What changed in this filing

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Item 1A. Risk Factors

2023-03-02 compared with 2022-03-09 · 420 added, 329 removed, 912 unchanged (45% of the section changed)

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We have incurred significant losses since our inception and anticipate that we will continue to incur significant losses for the foreseeable future.

These factors raise substantial doubt regarding our ability to continue as a going concern.

We are a clinical-stage biopharmaceutical company, and we have not yet generated significant income from operating activities.

We have incurred net losses in each year since our inception in 2002, including net losses of

$97.8 million and $159.6 million for the years ended December 31, 2021 and 2020 respectively.

We have incurred net losses in each year since our inception in 2002, including net losses of $96.3 million and $97.8 million for the years ended December 31, 2022 and 2021 respectively.

As of December 31, 2022, we had an accumulated deficit of $259.6 million.

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The amount of our future net losses will depend, in part, on the pace and amount of our future expenditures and our ability to obtain funding through equity or debt financings, strategic collaborations, or additional grants or tax credits.

To date, we have not generated any product revenue and we continue to advance the clinical and regulatory development of Viaskin Peanut in the

United States and European Union.

Even if we obtain regulatory approval to market Viaskin Peanut or any other product candidate, our future revenues will depend upon the size of any markets in which our product candidates have received approval, and our ability to achieve sufficient market acceptance, reimbursement from third-party payors and adequate market share for any approved products in those markets.

To date, we have not generated any product revenue and we continue to advance the clinical and regulatory development of Viaskin Peanut in the United States and European Union.

Even if we obtain regulatory approval to market Viaskin Peanut or any other

product candidate, our future revenues will depend upon the size of any markets in which our product candidates have received approval, and our ability to achieve sufficient market acceptance, reimbursement from third-party payors and adequate market share for any approved products in those markets.

Our near-term prospects, including our ability to finance our company and generate revenue, will depend heavily on the successful development, regulatory approval and commercialization of Viaskin Peanut.

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We anticipate that our expenses will increase substantially if and as we:

seek regulatory and marketing approvals and pursue commercial activities for Viaskin Peanut, and for which we continue to seek regulatory and marketing approvals in the United States;

seek regulatory approvals and pursue commercial activities for Viaskin Peanut, and for which we continue to seek regulatory approvals in the United States;

continue our research, pre-clinical and clinical development of our product candidates, including additional trials related to our pursuit of regulatory approval of Viaskin Peanut in the United States;

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;

seek regulatory 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 regulatory approval, especially in North America;

further develop the manufacturing process for our product candidates, including any modifications to our patch technology;

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expand the scope of our current clinical trials for our product candidates;

initiate and conduct any post-approval clinical trials, if required by the FDA, for our approved products, if any;

initiate and conduct any post-approval clinical trials, if required by the FDA or comparable foreign regulatory authorities, for our approved products, if any;

initiate additional pre-clinical, clinical or other studies for our other product candidates;

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In any particular period or periods, our operating results could be below the expectations of securities analysts or investors, which could cause the price of our ADSs or ordinary shares to decline.

Based on our current operations, as well as our plans and assumptions as revised pursuant to our change of strategy announced in December 2021, we expect that our balance of cash and cash equivalents of $77.3 million as of December 31, 2021 will be sufficient to fund our operations into the first quarter of 2023.

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.

Based on our current operations, as well as our plans and assumptions, we expect that our balance of cash and cash equivalents of $209.2 million as of December 31, 2022 will be sufficient to fund our operations for at least the next 12 months.

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 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.

The ongoing COVID-19 pandemic has already caused extreme volatility and disruptions in the capital and credit markets.

The COVID-19 pandemic 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.

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Developing product candidates is expensive, lengthy and risky, and we expect our research and development expenses to increase substantially in connection with our ongoing activities, particularly as we seek regulatory approval for Viaskin Peanut.

Furthermore, if we obtain marketing approval for Viaskin Peanut or any other product candidate that we may develop, we expect our commercialization expenses related to product sales, marketing, distribution and manufacturing to increase significantly as we develop the appropriate infrastructure to commercialize.

Furthermore, if we obtain regulatory approval for Viaskin Peanut or any other product candidate that we may develop, we expect our commercialization expenses related to product sales, marketing, distribution and manufacturing to increase significantly as we develop the appropriate infrastructure to commercialize.

In addition, our expenses could increase beyond expectations if the FDA requires us to perform nonclinical studies, clinical trials or post-approval clinical trials for our approved products, if any, in addition to those that we currently anticipate.

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Since our inception, we have primarily funded our operations with equity financings, and, to a lesser extent, public assistance aimed at supporting innovation and payments associated with research tax credits (Crédit d’Impôt Recherche).

We do not generate product revenue and continues to prepare for the potential launch of our first product in the United States and in the European Union, if approved.

We do not generate product revenue and continue to prepare for the potential launch of our first product in the United States and in the European Union, if approved.

We expect our operating losses to continue for the foreseeable future.

Based on our current operations, as well as our plans and assumptions as revised pursuant to our change of strategy announced in December 2021, we expect that our current cash and cash equivalents will be sufficient to fund our operations into the first quarter of 2023.

Based on our current operations, we expect that our current cash and cash equivalents will be sufficient to fund our operations for at least the next 12 months.

We expect that we will need to raise substantial additional capital as we prepare for the launch of Viaskin Peanut, if approved, and continue other research and development efforts.

The ongoing COVID-19 pandemic has already caused extreme volatility and disruptions in the capital and credit markets.

The COVID-19 pandemic 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.

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The incurrence of indebtedness would result in increased fixed payment obligations and we may be required to agree to certain restrictive covenants, such as limitations on our ability to incur additional debt, limitations on our ability to acquire, sell or license intellectual property rights and other operating restrictions that could adversely impact our ability to conduct our business.

We could also be required to seek funds through arrangements with collaborative partners or otherwise at an earlier stage than otherwise would be desirable and we may be required to relinquish rights to some of our technologies or product candidate or otherwise agree to terms unfavorable to us, any of which may have a material adverse effect on our business, operating results and prospects.

We could also be required to seek funds through arrangements with collaborative partners or otherwise at an earlier stage than otherwise would be desirable and we may be required to relinquish rights to some of our technologies or product candidates or otherwise agree to terms unfavorable to us, any of which may have a material adverse effect on our business, operating results and prospects.

If we are unable to obtain sufficient funding on a timely basis, we may be required to scale back our operating plan, significantly curtail, delay or discontinue one or more of our research or development programs or the commercialization of any product candidate, or be unable to expand our operations or otherwise capitalize on our business opportunities, as desired, which could materially affect our business, financial condition and results of operations.

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Under French law, our share capital may be increased only with shareholders’ approval at an extraordinary general shareholders’ meeting following the recommendation of our board of directors.

The shareholders may delegate to our board of directors either the authority ( de´le´gation de compe´tence

) or the power ( de´le´gation de pouvoir

) to carry out any increase in share capital.

In addition, the French Commercial Code imposes certain limitations on our ability to price any offering of our share capital without preferential subscription right ( sans droit pre´fe´rentiel de souscription

), which limitation may prevent us from successfully completing any such offering.

The shareholders may delegate to our board of directors either the authority ( délégation de compétence ) or the power ( délégation de pouvoir ) to carry out any increase in share capital.

Specifically, under the French Commercial Code, unless the offering is less than 10% of issued share capital, securities cannot be sold in an offering at a price that is more than a 10% discount to the volume weighted average trading price on Euronext Paris over the last three trading days preceding the commencement of the marketing of the transaction.

In addition, the combined shareholders’ meeting dated May 19, 2021 granted authority to our board of directors to increase our share capital up to 30% of issued share capital, if the investors in such offering fit within a category of persons meeting certain characteristics.

In this case securities cannot be sold in such an offering at a price that is more than a 15% discount to (i) the average trading price on Euronext Paris over five consecutive trading days chosen among the last thirty trading sessions preceding the commencement of the marketing of the transaction or (ii) the weighted average trading price the day preceding the commencement of the marketing of the transaction.

In addition, the combined shareholders’ meeting dated May 12, 2022 granted authority to our board of directors to increase our share capital up to 100% of issued share capital, if the investors in such offering fit within categories of persons meeting certain characteristics.

In this case securities cannot be sold in such an offering at a price that is more than a 15% discount to (i) the closing price of the Company’s shares on the regulated market Euronext Paris during the last trading session, (ii) the volume-weighted average (in the central order book and off-market blocks) of the Company’s share price on the Euronext Paris regulated market during the last three trading days, (iii) the average of five consecutive trading days chosen among the last thirty trading sessions, or (iv) the weighted average trading price the day, each of (i) to (iv) prior to the date on which the issue price is set.

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, or other macroeconomic conditions, which have in the past and may in the future negatively impact our business and financial performance.

The global economy, including credit and financial markets, has experienced extreme volatility and disruptions, including, among other things, severely diminished liquidity and credit availability, declines in consumer confidence, declines in economic growth, supply chain shortages, increases in inflation rates, higher interest rates and uncertainty about economic stability.

For example, the COVID-19 pandemic resulted in widespread

unemployment, economic slowdown and extreme volatility in the capital markets.

Federal Reserve recently raised interest rates multiple times in response to concerns about inflation and it may raise them again.

Higher interest rates, coupled with reduced government spending and volatility in financial markets may increase economic uncertainty and affect consumer spending.

If the equity and credit markets deteriorate, including as a result of political unrest or war, it may make any necessary debt or equity financing more difficult to obtain in a timely manner or on favorable terms, more costly or more dilutive.

Increased inflation rates can adversely affect us by increasing our costs, including labor and employee benefit costs.

On February 24, 2022, Russian forces launched significant military action against Ukraine, and sustained conflict and disruption in the region is possible.

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.

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 such disruptions may magnify the impact of the other risks described in this report.

COVID-19 may materially and adversely affect our business and our financial results

Our business could be materially and adversely affected by the effects of the ongoing COVID-19 pandemic in regions where we or third parties on which we rely have significant manufacturing facilities, concentrations of

clinical trial sites or other business operations.

The COVID-19 pandemic could materially affect our operations as well as causing significant disruption in the operations and business of third-party manufacturers, CROs, other services providers, and collaborators with whom we conduct business.

In response to the COVID-19 pandemic, many state, local and foreign governments, including the French and U.S.

governments, put in place quarantines, executive orders, shelter-in-place or stay-at-home orders and similar government orders and restrictions in order to control the spread of the disease.

While some restrictions have recently been relaxed, others have re-imposed following prior relaxation as a result of continually evolving incidence and rates of infection.

Such orders or restrictions, or the perception that such orders or restrictions could occur or continue for a protracted period of time, have resulted in business closures, work stoppages, slowdowns and delays, work- from-home policies, travel restrictions and cancellation of events, among other effects that could negatively impact productivity and disrupt our business and those of third-party manufacturers, CROs, other services providers, and collaborators with whom we conduct business.

While the rollout of vaccines has begun, the timing of vaccinations, lifting of movement restrictions, and reinstitution of in-person events is unknown.

As a result of the COVID-19 pandemic, our ability to conduct clinical trials has been and may continue to be affected by the COVID-19 pandemic.

For example, we have experienced slower than anticipated clinical site activation and patient enrollment in our MAG1C trial conducted as part of our collaboration with Nestlé.

Clinical site initiation, patient enrollment and patient visits (including food challenges) in any of our clinical trials may be suspended or delayed due to prioritization of hospital resources toward the COVID-19 pandemic, including vaccination efforts, or new or renewed shelter-in-place or stay-at-home orders.

Our business could be materially and adversely affected by the effects of the COVID-19 pandemic in regions where we or third parties on which we rely have significant manufacturing facilities, concentrations of clinical trial sites or other business operations.

The COVID-19 pandemic could materially affect our operations as well as cause significant disruption in the operations and business of third-party manufacturers, CROs, other services providers, and collaborators with whom we conduct business.

As a result of the COVID-19 pandemic, our ability to conduct clinical trials was and may continue to be affected clinical site initiation, patient enrollment and patient visits (including food challenges) in any of our clinical trials may be suspended or delayed due to prioritization of hospital resources toward the COVID-19 pandemic.

Some patients may not be able to comply with clinical trial protocols if quarantines impede patient movement or interrupt healthcare services.

Similarly, our ability to recruit and retain patients and principal investigators and site staff who, as healthcare providers, may have heightened exposure to COVID-19, may adversely impact our future clinical trial operations.

The pandemic and related government and private sector responsive actions have affected the broader economies and financial markets, triggering an economic downturn, which has at points adversely affected, and could again adversely affect, our ability to access capital, which could negatively affect our business.

In addition, a recession or resulting adverse impacts on the capital markets resulting from the ongoing spread of COVID-19 could materially affect our business.

It is impossible to predict all effects and the ultimate impact of the COVID-19 pandemic, as the situation continues to evolve.

The full extent of COVID-19’s impact on our clinical development and other operations and financial performance depends on future developments that are uncertain and unpredictable, including the timing of vaccine rollouts and herd immunity, virus mutations and variants, and any new information that may emerge concerning the virus, vaccines, and containment, all of which may vary across regions.

The pandemic and related government and private sector responsive actions affected the broader economies and financial markets, triggering an economic downturn, which at points adversely affected, and could again adversely affect, our ability to access capital, which could negatively affect our business.

In addition, the recession or resulting adverse impacts on the capital markets resulting from the ongoing spread of COVID-19 could materially affect our business.

It is impossible to predict all effects and the ultimate impact of the COVID-19 pandemic.

the full extent of COVID-19’s impact on our clinical development and other operations and financial performance depends on continuing developments that are uncertain and unpredictable, including the timing of vaccine rollouts and herd immunity, virus mutations and variants, and any new information that may emerge concerning the virus, vaccines, and containment, all of which may vary across regions.

Any of these factors could have a material adverse impact on our business, financial condition, operating results, and ability to execute and capitalize on our strategies.

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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 EMA, FDA or other regulatory agencies;

the costs of 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 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 marketing approval;

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;

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Uncertainty and dislocations in the financial markets have generally made equity and debt financing more difficult to obtain, and may have a material adverse effect on our ability to meet our future fundraising needs.

We cannot be certain that additional funding will be available to us on

acceptable terms, if at all.

We cannot be certain that additional funding will be available to us on acceptable terms, if at all.

