Top Technology Trends in Health and Wellness (Technical Insights)

Technologies for the betterment of the healthcare system

D4A9-TI June 2012

Contents
Section Executive Summary 3D Cell Culture Systems--Mimic In vivo Conditions Nanoparticle-based Therapies--Cancer Therapeutics Recombinant Expression SystemsPlant-based Transgenics for Protein Therapeutics Slide Numbers 3 6 11 16

Biosensing--Nanobiomedicine Approach
Next Generation Prebiotics--Targeted and Second-degree Prebiotics Genetically Engineered Foods--The 2nd Agricultural Revolution Nutrient Encapsulation--Ensuring Nutrient Delivery Nanofluidics and BioNEMs--Intelligent Miniaturized Systems Next Gen Sequencing--Thousand Dollar Genome Adult Stem Cell Therapies--The Commercial Cell of Origin

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26 31 36 41 46 52

The Frost & Sullivan Story

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Executive Summary

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Research Scope and Index

3D Cell Culture System Nanoparticle-based Therapies Recombinant Expression Systems

Technical Insights division of Frost & Sullivan evaluated technology trends in the Health and Wellness sector and has identified 10 technology trends that are likely to have an impact in the year 2012. The slides provide information on the following lines on a best effort basis, as applicable to the technology under consideration. They are as follows: Brief Snapshot of the Technology Recent Developments Key Stakeholders and their Solutions Future Scenario

Top Technology Trends

Biosensing Next-Generation Prebiotics Genetically Engineered Foods Nutrient Encapsulation Nanofluidics and BioNEMS Next-Gen Sequencing Adult Stem Cell Therapies

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Executive Summary--Research Process and Methodology

Technology Journals Periodicals Market Research Studies Technology Policy Information Sites Internal Databases Thought Leader Briefings

1. Patent Review

Technology Capabilities and Stakeholder Initiatives Technology/Business Challenges

Secondary Research

Innovators and Innovations

3. Assess Innovations

Application Market Potential and Needs

Primary Research
Engineers CTOs/CEOs/CIOs Technical Architects Research Heads Strategic Decision Makers Technology Policy Heads

2. Interview Participants

Technology/Business Drivers

Stakeholder Insights, Perspectives and Strategies

OUTCOME--Forecast Future of Technology, Market Adoption, and Potential Application Sectors

Research Methodology

Research Process

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3D Cell Culture Systems--Mimic In vivo Conditions

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Technology Snapshot
Overview
3D Cell Culture systems are ex-vivo cellular arrangements, generated in a scaffolds that intend to simulate the extracellular matrix (ECM) microenvironment to control culture conditions that propel cell proliferation. One of the main goals of these systems is the replication of in vivo conditions of organotypic cultured systems to perform in vitro diagnostic or in vitro metabolic studies. In particular, the spatial and temporal distribution of these signals is tightly controlled and unique to each organ.

Importance

Year of Impact

In the human body, all cells exist in a complex three-dimensional (3D) network mesh and this has motivated scientists to replicate the structure and composition of natural cellular environments. The architecture of such a culture system enables close interaction between cells, growth factors and extra-cellular matrix.

Products from 3D Biotek, Invitrogen, Millipore are already in the market. Increasing awareness should enhance adoption rates and newer application areas like 3D microspheres which would impact the market by 2013. 3D cell culture systems can reduce animal testing, improve efficiency and reduce cost and time of testing procedures.

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Global Footprint

USA/ Canada Extensive research in the areas of 3D microplates, coverglass, scaffolds, matrices, assay wells, organotypic microtissue models,. Greater adoption has been noted in the area of cell culture and by 2015 there would be transition from 2D to 3D cell culture.

Europe The main application areas include cellcell and cell-matrix interactions. Adoption is noted in the areas of 3D cell culture.

Intensity of Technology Development Very High High Medium Low Very Low

India 3D bioreactors, 3D scaffolds are available through distributors of top firms like Invitrogen, SigmaAldrich . Basic research in the area of 3Dscaffolds and matrices is observed.

Japan Research and adoption in the areas of cell culture applied to stem cells and various other kinds of cells or models to develop drugs and therapeutics

Australia/New Zealand 3D cell cultures 3D scaffolds 3D organotyping

Source: Frost & Sullivan.

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Stakeholders and Developments

Key Challenge: Petri dishes, tissue culture flasks, and micro-well plates are commonly used systems for cell culture owing to simplicity, convenience, and high-cell viability. These conventional flat systems or twodimensional (2D) mechanisms to culture cells played a vital role in understanding cell biology, but are insufficient for the new challenges of cellular biology or pharmaceutical assays. Company
Life Technologies Corporation Hamilton and Global Cell Solutions, Inc. Sigma-Aldrich Co. LLC 3D Biotek, LLC Synthecon Inc.

Product / Technology
Gibco Products

Details
Invitrogen (renamed as Life Technologies) provides extracellular matrices, scaffolds and proteins under the Gibco umbrella to support stem cell and other cell cultures. BioLevitator a benchtop incubator and bioreactor that uses GEM (Global Eukaryotic Microcarrier) technology that allows GEMs to be kept in suspension with the ability to automatically culture them, and minimizes the need for manual handling. The 3D matrices include HydroMatrix synthetic peptide, MaxGel human ECM, and Mouse ECM. These products provide three-dimensional environments in which cells are better able to mimic their in vivo counterparts. 3D Biotek is developing 3-D cell culture devices for stem cell/tissue engineering and drug discovery applications. Product 3D Insert--PCL has been chosen by the NIST as the reference 3D tissue engineering scaffold. Synthecon allows users to grow dynamic cultures in which the matrix, suspended in a fluid bath, and promotes 3-D cell growth

BioLevitator

3D Matrices

3D Insert

BIOFELT, Rotary Cell Culture Systems, Biomerix

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Impact on Application Areas

Tissue Engineering

3D matrices and scaffolds

Organ Engineering

Drug Discovery

Culturing tumor cells Drug testing

Target validation Secondary screening/ Lead optimization Safety assessment/ Toxicology DMPK Primary screening Stem cell culture Cell biology model systems Developmental biology Cell supply and cryopreservation

Basic Research

Cell culture methodology

2012

2014

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Nanoparticle-based Therapies--Cancer Therapeutics

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Technology Snapshot
Overview
Nanoparticles are used for a wide variety of biomedical applications to aid in laboratory diagnostics and in medical drug targeting. In targeted cancer therapies they are used as conjugates with cancer biotherapeutics such as peptides, proteins or antibodies. Among the next generation of nanoparticles that are being used for this purpose are superparamagnetic nanoparticles, gold nanoparticles, interactive nanoparticles composed of conjoined gold nanorods and iron oxide nanocrystals.

