POXEL SA

A société anonyme (French joint-stock company) with a share capital of EUR 579,041.00 euros

Registered office: 259/261 Avenue Jean Jaurès – Immeuble le Sunway – 69007 Lyon

510 970 817 RCS LYON

UNIVERSAL REGISTRATION DOCUMENT

This Universal Registration Document has been filed on May 4^th, 2022 with the Autorité des marchés financiers

(“AMF”), as competent authority under Regulation (EU) 2017/1129, without prior approval in accordance with

article 9 of Regulation (EU) 2017/1129.

The Universal Registration Document may be used for the purposes of a public offering of securities or the

admission of the Company's securities to trading on a regulated market if it is supplemented by a securities

note and, if applicable, a summary and any amendments to the Universal Registration Document. The resulting

document is then approved by the AMF in accordance with the Prospectus Regulation.

Pursuant to Article 19 of EU 2017/1129 dated June 14, 2017 and to the Commission delegated

regulation EU 2019/980, the statutory and consolidated financial statements for financial year 2020,

as well as the related statutory auditors’ reports, and the statutory and IFRS financial statements for

financial year 2019, as well as the related statutory auditors’ reports included in the registration

document filed with the AMF on March 25, 2021 under number D.21-0195 and on April 20, 2020

under number D.20-0319 are incorporated by reference in this Universal Registration Document .

This document is available without charge at the Company’s registered office, and in electronic form

on the website of the Autorité des Marchés Financiers (www.amf-france.org) as well as on the

Company’s website (www.poxel.com).

Page 2

TABLE OF CONTENTS

PRESENTATION OF POXEL...............................................................................................................5

Message from the CEO .............................................................................................................5

Key information related to Poxel and achievements over the period......................................7

Selected Financial information ...............................................................................................16

COMPANY’S ACTIVITIES................................................................................................................18

Business ..................................................................................................................................18

Risk factors..............................................................................................................................87

Material contracts.................................................................................................................118

Organizational structure and employees..............................................................................122

Corporate Social Responsibility Report ................................................................................132

FINANCIAL INFORMATION ..........................................................................................................162

Management discussion and analysis...................................................................................162

Consolidated Financial Statements for the years ended December 31, 2021 and 2020......182

Statutory financial statements as of December 31, 2021.....................................................235

Auditors’ reports...................................................................................................................267

Other financial information ..................................................................................................281

GOVERNANCE AND LEGAL INFORMATION......................................................................................283

Governance...........................................................................................................................285

Compensation.......................................................................................................................309

Shareholding and stock performance...................................................................................325

Related party transactions....................................................................................................328

Legal information..................................................................................................................335

APPENDIXES.............................................................................................................................362

Responsible Persons, third party information, expert reports and approval of the competent

1.1

1.2

1.3

2.1

2.2

2.3

2.4

2.5

3.1

3.2

3.3

3.4

3.5

4.1

4.2

4.3

4.4

4.5

5.1

authority ............................................................................................................................................362

5.2 Concordance Table ...............................................................................................................363

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GENERAL REMARKS

Definitions

In the Prospectus, unless otherwise specified, the terms « Company » or « Poxel » refer to Poxel, a

société anonyme (French joint-stock company) with a share capital of EUR 579,041.00, whose

registered office is located 259/261 Avenue Jean Jaurès – Immeuble le Sunway, 69007 Lyon, France,

and registered with the Lyon Registry of Commerce and Company under number 510 970 817. The

term « Group » refers to the Company and its subsidiaries and participations.

Forward-looking statements

This Universal Registration Document contains forward-looking statements about the Company’s

prospects and areas of growth. These statements are sometimes identified by the use of the future

tense, the conditional form, and forward-looking terms, such as “estimates”, “considers”, “targets”,

“expects”, “intends”, “should”, “wishes” and “may” or any other variations or similar terminology.

Readers are reminded that these prospects and areas of growth should not be interpreted as a

guarantee that the statements and forecasts mentioned will occur, nor that the assumptions will be

verified or the objectives achieved. This information is based on data, assumptions and estimations

considered as reasonable by the Company. Such data, assumptions and estimations are likely to evolve

or change due to uncertainties related to economic, financial, competition or regulatory factors. The

prospects may, consequently, not be achieved and information provided by the Prospectus may prove

to be erroneous. However, subject to applicable regulations, particularly to the AMF General

Regulations and the European Regulation (EU) No 596/2014 of the European Parliament and of the

Council of 16 April 2014 on market abuse (market abuse regulation), the Company shall not be under

any obligation to update the Prospectus.