If funds are not available, we may be required to delay, reduce the scope of, or eliminate one or more of our research or development programs or our commercialization efforts.

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As a result of being a U.S.

public company, and particularly during 2021, our first year filing reports with the SEC on U.S.

domestic issuer forms, management’s attention may be diverted from other business concerns, which could adversely affect our business and results of operations.

public company, management’s attention may be diverted from other business concerns, which could adversely affect our business and results of operations.

The Sarbanes-Oxley Act requires, among other things, that we maintain effective internal controls for financial reporting and disclosure controls and procedures.

In particular, we must perform system and process evaluations and testing of our internal controls over financial reporting to allow management to report on the effectiveness of our internal controls over financial reporting, as required by Section 404 of the Sarbanes-Oxley Act.

We have limited experience complying with Section 404, and such compliance may require that we incur substantial accounting expenses and expend significant management efforts.

Compliance with Section 404 may require that we incur substantial accounting expenses and expend significant management efforts.

Our independent registered public accounting firm may also be required, pursuant to Section 404 of the Sarbanes-Oxley Act, to report on the effectiveness of our internal control over financial reporting.

Our testing may reveal deficiencies in our internal controls over financial reporting that are deemed to be material weaknesses.

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.

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.

public company that is subject to these rules and regulations, we may find it is more expensive for us to obtain director and officer liability insurance, and we may be required to accept reduced coverage or incur substantially higher costs to obtain coverage.

These factors could also make it more difficult for us to attract and retain qualified members of our board of directors, particularly to serve on our audit committee and

compensation committee, and qualified executive officers.

These factors could also make it more difficult for us to attract and retain qualified members of our board of directors, particularly to serve on our audit committee and compensation committee, and qualified executive officers.

As a result of disclosure of information in filings required of a U.S.

public company, particularly as we are no longer a foreign private issuer, our business and financial condition will become more visible than they would be

if we were a privately-owned company or if our securities were listed only on Euronext Paris, which we believe may result in threatened or actual litigation, including by competitors and other third parties.

could divert the resources of our management and adversely affect our business and results of operations.

Further, being a U.S.

public company, particularly as we are no longer a foreign private issuer, our business and financial condition will become more visible than they would be if we were a privately-owned company or if our securities were listed only on Euronext Paris, which we believe may result in threatened or actual litigation, including by competitors and other third parties.

If such claims are successful, our business and results of operations could be adversely affected, and even if the claims do not result in litigation or are resolved in our favor, these claims, and the time and resources necessary to resolve them, could divert the resources of our management and adversely affect our business and results of operations.

Further, being both a U.S.

public company and a French public company has an impact on disclosure of information and compliance with two sets of applicable rules.

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We may not be successful in developing and commercializing Viaskin Peanut and our other product candidates, including Viaskin Milk, and our commercial opportunities may be limited.

We are currently engaged in discussions with the FDA in preparation for protocol submission and review for our Phase III pivotal study of the modified Viaskin Peanut, or mVP, patch, which will require additional clinical development and regulatory approval before we are permitted to commence its commercialization, if ever.

We are currently conducting VITESSE, a Phase 3 pivotal study in in children aged 4-7 years old with Type V Viaskin Peanut System, of the modified Viaskin Peanut system, which will need to have positive results in order for us to seek regulatory approval before we are permitted to commence its commercialization, if ever.

Viaskin Milk will also require substantial additional clinical development, testing, and regulatory approval before we are permitted to commence its commercialization, if ever.

Our other product candidates, such as Viaskin Egg or Viaskin rPT, are still in pre-clinical or early proof-of-concept phase development.

Many of our other product candidates are still in pre-clinical or early proof-of-concept phase development.

The clinical trials of our product candidates are, and the manufacturing and marketing of our product candidates will be, subject to extensive and rigorous review and regulation by numerous government authorities in the United States and in other countries where we intend to test and, if approved, market any product candidate.

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This process can take many years and may include post-marketing requirements and surveillance, including the completion of pediatric clinical trials to satisfy both U.S.

and EMA requirements, which will require the expenditure of substantial resources.

and EU requirements, which will require the expenditure of substantial resources.

Of the large number of drugs in development in the United States, only a small percentage successfully completes the FDA regulatory approval process and is commercialized.

Accordingly, even if we are able to obtain the requisite financing to continue to fund our development and clinical programs, we cannot assure you that any of our product candidates will be successfully developed or commercialized.

In addition, in some jurisdictions such as the EU, initiating Phase 3 clinical trials, including clinical trials in the pediatric population, is subject to a requirement to obtain approval or a waiver from the competent authorities of the EU Member States and/or the EMA.

If we do not obtain such approval our ability to conduct clinical trials and obtain marketing authorizations may be severely impaired and our business may be adversely impacted.

We are not permitted to market any of our product candidates in the United States or in any other country until we receive the requisite approval from the applicable regulators.

Obtaining requisite marketing approval in any country is a complex, lengthy, expensive and uncertain process, and the FDA or the applicable foreign regulatory agency 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 agency;

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 agency for marketing approval;

the FDA or the applicable foreign regulatory agency may disagree with the number, design, size, conduct or implementation of our clinical trials;

the FDA or the applicable foreign regulatory agency may require that we conduct additional clinical trials;

the FDA or the applicable foreign regulatory agency may not approve the formulation, labeling or specifications of a product candidate;

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 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 agency 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 agency may disagree with our analysis or interpretation of data from our pre-clinical studies and clinical trials;

the FDA or the applicable foreign regulatory agency 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 agency 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, as a condition of approval or post-approval;

the FDA or the applicable foreign regulatory agency may restrict the use of our products to a narrow population;

the FDA or the applicable foreign regulatory agency 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;

the FDA or the applicable foreign regulatory agency may change its approval policies or adopt new regulations.

Any of these factors, many of which are beyond our control, could jeopardize our ability to obtain regulatory approval for and successfully market any of our product candidates based on our Viaskin technology platform.

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;

the FDA or the applicable foreign regulatory authority may change their approval policies or new legislation governing the approval processes.

Any of these factors, many of which are beyond our control, could jeopardize our ability to obtain regulatory approval for and successfully market any of

our product candidates based on our Viaskin technology platform.

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.

Our product candidates have undergone and/or will be required to undergo clinical trials that are time- consuming and expensive, the outcomes of which are unpredictable, and for which there is a high risk of failure.

If clinical trials of our product candidates fail to satisfactorily demonstrate safety and efficacy to the FDA and other regulators, we, or our collaborators, may incur additional costs or experience delays in completing, or ultimately be unable to complete, the development and commercialization of these product candidates.

If clinical trials of our product candidates fail to satisfactorily demonstrate safety and efficacy to the FDA and other comparable foreign regulatory authorities, we, or our collaborators, may incur additional costs or experience delays in completing, or ultimately be unable to complete, the development and commercialization of these product candidates.

Pre-clinical testing and clinical trials are long, expensive and unpredictable processes that can be subject to extensive delays.

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Interim results of clinical trials do not necessarily predict final results, and success in pre-clinical testing and early clinical trials does not ensure that later clinical trials will be successful.

A number of companies in the pharmaceutical, biopharmaceutical and biotechnology industries have suffered significant setbacks in advanced clinical trials even after promising results in earlier trials, and we cannot be certain that we will not face similar setbacks.

The design of a clinical trial can determine whether its results will support approval of a product, and flaws in the

design of a clinical trial may not become apparent until the clinical trial is well advanced.

A number of companies in the pharmaceutical, biopharmaceutical and biotechnology industries have suffered significant setbacks in advanced clinical trials even after positive results in earlier trials, and we cannot be certain that we will not face similar setbacks.

The design of a clinical trial can determine whether its results will support regulatory approval of a product, and flaws in the design of a clinical trial may not become apparent until the clinical trial is well advanced.

An unfavorable outcome in one or more trials would be a major setback for our product candidates and for us.

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the results may not confirm the positive results of earlier testing or trials;

the results may not meet the level of statistical significance required by the FDA or other regulatory agencies to establish the safety and efficacy of our product candidates.

the results may not meet the level of statistical significance required by the FDA or other comparable regulatory authorities to establish the safety and efficacy of our product candidates.

The results of pre-clinical studies do not necessarily predict clinical success, and larger and later-stage clinical trials may not produce the same results as earlier-stage clinical trials.

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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 patch-site adhesion on efficacy and indicated the need for patch modifications, and subsequently a new human factor study.

The FDA also indicated that supplementary clinical data would need to be generated to support the modified patch, and requested additional Chemistry, Manufacturing and Controls, or CMC, data.

We are currently engaged in discussions with the FDA in preparation for protocol submission and review for our Phase III pivotal study of the mVP patch.

The FDA identified concerns regarding the impact of system adhesion on efficacy and indicated the need for modifications, and a new human factors study.

The FDA also indicated that supplementary clinical data would need to be generated to support the modified product, and requested additional Chemistry, Manufacturing and Controls, or CMC, data.

Further, in September 2022, we announced that FDA had imposed a partial clinical hold on the VITESSE trial, which was lifted in December 2022 after we made additional revisions to the protocol in order to address FDA concerns.

In addition, we cannot assure you that in the course of potential widespread use in future, some drawbacks would not appear in maintaining production quality, protein stability or allergenic strength.

Frequently, product candidates developed by pharmaceutical, biopharmaceutical and biotechnology companies have shown promising results in early pre-clinical studies or clinical trials,but have subsequently suffered significant setbacks or failed in later clinical trials.

In addition, clinical trials of potential products often reveal that it is not possible or practical to continue development efforts for these product candidates.

Frequently, product candidates developed by pharmaceutical, biopharmaceutical and biotechnology companies have shown positive results in early pre-clinical studies or clinical trials, but have

subsequently suffered significant setbacks or failed in later clinical trials.

In addition, clinical trials of potential products sometimes reveal that it is not possible or practical to continue development efforts for these product candidates.

If we do not successfully complete pre-clinical and clinical development, we will be unable to market and sell our product candidates and generate revenues.

Even if we do successfully complete clinical trials, those results are not necessarily predictive of results of additional trials that may be needed before a marketing application may be submitted to the FDA or an applicable foreign regulatory agency.

Although there are a large number of drugs and biologics in development in the United States and other countries, only a small percentage result in the submission of a marketing application to a regulatory agency, such as an NDA or a BLA to the FDA, even fewer are approved for commercialization, and only a small number achieve widespread physician and consumer acceptance following regulatory approval.

Even if we do successfully complete clinical trials, those results are not necessarily predictive of results of additional trials that may be needed before an application for regulatory approval may be submitted to the FDA or a comparable foreign regulatory authority.

Although there are a large number of drugs and biologics in development in the United States and other countries, only a small percentage result in the submission of an application for regulatory approval to a regulatory authority, such as an NDA or a BLA to the FDA, or comparable foreign regulatory authorities, even fewer are approved for commercialization, and only a small number achieve widespread physician and consumer acceptance following regulatory approval.

If our clinical trials are substantially delayed or fail to prove the safety and effectiveness of our product candidates in development, we may not receive regulatory approval of any of these product candidates and our business and financial condition will be materially harmed.

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In accordance with our food allergy clinical trial protocols, we utilize a double-blind, placebo-controlled food challenge procedure.

This consists of giving the offending food protein to patients to assess the sensitivity of

their food allergy, and thus evaluate the safety and efficacy of our product candidates versus placebo.

This consists of giving the offending food protein to patients to assess the sensitivity of their food allergy, and thus evaluate the safety and efficacy of our product candidates versus placebo.

The food challenge protocol is meant to induce objective symptoms of an allergic reaction.

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Human clinical trials are very expensive, time-consuming, and difficult to design, implement and complete.

The completion of trials for Viaskin Peanut or our other product candidates may be delayed for a variety of reasons, including delays in:

The completion of trials for Viaskin Peanut or our other product candidates may be delayed for a variety of reasons, including, but not limited to, delays in:

demonstrating sufficient safety and efficacy to obtain regulatory approval to commence a clinical trial;

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obtaining permission to proceed from the FDA under an investigational new drug, or IND, application, or foreign equivalent approval from regulatory authorities outside the United States;

obtaining institutional review board, or IRB, or independent ethics committee approval to conduct a clinical trial at a prospective clinical trial site;

obtaining institutional review board, or IRB, approval or positive Ethics Committee opinions as part of the single decision on the authorization of a clinical trial issues by EU Member States including input from the national competent authority and Ethics Committee, to conduct a clinical trial at a prospective clinical trial site;

determining dosing and clinical design and making related adjustments;

patient enrollment, which is a function of many factors, including the size of the patient population, the nature of the protocol, the proximity of patients to clinical trial sites, the availability of effective treatments for the relevant disease and the eligibility criteria for the clinical trial, and which has been impacted by the ongoing COVID-19 pandemic.

The commencement and completion of clinical trials for our product candidates may be delayed, suspended or terminated due to a number of factors, including:

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difficulty in patient monitoring and data collection due to failure of patients to maintain contact after treatment;

a regional disturbance where we or our collaborative partners are enrolling patients in our clinical trials, such as the ongoing COVID-19 pandemic or any other pandemic, terrorist activities or war, or a natural disaster;

varying interpretations of our data, and regulatory commitments and requirements by the FDA and similar foreign regulatory agencies.

Many of these factors may also ultimately lead to denial of our marketing applications for our product candidates.

a regional disturbance where we or our collaborative partners are enrolling patients in our clinical trials, such as the COVID-19 pandemic or any other pandemic, terrorist activities or war, or a natural disaster;

varying interpretations of our data, and regulatory commitments and requirements by the FDA and similar foreign regulatory authorities.

For example, we announced in September 2022 that FDA had imposed a partial clinical hold on the VITESSE trial, which was lifted in December 2022, resulting in a delay in initiation and conduct of the VITESSE trial.

Many of these factors may also ultimately lead to denial of our applications for regulatory approval for our product candidates.

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.

In addition, we may encounter delays or product candidate rejections based on new governmental regulations, future legislative or administrative actions, or changes in FDA or other similar foreign regulatory agency policy or interpretation during the period of product development.

If we obtain required regulatory approvals, such approvals may later be withdrawn.

or interpretation during the period of product development.

If we obtain required regulatory approvals, such approvals may later be withdrawn, varied or suspended.