Importance
Conventional cancer therapies such as chemotherapy using small molecules or even targeted therapy using antibodies do not target cancer cells with a high degree of precision. Nanoparticles can identify, target and kill specific cancer cells while leaving healthy cells undamaged. Nanoparticle conjugates of targeted cancer drugs show superior therapeutic efficacy, specificity and selectivity compared to conventional targeted therapies.

Year of Impact
Several nanoparticle-based conjugates are the products of research labs. Examples include the interactive nanoparticles and the RNA nanospheres (RNA encapsulated in lipid-based cationic nanoparticles), both from the Massachusetts Institute of Technology. Companies such as Cytimmune and NanoSpectra Biotherapies have already demonstrated heat-based nanoparticle treatment. The year of impact can be expected to be 2016 as several such conjugates have completed Phase I clinical trials.

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Global Footprint
North America USA has been active in this sector in both basic and applied research. Dr. Sangeetha Bhatias group at the Massachusetts Institute of Technology and the California Institute of Technology have pioneered the use of several types of nanoparticles from lipid-based cationic particles to gold nanorods. Companies such as CytImmune, Tempo Pharmaceuticals and Carigent Therapeutics are already developing nanoscale systems for the delivery of cancer drugs. Ortho Biotech, a subsidiary of Johnson and Johnson has already launched such a system using liposome nanoparticles (Doxil). Europe The Turku Center for Biotechnology , the University of London and the Karolinska Institut have been leading research efforts for the use of gold, porous silica and carbon-based nanoparticles in cancer therapy for prostate, pancreatic and non-small cell lung tumors. Nanobiotix and Ensemble Therapeutics based out of France and Magnamedics based out of Germany are notable companies developing nanaoparticle-based therapies for cancer. The European Commission has formulated a roadmap till 2020 to incorporate milestone-based developments for nanoparticle-based drug delivery.

Intensity of Technology Development Very High High Medium Low Very Low

Japan, Taiwan and Korea Japan has been exploring the use of platinum and silica nanoparticles for targeted cancer therapeutics through the Tokyo Institute of Medicine and the Riken Institute. Korea Institute of Science and Technology has pioneered the development of chitosan-based nanoparticles fro targeting tumors. The National Health Research Institute in Taiwan has optimized the use of nanoparticles in cancer by combining a diagnostic contrast agent with an anticancer drug.

Australia Work in this sector is limited to basic research. The Cancer Council SA has funded researchers from both the Hanson Institute at the Royal Adelaide Hospital and the Wark Institute at the University of South Australia to develop such nanoparticles.
Source: Frost & Sullivan.

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Funding Trends

Source: NIH, EC, KIST, ITRI

Source: Journal of Nanomedicine, IEEE EMBS

Nanomedicine has been stated as a key developmental area on the innovation agenda for a number of countries including the United States, South Korea, Taiwan and Japan. The European Commission has been maintaining nanomedicine as a key research focus since the 6th Framework Plan and has so far already committed $367 million USD to the field since 2004. Among the applications of nanomedicine, drug delivery which includes targeted cancer therapy is indicated to have the highest precedence with 59% funding being allocated to it in Europe and USA. NIH includes nanomedicine as a part of its Common Fund Program that is aimed at providing targeted funding and training programs for ten key research areas. Nanomedicine has been on the Common Fund since 2006.
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Impact of Technologies

Lipidbased/Liposomal nanoparticles Carbon nanotube-based particles Composite nanoparticles Silica-based porous nanoparticles

Companies like Tekmira Pharmaceuticals and Encapsula NanoSciences are already developing lipid nanoparticles for pharmaceutical use. McGill, University of Lancashire, University of South Florida and Stanford University have identified carbon nanotubes as conducive for drug delivery. MIT has demonstrated the use of interactive nanoparticles composites using gold nanorods and iron oxide particles. Silica-based porous nanoparticles have been proposed for photodynamic therapy by Nancy University. Cornell University is also a major participant. Gold nanoparticles have been used in conjugation with anticancer drugs by researchers at MITnanorods and colloidal particles.

Co-development and licensing projects with both government and pharma companies such as Merck, AstraZeneca and Novartis.

Applied research will be conducted in these fields with funding from NIAID, DARPA and the Medical Research Council. These nanoparticles will be exploited to carry and dispense drug payloads to breast and lung tumors in preclinical studies. These nanoparticles will be tested in preclinical studies by UCLA, NIST and NIH. Photoluminescent particles particularly useful for dermal drugs The efficacy of these particles is being tested with different biotherapeutics in vitro. Start-ups like Pilot Therapeutics are also involved.

Pictures

Gold Nanoparticles

2012
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Recombinant Expression Systems Plant-based Transgenics for Protein Therapeutics

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Technology Snapshot
Overview
Plant-based transgenics involve the use of plant-based material such as cash crops, vegetables or moss for the extraction of recombinant proteins for therapeutics and research. Human protein forms from antibodies to enzymes can all be isolated from plants. The most commonly used materials for such transgenics are tobacco, carrots and moss and the process sometimes involves genetic engineering or cross-transfections. Plant-based transgenics do not have standardized regulatory protocols.

Importance
Conventional recombinant expression systems such as yeast and bacterial systems require expensive infrastructure and production equipment in the form of fermenters. The yield percentage using yeast or bacterial system is usually around 35%-50%, much lower than the required rate for therapeutics dosage. Plant-based transgenics are cost-effective in terms of culture and production, can be used to derive naturally glycosylated proteins and require inexpensive raw materials.

Year of Impact
Plant-based transgenics are in demand as glycosylated proteins can be naturally derived from them. In addition, isolation and purification is cost-effective making it a conducive choice for the manufacture of biosimilars and biobetters. These products not only comply with the required safety standards but are also more humane and environmentfriendly as they do not use any animal-based raw materials. The year of impact for these systems is, therefore, likely to be 2015-16.

