VALBIOTIS : Investors presentation – April 2020

VALBIOTIS

INVESTORS PRESENTATION

APRIL 2020

01.

02.

03.

04.

05.

06.

2

VALBIOTIS / Corporate

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

TOTUM-070, to reduce hypercholesterolemia

TOTUM-854, to reduce blood pressure

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

FINANCIAL INFORMATION

© NON CONFIDENTIAL

A R&D company, committed	3
to scientific innovation,
for preventing and combating
metabolic diseases

Active substances from plants and based on science, to address unmet medical needs

• An innovative approach,
  enabled by a specific expertise of plants
• A high level of evidence, with clinical studies and health claims
• A pipeline of innovative active substances in Nutrition Healthcare, engineered in our R&D centers
• 4 patent families registered on 5 continents

© NON CONFIDENTIAL

4

Nutrition Healthcare:

a portfolio of active substances, in clinical stages

	Phase II	Phase II/III	Study launch	Results
TOTUM-63 / Prediabetes
		Mid-2020	S1 2022

TOTUM-070 / Hypercholesterolemia
	Q3 2020	Q4 2021

TOTUM-854 / Arterial hypertension
	Q4 2020	Q1 2022

TOTUM-448 / Fatty Liver
	S2 2021	-

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

2020

2019

2017

5

First strategic partnership with a global healthcare player

• Up to 71 M CHF upfront and milestones payments
• • Royalties on net sales
  • Supply revenue

Development of other products of the pipeline following TOTUM-63 standard

Initial Public Offering

• Internalization of the R&D platform
• Strategic patents granted for TOTUM-63
• Clinical validation of the first product, TOTUM-63
• 36 employees
• 1200m2 R&D platform in-house

Foundation of VALBIOTIS

2016

2014

• First fundraising
• Discovery of TOTUM-63: first studies and patent applications
• 4 employees and academic partners

© NON CONFIDENTIAL

25.2 million euros

raised since 2014 (equity)

An expert management	6
team for healthcare
innovation

Sébastien PELTIER	Jocelyn PINEAU	Pascal SIRVENT	Murielle CAZAUBIEL	Josep INFESTA
CEO, PhD - HDR.	MBA.	PhD - HDR.	M.Sc.	MD, MBA
Chairman of the Board of Directors	CFO, Member of the board	CSO, Member of the board	CMO, Member of the board	Head of Global Busines Development
20 years' experience in Research	20 years'experience in project	Over 15 years' research	25 years' experience in health	Medicine degree, 25 years' international
& Development for drug and food	management positions as part	experience in the field of	and nutrition. Founder and	experience in marketing and business
supplement industries. Unique, proven	of executive management boards,	metabolic diseases, with	former Executive Director of	development focused on Consumer
experience with health claims referring	in the agro-food and food	leadership positions and a	Biofortis Mérieux Nutrisciences	Healthcare, with top management
to the reduction of a disease risk	supplements industries.	strong background in	Europe.	positions. Former Vice President at
(EFSA - European Food Safety		international scientific		Sanofi, Johnson & Johnson and Pfizer.*
Authority - article 14.1a)		partnerships.

© NON CONFIDENTIAL

*External consultant

An expert management	7
team for healthcare
innovation
Supervisory Board

Laurent LÉVY, PhD	Agnès TIXIER	Sébastien BESSY
Chairman of the Supervisory Board	Audit Committee	Remuneration Committee
Remuneration Committee	Executive Director,	Vice President Global Strategic
CEO, co-founder,	Crédit Mutuel, Equity SCR	Operations, IPSEN
NANOBIOTIX

Dr Jean ZETLAOUI, MD, MBA

Audit Committee

Medical Affairs and Clinical

Development Consultant

30 years' experience as hospital

practitioner in anesthesia-reanimation(AP-HP), Head of scientific and medical affairs, market access at Sanofi, Nestlé Health Science and Novartis Pharma.

© NON CONFIDENTIAL

© NON CONFIDENTIAL

A unique partnership	8
in the field of
Nutrition Health

1. long-termstrategic partnership for the development and worldwide commercialization of TOTUM-63 in prediabetes.