Risk Factors

Investors are urged to give careful consideration to the risk factors described in Section 2.2 “Risk

factors” of this Universal Registration Document before making any investment decision. The

occurrence of any of these risks could have a material adverse effect on the Company, its business, its

prospects and ability to achieve its objectives, its financial position and/or development. Other risks

and uncertainties not identified by the Company on the date of the Universal Registration Document

or risks that it considers, on the same date, not to be significant may nonetheless exist and materialize,

and may also disrupt or have an adverse effect on the Company's business, financial situation, earnings

and prospects and/or on the Company's shares.

Page 4

1 PRESENTATION OF POXEL

1.1

Message from the CEO

Dear Madam, Dear Sir, Dear Shareholder,

I am happy to share with you this new edition of our Universal Registration Document, which is the

opportunity to review Poxel’s accomplishments during the year 2021 has been a particularly

important year in Poxel’s history, as it marks the first approval and launch of one of our drugs.

Indeed, in June 2021, we received, with our partner Sumitomo Pharma, a leading company in the

diabetes field in Japan, approval in Japan for TWYMEEG (Imeglimin), and this was followed by its

launch in September 2021. This major accomplishment resulted from the submission of a Japanese

New Drug Application for Imeglimin in July 2020, based upon an extensive preclinical and clinical

program, including positive results from the Phase 3 TIMES program in over 1,100 patients in Japan.

The TWYMEEG approval in Japan represents the culmination of several years of clinical development

work and a strong validation of our R&D capabilities and international footprint.

TWYMEEG is a first-in-class drug with a unique dual mechanism of action for the treatment of type 2

diabetes across the continuum of the current treatment paradigm. It was approved in Japan as a

monotherapy and as an add-on treatment to other glucose lowering therapy regimens. Poxel is

entitled to receive sales-based payments and escalating 8-18% royalties on product sales. We are

immensely proud to have brought TWYMEEG to patients in Japan through our fruitful partnership

with Sumitomo Pharma.

We also achieved significant milestones during 2021 in NASH. In September, we completed

enrollment in DESTINY-1, a dose-ranging Phase 2 trial evaluating PXL065 for the treatment of NASH.

PXL065 is a novel, proprietary deuterium-stabilized R-stereoisomer of pioglitazone.

Additionally, following a thorough review of the Company’s programs, Poxel has embarked on a new

chapter to drive shareholder value. We made the strategic decision to advance and expand our

portfolio of clinical assets in rare metabolic diseases which represents the intersection of high unmet

medical needs, promising pre-clinical and clinical data, opinion leader enthusiasm, significant

commercial opportunity, and attractive time horizons. We believe that by leveraging our existing

platforms and proven capabilities to develop products in rare metabolic diseases in addition to NASH,

we can be more efficient with our resources and more expediently deliver novel medicines to patients

with an even stronger potential to create significant value for the benefit of our shareholders.

Our first rare disease development program targets X-linked adrenoleukodystrophy (ALD), a serious

monogenic disorder with no approved pharmaceutical therapy. Our recent preclinical data with

PXL065 and PXL770 demonstrates that both approaches have substantial efficacy potential. During

2021, the team has been preparing for the initiation of two identical Phase 2a studies which will enroll

adult male patients with AMN, the most common form of ALD, and observe the effect of PXL065 and

PXL770 over 12 weeks of treatment on pharmacokinetics, safety, and efficacy. In February and April

2022, the FDA granted Fast Track Designation to PXL065 and PXL770, respectively, for the treatment

of ALD, designed to expedite development of pharmaceutical products which demonstrate the

Page 5

potential to address unmet medical needs in serious or life-threatening conditions. Drugs with Fast

Track Designation are eligible to apply for Accelerated Approval and Priority Review at the time of a

New Drug Application submission, which may result in faster product approval.

During 2021, we also strengthened the Company’s financial position, through the milestone payment

of JPY1.75 billion (EUR13.2 million) received from Sumitomo Pharma in July for the approval of

TWYMEEG, and the final tranche of EUR 13.5million of the IPF loan, which was contingent on the

successful approval of the Imeglimin in Japan.

Lastly, I would like to mention that in 2021 we launched our first Corporate Social Responsibility

initiative, that will be fully part of our corporate strategy, to continue developing the Company in a

even more responsible way. After completing a thorough assessment of existing actions at the

beginning of the year, we have then set up clear objectives and monitoring tools to support our

ambitious action plan, with the help of our entire team. You will find more about our ongoing plan in

the following pages, and I am looking forward to sharing our progress in the coming years.

In 2022, we expect several additional important milestones. Results from the PXL065 Phase 2 DESTINY

study in NASH are anticipated in Q3 2022, and the two studies in AMN/ALD, subject to financing, are

planned to initiate in midyear 2022, with data expected in early 2023. We are actively pursuing a

number of funding initiatives in parallel to extend our cash runway. We are in advanced discussions

with several parties and we are confident that at least one of these options will be completed before

Q3 2022, allowing us to continue to execute our strategic plan.