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Global Footprint
North America USA does not have a very strong presence in plant-based transgenic systems in terms of commercialization. This can be due to the lack of standardized FDA protocols for approving them. Basic and applied research are done extensively at a number of institutes including the Roswell Park Cancer Clinic, Arizona State University, School of Medicine and Cornell University. Companies such as Medicago and GreenVax have gone into Phase I clinical trials with their vaccines from Proficia and tobacco plants respectively. However, advancement to later phases has been a hurdle. Europe The most active countries in Europe pursuing plant-based transgenics for recombinant protein therapeutics are Israel and Germany. The former houses two major companies, Collplant and Protalix Biotherapeutics. The former develops recombinant virgin collagen while the latter is developing taliglucerase alfa for Gaucher, Fabry and autoimmune diseases Germany is home to Greenovation, the only company commercializing a moss-based recombinant expression platform. Icon Genetics is also a leading company there. The adoption footprint is Europe is considerably higher due to the provision of a risk analysis procedure from the European Commission.

Intensity of Technology Development Very High High Medium Low Very Low Australia and Africa AzarGen is an early stage recombinant expression platform developer in South Africa. Their technology is still in the design phase. CSL in Australia has a plant for the manufacture of recombinant proteins from plant-based products but acquires technology platforms for the same through in-licensing deals.

Source: Frost & Sullivan analysis

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Funding Trends

Source: NIH, EC

Plant-based protein has recently come into focus due to its applicability in producing recombinant human vaccines. Major government institutions such DARPA and NIAID have extended investments to aid the development of plant-based systems for recombinant proteins. The most ambitious project for plant-based recombinant systems in USA is GreenVax, a Texas-based initiative that is aimed at producing vaccines for infectious diseases using tobacco plants. Europe is already active in this space with the majority of funding being allocated to Italy and Germany. The latter is home to 2 major companies in this sector, Icon Genetics and Greenovation.
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Stakeholders and Technology Developments

Research Area

Stakeholders

Technology Developments & Trends

Development of virgin homogeneous human collagen from recombinant expression in tobacco plants. Two flagship productsVergenix for wound repair and the same as a flowable gel. They are also branching into orthopaedics applications with Pfizer (bone void filler). ProCellex platform for optimized genetic engineering and plant-based recombinant expression. Taliglucerase alfa for Fabry, Gaucher, biodefense and other autoimmune diseases. Ready for USA marketwas granted PDUFA status after successful Phase II trial, by FDA. Formerly subsidiary of Bayer with Nomad Biosciences, currently independent. Plant-based recombinant expression toolswork for any plant. Two major recombinant expression toolsnuclear transformation and plastid transformation suite. Highest soluble protein percentage and conversion quotient in industry. They are working on therapeutic products in collaboration with Pfizer.

Recombinant collagen from tobacco

Taliglucerase alfa from carrot and tobacco

Multi-stage drug delivery chips using nanoporous silicon particles

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Biosensing--Nanobiomedicine Approach

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Technology Snapshot
Overview
Carbon Nanotubes (CNTs) and other nanostructures, including Peptide Nanotubes (PNTs) exhibit ideal properties for use as a sensing material: high surface area, chemical and mechanical stability, which has resulted in the increasing design of a variety of sensors including biosensors, electrochemical sensors and gas sensors, to be applied in life sciences and biomedicine fields. The ability to incorporate any antibody without destroying the recognition function allows the development of new highly specific targeted therapies for a broad spectrum of diseases. CNTs/PNTs are excellent platforms for developing sensors due to the high effective area, together with excellent electrical, mechanical, thermal properties and chemical stability.

Importance
PNTs are useful nanomaterial building blocks that have been used to construct a variety of device geometries, as their self-assembly is robust, and locations for their immobilization on substrates can be targeted by biomolecular recognition. The biological functionalization of CNTs, attaching proteins and/or DNA or RNA, has received a great deal of interest due to the potential biomedical applications of the nanotubes in both diagnostics and therapeutics.

Year of Impact

This technology is expected to be increasingly adopted by 2013. Assembling PNT sensors with a simple chip geometry enables the electrical detection of viruses and other pathogenic organisms with an extremely low detection limit.

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Global Footprint

USA/Canada Nanoimmunology Microarrays and molecular diagnosis Implantable biosensing devices Implantable nano-tagreting devices Drug discovery and development based on nanobiosensing platforms

Europe Microarrays and molecular diagnostics Point-of-care systems New biomarkers discovery and development strategy Drug discovery and development based on nanobiosensing platforms

Intensity of Technology Development Very High High Medium Low Very Low Argentina/Brasil Molecular diagnosis Point-of-care systems

India Microarrays Molecular diagnostics New biomarkers discovery and development strategy

Japan Microarrays and molecular diagnostics Nanoimmunology New biomarkers discovery and development strategy Drug discovery and development based on nanobiosensing platforms

Australia/New Zealand Microarrays and molecular diagnostics Drug discovery and development based on nanobiosensing platforms
Source: Frost & Sullivan.

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Stakeholders and Developments

Research Area
Pathogen detection systems through nanoscale biosensing devices

Company
BioForce Nanosciences , Inc

Technology Developments
BioForce Nanosciences developed a platform for fast, sensitive and non-destructive virus detection, the ViriChip virus detection platform. The platform consists of a silicon chip functionalized with an ultramicro array of antibodies using the Nano eNabler, and a detection system based on Atomic Force Microscopy. Applied Nanotech has developed a nanotechnology based Metal Nanoparticle Sensor (MNPS) Platform, whose first product is a palladium nanoparticle-based hydrogen sensor. Nanoparticles of palladium provide high surface to bulk ratio compared to macro scale palladium thin films used for hydrogen sensing in biotech. The dotLab System uses dot technology to significantly shorten the transition from protein discovery to application in both research and diagnostics. New panelPlus Sensors simplify multiplexing, and allow the freedom to combine established markers with novel content. Biosensors International offers abluminal drug-eluting stents with a biodegradable coated, limus-eluting technology on its proven stent platforms, the S-Stent and Juno. The companys key R&D initiative in the interventional cardiology field is a family of "polymer-free" drug-eluting stent systems coated with proprietary BA9 anti-restenosis drug. The PoC system, Atolyzer , aims to address a wide range of important clinical markets including cardiology, maternal tests and prostate cancer.

