table of contents - valbiotis · biofortis mérieux nutrisciences europe. murielle cazaubiel m.sc...

2020JAN

TABLE OF CONTENTS

Jan. 2020 2

01. VALBIOTIS / Corporate

02. TOTUM-63, active substance

03. TOTUM-63, prediabetes: VALEDIA®

05. TOTUM-63, arterial hypertension

07. FINANCIAL INFORMATION

04. TOTUM-63, hepatic steatosis

© NON CONFIDENTIAL - VALBIOTIS

06. Other products in development

VALBIOTIS, highlights

Jan. 2020 3

A robust industrial property: 4 patent families worldwide, including strategic patents in the USA and Europe.

A team of managers highly qualified and experienced in their respective fields of expertise.

Founded in 2014 Euronext Growth (ALVAL) 3 locations in France (Périgny, La Rochelle, Riom) 36 employees: 75% in R&DProprietary preclinical platform

A R&D company, committed to scientific innovation, for preventing and combating metabolic diseases.

A new class of plant-based products, designed to reduce the risk of major metabolic diseasesthrough a multi-target approach.

An answer to unmet medical needs, specially in prediabetes and hepatic steatosis.

A program of clinical studies developped to bring out solid scientific evidence and obtain strong health claims.


An advanced pipeline,addressing unmet medical needs

Jan. 2020 4© NON CONFIDENTIAL - VALBIOTIS

Solid scientific results selectedby the major international scientific societies

Jan. 2020 5

13communications

duringscientific congresses

since 2016Including 7 accepted

communications in the 3 major diabetes congresses worldwide

3 selections by the Keystone Symposia


A global IP strategy across the portfolio

Jan. 2020 6

Demonstrates that innovative combinations of plant extracts are patentable for a healthcare purpose,for food products, supplements or pharmaceuticals > “ Plant extracts / molecules ”.

All patents consistently applied for in more than 60 countries, including Canadian, American and European territories.

4 PATENT FAMILIES APPLICATIONS WORLDWIDE ALREADY

A STRATEGIC PATENT GRANTED IN EUROPE AND IN THE US

US patent granted in 2018, with a triple protection:composition, method and use in the field of metabolic diseases.

National phases ongoing in more than 20 countries, incl. Canada.

Exclusivity2035

USAEUROPEEU patent granted in 2019, covering 39 countries.


An expert management for healthcare innovation

Jan. 2020 7

Sébastien PELTIER

20 years’ experience in Research& Development for drug and foodsupplement industries. Unique, proven experience with health claims referring to the reduction of a disease risk (EFSA – European Food Safety Authority – article 14.1a)

CEO, PhD - HDRChairman of the Boardof Directors

25 years’ experience in healthand nutrition. Founder and former Executive Director of Biofortis Mérieux NutrisciencesEurope.

Murielle CAZAUBIELM.ScCMO, Member of the board

Pascal SIRVENTPhD - HDRCSO, Member of the boardOver 15 years’ research experiencein the field of metabolic diseases, with leadership positions and a strong background in international scientific partnerships.

Laurent LÉVY, PhD Chairman of the Supervisory BoardRemuneration CommitteeCEO, co-founder,NANOBIOTIX

Agnès TIXIERAudit CommitteeInvestment Director, CM-CIC INVESTISSEMENT

SUPERVISORY BOARD

Sébastien BESSYRemuneration CommitteeVice President Global Strategic Operations, IPSEN

Dr Jean ZETLAOUI MD, MBAAudit CommitteeSpecial Scientific Advisor to the CEO, NOVARTIS PHARMA

Jocelyn PINEAUMBACFO, Member of the board20 years’experience in projectmanagement positions as partof executive management boards,in the agro-food and food supplementsindustries.

