o be therapy

7/29/2019 o Be Therapy

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RESEARCH IS TO SEE WHAT EVERYONE HAS SEEN

AND TO THINK WHAT NOBODY HAS THOUGHT.

"Albert Szent-Gyoergyi, nobel prize 1937.


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Lean genes allow you

to eat without gaining weight

Nature did it, ObeTherapy can reproduce it.


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The Company

Created by Dr Itzik HAROSH in January 2000

Strong team of 6 researchers

5 patents giving a full scientific protection One industry contract with Zambon Group SpA (Milan,

Italy)

Several biotech collaborations

One academic collaboration with INRA (France) Member of the Genopole at Evry, France


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Core Team

Itzik HAROSH, PhD, Chairman and Chief ScientistOfficer (CSO)

Georges GAUDRIAULT, PhD, Scientific Director Sandrine BRAUD, PhD, Project Leader

Vladimir CHARRON, Engineer

David SENAC, Engineer Christelle MOUGIN, Laboratory Manager


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5

Prof. M. Radman, Hpital Necker, Paris, France; specialist in genetics and evolution;

member of the "Acadmie des Sciences de l'Institut de France".

Prof. A. Levy, The Weizmann Institute of Science, Rehovot, Israel; specialist inbiotechnology and genetics.

Prof. T. Baasov, Chemistry Faculty Technion, Haifa, Israel; specialist in medicinal chemistryand chemical synthesis.

Prof. B. Peault, McGowan Institute for Regenerative Medicine, Pittsburgh, USA; specialist incellular models and biotechnology, pioneer of Systemix.

Dr Y. Champey, former Senior Vice President and Executive Medical Director at Rhne-Poulenc Rorer.

Prof. D. Bensimon, Ecole Normale Suprieure, Paris, France; specialist in biophysics of

DNA and proteins.

Prof. M. Rubinstein, Weizmann Institute, Israel; Geneticist, Expert in the obesity field.

Prof. D. Ricquier, PhD, Director of CEREMOD/CNRS Unit 9078, Hpital Necker-EnfantsMalades, France, Expert in the obesity field in which he is a major contributor; member of the

"Acadmie des Sciences de l'Institut de France".

Advisory board


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6Source: Farrigan C, Nat Rev Drug Discov, 1, 257

PRIMARY MARKET: OBESITY


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Mission

With a completely innovative strategy,

Obetherapy aims to develop medication forobesity.

By looking for lean genes or

expenditure genes in lean phenotype


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Obesity = imbalance betweenfood intake and energy expenditure

Food intake

Energy expenditure(metabolism& physical activity)

What is Obesity ?


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9ATP

Acetyl-CoAAcetyl-CoA

Metabolic Pathways Involved In Obesity

Absorption

ObesityType II diabete

Metabolism

Carbohydrate Proteins LipidsLipidsCarbohydrates

Appetite/Satiety (CNS)


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Genes linked or associated with obesity

- Single gene 7

- Mendelian disorders 41- Associated 90

- Linkage 322

- Total 460

http://obesitygene.pbrc.edu


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Targets for obesity treatment currently in research and development

Appetit

NPY

Orexin

PTP-1B

AGRP

MG

Axokine

CNTF

Canabinoid(Rimonabant)

Satiety

OBDB

CCKPOMCMCH

TubbyCART

AgoutyFAT

GLP-1MC4RMC4R

PYY (3-36)

Energyhomeostasis

UCP1

UCP2

UCP3

PKA-IIb

-Adrenergic R-Adrenergic R

ACC-2

Adiponectin(Famoxin)

PTP1B

S6K1

Fatmetabolism

PPAR-SREBP1

C/EBPs

FATPs

PL (Orlistat)MTP

Fat Absorption


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Why did we evolve to be obese?

Is obesity an advantage?


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Natural selection Darwin's grand idea of evolution by natural selection


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Natural selection Darwin's grand idea of evolution by natural selection

Is this an advantage?


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The thrifty genome theory(James Neel, 1962 Am. J.Hum. Genet.)

During thousand of years of evolution, when foodwas scare, long periods of famine have selectedindividuals having an efficient organism for foodabsorption and energy metabolism.

When food supply increased the thrifty genotypebecome a liability rather than an asset.

On the other hand, individuals with low efficiencyfor food absorption and energy metabolism became

rare.

This explains why we are, in the vast majority, veryefficient for food absorption and energy metabolism.


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Obetherapy strategy

Using the Lean Genes orExpenditure genesas

Potential Targets for theTreatment of Obesity andType II diabetes


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Target Identification

and Validation

Hit Identification

Lead Optimization

Structure

Activity

Relationship

Medicinal

Chemistry

Improved

Leads

Selection of a

Drug Candidate

Preclinical Development

Clinical Development

Registration

Launch Target n1

Research & Development Process

Target n2


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Our first target:

Blocking the lipidsabsorption

in collaboration with Zambon Group SpA


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ChylomicronsVLDL/LDL

HDL

Bile

Metabolism

Storage

Liver

Absorption

Intestine

Adipocytes

OBETHERAPY Target: The Gateway

Lipids are transported by chylomicrons (from intestine to liver) andby VLDL/LDL/HDL (from liver to target tissue). OBETHERAPY CAN

STOP TOTALLY OR PARTIALLY THE PROCESS.


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Transgenic (F1)

Control(F1)

Validation of our first target


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Status on target n1

Development collaboration signed in 2004 with ZambonGroup SpA. Zambon Group SpA was founded in Vicenzain 1906. It operates in Europe, South America and Asia.It employs 2,300 employees in 16 countries and hasconsolidated sales in the region around 500m.

Some scientific data: High throughput screening using ObeTherapys

proprietary technology was conducted late 2004.

HIT identification milestone was reached in April

2005. Lead identification milestone was reached in October2005.

Next milestone will characterize the Candidate Drugto enter preclinical mid 2007.


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SOME FACTS

5 PATENTS:

First ObeTherapys target on lipids (issued EU and US) Second ObeTherapys target on proteins (PCT application)

Biochemical in vitroassay: (issued F & US) List of hit compounds (PCT)

Cellular HTS (PCT)

2 PATENTS IN PREPARATION WITH ZAMBON GROUP SpA

OTHER MARKET FOR OBETHRAPY TECHNOLOGY:

DYSLIPIDEMIA

TYPE II DIABETESATHEROSCLEROSIS


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(i) Coinvest with Zambon and share risk on the

development of the first program.

(ii) Bring the second program to preclinical stage.

Investment opportunities

ObeTherapy is looking to raise

3 million euros for the next 2 years.


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Lean genes allow you

to eat without gaining weight...

Nature did it, ObeTherapy can reproduce it.

o be therapy

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