GeNeuro SA – 2021 Universal Registration Document

GENERAL OBSERVATIONS

Unless otherwise indicated, in this universal registration document (the “Universal Registration Document”) the

terms “Company” or “GeNeuro” mean GeNeuro SA and the term “Group” means the Company and its subsidiaries

GeNeuro Innovation SAS (“GeNeuro Innovation”), in France, and, until its liquidation in Q2 2021, GeNeuro

Australia Pty Ltd (“GeNeuro Australia”), in Australia.

This Universal Registration Document was prepared pursuant to Annex 1 and Annex 2 of the delegated regulation

(EU) 2019/980 of the Commission of 14 March 2019 which complements Regulation (EU) 2017/2019 of the

European Parliament and Counsel and, pursuant to article 19 of the Regulation (EU) 2017/1129, incorporates by

reference (i) the Company’s consolidated financial statements for the year ended December 31, 2019, prepared in

accordance with IFRS, and the auditors’ report related thereto presented in section 18.3 of the Universal

Registration Document filed with the AMF on April 30, 2020 and (ii) the Company’s consolidated financial

statements for the year ended December 31, 2020, prepared in accordance with IFRS, and the auditors’ report

related thereto presented in section 18.3 of the Universal Registration Document filed with the AMF on April 30,

2021.

This Universal Registration Document contains statements about the Group’s objectives. These statements are

sometimes identified by the use of the future tense, the conditional tense, and expressions with forward-looking

character, such as “think,” “has as an objective,” “expects,” “intends,” “should,” “with the ambition of,” “consider,”

“believe,” “wish,” “could,” etc. This information is based on data, assumptions, and estimates considered reasonable

by the Company. They may change or be changed because of uncertainties related to any business as well as to

the economic, financial, competitive and regulatory environment.

Furthermore, the achievement of the Group’s objectives assumes the success of its strategy, which is set forth in

Section 5.1.2 of the Universal Registration Document. The Company can make no commitment or give any

assurance that the objectives set forth in this Universal Registration Document will be achieved.

Investors are urged to give consideration to the risk factors set forth in Chapter 3 “Risk Factors” of this Universal

Registration Document before making their investment decision. The occurrence of such risks could have a negative

effect on the Group’s business, financial condition, results of operations, or prospects. Furthermore, other risks, not

presently identified or not considered material by the Company, could have the same negative effect, and investors

could lose all or part of their investment.

This Universal Registration Document also contains information about the markets in which the Group competes,

some of which information was obtained from sources external to the Company. Unless otherwise indicated, the

information relating to the markets in which the Group competes or its competitive position contained in this

Universal Registration Document comes from the Company’s internal estimates. These internal estimates are

based on reports of analysts, specialized studies, industry publications, any and all information published by market

survey companies, and public and governmental sources, as well as internal knowledge of the market by the

Company. Even though such information is considered reliable, it has not been independently verified by the

Company. Furthermore, in light of the very rapid changes occurring in France, in the world, and in the industry in

which the Group competes, it is possible that such information may prove erroneous or not be up-to-date. The

Group’s business, accordingly, could evolve in a different way from the one described in this Universal Registration

Document. The Company has not committed or agreed to publish any update of the information contained herein,

except in connection with any legal or regulatory obligation that may apply to it.

A glossary that contains definitions of certain technical terms used in this Universal Registration Document, as well

as an index of abbreviations used, are set forth in Appendix of this Universal Registration Document.

A reconciliation table with the Annual Financial Report is located at the end of this Universal Registration Document.

This Universal Registration Document has been prepared on the basis of the Company’s annual consolidated

financial statements for the financial years ending December 31, 2020 and 2021.

GeNeuro SA – 2021 Universal Registration Document

CHAPTER 1.

PERSONS RESPONSIBLE FOR THIS UNIVERSAL REGISTRATION DOCUMENT

1.1 Person Responsible For The Universal Registration Document

Mr. Jesús Martin-Garcia, Chairman of the Board of Directors and Chief Executive Officer of GeNeuro.

1.2 Certificate Of The Person Responsible For The Universal Registration Document

I certify that, to my knowledge, the information contained in this Universal Registration Document is in accordance

with the facts and contains no omission likely to affect its import.

I certify that, to my knowledge, the financial statements of GeNeuro have been prepared in accordance with

applicable accounting standards and give a fair view of the assets, liabilities, financial position and results of the

Company and all the subsidiaries included in the scope of consolidation, and that the management report of the

board of directors, as referenced in the cross reference list included on page 241 gives a true and fair view of the

business trends, results and financial position of the Company and its subsidiaries included in the scope of

consolidation and describes the main risks and uncertainties with which they have to contend.

Mr. Jesús Martin-Garcia, Chairman of the Board of Directors and Chief Executive Officer of GeNeuro.

1.3 Information From Third Parties, Experts’ Statements or Reports

Certain market information set forth in CHAPTER 5 , “Description of the Group’s Business” of this Universal

Registration Document, come from third-party sources. The Company certifies that such information has been

faithfully reproduced and that, to the Company’s knowledge, on the basis of data published or provided by such

sources, no fact has been omitted that would make the information reproduced inaccurate or misleading.

1.4 Declaration relating to the registration document

Not applicable.

1.5 Person Responsible For The Financial Information

Mr. Miguel Payró

Group Chief Financial Officer

3 chemin du Pré-Fleuri, CH-1228 Plan-les-Ouates, Switzerland

Telephone:

+41 22 552 4800

info@geneuro.com

www.geneuro.com

1.6 Indicative Timetable for Financial Communication

April 4, 2022

2021 annual results

April 15, 2022

May 31, 2022

Q1 2022 cash position

Annual general meeting of shareholders

Q2 2022 cash position

1H 2022 results

July 21, 2022

September 29, 2022

October 17, 2022

Q3 2022 cash position

* This timetable is indicative and the Company reserves the right to amend the above-mentioned dates should it

deem it necessary to do so.

GeNeuro SA – 2021 Universal Registration Document

CHAPTER 3.

RISK FACTORS

The Company operates in a changing environment that involves risks, some of which are out of its control.

Investors are advised to take into consideration all the information contained in this Universal Registration

Document, including the risk factors set forth in this chapter. Pursuant to Article 16 of Regulation (EU)

2017/1129 and of Delegated Regulation (EU) 209/980, this chapter only presents the risks that the Company

believes, as of the date of filing of this Universal Registration Document, in the event they should occur,

might have a material adverse effect on the Group’s business and operations, its results of operations, its

financial position, earnings, prospects or ability to hit its targets.

In order to identify and assess such risks, the Company has mapped the risks associated to its activity and

has grouped them into five categories below, it being stipulated that within each category and sub-

category, risk factors are presented by order of decreasing importance with an evaluation of their

probability (high, medium, low), negative impact (high, medium, low), and the net level of criticality,

estimated by combining for each risk its probability of occurrence and its negative impact, as assessed by

the Company as at the date on which the Registration Document was filed, together with taking into account

the potential actions and preventive measures undertaken by the Company at that date. The occurrence of

new events, both internal and external to the Company, may however alter this order of importance in the

future.

Impact of Russia-Ukraine war

The war in Ukraine launched by Russia on February 24, 2022 has significant economic and financial consequences

at the global level. Sanctions against Russia are likely to have significant implications for companies that do

business with or have a business relationship with Russia. Such sanctions and war may also have an impact for

companies conducting clinical trials in Russia or Ukraine. As at December 31, 2021, and at of the date of this

Universal Registration Document, the Company does not do business with or have a business relationship with

Russia nor conducts trials in Russia or Ukraine. However, the Company’s operations may be impacted in the future

by the direct or indirect consequences of the conflict, which cannot be accurately quantified at present. The

Company may in particular be exposed in the future to an increase in the costs associated with the clinical trials

entrusted to its CROs. As of the date of this Registration Document, the Company has not however observed an

increase in costs due to this conflict.