Medicine degree, 25 years’ international expérience in marketing and business development focused on Consumer Healthcare, with top management positions. Former Vice President at Sanofi, Johnson & Johnson and Pfizer. *

Josep INFESTAMD, MBAHEAD OF GLOBAL BUSINESS DEVELOPMENT

Finance & administration Discovery, preclinicaland translational

research

Development and medical affairs Global Business

Development

* External consultant


High-value scientific & medical supervisory Board

Jan. 2020 8

Pr. Jean-Marie BARD PharmD, PhD, PU-PH – Nantes University Hospital

Professor of biochemistry at the Faculty of Pharmacyand Head of the Biopathology Department at Institut

de Cancérologie de l’Ouest (ICO) in Nantes.

Pr. Samy HADJADJ MD, PhD, PU-PH - Nantes University Hospital

Professor of endocrinology, diabetology and metabolic diseases, Hospital practitioner.

André MARETTEPhD - Laval University Hospital INAF (Canada)Professor in the Faculty of Medicine. Researcher at the Quebec Heartand Lung Institute and Scientific Director of the Institute of Nutritionand Functional Foods (INAF) at Université Laval.

Nathalie BOISSEAU PhD, PU - Clermont Auvergne UniversityProfessor of sports physiology at STAPS UFR,member of the AME2P laboratory.

Thierry MAUGARDPhD, PU - La Rochelle UniversityProfessor of biochemistry inthe Biotechnology Department.

Bruno GUIGASPhD - Leiden University (Netherlands)

Assistant professor.


USA, Europe and Canada regulatory pathways

Jan. 2020 9

“VALEDIA® may reducethe risk of type 2 diabetes,

a disease associatedwith several risk factors.”

”VALEDIA® reducesfasting glycemia,

which increase is a risk factorfor type 2 diabetes.”

Composition, quality& safety

Set product specifications and qualitymanagement in accordance with the selected status.

Non-ambiguous proof of the efficacyof the product to reduce disease riskfactors in at-risk population, accordingto current regulation.

Composition, quality± safety

Quality + evidenceregarding safety and efficacy

Free claim, but strictlycompliant with clinical evidence.

HEALTH CLAIMS

Food supplement status Natural Health Product


A high level of evidence for prevention

Jan. 2020 10

A R&D processfollowing the outline

of pharmaceuticaldevelopment


A proprietary platform dedicated to metabolic diseases

Jan. 2020 11

In vivo screeningon relevant models of metabolicdiseases

1,200 m2 platform: models of metabolic diseases, radiolabelling, micro-surgery & clamp, histology,cellular culture, molecular biology, biochemistry.

Design ofactive substances(compliant withpharmacopeiaUS / EU)

Extraction processes,characterisation, purification, bio-engineering, pharmaco-modulation.

In vivo and in vitro studies:efficacy, safety,mode of action

Plant-basedchemistry & preclinical research

Discovery


The business model

Jan. 2020 12

TARGET POPULATIONSubjects at risk of developing metabolicdiseasesEx.: prediabetics for VALEDIA®

PRESCRIBERS /ADVISORSHealthcare professionals

RETAILMainly pharmacies network / drugstores + ad hoc omnichannelstrategy by country

COMMERCIALIZATION MODEL

STRATEGIC PARTNERSHIP MODELAgreement for clinical developmentand commercialization,at an international level.

Upfront± Funding of clinical studies

± Milestone payments+ Royalties

EUROPEUNITED-STATES

Our two prioritiestoday


TOTUM-63,to reduce the risk of metabolic diseases


TOTUM-63: an innovative active substance, patented,based on a combination of 5 plant extracts

Jan. 2020 14

Plant A

Plant B

Plant C

Plant D

Plant E

Dry extract

Dry extract

Dry extract

Dry extract

Dry extract

V%

W%

X%

Y%

Z%

Industrialextraction process

Complete characterisation

of the biomolecules(HPLC-UV/MS)

Active combination

of biomolecules

Patent family VALBIOTIS.001 (plant extracts / molecules)

VALBIOTIS owns all of the development rights

Patents applied for in more than 60 countries incl.:39 countries in Europe, USA and Canada

INTELLECTUAL PROPERTY

Exclusivity2035

USAEUROPE


Adipose tissue

Increases peripheral sensitivity:

• Improves insulin cellular signaling.

• Reduces adipose tissue inflammation.

TOTUM-63: a multi-target action on 5 key metabolic organs

Inhibits lipid storage(steatosis reduction).