Our vision as a company is focused on developing innovative drugs for chronic diseases with metabolic

pathophysiology, including NASH and rare metabolic disorders, starting with ALD. In addition to our

clinical-stage programs, we continue to evaluate external opportunities with a focus on chronic and

rare metabolic diseases, to expand our pipeline.

All the work and success we accomplished this year would not have been possible without the

incredible energy from our talented employees, and I want to thank them for all that we accomplished

during very challenging times. I am also grateful to the patients and physicians who take part in our

clinical trials. Lastly, I would like to thank you for your continuous support as a shareholder.

Sincerely,

Thomas Kuhn

Chief Executive Officer

Page 6

1.2

Key information related to Poxel and achievements over the period

1.2.1 General information, history and achievements over the period

Poxel is an international clinical-stage biopharmaceutical company focused on the development of

novel treatments for serious chronic diseases with metabolic pathophysiology, including rare

metabolic disorders and non-alcoholic steatohepatitis (NASH). With its expertise and understanding

of cellular energy regulation pathways related to metabolic diseases, and know-how in the

development of drug candidates, the Company is developing a portfolio of drug candidates, which

includes: PXL770 and PXL065, for both the treatment of NASH and the rare disease, X-linked

adrenoleukodystrophy (ALD). Poxel intends to advance into pivotal trials one program in NASH and

one in ALD. Earlier stage programs focusing on chronic and rare metabolic indications are also in

progress.

With its heritage in diabetes, Poxel’s first product, Imeglimin, was approved in June 2021 for the

treatment of type 2 diabetes in Japan and launched in September 2021 as TWYMEEG® by the

Company’s partner, Sumitomo Pharma. In a new chapter of the Company’s evolution to drive

shareholder value, Poxel continues to execute its strategic plan to advance and expand its portfolio

of clinical assets for both NASH and rare metabolic diseases, aligned with the Company’s strategic

shift announced in July 2021. This strategy leverages the Company’s scientific strengths with newer

promising pre-clinical and clinical data in rare metabolic indications which represent the intersection

of high unmet medical needs, opinion leader enthusiasm, significant commercial opportunity, and

attractive time horizons.

Poxel was founded in 2009 through a spin-off of Merck Serono’s metabolic-focused business, as part

of a strategic realignment following the acquisition of Serono by Merck. As part of this spin-off, the

Company assumed key personnel for this group and assets from Merck Serono, including Imeglimin

and the AMPK activator program that led to the Company’s discovery of PXL770. The Company’s

management team is composed of experts with extensive experience in metabolic diseases and rare

disorders. Key members of its team have experience from Merck Serono, Servier, Eli Lilly and Merck

& Co. and were involved in the discovery, clinical trial designs and regulatory approvals for a number

of products prescribed globally, including Glucophage^®(metformin), Trulicity^®(dulaglutide) and

Januvia^®(sitagliptin).

Page 7

Stages of Development of Principal Drug Candidates

The table below sets forth details relating to the current stages of development of the Company’s

clinical and preclinical drug candidates in rare diseases, NASH and type-2-diabetes:

Robust Mid-to-Late Stage Metabolic Pipeline

Focus on Rare Metabolic Diseases and NASH

Approved

Discovery /

Indication

MOA

PH1

PH2

PH3

Upcoming Milestones

Marketed

NASH

•

Phase 2 results expected Q3 2022

505(b)(2) pathway

Non-Genomic

TZD¹

PXL 065

NASH

AMPK²

Activator

•

Successful Phase 2a Study

PXL7 70

Evaluate next steps early 2023

Rare Metabolic Indications

•

Fast Track Designation granted April 2022

Initiate Phase 2a midyear 2022⁷

PXL7 70

ALD³

AMPKActivator

•

Fast Track Designation granted Feb 2022

Initiate Phase 2a midyear 2022⁷

Non-Genomic

TZD

PXL 065

ALD³

•

Completed preclinical; develop clinical strategy

Select lead candidate(s)

PXL7 70/Next -Gen AMPK

ADPKD⁴

AMPKActivator

Not

Disclosed

Non-Genomic

TZD

Next-Gen D-TZD

Type 2 Diabetes (T2D)

