effect as HIPAA.
There can be no assurance that any country that has price controls or reimbursement limitations for biopharmaceutical products will allow favorable reimbursement and pricing arrangements for any of our products. Historically, biopharmaceutical products launched in the European Union do not follow price structures of the United States and generally tend to have significantly lower prices.
There can be no assurance that any country that has price controls or reimbursement limitations for biopharmaceutical products will allow favorable reimbursement and pricing arrangements for any of our products. Historically, biopharmaceutical products launched in the European Union do not follow price structures 67 of the United States and generally tend to have significantly lower prices.
The EU Clinical Trials Regulation, or CTR, which was adopted in April 2014 and repeals the EU Clinical Trials Directive, became applicable on January 31, 2022. The CTR allows sponsors to make a single submission to both the competent authority and an ethics committee in each EU Member State, leading to a single decision for each EU Member State.
The EU Clinical Trials Regulation, or CTR, which was adopted in April 2014 and repeals the EU Clinical Trials Directive, became applicable on January 31, 2022. The CTR allows sponsors to make a single 72 submission to both the competent authority and an ethics committee in each EU Member State, leading to a single decision for each EU Member State.
Filing, prosecuting and defending patents, and defending other intellectual property rights such as trade secrets, on our product candidates 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.
Filing, prosecuting, defending, and maintaining patents, and defending other intellectual property rights such as trade secrets, on our product candidates 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.
If we or one of our licensing partners initiated legal proceedings against a third party to enforce a patent covering our product candidate, the defendant could counterclaim that the patent covering our product candidate is invalid and/or unenforceable. In patent litigation in the United States, defendant counterclaims alleging invalidity and/or unenforceability are commonplace.
If we or one of our licensing partners initiated legal proceedings against a third party to enforce a patent covering our product candidate, the defendant could counterclaim that the patent covering our product candidate is invalid 80 and/or unenforceable. In patent litigation in the United States, defendant counterclaims alleging invalidity and/or unenforceability are commonplace.
Obtaining requisite regulatory approval in any country is a complex, lengthy, expensive and uncertain process, and the FDA or the applicable foreign regulatory authority may delay, limit or deny approval of a Viaskin product, for many reasons, including, among others: • we may not be able to demonstrate that a product candidate is a safe and effective treatment, to the satisfaction of the FDA or the applicable foreign regulatory authority; • the results of our clinical trials or the clinical trials conducted by third party academic institutions and included in our application package may not meet the level of statistical or clinical significance required by the FDA or the applicable foreign regulatory authority for regulatory approval; • the FDA or the applicable foreign regulatory authority may disagree with the number, design, size, conduct or implementation of our clinical trials; • the FDA or the applicable foreign regulatory authority may require that we conduct additional clinical trials; • the FDA or the applicable foreign regulatory authority may not approve the formulation, labeling or specifications of a product candidate; • the clinical research organizations, or CROs, that we retain to conduct our clinical trials may take actions outside of our control that materially adversely impact our clinical trials; • the FDA or the applicable foreign regulatory authority may find the data from pre-clinical studies and clinical trials from a product candidate insufficient to demonstrate that the clinical or other benefits of either product candidate outweighs its respective safety risks; • the FDA or the applicable foreign regulatory authority may disagree with our analysis or interpretation of data from our pre-clinical studies and clinical trials; • the FDA or the applicable foreign regulatory authority may not accept data generated at our clinical trial sites; • an advisory committee, or similar body, may recommend against approval of our application or may recommend that the FDA or the applicable foreign regulatory authority require, as a condition of approval, additional pre-clinical studies or clinical trials, limitations on approved labeling or distribution and use restrictions; • the FDA or the applicable foreign regulatory agency may require development of a Risk Evaluation and Mitigation Strategy(or REMS), or comparable foreign requirements, as a condition of approval or post-approval; • the FDA or the applicable foreign regulatory authority may restrict the use of our products to a narrow population; • the FDA or the applicable foreign regulatory authority may not approve the manufacturing processes or facilities of our own or of third-party manufacturers with which we contract, or may issue inspectional findings that require significant expense and time to address; or • the FDA or the applicable foreign regulatory authority may change their approval policies or new legislation governing the approval processes.
Obtaining requisite regulatory approval in any country is a complex, lengthy, expensive and uncertain process, and the FDA or the applicable foreign regulatory authority may delay, limit or deny approval of a Viaskin product, for many reasons, including, among others: • we may not be able to demonstrate that a product candidate is a safe and effective treatment, to the satisfaction of the FDA or the applicable foreign regulatory authority; • the results of our clinical trials or the clinical trials conducted by third party academic institutions and included in our application package may not meet the level of statistical or clinical significance required by the FDA or the applicable foreign regulatory authority for regulatory approval; • the FDA or the applicable foreign regulatory authority may disagree with the number, design, size, conduct or implementation of our clinical trials; • the FDA or the applicable foreign regulatory authority may require that we conduct additional clinical trials; • the FDA or the applicable foreign regulatory authority may not approve the formulation, labeling or specifications of a product candidate; • the clinical research organizations, or CROs, that we retain to conduct our clinical trials may take actions outside of our control that materially adversely impact our clinical trials; 51 • the FDA or the applicable foreign regulatory authority may find the data from pre-clinical studies and clinical trials from a product candidate insufficient to demonstrate that the clinical or other benefits of such product candidate outweighs its respective safety risks; • the FDA or the applicable foreign regulatory authority may disagree with our analysis or interpretation of data from our pre-clinical studies and clinical trials; • the FDA or the applicable foreign regulatory authority may not accept data generated at our clinical trial sites; • an advisory committee, or similar body, may recommend against approval of our application or may recommend that the FDA or the applicable foreign regulatory authority require, as a condition of approval, additional pre-clinical studies or clinical trials, limitations on approved labeling or distribution and use restrictions; • the FDA or the applicable foreign regulatory authority may require development or implementation of a Risk Evaluation and Mitigation Strategy(or REMS), or comparable foreign requirements, as a condition of approval or post-approval; • the FDA or the applicable foreign regulatory authority may restrict the use of our products to a narrow population; • the FDA or the applicable foreign regulatory authority may not approve the manufacturing processes or facilities of our own or of third-party manufacturers with which we contract, or may issue inspectional findings that require significant expense and time to address; or • the FDA or the applicable foreign regulatory authority may change their approval policies or new legislation governing the approval processes.
If some investors find our ADSs less attractive as a result, there may be a less active trading market for our ADSs and our ADS price may be more volatile. U.S. Holders May Suffer Adverse Tax Consequences If We Are Characterized As A Passive Foreign Investment Company. Under the U.S.
If some investors find our ADSs less attractive as a result, there may be a less active trading market for our ADSs and our ADS price may be more volatile. 97 U.S. holders may suffer adverse tax consequences if we are characterized as a passive foreign investment company. Under the U.S.
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.
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 and prosecuted 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.
Our future capital requirements will depend on, and could increase significantly as a result of, many factors including: • the scope, progress in, results and the costs of, our pre-clinical studies and clinical trials and other research and development programs, particularly as we seek regulatory and marketing approvals for our product candidates that successfully complete clinical trials; • the approval of Viaskin Peanut by the FDA, European Commission, or other comparable regulatory authorities; • the costs of commercialization activities, including product sales, marketing, manufacturing and distribution, for any of our product candidates for which we receive regulatory approval, especially in North America; • the costs of securing manufacturing arrangements for commercial production; • revenue, if any, received from commercial sales of our product candidates, should any of our product candidates receive regulatory approval; • the scope, prioritization and number of our research and development programs; 44 Table of Contents • the costs, timing and outcome of regulatory review of our product candidates; • the achievement of milestones or occurrence of other developments that trigger payments under our existing collaboration agreements, and any additional collaboration agreements we may enter into; • the extent to which we are obligated to reimburse, or entitled to reimbursement of, clinical trial costs under our existing collaboration agreements and future collaboration agreements, if any; and • the costs involved in filing, prosecuting, enforcing and defending patent claims and other intellectual property rights.
Our future capital requirements will depend on, and could increase significantly as a result of, many factors including: • the scope, progress in, results and the costs of, our pre-clinical studies and clinical trials and other research and development programs, particularly as we seek regulatory and marketing approvals for our product candidates that successfully complete clinical trials; • the approval of Viaskin Peanut by the FDA, European Commission, or other comparable regulatory authorities; • the costs of commercialization activities, including product sales, marketing, manufacturing and distribution, for any of our product candidates for which we receive regulatory approval, especially in North America; • the costs of securing manufacturing arrangements for commercial production; • revenue, if any, received from commercial sales of our product candidates, should any of our product candidates receive regulatory approval; • the scope, prioritization and number of our research and development programs; • the costs, timing and outcome of regulatory review of our product candidates; • the achievement of milestones or occurrence of other developments that trigger payments under our existing collaboration agreements, and any additional collaboration agreements we may enter into; • the extent to which we are obligated to reimburse, or entitled to reimbursement of, clinical trial costs under our existing collaboration agreements and future collaboration agreements, if any; and • the costs involved in filing, prosecuting, enforcing and defending patent claims and other intellectual property rights.
In addition, data privacy and security laws have been proposed at the federal, state, and local levels in recent years, which could further complicate compliance efforts. Outside the United States, an increasing number of laws, regulations, and industry standards apply to data privacy and security.
In addition, data privacy and security laws have been proposed at the federal, state, and local levels in recent years, which could further complicate compliance efforts. 84 Outside the United States, an increasing number of laws, regulations, and industry standards apply to data privacy and security.
Legislators, policymakers and healthcare insurance funds in the EU may continue to propose and implement cost-containing measures to keep healthcare costs down; particularly due to the financial strain that the COVID-19 pandemic has placed on national healthcare systems of the EU Member States.
Legislators, policymakers and healthcare insurance funds in the EU may continue to propose and implement cost-containing measures to keep healthcare costs down; particularly due to the financial strain that the COVID-19 pandemic placed on national healthcare systems of the EU Member States.
If we choose to forgo patent protection or allow a patent application or patent to lapse purposefully or inadvertently, our competitive position could suffer. Legal actions to enforce our patent rights can be expensive and may involve the diversion of significant management time.
If we choose to forgo patent protection or allow a patent application or patent to lapse purposefully or inadvertently, our competitive position could suffer. Legal actions to enforce and/or defend our patent rights can be expensive and may involve the diversion of significant management time.
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. We may use hazardous chemicals and biological materials in our business.
Our financial statements are prepared in euros. 83 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. We may use hazardous chemicals and biological materials in our business.
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.
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 96 claim.
We have written agreements with collaborators that provide for the ownership of intellectual property arising from our collaborations. These agreements provide that we may have to 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.
We have written agreements with collaborators that provide for the ownership of intellectual property 78 arising from our collaborations. These agreements provide that we may have to 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.
Severe ransomware attacks, including by organized criminal threat actors, nation-states, and nation-state-supported actors, are becoming increasingly prevalent and severe and can lead to significant interruptions in our operations, loss of data and income, reputational harm, and diversion of funds.
Severe ransomware attacks, including by organized criminal threat actors, nation-states, and nation-state-supported actors, are becoming increasingly prevalent and severe and can lead to significant interruptions in our 86 operations, loss of data and income, reputational harm, and diversion of funds.
Guidelines from the EMA detail the type of quantity of supplementary data to be provided for different types of biological product. We also believe that our product candidates in the European Union should benefit from data and market exclusivity.
Guidelines from the EMA detail the type of quantity of supplementary data to be provided for different types of biological product. 63 We also believe that our product candidates in the European Union should benefit from data and market exclusivity.
Depending on the results of clinical trials and the process for obtaining regulatory approvals in other countries, we may decide to first seek regulatory approvals of a product candidate in countries other than the United States, or we may simultaneously seek regulatory approvals in the United States and other countries.
