Advanced Accelerator Applications First Bern Cyclotron Symposium, 6-7 June 2011 Luca Maciocco (R&D project manager, tech. coordinator) on behalf of Stefano Buono (President & CEO) AAA: Highlights • • • • • • • Privately held, international molecular diagnostics and therapeutics company founded in 2002 as a spin-off of CERN laboratory, headquartered in Saint Genis Pouilly, France Focus on molecular imaging and personalized medicines to treat serious conditions including oncology, CNS, cardiovascular and infectious diseases Specialist in production and commercialization of Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) products Growing international presence • 10 production and R&D facilities • 150 employees in six countries (France, Italy, Switzerland, Spain, U.S., Canada) • 33 R&D specialists 2009 revenues up 96% to €23.8m – 2006-2009 CAGR of 60% (estimated revenues in 2010 based on AAA accounting: €27.8M) 2009 EBITDA 5.84m – 2006-2009 CAGR of 82% (estimated EBITDA 2010 based on AAA accounting: €6.3M) Robust cash generation funds innovative research 2 Gluscan® - AAA’s leading PET product • High barriers to entry – 10 hour shelf life – Technical production challenges • Multiple pharmaceutical productions per day • Timing • Logistics • Know-how for fast problem-solving • AAA has unique industrial approach to FDG production – AAA laboratories have the most reliable pharmaceutical production in PET Doses available for injection vs. time after production of FDG • Best -in-class technology • Highest pharmaceutical standards – All laboratories combine production and R&D activities – Laboratories built for modularity and scalability, to meet future market demand 3 Sites status updated • AAA facilities Laboratories: – 6 production/R&D sites operational – 2 production/R&D sites waiting for GMP approval – 2 pure R&D sites (Arronax facility in Nantes, France; St. Louis, Missouri, U.S.) – New projects to be launched (Marseille, Paris already started) All AAA sites designed to produce Gluscan ®, PET investigational medical products (for human injection) and new PET commercial tracers • • Commercial partnerships for FDG production and distribution (first site: Geneva University Hospital, Switzerland) GLUSCAN® site training and licensing (first sites: NTP Radioisotopes, South Africa and Cyclopharma, Casablanca, Morocco) AAA is the fastest growing player in the European PET market 4 Annual PET Revenue Growth AAA * €25,000 75% CAGR in the period 2004-2010 €20,000 €15,000 €10,000 €5,000 €0 2004 2005 2006 2007 2008 2009 2010 * Revenue figures exclude SPECT business, i.e. Gipharma 5 The broadest PET product portfolio Product Use Status Gluscan® [18F]FDG PET tracer that assesses glucose metabolism Available in all European markets IASOflu® Sodium Fluoride 18 PET tracer indicated as a bone imaging agent Available in Italy and France - seeking approval in other markets IASOdopa® Aromatic amino acid that accumulates rapidly in target tissues- used in neurology and oncology. Available in France - seeking approval in other markets IASOcholine® Imaging agent used for oncologic diagnostic procedures where there is enhanced choline influx in specific organs or tissues Available in France - seeking approval in other markets Cardiogen® Myocardial perfusion PET imaging agent Phase III All PET products currently on the market worldwide are non-patented PET market will experience a significant growth with new patented products arriving 6 Research products • • • • • • • • • • CARDIOGEN® - myocardial perfusion PET imaging agent [18F]-FMC - choline uptake PET marker [18F]-FMISO - hypoxia PET marker [18F]-FLT - tumor proliferation PET marker [18F]-FET - amino acid PET tracer [18F]-FDDNP - amyloid plaque PET marker [18F]-MPPF - PET imaging of serotonin-1A (5HT1A) receptors [18F]-FALLYPRIDE - PET imaging of dopamine D2/3 receptors [99mTc]-ANNEXIN V-128 - apoptosis and necrosis SPECT marker [177Lu]-DOTA-OCTREOTATE (LUTATE) treatment of metastatic gastro-enteropancreatic neuroendocrine tumors (GEPNETs) 7 • Ephoran – a company founded by AAA, Bracco and BiPCa (Bioindustry Park of Canavese) to provide integrated multi-imaging solutions for pre-clinical and clinical research • Operates in close collaboration with CEIP (Center of Excellence for Preclinical Imaging), a public imaging platform in BiPCa (AAA’s Ivrea site). • • • CEIP platform (operated by Ephoran and AAA on request) includes 1100 m2 of laboratory, animal testing facility and imaging equipment at AAA’s Ivrea site Imaging equipment included animal PET, SPECT, MRI, optical imaging, High Frequency US, NMR, Electron Microscopy - being extended to CT and Echo 3D Animal models: oncology, cardiovascular, neurology, inflammation, others on customer request 8 AAA moving into SPECT • • • • SPECT - the largest segment of molecular nuclear medicine (approx. 