Impact of COVID-19 Pandemic

In addition to these risks and in the context of the COVID-19 outbreak, which was declared a “pandemic” by the

World Health Organization (WHO) on March 12, 2020, the Company has undertaken a full review of the impact of

the outbreak on its business and has strictly followed the recommendations issued by the World Health Organization

and by local governments in terms of health & hygiene and organizational standards, in order to ensure the health

and safety of its staff and their families.

Whilst the Company’s 40-patient Phase II Karolinska Trial in multiple sclerosis (“MS”) with temelimab, its main

product, saw its launch postponed by three months to prioritize healthcare resources behind the fight of COVID-19

and to reduce the risk for MS patients, the Company announced the completion of recruitment on February 18,

2021 and the last patient’s last visit on January 27, 2022, and announced top-line results from this study on March

21, 2022. Whilst the impact of COVID-19 has no immediate bearing on the Company’s financial situation over the

next 12 months, should the pandemic continue this could have a material adverse effect on the Company’s

business, results of operations, financial condition and cash flows.

For more information on the impact of the COVID-19 pandemic on the Company’s strategy, please refer to sections

3.1.3 and 5.3.1 of this Universal Registration Document.

Sec-

tion

3.1

Proba- Negative Net level of

Risks Factors

bility

impact

criticality

Risks Related To The Development and Potential Future

Commercialization of the Group’s Product Candidates

3.1.1 GeNeuro has developed a new approach, the therapeutic benefit of which High

has not yet been demonstrated, that is not based on confirmed pathways

such as the immunomodulation and immunosuppression approaches

used by existing therapies for the treatment of autoimmune diseases.

3.1.2 The Company’s products, including its most advanced product candidate, High

temelimab, may never be approved for marketing due to regulatory

reasons

High

GeNeuro SA – 2021 Universal Registration Document

Sec-

tion

Proba- Negative Net level of

Risks Factors

bility

impact

criticality

3.1.3 The Company’s product candidates may never be approved for High

High

marketing due to operational reasons.

3.1.4 The Company may not be competitive in its market.

3.1.5 The Company has limited visibility on its future prospects and financial Medium

results.

High

3.1.6 The uncertainty about reimbursement rates and measures to reform Medium

healthcare systems could delay or compromise acceptance of products

by the market.

3.1.7 Other clinical applications of temelimab for conditions such as T1D are High

based solely on pre-clinical work or on limited clinical data, and the

Company may never succeed in developing and marketing effective

treatments based on such technology.

High

Medium

3.2

Risks Related To The Company’s Financial Situation and Capital

Needs

3.2.1 The €17.5 million gross proceeds of the capital increase completed in High

January 2020 are expected to provide the Company with the means to

continue its development until Q2 2022 but the Company may not

succeed in obtaining additional funds needed to continue its clinical

development in the future.

High

3.2.2 The Company should continue to sustain operating losses (following High

losses of €6.4 million and €7.5 million, respectively, in 2021 and 2020)

in relation to its research and development activities.

3.2.3 The Group benefits from Research Tax Credits from the French Medium

government which regime may be challenged or modified in the future.

High

Low

High

Low

3.2.4 The Company could be unable to carry tax losses forward.

3.2.5 Full exercise of all securities carrying the right to acquire shares granted Medium

Medium

Low

and outstanding would result in a dilution of existing shareholders.

3.2.6 Exchange Rate Risk.

3.3 Risks Related To The Company, Its Operations and Organization

Medium

Low

3.3.1 The Company is dependent on its key employees and, as such, could Medium

fail to continue attracting and retaining its key employees and scientific

advisors.

High

Medium

3.3.2 The Company faces the risk of liability linked to its products or operations Medium

and it may not be able to obtain adequate insurance coverage at an

acceptable cost.

High

Low

Medium

Low

3.3.3 Shareholders might be unable to achieve a control premium in the event

of a change of control of the Company based on the fact that French and

Swiss regulations concerning mandatory public takeover offers are not

applicable.

Low

3.4

Risks Related To The Company’s Dependency on Third Parties

3.4.1 The Company does not have manufacturing capabilities and is exposed Medium

to the risks associated with relying on third party manufacturers for its

most advanced product candidate temelimab and its other products.

High

Medium

3.4.2 The Company does not have experience in the areas of sales, marketing

and distribution and may be required to rely on third parties and/or

mobilize new internal resources for this purpose.

High

Medium

3.4.3 The Company relies on external scientific collaborators.

Medium Medium

Medium

3.5

Risks Relating To The Company’s Intellectual Property Rights

3.5.1 If the Company is unable to maintain or protect its intellectual property Medium

rights, it could lose its competitive advantage and be unable to operate

profitably.

3.5.2 The Company’s products and technologies could infringe or be claimed Medium

to infringe patents and patent applications held or controlled by third

parties.

3.5.3 If the Company does not comply with its obligations under the license Medium

agreement with bioMérieux, it could lose rights that are very important

for its business.

3.5.4 The Company’s business could be affected if it is unable to protect the Medium

confidentiality of its information and know-how.

High

Medium

GeNeuro SA – 2021 Universal Registration Document

3.1 Risks Related To The Development and Potential Future Commercialization of The

Group’s Product Candidates

3.1.1 GeNeuro has developed a new approach, the therapeutic benefit of which has not yet been

demonstrated, that is not based on confirmed pathways such as the immunomodulation and

immunosuppression approaches used by existing therapies for the treatment of autoimmune diseases.

The Company has developed a new approach to the treatment of MS, which differentiates itself from therapies

being sold on the date hereof.

The Company is exploring a new medical path that involves HERV genes that constitute approximately 8% of the

human genome. The capacity for the abnormal expression of various elements of a HERV of the W family (“HERV-

W”) has been detected in chronic diseases like MS. The Company seeks to develop, on the basis of this finding, a

treatment designed to block the deleterious properties of a protein, W-ENV, which is encoded by genes of the

HERV-W family. Recent publications have demonstrated that W-ENV may directly inhibit remyelination and that

axonal injury in MS can be significantly driven by W-ENV through activation of microglia and that this contributes to

neurodegeneration, particularly in progressive forms of MS. Top-line results of ProTEct-MS, the Company’s Phase

2 clinical trial in MS conducted at the Karolinska Institutet in Stockholm, Sweden, have showed that the primary

endpoint of the study was met, with results confirming the excellent safety profile and tolerability of higher doses of

temelimab administered concomitantly with a high-efficacy anti-inflammatory drug; in addition, efficacy data,

obtained in this patient group already effectively treated against inflammation, showed that temelimab, an antibody

that neutralizes W-ENV, has a favorable impact on key MRI measures of neurodegeneration; the observed effect

sizes in this new patient population were consistent with the ones shown in the previous CHANGE-MS and ANGEL-

MS studies.

Publications from April 2021 show that W-ENV can be expressed by SARS-CoV-2 and that it is present in the blood

of COVID-19 patients, with a correlation between the level of its expression and the severity of the evolution of the

disease. Furthermore, data presented in July 2021 shows that W-ENV expression can also be triggered in the brain,

specifically in microglial cells that are also innate immune cells residing in the brain. The expression of W-ENV in

this organ had previously only been observed in the context of chronic neurological diseases, such as multiple

sclerosis or certain inflammatory forms of schizophrenia, where it fuels local inflammation and neurodegenerative

mechanisms. In the aftermath of COVID-19, the analysis of preliminary data from patients with post-COVID

depressive and/or cognitive disorders now also shows the persistence of W-ENV in the blood in significant numbers

of patients, suggesting that the neuropsychiatric symptomatology seen in “post-COVID” patients may be due to

activation of W-ENV expression by SARS-CoV-2 in these individuals, and to its persistence long after the acute

COVID phase. These data, presented at the first “Neuro Sciences Psychiatry and Neurology Days” held in Paris,

France, on July 1-2, 2021 provide a biologic rationale explaining why so many COVID-19 patients develop long-

term neurological and psychiatric symptoms. This could open the door for a therapeutic intervention with temelimab

targeting W-ENV.

