APRIL presentation 2020 - valbiotis.com€¦ · Biofortis Mérieux Nutrisciences Europe. Murielle...

2020APRIL

I nves torsp r e s e n t a t i o n

Table of contents

April 2020© NON CONFIDENTIAL – VALBIOTIS I 2

01. VALBIOTIS / Corporate

02. TOTUM-63, to reduce the risk of type 2 diabetes

03. TOTUM-070, to reduce hypercholesterolemia

05. TOTUM-448, to reduce non-alcoholic hepatic steatosis (NAFL)

04. TOTUM-854, to reduce arterial hypertension

06. FINANCIAL INFORMATION

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


An original multitarget approach,enabled by the use of plants.

A first strategic partnership,a template of collaboration agreement for the developmentand commercialization, at a global level.

A need for prevention:to reduce the risk of major metabolic diseases.

A high level of evidence,with clinical studies and health claims.

4 patent families,a robust intellectual property worldwidethanks to a specific know-how of plants.

A pipeline of innovative productsgenerated by a proprietary R&D 1200m2 platform.

SCIENCE BUSINESSA new class of Nutrition Healthproducts to address unmet medical needs

A model validated by a first globaland long-term strategic partnership

Founded in 2014 3 locations France: Périgny, La Rochelle, Riom 36 employees: 75% in R&D; > 50% womenProprietary preclinical platformEuronext Growth (ALVAL)

An advanced pipeline, addressing unmet medical needs


A unique partnership in the field of Nutrition Health


+ Tiered royalties on net sales+ Supply revenues

Milestones payments: up to CHF 66 million

Upfront: CHF 5 million

A long-term strategic partnershipfor the development and worldwide commercialization

of TOTUM-63 in prediabetes

A worldwide contractsigned beforepivotal phase

Commercializationpossible priorto health claim

A license and supplyagreement

Joint Advisory Committee

The success of an innovative model in health industry,proven effective in only 5 years


• Foundation of VALBIOTIS

• Discovery of TOTUM-63:first studies and patent applications

• Initial Public Offering

• Internalization of the R&D platform

• First strategic partnershipwith a global healthcare player

• Development of other products of thepipeline following TOTUM-63 standard

• Clinical validation of the first product, TOTUM-63

23.7 M €raised since 2014 (equity)

36 collaborators1200m2 R&D platform in-house4 employees

+ academic partners

Up to 71 M CHFupfront and milestones payments+ Royalties on net sales+ Supply revenue(1st partnership)• First fundraising

• Strategic patents grantedfor TOTUM-63

20142016

20172019

2020

An expert management team for healthcare innovation

April 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 experience 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

© NON CONFIDENTIAL - VALBIOTIS

Milestones 2020: TOTUM-63


FEBRUARYPartnership signedwith Nestlé HealthScience

MARCHREVERSE-IT launch (prediabetes, untreated Type 2 Diabetes)Phase II/III pivotal study, TOTUM-63

JUNE SEPTEMBER

REVERSE-IT: FPFV

High-value scientific & medical supervisory Board

April 2020 9

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.

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

Bruno GUIGASPhD - Leiden University (Netherlands)

Assistant professor.


A proprietary platform dedicated to metabolic diseases

April 2020 10

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


A high level of evidence for prevention


A R&D processfollowing the outline

of pharmaceuticaldevelopment

Health claims:well established regulatory processes


Set product specifications

and quality management.

Provide non-ambiguous proof of the efficacy

of the product in at-risk population,

according to current regulation.

HEALTH CLAIMS

F O O D S U P P L E M E N T S TAT U S NATURAL HEALTH PRODUCT

Different framesamong countries

“TOTUM-63 may reducethe risk of type 2 diabetes,

a disease associatedwith several risk factors.”

”TOTUM-63 reducesfasting glycemia,

which increase is a risk factorfor type 2 diabetes.”

Free claim, but strictlycompliant with clinical evidence.

Composition, quality& safety

Composition, quality± safety

Quality + evidence regardingsafety and efficacy

The business model


TARGET POPULATIONSubjects at risk of developingmetabolic diseases

PRESCRIBERS / ADVISORSHealthcare professionals

RETAILPharmacies / drugstoresnetwork, web+ ad hoc omnichannelstrategy by country

COM

MER

CIA

LIZA

TIO

N M

OD

EL

Upfront and milestones paymentsFunding of clinical studies

Royalties on salesSupply

LONG TERM STRATEGIC PARTNERSHIP

Global agreements along the products life cycle:- Last stages of clinical development- Galenic development and supply- Worldwide commercialization

REVENUE GENERATING GROWTH


4 Nutrition Health productsin clinical development stages,to reduce the risk of developing metabolic diseases

A global IP strategy across the portfolio


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

All patents registered internationally, including USA, Europe, Canada, China, Australia, Russia, Japan, Brazil.