Delays or failures in obtaining regulatory approvals may result in:

varying interpretations of data and commitments by the FDA and similar foreign regulatory agencies;

varying interpretations of data and commitments by the FDA and similar foreign regulatory authorities;

diminishment of any competitive advantages that such product candidates may have or attain.

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;

delays or termination in clinical trials or commercialization;

refusal by the FDA or similar foreign regulatory agencies to review pending applications or supplements to approved applications;

product recalls or seizures;

suspension of manufacturing;

withdrawals of previously approved marketing applications;

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;

fines, civil penalties, and criminal prosecutions.

If our product candidates are not approved by the FDA, we will be unable to commercialize them in the United States.

If our product candidates are not approved by the FDA, or comparable foreign regulatory authorities, we will be unable to commercialize them in the United States or in other countries.

The FDA must approve any new drug or biologic before it can be commercialized, marketed, promoted or sold in the United States.

We must provide the FDA with data from pre-clinical studies and clinical trials that demonstrate that, among other things, our product candidates are safe and effective for a defined indication

before they can be approved for commercial distribution.

We must provide the FDA with data from pre-clinical studies and clinical trials that demonstrate that, among other things, our product candidates are safe and effective for a defined indication before they can be approved for commercial distribution.

Clinical testing is expensive, difficult to design and implement, can take many years to complete and is inherently uncertain as to outcome.

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The processes by which regulatory approvals are obtained from the FDA to market and sell a new or repositioned product are complex, require a number of years and involve the expenditure of substantial resources.

We have already experienced several setbacks and delays in our previously anticipated ability to obtain FDA approval of Viaskin Peanut, and we may experience additional delays in the future.

We cannot assure you that any of our product candidates will receive FDA approval in the future, and the time for receipt of any such approval is currently incapable of estimation.

A fast track designation by the FDA may not actually lead to a faster development or regulatory review or approval process, and it does not increase the likelihood that our product candidates will receive marketing approval.

We have obtained fast track designation from the FDA for the development of Viaskin Peanut and Viaskin Milk in pediatric populations, and we may pursue that designation for other product candidates as well.

If a product is intended for the treatment of a serious or life-threatening condition and nonclinical or clinical data demonstrate the potential to address unmet medical needs for this condition, the sponsor may apply for FDA fast track designation.

We have already experienced several setbacks and delays in our previously anticipated ability to obtain approval of Viaskin Peanut from the FDA and the European Commission, and we may experience additional delays in the future.

We cannot assure you that any of our product candidates will receive FDA approval, or regulatory approval from a comparable foreign regulatory authority, in the future, and the time for receipt of any such approval is currently incapable of estimation.

A Fast Track designation by the FDA, or equivalent foreign programs, may not actually lead to a faster development or regulatory review or approval process, and it does not increase the likelihood that our product candidates will receive regulatory approval.

We have obtained Fast Track designation from the FDA for the development of Viaskin Peanut and Viaskin Milk, and we may pursue that designation for other product candidates as well.

If a product is intended for the

treatment of a serious condition and nonclinical or clinical data demonstrate the potential to address unmet medical needs for this condition, the sponsor may apply for FDA Fast Track designation.

The FDA has broad discretion to grant this designation, and even if we believe our product candidates are eligible for this designation, we cannot be sure that the FDA would decide to grant it.

Even if we do have Fast Track designation, we may not experience a faster development process, review or approval compared to conventional FDA procedures.

A fast track designation affords the possibility of rolling review, enabling the FDA to review portions of our marketing application before submission of a complete application, and priority review if supported by clinical data at the time of our BLA submission.

The FDA may withdraw fast track designation if it believes that the designation is no longer supported by data from our clinical development program.

The approval process outside the United States varies among countries and may limit our ability to develop, manufacture and sell our products internationally.

Failure to obtain marketing approval in international jurisdictions would prevent our product candidates from being marketed abroad.

In order to market and sell our product candidates in the European Union and many other jurisdictions, we, and our collaborators, must obtain separate marketing approvals and comply with numerous and varying regulatory requirements.

A Fast Track designation affords the possibility of rolling review, enabling the FDA to review portions of our marketing application before submission of a complete application .

The FDA may withdraw fast track designation if it elieves that the designation is no longer supported by data from our clinical development program.

The regulatory approval process outside the United States varies among countries and may limit our ability to develop, manufacture and sell our products internationally.

Failure to obtain regulatory approval in international jurisdictions would prevent our product candidates from being marketed abroad.

In order to market and sell our product candidates in the European Union and many other jurisdictions, we, and our collaborators, must obtain separate regulatory approvals and comply with numerous and varying regulatory requirements.

The approval procedure varies among countries and may involve additional testing.

We may, in the future, conduct clinical trials for, and seek regulatory approval to market, product

candidates in countries other than the United States.

We may, in the future, conduct clinical trials for, and seek regulatory approval to market, product candidates in countries other than the United States.

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.

If we or our collaborators seek marketing approvals for a product candidate outside the United States, we will be subject to the regulatory requirements of health authorities in each country in which we seek approvals.

With respect to marketing authorizations in Europe, we will be required to submit an MAA to the EMA which conducts a validation and scientific approval process in evaluating a product for safety and efficacy.

The approval procedure varies among regions and countries and may involve additional testing, and the time required to obtain approvals may differ from that required to obtain FDA approval.

Pursuing regulatory approvals from health authorities in countries outside the United States is likely to subject us to all of the risks associated with pursuing FDA approval described above.

In addition, marketing approval by the

FDA does not ensure approval by the health authorities of any other country, and approval by foreign health authorities does not ensure marketing approval by the FDA.

Even if we, or our collaborators, obtain marketing approvals for our product candidates, the terms of approvals and ongoing regulation of our products may limit how we or they market our products, which could materially impair our ability to generate revenue.

With respect to marketing authorizations in the European Union, we will be required to submit an MAA to the EMA which conducts a validation and scientific review process in evaluating a product for safety and efficacy.

The regulatory approval procedures vary among countries and may involve additional testing, and the time required to obtain approvals may differ from that required to obtain FDA approval.

Pursuing regulatory approvals from regulatory authorities in countries outside the United States is likely to subject us to all of the risks associated with pursuing FDA approval described above.

In addition, regulatory approval by the FDA does not ensure approval by the regulatory authorities of any other country, and approval by foreign regulatory authorities does not ensure regulatory approval by the FDA.

Even if we, or our collaborators, obtain regulatory approvals for our product candidates, the terms of approvals and ongoing regulation of our products may limit how we or they market our products, which could materially impair our ability to generate revenue.

Even if we receive regulatory approval for Viaskin Peanut or any of our other product candidates, this approval may carry conditions that limit the market for the product or put the product at a competitive disadvantage relative to alternative therapies.

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These restrictions could make it more difficult to market any product candidate effectively.

Accordingly, assuming we, or our collaborators, receive marketing approval for Viaskin Peanut or any of our other product candidates, we and our collaborators will continue to expend time, money and effort in all areas of regulatory compliance.

Any of our product candidates for which we, or our collaborators, obtain marketing approval in the future could be subject to post-marketing restrictions or withdrawal from the market and we, and our collaborators, may be subject to substantial penalties if we, or they, fail to comply with regulatory requirements or if we, or they, experience unanticipated problems with our products following approval.

Any of our product candidates for which we, or our collaborators, obtain marketing approval in the future, as well as the manufacturing processes, post-marketing requirements and commitments, labeling, advertising and promotional activities for such products, among other things, will be subject to continual requirements of and review by the FDA and other regulatory authorities.

Accordingly, assuming we, or our collaborators, receive regulatory approval for Viaskin Peanut or any of our other product candidates, we and our collaborators will continue to expend time, money and effort in all areas of regulatory compliance.

Any of our product candidates for which we, or our collaborators, obtain regulatory approval in the future could be subject to post-marketing requirements, post-marketing commitments or withdrawal from the market and we, and our collaborators, may be subject to substantial penalties if we, or they, fail to comply with regulatory requirements or if we, or they, experience unanticipated problems with our products following approval.

Any of our product candidates for which we, or our collaborators, obtain regulatory approval in the future, as well as the manufacturing processes, post-marketing requirements and commitments, labeling, advertising and promotional activities for such products, among other things, will be subject to continual requirements of and review by the FDA and other foreign regulatory authorities.

These requirements include submissions of safety and other post-marketing information and reports, registration and listing requirements, requirements relating to manufacturing, quality control, quality assurance and corresponding maintenance of records and documents and requirements regarding the distribution of samples to physicians and recordkeeping.

Even if marketing approval of a product candidate is granted, the approval will be subject to limitations on the indicated uses for which the product may be marketed or may be subject to other conditions of approval, including the FDA requirement to implement a REMS to ensure that the benefits of a drug or biological product outweigh its risks.

The FDA or foreign regulatory authorities may also impose requirements for costly post-marketing studies or clinical trials and surveillance to monitor the safety or efficacy of a product, such as long-term observational studies on natural exposure.

The FDA and other agencies, including the Department of Justice, closely regulate and monitor the post-approval marketing and promotion of products to ensure that they are manufactured, marketed, and distributed only for the approved indications and in accordance with the provisions of the approved labeling.

The FDA imposes 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 marketing 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 regulatory approval of a product candidate is granted, the approval will be subject to limitations on the indicated uses for which the product may be marketed or may be subject to other conditions of approval, including the FDA requirement to implement a REMS, or comparable foreign requirements to ensure that the benefits of a drug or biological product outweigh its risks.

The FDA or comparable foreign regulatory authorities may also impose requirements for costly post-marketing studies or clinical trials and surveillance to monitor the safety or efficacy of a product, such as long-term observational studies on natural exposure.

The FDA and other agencies, including the Department of Justice, and comparable foreign regulatory authorities closely regulate and monitor the post-approval marketing and promotion of products to ensure that they are manufactured, marketed, and distributed only for the approved indications and in accordance with the provisions of the approved labeling.

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.

Violation of the Federal Food, Drug, and Cosmetic Act, or FDCA, and other statutes, including the False Claims Act, relating to the promotion and advertising of prescription drugs may lead to investigations or allegations of violations of federal and state health care fraud and abuse laws and state consumer protection laws.

Failure to comply with EU and EU Member State laws that apply to the conduct of clinical trials, manufacturing approval, marketing authorization of medicinal products and marketing of such products, both before and after grant of the marketing authorization, or with other applicable regulatory requirements may result in administrative, civil or criminal penalties.

These penalties could include delays or refusal to authorize the conduct of clinical trials, or to grant marketing authorization, product withdrawals and recalls, product seizures, suspension, withdrawal or variation of the marketing authorization, total or partial suspension of production, distribution, manufacturing or clinical trials, operating restrictions, injunctions, suspension of licenses, fines and criminal penalties.

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.

These milestones may include our expectations regarding the commencement or completion of scientific studies, clinical trials, the submission of regulatory filings, or

commercialization objectives.

From time to time, we may publicly announce the expected timing of some of these milestones, such as the completion of an ongoing clinical trial, the initiation of other clinical programs, receipt of marketing approval, or a commercial launch of a product.

These milestones may include our expectations regarding the commencement or completion of scientific studies, clinical trials, the submission of regulatory filings, or commercialization objectives.

From time to time, we may publicly announce the expected timing of some of these milestones, such as the completion of an ongoing clinical trial, the initiation of other clinical programs, receipt of regulatory approval, or a commercial launch of a product.

The achievement of many of these milestones may be outside of our control.

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our available capital resources or capital constraints we experience;

our receipt of approvals, if any, by the FDA and other regulatory agencies and the timing thereof;

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;

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the securing of, costs related to, and timing issues associated with, product manufacturing, as well as sales and marketing activities;

impacts of the ongoing COVID-19 pandemic.

impacts of the COVID-19 pandemic.

If we fail to achieve announced milestones in the timeframes we expect, the commercialization of our product candidates may be delayed, our business and results of operations may be harmed, the trading price of the ADSs or ordinary shares may decline.

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We are dependent on third parties for the supply of various materials, chemical or biological products that are necessary to produce patches for our clinical trials or diagnosis patches, and will be necessary to produce patches for our commercial supply, if Viaskin Peanut is approved.

The supply of these materials could be reduced or interrupted at any time, including as a result of shelter-in-place, stay-at-home or similar orders or other impacts due to the ongoing COVID-19 pandemic.

The supply of these materials could be reduced or interrupted at any time, including as a result of impacts due to the COVID-19 pandemic or other unfavorable global economic conditions, including as a result of the ongoing conflict between Russia and Ukraine.

In such case, we may not be able to find other suppliers of acceptable materials in appropriate quantities at an acceptable cost.

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Currently, we have only one manufacturer, Sanofi S.A., or Sanofi, of the active pharmaceutical ingredients, or API, used in our Viaskin product candidates, including Viaskin Peanut, such as peanut protein extract and unmodified allergen milk extract.

In February 2020, Sanofi announced that it plans to create a new

company dedicated to the production and marketing to third parties of API, which will consolidate Sanofi’s API commercial and development activities currently conducted in six of its European API production sites.

While those API sites do not include the site in which the API used in our Viaskin product candidates is produced, there can be no assurances that this transition will not adversely impact our supply of API from Sanofi.

In February 2020, Sanofi announced that it plans to create a new company dedicated to the production and marketing to third parties of API.

Subsequently, Sanofi consolidated its API commercial and development activities conducted in six of its European API production sites.

While those API sites do not include the site in which the API used in our Viaskin product candidates is produced, there can

be no assurances that this transition will not adversely impact our supply of API from Sanofi.

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.

Further, we are aware that Sanofi has entered into a clinical collaboration with Regeneron and Aimmune Therapeutics, to evaluate treatment with Palforzia in combination with Dupilumab in peanut allergic patients, and commenced a Phase II clinical trial in October 2018 under this collaboration.

Further, we are aware that Sanofi has entered into a clinical collaboration with Regeneron and Aimmune Therapeutics, to evaluate treatment with Palforzia in combination with Dupilumab in peanut allergic patients, and commenced a Phase 2 clinical trial in October 2018 under this collaboration.

This potential competitive dynamic may make Sanofi less inclined to continue or renew their manufacturing arrangement with us on commercially reasonable terms or at all and, notwithstanding contractual protections, Sanofi may be able to utilize knowledge gained through their relationship with us in furtherance of their development of competitive therapies.