Metal nanoparticle sensors for hydrogen detection Protein interaction studies for quantitative assays on a single platform Interventional cardiology and critical care procedures

Applied Nanotech Holdings

Axela Inc

Biosensors International

Point-of-care systems

NeuroSearch (Atonomics A/S)

Label free biomolecular interaction measurement for bioprocess applications

SAW Instruments GmbH

The biosensor sam5 enables the label free measurement of biomolecular interactions and their kinetics in real time. Binding processes can be detected selectively and with highest sensitivity, and can further be analyzed.

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Impact on Application Areas

Diagnostics

Microarrays technology

Nano-beads for genetic diagnostics

Implantable biomarkers

High resolution and high throughput screening capabilities, which enable a wide variety of biological assays can be significantly enhanced by using novel biosensing platforms.

Therapeutics

Drug discovery and development

Nanotherapeutics, nanoimmunology assessment

Implantable targeting devices

The use of nanoscale biosensors is applied to therapeutic areas by evaluating cellular systems response in drug discovery process.

Clinical monitoring

Point-of-care assessment

Implantable postsurgical biosensing monitors Long term 2015-2017

With recent advances in micro, nanofabrication techniques and multidisciplinary research studies focusing on bridging sensing platforms for medical applications, new applications in clinical monitoring are arising.

Monitoring

Short term 2012-2013

Medium term 2013-2015

Nanotechnology has made it possible for a single chip to possess more than million features with supra-sensitive detection abilities than that of conventional methods. Because of the nature of this industry, breakthroughs in applications and solutions can be expected in the near future in the areas of sustainability, nanotechnology and biocybernetics.

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Next Generation Prebiotics--Targeted and Second-degree Prebiotics

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Technology Snapshot
Overview
Prebiotics are slightly fermented or non-fermented, non-digestible ingredient that promote the growth of beneficial microorganisms in the human intestine. Targeted prebiotics are unique ingredients from various carbohydrate and cellulose sources that promote the growth of specific bacteria for a particular function. Second-degree prebiotics prevent the growth of a particular species of pathogenic bacteria promoting immunity.

Importance
Prebiotics help in growth of bacteria in the intestine directly. Compared to probiotics, the survival rate of prebiotics is higher as the action of prebiotics starts inside the small intestine; whereas probiotic bacteria are affected by acidic pH of the stomach. Targeted and second degree prebiotics promote the functionality of prebiotics. Prebiotics are easy to be integrated into solid foods such as cereals. They can also be incorporated into beverages and powders.

Year of Impact

The year of impact of targeted beyond 2015 as it is in applied research stage. The year of impact of second-degree prebiotics is beyond 2013 as it is in clinical trials stage. Prebiotics ultimate aim is to be available as drug replacements over the counter. This is expected to impact beyond 2020

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Global Footprint

United States of America Prebiotic companies are researching the possibility of utilizing inulin as a targeted prebiotic ingredient since this has the highest market share in the world in the US.

UK Utilization of prebiotics for feeds of animals to prevent specific diseases.

Switzerland and Netherlands Leading companies such as Nestle and Danone are researching to add second-degree prebiotic ingredients in their food products .

France Leading cosmetic companies such as Loreal and Dedeor use prebiotics in their cosmetics.

Intensity of Technology Development Very High High Medium Low Very Low Latin America Native fruits and other ingredients are exported to the US and Europe to produce prebiotic ingredients. Australasia Unique vegetation helps in providing sources for next generation prebiotics.

Japan Japanese companies are researching and manufacturing prebiotic ingredients. They are focusing on prebiotics as drug replacers.

Source: Frost & Sullivan.

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Funding Trends

beverages 10%

cosmetics 5%

Funding sources Dairy Confectionery and processed foods Animal Feed Beverages Cosmetics

animal feed 15%

Dairy products 40%

confectionery and processed foods 30%

Source: NIH, FDA

The highest amount of funding is provided to dairy foods integrated with prebiotic ingredients. Prebiotics are sometimes mixed with probiotics to improve digestion. Hence the research is backed by both functional foods and dairy food companies. To reduce recalls of meat due to bacterial outbreaks, second degree prebiotics are being researched. This aspect is being aided by governments of various countries. Prebiotics in cosmetics is relatively new and is still in basic research stage. Leading cosmetic companies are funding the same.

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Impact of Technologies
Prebiotic blends are combination of two or more prebiotic ingredients. Combinations of inulin were tested and launched. Glasgow university researched the possibility of prebiotic ingredient glucomannan hydrolsylates to prevent acne Researchers across the world are developing prebiotic ingredients that can prevent gastrointestinal diseases. Prebiotic blend combinations of inulin and fructooligosaccharides (FOS) are likely to be launched and globally marketed. Loreal and Dedeor are likely to introduce skin products containing prebiotics based on their patented technologies Applied research is estimated to increase in the field of utilizing prebiotics to prevent cardiovascular diseases.

Prebiotic blends Prebiotics in cosmeceuticals Second generation prebiotics Synbiotics

Pictures
Blends of prebiotics and probiotics known as synbiotics are being clinically trialed by dairy companies to sample yoghurts.
Encapsulated prebiotics are being trialed for cosmeceuticals. They help in drug delivery apart from functioning as bacteria promoters. Possibility of combining targeted, second-degree and encapsulated prebiotic technologies could lead to drug replacement prebiotics.

Synbiotic yoghurt technologies are likely to be patented. Products are expected to start launching by the end of the year.
There is an estimated increase in the amount of research for encapsulated prebiotics to prevent specific diseases that are not intestine related. Along with Japan, the US and Europe, middle east and other Southeast Asian countries are likely to research in this area.