Preserves insulin secretion capacity.

Acts on intestinal microbiota composition:

• Increased overall richness.

• Positive impact on groups involved in insulin-resistanceand T2D.

Liver

Gut

PancreasMuscle

Jan. 2020© NON CONFIDENTIAL – VALBIOTIS I 15

TOTUM-63: main metabolic effects demonstrated in preclinical studies

Jan. 2020 16

Prevention of weight gain, improved body composition

Reduced fat mass, independent of food intake

Improvement of glucose metabolism

Fasting glycemia, glucose tolerance, insulin sensitivityProof of concept for the risk reduction of type 2 diabetes

Reduction of hepatic steatosisPrevention and reversion of steatosis

Standard diet High fat diet High fat diet + TOTUM-63

db/db miceControlHigh fat dietHigh fat diet + TOTUM-63


Jan. 2020 17

TOTUM-63: Phase IIA clinical results

• Multicenter, randomised, unbalanced (3:1, VALEDIA®:Placebo)and double-blind placebo-controlled study, 2 parallel-groups

• Supplementation period: 6 months, 5 g/day

• Primary endpoint: change in fasting glycemiabetween baseline and 6 months

• Main secondary endpoints: 2 hours OGTT glycemia, insulinsensitivity, anthropometric parameters, hemodynamicparameters lipid profile, safety

51 prediabetics with abdominal obesity associated with moderatehyperglycemia, hyperglycemia at 2 hours (OGTT) and hypertriglyceridemia.

• Age: 57.1 years• Gender: 35 female, 16 male• BMI: 31.3 kg/m2

• Fasting glycemia: 1.26 g/L• 2 hours OGTT glycemia: 1.85 g/L

• Fasting triglycerides: 1.78 g/L• Fatty liver index: 73.34• Fasting LDL-cholesterol: 1.42 g/L

STUDY DESIGN STUDY POPULATION

è Coordinating Investigator: Dr. David Gendre (MD Biofortis) è Expert: Pr. Jean-Marie Bard (PharmD, PhD, Professor of Basic and Clinical Biochemistry, Nantes, France)è ID-RCB Number: 2016-A00484-47


18


fasting glycemia;

2 hours OGTT glycemia;

triglycerides blood levels;

fatty Liver Index;

systolic blood pressure;

LDL-cholesterol blood level;

total cholesterol blood level;

body weight;

waist circumference.

Jan. 2020© NON CONFIDENTIAL - VALBIOTIS

Good safety and tolerance

6 months supplementation with TOTUM-63showed positive and significant evolution vs. placebo of:

Jan. 2020 19


Primary endpoint met: reduction in fasting glycemia vs. placebo


– 9.3%a

a Difference of the means of individual variations expressed in %

TOTUM-63

Jan. 2020 20


Secondary endpoint met: reduction in 2h-glycemia (OGTT) vs. placebo


– 22.5%a TOTUM-63


Jan. 2020 21


Secondary endpoints met: reduction in anthropometric parameters vs. placebo

a Difference of the means of individual variations


– 1.9 kga– 4.48 cma

TOTUM-63


Jan. 2020 22

Secondary criteria endpoints: reduction in triglyceridemia and in Fatty Liver Index vs. placebo


FLI ≥ 60 : High probability of steatosis


– 32.2%a – 18.7%a

TOTUM-63


Jan. 2020 23

Secondary endpoints met: reduction in total cholesterol and LDL-cholesterol vs. placebo



– 11.5%a– 11.7%a

* *

TOTUM-63

Values are expressed as mean ± SEM. * p<0.05 Values are expressed as mean ± SEM. * p<0.05


Jan. 2020 24

Secondary endpoint met: reduction in systolic blood pressure vs. placebo

a Difference of the means of individual variations


– 10.6 mmHga – 18.9 mmHga

Sub-population: subjects with high blood pressureOverall population

Values are expressed as mean ± SEM. *** p<0.001

TOTUM-63

Values are expressed as mean ± SEM. ** p<0.01

25


fasting glycemia;

2 hours OGTT glycemia;

triglycerides blood levels;

fatty Liver Index;

systolic blood pressure;

LDL-cholesterol blood level;

total cholesterol blood level;

body weight;

waist circumference.