Depending on the results of clinical trials and the process for obtaining 56 regulatory approvals in other countries, we may decide to first seek regulatory approvals of a product candidate in countries other than the United States, or we may simultaneously seek regulatory approvals in the United States and other countries.
We are subject to the reporting requirements of the Securities Exchange Act of 1934, or the Exchange Act, 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.
We are subject to the reporting requirements of the Securities 49 Exchange Act of 1934, or the Exchange Act, 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.
The market price of our securities may fluctuate significantly in response to numerous factors, many of which are beyond our control, including: • actual or anticipated fluctuations in our financial condition and operating results; • actual or anticipated changes in our growth rate relative to our competitors; • competition from existing products or new products that may emerge; • regulatory actions with respect to our products or our competitors’ products, including the potential resubmission to the FDA of a BLA for Viaskin Peanut; • announcements by us, our partners or our competitors of significant acquisitions, strategic partnerships, joint ventures, collaborations, or capital commitments; • failure to meet or exceed financial estimates and projections of the investment community or that we provide to the public; • issuance of new or updated research or reports by securities analysts; • fluctuations in the valuation of companies perceived by investors to be comparable to us; • price and volume fluctuations attributable to inconsistent trading volume levels of the ADSs and/or ordinary shares; • additions or departures of key management or scientific personnel; • disputes or other developments related to proprietary rights, including patents, litigation matters, and our ability to obtain patent protection for our technologies; • changes in the structure of healthcare payment systems; • changes to coverage policies or reimbursement levels by commercial third-party payors and government payors and any announcements relating to coverage policies or reimbursement levels; • announcement or expectation of additional debt or equity financing efforts; • sales of our ordinary shares or ADSs by us, our insiders or our other shareholders; and • general economic and market conditions, including as a result of the COVID-19 pandemic.
The market price of our securities may fluctuate significantly in response to numerous factors, many of which are beyond our control, including: • actual or anticipated fluctuations in our financial condition and operating results; • actual or anticipated changes in our growth rate relative to our competitors; • competition from existing products or new products that may emerge; • regulatory actions with respect to our products or our competitors’ products, including the potential resubmission to the FDA of a BLA for Viaskin Peanut; • announcements by us, our partners or our competitors of significant acquisitions, strategic partnerships, joint ventures, collaborations, or capital commitments; • failure to meet or exceed financial estimates and projections of the investment community or that we provide to the public; • issuance of new or updated research or reports by securities analysts; • fluctuations in the valuation of companies perceived by investors to be comparable to us; • price and volume fluctuations attributable to inconsistent trading volume levels of the ADSs and/or ordinary shares; • additions or departures of key management or scientific personnel; • disputes or other developments related to proprietary rights, including patents, litigation matters, and our ability to obtain patent protection for our technologies; • changes in the structure of healthcare payment systems; • changes to coverage policies or reimbursement levels by commercial third-party payors and government payors and any announcements relating to coverage policies or reimbursement levels; • announcement or expectation of additional debt or equity financing efforts; • sales of our ordinary shares or ADSs by us, our insiders or our other shareholders; and • general economic and market conditions.
We rely on a single supplier to produce, or contract for the production of, active ingredients and we rely on a single manufacturer to produce patches for our clinical trials and for our commercial supplies of any future approved products.
We rely on a single supplier to produce, or contract for the production of, active ingredients and we rely on a single manufacturer to produce patches for our clinical trials and for our commercial supplies of any future 60 approved products.
Employee misconduct could also involve the improper use of, including trading on, information obtained in the course of clinical trials, which could result in regulatory sanctions and serious harm to our reputation.
Employee misconduct could also involve the improper use of, including trading on, 81 information obtained in the course of clinical trials, which could result in regulatory sanctions and serious harm to our reputation.
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.
If any of our confidential or proprietary information, such as our trade secrets, were to be disclosed or 77 misappropriated, or if any such information was independently developed by a competitor, our competitive position could be harmed.
Any future litigation could result in substantial costs and divert our management’s attention and resources, which could cause serious harm to our business, operating results and financial condition.
Any future litigation could result in substantial costs and divert our management’s attention and resources, which could cause serious harm to our business, operating 82 results and financial condition.
Advisors LP, entities affiliated with Braidwell, L.P., entities affiliated with VR Adviser, LLC, and entities affiliated with Bpifrance Participations S.A., together beneficially own approximately 52% of our ordinary shares. As a result, these shareholders, acting together, will have significant influence over all matters that require approval by our shareholders, including the election of directors and approval of significant corporate transactions.
Advisors LP, entities affiliated with Braidwell, L.P., entities affiliated with VR Adviser, LLC, and entities affiliated with Bpifrance Participations S.A., together beneficially own approximately 47% of our ordinary shares. As a result, these shareholders, acting together, will have significant influence over all matters that require approval by our shareholders, including the election of directors and approval of significant corporate transactions.
Share ownership is concentrated in the hands of our principal shareholders and management, who will continue to be able to exercise a direct or indirect controlling influence on us. As of December 31, 2022, our executive officers, directors, current 5% or greater shareholders and affiliated entities, including entities affiliated with Baker Bros.
Share ownership is concentrated in the hands of our principal shareholders and management, who will continue to be able to exercise a direct or indirect controlling influence on us. As of December 31, 2023, our executive officers, directors, current 5% or greater shareholders and affiliated entities, including entities affiliated with Baker Bros.
In the event we identify significant deficiencies or material weaknesses in our internal controls that we cannot remediate in a timely manner, or if our independent registered public accounting firm is 45 Table of Contents unable to express an opinion that our internal controls over financial reporting are effective, the market price of our ordinary shares and ADSs could decline if investors and others lose confidence in the reliability of our financial statements, we could be subject to sanctions or investigations by the SEC or other applicable regulatory authorities and our business could be harmed.
In the event we identify significant deficiencies or material weaknesses in our internal controls that we cannot remediate in a timely manner, or if our independent registered public accounting firm is unable to express an opinion that our internal controls over financial reporting are effective, the market price of our ordinary shares and ADSs could decline if investors and others lose confidence in the reliability of our financial statements, we could be subject to sanctions or investigations by the SEC or other applicable regulatory authorities and our business could be harmed.
These milestones may include our expectations regarding the commencement or completion of scientific studies, clinical trials, the submission of regulatory filings, or commercialization objectives.
These milestones may include our expectations regarding the commencement or completion of scientific studies and clinical trials, the submission of regulatory filings, or commercialization objectives.
Factors that may inhibit our efforts to commercialize our product candidates on our own include: • our inability to recruit, hire, retain and incentivize adequate numbers of effective sales and marketing personnel; • the inability of sales personnel to obtain access to physicians or educate adequate numbers of physicians on the benefits of prescribing any future products; • the lack of complementary products to be offered by sales personnel, which may put us at a competitive disadvantage relative to companies with more extensive product lines; and 57 Table of Contents • unforeseen costs and expenses associated with establishing an independent sales and marketing organization.
Factors that may inhibit our efforts to commercialize our product candidates on our own include: • our inability to recruit, hire, retain and incentivize adequate numbers of effective sales and marketing personnel; • the inability of sales personnel to obtain access to physicians or educate adequate numbers of physicians on the benefits of prescribing any future products; • the lack of complementary products to be offered by sales personnel, which may put us at a competitive disadvantage relative to companies with more extensive product lines; and • unforeseen costs and expenses associated with establishing an independent sales and marketing organization.
The statutory deadlines for pursuing patent protection in individual foreign jurisdictions are based on the priority dates of each of our patent applications.
The statutory deadlines for pursuing patent protection in individual foreign jurisdictions are generally based on the priority dates of each of our patent applications.
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.
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 under certain circumstances.
If we do not achieve our projected development and commercialization goals in the timeframes we announce and expect, the commercialization of our product candidates may be delayed, and our business will be harmed. We sometimes estimate the timing of the accomplishment of various scientific, clinical, regulatory, and other product development objectives for planning purposes.
If we do not achieve our projected development and commercialization goals in the timeframes we announce and expect, the commercialization of our product candidates may be delayed, and our business will be harmed. We sometimes estimate the timing of the accomplishment of various scientific, clinical, regulatory, and other product development objectives or milestones for planning purposes.
These patent applications may have priority over patent applications filed by us. Obtaining and maintaining a patent portfolio entails significant expense and resources.
These patent applications may have priority over patent applications filed by us. 75 Obtaining and maintaining a patent portfolio entails significant expense and resources.
Side effects of, or manufacturing defects in, products that we develop could result in the deterioration of a patient’s condition, injury or even death. For example, product liability claims may be brought by patients participating in our clinical trials as a result of unexpected side effects from our product candidates.
Side effects of, or manufacturing defects in, products that we develop could result in the deterioration of a patient’s condition, injury or even death. For example, product liability claims may be brought by subjects participating in our clinical trials as a result of unexpected side effects from our product candidates.
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.
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, inter partes review, and equivalent proceedings in foreign jurisdictions, e.g., opposition proceedings.
Our development activities or clinical trials conducted in reliance on third parties may be delayed, suspended, or terminated if: • the third parties do not successfully carry out their contractual duties or fail to meet regulatory obligations or expected deadlines; 56 Table of Contents • we replace a third party; or • the quality or accuracy of the data obtained by third parties is compromised due to their failure to adhere to clinical protocols, regulatory requirements, or for other reasons.
Our development activities or clinical trials conducted in reliance on third parties may be delayed, suspended, or terminated if: • the third parties do not successfully carry out their contractual duties or fail to meet regulatory obligations or expected deadlines; • we replace a third party; or • the quality or accuracy of the data obtained by third parties is compromised due to their failure to adhere to clinical protocols, regulatory requirements, or for other reasons.
To date, more than twelve clinical trials of Viaskin Peanut and Viaskin Milk product candidates have been conducted both outside and inside of the United States in over 1,000 human patients to evaluate the safety and efficacy of these product candidates for the treatment of peanut allergies and milk allergies, respectively.
To date, more than twelve clinical trials of Viaskin Peanut and Viaskin Milk product candidates have been conducted both outside and inside of the United States in over 1,000 human subjects to evaluate the safety and efficacy of these product candidates for the treatment of peanut allergies and milk allergies, respectively.
Any such serious clinical event could potentially adversely affect our clinical development timelines, including a complete clinical hold on our food allergy clinical trials. We may also become liable to patients who participate in our clinical trials and experience any such serious or fatal reactions.
Any such serious clinical event could potentially adversely affect our clinical development timelines, including a complete clinical hold on our food allergy clinical trials. We may also become liable to subjects who participate in our clinical trials and experience any such serious or fatal reactions.
The investor concerned could also be declared criminally liable and be sanctioned, in particular, by exclusion from any public contract or by a fine which may not exceed the highest of the following three amounts: (i) twice the amount of the investment concerned, (ii) 10% of the Company’s annual pre-tax revenues and (iii) 5 million euros (for a 90 Table of Contents company) or 1 million euros (for an individual).
The investor concerned could also be declared criminally liable and be sanctioned, in particular, by exclusion from any public contract or by a fine which may not exceed the highest of the following three amounts: (i) twice the amount of the investment concerned, (ii) 10% of the Company’s annual pre-tax revenues and (iii) 5 million euros (for a company) or 1 million euros (for an individual).
If we experience delay, suspensions or terminations in a clinical trial, the commercial prospects for the related product candidate will be harmed, and our ability to generate product revenues will be delayed or such revenues could be reduced or fail to materialize.
If we experience delay, suspensions or terminations of a clinical trial, the commercial prospects for the related product candidate will be harmed, and our ability to generate product revenues will be delayed or such revenues could be reduced or fail to materialize.
If Sanofi does not continue to manufacture the API as required by us in a timely manner, we may not be able to find a substitute manufacturer on a timely basis and our commercialization efforts and clinic trials may be delayed.
If Sanofi does not continue to manufacture the API as required by us in a timely manner, we may not be able to find a substitute manufacturer on a timely basis and our commercialization efforts and clinical trials may be delayed.