As of the filing date of this Universal Registration Document, there is no treatment that targets endogenous retroviral

genes approved for sale by the competent authorities, and such a treatment intended to block a protein expressed

by a HERV is, therefore, unproven.

The Company’s Phase IIb clinical trials in the MS indication have shown that temelimab has only modest effects on

neuroinflammation in the “active inflammatory patients” population as a monotherapy, but also that temelimab has

positive impacts on key MRI measures associated with disease progression; as a result, GeNeuro is now focusing

on neurodegeneration and disease progression, most likely with temelimab as a combination therapy together with

marketed immunomodulatory drugs addressing neuroinflammation, rather than as a monotherapy for “non-active”

progressive patients. Whilst the Company’s latest clinical trial, ProTEct-MS, enrolled “non-active” progressive

patients, it is important to note that neurodegeneration, and disease progression as a biological feature, are present

from the onset of disease, i.e. before patients are categorized as being in progressive MS. This means that the

indication of temelimab is not restricted to the latter stage of disease, but may include all forms of MS.

Accordingly, the prospects for the development and profitability of the Company’s most advanced product

candidate, temelimab, for MS or other indications, its safety, its effectiveness, and its acceptance by patients,

prescribers, and paying agencies, are uncertain. The positive results observed for temelimab for MS in connection

with Phase I, on the one hand, and Phases IIa and IIb, on the other hand, and more generally, those relating to

existing or future products in the Company’s portfolio or based on its technology at the time of the research or

preclinical phase, may not be confirmed by future trial phases. Such a situation could have a very material adverse

impact on the Company’s business, results, financial situation, and prospects.

GeNeuro SA – 2021 Universal Registration Document

3.1.2 The Company’s products, including its most advanced product candidate, temelimab, may never be

approved for marketing due to regulatory reasons.

The Company is subject to regulations that are numerous and evolving and it may not be able to obtain the

necessary approvals to market and sell its products, including its product candidate at the most advanced stage of

development, temelimab. To obtain a product license for its candidate products, the Company must show, through

long, numerous and very expensive clinical trials with uncertain outcomes, that the use of the candidate products

is without danger and is effective in humans. Clinical trials are subject to supervision by regulatory authorities as

well as by ethics committees, in order to protect the persons participating in the medical research. If the Company

does not meet its development calendar (please see Section 5 of this Universal Registration Document), or if it is

unable to conduct the expected clinical trials successfully within applicable time limits, its business and operations

could be materially and adversely affected.

The Company’s ability to obtain product licenses for its products will depend on several factors, including, but not

limited to:

•

the possibility of pursuing the development of those of its products presently in early clinical trials, or presently

in pre-clinical development to a clinical stage;

its ability, or that of its partners, to conduct clinical trials successfully and within relevant time periods without

having to devote significantly greater resources than initially expected;

•

its clinical trials showing the efficacy and safety of its products;

its products being approved for the indication they are intended to treat, or for any indication of any kind; and

an announcement by its competitors of more promising clinical results with their own products, which makes

the Company’s economic equation unfavorable.

Traditionally in the biotechnology and pharmaceutical industries, it often happens that favorable results of pre-

clinical studies and Phase I/II clinical trials are not confirmed in later stages of clinical development. Regulatory

authorities in various countries in which the Company intends to market its products could block initiation of clinical

trials, or the pursuit of clinical developments, if the proposed clinical trials do not meet applicable regulatory

standards. Such authorities could likewise interpret results differently from the Company and, in any event, request

additional tests, on a discretionary basis (relating, among other things, to the study protocols, the characteristics

and number of patients, the length of treatment, the analytical methods, the preclinical safety, and post-treatment

follow-up), or impose additional or unexpected requirements at the time of such trials. Furthermore, the Company

might decide, or might be required by regulatory agencies, to suspend or terminate clinical trials, if new evidence

suggests that patients are exposed to unexpected risks. Deaths or other adverse events could occur during a clinical

trial, because of medical problems both linked and not linked to the treatments administered, forcing the Company

to delay or interrupt the trial. Also, on the basis of the trial’s results, the Company could decide to abandon

development projects that were initially identified as promising. Finally, products already approved could turn out to

be unsafe and then be withdrawn from the market, or they could produce different effects from those initially

expected, which could, in turn, limit or prevent them having any commercial use. The occurrence of all or some of

these events could have material adverse effects on the Company’s business, results, and prospects.

As of the date hereof, none of the Company’s products, including its most advanced product candidate, temelimab

for MS, has received a marketing authorization from any regulatory authority. The Company cannot be sure that it

will receive the necessary approvals to market and sell any of its products. The products may be subject to very

stringent laws, and regulatory requirements that are uncertain and subject to change and amendment (for a

summary presentation of such laws and regulations in the United States and Europe, please see Chapter 9

“Regulatory Environment”) of this Universal Registration Document). The U.S. Food and Drug Administration

(“FDA”) and the European Medicines Agency (the “EMA”) as well as their counterparts in other countries regulate,

among other things, research and development, pre-clinical tests, clinical trials, manufacturing, safety, efficacy,

records retention, labeling, and the marketing, sale, and distribution of therapeutic products. In particular, without

the FDA’s approval, it would be impossible for the Company to access the U.S. market, which is the largest

pharmaceutical market in the world, particularly for the therapeutic areas targeted by the Company (MS, COVID-

19, Amyotrophic Lateral Sclerosis (“ALS”), Type1 Diabetes (“T1D”), etc.).

These regulatory steps are costly; they may take several years; and their outcomes are unpredictable. The data

from pre-clinical and clinical developments may give rise to different interpretations, which could delay obtaining or

restrict the scope of regulatory approval. The requirements of the regulatory process vary greatly from one country

to another, so that the Company or its strategic partners may not be able to obtain approval on a timely basis in

each relevant country. Since the Company’s products are based on new, constantly changing technologies and

have not been tested on an in-depth basis in humans, the applicable regulatory requirements remain uncertain and

could be subject to significant differences of interpretation and changes. Changes in laws and regulations during

the development of a product and its regulatory review could cause delays in or the denial of approval.

GeNeuro SA – 2021 Universal Registration Document

In the United States, in Europe, and in other countries, applicable laws and regulations and changes to them could:

•

delay and/or significantly increase the cost of developing, testing, manufacturing, and marketing the

Company’s products;

•

limit the indications for which it might be authorized to market and sell its products;

impose new, stricter requirements, suspend approval of the Company’s products, or require the Company to

stop the clinical trials it is conducting or stop the marketing and sales of the products (for example, if

unexpected results are obtained during clinical trials by other researchers of products similar to those of the

Company); or

•

impose restrictive labeling.

If the Company does not comply with the laws and regulations applicable to its business and operations, it could

incur sanctions or penalties, which could include refusals to authorize pending applications, product recalls,

restrictions on sales, or the temporary or permanent suspension of its operations as well as civil and criminal

proceedings.

The Company has already completed for temelimab, its product candidate at the most advanced stage of

development, three clinical Phase I trials¹to define the pharmacological, immunogenic, and safe use on healthy

volunteers. The results of these trials have been published in scientific journals (Hartung et al.; MSJ2021) and are

considered positive regarding temelimab’s safety, tolerability and efficacy.

