Bio- and Nanotechnology: Emerging Medical Miracles on the Horizon

1. Bio- and Nanotechnology: Emerging Medical Miracles on the Horizon Marsha K. Millonig, MBA, RPh President & CEO Catalyst Enterprises, LCC ASAP Annual Industry & Technology Issues Conference January 15-17, 2009 St. Pete�s Beach, FL

3. Why is it Important?

4. Global Population Growth Earth�s capacity is estimated at 12 billion people It took 100 million years before Earth had 1 billion people in 1830 Yet only 170 years for the population to reach 6 billion plus 2005: 6,436,562,930 2009: 6,752,560,109 � the people who have ever lived are on the planet today Less than 100 years before we reach capacity

5. Biotechnology is needed to� Create better fuels that don�t harm environment Create tools to clean environment, feed a burgeoning global population, cure untold human suffering

6. Biotechnology Definition Use of cellular and biomolecular processes to solve problems or make useful products. Life sciences�biology/chemistry technology affecting discovery and development of products for: �Healthcare (therapeutics, diagnostics, drug delivery, cell and gene therapy, devices, drug/device combinations) �Agriculture (food, feed, fibers, transgenics) �Industrial and Environment (reduce pollution, clean energy) All driven by a new set of enabling technology (genomics, combinatorial chemistry, SNPs, proteomics, sequencing�)

7. Development is evolutionary� 4000-2000 BC: biotech used to leaven bread & ferment beer 1830: Proteins discovered 1833: First enzyme discovered 1865: Genetic science begins-Mendel discovers laws of heredity 1879: Chromosomes discovered

8. Development is evolutionary� 1906: The term genetics introduced 1919: The word biotechnology is first used in print 1938: The term molecular biology coined 1941: The term genetic engineering is first used

9. Development is evolutionary� 1953: Watson and Crick DNA Structure 1958: DNA made in test tube Sickle cell caused by AA change 1960: Messenger RNA discovered 1967: First automatic protein sequencer is perfected 1969: Enzyme synthesized in vitro the first time 1970: First enzyme discovered to cut DNA molecules at a specific site

10. Development is evolutionary� 1971: First complete synthesis of a gene 1973: First time DNA fragments linked 1975: First monoclonal antibodies made 1976: First NIH research guidelines Boyer co-founds Genentech, 1st bio co. 1978: Recombinant insulin first produced 1980: Oil-eating microbes patented by Exxon 1982: First recombinant DNA vaccine for livestock 1983: First whole plant grown from biotechnology

11. Development is evolutionary� 1980: First gene-synthesizers developed 1981: First transgenic animals 1982: First biotech drug: insulin 1983: First artificial chromosome synthesized First genetic markers for inherited disease found

12. Development is evolutionary� 1984: DNA fingerprinting developed 1985: Genetic fingerprinting entered as evidence in courtroom 1986: Interferon first anti-cancer drug from biotech First genetically engineered vaccine for humans: Hepatitis B Microbes used to clean oil spill

13. �but speeding up. 1988: First US patent for genetically altered animal�a transgenic mouse 1989: First DNA exoneration now 216 (4/08) 1990: First food product from biotech approved: modified yeast 1994: First FDA approval for first whole food product: FLAVRSAVR� tomato 1997: First weed & insect resistant crops developed First cloned animal: Hello Dolly!

14. �but speeding up. 1998: Human embryonic stem cells lines established Herceptin approved-considered first pharmacogenomic (personalized) medicine First complete animal genome: roundworm 2000: First complete map of a plant genome First draft human genome

15. �but speeding up. 2004: First genetically modified pet: the GloFish FDA clears genotyping test to aid in medication selection First cloned pet, a kitten 2005: Skin cells converted to embryonic stem cells 1 billionth acre biotech seed planted First complete dog genome: boxer 2006: FDA approves Gardasil-first vaccine for cancer-causing virus