Such proceedings could result in revocation or amendment of our patents in such a way that they no longer cover our product candidates or competitive products. The outcome following legal assertions of invalidity and unenforceability is unpredictable.
Such proceedings could result in revocation or amendment of our patents in such a way that they no longer cover, encompass, or protect our product candidates or competitive products. The outcome following legal assertions of invalidity and unenforceability is unpredictable.
Numerous biopharmaceutical and biotechnology companies, universities and other research entities are actively involved in the discovery, development and 59 Table of Contents commercialization of therapeutic options to treat allergies, making it a highly competitive field. We have competitors in several jurisdictions, many of which have substantially greater name recognition, commercial infrastructures and financial, technical and personnel resources than we have.
Numerous biopharmaceutical and biotechnology companies, universities and other research entities are actively involved in the discovery, development and commercialization of therapeutic options to treat allergies, making it a highly competitive field. We have competitors in several jurisdictions, many of which have substantially greater name recognition, commercial infrastructures and financial, technical and personnel resources than we have.
The completion of any investment (i) by (a) an individual of foreign nationality, (b) any individual of French nationality not domiciled in France within the meaning of article 4B of the French General Tax Code ( Code Général des Impôts ), (c) any entity governed by foreign law, and (d) any entity governed by French law controlled by one or more of the entities referred to in (a) to (c), (ii) which would result in (a) the acquisition of control—within the meaning of article L. 233-3 of the French Commercial Code (Code de Commerce)—of a French company, (b) the acquisition of all or part of a branch of activity of a French company, or (c) for individuals who are not nationals of a Member State of the European Union or of a State party to the agreement on the European Economic Area that has entered into an administrative assistance agreement with France and/or are not domiciled in one of these States, or for legal entities of which at least one of the members of the control chain is not governed by the law of one of these States or is not a national and/or is not domiciled there, to cross the threshold of 25% of the voting rights of a French company and (iii) whose activities concern, even occasionally, the research and development of so-called critical technologies, such as biotechnologies, and considered essential to the protection of public health, is subject to prior authorization by the French Minister of the Economy ( Ministère de l’Economie ).
The completion of any investment (i) by (a) an individual of foreign nationality, (b) any individual of French nationality not domiciled in France within the meaning of article 4B of the French General Tax Code ( Code Général des Impôts ), (c) any entity governed by foreign law, and (d) any entity governed by French law controlled by one or more of the entities referred to in (a) to (c), (ii) which would result in (a) the acquisition of control—within the meaning of article L. 233-3 of the French Commercial Code (Code de Commerce)—of a French company, (b) the acquisition of all or part of a branch of activity of a French company, or (c) for individuals who are not nationals of a Member State of the European Union or of a State party to the agreement on the European Economic Area that has entered into an administrative assistance agreement with France and/or are not domiciled in one of these States, or for legal entities of which at least one of the members of the control chain is not governed by the law of one of these States or is not a national and/or is not domiciled there, to cross the threshold of 25% of the voting rights of a French company, or (d) for individuals who are not nationals of a Member State of the EU or of a State party to the agreement on the EEA that has entered into an administrative assistance agreement with France and/or are not domiciled in one of these State, or for legal entities of which at least one of the members of the control chain is not governed by the law of one of these States or is not a national and/or is not domiciled there, to cross the threshold of 10% of the voting rights of a French company whose shares are admitted to trading on a regulated market and (iii) whose activities concern, even occasionally, the research and development of so-called critical technologies, such as biotechnologies, and considered essential to the protection of public health, is subject to prior authorization by the French Minister of the Economy ( Ministère de l’Economie ).
A failure of any of our contract manufacturers to establish and follow cGMPs and to document their adherence to such practices may lead to significant delays in the launch of products based on our product candidates into the market.
A failure of any of our contract manufacturers to establish and follow cGMPs and to document their adherence to such practices may lead to significant delays in the launch or availability of products based on our product candidates into the market.
At the federal level, in July 2021, the Biden administration released an executive order, “Promoting Competition in the American Economy,” with multiple provisions aimed at prescription drugs. In response to Biden’s executive order, on September 9, 2021, the U.S.
At the federal level, in July 2021, the Biden administration released an executive order, “Promoting Competition in the American Economy,” with multiple provisions aimed at prescription drugs. In response to the Biden administration’s executive order, on September 9, 2021, the U.S.
If we cannot conduct necessary operations or otherwise capitalize on our business opportunities because we lack sufficient capital, our business, financial condition and results of operations could be materially adversely affected. 41 Table of Contents Additional fundraising efforts may divert our management from their day-to-day activities, which may adversely affect our ability to develop and commercialize our product candidates.
If we cannot conduct necessary operations or otherwise capitalize on our business opportunities because we lack sufficient capital, our business, financial condition and results of operations could be materially adversely affected. Additional fundraising efforts may divert our management from their day-to-day activities, which may adversely affect our ability to develop and commercialize our product candidates.
Similarly, supply-chain attacks have 81 Table of Contents increased in frequency and severity, and we cannot guarantee that third parties and infrastructure in our supply chain or our third-party partners’ supply chains have not been compromised or that they do not contain exploitable defects or bugs that could result in a breach of or disruption to our information technology systems or the third-party information technology systems that support us and our services.
Similarly, supply-chain attacks have increased in frequency and severity, and we cannot guarantee that third parties and infrastructure in our supply chain or our third-party partners’ supply chains have not been compromised or that they do not contain exploitable defects or bugs that could result in a breach of or disruption to our information technology systems or the third-party information technology systems that support us and our services.
For any taxable year in which we are a PFIC, we will determine whether we will provide to U.S. holders the information required to make a QEF election; for the taxable year ending December 31, 2021, we have provided that information.
For any taxable year in which we are a PFIC, we will determine whether we will provide to U.S. holders the information required to make a QEF election; for the taxable year ending December 31, 2023, we have provided that information.
For example, in August 2020, we received a Complete Response Letter, or CRL, in which the FDA indicated it could not approve the Viaskin Peanut BLA in its current form. The FDA identified concerns regarding the impact of system adhesion on efficacy and indicated the need for modifications, and a new human factors study.
For example, in August 2020, we received a Complete Response Letter, or CRL, in which the FDA indicated it could not approve the Viaskin Peanut BLA in its then-current form. The FDA identified concerns regarding the impact of system adhesion on efficacy and indicated the need for modifications, and new human factors studies.
There may be significant delays in obtaining coverage and reimbursement for newly approved products, and coverage may be more limited than the purposes for which the drug is approved by the FDA or comparable foreign regulatory authorities.
There may be significant delays in obtaining coverage and reimbursement for newly approved products, and coverage may be more limited than the purposes for which the product is approved by the FDA or comparable foreign regulatory authorities.
In addition, during daily administration of the patches during treatments, depending on the severity of the allergies and patient response to treatment, precautionary measures are necessary when handling the patches after use due to risk of contamination.
In addition, during daily administration of the patches during treatments, depending on the severity of the allergies and subject response to treatment, precautionary measures are necessary when handling the patches after use due to risk of contamination.
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: • our available capital resources or capital constraints we experience; 53 Table of Contents • our receipt of approvals, if any, by the FDA and other comparable foreign regulatory authorities and the timing thereof; • the rate of progress, costs and results of our clinical trials and research and development activities, including the extent of scheduling conflicts with participating clinicians and collaborators, and our ability to identify and enroll patients who meet clinical trial eligibility criteria; • other actions, decisions or rules issued by regulators; • our ability to access sufficient, reliable and affordable supplies of compounds used in the manufacture of our product candidates; • the efforts of our collaborators with respect to the commercialization of our products; • the securing of, costs related to, and timing issues associated with, product manufacturing, as well as sales and marketing activities; and • impacts of the COVID-19 pandemic.
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: • our available capital resources or capital constraints we experience; • our receipt of approvals, if any, by the FDA and other comparable foreign regulatory authorities and the timing thereof; • the rate of progress, costs and results of our clinical trials and research and development activities, including the extent of scheduling conflicts with participating clinicians and collaborators, and our ability to identify and enroll patients who meet clinical trial eligibility criteria; • other actions, decisions or rules issued by regulators; • our ability to access sufficient, reliable and affordable supplies of compounds used in the manufacture of our product candidates; • the efforts of our collaborators with respect to the commercialization of our products; and • the securing of, costs related to, and timing issues associated with, product manufacturing, as well as sales and marketing activities.
In addition, any or all of these effects could disrupt our and our collaborators’ supply chains and adversely affect our and our collaborators’ ability to conduct ongoing and future clinical trials of our product candidates. The extent and duration of the military action, sanctions and resulting economic, market and other disruptions are impossible to predict, but could be substantial.
Any or all of the effects of these conflicts could disrupt our and our collaborators’ supply chains and adversely affect our and our collaborators’ ability to conduct ongoing and future clinical trials of our product candidates. The extent and duration of the military action, sanctions and resulting economic, market and other disruptions are impossible to predict, but could be substantial.
In particular, sales, marketing and business arrangements in the healthcare industry are subject to extensive laws and regulations intended to prevent fraud, misconduct, kickbacks, self- dealing and other abusive practices. These laws and regulations restrict or prohibit a wide range 76 Table of Contents of pricing, discounting, marketing and promotion, sales commission, customer incentive programs and other business arrangements.
In particular, sales, marketing and business arrangements in the healthcare industry are subject to extensive laws and regulations intended to prevent fraud, misconduct, kickbacks, self-dealing and other abusive practices. These laws and regulations restrict or prohibit a wide range of pricing, discounting, marketing and promotion, sales commission, customer incentive programs and other business arrangements.
Each pre-funded warrant has an exercise price of €0.10 per Warrant Share. Pursuant to a registration rights agreement (the “Registration Rights Agreement”) with the investors, the Company filed a registration statement with the SEC registering the resale of 59,269,629 ordinary shares issued in the PIPE financing, including ordinary shares underlying the pre-funded warrants.
Each pre-funded warrant has an exercise price of €0.10 per Warrant Share. Pursuant to a registration rights agreement (the “Registration Rights Agreement”) with the investors, the Company filed a registration statement with the SEC registering the resale of 59,269,629 ordinary shares issued in the June 2022 PIPE, including ordinary shares underlying the pre-funded warrants.
In April 2021, in accordance with the amended Nasdaq Quorum Requirement, we fulfilled such requirements, including filing with the SEC a Current Report on Form 8-K disclosing that we had submitted a letter from our independent French counsel to Nasdaq 85 Table of Contents stating that the laws of France mandate a lower quorum for shareholders’ meetings than that required by the Nasdaq Quorum Requirement, and that we cannot obtain an exemption or waiver from such requirements.
In April 2021, in accordance with the amended Nasdaq Quorum Requirement, we fulfilled such requirements, including filing with the SEC a Current Report on Form 8-K disclosing that we had submitted a letter from our independent French counsel to Nasdaq stating that the laws of France mandate a 90 lower quorum for shareholders’ meetings than that required by the Nasdaq Quorum Requirement, and that we cannot obtain an exemption or waiver from such requirements.

… 234 more changes not shown on this page.

Item 2. Properties

Properties — owned and leased real estate

2 edited+1 added−5 removed0 unchanged
Biggest changeOn March 28, 2022, we entered into a lease agreement, commencing on April 1, 2022 and effective for 38 months, for an office of 5,799 square feet in Basking Ridge, New Jersey. The company leased a commercial facility of 8,919 square feet and an additional 12,629 square feet in the same building in Summit, New Jersey.
Biggest changeOn March 28, 2022, we entered into a lease agreement, commencing on April 1, 2022 and effective for 38 months, for an office of 5,799 square feet in Basking Ridge, New Jersey. We consider our facilities to be suitable and adequate for the management and operation of our business.
Item 2. Properties. Our corporate headquarters are located in Montrouge, France. Our principal offices occupy a 4,470 square meter facility, pursuant to a lease agreement, signed on March 3, 2015, with an effective date of August 1, 2015 and which expires July 31, 2024. Our primary U.S. office is located in Basking Ridge, New Jersey.