Jan. 2020© NON CONFIDENTIAL - VALBIOTIS

Good safety and tolerance

6 months supplementation with TOTUM-63showed positive and significant evolution vs. placebo of:

PREDIABETES, RISK CONDITION FOR TYPE 2 DIABETESFASTING GLYCEMIA VALIDATED AS:• Primary endpoint for Phase IIB studies (REVERSE-IT and PREVENT-IT)• Claimed risk factor for authorities (EFSA, FDA, Health Canada)

HEPATIC STEATOSIS, RISK CONDITION FOR NASHVALIDATED PROOF OF CONCEPT

ARTERIAL HYPERTENSIONAND CARDIOVASCULAR RISKVALIDATED PROOF OF CONCEPT

TOTUM-63,to reduce the risk of type 2 diabetes: VALEDIA®


VALEDIA®: a worldwide innovation designed for people with prediabetes

Jan. 2020 27

First clinically proven and natural solutionspecifically created to reduce the risk of developing Type 2 Diabetes

Specific combination of 5 plant extracts, patented

Clinical evidence of efficacy already obtained in prediabetics, for the reductionof fasting glycemia, to obtain a healthclaim for the risk reduction of Type 2 Diabetes

Capsules with vegetal shell = 0 excipient

100% natural, perfect tolerance

1 to 2 takes / day, morning and/or night, before meals


Clinical development plan to obtain the health claim

Jan. 2020 28

LAUNCHREVERSE-IT PHASE IIB1 – PIVOT EUROPE

LAUNCHPREVENT-IT - PHASE IIB2PIVOT NORTH AMERICA

SUBMISSIONTO HEALTH AUTHORITIES

EFSA - CANADA HEALTH - FDA

VALEDIA® (TOTUM-63) – prediabetes, to reduce the risk of type 2 diabetes

2021

NEXT STEPS

PHASE I/II PHASE IIA

INDUSTRIAL PROCESS VALIDATEDWITH PIERRE FABRE GROUP

This status does not require Phase III studies


Prediabetes: an opportunity for diabetes prevention

Jan. 2020 29

“Prediabetes should not be considered as a diseasebut as a high-risk stage of developing T2 diabetes 1”

1 Standards of care in Diabetes, ADA 2017 ; 2 Tabak AJ. et al., Lancet, 2012 ; 3 Nathan DM. et al., Diabetes Care, 2007 ; 4 Knowler WC et al., N Engl J Med, 2002

RISK OF PROGRESSION TO TYPE 2 DIABETESWITHOUT INTERVENTION

Reversible metabolicimpairments

Irreversible metabolicimpairments in most cases

PREDIABETES1 year5% to 10%2

3-4 years25% to 37%3,4

Long term70% to 90%2

PREDIABETESAT-RISK STAGE TYPE 2 DIABETES

Lifelong treatments,costful and stressful follow-up

+ morbid complications


Prediabetes: a favourable medical environment for new products

30

Standards of care in Diabetes, ADA, 2017 ; Global Report on Diabetes, WHO, 2016 ; HAS – Référentiel de pratiques de l’examen périodique de santé, Prévention et dépistage du diabète de type 2, 2014

An easy diagnosis in primary care, based on simple blood tests:

Jan. 2020

And / Or

Moderate fasting hyperglycemiaFasting glycemia from 1.00 to 1.25 g/LOr HbA1c ≥ 5.7% and < 6.5%

Screening and diagnosis modalities

Recommendations for prediabetes management

A recognition by international scientificsocieties and health authorities

Impaired glucose toleranceGlycemia from 1.4 to 2.0 g/L,2 hours after a 75 g oral glucose intake

Moderate fasting hyperglycemiaFasting glycemia from 1.10 to 1.25 g/L

Impaired glucose toleranceGlycemia from 1.4 to 2.0 g/L,

2 hours after a 75 g oral glucose intake

And / Or


Prediabetes, market data USA + Top 5 Europe:millions of people concerned

Jan. 2020 31

Data: AEC Partners data on key VALBIOTIS markets: the United States, Canada and the 5 primary European countries (Germany, United-Kingdom, France, Spain and Italy ), 2019.