A worldwide contract signed before pivotal phase

A license and supply agreement

Milestones payments: up to CHF 66 million, covering the cost of TOTUM-63 development

• Upfront: CHF 5 million
• Tiered royalties on net sales
• Supply revenues

Joint Advisory Committee VALBIOTIS / Nestlé Health Science

Commercialization possible prior to health claim

2020-2022 strategic roadmap	9

Objectives

1. Commercial launch of TOTUM-63
2. Launch of new clinical programs, from R&D activities
3. Partnerships on other active substances in the portfolio

2020

TOTUM-63 (prediabetes, T2D)

1st patient Phase II/III REVERSE-IT(Mid 2020)

TOTUM-070(LDL-cholesterol)

1st patient Phase II (Q4)

New therapeutic

areas

2021

TOTUM-63 (prediabetes, T2D)

Scientific publications

TOTUM-854 (AHT)

1st patient Phase II (Q1)

TOTUM-448 (NAFL)

1st patient Phase II (S2)

TOTUM-070(LDL-cholesterol)

Results Phase II (Q4)

2022

TOTUM-63 (prediabetes, T2D)

• Phase II/III results (S1)
• Health claim file

TOTUM-854 (AHT)

Phase II results (Q1)

© NON CONFIDENTIAL

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Milestones 2020:

TOTUM-63

FEBRUARY 2020	MARCH 2020	JUNE 2020	SUMMER 2020	SEPT 2020

P A R T N E R S H I P R E V E R S E - I T	A D A	R E V E R S E - I T
Partnership signed with	REVERSE-IT launch	American Diabetes	FPFV (first patient, first visit)
Association,
Nestlé Health Science	(prediabetes, untreated
80th scientific sessions
	Type 2 Diabetes)
	Chicago, Illinois (USA)
	Phase II/III pivotal study,

TOTUM-63

© NON CONFIDENTIAL

E A S D

European Association for the Study of Diabetes, 56th annual meeting

Vienna, Austria

High-value scientific & medical	11
supervisory Board

700 scientific publications: Diabetes Care, The Lancet, Nature

Pr Samy HADJADJ	Bruno GUIGAS	Pr Jean-Marie BARD	Nathalie BOISSEAU	Thierry MAUGARD	André MARETTE
MD, PhD, PU-PH	PhD	PharmD, PhD, PU-PH	PhD, PU	PhD, PU	PhD - Laval University Hospital
Nantes University Hospital	Leiden University (Netherlands)	Nantes University Hospital	Clermont Auvergne University	La Rochelle University	INAF (Canada)
Professor of endocrinology,	Assistant professor.	Professor of biochemistry at	Professor of sports physiology.	Professor of biochemistry in	Professor in the Faculty of
diabetology and metabolic		the Faculty of Pharmacy and		the Biotechnology	Medicine. Researcher at the
diseases, Hospital practitioner.		Head of the Biopathology		Department.	Quebec Heart
		Department at Institut de			and Lung Institute and Scientific
		Cancérologie de l'Ouest (ICO)			Director of the Institute of Nutrition
		in Nantes.			and Functional Foods (INAF) at
					Université Laval.

© NON CONFIDENTIAL

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3 R&D centers dedicated to metabolic diseases

Plant-based chemistry

Design of active substances (compliant with pharmacopeia US / EU).

Extraction processes, characterisation, purification, bioengineering, pharmaco-modulation.

Discovery et Preclinical Research

In vivo screening on relevant models of metabolic diseases.

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

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

Clinical research

Design, lead and achieve all Phase I/II, II and II/III clinical studies. Clinical studies following the Good Clinical Practice standards (GCP), within specialized clinical investigation centers.

Nutrition Healthcare:	13
a high level of evidence
for prevention
A R&D process following the outline
of pharmaceutical development.
A short development cycle: 6-7 years

Research	Preclinical studies	Clinical studies	Regulatory approval
			FDA, EFSA
			Health Canada,
			other regulatory
			authorities
			by country

Phase I/II	Phase II	Phase II/III	Obtention
Security	Efficacy	Efficacy	of health claim
	on target	confirmation on
	population	target population

© NON CONFIDENTIAL

Unequivocal clinical evidence for the reduction of risk factors versus placebo

Industrial development of the product

© NON CONFIDENTIAL

Health claims: well established regulatory processes

Different frames among countries.

Set product specifications and quality management.

HEALTH CLAIMS

Provide non-ambiguous proof of the efficacy of the product in at-risk population, according to current regulation.