Item 2. Properties. Our corporate headquarters are located in Montrouge, France. Our principal office occupies a 4,470 square meter facility, pursuant to a lease agreement, signed on March 3, 2015, with an effective date of August 1, 2015 and which expires on July 31, 2024.
Removed
Both leases were initially intended to support the launch and commercialization of Viaskin Peanut in North America and were co-terminus on July 10, 2028, with extension options of two five-year periods.
Added
The company leased a commercial facility in Chatillon, France with early availability of the premises from November , 2023 and commencement of the lease on April 16, 2024. Our principal offices will represent 2 446,7 square meter facility. Our primary U.S office is located in Basking Ridge, New Jersey.
Removed
In light of our global restructuring and the current stage of regulatory interactions regarding Viaskin Peanut, the company entered into a termination agreement for the Summit, New Jersey leases effective on January 31, 2022, in exchange for a one-time lump sum early termination fee.
Removed
We also have facilities in North America that were initially intended to support our U.S. subsidiary as well as future commercialization needs. We lease 3,780 square feet of office space in Tower 49, New York, New York. This lease is for a period of 65 months.
Removed
In light of our global restructuring, the current stage of regulatory interactions regarding Viaskin Peanut, and the ongoing COVID-19 pandemic, we entered into a sublease agreement of this office space in June 2021. The lease and sublease both expire on March 31, 2023. We consider our facilities to be suitable and adequate for the management and operation of our business.
Removed
We believe that suitable additional or alternative space will be available to accommodate our future growth.

Item 3. Legal Proceedings

Legal Proceedings — active lawsuits and investigations

1 edited+0 added−7 removed0 unchanged
Biggest changeItem 3. Legal Proceedings. From time to time, we may become subject to various legal proceedings and claims that arise in the ordinary course of our business activities. We are not currently subject to any material legal proceedings.
Biggest changeItem 3. Legal Proceedings. From time to time, we may become subject to various legal proceedings and claims that arise in the ordinary course of our business activities. We are not currently subject to any material legal proceedings. Item 4. Mine Safety Disclosures. Not applicable. PART II
Removed
Class Action Complaint Dismissal A class action complaint was filed on January 15, 2019 in the United States District Court for the District of New Jersey, entitled Travis Ito-Stone v. DBV Technologies, et al., Case No. 2:19-cv-00525.
Removed
The complaint, as amended, alleged that we and our Chief Executive Officer, our current Chief Executive Officer, our former Deputy Chief Executive Officer, and our former Chief Business officer violated certain federal securities laws, specifically under Sections 10(b) and 20(a) of the Exchange Act, and Rule 10b-5 promulgated thereunder.
Removed
The plaintiffs seek unspecified damages on behalf of a purported class of persons that purchased our securities between February 14, 2018 and August 4, 2020 and also held our securities on December 20, 2018 and/or March 16, 2020 and/or August 4, 2020. A hearing was held on July 29, 2021 in the U.S.
Removed
District Court for the District of New Jersey where the Court entered an order granting our Motion to Dismiss the Second Amended Class Action Complaint without prejudice. As the dismissal was without prejudice, the Plaintiffs replead their case by filing a Third Amended Class Action Complaint on September 30, 2021 in the same Court.
Removed
We moved to dismiss third amended complaint on December 10, 2021. On July 29, 2022, the Court entered an order granting the Company’s Motion to Dismiss the Plaintiff’s Third Amended Compliant with prejudice.
Removed
The Court indicated that the Third Amended Complaint was deficient in a number of ways, failing to allege a violation of the Securities Exchange Act of 1934, and ordered the matter closed. Per court procedural rules, the Plaintiffs had 30 days to appeal the dismissal of the Third Amended Complaint.
Removed
The Plaintiffs failed to file an appeal of the dismissal of the Third Amended Complaint within the 30-day period and this matter is resolved with finality. 93 Table of Contents Item 4. Mine Safety Disclosures. Not applicable. PART II

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

3 edited+2 added−8 removed5 unchanged
Biggest changeHolders of Ordinary Shares As of February 28, 2023, there were approximately 395 holders of record of our ordinary shares and 2 holders of record of our ADSs. The actual number of holders is greater than these numbers of record holders, and includes beneficial owners whose ordinary shares or ADSs are held in street name by brokers and other nominees.
Biggest changeThe actual number of holders is greater than these numbers of record holders, and includes beneficial owners whose ordinary shares or ADSs are held in street name by brokers and other nominees. This number of holders of record also does not include holders whose shares may be held in trust by other entities.
This number of holders of record also does not include holders whose shares may be held in trust by other entities. The number of beneficial owners of the ADSs in the United States is likely to be much larger than the number of record holders of our ordinary shares in the United States.
The number of beneficial owners of the ADSs in the United States is likely to be much larger than the number of record holders of our ordinary shares in the United States.
Our ordinary shares have been trading on Euronext Paris under the symbol “DBV” since March 28, 2012. Prior to that date, there was no public trading market for our ADSs or our ordinary shares.
Our ordinary shares have been trading on Euronext Paris under the symbol “DBV” since March 28, 2012.
Removed
Recent Sales of Unregistered Equity Securities During the year ended December 31, 2022, we issued the following unregistered securities: • Pursuant to the authorizations granted by the General Meeting of the Shareholders held on May 12, 2022, the Company offered the opportunity to subscribe for warrants to purchase ordinary shares on May 12, 2022, and on June 9, 2022, the Chief Executive Officer authorized a capital increase for an amount of €3,285,566.90 through the issue of (i) 32,855,669 New Shares with a par value of €0.10 each and (ii) the issuance of 28,276,331 prefunded warrants, with cancellation of shareholders’ preferential subscription rights in favor of Braidwell LP, funds advised by Baker Bros.
Added
Prior to that date, there was no public trading market for our ADSs or our ordinary shares. 100 Holders of Ordinary Shares As of March 6, 2024, there were approximately 402 holders of record of our ordinary shares and 65 holders of record of our ADSs.
Removed
Advisor LP and BpiFrance Participations SA, existing shareholder of the Company and Venrock Healthcare Capital Partners; • On June 8, 2022, we entered into a securities purchase agreement with certain institutional and accredited investors pursuant to which we agreed to issue and sell to the investors i) 32,855,669 ordinary shares, nominal value €0.10 per share, at a price per ordinary share of €3.00 (corresponding to $3.22 on the basis of an exchange rate of $1.0739 = €1.00 published by the European Central Bank on June 8, 2022), and (ii) pre-funded warrants to purchase an aggregate of 28,276,331 ordinary shares (the “Warrant Shares”) at a pre-funded price per pre-funded warrant of €2.90 (corresponding to $3.11), which equals the per share price of the ordinary shares less the exercise price of €0.10 per Pre-Funded Warrant.
Added
Recent Sales of Unregistered Equity Securities During the year ended December 31, 2023, we issued the following unregistered securities: • On March 23, 2023, the issuance of an aggregate of 10,174 ordinary shares to U.S. and on-U.S. employees upon settlement of RSUs; • On May 29, 2023, the issuance of an aggregate of 2,500 ordinary shares to a non-U.S. employee upon settlement of RSUs; • On May 22, 2023, the issuance of an aggregate of 14,364 ordinary shares to non-U.S. employees upon settlement of RSUs; • On May 24, 2023, the issuance of an aggregate of 34,321 ordinary shares to U.S. and non-U.S. employees upon settlement of RSUs; • On September 23, 2023, the issuance of an aggregate of 2,599 ordinary shares to U.S. and non-U.S. employees upon settlement of RSUs None of the foregoing transactions involved any underwriters, underwriting discounts or commissions, or any public offering.
Removed
Each Pre-Funded Warrant has an exercise price of €0.10 per Warrant Share. The Pre-Funded Warrants are exercisable at any time after their original issuance and will expire ten years following their issuance.
Removed
The exercise price and number of shares of ordinary shares issuable upon exercise of the warrants may be adjusted in certain circumstances, including stock splits, stock 94 Table of Contents dividends, reclassifications and the like.
Removed
The pre-funded warrants issued in the PIPE provide that the holder of the pre-funded warrants will not have the right to exercise any portion of its pre-funded warrants if such holder, together with its affiliates, would beneficially own in excess of 9.99% of the number of ordinary shares outstanding immediately after giving effect to such exercise (the “Beneficial Ownership Limitation”).
Removed
The holder may increase or decrease the Beneficial Ownership Limitation, provided, however, that the holder may only increase the Beneficial Ownership Limitation by (i) obtaining authorization from the French Ministry of Economy in the event the Beneficial Ownership Limitation is being raised above 9.99%, and (ii) by providing 61 days’ notice to the Company, except that in no event will the Beneficial Ownership Limitation exceed 19.99%.
Removed
The securities issued by us pursuant to the securities purchase agreement and to be issued upon exercise of the warrants were not registered under the Securities Act of 1933, as amended, or the Securities Act, and may not be offered or sold in the United States absent registration or an applicable exemption from registration requirements.
Removed
Pursuant to the Registration Rights Agreement, the Company filed a registration statement with the Securities and Exchange Commission registering the resale of 59,269,629 ordinary shares issued in the PIPE financing, including ordinary shares underlying the pre-funded warrants. None of the foregoing transactions involved any underwriters, underwriting discounts or commissions, or any public offering.

Item 7. Management's Discussion & Analysis

Management's Discussion & Analysis (MD&A) — revenue / margin commentary

69 edited+24 added−33 removed33 unchanged
Biggest changeGAAP, for the years ended December 31, 2022 and 2021: December 31, (Dollar amounts presented in thousands, except per share amounts) 2022 2021 $ change % change Operating income $ 4,844 $ 5,708 (864 ) (15 )% Operating expenses Research and development expenses (75,543 ) (70,336 ) (5,207 ) 7 % Sales and marketing expenses (1,608 ) (4,387 ) 2,779 (63 %) General and administrative expenses (24,324 ) (30,520 ) 6,196 (20 %) Restructuring income (expenses) — 920 (920 ) (100 %) Total Operating expenses (101,475 ) (104,323 ) 2,848 (3 %) Financial income (expense) 427 425 2 1 % Income tax (70 ) 381 (451 ) (118 %) Net loss $ (96,274 ) $ (97,809 ) 1,535 (32 %) Basic/diluted Net loss per share attributable to shareholders (1.24 ) (1.78 ) 101 Table of Contents Operating Income The following table summarizes our operating income for the years presented: December 31, (Dollar amounts presented in thousands) 2022 2021 $ change % change Sales — — Other income 4,844 5,708 (864 ) (15 )% Research tax credit 5,718 7,505 (588 ) (24 %) Other operating (loss) income (874 ) (1,797 ) 923 (51 %) Total operating income 4,844 5,708 (864 ) (15 )% We generated operating income of $4.8 million for the year ended December 31, 2022 compared to $5.7 million for the year ended December 31, 2021, a decrease of 15%.
Biggest changeGAAP, for the years ended December 31, 2023 and 2022: December 31, $ change % change (Dollar amounts presented in thousands, except per share amounts) 2023 2022 Operating income $ 15,728 $ 4,844 10,885 225 % Operating expenses Research and development expenses (60,223 ) (75,543 ) 15,320 (20 %) Sales and marketing expenses (2,438 ) (1,608 ) (830 ) 52 % General and administrative expenses (29,500 ) (24,324 ) (5,176 ) 21 % Restructuring income (expenses) — — — — Total Operating expenses (92,161 ) (101,475 ) 9,314 (9 %) Financial income (expense) 3,714 427 3,286 769 % Income tax (7 ) (70 ) 63 (90 %) Net loss $ (72,726 ) $ (96,274 ) 23,548 (24 %) Basic/diluted Net loss per share attributable to shareholders (0.76 ) (1.24 ) Operating Income The following table summarizes our operating income for the years presented: December 31, $ change % change (Dollar amounts presented in thousands) 2023 2022 Sales — — Other income 15,728 4,844 10,884 225 % Research tax credit 8,766 5,718 3,048 53 % Other operating (loss) income 6,962 (874 ) 7,836 (896 %) Total operating income 15,728 4,844 10,884 225 % We generated operating income of $15.7 millions for the year ended December 31, 2023 compared to $4.8 millions for the year ended December 31, 2022.