PATENT FAMILIES APPLICATIONS WORLDWIDE

Patents applied for in + 60 countries

Solid scientific results selectedby major international scientific societies

April 2020© NON CONFIDENTIAL - VALBIOTIS 16

communicationsduring

scientific congressessince 2016

Including 7 acceptedcommunications in the 3 major

diabetes congresses worldwide

3 selections by the Keystone Symposia

13

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


Prediabetes: an opportunity for diabetes prevention


“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

Reversible metabolicimpairments

Irreversible metabolicimpairments

in most cases

PREDIABETESAT- R I S K S TA G E TYPE 2 DIABETES

Lifelong treatments,costful and stressful follow-up+ morbid complications

RISK OF PROGRESSION TO TYPE 2 DIABETES WITHOUT INTERVENTION

PREDIABETES1 year5% to 10%2

3-4 years25% to 37%3,4

Long term70% to 90%2

Prediabetes: a favourable medical environment for new products

19

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:

April 2020

And / Or

Moderate fasting hyperglycemiaFasting glycemia from 1.00 to 1.25 g/L

Or 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


TOTUM-63: a worldwide innovation designed for people with prediabetes


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

Already marketable in Europe, with authorizations granted, related to its status.

Different formulations: capsules, powder, or integrated into medical nutrition products.

100% natural, perfect tolerance.

First clinically proven and natural solutioncreated to reduce the risk of developing type 2 diabetes

Complete characterisationof the biomolecules (HPLC-UV/MS)

Combination of 5 alimentary plant extracts

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


TOTUM-63:preclinical data on type 2 diabetes prevention


Positive and significantresults on:

Fasting glycemiaInsulin-resistanceBody weightFat mass

High Fat Diet mice(HFD)

Diabetic mice model: db/db

Prevention protocols Control (n= 6)HFD (n= 12)HFD + TOTUM-63 (n=11)

Control (n=10)TOTUM-63 (n=10)

TOTUM-63:preclinical data on type 2 diabetes reversion


Positive and significantresults on:

Glycemia OGTTInsulin-resistanceBody weightFat mass

Reversion protocolsHigh Fat Diet mice (HFD)

Low fat diet, LFD (n= 10)High fat diet, HFD (n= 12)HFD + TOTUM-63 (n= 12)

April 2020 24

TOTUM-63: Phase II 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 (3 intakes)

• 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 withmoderate hyperglycemia, hyperglycemia at 2 hours (OGTT) and hypertriglyceridemia.

• Age*: 57.1 years (± 1.4)• Gender: 35 female, 16 male• BMI*: 31.3 kg/m2 (± 0.8)• Fasting glycemia*: 1.26 g/L (± 0.02)• 2 hours OGTT glycemia*: 1.85 g/L (± 0.08)

• Fasting triglycerides*: 1.78 g/L (± 0.10)

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


* Mean values ± SEM

April 2020 25


Primary endpoint met: reduction in fasting glycemia vs. placebo


– 9.3%a

a Difference of the means of individual variations expressed in %

TOTUM-63

April 2020 26


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


– 22.5%a TOTUM-63


April 2020 27


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


April 2020 28

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


FLI ≥ 60 : High probability of steatosis


– 32.2%a – 18.7%a

TOTUM-63


April 2020 29

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

TOTUM-63 : an innovative active substance in the last stage of clinical development


PHASE II/III: REVERSE-ITINTERNATIONAL PIVOTAL STUDY

PHASE IIPOSITIVE RESULTS

2020

INDUSTRIAL PROCESS VALIDATEDWITH PIERRE FABRE GROUP

HEALTH CLAIMS

EFSA - CANADA HEALTH - FDAAND OTHER REGULATORY AUTHORITIES BY COUNTRY

GLOBAL STRATEGIC PARTNERSHIPWITH NESTLÉ HEALTH SCIENCE

PHASE I/IIPOSITIVE RESULTS

REVERSE-IT: the international Phase II/III pivotal studyin prediabetics and untreated Type 2 diabetics


An international multicentric, randomized, placebo-controlled, double blind study.Dose: 5g/day2 regimens: 2 and 3 intakes/dayA 3-month follow-up period, post-supplementation

Study design

Prediabetics + early stage untreated Type 2 diabetics• Elevated fasting glycemia (≥ 1.10 g/L and ≥ 1.26 g/L)• Abdominal obesity: waist circumference ≥ 102 cm (men) and > 88 cm (women)