14

Food supplement status	Food supplement status	Natural health product
Composition, quality	Composition, quality	Quality + evidence regarding
& safety	± safety	safety and efficacy
"TOTUM-63 may reduce	"TOTUM-63 reduces	Free claim,
the risk of type 2 diabetes,	fasting glycemia,	but strictly compliant
a disease associated	which increase is a risk factor	with clinical evidence.
with several risk factors."	for type 2 diabetes."

The business model: strategic agreements with global health players

Long term strategic partnerships

Global agreements along the products life cycle:

• Last stages of clinical development
• Galenic development and supply
• Worldwide commercialization

Revenue generating growth

Upfront and milestones payments

Funding of clinical studies

• Royalties on sales
• Supply

15

Commercialization model

Target population

Subjects at risk of developing metabolic diseases

Advisors

Healthcare professionals

Retail

Pharmacies / drugstores

network, online sale

• ad hoc omnichannel strategy by country

© NON CONFIDENTIAL

16

Nutrition Healthcare

4 Nutrition Health products

in clinical development stages, to reduce the risk of developing metabolic diseases

© NON CONFIDENTIAL

© NON CONFIDENTIAL

17

A global IP strategy across the portfolio

4 patent families applications worldwide

Demonstrates that innovative combinations

of plant extracts are patentable for 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.

TOTUM-63

TOTUM-070

TOTUM-854

TOTUM-448

Patents applied for in + 60 countries

Solid scientific results		18
selected by major international
scientific societies

13

Communications during scientific congresses since 2016

Including 7 accepted communications in the 3 major diabetes congresses worldwide:

• American Diabetes Association (ADA)
• European Association for the Study of Diabetes (EASD)
• International Diabetes Federation (IDF)

© NON CONFIDENTIAL

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TOTUM-63, to reduce

the risk of type 2 diabetes

© NON CONFIDENTIAL

Prediabetes:

an opportunity for diabetes prevention

"Prediabetes should not be considered as a disease but as a high-risk stage of developing T2 diabetes"1

AT-RISK STAGE

PREDIABETES

REVERSIBLE

metabolic

impairments

© NON CONFIDENTIAL

Risk of progression to type 2 diabetes

without intervention

1year:

5% to 10%2

3-4 years:

25% to 37%3,4

Long term:

70% to 90%2

20

TYPE 2

DIABETES

IRREVERSIBLE

metabolic impairments

(in most cases)

Lifelong treatments,

costful and stressful follow-up

+ morbid complications

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

Prediabetes:

a favourable medical environment for new products

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

21

MODERATE FASTING HYPERGLYCEMIA	MODERATE FASTING HYPERGLYCEMIA
Fasting glycemia from:	HbA1c:	Fasting glycemia from:

© NON CONFIDENTIAL

1,00 to 1,25 g/L I ≥ 5,7% and < 6,5%	1,10 and 1,25 g/L
AND/OR	AND/OR
GLUCOSE INTOLERANCE	GLUCOSE INTOLERANCE
Glycemia from	Glycemia from
1,4 and 2 g/L	1,4 and 2 g/L
2 hours after a 75g	2 hours after a 75g
oral glucose intake	oral glucose intake

A recognition by international scientific societies and health authorities:

• Screening and diagnosis modalities
• Recommendations for prediabetes management

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

TOTUM-63:

a worldwide innovation designed for people with prediabetes

First clinically proven and natural solution created to reduce the risk of developing type 2 diabetes.

© NON CONFIDENTIAL

22

A combination of plant extracts

Complete characterisation of the biomolecules

(HPLC-UV/MS)

• Clinical evidence of efficacy already obtained in prediabetics, for the reduction of 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, possible integration into medical nutrition products.
• 100% natural, perfect tolerance.

TOTUM-63: an active substance for a multitarget action on several tissues involved in metabolic regulation

WHITE ADIPOSE TISSUE

Insulin

I

↓ Inflammation	IR IRS1
	PI3K

23

LIVER

• Expression lipid storage genes

				↓ Pro-inflammatory	Akt↑P	G
				Glucose
				macrophages
Intestinal microbiota	↑	Diversity		CD11c+	Improved
GUT
						insulin signaling
Sucrase-		Glucose G
Maltase-	GLUT2	SGLT1
Isomaltase	Glucoamylase
					G
		GLUT2		G			↑ Peripheral
	↓ Glucose absorption	G	G			glucose intake
	G	G

↓ATGL	↓Fsp27
LIPID	↓
	DROPLET	PLIN2
			↓Triglycerides
LIPOGENESIS		↓ Steatosis
↓Cd36, ↓Fabp1, ↓ Acaca