Encapsulated prebiotics Prebiotics as drug replacement

2012
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Genetically Engineered Foods--The 2nd Agricultural Revolution

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Technology Snapshot
Overview
Ever since advances in biological sciences have paved way to manipulate organisms at the DNA level, modern biology has made huge strides in improving life forms to suit humankind. This has extended to plants and animal food too. Genetically engineered food also known as biotech food are a class of agricultural (both animal and plant based) products that have been modified at the genetic level. These types of food are specially modified with enhanced properties that enable the food to either grow in a more sustained manner or to provide additional nutritive value to the final product

Importance

Year of Impact

The importance of genetically engineered food cannot be understated. Many times, such food helps overcome issues of poor consumption, in other instances such food aids in providing additional nutritional benefits to people who do no have easy access nutritional supplements. It is even possible to incorporate vaccines into genetically modified plants so that when consumed the food will provide the necessary immunity against dangerous diseases

Products that are meant for agricultural users are already available in the market with new technology incorporating multi-stacked traits. New, state-of the-art technology includes test tube food. Such kind of foods are excepted to be commercialized in the near future with the year of impact being 2014

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Global Footprint
The Food and Agriculture Organization of the United Nations (FAO) and the World Health Organization (WHO) established the CODEX Alimentarius, sets standards and guidelines to protect the health of consumers and ensure fair practices in the international food trade. In addition to standards for specific foods, the Codex Alimentarius contains general standards covering matters such as food labeling, food hygiene, food additives, pesticides and safety.

USA/Canada GM food need not be labelled. Does not follow CODEX standards

Europe Very strict labeling laws. Follows CODEX standards

Latin America Pro certain GM crops such as biofuels generating crops. Moderately strict in terms of GM food Crops. Follows CODEX standards in parts.

China Pro GMOs especially in case of GM Rice. Not too strict in following CODEX standards

Adherence to CODEX Standards Very High High Medium Low Very Low

India Moderate laws regarding GM crops. Strict when implied in food. Follows CODEX standards

Australia & New Zealand Strict Laws. Labelling laws similar to E.U. Follows CODEX standards.
Source: Frost & Sullivan.

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Stakeholders and Developments

Key Challenge: Difficulty in obtaining biological sequences; long R&D timelines and nature overcoming target mutations are the most significant technology related challenges. While high R&D costs, ill-perception of BT products, patent infringement and enforcement and lack of uniform laws for international trade are some of the most significant business challenges facing genetically engineered food as of today. Company Product / Technology Details
The Canadian based company has applied for permission to grow and market its arctic granny and arctic golden apples. The genetically engineered fruit, was originally developed in Australia and has the ability to keep their white flesh even when exposed for several hours. The browning of cut apples usually leads to the perception that the food has spoilt and increased wastage of good quality fruit. This innovation allows for the fruit to be wasted less easily The US based company has produced its in-house developed AquAdvantage Salmon. This is a genetically enhanced breed of salmon that grows faster than regular salmon. The company is currently seeking federal approval for the salmon. If approved, the salmon would be the first genetically engineered animal in the human food supply. Considering the fact that salmon (and hence even caviar) are a rare commodity, this should reduce strain on naturally occurring salmon population and preserve its diversity. The company plans to introduce its in-house developed modified Camelina that contains increased oil content. This is said to enhance biofuel production by making the process more economical.

Okanagan Specialty Fruits Inc

Modified Apples

AquaBounty Technologies

Modified Salmon

Agrargen

Modified Camelina

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Impact on Application Areas

2014 2016 2020

Crop Production Protection

Crop protection and production are the most important traits being imparted to crops currently. This trend will decrease in the long term once all popular crops have been suitably genetically modified. Currently, there are very few commercial animal products that have been genetically modified. With food security predicted to be a major issue in the long term, such foods will be more commonplace. Currently, functional foods have little bearing in the mainstream global market as theyre resigned for countries with poor nutritional access. This trend is expected to be continued in the long term. Pharmaceuticals are probably the biggest impact in the long term. This is due to long timelines of research and commercialization. Renewable chemicals will benefit from genetically engineered plants. Varieties that allow for greater productions and easier extraction of renewable chemical content will show greatest promise.

Animal Husbandry

Functional Foods

Pharmaceuticals

Renewable Chemicals

Legend:

Low

High

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Nutrient Encapsulation--Ensuring Nutrient Delivery

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Technology Snapshot
Overview
Nutrient Encapsulation involves the incorporation (entrapping or enveloping) of core materials that include food ingredients, enzymes, cells or other materials such as additives, nutrients, flavors, colors, micro organisms, essential oils, vitamins, minerals, in an enclosing material (carrier, shell, wall, capsule, or membrane). The enclosing materials are designed to protect the core material from the damage and to prevent unwanted reactions with the environment, moisture and heat. The coating materials are typically made from sugars, proteins, gums, natural and modified polysaccharides, synthetic polymers, and even fats.

Importance

Year of Impact

Nutrient Encapsulation helps in extended shelf life of the product and improved performance characteristics. It increases the bioavailability of the encapsulated ingredient and helps in controlling their reactions within a specific environment. It prevents loss of nutrients and prevents their interactions with atmosphere and other constituents during storage.

While encapsulated probiotics, nutrients (amino acids, vitamins and minerals) are available in market, controlled release and multi-functional products are expected to be widely adopted within early 2015. While early adoption of nanotechnology and microencapsulation for increasing product performance is perceived, they are expected to gain prominence by 2014.

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Global Footprint
USA/ Canada: Extensive research to ensure stability during processing and packaging, reduction of capsule size and enhancing bioavailability.

Rest of Europe: Focus on nanoencapsulation and microencapsulation techniques, especially in countries like Germany, The Netherlands, Israel and Sweden..

UK: Research efforts are more focused on novel encapsulation materials, controlled release and increasing bioavailability Australia/New Zealand Research efforts mimicking global trends. Current focus on novel encapsulation technologies and multi component encapsulation.

Intensity of Technology Development Very High High

Medium
Low Very Low
Source: Frost & Sullivan.

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Stakeholders and Developments

Key Challenge: While many nutrients are encapsulated, product stability and release of active ingredient at targeted site are the major challenges that need to be addressed for sustained growth of the industry.