16. �but speeding up. 2007: Successful reprogramming human skin cells to create cells indistinguishable from embryonic stem cells Biotech cattle that cannot develop prions=no mad cow disease 2008: draft corn genome 10 disease bearing stem cell lines created Mature human embryos created from adult skin cells: personalized stem cells for disease treatment First synthetic genome: the road to creating life First complete map of cancer patient genome First US FDA application for gene-therapy/cancer

17. 2005 and Today 2005: Biotechnology will transform industries, including health care Today: Biotechnology IS transforming industries Industrial convergence of farmers, doctors, drugmakers, chemical processors, computer and communication companies, energy companies and many others into the business of life science. Is revolutionizing healthcare and transforming economics of the Rx business. Will need to craft ways of dealing with industry�s new economic landscape. A single herd of goats may soon replace a $150 million drug factory�HBR 4/2000 2006: ATryn approved for DVT

18. The Human Genome & Biotechnology �A milestone in biology unlike any other.� �We�ve called the human genome the book of life, but it�s really 3 books: It�s a history book. It�s a shop manual and parts list. And, it�s a textbook of medicine more profoundly detailed than ever.� --Francis Collins, former director NHRI director A short 50 years after the discovery of DNA by Watson and Crick in 1953 A complete list of coded instructions to make a person Would fill a stack of paperbacks 200 feet high 50 years to type at 8 hours/day, 60 wpm

21. Since HGP� ENCODE: the Encyclopedia Of DNA Elements, in 9/2003, to ID all functional elements in the human genome sequence HAPMAP: haplotype map, will allow researchers to find genes/genetic variations that affect health and disease: 100 ID�d so far 1000 Genomes: extends HAPMAP through global collaboration to map 1,000 genomes in 3 years

22. Since HPG NIH Roadmap Project on genotype tissue expression: are variants of disease risk associated in relevant tissue Knock-Out Mouse Project (KOMP) Mammalian gene collection Cancer Genome Atlas: feasibility of full-scale effort to systematically explore entire spectrum of genomic changes involved in human cancer Molecular manual of disease created: 12/2008 Proteinpedia being created: largest free resource of experimental info human proteins

23. Goal Diagnostics to prevention Pharmacogenomic knowledge transfer to therapeutics for gene therapy, drug therapy Personalize genome + family history=personalized medicine Other non-profit commercial efforts underway

24. George Church, director of the Lipper Center for Computational Genetics at Harvard Medical School, Church has done more than imagine such an undertaking; he has launched it: The Personal Genome Project, an effort to make those correlations on an unprecedented scale, began last year with 10 volunteers and will soon expand to 100,000 participants. It will generate a massive database of genomes, phenomes, and even some omes in between. The first step is to sequence 1 percent of each volunteer's genome, focusing on the so-called exome � the protein-coding regions that, Church suspects, do 90 percent of the work in our DNA. It's a long way from sequencing all 6 billion nucleotides � the As, Ts, Gs, and Cs � of the human genome, but even so, cataloging 60 million bits multiplied by 100,000 individuals is an audacious goal. The PGP stands as the tent pole of what Church calls his "year of convergence," the moment when his 30 years as a geneticist, a technologist, and a synthetic biologist all come together. The project is a proof of concept for the Polonator G.007, the genetic-sequencing instrument developed in Church's lab that hit the market this spring. And the PGP will also put Church's expertise in synthetic biology to use, reverse engineering volunteers' skin cells into stem cells that could help diagnose and treat disease. If the convergence comes off as planned, the PGP will bring personal genomics to fruition and our genomes will unfold before us like road maps: We will peruse our DNA like we plan a trip, scanning it for possible detours (a predisposition for disease) or historical markers (a compelling ancestry).George Church, director of the Lipper Center for Computational Genetics at Harvard Medical School, Church has done more than imagine such an undertaking; he has launched it: The Personal Genome Project, an effort to make those correlations on an unprecedented scale, began last year with 10 volunteers and will soon expand to 100,000 participants. It will generate a massive database of genomes, phenomes, and even some omes in between. The first step is to sequence 1 percent of each volunteer's genome, focusing on the so-called exome � the protein-coding regions that, Church suspects, do 90 percent of the work in our DNA. It's a long way from sequencing all 6 billion nucleotides � the As, Ts, Gs, and Cs � of the human genome, but even so, cataloging 60 million bits multiplied by 100,000 individuals is an audacious goal. The PGP stands as the tent pole of what Church calls his "year of convergence," the moment when his 30 years as a geneticist, a technologist, and a synthetic biologist all come together. The project is a proof of concept for the Polonator G.007, the genetic-sequencing instrument developed in Church's lab that hit the market this spring. And the PGP will also put Church's expertise in synthetic biology to use, reverse engineering volunteers' skin cells into stem cells that could help diagnose and treat disease. If the convergence comes off as planned, the PGP will bring personal genomics to fruition and our genomes will unfold before us like road maps: We will peruse our DNA like we plan a trip, scanning it for possible detours (a predisposition for disease) or historical markers (a compelling ancestry).