We also expect to rely on Sanofi or other third-party manufacturers for the manufacturing of commercial supply of Viaskin Peanut, if approved, and any other product for which we obtain regulatory approval.

We also expect to rely on Sanofi and on FAREVA for the manufacturing of the patch and on other third-party manufacturers for the manufacturing of commercial supply of Viaskin Peanut, if approved, and any other product for which we obtain regulatory approval.

Sanofi may not be able to effectively scale its manufacturing capacity of our API to meet our commercialization needs and we may be unable to establish any agreements with other third-party manufacturers or to do so on acceptable terms.

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The discovery of previously unknown problems with a product or manufacturer may result in restrictions on the product, manufacturer or manufacturing facility, including withdrawal of the product from the market.

Any manufacturers with which we contract are required to operate in accordance with FDA-mandated current good manufacturing practices, or cGMPs.

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.

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.

Moreover, the constituent parts of a combination product retain their regulatory status (as a biologic or device, for example) and, as such, we or our contract manufacturers may be subject to additional requirements in the Quality System Regulation, or QSR, applicable to medical devices, such as design controls, purchasing controls, and corrective and preventive action.

Failure by third-party manufacturers to comply with applicable regulations could result in sanctions being imposed on us, including fines, injunctions, civil penalties, revocation or suspension of marketing approval for any products granted pre-market approvals, seizures or recalls of products, operating restrictions, and criminal prosecutions.

Our current and anticipated future dependence upon others for the manufacture of our product candidates or products, if approved, may adversely affect our future profit margins and our ability to commercialize any products that receive marketing approval on a timely and competitive basis.

Moreover, the constituent parts of a combination product retain their regulatory status (as a biologic or medical device, for example) and, as such, we or our contract manufacturers may be subject to additional requirements in the Quality System Regulation, or QSR, or comparable quality management systems in foreign countries, applicable to medical devices, such as design controls, purchasing controls, and corrective and preventive action.

We, our contract manufacturers, any future collaborators and their contract manufacturers could be subject to periodic unannounced inspections by the FDA or other comparable foreign regulatory authorities, to monitor and ensure compliance with cGMP.

Despite our efforts to audit and verify regulatory compliance, one or more of our third-party manufacturing vendors may be found on regulatory inspection by the FDA or other comparable foreign regulatory authorities to be noncompliant with cGMP regulations.

Failure by third-party manufacturers to comply with applicable regulations could result in sanctions being imposed on us, including shutdown of the third-party vendor, fines, injunctions, civil penalties, revocation or suspension of regulatory approval for any products granted pre-market approvals, invalidation of drug product lots or processes, seizures or recalls of products, operating restrictions, and criminal prosecutions.

Our current and anticipated future dependence upon others for the manufacture of our product candidates or products, if approved, may adversely affect our future profit margins and our ability to commercialize any products that receive regulatory approval on a timely and competitive basis.

Our Viaskin product candidates may not be able to be manufactured profitably on a large enough scale to support commercialization.

To date, our Viaskin product candidates have only been manufactured at a scale which is adequate to supply our research activities and clinical trials.

There can be no assurance that the procedures currently used to manufacture our product candidates will work at a scale which is adequate for commercial needs and we may encounter

difficulties in the production of Viaskin patches due to our or our partners’ manufacturing capabilities.

There can be no assurance that the procedures currently used to manufacture our product candidates will work at a scale which is adequate for commercial needs and we may encounter difficulties in the production of Viaskin patches due to our or our partners’ manufacturing capabilities.

For example, in large-scale use, there is a possibility that our electrospray manufacturing tool, ES GEN4.0, may have issues related to maintenance of production quality, protein stability, and allergenicity.

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regulatory authorities will make new regulations applicable to our production process, or if we will have any future disagreements with such regulatory authorities regarding our interpretation of the regulatory requirements.

We rely on a single supplier to produce, or contract for the production of, active ingredients 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 approved products.

Even if we were to obtain access to quantities of active ingredients sufficient to allow us otherwise to expand our Viaskin manufacturing capabilities, we may not be able to produce sufficient quantities of the product at an acceptable cost, or at all.

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Third party performance failures may increase our development costs, delay our ability to obtain regulatory approval, and delay or prevent the commercialization of our product candidates.

While we believe that there are

numerous alternative sources to provide these services, in the event that we seek such alternative sources, we may not be able to enter into replacement arrangements without incurring delays or additional costs.

While we believe that there are numerous alternative sources to provide these services, in the event that we seek such alternative sources, we may not be able to enter into replacement arrangements without incurring delays or additional costs.

Even if collaborators with which we contract in the future successfully complete clinical trials of our product candidates, those candidates may not be commercialized successfully for other reasons.

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For example, recruiting and training a sales force is expensive and time consuming and could delay any product launch.

If the commercial launch of a product candidate for which we recruit a sales force and establish marketing capabilities is delayed or does not occur for any reason, we would have prematurely or unnecessarily incurred these commercialization expenses.

commercial launch of a product candidate for which we recruit a sales force and establish marketing capabilities is delayed or does not occur for any reason, we would have prematurely or unnecessarily incurred these commercialization expenses.

This may be costly, and our investment would be lost if we cannot retain or reposition our sales and marketing personnel.

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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 persuade adequate numbers of physicians to prescribe any future products;

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;

unforeseen costs and expenses associated with establishing an independent sales and marketing organization.

If we enter into arrangements with third parties to perform sales, marketing and distribution services for the commercialization of Viaskin Peanut in the United States or the European Union, if approved, our product revenues or the profitability of these product revenues to us are likely to be lower than if we were to market and

sell any product candidates that we develop ourselves.

In addition, we may not be successful in entering into arrangements with third parties to sell and market Viaskin Peanut or any of our other product candidates or may be unable to do so when needed or on terms that are favorable to us.

We likely will have more limited control over such third parties, and any of them may fail to devote the necessary resources and attention to sell and market our product candidates effectively, or they may fail to comply with promotional requirements for prescription products that could render our products misbranded in violation of government regulations and thus potentially subject to enforcement.

If we do not establish sales and marketing capabilities successfully, either on our own or in collaboration with third parties, we will not be successful in commercializing Viaskin Peanut or any of our other product candidates that receive marketing approval, or any such commercialization may experience delays or limitations.

If we do not establish sales and marketing capabilities successfully, either on our own or in collaboration with third parties, we will not be successful in commercializing Viaskin Peanut or any of our other product candidates that receive regulatory approval, or any such commercialization may experience delays or limitations.

If we are not successful in commercializing Viaskin Peanut or any of our other product candidates, either on our own or through collaborations with one or more third parties, our business, results of operations, financial condition and prospects will be materially and adversely affected.

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, drugs) is not yet clear, and will depend on a number of marketplace and regulatory factors that are still developing and subject to interpretation.

The European Union provides opportunities for data and market exclusivity related to marketing authorizations.

Upon receiving a marketing authorization, innovative medicinal products are generally entitled to receive eight years of data exclusivity and 10 years of market exclusivity.

Data exclusivity, if granted, prevents regulatory

authorities in the European Union 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 marketing authorization application can be submitted, and the innovator’s data may be referenced.

The market exclusivity period prevents a successful generic or biosimilar applicant from commercializing its product in the European Union until 10 years have elapsed from the initial marketing authorization of the reference product in the European Union.

The overall ten-year period may, occasionally, be extended for a further year to a maximum of 11 years if, during the first eight years of those ten years, the marketing authorization holder obtains an authorization for one or more new therapeutic indications which, during the scientific evaluation prior to their authorization, are held to bring a significant clinical benefit in comparison with existing therapies.

However, there is no guarantee that a product will be considered by the European Union’s regulatory authorities to be a new chemical/biological entity, and products may not qualify for data exclusivity.

In the European Union, there is a special regime for biosimilars, or biological medicinal products that are similar to a reference medicinal product but that do not meet the definition of a generic medicinal product.

For such products, the results of appropriate preclinical or clinical trials must be provided in support of an application for MA.

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.

As with the U.S., however, if competitors obtain marketing authorization for their biosimilar products, our products may become subject to competition from these biosimilars, with the attendant competitive pressure and consequences.

Even if any of our product candidates are commercialized, they may not be accepted by physicians, patients, or the medical community in general.

Even if we, or our collaborators, are able to commercialize our product candidates, the products may become subject to market conditions that could harm our business.

Even if the medical community accepts a product as safe and efficacious for its indicated use, physicians 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

We cannot predict the degree of market acceptance of any product candidate that receives marketing approval, which will depend on a number of factors, including, but not limited to:

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.

We cannot predict the degree of market acceptance of any product candidate that receives regulatory approval, which will depend on a number of factors, including, but not limited to:

the demonstration of the clinical efficacy and safety of the product;

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The biopharmaceuticals industry is highly competitive.

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.

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.

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In the case of food allergies, we are aware of several food allergy academic studies and pharmaceutical developmental efforts connected with such studies that are currently being conducted in major medical centers and hospitals worldwide.

These studies are evaluating forms of allergen desensitization treatments such as oral, or OIT, sublingual or SLIT, subcutaneous, or SCIT;

or intranasal immunotherapy, or products using synthetic allergens, or denatured allergens, medicinal herbs, or combinations of medicines or methods, or medicines using traditional methods such as Chinese herbs.

These studies are evaluating forms of allergen desensitization treatments such as oral, or OIT, sublingual or SLIT, subcutaneous, or SCIT, or intranasal immunotherapy, or products using synthetic allergens, or denatured allergens, medicinal herbs, or combinations of medicines or methods, or medicines using traditional methods such as Chinese herbs.

Studies combining other methods of allergen immunotherapy, such as OIT, with anti-IgE monoclonal antibodies treatments are being conducted currently.

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Monoclonal antibodies, used alone or in combination with allergen immunotherapy, may become significant competitors with to our products.

There is one FDA- and EMA-approved treatment for peanut allergy:

There is one treatment for peanut allergy, which has been approved by the FDA and the European Commission:

Palforzia, a formulation of peanut flour developed by Aimmune Therapeutics, Inc., or Aimmune.

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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.

Moreover, eligibility for coverage and reimbursement does not imply that a product will be paid for in all cases or at a rate that covers our costs, including research, development, manufacture, sales and distribution.

Moreover, eligibility for coverage and reimbursement does not imply that a product will be paid for in all cases or at a rate

that covers our costs, including research, development, manufacture, sales and distribution.

Third-party payors are increasingly reducing reimbursements for medical products, drugs and services.

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However, there have been executive, judicial and Congressional challenges to certain aspects of the ACA.

For example, on December 22, 2017, President Trump signed into law The Tax Cuts and Jobs Act of 2017, or Tax Act, which includes a provision repealing the individual mandate to maintain health insurance coverage under the ACA effective January 1, 2019.

In addition, the 2020 federal spending package permanently eliminated, effective January 1, 2020, the ACA-mandated “Cadillac” tax on high-cost employer- sponsored health coverage and medical device tax and, effective January 1, 2021, also eliminates the health insurer tax.

On June 17, 2021 the U.S.

For example, on June 17, 2021 the U.S.

Supreme Court dismissed a challenge on procedural grounds that argued the ACA is unconstitutional in its entirety because the “individual mandate” was repealed by Congress.

Thus, the ACA will remain in effect in its current form.

Prior to the U.S.

Supreme Court ruling, on January 28, 2021, President Biden issued an executive order that initiated a special enrollment period for purposes of obtaining health insurance coverage through the ACA marketplace.

The executive order also instructed certain governmental agencies to review and reconsider their existing policies and rules that limit access to healthcare, including among others, reexamining Medicaid demonstration projects and waiver programs that include work requirements, and policies that create unnecessary barriers to obtaining access to health insurance coverage through Medicaid or the ACA.

It is possible that the ACA will be subject to judicial or

Congressional challenges in the future.

It is unclear how such challenges and the healthcare reform measures of the Biden administration will impact the ACA.

On August 16, 2022, President Biden signed the Inflation Reduction Act of 2022, or IRA, into law, which, among other things, extends enhanced subsidies for individuals purchasing health insurance coverage in ACA marketplaces through plan year 2025.

The IRA also eliminates the “donut hole” under the Medicare Part D program beginning in 2025 by significantly lowering the beneficiary maximum out-of-pocket cost and creating a new manufacturer discount program.

It is possible that the ACA will be subject to judicial or Congressional challenges in the future.

It is unclear how such challenges and the healthcare reform measures of the Biden administration will impact the ACA or operations.

Following ACA, both the Budget Control Act of 2011 and the American Taxpayer Relief Act of 2012, or the ATRA, include, among other things, mandatory reductions in Medicare payments to certain providers.

Additionally, in the United States, there have been several recent Congressional inquiries and federal and state legislative activity designed to, among other things, bring more transparency to drug pricing, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for drugs.

At the federal level, the Trump administration used several means to propose or implement drug pricing reform, including through federal budget proposals, executive orders and policy initiatives.

For example, on July 24, 2020 and September 13, 2020, the Trump administration announced several executive orders related to prescription drug pricing that seek to implement several of the administration’s proposals.

As a result, the FDA concurrently released a final rule and guidance in September 2020 providing pathways for states to build and submit importation plans for drugs from Canada.

Further, on November 20, 2020, HHS finalized a regulation removing safe harbor protection for price reductions from pharmaceutical manufacturers to plan sponsors under Medicare Part D, either directly or through pharmacy benefit managers, unless the price reduction is required by law.

The implementation of the rule has been delayed by the Biden administration from January 1, 2022 to January 1, 2023.

The rule also creates a new safe harbor for price reductions reflected at the point-of-sale, as well as a new safe harbor for certain fixed fee arrangements between pharmacy benefit managers and manufacturers, the implementation of which have also been delayed until January 1, 2023.

On November 20, 2020, CMS issued an interim final rule implementing the Trump administration’s Most Favored Nation executive order, which would tie Medicare Part B payments for certain physician-administered drugs to the lowest price paid in other economically advanced countries, effective January 1, 2021.

As a result of litigation challenging the Most Favored Nation model, on December 27, 2021, CMS published a final rule that rescinded the Most Favored Nation model interim final rule.

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, HHS released a Comprehensive Plan for Addressing High Drug Prices that outlines principles for drug pricing reform and sets out a variety of potential legislative policies that Congress could pursue as well as potential administrative actions HHS can take to advance these principles.