We intend to seek additional capital as we prepare for the launch of Viaskin Peanut, if approved, and continue other research and development efforts. We may seek to finance our future cash needs through a combination of public or private equity or debt financings, collaborations, license and development agreements and other forms of non-dilutive financings.
We intend to seek additional capital as we prepare for the launch of Viaskin Peanut, if approved, and continue other research and development efforts. We may seek to finance our future cash needs through a combination of public or private equity or debt financings, collaborations, license and development agreements and other forms of non-dilutive financings.
Research and development expense consists primarily of: • cost of third-party contractors such as contract research organizations, or CROs, that conduct our non-clinical studies and clinical trials; • personnel costs, including salaries, related benefits and share-based compensation, for our employees engaged in scientific research and development functions; • purchases, real-estate leasing costs, as well as conferences and travel costs; and • depreciation, amortization and provisions.
Research and development expense consists primarily of: • cost of third-party contractors such as contract research organizations, or CROs, that conduct our non- clinical studies and clinical trials; • personnel costs, including salaries, related benefits and share-based compensation, for our employees engaged in scientific research and development functions; 103 • purchases, real-estate leasing costs, as well as conferences and travel costs; and • depreciation, amortization and provisions.
In addition, the 2022 Warrants do not provide any guarantee of value or return. Accordingly, the pre-funded warrants are classified as equity and accounted for as a component of additional paid-in capital at the time of issuance. Smaller Reporting Company Status We are a smaller reporting company as defined in the Securities Exchange Act of 1934, as amended.
In addition, the 2022 Warrants do not provide any guarantee of value or return. 115 Accordingly, the pre-funded warrants are classified as equity and accounted for as a component of additional paid-in capital at the time of issuance. Smaller Reporting Company Status We are a smaller reporting company as defined in the Securities Exchange Act of 1934, as amended.
Some of the information contained in this discussion and analysis or set forth elsewhere in this Annual Report on Form 10-K, including statements of our plans, objectives, expectations and intentions, contain forward-looking statements that involve risks and uncertainties.
Some of the information contained in this discussion and analysis or set forth elsewhere in this Annual Report on Form 10-K, including statements of our plans, objectives, expectations and 101 intentions, contain forward-looking statements that involve risks and uncertainties.
We anticipate that our expenses will increase substantially in connection with our ongoing activities, as we: • continue our research, pre-clinical and clinical development of our product candidates, including expanding the scope of our trials for Viaskin Peanut; • seek regulatory and marketing approvals and pursue commercial activities for Viaskin Peanut, primarily in North America and in the European Union; • seek regulatory and marketing approvals for our other product candidates that successfully complete clinical trials; • continue to establish a sales, marketing and distribution infrastructure to commercialize Viaskin Peanut, if approved, and any other products for which we may obtain marketing approval, especially in North America and in the European Union; 96 Table of Contents • further develop the manufacturing process for our product candidates; • change or add additional manufacturers or suppliers; • initiate and conduct any post-approval clinical trials, if required by the FDA or by the EMA, for our approved products, if any; • initiate additional pre-clinical, clinical or other studies for our product candidates; • seek to identify and validate additional product candidates; • acquire or in-license other product candidates and technologies; • make milestone or meet other payments deadlines under any in-license agreements; • maintain, protect and expand our intellectual property portfolio; • attract and retain new and existing skilled personnel; • add operational, financial and management information systems and personnel, including personnel to support our product development and commercialization efforts, as well as a company listed on both the U.S. and French stock markets; • experience any delays or encounter issues with any of the above.
We anticipate that our expenses will increase substantially in connection with our ongoing activities, as we: • continue our research, pre-clinical and clinical development of our product candidates, in particular expanding the scope of our trials for Viaskin Peanut; • seek regulatory and marketing approvals and pursue commercial activities for Viaskin Peanut, primarily in North America and in the European Union; • seek regulatory and marketing approvals for our other product candidates that successfully complete clinical trials; • establish a sales, marketing and distribution infrastructure to commercialize Viaskin Peanut, if approved, and any other products for which we may obtain marketing approval, especially in North America and in the European Union; • further develop the manufacturing process for our product candidates; • change or add additional manufacturers or suppliers; • initiate and conduct any post-approval clinical trials, if required by the FDA or by the EMA, for our approved products, if any; • initiate additional pre-clinical, clinical or other studies for our product candidates; • seek to identify and validate additional product candidates; • acquire or in-license other product candidates and technologies; • make milestone or meet other payments deadlines under any in-license agreements; • maintain, protect and expand our intellectual property portfolio; • attract and retain new and existing skilled personnel; • add operational, financial and management information systems and personnel, including personnel to support our product development and commercialization efforts, as well as a company listed on both the U.S. and French stock markets; • experience any delays or encounter issues with any of the above.
The duration, costs and timing of clinical trials and development of our product candidates will depend on a variety of factors, many of which are outside of our control including: • the FDA’s approval of our BLA for Viaskin Peanut; • the costs of future commercialization activities, including product sales, marketing, manufacturing and distribution, for any of our product candidates for which we receive marketing approval, especially in North America; • the costs of securing manufacturing arrangements for commercial production; 98 Table of Contents • revenue, if any, received from commercial sales of our product candidates, should any of our product candidates receive marketing approval; • the scope, progress in, results and the costs of, our pre-clinical studies and clinical trials and other research and development programs, particularly as we seek regulatory and marketing approvals for our product candidates that successfully complete clinical trials; • the scope, prioritization and number of our research and development programs; • the costs, timing and outcome of regulatory review of our product candidates; • the achievement of milestones or occurrence of other developments that trigger payments under our existing collaboration agreements, and any additional collaboration agreements we may enter into; • the extent to which we are obligated to reimburse, or entitled to reimbursement of, clinical trial costs under our existing collaboration agreements and future collaboration agreements, if any; and • the costs involved in filing, prosecuting, enforcing and defending patent claims and other intellectual property rights.
The duration, costs and timing of clinical trials and development of our product candidates will depend on a variety of factors, many of which are outside of our control including: • the FDA’s approval of our BLA for Viaskin Peanut; • the costs of future commercialization activities, including product sales, marketing, manufacturing and distribution, for any of our product candidates for which we receive marketing approval, especially in North America; • the costs of securing manufacturing arrangements for commercial production; • revenue, if any, received from commercial sales of our product candidates, should any of our product candidates receive marketing approval; • the scope, progress in, results and the costs of, our pre-clinical studies and clinical trials and other research and development programs, particularly as we seek regulatory and marketing approvals for our product candidates that successfully complete clinical trials; • the scope, prioritization and number of our research and development programs; • the costs, timing and outcome of regulatory review of our product candidates; • the achievement of milestones or occurrence of other developments that trigger payments under our existing collaboration agreements, and any additional collaboration agreements we may enter into; • the extent to which we are obligated to reimburse, or entitled to reimbursement of, clinical trial costs under any collaboration agreements or future collaborations, if any; and • the costs involved in filing, prosecuting, enforcing and defending patent claims and other intellectual property rights.
GAAP 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 facts and circumstances concerned.
GAAP are based on complex and subjective 113 assessments by our management or on estimates based on past experience and assumptions deemed realistic and reasonable based on the facts and circumstances concerned.
Collaboration agreement with Nestlé Health Science On May 31, 2016, we announced our entry into an exclusive global collaboration with Nestlé Health Science to develop MAG1C, a ready-to-use and standardized atopy patch test tool for the diagnosis of cow’s milk protein allergy in infants and toddlers.
Revenue Recognition —Collaboration Agreement with Nestlé Health Science On May 31, 2016, we announced our entry into an exclusive global collaboration with Nestlé Health Science to develop MAG1C, a ready-to-use and standardized atopy patch test tool for the diagnosis of cow’s milk protein allergy in infants and toddlers.
The following table provides a breakdown of our direct research and development expenses for our two lead development programs, as well as expenses not allocated to the programs and share-based compensation expenses included in research and development expenses, for the years ended December 31, 2022 and 2021, respectively: Year Ended December 31, 2022 2021 (thousands of U.S.
The following table provides a breakdown of our direct research and development expenses for our two lead development programs, as well as expenses not allocated to the programs and share-based compensation expenses included in research and development expenses, for the years ended December 31, 2023 and 2022, respectively: Year Ended December 31, 2023 2022 (thousands of U.S.
We may be a smaller reporting company in any year in which (i) the market value of our voting and non-voting ordinary shares held by non-affiliates is less than $250.0 million measured on the last business day of our second 109 Table of Contents fiscal quarter or (ii) (a) our annual revenue is less than $100.0 million during the most recently completed fiscal year and (b) the market value of our voting and non-voting ordinary shares held by non-affiliates is less than $700.0 million measured on the last business day of our second fiscal quarter.
We may be a smaller reporting company in any year in which (i) the market value of our voting and non-voting ordinary shares held by non-affiliates is less than $250.0 million measured on the last business day of our second fiscal quarter or (ii) (a) our annual revenue is less than $100.0 million during the most recently completed fiscal year and (b) the market value of our voting and non-voting ordinary shares held by non-affiliates is less than $700.0 million measured on the last business day of our second fiscal quarter.
Our therapeutic approach is based on epicutaneous immunotherapy, or EPIT TM , our proprietary method of delivering biologically active compounds to the immune system through intact skin using Viaskin, an epicutaneous patch (i.e., a skin patch). We have generated significant data demonstrating that Viaskin’s mechanism of action is novel and differentiated.
Our therapeutic approach is based on epicutaneous immunotherapy, or EPITTM, our proprietary method of delivering biologically active compounds to the immune system through intact skin using Viaskin, an epicutaneous patch (i.e., a skin patch). We have generated significant data demonstrating that Viaskin’s mechanism of action is novel and differentiated.
The ongoing COVID-19 pandemic and conflict in Ukraine have already caused extreme volatility and disruptions in the capital and credit markets. A severe or prolonged economic downturn could result in a variety of risks to us, including reduced ability to raise additional capital when needed or on acceptable terms, if at all.
The COVID-19 pandemic and the conflict in Ukraine caused extreme volatility and disruptions in the capital and credit markets. A severe or prolonged economic downturn could result in a variety of risks to us, including reduced ability to raise additional capital when needed or on acceptable terms, if at all.
The expenditures taken into account for the calculation of the research tax credit involve only research expenses. 99 Table of Contents If a company meets certain criteria in terms of sales, headcount or assets to be considered a Small and Medium-sized Enterprises, or SMEs, under EU law, immediate payment of the CIR can be requested.
The expenditures taken into account for the calculation of the research tax credit involve only research expenses. 105 If a company meets certain criteria in terms of sales, headcount or assets to be considered a Small and Medium- sized Enterprises, or SMEs, under EU law, immediate payment of the CIR can be requested.
Our direct research and development expenses consist principally of external costs, such as startup fees paid to investigators, consultants, central laboratories, and CROs in connection with our clinical trials, and costs related 97 Table of Contents to acquiring and manufacturing clinical study materials.
Our direct research and development expenses consist principally of external costs, such as startup fees paid to investigators, consultants, central laboratories, and CROs in connection with our clinical trials, and costs related to acquiring and manufacturing clinical study materials.
Components of Our Results of Operations Operating Income Our operating income consists of other operating income, as described below, as we generated no revenue from our operating activities in 2022 or 2021.
Components of Our Results of Operations Operating Income Our operating income consists of other operating income, as described below, as we generated no revenue from our operating activities in 2023 or 2022.