25. Other Efforts Bringing the genome into the light, Church says, is the great project of our day. �To Church, who built his first computer at age 9 and taught himself three programming languages by 15, all of this is unfolding according to the same laws of exponential progress that have propelled digital technologies, from computer memory to the Internet itself, over the past 40 years: Moore's law for circuits and Metcalfe's law for networks. These principles are now at play in genetics, he argues, particularly in DNA sequencing and DNA synthesis.� ---Wired

26. Personal Genome Mapping Polonator G.007 $150K machine using open architecture like IBM in 80�s fueling PC revolution DeCodeMe 23andMe Navigenics KNOME Price range $400 to $350,000

27. Gene Map Becomes a Luxury Item� 3/2008 �I�d rather spend my money on my genome than a Bentley or an airplane.� Dan Stoicescu, millionaire retired Biotech exec X Prize Foundation: $10 million to first group to sequence 100 human genomes in 10 days for $10K or less Commercial goal: get price to $1K or less Has dropped by 4 orders of magnitude in 5 years Scientists call for better government regulation of genetic tests DNA databases blocked from public by NIH after study show a new type of DNA analysis could confirm ID of individual in a pool of masked data if that person�s gene profile was already known

29. �Personalized Medicine Poised for Progress in 2009� 12/24/2008 �poised for dramatic progress in 2009� in the clinic and laboratory �personal, predictive, preventive� �We�ve finally gotten to the point where we can tell people about how their DNA impacts their health,� Elissa Levin, 23andMe

31. Specialty Pharmaceuticals Created when many products moved from �medical� side to the �pharmacy� side of the budget=PBM control No specific criteria, but general attributes: Expense with annual therapy costs between $20,000 and $250,000 Treatment for chronic condition, possible lifetime therapy Special handling, route of administration, patient support

32. What Does It Mean to the Market? IMS Health estimates specialty pharmacy sales of $85 billion in 2008 Expected to reach $100 billion in 2010 18% growth next 2 years Global biotech Rx sales grew 12.5% 2007 to $75 billion Biotech growing 2x pharma (6.4%) US sales 56% of total ($42 billion)

33. Market Trends 22 biotech products generated >$1 billion sales compared to 6 in 2002 Biotech products represent 25% of the Rx pipeline http://www.phrma.org/files/Biotech%202008.pdf

36. Major Diseases Autoimmune: rheumatoid arthritis, MS, lupus, chronic fatigue syndrome CV: CHF, MI, PAD, hypercholesterimia Gene disorders: CF, Gaucher�s ID: Hep A, B, C, tuberculosis, anthrax, bird flu Neurodisorders: AD, PD, muscular dystrophy, spinal cord injuries

37. Impact on People Cancer 1.5 million US $219 B CVD 71 million US $403 B Alzheimer�s 5 million US $148 B Parkinson�s 1 million US $35.5 B MS 400,000 US $10 B Diabetes 24 million US $132 B HIV 1.2 million US $37 B Hep A B C >5 million US $3 B