TWYMEEG ^®Japan /Asia ⁵

•

TWYMEEG approved for T2D in Japan in June 2021

Product launchedSeptember 2021

MRC⁶

Modulator

T2D

Poxel entitled to receive 8-18% royalty on net sales

Imeglimin

US / EU / Other

MRC Modulator

•

Considering speciﬁc territories partnerships

Deuterium-mo diﬁed thiazolidined ion e

5. Includes: China, South Korea, Taiwan, Indonesia, Vietnam, Thailand, Malaysia, Philippines,

Singapore, Myanmar, Cambo dia, Laos

6. Mitochondrial Respiratory Chain

2. AMP-kinase

3. X-linked Adrenoleukodystrophy

4. Autosomal dominant polycystic kidney disease

Subje ct to additio nal ﬁnancing

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Non-alcoholic steatohepatitis (NASH)

NASH is a severe form of non-alcoholic fatty liver disease (NAFLD) that results in an accumulation of

fat in the liver and is one of the most common liver diseases in the United States. It affects

approximately 20% of the world's population and up to 70% of type 2 diabetes patients. According to

published estimates, about 10% to 30% of NAFLD patients also suffer from NASH. A scientific

publication in 2018 estimated that there were approximately 16.5 million prevalent NASH cases in the

United States in 2015, which was projected to increase by 63% to 27.0 million cases by 2030.

With no approved drug treatments, NASH can lead to life-threatening conditions like cirrhosis, liver

failure, liver cancer and death. NASH is considered one of the main causes of cirrhosis in adults. NASH

is also under-diagnosed and is a silent disease, meaning patients have no symptoms until the first

signs of liver failure appear. Many patients with NASH have type 2 diabetes (estimated 47%)¹and

many patients with type 2 diabetes also have NASH (estimated 26%)². In addition, patients with NASH

and coexisting type 2 diabetes are more likely to have progressive fibrosis. Cases of liver cirrhosis

related to NASH are the second leading cause of liver transplants in the United States and are

expected in the next few years to become the leading cause of transplantation, ahead of hepatitis C

and alcoholic cirrhosis.

PXL065 - NASH

PXL065 offers a potential new approach to treating NASH. In August 2018, the Company acquired

exclusive, worldwide ownership of PXL065 (deuterium-stabilized R-pioglitazone), a clinical-stage

program being pursued for the treatment of NASH, from DeuteRx. As part of the PXL065 acquisition,

the Company also acquired additional programs, including other deuterated drug candidates for

metabolic, specialty and rare diseases. The Company fully owns development and commercialization

rights for PXL065.

Pioglitazone is a mixture, in equal proportions, of two mirror molecules (R and S stereoisomers) that

interconvert in vivo. Like all other products in its class, pioglitazone targets both activation of

peroxisome proliferator-activated gamma receptors (“PPARy”) and modulation of non-genomic

targets including inhibition of the mitochondrial pyruvate carrier (“MPC”) and long chain acyl-CoA

synthetase 4 (“ACSL4”).

In addition to its established role in the treatment of type 2 diabetes, pioglitazone has been the

subject of a large number of clinical trials in the treatment of NASH, which have demonstrated its

ability to target disease resolution and to improve fibrosis.³

Pioglitazone is the only drug recommended in guidelines of the American Association for the Study of

Liver Diseases (the “AASLD”), and is the only drug identified as a potential treatment by the European

Association for the Study of the Liver (the “EASL”), for the treatment of biopsy-confirmed cases of

NASH. However, pioglitazone is not approved for NASH and its use is restricted due to the adverse

effects associated with the activation of PPARy receptors, such as weight gain, bone fractures and

fluid retention. PXL065, the R stereoisomer, has little or no observed PPARy activity or associated

adverse effects that appear to be related to the S stereoisomer of pioglitazone. Preclinical models

1 Younossi ZM et al; Hepatology 2016.

2 Cusi et al, Diabetes Obes Metab. 2017; Portillo/Cusi et al, J Clin Endocrinol Metab 2015

3 Musso G. Hepatology 2017; 65:1058-61.

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have shown that PXL065 should retains efficacy that is similar to pioglitazone in NASH with little or no

weight gain or fluid retention.⁴

In September 2021, Poxel announced the completion of enrollment in the Phase 2 NASH trial for

PXL065 (DESTINY 1) in biopsy-proven patients which initiated enrollment in September 2020. Topline

data from this Phase 2 NASH trial is anticipated in Q3 2022. DESTINY 1 (Deuterium-stabilized R-

pioglitazone (PXL065) Efficacy and Safety Trial in NASH) is a Phase 2 36-week, randomized, dose-

ranging, double-blind, placebo-controlled, parallel group study designed to assess the efficacy and

safety of three doses of PXL065 in 123 noncirrhotic biopsy-proven NASH patients across multiple

clinical sites in the US. The primary endpoint of the study will measure the relative change in the

percentage of liver fat content based on magnetic resonance imaging-estimated proton density fat

fraction (MRI-PDFF). The study will also assess the effects of PXL065 on liver histology and other

metabolic and non-metabolic biomarkers. The results will be used to help identify the dose or doses

for a Phase 3 registrational trial.

