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RESEARCH IS TO SEE WHAT EVERYONE HAS SEEN AND TO THINK WHAT NOBODY HAS THOUGHT.

RESEARCH IS TO SEE WHAT EVERYONE HAS SEEN AND TO THINK WHAT NOBODY HAS THOUGHT. "Albert Szent-Gyoergyi, nobel prize 1937. Lean genes allow you to eat without gaining weight…. Nature did it, ObeTherapy can reproduce it. The Company. Created by Dr Itzik HAROSH in January 2000

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RESEARCH IS TO SEE WHAT EVERYONE HAS SEEN AND TO THINK WHAT NOBODY HAS THOUGHT.

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  1. RESEARCH IS TO SEE WHAT EVERYONE HAS SEEN AND TO THINK WHAT NOBODY HAS THOUGHT. "Albert Szent-Gyoergyi, nobel prize 1937.

  2. Lean genes allow you to eat without gaining weight… Nature did it, ObeTherapy can reproduce it.

  3. 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

  4. Core Team • Itzik HAROSH, PhD, Chairman and Chief Scientist Officer (CSO) • Georges GAUDRIAULT, PhD, Scientific Director • Sandrine BRAUD, PhD, Project Leader • Vladimir CHARRON, Engineer • David SENAC, Engineer • Christelle MOUGIN, Laboratory Manager

  5. Advisory board Prof. M. Radman, Hôpital Necker, Paris, France; specialist in genetics and evolution; member of the "Académie des Sciences de l'Institut de France". Prof. A. Levy, The Weizmann Institute of Science, Rehovot, Israel; specialist in biotechnology and genetics. Prof. T. Baasov, Chemistry Faculty Technion, Haifa, Israel; specialist in medicinal chemistry and chemical synthesis. Prof. B. Peault, McGowan Institute for Regenerative Medicine, Pittsburgh, USA; specialist in cellular models and biotechnology, pioneer of Systemix. Dr Y. Champey, former Senior Vice President and Executive Medical Director at Rhône-Poulenc Rorer. Prof. D. Bensimon, Ecole Normale Supérieure, 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, Hôpital Necker-Enfants Malades, France, Expert in the obesity field in which he is a major contributor; member of the "Académie des Sciences de l'Institut de France".

  6. PRIMARY MARKET: OBESITY Source: Farrigan C, Nat Rev Drug Discov, 1, 257

  7. Mission With a completely innovative strategy, Obetherapy aims to develop medication for obesity. By looking for « lean genes » or « expenditure genes » in lean phenotype

  8. What is Obesity ? Obesity = imbalance between food intake and energy expenditure Energy expenditure (metabolism& physical activity)        Food intake        

  9. Obesity Type II diabete Absorption Metabolism Carbohydrate Proteins Lipids Lipids Carbohydrates  Acetyl-CoA Acetyl-CoA ATP Metabolic Pathways Involved In Obesity Appetite/Satiety (CNS)

  10. Genes linked or associated with obesity - Single gene 7 - Mendelian disorders 41 - Associated 90 - Linkage 322 - Total 460 http://obesitygene.pbrc.edu

  11. Targets for obesity treatment currently in research and development Fat metabolism Energy homeostasis Appetit Satiety UCP1 UCP2 UCP3 PKA-IIb -Adrenergic R -Adrenergic R ACC-2 Adiponectin (Famoxin) PTP1B S6K1 NPY Orexin PTP-1B AGRP MG Axokine CNTF Canabinoid (Rimonabant) OB DB CCK POMC MCH Tubby CART Agouty FAT GLP-1 MC4R MC4R PYY (3-36) PPAR-g SREBP1 C/EBPs FATPs Fat Absorption PL (Orlistat) MTP

  12. Why did we evolve to be obese? Is obesity an advantage?

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

  14. Natural selection Darwin's grand idea of evolution by natural selection Is this an advantage?

  15. The thrifty genome theory (James Neel, 1962 Am. J.Hum. Genet.) • During thousand of years of evolution, when food was scare, long periods of famine have selected individuals having an efficient organism for food absorption and energy metabolism. • When food supply increased the thrifty genotype become a liability rather than an asset. • On the other hand, individuals with low efficiency for food absorption and energy metabolism became rare. • This explains why we are, in the vast majority, very efficient for food absorption and energy metabolism.

  16. Obetherapy strategy Using the « Lean Genes » or « Expenditure genes »as Potential Targets for the Treatment of Obesity and Type II diabetes

  17. Research & Development Process Target Identification and Validation Structure Activity Relationship Hit Identification Improved Leads Medicinal Chemistry Lead Optimization Preclinical Development Clinical Development Registration Launch Selection of a Drug Candidate Target n°1 Target n°2

  18. Our first target: Blocking the lipids absorption in collaboration with Zambon Group SpA

  19. OBETHERAPY Target: The Gateway Chylomicrons VLDL/LDL Bile HDL Liver Metabolism Adipocytes Intestine Storage Absorption Lipids are transported by chylomicrons (from intestine to liver) and by VLDL/LDL/HDL (from liver to target tissue). OBETHERAPY CAN STOP TOTALLY OR PARTIALLY THE PROCESS.

  20. Validation of our first target Transgenic (F1) Control (F1)

  21. Status on target n°1 • Development collaboration signed in 2004 with Zambon Group SpA. Zambon Group SpA was founded in Vicenza in 1906. It operates in Europe, South America and Asia. It employs 2,300 employees in 16 countries and has consolidated sales in the region around €500m. • Some scientific data: • High throughput screening using ObeTherapy’s proprietary technology was conducted late 2004. • HIT identification milestone was reached in April 2005. • Lead identification milestone was reached in October 2005. • Next milestone will characterize the Candidate Drug to enter preclinical mid 2007.

  22. SOME FACTS • 5 PATENTS: • First ObeTherapy’s target on lipids (issued EU and US) • Second ObeTherapy’s target on proteins (PCT application) • Biochemical in vitro assay: (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 DIABETES • ATHEROSCLEROSIS

  23. Investment opportunities ObeTherapy is looking to raise 3 million euros for the next 2 years. Coinvest with Zambon and share risk on the development of the first program. Bring the second program to preclinical stage.

  24. Lean genes allow you to eat without gaining weight... Nature did it, ObeTherapy can reproduce it.

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