38. Therapeutic Technologies

39. Pharming FDA guidelines governing genetic engineering of animals for food, drugs, or medical devices Released 9/2008

40. Pharming Plant produced therapeutic proteins: mabs, antigens, growth factors, hormones, enzymes, blood proteins, collagen Alfalfa, corn, duckweek, potatos, rice, safflower, soybeans, tobacco Across the array of diseases FDA/USDA

42. Convergence� Knowledge of biology Knowledge of DNA Knowledge of diseases Devices, Diagnostics, Therapeutics = Theranostics

43. Diagnostic Advances 1,200 tests based on biotechnology in clinical use New pregnancy, strep/ID faster, more accurate Early diagnosis of type 1 diabetes, CF, AD, PD, CVD, autism, Lou Gehrig�s, ovarian cancer (99% accurate) Survival predictions for lung cancer Gene test for aggressive breast cancer marketed: 7/2008

44. 2008 Advances Protein behind cancer spread ID�d Biomarkers for breast, oral, prostate cancer Researchers find memory gene Gene mutations linked to breast, colon, prostate cancers, heart attacks, hypertension, lupus, baldness, schizophrenia Gene variants linked to obesity Protein lack tied to autistic savant qualities Proteins causing PD, tumor response to chemo, curing macular degeneration/diabetic retinopathy Gene therapy for alcoholism, transplant patients

45. 2008 Advances Turning off 2 proteins stimulates nerve-cell regeneration in mice Satellite cells in mice that act like stem cells could regenerate skeletal muscle Cell regeneration in mice inner retina triggered by growth factor injection Beating heart created in lab with dead rat/pig hearts Therapeutic cloning (somatic-cell nuclear transfer) txts PD in mice Neurons created from an ALS patient�s skin cells

46. 2008 Advances: Stem Cells Multipurpose cells crafted from adult skin cells not ESC Stem cells reverse neural damage in mice exposed to heroin in womb Mature cloned human embryos created-personalized stem cells/tissue replacements Red blood cells made from HE stems Tests to tell �good� from �bad� stem cells Safer method to produce stem cells without retroviruses that may cause tumors Discovery of brain stem cells that may restore hearing Barriers overcome to using stem cells to build patches for damaged hearts

47. 2008 Advances: Stem Cells Mice ESC used to grow muscles ESC used to create a functional immune system Protein in ESC inhibits skin cancer International Society for Stem Cell Research: Guidelines for Stem Cell Treatments�impetus use of unproven therapies in China, Costa Rica and Barbados

48. 2008 Advances Quicker method to create human antibodies Technique to improve artificial antibody action Technique to improve stem cell capture Gene modification to change one cell to another without stem cells/embryos Artificial DNA developed 16-year frozen mice cloned with nuclear transfer

49. Next Up: Synthetic Biology The only limit if the imagination of the scientist who takes on the role of innovator and artist Employed to produce biological systems free from evolutionary constraint J. Craig Ventor Institute: building designer bugs to absorb greenhouse gas Synthetic genomics

50. J Craig Venter 6-2008 What is life? Can we pare it to basic components? Can we digitize it? Can we regenerate it back to the analogue world? JCVI.org 2007: Report for Governance Synthetic Genomics

51. Now, Add Nanotechnology� The creation of functional materials, devices and systems through control of matter at the scale of 1 to 100 nanometers, and the exploitation of novel properties and phenomena at the same scale. Think STRONG + SMALL=EFFICIENCY Why so small? Researchers have discovered that matter at this tiny scale often behaves very differently. While some of the science behind this phenomenon is still shrouded in mystery, the commercial potential of the infinitesimal is coming sharply into focus. Familiar materials -- from gold to carbon soot -- display startling and useful new properties. Some transmit light or electricity. Others become harder than diamonds or turn into potent chemical catalysts. What's more, researchers find that a tiny dose of nanoparticles can transform the chemistry and nature of far bigger things, creating everything from fortified fenders to superefficient fuel cells. Engineers working at the nano scale have a brand-new tool kit that's full of wonder and brimming with potential riches.Why so small? Researchers have discovered that matter at this tiny scale often behaves very differently. While some of the science behind this phenomenon is still shrouded in mystery, the commercial potential of the infinitesimal is coming sharply into focus. Familiar materials -- from gold to carbon soot -- display startling and useful new properties. Some transmit light or electricity. Others become harder than diamonds or turn into potent chemical catalysts. What's more, researchers find that a tiny dose of nanoparticles can transform the chemistry and nature of far bigger things, creating everything from fortified fenders to superefficient fuel cells. Engineers working at the nano scale have a brand-new tool kit that's full of wonder and brimming with potential riches.