The Company has also completed four Phase II trials on a patient population having MS and one Phase II trial on

a patient population having T1D:

•

a Phase IIa clinical trial for MS², intended principally to show temelimab’s tolerance over a period of one year

by the injection of potentially therapeutic doses and, secondarily, to take initial measurements on the clinical

evolution of treated patients; and

•

a 1-year Phase IIb clinical trial (CHANGE-MS³) for MS in patients with the remitting relapsing form of MS

(RRMS), with a primary endpoint evaluating the efficacy of repeated doses of temelimab versus placebo in

patients based on the cumulative number of Gadolinium-enhancing (“Gd+”) T1 lesions on brain MRIs and

with secondary endpoints to evaluate measures of MRI markers associated with neuroprotection, notably

brain atrophy, hypointense T1 lesions (“black holes”) and magnetization transfer ratio (“MTR”), considered to

be an indirect measure of the integrity of myelin; and

•

a 1-year Phase II extension study of CHANGE-MS (ANGEL-MS⁴) of the above Phase IIb clinical trial, which

allowed patients who took part in the Phase IIb study to benefit from two additional years of treatment;

following the decision from the Company’s former development partner, in September 2018, not to exercise

its option for a license on temelimab, this extension study underwent an early termination and topline results

were presented on March 12, 2019; and

a Phase IIa clinical trial (ProTEct-MS) for MS in patients treated with rituximab and in whom disability was

worsening in the absence of relapses. This 1-year clinical trial enrolled patients with confirmed disability

progression without relapses, following previous treatment with the anti-CD20 drug rituximab, a highly potent

and efficacious drug against acute disease activity (relapses and brain lesion formation). All patients in the

trial received rituximab in the eight weeks preceding their enrollment in ProTEct-MS. The primary endpoint

for the study was safety of temelimab in combination with rituximab, and secondary and exploratory endpoints

were designed to assess efficacy measures based on the latest imaging and biofluid markers associated with

disease progression. Top-line results were presented on March 21, 2022 and showed that the primary

endpoint of the ProTEct-MS study was met, with results confirming the excellent safety profile and tolerability

of higher doses of temelimab administered concomitantly with a high-efficacy anti-inflammatory drug; in

addition, efficacy data, obtained in this patient group already effectively treated against inflammation, showed

that temelimab has a favorable impact on key MRI measures of neurodegeneration; the observed effect sizes

in this new patient population were consistent with the ones shown in the previous CHANGE-MS and ANGEL-

MS studies;

•

In addition, the Company has completed a Phase IIa clinical trial for T1D in adult patients, which has met its

primary endpoint of safety at six months, and whose full 12-month results were announced in May 2019.

The Company has also announced in September 2021 the launch of an extension study, in order to provide patients

having completed their one-year ProTEct-MS treatment duration the possibility of continued treatment with

¹“Preclinical” and “clinical” phases are defined in the Appendix.

²Source: Derfuss T et al Mult Scler. 2015 Jun;21(7):885-93.

³Source: Hartung et al., Efficacy and safety of temelimab in multiple sclerosis: Results of a randomized phase 2b and extension

study, Multiple Sclerosis Journal, July 2021

⁴Source: Hartung et al. ibid

GeNeuro SA – 2021 Universal Registration Document

temelimab. However, the current lot of temelimab used for this extension will expire at the end of April 2022. Due

to the worldwide shortage in the supply of culture media for antibody manufacturing during the COVID-19 pandemic,

delivery of the new batch of temelimab has been delayed until the summer. As a result, GeNeuro has decided to

close at the end of April 2022 this extension study, which was not designed to generate additional MRI data.

The use of temelimab for MS requires additional clinical development to be completed, including Phase III clinical

trials. Accordingly, if the Company does not receive approval of temelimab for the treatment of MS, its financial

condition, results of operations, and prospects will be significantly and adversely affected.

3.1.3 The Company’s product candidates may never be approved for marketing due to operational reasons.

The Company’s clinical trials, especially for its leading product candidate, temelimab, could be delayed or not occur

in a satisfactory manner.

The Company’s ability to conduct clinical trials successfully depends on many factors, especially on the pace of

patient recruitment, the size of the eligible patient population, the type of clinical protocol, the proximity of patients

to clinical sites, eligibility criteria, possible secondary effects, and competition with other clinical trials conducted on

product candidates developed by competing companies with, among other things, financial resources that may be

greater than the Company’s.

In general, the Company could encounter difficulties in recruiting and retaining patients to participate in future clinical

trials of its products, in particular for its most advanced product candidate for MS and T1D, temelimab. The strict

criteria for inclusion in the trials could also make recruitment of patients difficult. Once recruited, the patients

participating in such trials could suspend or terminate their participation at any time without cause, or might be

unable to continue participating in a trial if medical, or other, emergencies (such, for example as the current COVID-

19 pandemic) lead governments to impose quarantines or enforced isolation or require existing medical human

resources or medical amenities to be solely dedicated to the treatment of such emergencies. Delays in patient

recruitment could also increase the costs, delay, or even cause the cancellation of clinical trials (including in relation

to the potential need to adjust existing protocols and have such adjustments be agreed by the regulators). Finally,

if too many patients terminate their participation in a clinical trial, the analysis of the results of such trial could lack

sufficient statistical significance.

Furthermore, large-scale clinical trials could lead to complexity in the management and supply of inventories of the

product candidate temelimab. Logistical difficulties and errors in storing and shipping products, and/or poor

management of inventories and their supply could cause delays in the completion of the trials.

Likewise, clinical trials designed and coordinated by the Company are conducted by medical and hospital centers

and companies that specialize in the organization of trials (a contract research organization or “CRO”) and the

quality of their work (the selection of populations, base-line measurements, compliance with protocols, doses, the

number of administrations, intermediate delays and the collection of data) is determinant in the analysis and

precision of results. In addition, because Phase II and Phase III clinical trials are typically conducted in numerous

centers located in multiple countries, the Company cannot rule out heterogeneity and errors in the performance of

such centers, which could impact the precision of the results.

Furthermore, the Company has limited experience in conducting clinical trials at multiple centers and has turned or

will turn, now and in the future, to third parties to assist it in supervising and monitoring its trials. A breach or failure

by one of such third parties or CROs in performing their task or their failure to comply with applicable regulatory

standards could cause delays or even the premature termination of the trials.

3.1.4 The Company may not be competitive in its market

The market for MS treatments for which temelimab is intended, as well as the markets for which its other products

are intended, are characterized by rapid technological change, the predominance of protected products, and intense

competition. Many organizations, including pharmaceutical and biotechnology companies, academic institutions,

and other research entities, are actively engaged in the discovery, research, development, and marketing and sale

of products intended to treat MS. If the Company were to obtain a marketing license for temelimab, it might compete

with other presently prescribed therapies and/or those under development. Whilst there are today in MS no

approved drugs that address disease progression (as opposed to reducing the number of inflammatory relapses,

which is the area for which the existing immunotherapies such as immunomodulators and immunosuppressors

drugs have been approved), it is possible that new drugs under development could prove effective against

neurodegeneration and disease progression and thus be direct and strong competitors to temelimab.

A great number of companies developing immunomodulators or immuno-suppressors for MS, when compared with

GeNeuro, have much greater resources and experience in management, manufacturing, marketing and sales, and

research. In particular, major pharmaceutical companies like Bayer, Biogen, Bristol-Myers Squibb, Johnson &

Johnson, Merck KGaA, Novartis, Roche Sanofi and Teva, which market and sell medications for MS, have much

GeNeuro SA – 2021 Universal Registration Document

greater experience than GeNeuro in conducting clinical trials and obtaining regulatory approvals. All such

companies could also compete with the Company to acquire rights to promising antibodies as well as other

complementary technologies. The Company can give no assurance that its products:

•

will be granted regulatory approval, protected by patents, or marketed sooner than those of its competitors;

will remain competitive against other products developed by its competitors that are safer, more effective, or

less costly;

•

will be competitive against products of companies that might be more efficient in their production, marketing

and sales;

•

will be a commercial success; or

will not be made obsolete or unprofitable by technological progress or other therapies developed by its

competitors.