Company
Technion Israel Institute of Technology

Product / Technology
Nano capsules to protect hydrophobic nutraceuticals Mesoporous Silica as encapsulating material Fatty acid enriched fruit juices ProTectis and ProDentis

Details
Nano capsules (conjugates) made of casein and maltodextrin are developed to protect hydrophobic nutraceuticals such as vitamin D. The conjugates were used for the enrichment of clear beverages . The development of nano capsules have the additional benefit of masking off-flavors and off-odors. Mesoporous silica particles are developed as an encapsulation material using nanotechnology. The material is perceived to be safe, stable, cost effective and is capable of addressing the challenges such as off-taste masking, controlled release and increasing nutrient bioavailability

Nanologica

Tropicana Products

Fortified fruit juices with omega 3 essential fatty acids using double encapsulation techniques to ensure nutrient bioavailability and to ensure increased performance characteristics.
Encapsulated probiotic strain, Lactobacillus reuteri in chewable tablets, capsules and other carriers to promote oral health, combat infant colic and digestive aliments. Micorencapsulation techniques used for coating the microparticles of phytosterols, thereby, providing a water-dispersible form to supplement phytosterols into the daily diet.

Biogaia AB

Lipofoods

Lipophytol

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Technology Roadmap
Nutrient Encapsulation aid in incorporating reactive additives and other ingredients into stable ingredients to add value to the final product. The development of encapsulation technologies has the ability to transform health and wellness industry and helps in expansion of application areas such as nutraceuticals, fortified and other functional foods apart from conventional applications that include taste-, color- and odor- masking and flavor stabilization,

Droplet technologies Powdered Technology Targeted Delivery Hybrid Technologies Microencapsul ation Controlled release Mechanism

Self assembled Nutrients

Nano capsules

2010

2013

2015

2017

2019
Source: Frost & Sullivan.

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Nanofluidics and BioNEMs--Intelligent Miniaturized Systems

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Technology Snapshot
Overview
Nanofluidics refers to the control and manipulation of excessively small fluids of dimension less than 1nm. Fluids in the nano-scale range exhibit behavior normally not observed in the macro scale. This industry is experiencing considerable growth in recent years. A benefit of nanofluidics is that it offers the possibility of exploring fluid behaviour using controlled regular nanostructures. This technology has had a great impact on drug delivery devices as the systems have the ability to completely control drug release rate depending on the on-demand requirements for extended periods of time.

Importance

Strength

The use of NEMS based technology in medical applications is an area with immense potential. Demand for improved healthcare at reduced cost, along with point-of-care applications for the elderly population, has made nano-scale biomedical technologies an attractive opportunity for investors and manufacturers..

Nanofluidic technology has been successfully implemented in technologies involving analytical separations and the manipulation of proteins, RNA and DNA. However most of the applications are in combination with bioMEMS technology. The number of application areas is emerging enabled by innovative fabrication methods. An important advantage of nano-scaled systems is the small amount of sample or reagent used for analysis. This reduces the time required for sample processing and further speeds up the processes thereby increasing throughput of the analysis.

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Global Footprint

Nanofluidics is a converging technology and OEMs are manufacturing NEMS based devices in combination with MEMS based systems. BioMEMS technology has revolutionised drug discovery and molecular based diagnostics. It is expected that these two applications will boost the nanofludics and bioNEMS technology in a similar fashion. In the western countries such as North America (NA) and European Union (EU), nanofludics technology is currently driven by the government initiatives and funding undertaken for promoting nano-based technologies. The Chinese market is slowly catching up with the western and European countries in terms of the bioMEMS industry. Chinese medical companies have traditionally distributed North American and European products on their home market. That is starting to change slowly and China is emerging as a key participant in the bioMEMS field. Given the current technology development trends taking place in China, it can be expected that China will soon emerge as a key global player in this field.
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Stakeholders and Developments

The regulatory barrier is a huge challenge for companies in this field. Companies might have the expertise to manufacture bioNEMS but they have modest experience in the rigorous regulatory process. Apart from the regulations that medical devices must comply with, there are additional standards for bioMEMS devices, applicable for NEMS based devices as well which manufacturers must comply with.

Company

Product

Description
Minute samples are utilised by the nanoAnalyzer System to analyze several gigabases per hour. Valuable information is obtained about the genome structure as the sample is analysed without breaking up the molecules. The technology enables high-throughput processing. The proprietary nanoAnalyzer technology is capable of delivering precise genetic data in a fraction of the time and at a cost which is a fraction of existing technologies. RainDance Technologies (RDT) is a company which develops a proprietary microdroplet-based technology with special emphasis in the prediction and prevention of human disease. Some of the proven application of this technology are for assays such as PCR and cell sorting. The technology proposed by RainDance produces picoliter-volume droplets at a rate of 10 million per hour, avoiding complex automation solutions. Topical local anesthetic delivery system indicated for use on normal intact skin to provide local analgesia for superficial dermatological procedures such as venipuncture, intravenous cannulation, and laser ablation of superficial skin lesions. The TAXUS stent uses Translute Polymer which is a proprietary polymer carrier technology, to control drug release. The Translute Polymer protects the drug and maintains coating integrity during preparation, delivery, and stent expansion. FluidFM technology utilises hollow connecting cantilevers with a microfluidic system for fluid application. The technology is used for dispensing and stimulating single cells under a physiological condition. Nanofluidic channels allow soluble molecules to get dispensed through submicrometer aperture in the AFM tip.

BioNano Genomics

NanoAnalyzer System

RainDance Technologies

RDT 1000

Vyteris Inc

LidoSite Topical System

Boston Scientific

TAXUS Express

Cytosurge

FluidFM

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Application Roadmap

In Vitro Analysis

Nano-In Vivo Analysis

Nano Robotics, Nano sensors

BioNEMS

Nanodrugs, Drug Delivery, Diagnostics, cancer Treatment

Nanomaterials and Implants

Injectable BioMEMS Implantable LOC LOC

Digestable sensors

Lab Automation TAS

Implantable Devices

Benchtop Devices

Portable Devices

Wearable Devices

2010

2015

2020

2025

Beyond--
Source: Frost & Sullivan.

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Next Gen Sequencing--Thousand Dollar Genome

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Technology Snapshot
Overview
Next Gen Sequencing involves technologies that can significantly decrease the cost and time of sequencing while improving accuracy and length of reads. Technologies, such as real-time single molecule detection, nanopore sequencing, high-density semiconductors allow multiplexing, label-free detection, increased read-lengths, and reduced overall costs and time. Use of novel materials and the integration of biology, chemistry, electronics, and micro/ nanofluidics is playing a significant role in development of follow on next gen sequencing technologies. Portable sequencers, (PoC) which are cost effective and can be used for small size runs will find increased applications in diagnostics and regular point-of-care clinical studies.