Current average diagnosis rate (US/EU) = 10%

Prediabetic adult population per country (millions)TOTAL = 134 millions person with prediabetes

Today,13.4 millions people diagnosed

with prediabetes, waiting for a solution

millions diagnosedin the USA10


Once diagnosed, prediabetics left alone facing their health

Jan. 2020 32

”Overwhelmed”

”Responsible for my own health”

”Misunderstood by doctors, friends and family”

”Frustrated not to make any progress”

”Tired of this permanent struggle”

”Passive about the risk of diabetes”

Reporting concerns and frustration

All social / ethnic profiles

+ 45 years old *

45–64 years: 41%+ 65 years: 48%

Health profile- Overweight and obesity- Dyslipidemia, hypertension

& cardiovascular diseases- Sedentary lifestyle

Both menand women*

Men: 37%Women: 31 %

Data AEC Partners, 2019

* Percentages indicate the prevalencein the specific population


A fast growing market in the coming decade

Jan. 2020 33

1.4

0.6

1.8

1.2

0.80.7

1.0

0.9

1.6

2018 2019 2020 2021 2022 2023 2024 2025 2026 2027

Marketvalue

(billions €)

X3in 10 years

GROWTH LEVERS

• Increasing prevalence of prediabetes

• Continuous progression of screening

• Development of preventionprograms

• Growth of the market of prediabetes healthcare products

Annual growth rate: 12%

Data: AEC Partners data on key VALBIOTIS markets: the United States, Canada and the 5 primary European countries (Germany, United-Kingdom, France, Spain and Italy ), 2019.


TOTUM-63,to reduce non-alcoholic hepatic steatosis


Hepatic steatosis: an opportunity to prevent NASH and its complications

Jan. 2020 35

”The progression from NAFL to NASH dramatically increases the risksof cirrhosis, liver failure, and hepatocellular carcinoma” 1

1. Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis; World Gastroenterology Organization, 2012 ; 2. EASL–EASD–EASO 2016 Clinical Practice Guidelines on the management of non-alcoholic fatty liver disease. J Hepatol 2016

Without intervention, up to 40% of subjects with non-alcoholichepatic steatosis will at least develop NASH within 8 to 13 years. 2


Non alcoholic hepatic steatosis,an emerging medical need with specific medical practices

Jan. 2020 36

1. Bedogni, G. et.al., BMC Gastroenterology; 2006 ; 2. EASL–EASD–EASO 2016 Clinical Practice Guidelines on the management of non-alcoholic fatty liver disease. J Hepatol 2016 ; 3. Global Guidelines Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis, World Gastroenterology Organisation, 2012 ; 4. Hernaez R et al. Hepatology. 2011.

Not expensive, largely available,highly sensitive for moderateto severe steatosis. 4

Liver ultrasonography: the recommendednon invasive first line exam for diagnosis 2,3

Fatty Liver Index (FLI):a predictive score for screening in primary care 1

Based on routine clinical examinations:

• Body Mass Index (BMI) and waist size• Blood triglycerides level• Blood Gamma GT (liver enzyme) level

FLI < 30è No steatosis

FLI ≥ 60è High probability of steatosis

Patients with obesity, insulin-resistance,metabolic syndrome, type 2 diabetes.

Recent recommendations for systematicscreening in at-risk populations 2


TOTUM-63,to reduce the risk of cardiovascular diseases


Arterial hypertension (AHT)

Jan. 2020 38

AHT is consensually defined as arterial blood pressure ≥ 140/90 mmHg* persisting over time 2

or ≥ 130 /85 mmHg in subjects with metabolic syndrome. 3

The leading cardiovascular risk factor in the world1,2

billions people with AHT in the world (2015). 1

Efficient management of AHT decreases the risk of cardiovascular complications and contributes to longer life expectancy. 2

