VALBIOTIS
INVESTORS PRESENTATION
APRIL 2020
01.
02.
03.
04.
05.
06.
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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
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A unique partnership | 8 |
in the field of | |
Nutrition Health |
- 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
- Commercial launch of TOTUM-63
- Launch of new clinical programs, from R&D activities
- 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)
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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. |
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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 |
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Unequivocal clinical evidence for the reduction of risk factors versus placebo
Industrial development of the product
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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.
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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
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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
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Nutrition Healthcare
4 Nutrition Health products
in clinical development stages, to reduce the risk of developing metabolic diseases
© NON CONFIDENTIAL
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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 |
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Communications during scientific congresses since 2016
Including 8 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
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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.
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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
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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
- Well tolerability
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 |
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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, TOTUM-63: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
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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
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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
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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.
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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
13.00 EUR
Target price (data June 2020)
Invest Securities
Thibaut VOGLIMACCI-STEPHANOPOLI
© NON CONFIDENTIAL
59.3%
Individuals and 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: € 1,913 K of which :
- Research Tax Credit: € 1,219 K
- Operating grants: € 602 K
Cash Position: € 8.03 million
(at 31/12/2019)
Not included: collection of Research Tax Credit 2019 (€ 1.2 M), public grants (€ 0,4 M) and upfront payment from Nestlé Health Science (CHF 5 M).
55
IFRS en K€, au 31 décembre | 2019 | 2018 |
Operating income, including | 1,913 | 1,509 |
Grants | 602 | 46 |
Research Tax Credit | 1,219 | 1,183 |
R&D expenses | (3,974) | (3,826) |
Sales and marketing expenses | (1,473) | (1,059) |
Overhead costs | (1,343) | (1,284) |
Operating profit for the period | (5,157) | (4,876) |
Operating profit | (5,157) | (4,876) |
Earnings before tax | (5,504) | (4,967) |
Net profit | (5,504) | (4,967) |
VALBIOTIS
INVESTORS PRESENTATION
APRIL 2020
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Valbiotis SA published this content on 12 June 2020 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 12 June 2020 09:17:02 UTC