Key Results of 2008 Leem Nanomedecine Study Nanobio Dialogue Session Annick Schwebig,, M.D., General Manager, Actelion Pharmaceuticals France Vice-President of Leem Biotech Committee EuroBio,, Paris, October 8 th 2008 1
Why this study? Within the Leem (French Pharmaceutical Companies Association), the Leem Biotechnology Commission represents Life Sciences companies that have a strong focus on the red biotech sector. It positions itself as a think tank that provides the Leem, key decision makers and the general public with analyses, reports and recommendations aiming at foreseeing trends and innovation brought by biotechnologies as well as understanding France attractiveness and competitive position. Since 2004, the following areas are the main that have been investigated by the Commission: bioproduction, employment, careers and formation in healthcare, cell therapy & tissue engineering In 2007, the Biotechnology Commission was also particularly involved in the White Book «Health Innovation in 2015» leaded by the Leem Research. In this context, in 2008, the Leem Biotechnology Commission with the help of consulting firm Bionest Partners, decided to launch a large survey to assess the competitiveness of France in the field of nanomedicine. 2
Nanoproducts size could be beyond the nanometer scale (between 1 and 100 nm) 10-1 nm H 2 O molecule ADN 10 0 nm Protein 10 1 nm Ribosome 10 2 nm Nuclear Pore 10 3 nm Mitochondrion 10 4 nm Cell >10 5 nm Tissue Virus-Like Particles Dendrimers Liposomes Nanoparticules (e.g. nanotubes, fullerenes, quantum dots) Nanotechnologies lead to the creation of structures, devices and systems where the size of the active component is comprised between 1 and 100 nanometers (nm) Nanotechnologies could also encompass elements of a size that exceeds the nanometer scale (e.g. micrometer) but only if the miniaturization confers them new physical properties (e.g. microfluidics, liposomes) Source: Bionest Partners analysis 3
The boom and future development of nanomedicine will mainly rely on synergies between four scientific areas Biology Cellular Molecular Functional Clinics Physiopathology Therapeutics Clinical Trials Chemistry Complex Supramolecular Physics Electrotechnical Electronics Engineering Quantum effects Source: Bionest Partners analysis 4
In healthcare,, nanotechnologies applications could range from diagnostic to monitoring of treatments Diagnostic Monitoring Bioassays Imaging Monitoring Monitoring of therapeutic response In Vitro Diagnostic, Imaging and Biotech industries Pharma and Med Tech industries Nanotechnologies and Health Treatment Personalized Medicine Implants Drugs Drug Delivery Source: Bionest Partners analysis Pharma, Biotech and Med Tech industries 5
More specifically,, nanotechnologies allow a better specificity and sensibility of diagnostics and therapeutics tools Medical applications of nanotechnologies Nanotechnologies allow to get elements that are: Miniaturized, Biologically active, More specific of tissue, cell or subcellular dysfunctional compartment Benefits of nanometer scale in healthcare Nanotechnologies find applications in various medical areas: Target discovery Gene or drug delivery In vitro diagnostic testing (e.g. nanoarray) and in vivo (e.g. contrast agents) Monitoring tools Source: CLINAM, interviews, Bionest Partners analysis 6
Applications - New in vitro diagnostic tools Benefits Increase test performance : sensibility, detection threshold, speed Reliability and accuracy of results Miniaturization of tools Biological elements stabilization Decrease of reagents consumption per analysis (cost reduction) Examples Sensors Chemo-sensors Bio-sensors Nanoanalytical tools Surface microscopy Imaging mass spectrometry Advanced ultrasonic technologies 7
Applications - New in vivo diagnostic tools Benefits Early detection of diseases More powerful imaging technologies Increase of targeting and specificity Miniaturization of tools Decrease of detection threshold Examples Imaging markers Fluorescent and luminescent particles Radioactive tracers Dispositifs Endoscopic probes Imaging endoscopic shells Catheters coupled with nanosensors 8
Applications New therapeutic tools Benefits Increase of drug efficacy Decrease of adverse effects and limitation of toxicity Treatment cost reduction (decrease of quantity of active ingredients needed) More targeted therapies Development of new therapeutic approaches and mechanism of action Examples Drug delivery systems Devices Liposomes Nanocristals Virus-like particles Cardiac surgery assistance Active nanoelements Subject to activation Naturally active Injectable or implantable nanoparticles that could be activated by ultrasounds or magnetic fields Embospheres 9
In drug delivery, nanoparticles could open new development possibilities for toxic molecules Example : TAK 779 anti-hiv molecule Traditional Approach Interaction Satisfactory therapeutic effects BUT Development stopped TAK 779 Active molecule FREE STATE Cells Strong adverse effects Nano Approach Gold Nanoparticle TAK 779 Active molecule COUPLED Interaction Cells Increase of expected therapeutic effects AND Decrease of adverse effects Promising results of TAK 779 coupled with a nanoparticle Source: Bowman et al. J Am Chem Soc. 2008, Bionest Partners analysis 10