No legislation or administrative actions have been finalized to implement these principles.

It is unclear whether these or similar policy initiatives will be implemented in the future.

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.

Department of Health and Human Services, or HHS, released a Comprehensive Plan for Addressing High Drug Prices that outlines principles for drug pricing reform and sets out a variety of potential legislative policies that Congress could pursue as well as potential administrative actions HHS can take to advance these principles.

In addition, the IRA, among other things, (i) directs HHS to negotiate the price of certain high-expenditure, single-source drugs and biologics covered under Medicare, and subject drug manufacturers to civil monetary penalties and a potential excise tax by offering a price that is not equal to or less than the negotiated “maximum fair price” for such drugs and biologics under the law, and (ii) imposes rebates with respect to certain drugs and biologics covered under Medicare Part B or Medicare Part D to penalize price increases that outpace inflation.

It is currently unclear how the IRA will be implemented but is likely to have a significant impact on the pharmaceutical industry.

Further, the Biden administration released an additional executive order on October 14, 2022, directing HHS to submit a report on how the Center for Medicare and Medicaid Innovation can be further leveraged to test new models for lowering drug costs for Medicare and Medicaid beneficiaries.

It is unclear whether this executive order or similar policy initiatives will be implemented in the future.

At the state level, legislatures have increasingly passed legislation and implemented regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.

It is also possible that additional governmental action is taken in response to the COVID-19 pandemic.

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.

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For example, the European Union provides options for its Member States to restrict the range of medicinal products for which their national health insurance systems provide reimbursement and to control the prices of medicinal products for human use.

A member state may approve a specific price for a 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 a 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.

Many EU Member States periodically review their reimbursement procedures for medicinal products, which could have an adverse impact on reimbursement status.

We expect that legislators, policymakers and healthcare insurance funds in the EU Member States will continue to propose and implement cost-containing measures, such as lower maximum prices, lower or lack of reimbursement coverage and incentives to use cheaper, usually generic, products as an alternative to branded products, and/or branded products available through parallel import to keep healthcare costs down.

Moreover, in order to obtain reimbursement for our products in some European countries, including some EU Member States, we may be required to compile additional data comparing the cost-effectiveness of our products to other available therapies.

Health Technology Assessment, or HTA, of medicinal products is becoming an increasingly common part of the pricing and reimbursement procedures in some EU Member States, including those representing the larger markets.

The HTA process is the procedure to assess therapeutic, economic and societal impact of a given medicinal product in the national healthcare systems of the individual country.

The outcome of an HTA will often influence the pricing and reimbursement status granted to these medicinal products by the competent authorities of individual EU Member States.

The extent to which pricing and reimbursement decisions are influenced by the HTA of the specific medicinal product currently varies between EU Member States.

In December 2021, Regulation No 2021/2282 on Health Technology Assessment, or HTA, amending Directive 2011/24/EU, was adopted in the EU.

This Regulation, which entered into force in January 2022 and will apply as of January 2025, is intended to boost cooperation among EU Member States in assessing health technologies, including new medicinal products, and providing the basis for cooperation at EU level for joint clinical assessments in these areas.

The Regulation foresees a three-year transitional period and will permit EU Member States to use common HTA tools, methodologies, and procedures across the EU, working together in four main areas, including joint clinical assessment of the innovative health technologies with the most potential impact for patients, joint scientific consultations whereby developers can seek advice from HTA authorities, identification of emerging health technologies to identify promising technologies early, and continuing voluntary cooperation in other areas.

Individual EU Member States will continue to be responsible for assessing non-clinical (e.g., economic, social, ethical) aspects of health technologies, and making decisions on pricing and reimbursement.

If we are unable to maintain favorable pricing and reimbursement status in EU Member States for product candidates that we may successfully develop and for which we may obtain regulatory approval, any anticipated revenue from and growth prospects for those products in the EU could be negatively affected.

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.

These measures could include limitations on the prices we would be able to charge for product candidates that we may successfully develop and

for which we may obtain regulatory approval or the level of reimbursement available for these products from governmental authorities or third-party payors.

Further, an increasing number of EU and other foreign countries use prices for medicinal products established in other countries as “reference prices” to help determine the price of the product in their own territory.

Consequently, a downward trend in prices of medicinal products in some countries could contribute to similar downward trends elsewhere.

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.

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Guidelines and recommendations published by various organizations may impact the use or reimbursement of Viaskin Peanut, if approved.

Government agencies promulgate regulations and guidelines that may be directly applicable to us and any approved products.

Government authorities promulgate regulations and guidelines that may be directly applicable to us and any approved products.

However, professional societies, practice management groups, insurance carriers, physicians’ groups, private health and science foundations and organizations involved in various diseases also publish guidelines and recommendations to healthcare providers, administrators and payors, as well as patient communities.

Recommendations by government agencies or other groups and organizations may relate to such matters as usage, dosage, route of administration and use of related therapies, and a growing number of organizations are providing assessments of the value and pricing of pharmaceutical products.

Recommendations by government authorities or other groups and organizations may relate to such matters as usage, dosage, route of administration and use of related therapies, and a growing number of organizations are providing assessments of the value and pricing of pharmaceutical products.

These assessments may come from private organizations, such as the Institute for Clinical and Economic Review, or ICER, which publish their findings and offer recommendations relating to the products’ reimbursement by government and private payors.

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In addition, the occurrence of any of the foregoing, or the perception by the investment community or shareholders that such recommendations or guidelines will result in decreased use or reimbursement of Viaskin Peanut, if approved, could adversely affect the market price of our securities.

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

Our product candidates are being developed to address the needs of severely allergic patients, for some of whom they can have a profound and life-threatening adverse reaction if exposed to even minute amounts of an allergen.

Our product candidates are being developed to address the needs of allergic patients, for some of whom they can have a profound and life-threatening adverse reaction if exposed to even minute amounts of an allergen.

Accordingly, safety is of paramount importance in developing these product candidates.

To date, more than ten 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 patients to evaluate the safety and efficacy of these product candidates for the treatment of peanut allergies and milk allergies, respectively.

Adverse events observed in these clinical trials have primarily involved general disorders such skin and subcutaneous tissue, immune system and administration site conditions, such as erythema, pruritus, edema and urticaria.

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It is worth noting that, as a desensitization patch bringing the allergen into contact with the skin, reactions, which are a source of itching and discomfort for the patient, are common.

This reaction is typically temporary in duration and fades after a few weeks of use.

reaction is typically temporary in duration and fades after a few weeks of use.

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.

Undesirable side effects caused by our product candidates could cause us or regulatory authorities to interrupt, delay, halt or terminate clinical trials and could result in a more restrictive label or the delay or denial of regulatory

approval by the FDA or other regulatory authorities.

Further, if our Viaskin patch product candidates receive marketing 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:

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;

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Foreign sales of Viaskin patch products could also be adversely affected by the imposition of governmental controls, political and economic instability, trade restrictions and changes in tariffs.

The United Kingdom’s withdrawal from the EU may have a negative effect on global economic conditions, financial markets and our business, which could reduce the price of our common shares.

Following the result of a referendum in 2016, the United Kingdom left the EU on January 31, 2020, commonly referred to as Brexit.

Pursuant to the formal withdrawal arrangements agreed between the United Kingdom and the EU, the United Kingdom, or the UK, was subject to a transition period until December 31, 2020, or the Transition Period, during which EU rules continued to apply.

The UK and the EU have signed a EU-UK Trade and Cooperation Agreement, or TCA, which became provisionally applicable on January 1, 2021 and entered into force on May 1, 2021.

This agreement provides details on how some aspects of the UK and EU’s relationship will operate going forwards however there are still many uncertainties.

The TCA primarily focuses on ensuring free trade between the EU and the UK in relation to goods, including medicinal products.

Although the body of the TCA includes general terms which apply to medicinal products, greater detail on sector-specific issues is provided in an Annex to the TCA.

The Annex provides a framework for the recognition of Good Manufacturing Practice, or GMP, inspections and for the exchange and acceptance of official GMP documents.

The regime does not, however, extended to procedures such as batch release certification.

Among the changes that have occurred are that Great Britain (England, Scotland and Wales) is treated as a “third country,” a country that is not a member of the EU and whose citizens do not enjoy the EU right to free movement.

Northern Ireland continues to follow many aspects of the EU regulatory rules, particularly in relation to trade in goods.

As part of the TCA, the EU and the UK recognize GMP inspections carried out by the other party and the acceptance of official GMP documents issued by the other party.

The TCA also encourages, although it does not oblige, the parties to consult one another on proposals to introduce significant changes to technical regulations or inspection procedures.

Among the areas of absence of mutual recognition are batch testing and batch release.

The UK has unilaterally agreed to accept EU batch testing and batch release.

However, the EU continues to apply EU laws that require batch testing and batch release to take place in the EU territory.

This means that medicinal products that are tested and released in the UK must be retested and re-released when entering the EU market for commercial use.

As it relates to marketing authorizations, Great Britain has a separate regulatory submission process, approval process and a separate national marketing authorization.

Northern Ireland continues, however, to be covered by the marketing authorizations granted by the European Commission.

For example, the scope of a marketing authorization for a medicinal product granted by the European Commission or by the competent authorities of EU Member States will no longer encompass Great Britain (England, Scotland and Wales).

In these circumstances, a separate marketing authorization granted by the UK competent authorities is required to place medicinal products on the market in Great Britain.

Northern Ireland continues, however, to be covered by the marketing authorizations granted by the European Commission.

It is currently unclear to what extent the UK will seek to align its regulations with the EU in the future.

The UK regulatory framework in relation to clinical trials is derived from existing EU legislation (as implemented into UK law, through secondary legislation).

However, the Retained EU Law (Revocation and Reform) Bill published in late 2022 which is intended to remove all EU-derived legislation from the UK statute book by the end of 2023, may result in a divergence of approach between the EU and the UK.

Since a significant proportion of the regulatory framework in the UK which may be applicable to our business and our product candidates is derived from EU Directives and Regulations, Brexit, following the Transition Period, could materially impact the regulatory regime with respect to the development, manufacture, importation, approval and commercialization of our product candidates in the UK or the EU, now that UK legislation has the potential to diverge from EU legislation.

All of these changes could increase our costs and otherwise adversely affect our business.

Any delay in obtaining, or an inability to obtain, any regulatory approvals, as a result of Brexit or otherwise, would prevent us from commercializing our product candidates in the UK or the EU and restrict our ability to generate revenue and achieve and sustain profitability.

In addition, we may be required to pay taxes or duties or be subjected to other hurdles in connection with the importation of our product candidates

If any of these outcomes occur, we may be forced to restrict or delay efforts to seek regulatory approval in the UK or the EU for our product candidates, or incur significant additional expenses to operate our business, which could significantly and materially harm or delay our ability to generate revenues or achieve profitability of our business.

Any further changes in international trade, tariff and import/export regulations as a result of Brexit or otherwise may impose unexpected duty costs or other non-tariff barriers on us.

These developments, or the perception that any of them could occur, may significantly reduce global trade and, in particular, trade between the impacted nations and the UK.

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.

Healthcare providers, physicians and others will play a primary role in the recommendation and prescription of Viaskin patch products, if approved.

Our arrangements with such persons and third-party payors will expose us

to broadly applicable fraud and abuse and other healthcare laws and regulations that may constrain the business or financial arrangements and relationships through which we research, market, sell and distribute Viaskin patch products, if we obtain marketing approval.

Healthcare providers and others will play a primary role in the recommendation and prescription of Viaskin patch products, if approved.

Our arrangements with such persons and third-party payors will expose us to broadly applicable fraud and abuse and other healthcare laws and regulations that may constrain the business or financial arrangements and relationships through which we research, market, sell and distribute Viaskin patch products, if we obtain regulatory approval.

Restrictions under applicable federal, state and foreign healthcare laws and regulations include but are not limited to the following:

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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.

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 European countries, national sunshine rules, regulations, industry self-regulation codes of conduct and physicians’ codes of professional conduct.

Failure to comply with these requirements could result in reputational risk, public reprimands, administrative penalties, fines or imprisonment.

Ensuring that our business arrangements with third parties comply with applicable healthcare laws and regulations could be costly.

Because of the breadth of these laws and the narrowness of the statutory exceptions and safe harbors available, it is possible that some of our current and/or future business activities could be subject to challenge under one or more of these laws.

If our operations were 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 civil, criminal and administrative penalties, damages, fines, disgorgement, imprisonment, exclusion from government funded healthcare programs, such as Medicare and Medicaid, integrity obligations, contractual damages, reputational harm, diminished profits and future earnings, and curtailment of operations, any of which could substantially disrupt our operations.

If our operations were 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 civil, criminal and administrative penalties, damages, fines, disgorgement, 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 curtailment of operations, any of which could substantially disrupt our operations.

Defending against any such actions can be costly, time-consuming and may require significant financial and personnel resources.

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If the physicians or other providers or entities with whom we expect to do business are found not to be in compliance with applicable laws, they may be subject to significant criminal, civil or administrative sanctions, including exclusion from government funded healthcare programs.

Changes in regulatory requirements, FDA guidance or guidance from certain European regulatory authorities or unanticipated events during our clinical trials of Viaskin patch products may occur, which may result in changes to clinical trial protocols or additional clinical trial requirements, which could result in increased costs to us and could delay our development timeline.

Changes in regulatory requirements, FDA guidance or guidance from certain European regulatory authorities or unanticipated events during our clinical trials may force us to amend clinical trial protocols or the FDA or certain European regulatory authorities may impose additional clinical trial requirements.

Changes in regulatory requirements, or guidance from the FDA or comparable foreign regulatory authorities or unanticipated events during our clinical trials of Viaskin products may occur, which may result in changes to clinical trial protocols or additional clinical trial requirements, which could result in increased costs to us and could delay our development timeline.

Changes in regulatory requirements, or guidance from the FDA or comparable foreign regulatory authorities or unanticipated events during our clinical trials may force us to amend clinical trial protocols or the FDA or certain foreign regulatory authorities may impose additional clinical trial requirements.

Discussions with regulatory authorities have caused us to adjust certain trial protocols.

Amendments to our clinical trial protocols would require resubmission to the FDA and IRBs for review and approval, which may adversely impact the cost, timing or successful completion of a clinical trial.