Based on the Company’s pre-investigational new drug meeting with the FDA in the United States in

the fourth quarter of 2019, the Company plans to pursue the 505(b)(2) regulatory pathway for

PXL065, which has the potential for expedited development. Section 505(b)(2) of the Federal Food,

Drug, and Cosmetic Act (the “FDCA”) permits the filing of an application for marketing approval where

at least some of the information required for approval comes from clinical trials conducted by others

for other approved drugs. The Company plans to pursue a regulatory pathway under section 505(b)(2)

for PXL065 that relies on data from the parent drug, pioglitazone, which has been approved and

prescribed since 1999.

PXL770 - NASH

PXL770 is a direct activator of AMP activated protein kinase (AMPK). Poxel fully owns development

and commercialization rights for PXL770. AMPK is a central regulator of multiple metabolic pathways

leading to the control of lipid metabolism, glucose homeostasis and inflammation. Based on its central

metabolic role, the Company believes that targeting AMPK offers the opportunity to pursue a wide

range of indications to treat chronic metabolic diseases, including diseases that affect the liver, such

as NASH.

Since it is the Company’s intention to advance one candidate, either PXL065 or PXL770, in NASH and

the other candidate in X-linked adrenoleukodystrophy (ALD), the initiation of the NASH Phase 2b trial

for PXL770 is postponed, pending results from the ongoing PXL065 Phase 2 trials in NASH, expected

in Q3 2022, and both Phase 2a biomarker studies for PXL065 and PXL770 in ALD to be initiated midyear

2022, with results expected in early 2023.

On October 1, 2020, the Company announced positive top-line results for the STAMP-NAFLD PXL770

Phase 2a trial which was launched in April 2019. The Phase 2a trial was a 12-week, randomized,

parallel group study, in 120 presumed NASH patients with or without type 2 diabetes. This Phase 2a

trial produced positive effects that are potentially predictive of longer term efficacy NASH. In the per

protocol population, PXL770 was observed to produce a statistically significant mean relative decrease

of -18% in liver fat mass from baseline at 12-weeks in the 500 mg QD dose group as measured by MRI-

PDFF. A greater proportion of patients who received PXL770 also achieved a >30% relative reduction

in liver fat content compared to placebo. Despite nearly normal mean baseline HbA1c values (6.03-

6.30%) across all groups (patients with and without diabetes), a significant reduction in mean HbA1c

4 Jacques V et al. Hepatol Comm 2021 ;5:1412-25.

Page 10

was also observed. A similar trend was also observed on fasting plasma glucose. PXL770 was observed

to be generally safe and well tolerated. The number of patients with treatment-emergent adverse

events in each group were similar to placebo and these events were mainly mild-to-moderate. The

safety results from the Phase 2a trial are consistent with the PXL770 PK/PD trial and Phase 1 program.

In patients with type 2 diabetes (41-47% of each group), PXL770 treatment resulted in a greater mean

relative reduction in liver fat content (-27% at 500 mg QD; p=0.004 versus baseline). Additional

findings in this sub group included: a significant increase in the proportion of responders (>30%

reduction in liver fat); dose-responsive and significant mean decreases in alanine transaminase (ALT)

and aspartate transaminase (AST) levels that were achieved despite only slightly elevated mean

baseline ALT levels (36-47 IU/L; normal range <41 IU/L). In these patients, baseline fasting glucose

(121-144 mg/dL) and HbA1c (6.6-7.1%) levels were well controlled, and in this context, significant

placebo-adjusted decreases were observed in both glycemic parameters along with improvements in

commonly used fasting indexes of insulin sensitivity (HOMA-IR and QUICKI scores). In the T2DM

subpopulation, PXL770 was generally safe and well tolerated and was similar to the whole trial

population.

Rare Metabolic Disease – X-Linked Adrenoleukodystrophy (ALD)

X-linked adrenoleukodystrophy – ALD – is a deadly, inherited rare metabolic disease characterized by

neurodegeneration. ALD is a monogenic inborn error of metabolism due to mutations in the ABCD1

gene which encodes a key cellular fatty acid transporter – this defect results in accumulation of very

long chain fatty acids (VLCFA) with resulting damage to several tissues in particular neurons.

ALD is increasingly being diagnosed based on the recent and broad-based adoption of newborn

screening. Thus, the prevalence of ALD is similar to hemophilia or spinal muscular atrophy – about

20,000 in the US alone.⁵Globally it may affect more than 400,000 people.