If the Company succeeds in obtaining regulatory approval to introduce products based on its technology, it will also

need time to gain the support of the medical community, including healthcare providers, patients, and third-party

payors. The degree of acceptance by the market will depend on many factors, including:

•

the safety and efficacy of its therapeutic products, as demonstrated during clinical trials;

the existence of undesirable side effects;

ease of administration;

the success of its marketing, sales, and public relations strategy;

the availability of alternative treatments;

pricing;

the reimbursement policies of governments and other third parties;

the effective adoption and implementation of a publication strategy; and

obtaining the support of recognized external opinion leaders.

Even if temelimab for MS is approved for marketing, the market targeted by the Company could turn out to be less

significant than previously thought. The revenues that the Company may receive in connection with the marketing

and sale of temelimab may be limited by the number of patients with MS, by the categories of patients who respond

well to treatment, by the perception of health providers as to the therapeutic benefit, by its ability to achieve

appropriate pricing and reimbursement levels, and by the impact of competition.

If the Company does not market and sell temelimab successfully, its revenues could not materialize and / or

decrease as a result, and it could find itself unable to finance the development and marketing of other products for

other indications.

3.1.5 The Company has limited visibility on its future prospects and financial results.

GeNeuro has a limited operating history, which does not allow it to estimate its prospects and future revenues. The

Company’s operations have been so far limited to developing a humanized monoclonal antibody technology aimed

at a pathogenic protein expressed by a HERV and, on the basis of such technology, to conduct, with the assistance

of CROs, pre-clinical and clinical trials for the purpose of developing, marketing and selling therapeutic solutions.

Notwithstanding the experience and abilities of its management and scientific team, the Company has not yet shown

an ability to overcome the high number of risks and uncertainties that are frequently encountered by

biopharmaceutical companies in a rapidly evolving, highly uncertain and speculative industry. The Company’s ability

to evaluate its future results or commercial prospects with precision, similarly, is more limited than if it had a long

operating history or products that had already received marketing approval.

As a result, the likelihood of the Company’s success must be evaluated in light of the numerous potential challenges

and contingencies that are faced, at an early stage, by a company operating in the business of developing

medications, most of which are beyond its control. In light of its development schedule and, assuming the receipt

of relevant regulatory authorizations and the commercialization and marketing of its product candidate, GeNeuro

estimates as of the date of this Universal Registration Document that the potential sale of its most advanced product

candidate, temelimab, could commence between 2025 and 2027 for MS and/or post-COVID. This timing is however

dependent on the success of the Phase III trial, or possibly of a Phase II/III trial that could be registration enabling

GeNeuro SA – 2021 Universal Registration Document

subject to its results, the absence of any event or setback delaying the proper conduct of the trials, and the absence

of other events which the Company is currently unable to identify or anticipate.

3.1.6 The uncertainty about reimbursement rates and measures to reform healthcare systems could delay or

compromise acceptance of products by the market.

The uncertainty about reimbursement rates and measures to reform healthcare systems could delay or compromise

acceptance of products by the market.

If the Company succeeds in marketing and selling the products developed in collaboration with partners, or by itself,

their acceptance in the market will depend, in part, on the rate at which government health funds and private insurers

reimburse them. Primary insurance health funds and other third-party payors often attempt to limit the cost of care

by restricting or refusing to cover costly products and therapies. At present there are several immunomodulating

products for the treatment of MS, but none specifically targets a causal factor or the progression of the illness, so

that there is little or no experience relating to potential payments for such a treatment by insurance providers.

In some foreign markets, the price of prescription pharmaceuticals is subject to control by the government. The

Company’s ability to market and sell its products successfully will depend, in part, on the establishment by

governmental authorities, private insurers, and other agencies in the United States and Europe of a sufficient

reimbursement rate for its products and related treatments. In addition, the determination of the price and the

reimbursement rate for the Company’s products could be influenced by an announcement by competitors of more

promising clinical results than those of the Company’s products. Such a situation could have an adverse effect on

the conditions for setting the price and the reimbursement rate of products that could lose their competitive

advantage over other competing products. Third-party payors are questioning the price of therapeutic products and

medical services more and more frequently. Cost control measures that healthcare service providers and

reimbursement agencies adopt and healthcare system reforms could adversely affect the Company’s operating

results. Also, as a result of the COVID-19 Pandemic, it may be expected that healthcare will be an important public

policy subject of focus and that associated increase of healthcare spending will be more carefully monitored. The

Company could thus fail to obtain satisfactory reimbursement for its products, which could impede their acceptance

by the market, in which case the Company would be unable to earn a sufficient return on its research and

development investments.

The Company’s relations with clients and third-party payors are subject to U.S. anti-corruption (anti-kickback), anti-

fraud, and anti-abuse laws or other laws and regulations relating to healthcare which could expose it to civil penalties

and sanctions, damages, and interest, injury to its reputation, and diminution of its profits and future income.

Healthcare professionals, doctors, and third-party payors play a key part in the recommendation and prescription

of any product for which the Company may obtain a product license. Its future agreements with third-party payors

and customers could expose it more broadly to U.S. anti-fraud and anti-abuse laws and regulations, or other laws

and regulations relating to healthcare that may restrict business or financial agreements as well as relationships on

the basis of which the Company markets, sells, and distributes any product for which it may hold a product license.

Restrictions in accordance with U.S. federal anti-kickback, anti-fraud, and anti-abuse or other laws relating to

healthcare are as follows:

•

the U.S. federal anti-kickback statute prohibits people from, among other things, deliberately and knowingly

soliciting, offering, receiving, or supplying compensation, directly or indirectly, in cash or in kind, to induce or

compensate a business connection, or from purchasing, ordering, or recommending any product or service

payment which could be made in connection with a healthcare program in the United States, such as

Medicare and Medicaid;

•

U.S. federal law intended to prevent fraud by companies that are parties to public contracts (the “U.S. False

Claims Act”) provides, among other things, for civil and criminal sanctions against individuals or companies

that knowingly present false or fraudulent requests for payment to the U.S. federal government, or make false

statements to avoid, reduce, or hide an obligation to pay money to the U.S. government. Such specific actions

are open to whistleblowers or any other entity (qui tam actions);

•

under the U.S. Health Insurance Portability and Accountability Act of 1996 (“HIPAA”) a perpetrator of actions

intended to defraud any program for providing healthcare services or who makes false statements relating to

healthcare problems may be held civilly or criminally liable;

HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act and

regulations thereunder, also imposes obligations, including mandatory contractual language, to protect the

confidentiality, security, and transmission of personally identifiable health information;

U.S. federal law requires that manufacturers of medications report payments and other transfers of value to

doctors and university hospitals; and

GeNeuro SA – 2021 Universal Registration Document

•

analogous laws and regulations of U.S. or foreign states, such as anti-kickback laws, and those prohibiting

false claims, could apply to sales or commercial agreements as well as to claims about health products or

services reimbursed by non-governmental third-party payors, including private insurers.

If the Company’s operations are deemed to be contrary to applicable U.S. law and regulations, the Company could

be liable for significant sanctions and penalties, including fines, damages, imprisonment, civil and criminal

prosecution, or exclusion of its products from governmental healthcare programs, such as Medicare or Medicaid,

or even the restructuring of its business. Any doctor, healthcare professional, or company involved in commercial

activities found to violate applicable laws and regulations could be exposed to civil or criminal actions or

administrative sanctions, including exclusion from government healthcare programs.

3.1.7 Other clinical applications of temelimab for conditions such as COVID-19 are based solely on pre-clinical

work, and the Company may never succeed in developing and marketing effective treatments based on

such technology.

Temelimab has been tested pre-clinically for its effect on chronic inflammatory demyelinating

polyradiculoneuropathy (CIDP), for which temelimab has received Orphan Drug Designation from the U.S. Food

and Drug Administration (the “FDA”) in February 2018. Temelimab has also been tested in a Phase IIa trial for T1D

in adult patients, which has met its primary endpoint of safety at six months, and whose full 12-month results were

announced in May 2019⁵. Research data recently published also opens the potential of temelimab as a therapeutic

candidate in COVID-19, in particular in post-COVID/PASC (Post Acute Sequelae of SARS-CoV-2 infection)

patients, i.e., COVID-19 patients who develop long-term neurological and psychiatric post-COVID

("neuropsychiatric") symptoms.