1 ESC/ESH Guidelines for the management of arterial hypertension, European Heart Journal, 2018 ;2 Prise en charge de l’hypertension artérielle de l’adulte, Recommandation de bonne pratique, HAS, 2016 www.has-sante.fr/jcms/c_2059286/fr/prise-en-charge-de-l-hypertension-arterielle-de-l-adulte ;3 International Diabetes Federation, 2006. Professors Sir George Alberti and Paul Zimmet.The IDF consensus worldwide definition of the METABOLIC SYNDROME* Arterial blood pressure is expressed in mercury millimeters (mmHg)

1,1

Normal arterial blood pressure in adults is established 120 mmHg at heart contraction (systolic pressure)and 80 mmHg at heart relaxation (diastolic pressure). 2

Leading chronic disease and cause of premature death worldwide (10 millions deaths in 2015). 1

Causing severe and fatal cardiovascular complications:heart failure, stroke, arterial peripheral diseases, chronic kidney disease, etc. 1

Often combined with other metabolic risk factors: dyslipidemia, glucose intolerance, etc.1


http://www.has-sante.fr/jcms/c_2059286/fr/prise-en-charge-de-l-hypertension-arterielle-de-l-adulte

Other products in development,in the field of metabolic diseases

Jan. 2020 39

VAL-070 (Hypercholesterolemia) / LpD64 (Obesity / Overweight)


VAL-070, targeting blood LDL-cholesterol,risk factor for cardiovascular diseases

Jan. 2020 40

Activesubstance

Plant A

Plant B

Plant C

Plant F

Dry extract

Dry extract

Dry extract

Dry extract

Industrialextraction process

P%

Q%

R%

S%



Patent applied for in 2016, protection till 2036once delivered


VALIDATED CLINICAL PHASE I/II

Safety and tolerance confirmed

LDL-cholesterol validated as primary endpoint for clinical Phase II trials

Complete characterisation(HPLC-UV/MS)

Active combination

of biomolecules


LpD64, targeting fat mass regulation in overweight or obese subjects

Jan. 2020 41

Blendof plants

Complete characterisation(HPLC-UV/MS)

Active combination

of biomoleculesVALIDATED CLINICAL PHASE I/II

Safety and tolerance confirmedProof of concept in Humans

Industrialextraction

process

Plant A

Plant B

Plant C

Plant D

Plant E

V%

W%

X%

Y%

Z%



Patent applied for in 2015, protection till 2035 once delivered


Dry extractfrom blendof 5 plants


LpD64, targeting fat mass regulation in overweight or obese subjects

Jan. 2020 42

A possible microbiota-based mode of action, supported by first positive data

LpD64 has a clear effect on gut dysbiosis associated with obesity

qPCR and metasequencing analysis in cecal and fecal microbiotas (obese preclinical models)

Firmicutes / Bacteroidetesratio


Financial informations


ALVAL-FR - Shareholders breakdown

Jan. 2020 44

Management

Dilutivesinstruments(BSA, BSPCE)

FREE FLOAT

77.9%13.9%

5.3%

2.9%Other shareholders

ANALYSTS Portzamparc Christophe DOMBUTarget price: 7,50 EUR (data November 2019)

Invest Securities Thibaut VOGLIMACCI-STEPHANOPOLITarget price: 11,00 EUR (data October 2019)


Cash and R&D expenses

Jan. 2020 45

Total operating income: € 1,023 K

of which: § Research Tax Credit: € 605 K§ Operating grants: € 372 K

Cash Position : €3.9 millionsat 30/06/2019.

Not included:collection of Research Tax Credit 2019 (1.2 M€)and gross revenue of Oct. 2019 capital increase (7.2 M€)

Total operating income 1,023 1,509

R&D expenses (2,105) (3,826)

Operating and sales expenses (1,464) (2,343)

Current operating income (2,639) (4,876)

Operating income (2,639) (4,876)

Income before tax (2 724) (4,967)

Group net income (2,724) (4,967)

30/06/2019 31/12/2018In € ‘000 - IFRS


2020NOV

table of contents - valbiotis · biofortis mérieux nutrisciences europe. murielle cazaubiel m.sc...

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