70%), but growing more slowly than PET due to poor innovation In 2009 AAA acquired Gipharma - an Italian pharmaceutical contract manufacturer of injectable and freeze dried products, specialized in SPECT radiopharmaceuticals Current products used to perform nuclear medicine diagnostic procedures in lung scintigraphy; lymphoscintigraphy; sentinel node detection in breast cancer surgery; and hepatobiliary system imaging First commercial products: – MIBITEC : generic version of the widest used SPECT cardiac imaging agent – Leukokit : medical device that improves safety of peripheral leukocyte labelling procedure in molecular nuclear medicine 9 Fostering innovation with SPECT • • • AAA is investing US$6m in Atreus (Canada) to allow it to move its leading compound Annexin V-128 for early diagnosis of rheumatoid arthritis into phase II Annexin V licensed by Stanford University Demonstrated ability to image cellular apoptosis and necrosis conditions associated with diseases including – – – – – – • Crohn’s Alzheimer’s Myocarditis Cardiac transplant rejection Acute myocardial infarction Unstable atherosclerotic carotid artery disease Tc-99m labelled Annexin used to evaluate response to treatment for lymphoma and lung cancer 10 AAA’s therapeutic business • Molecular Nuclear Therapy using β- - emitting radioisotopes • AAA has set-up a unique industrial process to produce Radio Metabolic Therapy products • AAA facility in Ivrea about to be approved by AIFA to produce therapeutic radiopharmaceuticals in injectable form – Likely to be first industrial pharmaceutical laboratory for RMT products in the world approved by a central authority – To be followed by a second facility in Forli in 2011 11 BioSynthema • BioSynthema, located in St. Louis, Missouri, U.S, acquired in June 2010 • Discovers and develops unique pharmaceuticals targeted to cell surface receptors over-expressed by various lesions • Technology makes specific tumors highly visible using diagnostic imaging methods, enabling earlier, more accurate diagnosis and personalized therapy • Developing new, effective products for diagnosis and treatment of Gastero-Entero-Pancreatic NeuroEndocrine Tumors (GEPNETs) • Lead product Lutate has been proven safe and effective in over 600 patients • – Reduces tumor size – Extends life by 3.5 to 6 years – Improves quality of life Orphan drug status in EU and USA. – expected to enter phase III in 2011 – U.S. marketing application expected in 2015 12 Commercial network AAA operates: • Directly in 4 European countries – France, Italy, Spain and Switzerland • Through agents or distributors in 27 countries – UK, Ireland, Belgium, Netherland, Luxembourg, Norway, Denmark, Sweden, Finland, Czech Republic, Turkey, Greece, Austria, Germany, Slovakia, Hungary, Poland, Romania, Bulgaria, Ukraine, Portugal, Croatia, Serbia, Slovenia, Bosnia, Montenegro, Macedonia 13 Research & Development • Strategy of continuously developing new compounds to bring to market is implicit in AAA’s mission statement : “Bridging science with life” • R&D department includes more than 30 people out of 130 employees • Most opportunities for new MNM products come from academia - public partnerships as important as private companies • AAA working closely with 32 partners (70% in the public and 30% in the private sectors) on approx. 25 projects 14 Next generation growth – product pipeline Indication Discovery Apoptosis and necrosis Annexin atherosclerosis myocardial infarction stroke Atheroma peptide myocardial perfusion estrogen cancers neuroendocrine cancers brachytherapy Preclinical Phase I Phase II Phase III Filing Diagnostics: SPECT Cardiogen® Diagnostics: PET Er Carrier peptide Lutate THERAPEUTICS Theranean 15 Thank you for your attention 16