Importance
The large scale adoption of sequencing can be useful for clinical diagnostics and drug discovery in addition to basic biomedical research and genetics studies. Regular genetic testing can improve clinical management of diseases based on patient stratification and personalized therapy design. Regular use of sequencing can reduce healthcare costs, bring down drug development costs and timelines and improve therapeutic outcomes for many diseases. Predictive disease models can be developed with use of valuable sequencing data.
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Year of Impact
Several next gen sequencers are already in the market and these
include Pacific Biosciences SMRT sequencer, Ion Torrents Ion Proton and Oxford Nanopores GridION and MinION. Solid state nanopore based sequencers. should enter the market by 2013
Regular application in clinical diagnostics and genetic screening tests by 2013 or 2014. Microbiome research and research on human pathogen interactions should find increased applications by 2015. Whole genome sequencing lower than $1000 combined with low instrumentation costs is likely to be achieved by 2013.
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Global Footprint
USA/ Canada Highest amount of research and funding for next gen sequencing projects. Most of the Tier 1 companies as well as mid and small sized innovation driven companies are based in USA and research on DNA methylation , RNA profiling, epigenetics and so on. Adoption of next gen sequencing in drug discovery, genetic tests is the highest in US and several partnerships between sequencing developers and research labs, allied tech developers is helping to increase adoption and shorten time to market. The government initiatives are the maximum in US and these include $1000 genome project, Human Microbiome Project(HMP), 1000 genomes project- supported by NHGRI. Europe More than 220 high throughput next gen sequencing facilities in focusing on different applications. The adoption of gene screening tests for genetic diseases is relatively low in EU. EU Epigenomics Consortium , E-Rare are some of the initiatives focused of NGS technologies and applications. The developments of NGS technologies is moderate except a few countries such as UK and Germany that have developed innovative sample preparation methods and sequencers, China BGI (Beijing Institute of Genomics), the largest global genomics center is the pioneer in sequencing research and has partnerships with US companies and institutions around the globe. However, the developments in terms of next gen sequencing technologies has been slow in China and increased private and federal investments combined with increased collaborations will help develop better analytical systems .

Intensity of Technology Development Very High High Medium Low Very Low

India Research is relatively low - mainly in the area of bioinformatics for next gen sequencing. Adoption of next gen sequencing is witnessed mainly in basic research (plant genomics, cancer genomics) and so on. Tier 1 company Life Technologies(Ion Torrent) recently launched its Ion Proton to increase adoption for drug discovery and diagnostics applications. Currently there are about 15 sequencing centers in the country.

Australia/New Zealand The research is slow paced and the number of sequencing providers are also few in number.
Source: Frost & Sullivan.

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Stakeholders and Technology Segments

Technology Segments Stakeholders Trends/ Developments The development of single molecule analysis SBS methods such as Life Technologies- Ion Torrents products has led to drastic improvements in accuracy and read lengths while bringing down the costs of sequencing. Non optical detection techniques that detect based on changes in pH or current will help reduce reagent costs. Use of non labeled nucleotides are simplifying the sequencing process. Development of high density chips such as Ion Torrents Ion Proton that can improve throughput and generate large amounts of data per run. Generally read lengths are short with SBL methods; new platforms are aimed at improving the read lengths. Hairpin DNA system using magnetic beads being developed by the startup Picoseq can be used for high throughput sequencing using hybridization.

Sequencing by Synthesis

Sequencing by Ligation

Nanopore Sequencing

Highly scalable technology area that can revolutionize sequencing in terms of costs, speed and throughput. This single molecule, label free method of sequencing area is being actively explored by companies and academia, which are working on different types of nanopores and different detection methods. Oxford Nanopore has launched its first nanopore based sequencer recentlyboth portable and desktop versions have been introduced. A few of the nanopore sequencers are expected to enter the market in the next 2-3 years ( eg. Noblegen Biosciences, Stratos Genomics, Genia).
Only a handful of companies are working on direct microscopy based sequencing methods- still in research phase and far from commercialization The instrument is prohibitively expensive but the sequencing costs would drop drastically. TEM(Transmission electron microscopy), SEM( Scanning electron microscopy) and AFM (atomic force microscopy) are some of the microscopy based sequencing platforms under development.

Direct Imaging by Advanced Microscopy

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Recent Developments
Company Product / Technology Details The company is developing a nanopore sequencer based on DNA expansion technology. The DNA is encoded into constructs called Xpandomers (reporters) . These reporters have a high signal to noise ratio and are best adapted for nanopore detection and Stratos is developing a sequencing instrument based on this. The desktop microfluidic sequencer to be launched later in 2012 is based on SBH chemistry. The integrated sequencing platform is centered around picoinjector technology that the company licensed exclusively from Harvard University. Sample preparation, target enrichment, sequencing, and data analysis can be done in microfluidic channels in a much simpler and rapid fashion when compared to competing methods. MinION ( disposable chip for PoC settings) and GridION (high throughput desktop sequencer) launched in 2012 utilize biological nanopores for low cost, rapid and high throughput sequencing. Illumina has made investments in ONT and the company has a number of other collaborations with academia, working on advanced technologies. Optipore is an enzyme free, optical method that uses nanopores. It allows analysis at single molecule and it is a highly multiplexed, rapid method of sequencing in a highly cost effective manners. The system converts DNA into a synthetic coded version that is then captured by a beacon as it passes through the nanopores and the color codes correspond to the bases. The second prototype of the sequencer is under development and the company expects to go commercial in the next 1-2 years.

Stratos Genomics

Sequencing by Expansion (SBX)

GnuBIO Inc

Integrated GnuBIO system

Oxford Nanopore Technologies

GridION and MinION

Noblegen Biosciences

Optipore

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Industry Landscape--2015

Efficient massive parallelisation and automation of sample preparation, combined with improved sensitivities will enable reduced sample preparation time, costs and IT burden. Technology Developments Portable sequencers that will be capable of sequencing entire genomes of bacteria, viruses and larger genomes. Solid state nanopores and the use of semiconductors more regularly in sequencing applications

Sequencing research is expected to reach significant height by the year 2015. With increase in federal and Academic and Corporate Research venture funding for core and allied technologies, technology developers are poised to deliver a number of products in the next couple of years. Many consortia and research groups are working on bioinformatics tools and cloud based data management systems that can be effectively used for data analysis.