• Fas, ↓ Scd1
• • Expression

lipogenesis genes

BLOOD

BROWN

ADIPOSE TISSUE

MUSCLE

Glucose

Insulin

I

IR IRS1

PI3K

• Expression thermogenesis genes

↑Ucp1 ↑Dio2 ↑Cox8b

↓ Size

lipid droplets

Decrease in fasting glycemia Improved glucose tolerance

G

GLUT4 GLUT4

• Akt↑P

Improved insulin signaling

TOTUM-63: preclinical data on type 2 diabetes prevention

24

Diabetic mice model: db/db	High Fat Diet mice
	(HFD)

Prevention protocols

Positive and significant results on:

• Fasting glycemia
• Insulin-resistance
• Body weight
• Fat mass

© NON CONFIDENTIAL

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

TOTUM-63:	25
preclinical data
on type 2 diabetes
reversion

Reversion protocols

High Fat Diet mice

Positive and significant results on:

• Post-prandialglycemia
• Insulin-resistance
• Body weight
• Fat mass

Low fat diet, LFD (n= 10)

High fat diet, HFD (n= 12)

HFD + TOTUM-63 (n= 12)

© NON CONFIDENTIAL

TOTUM-63:

Phase II clinical results

Study design

• Multicenter, randomised, unbalanced
  (3:1, VALEDIA®:Placebo) and double-blindplacebo-controlled study, 2 parallel-groups
• Supplementation period: 6 months, 5 g/day (3 intakes)
• Primary endpoint: change in fasting glycemia between baseline and 6 months
• Main secondary endpoints: 2 hours OGTT glycemia, insulin sensitivity, anthropometric parameters, hemodynamic parameters lipid profile, safety

26

Study population

51 prediabetics with abdominal obesity associated with moderate 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)
• • Mean values ± SEM

© NON CONFIDENTIAL

Coordinating Investigator: Dr. David Gendre (MD Biofortis)

Expert: Pr. Jean-Marie Bard (PharmD, PhD, Professor of Basic and Clinical Biochemistry, Nantes, France)

ID-RCB Number: 2016-A00484-47

TOTUM-63:	27
Phase II clinical results
Primary endpoint met:
reduction in fasting glycemia vs. placebo

TOTUM-63

- 9.3%a

© NON CONFIDENTIAL

aDifference of the means of individual variations expressed in %

TOTUM-63:	28
Phase II clinical results
Secondary endpoint met:
reduction in 2h-glycemia (OGTT)
vs. placebo

TOTUM-63

- 22.5%a

© NON CONFIDENTIAL

aDifference of the means of individual variations expressed in %

TOTUM-63:	29
Phase II clinical results
Secondary endpoints met:
reduction in anthropometric parameters
vs. placebo

NON CONFIDENTIAL

- 1.9 kga

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

TOTUM-63

- 4.48 cma

©

aDifference of the means of individual variations

© NON CONFIDENTIAL

TOTUM-63:	30
Phase II clinical results
Secondary endpoints met:
reduction in triglyceridemia and Fatty Liver Index
vs. placebo

TOTUM-63

- 32.2%a

- 18.7%a

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

FLI ≥ 60: High probability of steatosis

aDifference of the means of individual variations expressed in %

TOTUM-63:

Phase II clinical results

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

Overall population

Systolic blood pressure evolution

(from baseline to 6 months), overall population

-10.6 mmHga

31

Sub-population: subjects with high

blood pressure

Systolic blood pressure evolution

(from baseline to 6 months), subpopulation SBP >130mmHg

TOTUM-63

- 18.9 mmHga

© NON CONFIDENTIAL

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

aDifference of the means of individual variations

TOTUM-63:	32
an innovative active substance
in the last stage of clinical
development

	Industrial
	process				Phase II/III :
	validated with	Phase II
	Pierre Fabre		Global strategic	REVERSE-IT
	Groupe	positive		international
Phase I/II	May	results		partnership with	pivotal study
	July /		NHS	mid-2020
positive
	September		February
results
2017
2019		Health claims
	EFSA - Health
	Canada - FDA and
	other regulatory
			2020authorities

by country

© NON CONFIDENTIAL

REVERSE-IT:

the international Phase II/III pivotal study in prediabetics and untreated Type 2 diabetics

Study design

An international multicentric, randomized, placebo-controlled, double blind study.