52. Nanotechnology 1980: the scanning tunneling microscope-allowed pictures of individual atoms 1990: buckytubes-strong rolled up sheets of graphite Today: Promises are big �The Next Industrial Revolution��4/27/2005 Pew Trust Launch Emerging Nanotech Project $377 billion 2015 $70 billion 2015 from $165 million 2004 in drugs/devices

53. Tools: Now Materials: 3 years Energy: 5 years Healthcare: 8 years Nanoelectronics: 10 years 2005:

54. Consumer Applications Then Hummer H2 Sport Utility Truck nanocomposite material cargo bed lighter and more scratch proof NanoDynamics golf ball: nanoparticles spin less, which should mean less slices and hooks Samsung fridges & washing machines with nanocoatings to prevent nasty bugs Samsung 8 GB Compact Flash Card LabNow portable blood analyser

55. Consumer Applications Now 800+ manufacturer-identified nanotechnology-based consumer products from 420 cos. in 21 countries http://www.nanotechproject.org/inventories/consumer/ Products tripled between 3/2006 and 2/2007

57. What are they? Everything! Cosmetics (126 products), Clothing (115), Personal Care (153), Sporting Goods (82), Sunscreen (33), and Filtration (40) Cleaners, sheets, iPhone, golfshafts, toothpaste, processors, curling irons/hair dryers, functional sportwear, graffiti shields, & more

58. Nanotechnology in Health Nanodiagnostics Nanotherapeutics Nanobiodevices Better ways to sense disease, deliver treatments Future: nanoprobes, nanoneedles, substrates, on/off switches for drug delivery devices, sensors for heart patients

59. Nanotechnology in Medicine CytImmune- Gold nanoparticles for targeted delivery of drugs to tumors Nucryst-Antimicrobial wound dressings using silver nanocrystals Nanobiotix-Nanoparticles that target tumor cells, when irradiated by xrays the nanoparticles generate electrons which cause localized destruction of the tumor cells. Oxonica- Disease identification using gold nanoparticles (biomarkers) Nanotherapeutics-Nanoparticles for improving the performance of drug delivery by oral, inhaled or nasal methods� NanoBio-Nanoemulsions for nasal delivery to fight viruses (such as the flu and colds) and bacteria BioDelivery Sciences-Oral drug delivery of drugs encapuslated in a nanocrystalline structure called a cochleate NanoBioMagnetics-Magnetically responsive nanoparticles for targeted drug delivery and other applications

60. Advances 2008 Nanotech sensor detects toxins in living cells, including cancer inducers/drugs Device uses nanoparticles to control drug delivery Nanotechnology used to create designer enzymes not normally catalyzed in nature using chemistry, mathematics, physics=molecular manufacturing Used to study vancomycin mechanisms with potential to combat resistant infections Nano-diamond covered patches used to reduce cancer patients exposure to adverse effects chemo

61. Not Without Issues �Nanotube effects may lead to cancer� 5/2008 Scientists call for more safety research NRC report calls for more research into nanotech risks: government should craft a more comprehensive plan �Could become the next asbestos or worse��A Gillies International Risk Governance Council Conference on Nanotechnology 1/2006: inclusive, globally focused risk governance framework addressing ST/LT applications of nanotech

62. 2005:Medical Devices and Implants Converging and changing rapidly with computer, nano and bio-science