Extended target population

• Primary endpoint: reduction in fasting glycemia (a risk factor for type 2 diabetes)with TOTUM-63, 3 intakes/day, vs placebo

• Other critera: 2h glycemia (Oral Glucose Tolerance Test, OGTT), body weight, waistcircumference, body fat mass (DEXA)* + other metablic parameters

TOTUM-635.0 g

(3 intakes) / day

N=200

Placebo3 intakes

/ day

N=200

TOTUM-635.0 g

(2 intakes) / day

N=200(open label)

1 to 4 weeks

Follow-up post-supplementation3 months

Randomization

Duration= 6 months

600 subjects

Same endpoints as in clinical Phase II

Prediabetes market data

April 2020 32

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 USA, Canada, Top 5 Europe:134 millions persons with prediabetes

Today,13.4 millions people diagnosed

with prediabetes, waiting for a solutionmillions diagnosedin the USA10


900 million prediabeticsin the world

A fast-growing market in the coming decade: estimate for North America and Top 5 Europe

April 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-070,to reduce hypercholesterolemia


Hypercholesterolemia:a major component of cardiovascular risk worldwide


Excessive concentration of "bad" cholesterol (LDL cholesterol) in the blood.Can be associated with an excess of triglycerides or with too low blood "good" cholesterol (HDL cholesterol).

people with hypercholesterolemia in USA and Europe 3. 268 million

Diagnosis criteria: LDL-cholesterol > 1.60 g/L; HDL-cholesterol < 0.40 g/L; total cholesterol > 2.00 g/L.

Checkups are necessary on a regular basis, especially for people with other cardiovascular risk factors.

A frequent metabolic abnormality which affects 39% of the adult world populationand 30% of the French population 1,2.

A major risk factor for atherosclerosis, as obesity, diabetes and high blood pressure,which causes cardiovascular disease: ischemic heart disease, stroke, peripheral arterial disease 2.

1. Global Health Observatory (GHO) data, Organisation Mondiale de la Santé, 2008, www.who.int/gho/ncd/risk_factors/cholesterol_prevalence/en/ ; 2. Ferrières J, Dyslipidémies et risque cardiovasculaire : données épidémiologiques, Endocrinologie et nutrition, 2010.3. Cardiovascular research Group 2011.

http://www.who.int/gho/ncd/risk_factors/cholesterol_prevalence/en/

TOTUM-070: an active substance for people with hypercholesterolemia,at risk of cardiovascular diseases


Complete characterisationof the biomolecules

(HPLC-UV/MS)

A combinationof alimentaryplant extracts

Mild to moderate elevated blood LDL-cholesterol (“bad cholesterol“),risk factor for cardiovascular diseases

TOTUM-854,to reduce arterial hypertension


Arterial hypertension (AHT):the leading cardiovascular risk factor in the world


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

AHT defined as arterial blood pressure ≥ 140/90 mmHg* persisting over time 2,or ≥ 130 /85 mmHg in subjects with metabolic syndrome. 3

people with AHT in the world (2015). 1

Efficient management of AHT decreases the risk of cardiovascular complications and contributes to longer life expectancy. 21 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 billion

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

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

TOTUM-854: an active substance for people with high blood pressure,at risk of cardiovascular diseases



(HPLC-UV/MS)


Mild to moderate elevated blood pressure,risk factor for cardiovascular diseases

TOTUM-448,to reduce non-alcoholic hepatic steatosis


Hepatic steatosis: an opportunity to prevent NASH and its complications

April 2020 41

”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

April 2020 42

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.

Recommendations for systematicscreening in at-risk populations 2


TOTUM-448: an active substance for people at risk of NASH


Reduction of non-alcoholic hepatic steatosis (NAFL),risk condition for NASH


(HPLC-UV/MS)


ALVAL-FR - Shareholders breakdown

April 2020 45

ANALYSTS Portzamparc Christophe DOMBUTarget price: 10,50 EUR (data February 2020)

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


Management

Sofimac Partners

Individuals and institutions

59.3% 15.0%

7.1%

Family offices

18.6%

FREE FLOAT77.9%

Cash and R&D expenses

April 2020 46

Total operating income: € 1,023 K

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

Cash Position : €3.9 millionat 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) and upfront payment from Nestlé Health Science (€ 4.7 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


2020APRIL

APRIL presentation 2020 - valbiotis.com€¦ · Biofortis Mérieux Nutrisciences Europe. Murielle...

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Transcript of APRIL presentation 2020 - valbiotis.com€¦ · Biofortis Mérieux Nutrisciences Europe. Murielle...