Current initiatives such as the $1000 Genome, 1000 genome project, Human Microbiome Project in the USA Government Initiatives and few EU initiatives will eventually allow next gen sequencing to find increased utility in drug discovery , companion diagnostics and regular genetic screening and SNP testing. Regulatory policies that favor the rational use of next gen sequencing for healthcare applications is likely to become more standardized.

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Adult Stem Cell Therapies--The Commercial Cell of Origin

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Technology Snapshot
Overview
Adult stem cells are undifferentiated cells found among differentiated cells in tissue/organ. They can differentiate themselves to yield some or all of the major specialized cell types of that tissue/organ for replacement of damaged or injured tissue. Adult stem cells can be derived from marrow (stromal cells) or from placental cord blood. Therapies are being developed for a range of diseases from myocardial infarction to liver disease and diabetes. Stromal cells are extracted from the patient and differentiated in vitro. Globally, more than 200 companies are involved in developing stem cell products and the therapies are likely to be disruptive treatments for medical sectors (For instance knee implants, bone marrow transplant, heart muscle repair).

Importance
Adult stem cell therapies are more feasible lines of treatment compared to embryonic stem cells as their use is not impeded by ethical issues and the policies are globally uniform. Adult stem cell therapies are also less time-consuming in terms of developmental cycle and therefore, more attractive for technology investors. In addition, as the cells are extracted from the patients own marrow, they preclude the possibilities of immunogenic reactions, making the therapy viable with respect to regulatory standards.

Year of Impact

Adult stem cell therapeutics are still in their infancy in the United States and Europe as no stem cell therapies have been approved to date.

The most advanced therapies such as those from Cytori Therapeutics, Osiris Therapeutics and Aastrom are in early or late Phase 3. These therapies are for autoimmune or cardiovascular diseases. Other therapies for oncology, neurology and dermatology are being developed and are in Phase I or II. The year of impact is therefore, 2017-20.

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Global Footprint
North America USA has five states most active in the development of adult stem cell therapeuticsNew York, New Jersey, Maryland, California and Massachusetts. Osiris Therapeutics and Aastrom have stem cell therapies for cardiovascular diseases and autoimmune diseases. In Phase III trials. All the above-mentioned states have state-centric funding as well as regulatory guidance institutions to accelerate the development process. Europe UK, Sweden and Denmark are the countries in Europe that have more permissible policies and are concentrating on adult stem cell therapies, particularly for autoimmune diseases and oncology. ReNeuron, Capsant, NsGene A/S and the Karolinska and Lund research centers are the centers of development. Stem cell therapies are mostly in Phase I or II and commercialization is slower.

Intensity of Technology Development Very High High Medium Low Very Low

China The Ministry of Science and Technology has made available up to $293 million for stem cell research/spinoffs from 2006-2010. The Chinese Academy of Science provides an additional $20 million as well as set-up assistance for new start-ups in this field. There is also a clear focus of resources on the applications of stem cell research, such as therapeutic uses and drug testing. Rest of APAC The biggest participants in the stem cell industry are Singapore, Australia and Israel. Pluristem Therapeutics and Gamida Cell already have products for autoimmune diseases and cell expansion (inflammatory diseases) in Phase II/III. Mesoblast in Australia is both developing and promoting APSCs for cardiovascular, diabetes, oncology, eye disease, and orthopedic therapies. All products are in Phase I/II.

Source: Frost & Sullivan.

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Funding Trends
NIH Stem Cell Funding 2002-2010
400 350
Funds ($ million)

SBIR Funding 2006-2010

Funding ($ million) 3 2 1

300 250 200 150 100 50

0
Embryonic Non-embryonic
ARRA

0
2006 2007 2008 Year 2009 2010

2002

2003

2004

2005

2006 Year

2007

2008

2009

2010

Source: NIH, EC, MRC

NIH is the primary institute for stem cell funding, particularly for start-ups engaged in the development of adult stem cell therapies. It has shown a steadily increasing trend and the investment was close to $350 million in 2010, excluding ARRA funding. The Small Business Innovation Research grant has also been a good source of funding for early-stage startups but has shown a decline since 2010. It has however, increased till 2011, with the allocated budget for 2012 being $3.1 million.
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Technology Benchmarking
Dashboard Summary
Aastrom
Low
1 2 3 4 5

Development (Stage and Progress)

High Low
1

Disease Market
High
2 3 4 5

Therapeutic Efficacy
Low
1 2 3 4 5

Total 15 Points
High

12.9 13.4 13.5 11.9 13.1 13.0

Osiris Therapeutics
Mesoblast ReNeuron Gamida Cell Pluristem Therapeutics

Low
1 2 3 4 5

High High
1 2 3 4 5

Low
1 2 3 4 5

High

Low
1 2 3 4 5

High High
1 2 3 4 5

Low Low
1 2 3 4 5

Low
1 2 3 4 5

High
High
1 2 3 4 5

Low Low
1 2 3 4 5

High High
1 2 3 4 5

Low Low
1 2 3 4 5

High High
1 2 3 4 5

Low Low
1 2 3 4 5

High High

Low Low

High

Low

High

The companies have been rated on the basis of the stage and progress of development of the therapy, the market for the diseases at which the therapies are targeted and the therapeutic efficacy of the treatment (as indicated by results of clinical trials). Aastrom and Osiris Therapeutics have both scored the highest with respect to the development stage and progress of their therapies. They are both US companies, implying that easy access to the streamlined regulatory process provided by the FDA for APSC therapies. Mesoblast has a leading position in terms of disease market as it is currently running clinical trials for the top 3 diseases identified by WHO and NIH for highest healthcare burden and mortality rates, i.e., diabetes, cardiovascular diseases and oncology. The only other company that has a disease portfolio close to that of Mesoblast is Pluristem Therapeutics. ReNeuron and Gamida Cell have scored the highest in terms of therapeutic efficacy of their treatments. Both companies have reported successful Phase IIa trials with over 70% efficacy quotients. Although the other companies have also advanced to Phase III trials, the efficacy quotient has been less and the pharmaco-toxicity profile is not at the same level as the treatments from these two companies.
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