Viaskin targets specific antigen-presenting immune cells in the skin, called Langerhans cells, that capture the antigen and 95 Table of Contents migrate to the lymph node in order to activate the immune system without passage of the antigen into the bloodstream, minimizing systemic exposure in the body.
Viaskin targets specific antigen-presenting immune cells in the skin, called Langerhans cells, that capture the antigen and migrate to the lymph node in order to activate the immune system without passage of the antigen into the bloodstream, minimizing systemic exposure in the body.
Sales and Marketing Sales and marketing expense consists primarily of personnel costs, consultant fees and share-based compensation for sales and marketing employees, as well as fees related to pre-commercialization activities for Viaskin Peanut in North America and in the European Union, other consulting fees and travel costs.
Sales and Marketing Sales and marketing expense consists primarily of personnel costs, consultant fees and share-based compensation for sales and marketing employees, as well as fees related to pre-commercialization activities for Viaskin Peanut in North America and in the European Union.
Risk-free interest rate The risk-free interest rate is based on French government bonds (GFRN) with a maturity corresponding to the maturity of the share options. 108 Table of Contents Expected term We determine the expected term based on the average period the stock options are expected to remain outstanding.
Risk-free interest rate The risk-free interest rate is based on French government bonds (GFRN) with a maturity corresponding to the maturity of the share options. Expected term We determine the expected term based on the average period the stock options are expected to remain outstanding.
Dollars) 2021 — — — — 2022 194,446 — — 194,446 Total 194,446 — — 194,446 We have incurred net losses each year since our inception. Substantially all of our net losses resulted from costs incurred in connection with our development programs and from general and administrative expenses associated with our operations. We have not incurred any bank debt.
Dollars) 2022 194,446 — — 194,446 2023 6,921 — — 6,921 Total 201,367 — — 201,367 We have incurred net losses each year since our inception. Substantially all of our net losses resulted from costs incurred in connection with our development programs and from general and administrative expenses associated with our operations. We have not incurred any bank debt.
We expect that our research and development expenses will continue to increase in the foreseeable future as we initiate clinical trials for certain product candidates and pursue later stages of clinical development of our product candidates. In the year ended December 31, 2022, we spent $75.5 million in research and development expenses to advance the development of our product candidates.
We expect that our Research and Development expenses will continue to increase in the foreseeable future as we initiate clinical trials for certain product candidates and pursue later stages of clinical development of our product candidates. In the year ended December 31, 2023, we spent $60.2 million in research and development expenses to advance the development of our product candidates.
Net loss per share (based on the weighted average number of shares outstanding over the period) was $1.24 and $1.78 for the year ended December 31, 2022 and 2021, respectively.
Net loss per share (based on the weighted average number of shares outstanding over the period) was $0.76 and $1.24 for the year ended December 31, 2023 and 2022, respectively.
The amount is classified in other non-current financial assets in our statement of financial position. At December 31, 2022, 149,793 shares and $0.3 million were in the liquidity account. The liquidity agreement has a term of one year and will renew automatically unless otherwise terminated by either party.
The amount is classified in other non-current financial assets in our statement of financial position. At December 31, 2023, 222,988 shares and $0.2 million were in the liquidity account. The liquidity agreement has a term of one year and will renew automatically unless otherwise terminated by either party.
General and administrative expense also consists of costs related to obtaining a directors and officers liability insurance policy and fees for professional services, mainly related to audit, tax and legal services, real-estate leasing costs, insurance costs, consulting costs, investor relations costs and corporate communication and travel costs.
General and Administrative expense also consists of Information Systems architecture, software licenses, IT equipment and, to obtaining a directors and officers liability insurance policy and fees for professional services, mainly related to audit, tax and legal services, real-estate leasing costs, insurance costs, consulting costs, investor relations costs and corporate communication and travel costs.
We estimated the following assumptions for the calculation of the fair value of our stock options: Assumptions per year ended December 31, Stock options per grant date 2022 2021 Weighted average shares price at grant date (in €) 2.33 5.71 Weighted average expected volatility 98.9 % 90.2 % Weighted average risk-free interest rate 2.2 % (0.06 )% Weighted average expected term (in years) 6 6 Dividend yield 0 0 Weighted average fair value of stock-options (in €) 2.23 4.17 * The weighted average fair value of underlying shares is presented in euros, as we are incorporated in France and the euro is the currency used for the grants.
We estimated the following assumptions for the calculation of the fair value of our stock options: Assumptions per year ended December 31, Stock options per grant date 2023 2022 Weighted average shares price at grant date in € 2,08 2,33 Weighted average expected volatility 97,02 % 98,90 % Weighted average risk-free interest rate 2,99 % 2,20 % Weighted average expected term (in years) 6 6 Dividend yield — — Weighted average fair value of stock-options in € 1,33 2,23 * The weighted average fair value of underlying shares is presented in euros, as we are incorporated in France and the euro is the currency used for the grants.
Income tax Our income tax expense was $70,000 for the year ended December 31, 2022, compared to a US Tax income of $381,000 for the year ended December 31, 2021. Net loss Net loss was $96.3 million for the year ended December 31, 2022, compared to $97.8 million for the year ended December 31, 2021.
Income tax Our income tax expense was $7,000 for the year ended December 31, 2023, compared to a US Tax income of $70,000 for the year ended December 31, 2022. Net loss Net loss was $72.7 million for the year ended December 31, 2023, compared to $96.3 million for the year ended December 31, 2022.
Results of Operations Comparison of the Years Ended December 31, 2022 and 2021 The following table summarizes our results of operations, derived from our consolidated financial statements, prepared in compliance with generally accepted accounting principles in the United States, or U.S.
We expect to continue this investment strategy. 107 Results of Operations Comparison of the Years Ended December 31, 2023 and 2022 The following table summarizes the results of our operations, derived from our consolidated financial statements, prepared in compliance with generally accepted accounting principles in the United States, or U.S.
As of December 31, 2022, expenses associated with the ongoing trials amounted globally to $126.1 million, and we had non-cancellable contractual obligations with CRO until year ended 2025 amounting to $48.7 million. 106 Table of Contents Cash flows The table below summarizes our sources and uses of cash for the years ended December 31, 2022 and 2021.
As of December 31, 2023, expenses associated with the ongoing trials amounted globally to $114.4 million, and we had non-cancellable contractual obligations with CRO until year ended 2025 amounting to $44.2 million. Cash flows The table below summarizes our sources and uses of cash for the years ended December 31, 2023 and 2022.
Sales and Marketing Expenses The following table summarizes our sales and marketing expenses for the years presented: December 31, (Dollar amounts presented in thousands) 2022 2021 $ change % change Sales and marketing expenses Employee-related costs incl. share-based payment expenses 914 1,885 (971 ) (52 %) External professional services and other costs 694 2,502 (1,808 ) (72 %) Total Sales and marketing expenses 1,608 4,387 (2,779 ) (63 %) Sales and marketing expenses primarily included payroll for the U.S. employees as well as fees related to pre-commercialization activities for Viaskin Peanut in North America.
Sales and Marketing Expenses The following table summarizes our sales and marketing expenses for the years presented: December 31, $ change % change (Dollar amounts presented in thousands) 2023 2022 Sales and marketing expenses Employee-related costs incl. share-based payment expenses 754 914 (160 ) (18 %) External professional services and other costs 1,784 694 990 143 % Total Sales and marketing expenses 2,438 1,608 830 52 % Sales and marketing expenses primarily included payroll for the U.S. and European employees as well as fees related to pre- commercialization activities for Viaskin Peanut in North America.
A one-time lump sum early termination fee of $1.5 million was paid in 2022 and offset by the recognition of an income of $1.2 million due to the early termination of this lease. • In June 2021, we entered into a sublease agreement of our 3,780 square feet office space in Tower 49, New York, New York that both expire in the first quarter of 2023, simultaneously with the lease term.
A one-time lump sum early termination fee of $1.5 million was paid in 2022 and offset by the recognition of an income of $1.2 million due to the early termination of this lease. • In June 2021, we entered into a sublease agreement of our 3,780 square feet office space in Tower 49, New York, New York that both expire in the first quarter of 2023, simultaneously with the lease term. 112 Purchase obligations—Obligations Under the Terms of CRO Agreements In connection with the launch of our clinical trials for Viaskin Peanut and Viaskin Milk, we signed agreements with several contract research organizations.
In light of the current stage of regulatory interactions regarding Viaskin Peanut, we are achieving the resizing of our facility use in North America that were initially intended to support our U.S. subsidiary as well as future commercialization needs: • In January 2022, we entered into a termination agreement for our 21,548 square feet commercial facility in Summit, New Jersey.
In light of the current stage of regulatory interactions regarding Viaskin Peanut, we achieved the resizing of our facility use in North America that was initially intended to support our U.S. subsidiary as well as future commercialization needs, explaining partially operating leases costs as of December 31, 2023 and December 31, 2022 : • In January 2022, we concluded a termination agreement for our 21,548 square feet commercial facility in Summit, New Jersey.
Our most advanced product candidate is Viaskin Peanut, which has been evaluated as a potential therapy for children with peanut allergy in nine clinical trials, including four Phase 2 trials and three completed Phase 3 trials.
Our most advanced product candidate is Viaskin Peanut, which has been evaluated as a potential therapy for children with peanut allergy in twelve clinical trials, including three Phase 2 trials and four completed Phase 3 trials. We have two ongoing Phase 3 trial of Viaskin Peanut in children ages one to three and ages four to seven with peanut allergy.
As such, no adjustments have been made to the financial statements relating to the recoverability and classification of the asset carrying amounts or classification of liabilities that might be necessary should we not be able to continue as a going concern.
As such, no adjustments have been made to the financial statements relating to the recoverability and classification of the asset carrying amounts or classification of liabilities that might be necessary should we not be able to continue as a going concern. Business Trends We engage in substantial research and development efforts to develop innovative pharmaceutical product candidates.
We cannot guarantee that we will be able to obtain the necessary financing to meet our needs or to obtain funds at attractive terms and conditions, including as a result of disruptions to the global financial markets due to the ongoing COVID-19 pandemic and conflict in Ukraine.
We cannot guarantee that we will be able to obtain the necessary financing to meet our needs or to obtain funds at attractive terms and conditions, including as a result of disruptions to the global financial markets due any 111 future pandemics, epidemics or global health crises and conflict in Ukraine or other global political or military crises.
We anticipate that our general and administrative expenses will increase in the future as we increase our headcount to support the expected growth in our research and development activities and the potential launch and commercialization of Viaskin Peanut in North America and in European Union, if approved.
We anticipate that our General and Administrative expenses will increase in the future to support the expected growth in our Research and Development activities and the potential launch and commercialization of Viaskin Peanut in North America and in European Union, if approved. We also anticipate continued increased expenses associated with being a public company in the United States.
Sources of Liquidity and Material Cash Requirements Based on its current operations, plans and assumptions as revised pursuant to 2022 announcements related to EPITOPE Phase 3 study topline results and VITESSE Phase 3 partial clinical hold lift, as well as ATM and PIPE financings, the Company expects that its balance of cash and cash equivalents of $209.2 million as of December 31, 2022 will be sufficient to fund its operations for at least the next 12 months.
Sources of Liquidity and Material Cash Requirements Based on its current operations, plans and assumptions as revised pursuant to 2023 announcements related to EPITOPE Phase 3 study topline results and VITESSE Phase 3 partial clinical hold lift, the Company expects that its balance of cash and cash equivalents of $141.4 million as of December 31, 2023 will be sufficient to fund its operations until December 31, 2024.
The Company records the related reimbursement of research and development costs under these agreements as income in the period in which such costs are incurred.
Certain Research and Development projects are, or have been, partially funded by collaboration agreements, The Company records the related reimbursement of research and development costs under these agreements as income in the period in which such costs are incurred.
Savings and deposit accounts generate a limited amount of interest income, with very low counterparty risks. We expect to continue this investment strategy.