Most of nanomedicine patents are concerning drug delivery applications, the United States being particularly active in patent filing Worldwide nanomedicine patents over the 1993 2003 period By area By country Therapeutic molecules 3% Biomaterials 8% Active implants 3% Others 23% Imaging 13% In vitro diagnostic 14% Drug delivery 59% France 3% UK 3% Japan 5% Germany 12% USA 54% Source: European Patent Office, Bionest Partners analysis 11
By 2015, it is anticipated that nanomedicine applications will dramatically increase their share in the whole nanotechnology market Nanotechnology market 2007 2015 Defense 3% Electronics 7% Nanomedicine 2% Defense 6% Automotive 4% Others 5% Semi-conductors 31% Semiconductors 35% $135 billion Chemical Products 53% Electronics 28% $1000 billion Nanomedicine 17% Chemical Products 9% In 2015, the nanomedicine market could represent a $170 billions opportunity Source: Cientifica, Bionest Partners analysis 12
Medical nanoproducts are already commercialized, the majority of which being drug delivery tools Nanoproducts on the market In vitro Diagnostic 6% Implants 3% In vivo Imaging 8% Over thirty products are already commercialized Biomaterials 25% n=36 Drug delivery 58% The majority of products are formulations of existing or newly developed drugs Source: Bionest Partners analysis 13
Liposomes and nanocristals represent the majority of nanodelivery products on the market Nanodelivery products on the market Ex : Gardasil HPV vaccine Hepaxal Hepatitis A vaccine Virosome 19% Polymer 5% Micelle 5% Nanocristal 24% Resin 5% Liposome 42% n=21 Ex : Daunoxome (daunorubicin) Kaposi Sarcoma treatment Ambisome (amphotericin B) antifungal Ex : Tricor (fenofibrate) - Lowering cholesterol agent Rapamune (sirolimus) Immunomodulator - Transplantation Source: Bionest Partners analysis 14
The US, Japan, Germany and South Korea are the most advanced countries in the nanomedicine area Global competitiveness in nanotechnologies Level of activity in nanotechnologies + Cluster #1 : «Dominant countries» where activity, R&D intensity and Government support are very high Cluster #2 : «Followers» where effort dedicated to nanotech activities is reasonable Cluster #3 : «Niche countries» where limited nanotech activities exist but with an intense commitment of Governments Country commitment to support nanotechnology + Cluster #4 : «Laggards» where development intensity is reasonable but level of activities is low Source: Lux research, Bionest Partners 15
Two reference centers with international reach are involved in the nanomedicine field in France Châtenay-Malabry Besançon Grenoble International center National center Research team Besides international centers of excellence, centers and research teams with national reach are also involved in the field of nanomedicine Source: réseau Nanomat, interviews, Bionest Partners analysis 16
Public funding of nanotechnologies in France Public financing Evolution over the 2001 2005 period (M ) Split of public R&D funding (2005) 90 80 70 60 143,5 165,1 210,1 255 277,4 MINEFI 16,2% INSERM 2,7% CNRS 31,6% 50 40 30 CEA 24,5% 277,4 M 20 10 0 2001 2002 2003 2004 2005 MESR 26,5% OSEO-ANVAR INSERM MINEFI CEA MESR CNRS + OSEO ANVAR (0,1%) N.B: Total of public funding per year is stated on top of bar charts N.B: M = million euros Source: Ministère de l Enseignement Supérieur et de la Recherche, Bionest Partners analysis 17
With 12 active companies,, France presents the second concentration of nanomedicine companies in Europe 1 Medsqual Therapeutics (active nanoparticles) Therapeutics (drug delivery) Diagnostics Research Tools Source: NanoVip, Nanoforum, Nanowerk, Bionest Partners analysis 18
Example of the InNaBioSanté Foundation in Toulouse InNaBioSanté Foundation Research Foundation launched in 2005 Goals: definition, promotion and financing of partnerships allowing the development of R&D activities in the Life Sciences field, and in oncology in particular Actively back the development of Nanotechnologies, Infotechnologies, Biotechnology and different radiotherapy techniques Funding of 21.5 million brought by industrials, National Research Agency and Ministry of Research Examples of projects funded by the Foundation Nano-Oncology: Development of nanoparticles with magnetic core with application in medical oncology Modic (MOlecular Diagnostic and Imaging Cancer) : Improvement of early detection and diagnostic of cancer Oncomate (Olfactive Nano-detection of Cancers Obtained from MAchine-learning Technology) Source: InNaBioSanté, Bionest Partners analysis 19
The FP7 dedicated a 730M budget for research and development projects in nanomedicine Framework Program budgets dedicated to nanotechnologies 3,5 3 Total FP7 : 50.5 billion Other Nanotechnologies Nanomedicine, Nanobiotechnologies 2,5 Billion 2 1,5 Total FP6 : 17.5 billion 2,74 1 0,5 0 Total FP4 : 12.5 billion Total FP5 : 14.9 billion 0,11 0,005 0,21 1,1 0,01 0,22 0,73 FP4 FP5 FP6 FP7 1.4% of total FP7 budget Besides pure R&D projets, FP 5 et 6 have allowed to finance 14 projects dedicated to assess the environmental impact of nanoparticles Source: Commission Européenne, Bionest Partners analysis 20
www.bionest.com 21