Dose: 5 g/day

2 regimens: 2 and 3 intakes/day

A 3-monthfollow-up period, post-supplementation

600 subjects

Randomization

TOTUM-63		Placebo
5.0 g		3 intakes
(3 intakes)		/ day
/ day
N=200		N=200

33

TOTUM-63

5.0 g

(2 intakes)

/ day

N=200

(open label)

© NON CONFIDENTIAL

Extended target population

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)

Same endpoints as the previous clinical Phase II

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,

waist circumference, body fat mass (DEXA)* + other metabolic parameters of interest

Duration = 6 months

Results

expected

S1 2022

* Not tested in Phase II

© NON CONFIDENTIAL

Prediabetes market data

900 million

prediabetics in the world

134 million

adults with prediabetes

(total USA, Canada, Top 5 Europe)

13.4 million

adults diagnosed with prediabetes, waiting for a solution

10 million

adults diagnosed in the USA

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

34

86				Prediabetic adult
(33.9%)
			population per country
					Million adult
				(% of overall adult population)
	14
	(20.2%)
		12
		(24.2%)
			6	6
			(22.1%)
				(15.8%)	5
					(10.1%)	4
						(8.4%)
United States	Germany	UK	Canada	Spain	Italy	France

Note: estimation for 2018

Data: AEC Partners data on key VALBIOTIS markets: the United States, Canada and the 5 primary European countries 2019‬

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

12%35

annual growth rate

x3

in 10 years

			1.8									1.8
•	Increasing prevalence of prediabetes		1.6								1.6
•	Continuous progression of screening	€)								1.4
•	Development of prevention programs	(billions	1.4
•	Growth of the market of prediabetes
value							1.2
	healthcare products	1.2
		Market						1.0
			1.0
						0.9
			0.8			0.8
				0.7
© NON CONFIDENTIAL			0.6
		2018	2019	2020	2021	2022	2023	2024	2025	2026	2027

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

36

TOTUM-070,

to reduce hypercholesterolemia

© NON CONFIDENTIAL

© NON CONFIDENTIAL

LDL hypercholesterolemia:

a risk factor for cardiovascular diseases

"LDL-cholesterol is the primary cause of atheroscerosis."1

Atheroma plates

weakening and clogging arteries

Hyper

cholesterolemiaAtherosclerosis

LDL

Alone or associated		Risk ++ of cardiovascular mortality
with other cardiovascular
risk factors		Atheroma plate breakage
(arterial hypertension,
	is the cause of
diabetes, obesity, etc.)
		80% of sudden deaths.2

37

Stroke

Myocardial

infarction

Peripheral

arterial disease

12018 Guideline on the Management of Blood Cholesterol, a report from the American College of Cardiology/American Heart Association, Journal Of The American College Of Cardiology, 2019 2www.inserm.fr/information-en-sante/dossiers-information/atherosclerose, accessed 2 April 2020

TOTUM-070:

developed for people with mild to moderate

LDL hypercholesterolemia, a risk factor for cardiovascular diseases

© NON CONFIDENTIAL

38

A combination of plant extracts

Complete characterisation of the biomolecules (HPLC-UV/MS)

• An innovating composition, 100% natural, patented, without phytosterol nor red rice yeast.
• A Phase I/II clinical study validated the tolerance and suggested a 7-10% reduction in LDL cholesterol for the next Phase II study, in people with mild to moderate hypercholesterolemia.
• • A 10% reduction in cholesterol reduces by 50% the risk of developping a heart disease within 5 years. 1
• An upcoming clinical development to obtain a proprietary health claim related to the reduction of LDL-cholesterol, risk factor for cardiovascular diseases.

1In 40 y.o. men,www.who.int/gho/ncd/risk_factors/cholesterol_text/en/accessed 10 April 2020

TOTUM-070: the main hypothesis currently studied, for a multitarget mode of action on lipid metabolism