Savings and deposit accounts generate a limited amount of interest income, with very low counterparty risks.
Gross proceeds from PIPE financing total $194 million ($180.4 million net of transaction costs), before deducting private placement expenses. During the years ended December 31, 2022 and 2021, we obtained the following financing on the public markets by issuance of securities, net of commissions and estimated offering expenses: Equity capital Bank Loans Other debt Total (Amounts in thousands of U.S.
During the years ended December 31, 2023 and 2022, we obtained the following financing on the public markets by issuance of securities, net of commissions and estimated offering expenses: Equity capital Bank Loans Other debt Total (Amounts in thousands of U.S.
We anticipate that our sales and marketing expenses will increase in the future as we prepare for the potential launch and commercialization of Viaskin Peanut in North America and in the European Union, if approved. General and Administrative General and administrative expense consists primarily of personnel costs and share-based compensation for finance, legal, IT and administrative employees.
We anticipate that our sales and marketing expenses will increase significantly in the future as we prepare for the potential launch and commercialization of Viaskin Peanut in North America and in the European Union, if approved.
We cannot determine with certainty the duration and completion costs of the current or future clinical trials of our product candidates or if, when, or to what extent we will generate revenue from the commercialization and sale of any of our product candidates that obtain regulatory approval.
(2) If we exclude Mag1c impact the percentage of research and development expenses related to Viaskin Peanut in 2023 would be 84% (3) If we exclude Mag1c impact the percentage of research and development expenses related to Viaskin Milk in 2023 would be 8% We cannot determine with certainty the duration and completion costs of the current or future clinical trials of our product candidates or if, when, or to what extent we will generate revenue from the commercialization and 104 sale of any of our product candidates that obtain regulatory approval.
The Company intent is to use the net proceeds, if any, of sales of ADSs issued under the program, together with its existing cash and cash equivalents, primarily for activities associated with potential approval and launch of Viaskin Peanut, as well as to advance the development of the Company’s product candidates using its Viaskin Platform and for working capital and other general corporate purposes. 104 Table of Contents Pursuant to the ATM program, we issued and completed sales of new ordinary shares in form ADSs for a total gross amount of $15.3 million ($14.1 million net of transaction costs), each ADS representing one-half of one ordinary shares of the Company.
The Company intent is to use the net proceeds, if any, of sales of ADSs issued under the program, together with its existing cash and cash equivalents, primarily for activities associated with potential approval and launch of Viaskin Peanut, as well as to advance the development of the Company’s product candidates using its Viaskin Platform and for working capital and other general corporate purposes.
Determining the fair value of the share-based payments at the grant date requires judgment. We calculated the fair value of stock options on the grant date using the Black-Scholes option pricing model. The Black-Scholes model requires the input of highly subjective assumptions, including the expected volatility, expected term, risk- free interest rate and dividend yield.
Determining the fair value of the share-based payments at the grant date requires judgment. We calculated the fair value of stock options on the grant date using the Black-Scholes option pricing model.
These funds are recognized as other income in our consolidated statement of operations for the fiscal year that recorded the financed expenses or expenditures. Research Tax Credits The Research Tax Credit ( Crédit d’Impôt Recherche , or CIR) is granted to companies by the French tax authorities in order to encourage them to conduct technical and scientific research.
Other Operating Income Research Tax Credits The Research Tax Credit ( Crédit d’Impôt Recherche , or CIR) is granted to companies by the French tax authorities in order to encourage them to conduct technical and scientific research.
If we are not successful in our financing objectives, we could have to scale back our operations, notably by delaying or reducing the scope of our research and development efforts or obtain financing through arrangements with collaborators or others that may require us to relinquish rights to our product candidates that we might otherwise seek to develop or commercialize independently.
We cannot guarantee that we will be able to obtain the necessary financing to meet our needs or to obtain funds at attractive terms and conditions, including as a result of disruptions to the global financial markets resulting from geopolitical instability, macroeconomic conditions, global health crises, or other factors. 102 If we are not successful in our financing objectives, we could have to scale back our operations, notably by delaying or reducing the scope of our research and development efforts or obtain financing through arrangements with collaborators or others that may require us to relinquish rights to our product candidates that we might otherwise seek to develop or commercialize independently.
Our principal offices occupy a 4,470 square meter facility, pursuant to a lease agreement dated March 3, 2015 and represents a $3.4 million cash requirement as of December 31, 2022 which expires March 8, 2024. Our primary U.S. office is located in Basking Ridge, New Jersey.
Our principal offices occupy a 4,470 square meter facility, pursuant to a lease agreement dated March 3, 2015 and represents a $1.1 million cash requirement as of December 31, 2023 until July, 2024.
The following table presents our material cash requirements for future periods: Material Cash Requirements Due by the Year Ended December 31, 2023 2024 2025 Thereafter Total (Amounts in thousands) Operating leases 2,051 1,243 71 — 3,364 Purchase obligations—Obligations Under the Terms of CRO Agreements 23,336 20,021 5,378 — 48,735 Total 25,387 21,264 5,449 — 52,099 105 Table of Contents The commitment amounts in the table above are associated with contracts that are enforceable and legally binding and that specify all significant terms, including interest on long-term debt, fixed or minimum services to be used, fixed, minimum or variable price provisions, and the approximate timing of the actions under the contracts.
The following table presents our material expenses commitments for future periods: Material expenses Commitments Due by the Year Ended December 31, 2024 2025 2026 Thereafter Total (Amounts in thousands) Operating leases 1,205 65 421 5,514 7,205 Purchase obligations—Obligations Under the Terms of CRO commitments 22,732 11,006 1,406 1,831 36,974 Total 23,937 11,071 1,827 7,345 44,179 The commitment amounts in the table above are associated with contracts that are enforceable and legally binding and that specify all significant terms, including interest on long-term debt, fixed or minimum services to be used, fixed, minimum or variable price provisions, and the approximate timing of the actions under the contracts.
The Company records upfront, non-refundable payments made to outside vendors, or other payments made in advance of services performed or goods being delivered, as prepaid expenses, which are expensed as services are performed or the goods are delivered. 100 Table of Contents Certain research and development projects are, or have been, partially funded by collaboration agreements, and the expenses related to these activities are included in research and development costs.
The Company records upfront, non-refundable payments made to outside vendors, or other payments made in advance of services performed or goods being delivered, as prepaid expenses, which are expensed as services are performed or the goods are delivered.
External professional services and other costs decreased by $1.8 million for the year ended December 31, 2022 compared to the year ended December 31, 2021, primarily as a result of budget discipline measures of pre-commercialization activities for Viaskin Peanut in North America.
External professional services and other costs increased by $1.0 million for the year ended December 31, 2023 compared to the year ended December 31, 2022, mainly due to an increase in fees related to pre-commercialization activities for Viaskin Peanut in North America.
Under the terms of the exclusive collaboration, we are responsible for leading the development activities of MAG1C up through a pivotal Phase 3 clinical program, and if appropriate regulatory approvals are received, Nestlé Health Science will support the commercialization of MAG1C globally, while prioritizing certain agreed-upon countries. We entered into an amendment with Nestlé Health Science on July 12, 2018.
Under the terms of the Collaboration Agreement, the Company was responsible for leading the development activities of MAG1C up through a pivotal Phase 3 clinical program, and if the appropriate regulatory approvals were received, Nestlé Health Science would support the commercialization of MAG1C globally.
Dollars) Research and development expenses related to Viaskin Peanut (1) $ 47,766 $ 47,961 As a percentage of research and development expenses, excluding share-based compensation expense 65 % 70 % Research and development expenses related to Viaskin Milk (1) $ 8,180 $ 5,861 As a percentage of research and development expenses excluding share-based compensation expense 11 % 9 % Other research and development expenses (1) $ 17,295 $ 14,868 Total research and development expenses, excluding share-based compensation expense $ 73,241 $ 68,690 Share-based compensation expenses included in research and development expenses $ 2,303 $ 1,646 Total research and development expenses $ 75,543 $ 70,336 (1) Excludes employee share-based compensation expense.
Dollars) Research and development expenses related to Viaskin Peanut (1) $ 60,329 $ 47,766 As a percentage of research and development expenses, excluding share-based compensation Expense (2) 105 % 65 % Research and development expenses related to Viaskin Milk (1) $ 6,019 $ 8,180 As a percentage of research and development expenses excluding share-based compensation Expense (3) 10 % 11 % Other research and development expenses (1) $ (8,621 ) $ 17,295 Total research and development expenses, excluding share-based compensation expense $ 57,727 $ 73,241 Share-based compensation expenses included in research and development expenses $ 2,496 $ 2,303 Total research and development expenses $ 60,223 $ 75,543 (1) Excludes employee share-based compensation expense after $19,9 millions loss on completion accrual reversal as of December 2023.
Research and development costs include all direct costs, including salaries, share-based payments and benefits for research and development personnel, outside consultants, costs of clinical trials, costs related to manufacturing clinical study materials, sponsored research, clinical trials insurance, other outside costs, depreciation, and facility costs related to the development of drug candidates.
Consultants, costs of clinical trials 106 costs related to manufacturing clinical study materials, sponsored research, clinical trials insurance, other external costs, depreciation (of Research and Development equipments and other depreciation related to Research and Development like loss on completion on MAG1C study), and facility costs related to the development of drug candidates.
Operating Expenses Research and Development Expenses The following table summarizes our research and development expenses for the years presented: December 31, (Dollar amounts presented in thousands) 2022 2021 $ change % change Research and development expenses External clinical-related expenses 42,248 39,386 2,862 7 % Employee-related costs excl. share-based payment expenses 10,752 12,950 (2,198 ) (17 %) Share-based payment expenses 2,303 1,646 656 40 % Depreciation and amortization 12,965 9,878 3,087 31 % Other costs 7,276 6,476 800 12 % Total Research and development expenses 75,543 70,336 5,207 7 % Our research and development expenses consisted primarily of external costs, such as startup fees paid to investigators, consultants, central laboratories and CROs in connection with our clinical trials, and costs related to acquiring and manufacturing clinical study materials.
Other operating income increased by $7.8 millions for the year ended December 31, 2023 compared to the year ended December 31, 2022 mainly due the reversal of deferred revenue following the Mutual Termination Letter Agreement, effective October 30, 2023, of the Collaboration Agreement between the Company and Nestlé Health Science. 108 Operating Expenses Research and Development Expenses The following table summarizes our research and development expenses for the years presented: December 31, $ change % change (Dollar amounts presented in thousands) 2023 2022 Research and development expenses External clinical-related expenses 49,044 42,248 6,796 16 % Employee-related costs excl. share-based payment expenses 14,401 10,752 3,649 34 % Share-based payment expenses 2,496 2,303 193 8 % Depreciation and amortization (13,658 ) 12,965 (26,623 ) (205 %) Other costs 7,940 7,276 664 9 % Total Research and development expenses 60,223 75,443 (15,320 ) (20 %) Our research and development expenses consisted primarily of external costs, such as startup fees paid to investigators, consultants, central laboratories and CROs in connection with our clinical trials, and costs related to acquiring and manufacturing clinical study materials.
The table does not include obligations under agreements that we can cancel without a significant penalty. Future events could cause actual payments to differ from these estimates. Conditional advances In 2014, BpiFrance Financement granted an interest-free Innovation loan to DBV Technologies to help financing the pharmaceutical development of Viaskin™ Milk.
The table does not include obligations under agreements that we can cancel without a significant penalty. Future events could cause actual payments to differ from these estimates. Operating leases Our corporate headquarters are located in Montrouge, France.
Net cash used for operating activities was $55.7 and $108.2 million for the years ended December 31, 2022 and 2021, respectively. As of December 31, 2022, we recorded a net loss of $96.3 million. Our net cash flows provided by financing activities totaled $194.1 million in 2022, mainly consisting of our global offering in the second quarter of 2022.