Forms of this disease include cerebral ALD (C-ALD) and adrenomyeloneuropathy (AMN) which is the

most common form – typically occurring in adolescence through adulthood. AMN is characterized by

chronic and progressive distal axonopathy involving the long tracts of the spinal cord and to a lesser

extent the peripheral nerves resulting in progressive stiffness and weakness in the legs, impaired gait

and balance, incontinence, and loss of sensation. As an X-linked disease, nearly all men with a

diagnosis of ALD will develop AMN and are more severely affected, but many women also present

with features of AMN with a later onset. C-ALD is characterized by inflammatory demyelination of

cells in the brain and typically afflicts children, but many men with AMN may also develop cerebral

disease; these white matter brain lesions lead to severe neurologic deficits and death.

There are currently no approved medicines for ALD (other than glucocorticoid supplements for

associated adrenal insufficiency). Cerebral-ALD (C-ALD), when first detected in early childhood, can

be treated with hematopoietic stem cell transplantation, but it is currently limited to early stage of C-

ALD and this procedure is at risk of severe adverse reactions.

PXL065 & PXL770 in ALD

Following the new strategic direction announcement made in July 2021, Poxel is investigating the

potential of PXL065 and PXL770 in ALD. The Company is preparing to initiate two identical Phase 2a

clinical proof-of-concept (POC) biomarker studies for PXL065 and PXL770 in adrenomyeloneuropathy

(AMN), the most common form of the disease. AMN afflicts adults with ALD resulting in progressive

5 Bezman L. Am J Med Genet. 1998; 76:415-19.; Matteson J. Int J Neonatal Screen. 2021, 7:22

Page 11

spinal cord axonal degeneration that leads to spasticity, impaired balance and gait, bladder and bowel

dysfunction, impotence. These deficits ultimately cause severe disabilities. Over 90% of male ALD

patients develop AMN by age 60 ⁶

Two identical Phase 2a studies will enroll adult male patients with AMN and observe the effect of

PXL065 and PXL770 over 12 weeks of treatment on pharmacokinetics, safety, and efficacy using

relevant biomarkers, including potential impact on elevated VLCFA, the hallmark plasma marker of

the disease. These two studies are planned to initiate in midyear 2022, with data expected in early

2023. The data from these studies will be utilized to select which compound, PXL065 or PXL770,

possesses the preferred profile to advance into a pivotal study in 2023.

In February and April 2022, the FDA granted Fast Track Designation (FTD) to PXL065 and PXL770,

respectively, for the treatment of ALD. FTD is designed to expedite development of pharmaceutical

products which demonstrate the potential to address unmet medical needs in serious or life-

threatening conditions. FTD provides Poxel with substantially enhanced access to FDA, including

opportunities for face-to-face meetings and written consultations throughout the remaining

development of PXL065. Drugs with FTD are eligible to apply for Accelerated Approval and Priority

Review at the time of a New Drug Application (NDA) submission, which may result in faster product

approval.

In ALD pathophysiology, increases in VLCFA, specifically saturated C26 fatty acid, are the primary

driver of disease with downstream pathologies leading to axonal degeneration for both cerebral and

spinal cord disease. Both PXL065 and PXL770 have the potential to target ALD pathophysiology; this

could include suppression of elevated VLCFA, specifically saturated C26:0 fatty acid, the primary driver

of disease. In addition, downstream pathologies such as inflammation and mitochondrial dysfunction

could be ameliorated. Net effects could include reduced axonal degeneration for both cerebral and

spinal cord disease.

Importantly, multiple recent publications support the utility of both AMPK activation and deuterated

thiazolidinediones (D-TZD)-related pathways for the treatment of ALD.⁷The Company has developed

evidence to show that both AMPK activation and D-TZDs can be leveraged to address this

pathophysiology to correct the primary defect - suppressing VLCFA levels - and by potentially

ameliorating downstream consequences that include mitochondrial dysfunction, inflammation and

cell death.

Both PXL065 and PXL770 mediate neurologic benefits. The Company has studied both of its lead

molecules in classical ALD preclinical models, patient derived-cells and the ABCD1 null mouse. In these

data, it has been observed that both compounds produced substantial reductions in VLCFA both in

vitro and in vivo, including in brain and spinal cord. In more recent experiments that were also

conducted using ABCD1 mouse, evidence of improved neural histology and neuro-behavior were

observed with both PXL065 and PXL770.