39

Bile acids	CYP7A1
Ongoing
ABCG5/G8

Fatty acids

Bile acids

GUT

Cholesterol

Bile duct

Ongoing

Cholesterol

OngoingOngoing

Intestinal

microbiota

CD36

Enterocyte

IBAT

Bile

acidsResidual chylomicron

NPC1L1

TG

Fatty acids

Ongoing

ApoB48

NPC1L1

ApoER

ApoB100

TGDegradation

VLDL

ABCA1

LDLR

P

AMPK

Squalene	HMGCR
Mevalonate	-CoA
	HMG
	HMGCR
	LDLR
SREBP2	PCSK9

LIVER

Degradation

PCSK9

LPL LPL

Ongoing

LDL

PCSK9

ChylomicronChylomicron

VLDLHDL

CETP

Ongoing

© NON CONFIDENTIAL

Ongoing	Lymph		Residual
BLOOD	VLDL
		LPL

Ongoing

Fatty acids

© NON CONFIDENTIAL

2020-2021: a Phase II clinical study to reduce LDL blood cholesterol

Study design	Randomization
A randomized, placebo-controlled, double blind study
Population: 120 subjects
	TOTUM-070
Dose: 3.75 g/day
	3.75 g
		/ day
Study population		N=60

People with mild to moderate LDL hypercholesterolemia

• LDL cholesterol blood level between 1.3 g/L and 2.2 g/L

Objectives

Primary endpoint: reduction in blood LDL cholesterol, a cardiovascular risk factor, with TOTUM-070,vs. placebo

Other criteria: several metabolic parameters of interest

120 subjects

FPFV:

Q4 2020

Duration:

6 months

Results

expected Q4 2021

40

Placebo

3.75 g / day

N=60

*Not tested in Phase II

Mild to moderate

LDL hypercholesterolemia:

1.2

41

© NON CONFIDENTIAL

the market data

Adults with moderately elevated LDL* (total USA & Top 5 Europe)

Patients diagnosed and who use food supplements to control their cholesterol levels (total USA & Top 5 Europe)

39%

of adults worldwide

with high cholesterol 1

174 million

83 million

34 million

billion euros

A large and well established market in USA & Europe Top 5

Adults diagnosed

(total USA & Top 5 Europe)

Current average diagnosis rate (USA/UE) = 48%

Data AEC Partners, Elevated LDL preliminary market estimation, 2020.

42

TOTUM-854,

to reduce blood pressure

© NON CONFIDENTIAL

© NON CONFIDENTIAL

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

"The continuous relationship between blood pressure and risk of cardiovascular events has been shown at all ages and in all ethnic groups, and extends from high blood pressure levels to relatively low values."

Weakened arteries

Major risk of mortality	Arterial
and disability	hypertension

First cause of premature

death in the world:

10 million in 2015.1

• 40 % of disability adjusted

life years related to high blood

pressure since 1990.1

43

Stroke	- Hemorrhagic
- Ischemic

Ischemic	- Myocardial infarction
heart disease	- Heart failure

Renal failure

Peripheral

artery disease

1ESC/ESH Guidelines for the management of arterial hypertension, European Heart Journal, 2018

Arterial hypertension (AHT):	44
the leading cardiovascular risk
factor in the world

1,1 billion

people with AHT in the world (2015).1 the world's first chronic disease.

The normal blood pressure of an adult is established at 120 mmHg * when the heart contracts (systolic pressure) and at 80 mmHg when the heart relaxes (diastolic pressure)2.

In Europe, AHT defined as arterial blood pressure ≥ 140/90 mmHg* persisting over time2, or ≥ 130 /85 mmHg in subjects with metabolic syndrome.3

In USA, the hypertension threshold has been lowered to 130/90 mmHg.

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

© NON CONFIDENTIAL

*Blood pressure is expressed in millimeters of mercury (mmHg)

1ESC/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

TOTUM-854: developed for people with mild to moderate elevation of blood pressure, a risk factor for cardiovascular diseases

© NON CONFIDENTIAL

45

A combination of plant extracts

Complete characterisation of the biomolecules (HPLC-UV/MS)

• An innovating composition, 100% natural, patented.
• An ongoing partnership with the University of Avignon Pharm- Ecology Cardiovascular Laboratory (EA 4278) to deepen the mechanism of action of TOTUM-854.
• An upcoming clinical development to obtain a proprietary health claim in Europe and North America, related to the reduction of systolic blood pressure, risk factor for cardiovascular diseases.