As of December 31, 2023, we recorded a net loss of $72.7 million. Our net cash flows provided by financing activities totaled $7.1 million in 2023, mainly consisting of the proceeds from our ATM program.
Sales and marketing expenses decreased by $2.8 million for the year ended December 31, 2022 compared to the year ended December 31, 2021, primarily due to a decrease in employee-related costs, external professional services, and share-based payment expenses.
Sales and Marketing expenses increased by $0.8 million for the year ended December 31, 2023 compared to the year ended December 31, 2022, primarily due to an increase in fees related to pre-commercialization activities for Viaskin Peanut in North America. 109 Employee-related costs (including share-based payments expenses) related to payroll for the U.S. and European employees, decreased by $0.2 million for the year ended December 31, 2023 compared to the year ended December 31, 2022, due to employee departure in the US.
General and Administrative Expenses The following table summarizes our general and administrative expenses for the years presented: December 31, (Dollar amounts presented in thousands) 2022 2021 $ change % change General and administrative expenses External professional services fees 5,947 7,944 (1,997 ) (25 %) Employee-related costs excl. share-based payment expenses 7,320 8,194 (874 ) (11 %) Share-based payment expenses 2,688 1,163 1,525 131 % Depreciation, amortization and other costs 8,369 13,219 (4,865 ) (37 %) Total General and administrative expenses 24,324 30,520 (6,196 ) (20 %) General and administrative expenses decreased by $6.2 million for the year ended December 31, 2022 compared to the year ended December 31, 2021, primarily due to cost containment measures and decreased external professional fees (decreased by 2.0 million), partially offset by an increase in share-based payment expenses. 103 Table of Contents The average workforce dedicated to general and administrative expenses decreased from 31 employees in 2021 to 27 employees in 2022.
General and Administrative Expenses The following table summarizes our general and administrative expenses for the years presented: December 31, $ change % change (Dollar amounts presented in thousands) 2023 2022 General and administrative expenses External professional services fees 8,750 5,947 2,803 47 % Employee-related costs excl. share-based payment expenses 8,200 7,320 881 12 % Share-based payment expenses 3,389 2,688 701 26 % Depreciation, amortization and other costs 9,161 8,369 2,523 30 % Total General and administrative expenses 29,500 24,324 5,176 21 % General and administrative expenses increased by $5.2 millions for the year ended December 31, 2023, compared to the year ended December 31, 2022.
Dollars) 2022 2021 Net cash flows used in operating activities (55,666 ) (108,242 ) 52,576 (49 %) Net cash flows used in investing activities (100 ) (433 ) 333 (77 %) Net cash flows provided by financing activities 194,120 274 193,846 * Effect of exchange rate changes on cash and cash equivalents (6,461 ) (10,651 ) 4,190 (39 %) Net (decrease) increase in cash and cash equivalents 131,893 (119,051 ) 250,944 * * Percentage not meaningful Operating Activities Our net cash flows used in operating activities were $55.7 million and $108.2 million in 2022 and 2021 respectively.
Dollars) 2023 2022 Net cash flows used in operating activities (79,653 ) (55,666 ) (23,982 ) 43 % Net cash flows used in investing activities (808 ) (100 ) (1,017 ) 1016 % Net cash flows provided by financing activities 6,767 194,120 (187,045 ) (96 %) Effect of exchange rate changes on cash and cash equivalents 5,867 (6,461 ) 12,328 (191 %) Net (decrease) increase in cash and cash equivalents (67,827 ) 131,893 (199,716 ) * * Percentage not meaningful Operating Activities Our net cash flows used in operating activities were $79.7 millions and $55.7 millions in 2023 and 2022 respectively.
Our estimation of costs yet to be incurred and revenues yet to be recognized for the completion of the Phase 2 trial contains uncertainties because they require management to make assumptions and to apply judgment to estimate future cost and timeline for new patient enrollment in this PII.
Our estimation of costs yet to be incurred for the completion of the study contains uncertainties as they require management to make assumptions and to apply judgment to estimate future cost and timelines to finish the study. These estimates are subjective and our ability to achieve current best estimates may be affected by factors.
Financing Activities Our net cash flows resulting from financing activities increased to $194.1 million in 2022 from $0.3 million in 2021. For the year ended December 31, 2022, financing activities are primarily composed of the net proceeds of our global offering in the second quarter of 2022.
For the year ended December 31, 2023, financing activities are primarily composed of the ATM in June 2023 compared to $194.4 millions during for the year ended December 31, 2022 (that consisted of our May 2022 ATM and June 2022 PIPE offering in second quarter of 2022).
We also anticipate continued increased expenses associated with being a public company in the United States. Finance Income (Expense) Our cash and cash equivalents have been deposited primarily in savings and deposit accounts with a remaining maturity at the date of purchase of three months or less, allowing the funds to be freely withdrawn at any time without significant penalty.
Finance Income (Expense) Our cash and cash equivalents have been deposited primarily in savings and deposit accounts with a short term remaining maturity at the date of purchase or less, refundable within one month, for which the risk of changes in value is considered to be insignificant.
Exercise price The exercise price of our stock options is based on the fair market value of our ordinary shares.
The Black-Scholes model requires the input of highly subjective assumptions, including the expected volatility, expected term, risk- free interest rate and dividend yield. 114 Exercise price The exercise price of our stock options is based on the fair market value of our ordinary shares.
Depreciation, amortization and other costs decreased by $4.9 million mainly due to the decrease of insurance policies by $2.7 million, mainly due to the decrease in Directors and Officers insurance premium. Financial income (loss) Our financial income was $0.4 million in 2022 and 2021, and primarily includes the financial income on our financial assets and foreign exchange gains.
The workforce dedicated to general and administrative activities increased from 27 employees in 2022 to 34 employees in 2023. Financial income (loss) Our financial income was $3.7 millions in 2023 and $0.4 million in 2022, and primarily includes the financial income on our financial assets and foreign exchange gains.
The revision of the estimated costs for the year ended December 31, 2022 was $19.8 million compared to December 31, 2021, $9.8 million. Operating Expenses Since inception, our operating expenses have consisted primarily of research and development activities, general and administration costs and sales and marketing costs.
This accrual represents our best estimate of the remainder expenses related to the ongoing clinical study which will be incurred after December 31, 2023 and until the end of the study. Operating Expenses Since our inception, our operating expenses have consisted primarily of Research and Development activities, General and Administration costs and to lesser extent sales and marketing costs.
See Note 1 to our financial statements for a description of our other significant accounting policies. 107 Table of Contents Revenue Recognition —Collaboration agreement with Nestlé Health Science On May 31, 2016, we announced our entry into an exclusive global collaboration with Nestlé Health Science to develop MAG1C, a ready-to-use and standardized atopy patch test tool for the diagnosis of cow’s milk protein allergy in infants and toddlers.
The Collaboration Agreement related to an exclusive global collaboration with Nestlé Health Science for the development and, if approved, commercialization of MAG1C, a ready-to-use and standardized atopy patch test tool for the diagnosis of CMPA (non-mediated IgE) in infants.
We are eligible to receive up to €100.0 million in potential development, clinical, regulatory and commercial milestones, inclusive of a non-refundable upfront payment of €10.0 million that we received in July 2016.
The Company was eligible to receive up to €100.0 millions ($105.0 millions at December 31, 2023 closing exchange rate) in potential development, clinical, regulatory and commercial milestones, including an upfront payment of €10.0 millions received in July 2016. On October 30, 2023, the Company and NESTEC entered into a Mutual Termination Letter Agreement terminating the Collaboration Agreement.
These estimates are subjective and our ability to achieve current best estimates is affected by factors such as ongoing COVID-19 pandemic and conflict in Ukraine. Share-Based Compensation We have various share-based compensation plans for employees and non-employees. We account for share-based compensation in accordance with the authoritative guidance on share-based compensation.
A $2.3 millions provision representing our current best estimates of costs yet to be incurred for the completion of the study was booked as of December 31, 2023. Share-Based Compensation We have several share-based compensation plans for employees and non-employees. We account for share-based compensation in accordance with the authoritative guidance on share-based compensation.
Liquidity and Capital Resources Financial Condition On December 31, 2022, we had $209.2 million in cash and cash equivalents compared to $77.3 million of cash and cash equivalents on December 31, 2021. We have incurred operating losses and negative cash flows from operations since our inception.
Liquidity and Capital Resources Financial Condition On December 31, 2023, we held $141.4 millions in cash and cash equivalents compared to $209.2 millions of cash and cash equivalents on December 31, 2022.. Net cash used for operating activities was $79.6 and 110 $55.7 million for the years ended December 31, 2023 and 2022, respectively.
Research and development expenses increased by $5.2 million for the year ended December 31, 2022 compared to the year ended December 31, 2021.
Employee-related costs, excluding share-based payment expenses, increased by $3.6 million for the year ended December 31, 2023 compared to the year ended December 31, 2022 due to the workforce increase to support research and development activities on VITESSE trial and the new safety study for toddlers and children.
Removed
We recently completed a Phase 3 trial of Viaskin Peanut in children ages one to three with peanut allergy and we also have an ongoing Phase 3 trial of Viaskin Peanut in children ages four to seven with peanut allergy.
Added
Based on its current operations, the Company expects that its balance of cash and cash equivalents of $141.4 million as of December 31, 2023 will be sufficient to fund its operations until December 31, 2024. The company has incurred operating losses and negative cash flows from operations since inception.
Removed
Based on its current operations, plans and assumptions as revised pursuant to 2022 announcements related to EPITOPE Phase 3 study topline results and VITESSE Phase 3 partial clinical hold lift, as well as ATM and PIPE financings, the Company expects that its balance of cash and cash equivalents of $209.2 million as of December 31, 2022 will be sufficient to fund its operations for at least the next 12 months.
Added
As of the date of the filing, our available cash is not projected to be sufficient to support our operating plan for at least the next 12 months. As such, there is substantial doubt regarding our ability to continue as a going concern.
Removed
Impact of COVID-19 on our Business The COVID-19 pandemic has adversely affected global economies, financial markets and the overall environment in which we do business. Our ability to conduct clinical trials was and may continue to be affected by any future resurgences of the COVID-19 pandemic.
Added
We intend to seek additional capital as we prepare for the launch of Viaskin Peanut, if approved, and continue other research and development efforts. The Company will require substantial additional capital to fund its research and development and ongoing operating expenses. These capital requirements are expected to be funded through debt and equity offerings before December 31, 2024.
Removed
As the full impact of the COVID-19 pandemic on our business continues to develop, we are closely monitoring the global situation. We are unable to predict the full impact that COVID-19 will have on our operations, liquidity and financial results, and, depending on the magnitude and duration of any future resurgences of the COVID-19 pandemic, such impact may be material.
Added
During the fiscal year ending December 31, 2023, the Company received the reimbursement of the 2022 fiscal year research tax credits for a total amount of $5.9 million. Collaboration Agreement with Nestlé Health Science In May 2016, we entered into a Development Collaboration and License Agreement (the “Collaboration Agreement”) with Société des Produits Nestlé S.A. (formerly NESTEC S.A.) (“NESTEC”).
Removed
Accordingly, current results and financial condition discussed herein may not be indicative of future operating results and trends. For further discussion of the business risks associated with COVID-19, see Item 1A, Risk Factors, within this Form 10-K report. Business Trends We engage in substantial research and development efforts to develop innovative pharmaceutical product candidates.
Added
Each party remains responsible for its own costs and expenses related to its respective wind-down activities. Any and all licenses and sublicenses, granted by either party to the other party under the Collaboration Agreement, including, without limitation, any licenses to intellectual property, were revoked and terminated.
Removed
Other Operating Income Government Assistance Due to the innovative nature of our product candidate development programs, we have benefited from a number of sources of assistance from the central French government or local public authorities, intended to finance our research and development efforts or the recruitment of specific personnel.

… 46 more changes not shown on this page.

Other DBVT 10-K year-over-year comparisons