Amendments to our clinical trial protocols would require resubmission to the FDA and IRBs or competent foreign regulatory authorities, such as the national

competent authorities of EU Member States and Ethics Committees, for review and approval, as applicable, which may adversely impact the cost, timing or successful completion of a clinical trial.

If we experience delays completing, or if we terminate, any of our clinical trials, or if we are required to conduct additional clinical trials, the commercial prospects for the Viaskin patch product candidates, or any other product candidates, may be harmed and our ability to generate product revenue will be delayed.

The FDA and other regulatory agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses.

In addition, the policies of the FDA, the competent authorities of the EU Member States, the EMA, the European Commission and other comparable regulatory authorities responsible for clinical trials may change and additional government regulations may be enacted.

For instance, the regulatory landscape related to clinical trials in the EU recently evolved.

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 assessment procedure for the authorization of clinical trials has been harmonized as well, including a joint assessment by all EU Member States concerned, and a separate assessment by each EU Member State with respect to specific requirements related to its own territory, including ethics rules.

Each EU Member State’s decision is communicated to the sponsor via the centralized EU portal.

Once the clinical trial approved, clinical study development may proceed.

The CTR foresees a three-year transition period.

The extent to which ongoing and new clinical trials will be governed by the CTR varies.

For clinical trials in relation to which application for approval was made on the basis of the Clinical Trials Directive before January 31, 2022, the Clinical Trials Directive will continue to apply on a transitional basis for three years.

Additionally, sponsors could choose to submit a clinical trial application under either the Clinical Trials Directive or the CTR until January 31, 2023 and, if authorized, those will be governed by the Clinical Trials Directive until January 31, 2025.

By that date, all ongoing trials will become subject to the provisions of the CTR.

Compliance with the CTR requirements by us and our third-party service providers, such as CROs, may impact our developments plans.

It is currently unclear to what extent the UK will seek to align its regulations with the EU in the future.

The UK regulatory framework in relation to clinical trials is derived from existing EU legislation (as implemented into UK law, through secondary legislation).

On January 17, 2022, the UK Medicines and Healthcare products Regulatory Agency, or MHRA, launched an eight-week consultation on reframing the UK legislation for clinical trials.

The consultation closed on March 14, 2022 and aims to streamline clinical trials approvals, enable innovation, enhance clinical trials transparency, enable greater risk proportionality, and promote patient and public involvement in clinical trials.

The outcome of the consultation will be closely watched and will determine whether the UK chooses to align with the regulation or diverge from it to maintain regulatory flexibility.

A decision by the UK not to closely align its regulations with the new approach that will be adopted in the EU may have an effect on the cost of conducting clinical trials in the UK as opposed to other countries and/or make it harder to seek a marketing authorization in the EU for our product candidates on the basis of clinical trials conducted in the UK.

If we are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies governing clinical trials, our development plans may be impacted.

The FDA and other comparable foreign regulatory authorities actively enforce the laws and regulations prohibiting the promotion of off-label uses.

If we are found to have improperly promoted off-label uses, we may become subject to significant liability.

The FDA and other regulatory agencies strictly regulate the promotional claims that may be made about prescription products, such as Viaskin patch products, if approved.

In particular, a product may not be promoted for uses that are not approved by the FDA or such other regulatory agencies, as reflected in the product’s approved labeling.

If we receive marketing approval for Viaskin patch products as a treatment for a particular allergy, physicians, in their professional medical judgment, may nevertheless prescribe Viaskin patch products to their patients in a manner that is inconsistent with the approved label.

Additionally, it is permissible to share in certain circumstances truthful and non-misleading information that is consistent with, but not contained in, the product’s approved labeling.

If we are found to have promoted such off-label uses, we may become subject to significant liability under the FDCA and other statutory authorities, such as laws prohibiting false claims for reimbursement.

The FDA and other comparable foreign regulatory authorities strictly regulate the promotional claims that may be made about prescription products, such as Viaskin patch products, if approved.

In particular, a product may not be promoted for uses that are not approved by the FDA or such other comparable foreign regulatory

authorities, as reflected in the product’s approved labeling.

If we receive regulatory approval for Viaskin patch products as a treatment for a particular allergy, physicians, in their independent professional medical judgment, may nevertheless prescribe Viaskin patch products to their patients in a manner that is inconsistent with the approved label.

Additionally, it is permissible to share in certain circumstances and in accordance with applicable FDA guidance and regulations truthful and non-misleading information that is consistent with, but not contained in, the product’s approved labeling.

If we are found to have promoted off-label uses or promoted our product before approval, we may become subject to significant liability under the FDCA and other statutory authorities, such as laws prohibiting false claims for reimbursement.

The federal government has levied large civil and criminal fines against companies for alleged improper promotion and has enjoined several companies from engaging in off-label promotion.

The FDA has also requested that companies enter into consent decrees or permanent injunctions under which specified promotional conduct is changed or curtailed.

If we cannot successfully manage the marketing of Viaskin patch

products, if approved, by restricting off-label promotion, we could become subject to significant liability, which would materially adversely affect our business and financial condition.

The FDA and other U.S.

government agencies has also requested that companies enter into consent decrees or permanent injunctions under which specified promotional conduct is changed or curtailed.

If we cannot successfully manage the marketing of Viaskin patch products, if approved, by restricting off-label promotion, we could become subject to significant liability, which would materially adversely affect our business and financial condition.

Similar limitations and penalties are provided in the EU both at EU level and at national level in individual EU Member States.

Our product development programs may require substantial financial resources and may ultimately be unsuccessful.

The success of our business depends primarily upon our ability to identify, develop and commercialize products to treat food allergies.

In addition to Viaskin Peanut, we may pursue development of our other development programs, including Viaskin Milk, Viaskin Egg and Viaskin rPT.

In addition to Viaskin Peanut, we may pursue development of our other development programs, including Viaskin Milk.

None of our other product candidates and potential product candidates has commenced any clinical trials since we scaled down our research and clinical development efforts in 2020 and 2021 to focus on Viaskin Peanut.

There are a number of FDA requirements that we must satisfy before we can commence clinical trials.

There are a number of FDA or foreign requirements that we must satisfy before we can commence clinical trials.

Satisfaction of these requirements will entail substantial time, effort and financial resources.

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We may never commence clinical trials of such development programs despite expending significant resources in pursuit of their development.

If we do commence clinical trials of our other potential product candidates, such product candidates may never be approved by the FDA.

If we do commence clinical trials of our other potential product candidates, such product candidates may never be approved by the FDA or comparable foreign regulatory authorities.

If any of these events occur, we may be forced to abandon our development efforts for a program or programs, which would have a material adverse effect on our business and could potentially cause us to cease operations.

If we do not secure collaborations with strategic partners to test, commercialize and manufacture certain product candidates outside of food allergies, we may not be able to successfully develop products and generate meaningful revenues.

A key aspect of our current strategy is to selectively enter into collaborations with third parties to conduct clinical testing, as well as to commercialize and manufacture product candidates outside of food allergies.

A key aspect of our current strategy is to selectively enter into collaborations with third parties to conduct clinical testing.

Our ability to generate revenues from these arrangements will depend on our collaborators’ abilities to successfully perform the functions assigned to them in these arrangements.

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Our ability to compete may decline if we do not adequately protect our proprietary rights.

Our commercial success depends on obtaining and maintaining proprietary rights to our product candidates for the treatment of common food allergies, as well as successfully defending these rights against third-party challenges.

Our commercial success depends on obtaining and maintaining proprietary rights to our product candidates for the treatment of common food or other allergies, as well as successfully defending these rights against third-party challenges.

We will only be able to protect our product candidates, and their uses from unauthorized use by third parties to the extent that valid and enforceable patents, or effectively protected trade secrets, cover them.

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There are many issued U.S.

and foreign patents relating to chemical compounds and therapeutic products, and some of these relate to compounds we intend to commercialize.

and foreign patents relating to biological or chemical compounds and therapeutic products, and some of these relate to compounds we intend to commercialize.

Numerous U.S.

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Obtaining and maintaining a patent portfolio entails significant expense and resources.

Part of the expense includes periodic maintenance fees, renewal fees, annuity fees, various other governmental fees on patents and/or

applications due in several stages over the lifetime of patents and/or applications, as well as the cost associated with complying with numerous procedural provisions during the patent application process.

Part of the expense includes periodic maintenance fees, renewal fees, annuity fees, various other governmental fees on patents and/or applications due in several stages over the lifetime of patents and/or applications, as well as the cost associated with complying with numerous procedural provisions during the patent application process and after a patent grants.

We may or may not choose to pursue or maintain protection for particular inventions.

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Accordingly, rights under any issued patents may not provide us with sufficient protection against competitive products or processes.

In addition, changes in or different interpretations of patent laws in the United States and foreign countries may permit others to use our discoveries or to develop and commercialize our technology and products without providing any compensation to us, or may limit the number of patents or claims we can obtain.

providing any compensation to us, or may limit the number of patents or claims we can obtain.

The laws of some countries do not protect intellectual property rights to the same extent as U.S.

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

In addition, the Leahy-Smith America Invents Act, or the America Invents Act, which was signed into law in

2011, includes a number of significant changes to U.S.

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.

For example, recently the federal courts and the Supreme Court have issued (or will issue) rules generally related to standards for upholding the validity of biological and chemical “genus” claims.

Any rulings that make it more difficult to uphold the validity of biological or chemical “genus” claims could potentially negatively impact our patent portfolio and negatively impact our business.

In addition, the Leahy-Smith America Invents Act, or the America Invents Act, which was signed into law in 2011, includes a number of significant changes to U.S.

These changes include a transition from a “first-to-invent” system to a “first-to-file” system, changes to the way issued patents are challenged, and changes to the way patent applications are disputed during the examination process.

These changes may favor larger and more established companies that have greater resources to devote to patent application filing and prosecution.

The USPTO has developed new and untested regulations and procedures to govern the full implementation of the

America Invents Act, and many of the substantive changes to patent law associated with the America Invents Act, and, in particular, the first-to-file provisions, became effective on March 16, 2013.

The USPTO has developed new and untested regulations and procedures to govern the full implementation of the America Invents Act, and many of the substantive changes to patent law associated with the America Invents Act, and, in particular, the first-to-file provisions, became effective on March 16, 2013.

Substantive changes to patent law associated with the America Invents Act may affect our ability to obtain patents, and if obtained, to enforce or defend them.

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

Accordingly, it is not clear what, if any, impact the America Invents Act will have on the cost of prosecuting our patent applications, our ability to obtain patents based on our discoveries and our ability to enforce or defend any patents that may issue from our patent applications, all of which could have a material adverse effect on our business.

In addition, over the past few years, bills in the U.S.

Congress have bene proposed that, if passed, would make changes to the America Invents Act.

For example, bills have been introduced that would reduce the discretion of the Patent Trial and Appeal Board (PTAB) to deny post-grant review.

In addition, bills have introduced that would provide the director of the U.S.P.T.O more authority to set aside PTAB decisions.

If these bills are eventually passed by the U.S.

Congress, it could impact our ability to enforce/defend patents by allowing third parties more opportunities to challenge them.

If we are unable to protect the confidentiality of our trade secrets, our business and competitive position would be harmed.

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However, trade secrets are difficult to protect.

We expect to enter into confidentiality and intellectual property assignment agreements with our employees, consultants, outside scientific collaborators, sponsored researchers, and other advisors.

These agreements generally require that the other party keep confidential and not disclose to third

parties all confidential information developed by the party or made known to the party by us during the course of the party’s relationship with us.

We do, and expect to, enter into confidentiality and intellectual property assignment agreements with our employees, consultants, outside scientific collaborators, sponsored researchers, and other advisors.

These agreements generally require that the other party keep confidential and not disclose to third parties all confidential information developed by the party or made known to the party by us during the course of the party’s relationship with us.

These agreements also generally provide that inventions conceived by the party in the course of rendering services to us will be our exclusive property.

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Enforcing a claim that a party illegally disclosed or misappropriated a trade secret can be difficult, expensive, and time-consuming, and the outcome is unpredictable.

In addition, courts outside the United States may be less willing to protect trade

In addition, courts outside the United States may be less willing to protect trade secrets.

Trade secrets may be independently developed by others in a manner that could prevent legal recourse by us.

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We will not seek to protect our intellectual property rights in all jurisdictions throughout the world and we may not be able to adequately enforce our intellectual property rights even in the jurisdictions where we seek protection.

Filing, prosecuting and defending patents on our 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 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.

In addition, the laws of some foreign countries do not protect intellectual property rights to the same extent as federal and state laws in the United States.

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The statutory deadlines for pursuing patent protection in individual foreign jurisdictions are based on the priority dates of each of our patent applications.

Competitors may use our technologies in jurisdictions where we do not pursue and obtain patent protection to develop their own products and further, may export otherwise infringing products to territories where we have

patent protection, but enforcement is not as strong as that in the United States.

These products may compete with our products and our patents or other intellectual property rights may not be effective or sufficient to prevent them from competing.

Even if we pursue and obtain issued patents in particular jurisdictions, our patent claims or other intellectual property rights may not be effective or sufficient to prevent third parties from so competing.

The laws of some foreign countries do not protect intellectual property rights to the same extent as the laws of the United States.

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Proceedings to enforce our patent rights in foreign jurisdictions could result in substantial costs and divert our efforts and attention from other aspects of our business, could put our patents at risk of being invalidated or interpreted narrowly, could put our patent applications at risk of not issuing and could provoke third parties to assert claims against us.

We may not prevail in any lawsuits that we initiate and the damages or other remedies awarded, if any, may not be commercially meaningful.

We may not prevail in any lawsuits that we initiate and the damages or other remedies

awarded, if any, may not be commercially meaningful.

In addition, changes in the law and legal decisions by courts in the United States and foreign countries may affect our ability to obtain adequate protection for our technology and the enforcement of intellectual property.

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We have written agreements with collaborators that provide for the ownership of intellectual property arising from our collaborations.

These agreements provide that we must negotiate certain commercial rights with collaborators with respect to joint inventions or inventions made by our collaborators that arise from the results

of the collaboration.

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.

In some instances, there may not be adequate written provisions to address clearly the resolution of intellectual property rights that may arise from a collaboration.