63. 2009 The science of Neurotechnology=biotechnology and neuroscience Neuroengineering: evolved machines NIO: Neurotechnology Industry Organziation Combines engineering, physiology, chemistry, computer science New solutions for damaged sensory systems, neuro systems

64. Advances Artificial device for hearing for deaf Work underway for the blind BrainGate: transfer motor signals from brain to language computer understands to control devices: allowing paralytics to control a machine by altering their brain waves Two-way transmission under research Implantable chips to strengthen neural connections: spinal injuries

65. 2005: Neuromorphic Electronics

66. �The Mind Machine Interface� Researchers combine brain cells and computer chips -3/2006 HRL Labs researches neuromorphic electronics that function like the brain: SyNAPSE-10/2008 Cognitive enhancers? Engineering soldiers?

67. NIO Founder Zack Lynch Historical pattern of human progression: hunters/gatherers to agricultural to industrial to informational society Neurotechnology is the answer to the next �new society,� the �neuro-society�

68. Imagine the Impact on People�. 2 billion people worldwide 100 million people in North America Brain disorders cost $1 trillion annually And the impact on you and your partners�

70. Practice Impact Genomic tests the domain of primary care doctors? Some now offered in pharmacies. Pharmacists recommend appropriate therapy--how to parlay pharmacy Rx care programs? Assay tests for individualized therapy. Models to manage products that have high-risk, are in short supply, have short shelf life and be non-returnable Performance-based networks and other specialty networks: Mirixa

71. Impact on Pharmacy & Partners� Direct to MD results from new devices�challenge to how to keep pharmacists engaged with needed information MD/Pharmacist interface even more important for non-Rx data Start by getting MD/Rx connection ready-SureScripts More and new kinds data related to specific therapeutic disease states and conditions�system flexibility and size

72. Impact on Pharmacy & Partners� Closer working relationships to evolve provider-driven patient care platforms�interoperable with other practitioners, systems, EHRs, PHRs More standardized, integrated, interoperable data and systems across practice settings/sites/caregivers Continuous system improvement, faster, better, cheaper�systems that repurpose data� �with state of the art privacy/security

73. Most Are Unprepared Study finds health professionals, public unprepared for genomic medicine RAND 3/2008 Need for large scale educational effort Primary docs need to incorporate Consumers worried about testing, loss of privacy, discrimination

74. Privacy/Security Genetic Information Nondiscrimination Act (GINA) signed into law 5/2008 Prohibits employers from using genetic information in hiring, firing, pay or promotion Forbids health insurers from requiring a genetic test Bars them from rejecting coverage/raising premiums based on personal/familial genetic predisposition

75. How Can You Prepare? Keep up on technology developments: Computer Talk Magazine & the American Society of Automation in Pharmacy Meetings Position yourself as knowledge broker: Biotech and nanotech shows great opportunity but often pharmacy is left out Read all you can on biotechnology, nanotechnology medicine Attend biotech sessions at professional meetings

76. Resources to Keep Up www.genome.gov www.jcvi.org www.fda.gov: pipeline and approvals www.pharmalive.com: pipeline database/newsletters www.bio.org and www.phrma.org: meds in development www.burrillandco.com--the �IMS of Biotech� Burrill & Company www.nanotechproject.org www.understandingnano.com www.biosynergyonline.com http://www.smartbrief.com/signup/

77. 2/3rds of all people have at least 1 copy of a DNA sequence that makes them more likely to be depressed after stressful life event. I think it�s just easier to develop neurotechnologies that will enable us to make people as happy and intelligent as possible. Ed Boyden, MIT neuroengineering group I�m inherently an optimist. I want to improve human life. Playing God is a crappy phrase. -James Watson

78. Normal is merely a statistic. Ed Boyden The most exciting breakthrough of the 21st century will occur not because of technology, but because of an expanding concept of what it means to be human. John Naisbitt

79. Anything is possible�we�ve come a long way in 40 years!

80. Thanks for Having Me! www.catalystenterprises.net mmillonig@catalystenterprises.net Tel: 651-905-9002