On December 13, 2021, the Company announced it had been selected as one of the four projects retained by the

Swiss Federal Office of Public Health (“FOPH”) within the framework of the CHF 50 million “Federal Funding

Programme for COVID-19 Medicines” incentive, and that it would receive a grant of 6.7 million Swiss francs (€6.4

million) to co-fund (up to 50%) a Phase II clinical trial to treat patients with long-standing COVID who exhibit

neurological and psychiatric ("neuropsychiatric") symptoms.

The Company is also using the technology it has developed in the area of endogenous retroviruses to develop new

approaches through pre-clinical programs that target, for example, inflammatory psychoses (schizophrenia and

bipolar disorders) and ALS. In 2017, the Company entered into a research agreement with the U.S. National

Institutes of Health (“NIH”) for developing new approaches against pHERV-K Env protein as a target in the treatment

of ALS, following which the Company has signed in October 2018 an exclusive worldwide license with the National

Institute of Neurological Disorders and Stroke (“NINDS”), part of the NIH. The agreement covers the development

of an antibody program to block the activity of pHERV-K Env (pathogenic envelope protein of the HERV-K family of

Human Endogenous Retroviruses), a potential key factor in the development of ALS (see Chapter 20 of the 2020

Universal Registration Document). In October 2021, the NINDS presented at the American Neurological Association

(“ANA”) annual meeting novel pre-clinical results confirming in pre-clinical models of ALS the neurotoxic properties

of HERV-K ENV, a retroviral envelope protein encoded by a pathogenic member of the HERV-K family of

endogenous human retroviruses, and the therapeutic potential of GeNeuro's antibody developed to neutralize

HERV-K ENV. Additional data was presented in December 2021 at “The Lancet Summit: Presymptomatic

Prevention and Treatment of Neurodegenerative Diseases”.

If the Company wishes to complete the development of its products and sell them for such indications, it will have

to devote significant research effort and undertake numerous tests and clinical trials, obtain regulatory approvals,

and make significant financial investments. In developing and marketing products based on its technology, the

Company is confronted with a high degree of risk and uncertainty that could slow or even suspend its efforts to

develop its products and have a material adverse effect on its business and operations. Even if the Company were

in a position to obtain and maintain regulatory approvals for marketing its products, it is possible that:

•

it may not obtain the regulatory approvals required for it to conduct clinical trials for such indications;

it may neither develop nor obtain a marketing approval for its products quickly enough to ensure a competitive

position in the target markets;

•

it may not be in a position to manufacture and market its future products successfully at a price,

reimbursement rate, or scale that allow them to be profitable;

its future products may not be accepted by medical centers, hospitals, practitioners, and patients, nor be

preferred to existing treatments at the time they are introduced, nor, more generally, meet with the expected

commercial success;

•

its future products may lose their competitive advantage and may become obsolete by the development of

new competing products; or

its future products may not be marketable because of third-party property rights.

⁵Source: Curtin et al Diabetes Obesity and Metabolism, submitted 2019

GeNeuro SA – 2021 Universal Registration Document

If the Company is not successful in developing and marketing other products resulting from its technologies, its

revenues will continue to be limited, and its operating results could be significantly affected.

3.2 Risks Related To The Company’s Financial Situation and Capital Needs

3.2.1 The Company may not succeed in obtaining additional funds needed to continue its clinical development

in the short term and the future.

All of the Company’s products are currently in the pre-clinical or clinical trial phase and the Company will need to

finance additional studies necessary for the development of temelimab for MS or other indications until the Company

may eventually apply for and receive a marketing authorization.

Since its incorporation, the Company has mainly financed its growth by capital increases, including notably the

capital increase completed at the time of its initial public offering and listing on the regulated market of Euronext

Paris and is not exposed to liquidity risk resulting from indebtedness. The Company will be required to seek

additional funding to continue its development in MS, post-COVID or ALS, which may include, without limitation,

revenues from new partnership agreements, funds from capital increases or other funding, such as subsidies,

grants, or other forms of financing.

As of December 31, 2021, cash and cash equivalents of the Company amounted to €5.5 million.

The Company has performed a specific review of its liquidity risk as of the filing date of this Universal Registration

Document, taking into account the fact that the post-COVID Phase II trial would only be launched if the additional

funding is secured. The continuation of the Company’s clinical development requires the Company to raise

additional funds; in the absence of such new financing during the first half of 2022 and based on its current cash

position, the Company will implement its fallback operating plan, which includes a restructuring of its activities. On

this basis, the Company considered that on the filing date of this Universal Registration Document its financial

resources are sufficient to cover its upcoming deadlines and operational expenses and investments for at least 12

months after the filing date of this Universal Registration Document, and the Company expects that its current cash

will suffice to fund its operations into Q2 2023.

The Company’s historical cash burn was €6.8 million during 2021, following €7.2 million during 2020 and €9.9 million

during 2019, whereas the Company expects that its cash burn for 2022 will be significantly lower than in 2021 due

to the completion of its ProTEct-MS trial and its current research and development programs. For 2022, the

Company’s cash burn will depend largely upon its ability and decision to launch the post-COVID Phase II trial,

which, as mentioned above, the Company will only launch if it secures additional funding to complement the co-

funding €6.4 million grant it has received from the FOPH. However, this is not necessarily indicative of future cash

burn that will largely depend on future R&D programs actually undertaken.

Although management continues to pursue its plans to finance the development of its products, there is no

assurance that the Company will be successful in obtaining sufficient funding in the future, when needed or at all,

on terms acceptable to the Company to fund its continuing operations.

The Company will have to bear, if it obtains approval from a country’s authorities to test its product candidate in

humans in that territory, the significant cost of development of temelimab. Such costs would likely exceed €100

million for a Phase III study in MS.

In order to finance the continued clinical development of temelimab in MS, the Company is seeking to enter into

licensing and distribution, or other agreements with pharmaceutical companies which will be expected to have

sufficient capability for conducting the Phase III trials, manufacturing on an industrial scale, and distributing,

marketing and selling the product. GeNeuro is engaged in these partnering discussions but there is no certainty

that these discussions may result in a new partnership.

The Company also believes that the negative cash flow from its operations may increase significantly during future

years as a result of conducting clinical trials, manufacturing its products, and extending its research and

development programs. It will need considerable funding to pursue its research and development programs,

conduct other pre-clinical and clinical trials of its products, and extend its manufacturing, quality control capabilities,

and regulatory and administrative capabilities.

The Company’s future capital needs will depend on many factors, such as, among others:

•

the progress of its research and development programs;

the scale of such programs;

GeNeuro SA – 2021 Universal Registration Document

the extent of the costs and results of pre-clinical and clinical trials;

•

the time and costs necessary for obtaining regulatory approvals, including the time to prepare the application

files for regulatory bodies;

•

the marketing and sale of product, especially temelimab for MS or for post-COVID;

the Company’s ability to establish and maintain collaboration agreements with new partners;

the cost of improving its manufacturing and marketing capabilities; and/or

its need to acquire additional technologies or products, as the case may be.

The Company’s level of financing needs and their scheduling over time also depends on matters that are largely

beyond the Company’s control, including:

•

costs associated with possible requests or requirements (for example if trials are interrupted by emergencies

such as the current COVID-19 epidemic) to change studies, or to include a greater number of patients;

•

costs of preparing, filing, defending, and maintaining its patents and other intellectual property rights;

competing technological developments; and/or

higher costs and longer lead times than those anticipated to obtain regulatory approvals for the marketing of

its products and access to reimbursement.