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We employ individuals who were previously employed at universities or other biopharmaceutical companies, including our competitors or potential competitors.

Although we try to ensure that our employees and consultants

do not use the proprietary information or know-how of others in their work for us, we may be subject to claims that we or our employees, consultants or independent contractors have inadvertently or otherwise used or disclosed intellectual property, including trade secrets or other proprietary information, of a former employer or other third parties.

Although we try to ensure that our employees and consultants do not use the proprietary information or know-how of others in their work for us, we may be subject to claims that we or our employees, consultants or independent contractors have inadvertently or otherwise used or disclosed intellectual property, including trade secrets or other proprietary information, of a former employer or other third parties.

Litigation may be necessary to defend against these claims.

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Patent and other types of intellectual property litigation can involve complex factual and legal questions, and their outcome is uncertain.

Any claim relating to intellectual property

infringement that is successfully asserted against us may require us to pay substantial damages, including treble damages and attorney’s fees if we are found to be willfully infringing another party’s patents, for past use of the asserted intellectual property and royalties and other consideration going forward if we are forced to take a license.

Any claim relating to intellectual property infringement that is successfully asserted against us may require us to pay substantial damages, including treble damages and attorney’s fees if we are found to be willfully infringing another party’s patents, for past use of the asserted intellectual property and royalties and other consideration going forward if we are forced to take a license.

In addition, if any such claim were successfully asserted against us and we could not obtain such a license, we may be forced to stop or delay developing, manufacturing, selling or otherwise commercializing Viaskin patch products.

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The loss of the services of any of these individuals would likely have an adverse effect on us.

success also will depend upon our ability to attract and retain additional qualified management.

Our success also will depend upon our ability to attract and retain additional qualified management.

Recruiting and retaining qualified scientific, clinical, manufacturing, sales and marketing personnel will also be critical to our success.

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Misconduct by employees could include intentional failures to:

comply with the regulations of the FDA and applicable non-U.S.

regulators, provide accurate information to the FDA and applicable non-U.S.

regulators, comply with fraud and abuse and other healthcare laws and regulations in the United States and abroad, report financial information or data accurately or disclose unauthorized activities to us.

comply with the regulations of the FDA and applicable foreign regulatory authorities, provide accurate information to the FDA and applicable foreign regulatory authorities, comply with fraud and abuse and other healthcare laws and regulations in the United States and abroad, report financial information or data accurately or disclose unauthorized activities to us.

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.

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.

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.

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The complaint, as amended, alleged that we and our former 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.

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.

The plaintiffs sought 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.

The complaint, as amended, was dismissed with prejudice on July 29, 2022, and the matter was resolved with finality thirty days thereafter.

See the section of this Annual Report titled “Legal Proceedings” for additional information on this matter.

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Our inability to obtain and retain sufficient product liability insurance at an acceptable cost to protect against potential product liability claims could prevent or inhibit the commercialization of product candidates we develop.

We currently carry product liability insurance coverage for our clinical trials with a €15.0 million (equivalent to $18.4 million using closing exchange rate) annual aggregate coverage limit.

We currently carry product liability insurance coverage for our clinical trials.

Although we maintain such insurance, our insurance coverage may be insufficient to reimburse us for any expenses or losses we may suffer.

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

As a French technology company, we have benefited from certain tax advantages, including, for example, the French research tax credit ( credit d’impôt recherche

The CIR is a French tax credit aimed at stimulating

research and development.

As a French technology company, we have benefited from certain tax advantages, including, for example, the French research tax credit ( credit d’impôt recherche ), or CIR.

The CIR is a French tax credit aimed at stimulating research and development.

Beginning in the fiscal year ending December 31, 2021, the Company recovered its Small and Medium-sized Enterprises, or SMEs, status under EU law, and became therefore eligible again for the immediate reimbursement of the Research Tax Credit.

The Company will request the immediate reimbursement of the 2021 fiscal year CIR, as well as former tax credit receivables, which were originally refundable three years after the tax declaration in case the Company wouldn’t have been able to offset it against corporate income tax due.

During the fiscal year ending December 31, 2022, the Company received the reimbursement of the 2019, 2020 and 2021 fiscal year research tax credit for a total amount of $26.1 million.

The CIR is calculated based on our claimed amount of eligible research and development expenditures in France and represented $5.7 million and $7.5 million, as of December 31, 2022 and 2021 respectively.

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Furthermore, if the French Parliament decides to eliminate, or reduce the scope or the rate of, the CIR benefit, either of which it could decide to do at any time, our results of operations could be adversely affected.

We may be forced to repay conditional advances prematurely if we fail to comply with our contractual obligations under the applicable innovation grant agreements.

Since inception through December 31, 2021, we have received multiple conditional advances totaling around $5 million for innovation granted by OSEO, the French Agency for Innovation and part of the Banque Publique d’Investissement.

If we fail to comply with our contractual obligations under the applicable innovation grant agreements, including if we lose our exclusive right to commercially develop our product candidates, we could be forced to repay the sums advanced ahead of schedule.

Such premature repayment could adversely affect our ability to finance our research and development projects.

In addition, we cannot ensure that we will then have the additional financial means needed, the time or the ability to replace these financial resources with others.

We may be exposed to significant foreign exchange risk.

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dollar revenue and earnings, if any, would be translated into euros at a reduced value.

We cannot predict the impact of foreign currency fluctuations, and foreign currency fluctuations in the future may adversely affect our financial condition, results of operations and cash flows.

We cannot predict the impact of foreign currency fluctuations, and foreign currency fluctuations in the future may adversely affect our financial condition, results

of operations and cash flows.

The ADSs are quoted in U.S.

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For example, in production, the confinement of the electrospray function and the use of the allergen in liquid form make it possible to prevent the allergens from contaminating the environment.

However, we cannot assure you that in case of malfunction during the handling, storage or

production process, allergen would not be released into the atmosphere and sensitize the persons present in the environment.

However, we cannot assure you that in case of malfunction during the handling, storage or production process, allergen would not be released into the atmosphere and sensitize the persons present in the environment.

We may be sued for any injury or contamination that results from our use or the use by third parties of these materials, and our liability may exceed any insurance coverage and our total assets.

Federal, state, local or foreign laws and regulations govern the use, manufacture, storage, handling and disposal of these hazardous materials and specified waste products, as well as the discharge of pollutants into the environment and human health and safety matters.

Compliance with environmental laws and regulations may be expensive and may impair our research and development efforts.

An allegation of noncompliance by applicable regulatory authorities with environmental laws and regulations may be expensive and may impair our research and development efforts.

If we fail to comply with these requirements, we could incur substantial costs, including civil or criminal fines and penalties, clean-up costs or capital expenditures for control equipment or operational changes necessary to achieve and maintain compliance.

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In the ordinary course of business, we collect, receive, store, process, generate, use, transfer, disclose, make accessible, protect, secure, dispose of, transmit, and share (collectively, processing) personal data and other sensitive information, including proprietary and confidential business data, trade secrets, intellectual property, data we collect about trial participants in connection with clinical trials, and sensitive third-party data.

Our data processing activities subject us to numerous data privacy and security obligations, such as various laws, regulations, guidance, industry standards, external and internal privacy and security policies, contracts, and other obligations that govern the processing of personal data by us and on our behalf.

Our data processing activities subject us to numerous data privacy and security obligations, such as various laws, regulations, guidance, industry standards, external and internal privacy and security policies, contractual requirements, and other obligations that govern the processing of personal data by us and on our behalf.

In the United States, federal, state, and local governments have enacted numerous data privacy and security laws, including data breach notification laws, personal data privacy laws, and consumer protection laws.

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Other states have enacted data privacy laws.

For example, Virginia passed the Consumer Data Protection Act, and Colorado passed the Colorado Privacy Act, both of which become effective in 2023.

For example, Virginia

passed the Consumer Data Protection Act, and Colorado passed the Colorado Privacy Act, both of which become

effective in 2023.

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.

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For example, under the EU GDPR, government regulators may impose temporary or definitive bans on data processing, as well as fines of up to 20 million euros or 4% of annual global revenue, whichever is greater.

Further, individuals may initiate litigation related to processing of their personal data.

Certain jurisdictions have enacted data localization laws and cross-border personal data transfer laws, which could make it more difficult to transfer information across jurisdictions (such as transferring or receiving personal data that originates in the EU or in other foreign jurisdictions).

Existing mechanisms that facilitate cross-border personal data transfers may change or be invalidated.

For example, absent appropriate safeguards or

other circumstances, the EU GDPR generally restricts the transfer of personal data to countries outside of the European Economic Area, or EEA, such as the United States, that the European Commission does not consider to provide an adequate level of data privacy and security.

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.

Although there are currently various mechanisms that may be used to transfer personal data from the EEA and UK to the United States in compliance with law, these mechanisms are subject to legal challenges, and there is no assurance that we can satisfy or rely on these measures to lawfully transfer personal data to the United States.

The EU GDPR generally restricts the transfer of personal data to countries outside of the European Economic Area, or EEA, such as the United States, that the European Commission does not consider to provide an adequate level of data privacy and security.

The European Commission released a set of “Standard Contractual Clauses,” or SCCs, that are designed to be a valid mechanism to facilitate personal data transfers out of the EEA to these jurisdictions.

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In addition, Switzerland and the UK similarly restrict personal data transfers outside of those jurisdictions to countries, such as the United States, that do not provide an adequate level of personal data protection, and certain countries outside Europe (e.g., Russia, China, Brazil) have also passed or are considering laws requiring local data residency or otherwise impeding the transfer of personal data across borders, any of which could increase the cost and complexity of doing business.

If we cannot implement a valid compliance mechanism for cross-border data transfers, we may face increased exposure to regulatory actions, substantial fines, and injunctions against processing or transferring personal data from Europe or other foreign jurisdictions.

If we cannot transfer personal data from the EEA, the UK or other jurisdictions to the United States in a lawful manner, or if the costs for such lawful transfers of personal data are too high, we may face increased exposure to regulatory actions, substantial fines and penalties, and injunctions against processing or transferring personal data from Europe or other foreign jurisdictions.

The inability to import personal data to the United States could significantly and negatively impact our business operations;

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or requiring us to increase our personal data processing capabilities and infrastructure in foreign jurisdictions at significant expense;

or interrupting or adversely impacting our operations.

Our obligations related to data privacy and security are quickly changing in an increasingly stringent fashion, creating some uncertainty as to the effective future legal framework.

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Moreover, despite our efforts, our personnel or third parties upon whom we rely may fail to comply with such obligations, which could negatively impact our business operations and compliance posture.

For example, any failure by a third-party processor to comply with applicable law, regulations, or contractual obligations could result in adverse effects, including inability to or interruption in our ability to operate our business and proceedings against us by governmental entities or others.

For example, any failure by a third-party processor to comply with applicable law, regulations, or contractual obligations including, providing appropriate notice to data subjects, obtaining necessary consents, or establishing a legal basis for the transfer and processing of the data by us, could result in adverse effects, including inability to or interruption in our ability to operate our business and proceedings against us by governmental entities or others.

If we fail, or are perceived to have failed, to address or comply with data privacy and security obligations, we could face significant consequences.

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adverse publicity;

or revision or restructuring of our operations.

revision or restructuring of our operations;

or loss of revenue or profits;

and other adverse business consequences.

If our information technology systems or sensitive information, or those of third parties upon which we rely, are or were compromised, we could experience adverse consequences resulting from such compromise, including but not limited to regulatory investigations or actions;

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and other adverse consequences.

In the ordinary course of our business, we may process proprietary, confidential, and sensitive data, including personal data (such as health-related data), intellectual property, and trade secrets (collectively, sensitive

information).

In the ordinary course of our business, we and the third parties upon which we rely, may process proprietary, confidential, and sensitive data, including personal data (such as health-related data), intellectual property, and trade secrets (collectively, sensitive information).

We may rely upon third-party service providers and technologies to operate critical business systems to process sensitive information in a variety of contexts, including, without limitation, third-party providers of cloud-based infrastructure, encryption and authentication technology, employee email, and other functions.

Our ability to monitor these third parties’ information security practices is limited, and these third parties may not have adequate information security measures in place.

We may share or receive sensitive information with or from third parties.

Cyberattacks, malicious internet-based activity, and online and offline fraud are prevalent and continue to increase.

These threats come from a variety of sources, including traditional computer “hackers,” threat actors, personnel (such as through theft or misuse), sophisticated nation states, and nation-state-supported actors.

If our third-party service providers experience a security incident or other interruption, we could experience adverse consequences.

While we may be entitled to damages if our third-party service providers fail to satisfy their privacy or security-related obligations to us, any award may be insufficient to cover our damages, or we may be unable to recover such award.

Cyberattacks, malicious internet-based activity, and online and offline fraud threaten the confidentiality, integrity, and availability of our sensitive information and information technology systems, and those of the third parties upon which we rely.

These threats are prevalent and continue to increase.

These threats come from a variety of sources, including traditional computer “hackers,” threat actors, “hacktivists”, organized criminal threat actors, personnel (such as through theft or misuse), sophisticated nation states, and nation-state-supported actors.

Some actors now engage and are expected to continue to engage in cyber-attacks, including, without limitation, nation-state actors for geopolitical reasons and in conjunction with military conflicts and defense activities.

During times of war and other major conflicts, we and the third parties upon which we rely may be vulnerable to a heightened risk of these attacks, including cyber-attacks that could materially disrupt our systems and operations, supply chain, and ability to produce, sell and distribute our goods and services.

We and the third parties upon which we rely may be subject to a variety of evolving threats, including, but not limited to, social-engineering attacks (including through phishing attacks), malicious code (such as viruses and worms), malware (including as a result of advanced persistent threat intrusions), denial-of-service attacks (such as credential stuffing), personnel misconduct or error, ransomware attacks, supply-chain attacks, software bugs, server malfunctions, software or hardware failures, loss of data or other information technology assets, adware, telecommunications failures, and other similar threats.

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.

We and the third parties upon which we rely may be subject to a variety of evolving threats, including, but not limited to, social-engineering attacks (including through phishing attacks), malicious code (such as viruses and worms), malware (including as a result of advanced persistent threat intrusions), denial-of-service attacks (such as credential stuffing), credential harvesting, personnel misconduct or error, ransomware attacks, supply-chain attacks, software bugs, server malfunctions, software or hardware failures, loss of data or other information technology assets, adware, telecommunications failures, earthquakes, fires, flood and other similar threats.