Diabetes

According to the International Diabetes Foundation, in 2021 an estimated 537 million people between

the ages of 20 and 79 are living with diabetes globally (1 in 10), with more than 90% of those affected

having type 2 diabetes. This estimate is predicted to rise to 643 million by 2030 and 783 million by

2045. Diabetes caused at least USD 966 billion in total healthcare expenditures in 2021, a 316%

6 Huffnagel IC. J Clin Endocrinol Metab. 2019; 104:118-26.

7 Morato L. Brain. 2013; 136:2432-43; Weidling I. J Neurochem 2016:138:10-13.

Page 12

increase over the last 15 years. Globally, 541 million adults have Impaired Glucose Tolerance, which

places them at high risk of type 2 diabetes.

Decision Resources, an independent market analysis firm, estimates that diabetes treatments

generated sales of over $61.3 billion in 2017 in the United States, Japan, Germany, Italy, the United

Kingdom, France and Spain, which the Company refers to as the G7 countries, and that sales in these

markets are projected to grow to $75.5 billion by 2027. According to Decision Resources, the diabetes

monotherapy treatment market in the G7 countries was approximately $1.7 billion in 2017 (with the

current standard of care, metformin, used for the treatment of approximately 60% of type 2 diabetes

patients in the G7 countries), while the market for new oral combination therapies was approximately

$21.5 billion in 2017 (with sitagliptin accounting for a 46% market share within its class).

Japan

According to Decision Resources, Japan is the second largest diabetes market worldwide, behind the

United States, with a compounded annual growth rate of more than 18% between 2008 and 2012 and

could grow by more than 20% by 2023. According to Decision Resources, estimated sales in Japan are

expected to grow to $4.2 billion by 2020.

There are an increasing number of patients seeking treatment for diabetes in Japan, both type 1 and

type 2, Japan is among the top five countries in Asia for prevalence of diabetes; the latest estimate is

11 million patients⁸. The Company believes that this market trend is likely to continue, in particular,

given that the Japanese government has identified diabetes as a target disease in its ten-year plan for

National Health Promotion.

Imeglimin for Type 2 Diabetes

Poxel’s first product, Imeglimin, was approved in June 2021 for the treatment of type 2 diabetes in

Japan and launched in September 2021 as TWYMEEG® by the Company’s partner, Sumitomo Pharma.

Imeglimin is a novel, first-in-class diabetes treatment because it has the ability to target mitochondria

and cellular energy metabolism leading to a dual mechanism of action; to the Company’s knowledge,

there are no approved products or product candidates in advanced development by third parties

which modulate cellular bioenergetics by directly targeting mitochondria for the treatment of

diabetes.

The Company also believes Imeglimin is the only oral compound with a dual mechanism of action

designed to both increase insulin secretion in response to glucose and to reduce insulin resistance. As

a consequence of these effects, the Company believes that Imeglimin has the potential to slow disease

progression and provide therapeutic options to patients who no longer respond to current

treatments. It may also have the potential to complement existing treatments and to decrease the

risk of cardio-renal disease. To date, Imeglimin has been evaluated in 28 clinical trials and

administered to an aggregate of 400 non-diabetic subjects and over 1,800 type 2 diabetes patients.

Imeglimin has been well-tolerated in these trials and the Company has observed statistically

significant reductions of hemoglobin A1c, or HbA1c, and other glycemic parameters versus placebo.

Commercial Partner – Sumitomo Pharma

In 2017, the Company has entered into a partnership agreement for Imeglimin with Sumitomo

Pharma, for commercialization and development rights in Japan, China and eleven other East and

8 International Diabetes Federation 2021 Atlas;

https://diabetesatlas.org/idfawp/resource-files/2021/07/IDF_Atlas_10th_Edition_2021.pdf

Page 13

Southeast Asian countries (see Sections 2.3.2 “Sumitomo Pharma License Agreement" for more details

on this agreement). As per this agreement, the Company has received upfront payments and

payments related to achieving clinical development and regulatory milestones totaling JPY 7.0 billion

(approximately EUR 53 million) between 2017 and 2021. The Company is entitled to receive sales-

based payments up to JPY26.5 billion (approximately EUR 200 million, USD 227 million) and escalating

8-18% royalties on net sales under the Sumitomo Pharma license Agreement. As part of the Merck

Serono licensing agreement (see Sections 2.3.1“Merck Serono Agreement" for more details on this

agreement), Poxel will pay Merck Serono the first 8% royalty based on the net sales of Imeglimin,

independent of the level of sales. Poxel retains the net royalties above 8%. Based on the current

forecast, the Company expects an 8% royalty rate through Sumitomo Pharma’s Fiscal Year 2022

(March 2023). Therefore, the royalty stream will be cash neutral until TWYMEEG revenues cross the

first threshold. When TWYMEEG achieves the next commercial threshold, the royalty rate will

increase to the next level for a positive net cash flow to Poxel. Based on the Sumitomo Pharma

forecast submitted to the Japanese pricing authority, the next threshold and sales based payment

would occur after March 2023. The Company expects to receive double digit royalties for most of the

time of TWYMEEG’s commercial life, after March 2023.