Finally, if the necessary funds should not be available or not available on a timely basis, the Company may be

forced to:

•

delay, reduce, or eliminate the number and scope of its pre-clinical and clinical trials;

grant licenses to technologies to partners or third parties;

enter into new collaboration agreements on terms and conditions less favorable to it than those that it might

have been able to obtain in different circumstances;

•

obtain funds through alliance, collaboration or partnering agreements that could force the Company to give

up rights to certain of its technologies or its products, rights which it would not have given up in different

circumstances; and/or

delay, reduce, or even cancel research and development programs, and reduce the number of its employees;

The occurrence of one or more of the risks mentioned above could have a material adverse effect on the Group’s

business, financial condition, results, development, and prospects.

3.2.2 The Company should continue to sustain operating losses in relation to its research and development

activities.

The Company has sustained operating losses since its formation, except for the 2014 financial year. Such losses,

which amounted to €7.5 million for the 2020 financial year and €6.4 million for the 2021 financial year, reflect both

the significance of the expenses incurred in research and development and the absence of revenues. The Company

foresees that such losses will continue over the next few years, at least until the potential marketing and sale of its

products, because of the significant investments required for research, development, manufacture, quality control,

and distribution of its products, pre-clinical and clinical trials, administrative activities, and activities linked to the

development of intellectual property, as well as license agreements for new products and for the acquisition of new

technologies that may become necessary, as the case may be.

The Company expects that its operating losses will increase in the near future, particularly when:

•

some of its products move beyond the stage of pre-clinical development to clinical development;

it is confronted with increased regulatory requirements for manufacturing, and trials for its product candidates

(including temelimab for MS, which is its only product in an advanced stage of development);

•

it begins to pay fees in connection with applications for product licenses from regulatory bodies;

it increases its portfolio of products by adding new products for future development;

it makes milestone payments to third parties (such as bioMérieux) which have already licensed their

technologies to it;

GeNeuro SA – 2021 Universal Registration Document

•

it develops its research and development activities and buys new technologies, products or licenses, as the

case may be;

•

it develops its business worldwide; and

it has to finance structural expenses consistent with the growth of its business.

The amount of net losses and the time needed to reach sustained profitability are difficult to estimate and will depend

on several factors, including:

•

the degree of advancement of the Company’s research and development activities, particularly pre-clinical

developments and clinical trials;

the calendar of regulatory procedures in connection with the preparation, review, and protection of patents

and intellectual property rights;

•

changes in collaboration arrangements made by the Company; and

other factors, a great number of which are beyond the Company’s control.

Given the development stage of its most advanced product, the Company has not yet received any revenue from

product sales and the Company’s operating revenue and operating profit (or loss) have fluctuated in the past and

could continue to do so in the future. Accordingly, its revenues for a given period are not a reliable indicator of its

future performance and the Company may never market or sell any products and, as a result, may never become

profitable. The Company expects that its main sources of revenue and funds until the potential marketing and sale

of its first product candidate, temelimab for MS or post-COVID, will be:

•

payments that may be made by future partners of the Company, if the Company enters into one or more

agreements with future partners relating to the development and/or marketing and sale of temelimab for MS

or post-COVID or other revenue of the Company;

•

public and private subsidies, including the CHF 6.7 million subsidy from the Swiss FOPH and other public

funding it is continuing to seek; and

potential net proceeds of funds raised by the Company through capital markets transactions (notably to match

the CHF 6.7 million grant from the Swiss FOPH, in accordance with the grant terms).

Any interruption of such financing sources could have a material impact on the operating revenue and operating

profit (loss) of the Company.

3.2.3 The Group benefits from Research Tax Credits from the French and Australian governments which

regime may be challenged or modified in the future.

The Company’s subsidiary GeNeuro Innovation, a French company, benefits from the French Research Tax Credit

(Crédit Impôt Recherche, “CIR”) that provides a tax incentive to support the scientific and technical research efforts

of French companies. The research expenses that are eligible for the CIR include, under certain conditions, the

salaries and compensation of researchers and research technicians, the amortization of fixed assets dedicated to

research, services subcontracted to approved research entities (public or private), and expenses for maintaining

patents.

The amounts received by GeNeuro Innovation in respect of the CIR are as follows:

•

payment of the CIR for financial years 2011 to 2015 of €3,553 K, all of which was received;

payment of the CIR for financial year 2016 of €519 K, received in September 2017;

payment of the CIR for financial year 2017 of €791 K, received in March 2019;

payment of the CIR for financial year 2018 of €593 K, received in August 2019;

payment of the CIR for financial year 2019 of €680 K, received in April 2020; and

payment of the CIR for financial year 2020 of €583 K, received in August 2020.

The Company had accrued a net amount of €556 K for CIR for the financial year 2020, taking into account certain

provisions, but the full gross amount of €583 K was received. For the financial year 2021, the Company has accrued

an amount of €1,007 K, which it expects to recover during Q3 of 2022.

Companies must provide evidence to the French tax authorities, upon request, of the outstanding amount of the

CIR and the eligibility of the operations taken into account to benefit from this aid.

GeNeuro SA – 2021 Universal Registration Document

GeNeuro Innovation benefits from the early payment of the CIR (i.e., immediately, rather than three years following

application). If in the future it should no longer receive amounts under the CIR, or its status or calculations should

be questioned, this could have a material adverse effect on the Group’s business, prospects, ability to achieve its

objectives, financial condition, cash position or operating profit (loss).

3.2.4 The Company could be unable to carry tax losses forward.

As of December 31, 2021, the Company had carried-forward tax losses amounting to € 55,902 K (being

CHF 57,753 K converted at the December 31, 2021 closing rate). In Switzerland, tax carryforwards may be used

within seven years of incurrence and are as follows:

•

€

8,121.3 originated in 2021 and expiring in 2029

€ 11,219.7 originated in 2020 and expiring in 2028

€

4,650.4 originated in 2019 and expiring in 2027

6,125.3 originated in 2018 and expiring in 2026

4,972.1 originated in 2017 and expiring in 2025

€ 14,372.9 originated in 2016 and expiring in 2024

6,440.7 originated in 2015 and expiring in 2023

€

No carried-forward tax loss expired in 2022 as the Company generated a profit in 2014.

It is possible that future changes to tax law could alter such provisions by limiting or eliminating the possibilities for

attributing the tax loss carryforwards, which could have a material adverse effect on the Group’s business,

prospects, ability to achieve its objectives, financial condition, cash position, or operating profit (loss).

3.2.5 Dilution Risk

Since its formation, the Company has granted stock options to its management and employees. On March 18, 2022,

the Board of Directors awarded an additional 203,627 stock options to executive managers and selected employees

of the Company. Accordingly, as of the filing date of this Universal Registration Document and taking into account

the expiration of unexercised stock options and the cancelation of unvested stock options for departing employees,

full exercise of all securities carrying the right to acquire shares granted and outstanding as of the date hereof would

lead to the issuance of 1,148,521 shares, resulting in a potential dilution of 4.9% (such options are described in

section 13.1.3 of the Universal Registration Document). The weighted average exercise price of all such securities

is €7.52, compared to the market closing price for the Company’s shares on Euronext Paris of €3.22 on April 25,

2022.

In connection with its incentive strategy for motivating its executives and employees and to attract additional skills,

the Company could issue or award shares or new equity securities carrying the right to acquire shares in the future,

which could cause further dilution, potentially material, for present and future shareholders of the Company. Dilution

could cause a drop in the price of the Company’s shares.

3.2.6 Exchange Rate Risk

The Company is exposed to exchange rate risks relating to changes in the exchange rate between the euro (“EUR”)

and the Swiss franc (“CHF”) because a portion of the Company’s operating expenses is incurred in the latter

currency. Due to the activities of its Australian subsidiary being terminated since Q2 2021 and there being no assets

in Australian Dollar (“AUD”), there is no longer an exchange rate risk with the AUD.