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.

Extortion payments may alleviate the negative impact of a ransomware attack, but we may be unwilling or unable to make such payments due to, for example, applicable laws or regulations prohibiting such payments.

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.

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.

Additionally, the COVID-19 pandemic and our remote workforce poses increased risks to our information technology systems and data, as more of our employees work from home, utilizing network connections, computers, and devices outside our premises or network, including working at home, while in transit and in public locations.

outside our premises.

Future or past business transactions (such as acquisitions or integrations) could also expose us to additional cybersecurity risks and vulnerabilities, as our systems could be negatively affected by vulnerabilities present in acquired or integrated entities’ systems and technologies.

Any of the previously identified or similar threats could cause a security incident or other interruption.

A security incident or other interruption could result in unauthorized, unlawful, or accidental acquisition, modification, destruction, loss, alteration, encryption, disclosure of, or access to our sensitive information.

A security incident or other interruption could disrupt our ability (and that of third parties upon whom we rely) to conduct our business operations.

Furthermore, we may discover security issues that were not previously identified while conducting due diligence acquired or integrated entities and it may be difficult to integrate companies into our information technology environment and security program.

Any of the previously identified or similar threats could cause a security incident or other interruption that could result in unauthorized, unlawful, or accidental acquisition, modification, destruction, loss, alteration, encryption, disclosure of, or access to sensitive information held by us or our information technology systems, or those of the third parties upon whom we rely.

A security incident or other interruption disrupt our ability (and that of third parties upon whom we rely) to conduct our business operations.

We may expend significant resources or modify our business activities to try to protect against security incidents.

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While we have implemented security measures designed to protect against security incidents, there can be no assurance that these measures will be effective.

We may be unable in the future to detect vulnerabilities in our information technology systems because such threats and techniques change frequently, are often sophisticated in nature, and may not be detected until after a security incident has occurred.

Despite our efforts to identify and remediate vulnerabilities, if any, in our information technology systems, our efforts may not be successful.

We take steps to detect and remediate vulnerabilities but we may not be able to detect and remediate all vulnerabilities because threats and techniques used to exploit the vulnerability change frequently, are often sophisticated in nature.

Therefore, such vulnerabilities could be exploited but may not be detected until after a security incident has occurred.

These vulnerabilities pose material risks to our business.

Further, we may experience delays in developing and deploying remedial measures designed to address any such identified vulnerabilities.

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We may engage third parties to sell our products sell our products outside the United States, to conduct clinical trials, and/or to obtain necessary permits, licenses, patent registrations, and other regulatory approvals.

direct or indirect interactions with officials and employees of government agencies or government-affiliated hospitals, universities, and other organizations.

We have direct or indirect interactions with officials and employees of government agencies or government-affiliated hospitals, universities, and other organizations.

We can be held liable for the corrupt or other illegal activities of our employees, agents, contractors, and other collaborators, even if we do not explicitly authorize or have actual knowledge of such activities.

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This may result in weaknesses in our infrastructure, give rise to operational mistakes, loss of business opportunities, loss of employees and reduced productivity among remaining employees.

Any physical expansion of our operations may lead to significant costs and may divert financial resources from other projects, such as the development of our product candidates.

Any physical expansion of our operations may lead to significant

costs and may divert financial resources from other projects, such as the development of our product candidates.

If our management is unable to effectively manage our expected development and expansion, our expenses may increase more than expected, our ability to generate or increase our revenue could be reduced and we may not be able to implement our business strategy.

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Our ADSs were sold in our initial public offering on Nasdaq in October 2014 at a price of $21.64 per share, and the price per ADS has ranged from as low as $1.08 and as high as $3.43 during 2022.

During this same period, our ordinary share prices have ranged from as low as €2.87 to as high as €13.69 The market price of our securities may fluctuate significantly in response to numerous factors, many of which are beyond our control, including:

During this same period, our ordinary share prices have ranged from as low as €2.17 to as high as €5.48.

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;

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sales of our ordinary shares or ADSs by us, our insiders or our other shareholders;

general economic and market conditions, including as a result of the ongoing COVID-19 pandemic.

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

general economic and market conditions, including as a result of the COVID-19 pandemic.

These and other market and industry factors may cause the market price and demand for our securities to

fluctuate substantially, regardless of our actual operating performance, which may limit or prevent investors from readily selling their ADSs or ordinary shares and may otherwise negatively affect the liquidity of our ADSs and ordinary shares.

In addition, the stock market in general, and biopharmaceutical companies in particular, have experienced extreme price and volume fluctuations that have often been unrelated or disproportionate to the operating performance of these companies.

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, 2021, our executive officers, directors, current 5% or greater shareholders and affiliated entities, including entities affiliated with Caisse de Dépots et Consignations and entities affiliated with Baker Bros.

Advisors LP together beneficially own approximately 29.9% of our ordinary shares.

As of December 31, 2022, our executive officers, directors, current 5% or greater shareholders and affiliated entities, including entities affiliated with Baker Bros.

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.

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Our ADSs are currently listed on The Nasdaq Global Market.

In order to maintain that listing, we must satisfy certain continued listing requirements and standards, including, among others, minimum stockholders’

equity, minimum share price, director independence and independent committee requirements, and certain corporate governance requirements.

In order to maintain that listing, we must satisfy certain continued listing requirements and standards, including, among others, minimum stockholders’ equity, minimum share price, director independence and independent committee requirements, and certain corporate governance requirements.

There can be no assurances that we will be able to comply with the applicable listing standards.

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company that is lower than that required by Nasdaq, provided the company fulfill certain 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 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.

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.

We also posted a statement regarding our reliance on the exception from the Nasdaq Quorum Requirement on our website.

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Such a delisting would also likely have a negative effect on the price of our ADSs and would impair your ability to sell or purchase our ADSs when you wish to do so.

In the event of a delisting, we may take actions to restore our compliance with Nasdaq’s listing requirements, but we can provide no assurance that any such action taken by us would allow our ADSs to become listed again, stabilize the market price or improve the liquidity of our ADSs, prevent our ADSs from dropping below Nasdaq minimum bid price requirement or prevent future non-compliance with Nasdaq’s listing requirements.

non-compliance with Nasdaq’s listing requirements.

We do not currently intend to pay dividends on our securities and, consequently, your ability to achieve a return on your investment, if any, will depend on appreciation in the price of the ADSs.

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If holders of these shares sell, or indicate an intent to sell, substantial amounts of our securities in the public market, the trading price of our securities could decline significantly.

In June 2022, we completed a $194 million PIPE financing from the sale of (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.

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.

The Company also filed a registration statement with the SEC registering the resale of 11,593,170 ordinary shares by Entities affiliated with Baker Bros.

Advisors, issued in the PIPE financing, including ordinary shares underlying the pre-funded warrants.

As a result, subject to certain beneficial ownership limitations contained in the pre-funded warrants, these shares are freely tradable, without restriction, in the public market.

In addition, the exercise of some or all of the pre-funded warrants will increase the number of our outstanding ordinary shares, which may dilute the ownership percentage or voting power of our shareholders.

In addition, we have filed a registration statement with the SEC to register the ordinary shares that may be issued under our equity incentive plans.

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These provisions include the following:

under French law, a non-French resident as well as any French entity controlled by non-French residents may have to file a declaration for statistical purposes with the Banque de France

, within 20 working days following the date of certain direct foreign investments in us, including any purchase of our ADSs.

under French law, a non-French resident as well as any French entity controlled by non-French residents may have to file a declaration for statistical purposes with the Banque de France , within 20 working days following the date of certain direct foreign investments in us, including any purchase of our ADSs.

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 residents 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 a Member State of the European Union or in a state party to the EEA Agreement, including from the main French Stock Exchange, has the right to force out minority shareholders following a tender offer made to all shareholders;

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;

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In addition, you may not be able to cancel your ADSs and withdraw the underlying ordinary shares when you owe money for fees, taxes and similar charges and when it is necessary to prohibit withdrawals in order to comply with any laws or governmental regulations that apply to ADSs or to the withdrawal of ordinary shares or other deposited securities.

The biotechnology industry has been included in the list of critical technologies subject to foreign investment control procedure in France, which may limit the ability to certain non-French investors to participate in this or any other offering of our securities.

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 ).

In addition, French Decree ( Décret ) No.

2020-892 of July 22, 2020 as amended by French Decree No.

2020-1729 of December 28, 2020, French Decree No.

2021-1758 of December 22, 2021 and French Decree No.

2022-1622 of December 23, 2022 (i) lowers the scope of application of the foreign investment regime until December 31, 2023 to the crossing of the threshold of 10% of the voting rights of French companies whose shares are admitted to trading on a regulated market and (ii) subjects this new threshold to a fast track review procedure (filing of a simplified form, delay for the Minister to respond limited to 10 days, transaction deemed authorized in the absence of a response at the end of the delay).

If an investment in the Company requiring the prior authorization of the Minister of the Economy is made without such authorization having been granted, the Minister of the Economy may cancel the transaction or order (possibly under financial penalty) the investor concerned (i) to submit an application for authorization, (ii) to have the previous situation restored at its own expense or (iii) to modify the investment.

In addition, the Minister may impose undertakings and conditions on the investor (including regular reporting commitments).

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).

The application of these regulations is likely to constitute a potential barrier to investments made by investors located outside the European Economic Area and could therefore limit the Company’s access to sources of financing.

Investors may have difficulty enforcing civil liabilities against our company and directors and senior management.

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Under the U.S.

Internal Revenue Code of 1986, as amended, or Code, we will be a passive foreign investment company, or PFIC, for any taxable year in which, after the application of certain “look-through” rules with respect to subsidiaries, either (i) 75% or more of our gross income consists of “passive income,” or (ii) 50% or more of the average quarterly value of our assets, including cash, consists of assets that produce, or are held for the production of, “passive income.” Passive income generally includes interest, dividends, rents, certain non-active royalties and capital gains.

Whether we will be a PFIC in any year depends on the composition of our income and assets, and the relative fair market value of our assets from time to time, which we expect may vary substantially over time.

Based on the composition of our gross income and gross assets, we believe that we are likely not a PFIC for the taxable year ending December 31, 2021.

We are not able to provide any assurance as to whether we will, or will not be classified as a PFIC for the current taxable year ending December 31, 2022.

Because the determination of our PFIC status is based on complicated provisions of the Code and applicable administrative authorities, there can be no assurance that our conclusions concerning our PFIC status for the taxable year ending December 31, 2021 are accurate and will not be successfully challenged by applicable tax authorities, and we cannot provide any assurance regarding our PFIC status for the current taxable year or any future taxable year.

Internal Revenue Code of 1986, as amended, or the Code, we will be a passive foreign investment company, or PFIC, for any taxable year in which, after the application of certain “look-through” rules with respect to subsidiaries, either (i) 75% or more of our gross income consists of “passive income,” or (ii) 50% or more of the average quarterly value of our assets, including cash, consists of assets that produce, or are held for the production of, “passive income.” Passive income generally includes interest, dividends, rents, certain non-active royalties and capital gains.

Whether we will be a PFIC in any year depends on the composition of our income and the nature and composition of our assets, which we expect may vary substantially over time.

Based on the composition of our gross income and the nature and composition of our gross assets, we believe that we may have been a PFIC for the taxable year ending December 31, 2022.

Because the determination of our PFIC status is based on complicated provisions of the Code and applicable administrative authorities, there can be no assurance that our conclusions concerning our PFIC status for the taxable year ending December 31, 2022 are correct and will not be successfully challenged by applicable tax authorities, and we cannot provide any assurance regarding our PFIC status for the current taxable year or any future taxable year.

If you are a U.S.

Holder (as defined below) during the taxable year when the Company is considered a PFIC, then you may be subject to adverse tax consequences if a mark-to-market election or a qualified electing fund, or QEF, election has not been made with respect to its ADSs.

Holder may incur significant additional U.S.

federal income taxes on income resulting from certain distributions on, or any gain from the disposition of, such shares including ADSs, as such income generally would be allocated over the U.S.

Holder’s holding period for its shares.

The amount allocated to the current taxable year ( i.e.

, the year in which the distribution occurs or the gain is recognized) and any year prior to the first taxable year in which we are a PFIC would be subject to tax as

ordinary income earned in the current year, and all other amounts would be subject to tax at the highest rates of U.S.

federal income taxation in effect for such years, with an interest charge then imposed on the resulting taxes in respect of such income.

Furthermore, if we are a PFIC for any taxable year during which the U.S.

Holder holds ADSs, dividends paid by us would not be eligible for preferential individual rates of U.S.

federal income tax.

In addition, U.S.

Holders that own an interest in a PFIC are required to comply with certain reporting requirements.

Holder may in certain circumstances mitigate the adverse tax consequences of the PFIC rules by filing an election to treat the PFIC as a QEF, or, if shares of the PFIC are “marketable stock” for purposes of the PFIC rules, by making a mark-to-market election with respect to the shares of the PFIC.

holder (as defined below under “Material Income Tax Considerations—Certain Material U.S.

Federal Income Tax Considerations”) during a taxable year when the Company is considered a PFIC, then regardless of whether we continue to be characterized as a PFIC in subsequent taxable years, you may suffer adverse tax consequences, including the treatment of gains realized on the sale of our ADSs as ordinary income, rather than as capital gain, the inapplicability of the preferential rate that otherwise would be applicable to dividends received on our ADSs by individual U.S.

Holders, the addition of interest charges to the tax on such gains and certain distributions, and additional reporting requirements.

holder in certain circumstances may mitigate the adverse tax consequences of the PFIC rules by filing an election to treat the PFIC as a QEF, or, if shares of the PFIC are “marketable stock” for purposes of the PFIC rules, by making a mark-to-market election with respect to the shares of the PFIC.

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, provided that there is no assurance that such information will be provided.

holders the information required to make a QEF election;

for the taxable year ending December 31, 2021, we have provided that information.

However, there is no assurance that such information will be provided in future taxable years, and prospective investors should not assume that a QEF election will be available.

Holders are strongly urged to consult with, and rely solely upon, their personal tax advisors regarding the implications of the tax provisions applicable to U.S.

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Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1A. Risk Factors