Bio- and Nanotechnology: Emerging Medical Miracles on the Horizon

Marsha K. Millonig, MBA, RPh President & CEO Catalyst Enterprises, LCC

Todays Objectives
Understand biotechnology and nanotechnology Describe the biotechnology market size Explain what fields are parts of the emerging business of life science List a number of new therapies resulting from bio and nanotechnology Discuss the implications of these new therapies on pharmacy and its technology partners

Why is it Important?

Global Population Growth

Earths 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

Biotechnology is needed to
Create better fuels that dont harm environment Create tools to clean environment, feed a burgeoning global population, cure untold human suffering

Biotechnology Definition
Use of cellular and biomolecular processes to solve problems or make useful products. Life sciencesbiology/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)

The firsts

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

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

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

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

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

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

but speeding up.

1988: First US patent for genetically altered animala 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!

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

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

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

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 industrys new economic landscape.

A single herd of goats may soon replace a $150 million drug factoryHBR 4/2000 2006: ATryn approved for DVT

The Human Genome & Biotechnology

A milestone in biology unlike any other. Weve called the human genome the book of life, but its really 3 books: Its a history book. Its a shop manual and parts list. And, its 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

The Human Genome: Fun Facts

30,000-40,000 genes not the 100-120,000 thought earlier Five times as many as in bakers yeast About twice as many as that needed to grow a worm or fly! Bananas share about our genome while mice share 90%!

BUT, each single human gene can make 10 proteins vs. a worm or flys genes making just one or two. We have the Cuisinart vs. the paring knife --Francis Collins

 5 million strands of DNA can fit through the eye of a needle

All our DNA laid end to end would go to the sun and back 600 times! The genetic instructions for making a person take up less than 1 of the 6-ft long strand of DNA in each cell

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 IDd so far 1000 Genomes: extends HAPMAP through global collaboration to map 1,000 genomes in 3 years

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

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

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

Personal Genome Mapping

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

Gene Map Becomes a Luxury Item

3/2008 Id 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 persons gene profile was already known

Future Environment
Personalization of medicine
Present Disease by symptomsdiagnosis Disease uniformityguidelines, formularies Future Disease by mechanicsprognosis Disease heterogeneity customization, targeted Rx

Patient uniformitycare standards

BlockbustersUniversal Rx Consumer ignoranceacute care

Patient variabilitytailored care

Multibusterspharmacogenetics Consumer empowermentpreventive care

Personalized Medicine Poised for Progress in 2009

12/24/2008 poised for dramatic progress in 2009 in the clinic and laboratory personal, predictive, preventive Weve finally gotten to the point where we can tell people about how their DNA impacts their health, Elissa Levin, 23andMe

Promises and Implications BIG*

Promise: Rapid technological innovation and vast number of new targets identified and predictive tests Today 483 targets account for all Rx drugs marketed, tomorrow 510,000 targets Rapid acceleration in pace of new therapeutic introductions Drugs and treatments that are more tailored to specific patients Implications: Development becomes a bottleneck Shorter product life cycles Market fragmentation Blurring distinction between product and service
* Gary Pisano, HBS 3/2000, adapted

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

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)

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/Bio tech%202008.pdf

Biotech Product Trends

Development of biotech compounds is explosive 633 biotech medicines in US pipeline 2001: Most compounds focused in the oncology arena, followed by infectious disease, CV and neuroscience 2007: Cancer 254, infectious disease 162, autoimmune disease 59, HIV/AIDS 34, CV 25, diabetes 19 Breakthrough treatments may provide new hope of some diseases

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

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

Therapeutic Technologies

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

. . . Contact us for the rest of the presentation

www.catalystenterprises.net mmillonig@catalystenterprises.net Tel: 651-905-9002