TOTUM-854: the main hypothesis currently studied, for a multitarget mode of action on blood pressure

46

Angiotensinogène

	Ongoing
Angiotensin I
ACE	Angiotensin Conversion
	Enzyme
Angiotensin II
	Ongoing

R-AT1

Ongoing

NADPH	Oxidase

Ongoing

TLR4

MAPK

Inflammation

NF-kB

ROS

PI3K

Ongoing

Autophagy

• AMPK SIRT1

	eNOS
Akt P	Ongoing

NO

© NON CONFIDENTIAL

Mitochondrie

Ongoing

2020-2022: a Phase II clinical study for the reduction of blood pressure

Design study

A randomized, placebo-controlled, double blind study

Population: 100 subjects

Dose: 2.5 g/day

Population study

People with mild to moderate elevation of blood pressure, untreated

• Blood pressure between 130/80 mmHg and 160/90 mmHg

47

100 subjects

Randomization

TOTUM-854	FPFV:	Placebo
2.5 g	Q1 2021	2.5 g
/ day		/ day
N=50	Duration:	N=50
6 months

© NON CONFIDENTIEL

Objectives	Results
expected
Primary endpoint: reduction in systolic blood pressure,	Q1 2022
a cardiovascular risk factor, with TOTUM-854,vs. Placebo
(measurement in clinical investigation center)
Others endpoints: blood pressure ambulatory measurement over 24h

*Not tested in Phase II

© NON CONFIDENTIAL

Mild to moderate elevation of blood pressure: the market data

Adults with moderate elevation of blood pressure (total USA & Top 5 Europe)

Adults diagnosed and who use food supplements to control their blood pressure (total USA & Top 5 Europe)

124 million

77 million

32 million

48

1.15

billion euros

The mild to moderate raise of blood pressure market in USA + Europe Top 5

Adults diagnosed

(total USA & Top 5 Europe)

Current average diagnosis rate (USA/UE) = 61%

Données AEC Partners, Pre-HTA preliminary marjet estimation, 2020.

49

TOTUM-448, to reduce non-alcoholic hepatic steatosis

© NON CONFIDENTIAL

© NON CONFIDENTIAL

Hepatic steatosis:

an opportunity to prevent NASH and its complications

"The progression from NAFL to NASH dramatically increases the risks

of cirrhosis, liver failure,

and hepatocellular carcinoma"1

Reversible triglycerides accumulation in

> 5% of hepatocytes 1

HEALTHY	HEPATIC
LIVER	STEATOSIS

Risk of progression to NASH without intervention

Without intervention, up to

40% of subjects with non- alcoholic hepatic steatosis

will at least develop NASH

within 8 to 13 years.2

50

Fibrosis,

NASHCirrhosis,

Hepatocellular carcinoma,

Liver failure

• Ballooning » +inflammation1

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

© NON CONFIDENTIAL

Non alcoholic hepatic steatosis,	51
established specific medical practices

Recommendations for systematic screening in at-risk populations2:

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

Liver ultrasonography: the recommended non invasive first line exam for diagnosis.2,3 - Not expensive, largely available, highly sensitive for moderate to severe steatosis.4

Fatty Liver Index (FLI): a predictive score for screening in primary care1

Based on routine clinical examinations:

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

FLI < 30: No steatosis

FLI ≥ 60: High probability of steatosis

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

TOTUM-448: developed for people with non-alcoholic fatty liver disease,

at risk of NASH

© NON CONFIDENTIAL

52

A combination of plant extracts

Complete characterisation of the biomolecules (HPLC-UV/MS)

Initiation of the Phase II clinical study planned for S2 2021

53

Financial information

© NON CONFIDENTIAL

ALVAL-FR:

Shareholders breakdown

10,50 EUR

Target price (data February 2020)

Portzamparc

Christophe DOMBU

11,00 EUR

Target price (data October 2019)

Invest Securities

Thibaut VOGLIMACCI-STEPHANOPOLI

© NON CONFIDENTIAL

59.3%

Individuals et institutions

54

15.0%

Management

7.1%

Sofimac Partners

18.6%

Family Offices

77.9%

Free float

At 24/12/2019

© NON CONFIDENTIAL

Cash and

R&D expenses

Total operating income: € 1,023 K of which :

• Research Tax Credit: € 605 K
• Operating grants: € 372 K

Cash Position: € 3.9 million

(at 30/06/2019)

Not included:

collection of Research Tax Credit 2018 (€ 1.2 M) and gross revenue of

Oct. 2019 capital increase (€ 7.2 M) and upfront payment from Nestlé

Health Science (CHF 5 M).

55

In € '000 - IFRS	30/06/2019	31/12/2018
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)

VALBIOTIS

INVESTORS PRESENTATION

APRIL 2020