On June 23, 2021, The Company and Sumitomo Pharma announced the approval of TWYMEEG, the

name for Imeglimin hydrochloride, for the treatment of type 2 diabetes in Japan. Japan is the first

country in the world to approve Imeglimin. The approval triggered a JPY1.75 billion (approximately

EUR 13.2 million, USD 15.8 million)⁹milestone payment to the Company. The product launch of

TWYMEEG, 500mg tablets for the treatment of type 2 diabetes in Japan, started September 16, 2021.

9 Converted at the exchange rate as of June 21, 2021.

Page 14

1.2.2 Other information about the Company

1.2.2.1 Name of the Company

The name of the Company is: Poxel.

1.2.2.2 Place of registration and registration number of the Company

The Company is registered with the Lyon Trade and Company Registry (RCS) under the number

510 970 817.

The Company’s NAF (business activity) code is 7219Z.

The Company’s LEI (legal entity identifier) is 9695003OIX0T7NX72N26.

1.2.2.3 Date of incorporation and term

The Company was incorporated on March 11, 2009, for a term of 99 years expiring on March 11, 2108,

save in the event of early dissolution or an extension.

1.2.2.4 Registered Office of the Company, legal form and applicable law

The Company is a French société anonyme (public limited company) with a Board of Directors.

The Company, governed by French law, is primarily subject to article L. 225-1 et seq. of the French

Commercial Code.

The registered office of the Company is:

259/261 Avenue Jean Jaurès – Immeuble le Sunway – 69007 Lyon

Phone: 0033 4 37 37 20 10

Fax: 04 37 70 88 15

Email: investors@poxelpharma.com

Website: www.poxel.com

Information about the Company are available on the Company's website: www.poxel.com

Information from the Company’s website does not form part of the Universal Registration Document.

Page 15

1.3

Selected Financial information

The financial informations are presented in millions of euros. Amounts are rounded to the nearest

million and include individually rounded data. Arithmetic calculations based on rounded items may

differ from the aggregates or subtotals shown.

1.3.1 Selected Financial Information

The following selected consolidated statements of income (loss) data for the two years ended

December 31, 2020 and 2021 and the selected consolidated statements of financial data as of

December 31, 2020 and 2021 have been derived from the Group’s audited consolidated financial

statements included elsewhere in this Universal Registration Document.

Selected Consolidated Statements of Income (Loss) Data

(in thousands, except shares and per share amounts)

December

31, 2021

December

31, 2020

Change

Change %

97%

Revenue

13,397

-59

6,806

6,592

-59

COGS

Gross margin

13,339

-27,479

2,305

-10,627

-22,463

-2,950

868

6,806

-29,219

2,517

6,533

1,740

-212

96%

-6%

Research and development expenses

Subsidies

-8%

General and administrative expenses

Operating income (loss)

Financial expenses

Financial income

-9,923

-29,819

-1,727

1,722

-704

7,356

-1,223

-854

-25%

71%

-50%

-140%

-34%

-25%

-93%

-25%

Exchange gain (loss)

Financial income (loss)

Net income (loss) before taxes

Income taxes

785

-1,970

-1,975

-31,794

-36

2,755

678

-1,297

-23,760

-2

8,034

Net income (loss)

-23,762

-31,831

8,069

Basic and diluted earnings (loss) per share

(0.83)

(1.16)

Number of shares used for computing basic and diluted

earnings (loss) per share

28,642,334

27,528,783

Page 16

Consolidated Statement of Financial Position

Data (in thousands)

December 31, 2021 December 31, 2020

Change

Change %

Cash and cash equivalents

Total assets

32,287

54,889

8,206

40,203

65,077

27,065

21,554

16,459

38,013

65,077

-7,915

-10,188

-18,859

9,228

-20%

-16%

-70%

43%

-3%

Total shareholders’ equity

Total non-current liabilities

Total current liabilities

Total liabilities

30,782

15,901

46,683

54,889

-558

8,671

23%

-16%

Total liabilities and shareholders’ equity

-10,188

1.3.2 Investments

1.3.2.1 Principal investments made over the last two financial years

The Group’s investments made over the last two financial years essentially concern the acquisition of

IT and office equipment.

1.3.2.2 Principal investments in progress

No significant investment has been made since January 1, 2022.

1.3.2.3 Principal planned investments

The Company does not currently intend to make significant investments in the coming years, for which

the management bodies of the Company have made firm commitments.

Page 17

2 COMPANY’S ACTIVITIES

2.1

Business

2.1.1 General presentation