If the Company succeeds in marketing and selling its products in the United States, it could earn a portion of its

revenue in U.S. dollars and, therefore, would be exposed to an exchange rate risk relating to changes in the

exchange rate between the U.S. dollar and the euro.

The Company will follow changes in its exposure to exchange rate risks on the basis of changes in its situation. If

the Company does not manage to take effective hedging steps in the future, its results of operations could be

negatively impacted.

GeNeuro SA – 2021 Universal Registration Document

3.3 Risks Related To The Company, Its Operations and Organization

3.3.1 The Company is dependent on its key employees and, as such, could fail to continue attracting and

retaining its key employees and scientific advisors.

The Company’s success depends largely on the work and experience of its executive management and its key

scientific personnel, especially its Chairman and Chief Executive Officer (Président Directeur Général), Mr. Jesús

Martin-Garcia; its Chief Medical Officer, Dr. David Leppert; its Chief Scientific Officer, Dr. Hervé Perron; its Chief

Financial Officer, Mr. Miguel Payró; and its Chief Development Officer, Dr Alois B Lang. The loss of their expertise

could alter the Company’s ability to reach its objectives. Furthermore, the Company will need to recruit new qualified

executives and scientific staff as it expands in areas that require additional abilities, such as marketing,

manufacturing, clinical trials, and regulatory affairs. The Company competes with other companies, research

organizations, and academic institutions to recruit and retain highly qualified scientific, technical, and management

staff. To the extent such competition is very intense, the Company could be unable to attract or retain such key staff

on terms and conditions that are acceptable from an economic point of view. Its inability to attract and retain such

key personnel could prevent it from reaching its overall objectives.

3.3.2 The Company faces the risk of liability linked to its products or operations and it may not be able to

obtain adequate insurance coverage at an acceptable cost .

The Company is exposed to the risk of liability, particularly product liability, arising in connection with the

manufacture and sale of therapeutic products for use in humans. Liability against the Company may also result

from clinical trials in connection with the testing of therapeutic products or unexpected adverse side effects resulting

from the administration of such products. Complaints or legal proceedings could be filed or brought against the

Company by patients, regulatory authorities, biotechnology and biopharmaceutical companies, and other third

parties using or selling its products. Such actions could include complaints resulting from actions by its partners,

licensees, and subcontractors over which it has little or no control. The Company can give no assurance that its

present insurance coverage will suffice to respond to liability actions that could be brought against it. If its partners,

licensees, and subcontractors or the Company itself are not in a position to obtain and maintain appropriate

insurance coverage at an acceptable cost or protect themselves in some way against product liability actions, they

could be held significantly liable, which could have the consequence of seriously affecting marketing and sale of

the Company’s products and, more generally, harm its business.

The Company is also subject to environmental protection and health and safety laws and regulations that could

expose it to liability and restrict its operations. In its research and development programs and pre-clinical tests, the

Company uses hazardous substances and biological materials such as human cell lines. Accordingly, in countries

in which the Company operates, it is subject to environmental protection and safety laws and regulations governing

the use, storage, manipulation, production, and disposal of hazardous substances, including chemical and

biological products. The Company is also subject to laws and regulations relating to the use and manipulation of

genetically modified organisms under French, European, and U.S. laws and regulations.

In the event of a failure to comply with applicable laws and regulations, the Company could be subject to fines and

might have to suspend

part or all of its operations. To comply with environmental, and health and safety laws

and regulations, the Company would incur additional costs and it could, in the future, incur significant expenses in

doing so in the relevant jurisdictions in which it operates. In complying with environmental, health and safety laws

and regulations, the Company may have to acquire equipment, modify facilities, and more generally, incur other

material expenses. In the event of accidental contamination, injuries, or any kind of damage, the Company could

be held liable for damages, which might not be paid by or covered under its insurance policies and which could

harm the Company’s business.

3.3.3 Shareholders might be unable to achieve a control premium in the event of a change of control of the

Company based on the fact that French and Swiss regulations concerning mandatory public takeover offers

are not applicable.

In so far as the Company’s registered office is in Switzerland whilst its shares are listed only on Euronext Paris’s

regulated market, neither French regulations on mandatory public tender offers and buyouts, nor Swiss regulations

on public takeover offers (purchase or exchange offer) are applicable to public tender offers concerning the

Company’s shares.

Under these conditions, a person might acquire shares in the Company to an extent representing a controlling stake

as defined under Swiss or French law without a legally enforceable obligation to file a public tender offer to all the

shareholders.

Similarly, because of the unenforceability of French and Swiss law on compulsory public tender offers, a person

could issue a public tender offer to some, but not all, shareholders.

GeNeuro SA – 2021 Universal Registration Document

3.4 Risks Related To The Company’s Dependency on Third Parties

3.4.1 The Company does not have manufacturing capabilities and is exposed to the risks associated with

relying on third party manufacturers for its most advanced product candidate temelimab and its other

products

The Company has chosen to outsource the manufacturing of its products. Its dependence on third parties to

manufacture and assemble certain of its products and its lack of experience in manufacturing other products on an

industrial scale could affect its ability to develop and sell its products within a reasonable timeframe and on a

competitive basis. In particular, the Company depends on third parties to produce its most advanced product

candidate, temelimab for MS. In this respect, it has entered into an agreement with the contract manufacturing

organization (“CMO”) Polymun Scientific GmbH (“Polymun”), to manufacture its antibody on the basis of good

manufacturing practices (“GMP”), for determined quantities of product at a pre-determined cost, without future

royalties. The Company will also depend on subcontracting agreements for the fill and finish of its products, both

for future clinical trials and for subsequent stages of sales and marketing.

The Company could also be unable to enter into subcontracting agreements for the future commercial supply of

temelimab, or to do so on acceptable terms and conditions. If it is unable to enter into acceptable subcontracting

agreements, the Company may be unable to market and sell temelimab successfully.

In the current COVID-19 pandemic and geopolitical situation, supply of culture media for antibody manufacturing

and other products is facing considerable strain and competition for deliveries, which may lead to delays in the

manufacturing of future batches of temelimab.

Furthermore, dependency on third-party manufacturers involves additional risks to which the Company might not

be exposed if it manufactured temelimab itself, such as:

•

non-compliance of such third parties with regulatory and quality control standards;

the violation of such agreements by such third parties;

the termination or non-renewal of such agreements for reasons beyond its control; and

the insolvency of such third parties.

If the products manufactured by such third-party suppliers do not comply with regulatory standards, sanctions and

penalties could be imposed. Such sanctions could include fines; court orders; civil penalties; refusal of regulatory

authorities to grant product licenses; delays, suspension or withdrawal of approvals; revocation of product licenses;

product recalls or seizures; operating restrictions and criminal prosecutions, all of which are measures that could

have a material adverse effect on the Company’s business, operations, its financial position and its financial results.

If the Company is unable to maintain its collaboration agreements with its existing partners, including the CMO

Polymun, or enter into new agreements on acceptable terms and conditions, it will have to develop and sell its

products at its own expense, or it will have to turn to other partners. This could increase its capital needs and limit

its growth and marketing and sales efforts to other areas. In addition, even if the Company, in connection with its

agreements, has included provisions designed to impose strict compliance by its partners with their commitments,

it cannot control either the extent or the timing of the resources that its existing and future partners will devote to

the development or sale of the Company’s products. Such partners might also not meet their obligations as set out

in the contracts that the Company has, or may have, with them or under the terms it is expecting. In such cases,

the Company could be confronted with significant delays and not achieve success in obtaining the support of third

parties for the Company’s new technology based on the neutralization of W-ENV, or support for the introduction of

the Company’s products in various markets.

Even though the Company tries to include non-competition clauses in its collaboration agreements, no assurance

can be given that such restrictions will ensure sufficient protection to the Company. The Company’s partners could

develop technologies alone or together with others, including its competitors.