Targteted Drug Delivery - Technologies and Applications

Targeted Drug Delivery--Technologies

and Applications

28th November 2013

Aiswariya Chidambaram

Novel Drug Delivery Systems and Clinical Trial

Management China 2013

2

Focus Points

Focus Points

Importance of Targeted Drug Delivery

Segmentation of Targeted Drug Delivery

Technology Capability – Drug Delivery Carriers

Technology Value Chain

Targeted Drug Delivery – Key Innovations

Targeted Drug Delivery – Drivers and Challenges

Key Technology Developments – Drug Delivery Carriers

Life Cycle Analysis of Drug Delivery Systems

Demand Side Analysis

Potential Applications by Therapeutic Area

Patent Distribution and Publishing Trends

About Frost & Sullivan

3

Importance of Targeted Drug Delivery

Maximize precision

Moderate release

Minimize toxicity

Blood Brain Barrier (several

factors lead to ineffective delivery to

brain)

Mucous Barrier

(lungs, nose, and cancer

cells)

Subcellular Targeting

(cytosol, ER, nucleus

targeting)

Ineffective Ligand

Targeting

(disease specific

ligands on cell surface)

Other Barriers

(pH, osmotic

potential, electric charge)

Size Exclusion

(size barrier of different

membranes)

Targeted drug delivery is a system of drug delivery which increases the concentration of the drug in specific organs and tissues

relative to the others. This helps improve the efficacy of the drug while reducing side effects. Cancer, autoimmune diseases,

neurological disorders, pulmonary diseases, cardiovascular diseases and most other conditions that require effective, safe ,

specific targeting of certain receptors or direct delivery into the organ are attractive targets for targeted drug delivery.

Criticality of Targeted Drug Delivery Physiological and Biological Barriers to Drug Delivery

Source: Frost & Sullivan

4 D4C1-TI

Targeted Drug Delivery Carriers

Lipid-based

Polymer-based

Inorganic Nanoparticles

Magnetic Particles

Nucleic Acid/ Peptide-based

Cell-based

• Oncology and neurology are the two most widely

researched diseases for targeted drug delivery.

• Delivery to the lungs, eyes, and nose are other areas of

interest as targeting these organs is relatively difficult.

• Liposomes - nanoliposomes, stimuli responsive

liposomes, and conjugated liposomes with other functional

attributes are gaining attention from researchers.

• Peptides and nucleic acids -Chimeric peptides are formed

when a drug that is normally not transported through the

BBB is conjugated to a brain drug-targeting vector.

• Engineered polymers - PEG, polymeric nanomicelles and

other co-polymers; polymers designed to respond to

specific biological changes (such as pH, temperature,

chemicals and so on) so that the drug load is released

only upon stimulation.

• Conjugates - antibody conjugated liposomal carriers,

multifunctional nanocarriers, and other particles that form

conjugates with the drug.

Segmentation of Targeted Drug Delivery


5

Technology Capability–Lipid-Based Carriers

Liposomes are widely used for insoluble drugs and advances in conjugation technologies is enabling them to be used as

targeted delivery systems. For example, the biocompatibility and possible diversity with structures and compositions make them

suitable for a number of targeted delivery applications.

Drawbacks

Rapid degradation (uptake by RES(reticuloendothelial system)

Poor scale up/need for extensive modifications

Short shelf life

Advantages

Enables passive/active targeting

Easy and rapid internalization

Low immunogenicity

Improves solubility/ bioavailability

Drug protection/

Biocompatibility

Stimuli Responsive Liposomes

Liposomes will find more adoption with the development of nanoscale liposomes embedded with drug depot and

polymer depots. Targeted liposomes and environment sensitive liposomes are the ones with maximum potential for

tumors and neurodegenerative disorders, and a number of existing chemotherapeutics are being encapsulated in

stimuli responsive liposomes.

Polymer

Composite

Liposomes

Stealth

Liposomes Conventional

Liposomes

Targeted

Liposomes


6

Technology Capability–Polymer-Based Carriers

Definition: Polymers have been widely used for sustained release of drugs, and adding functional targeting groups and other

moeties has enabled them to be used as targeted delivery vehicles. A number of natural and synthetic polymers

(degradable/nondegradable, hydrophilic/hydrophobic) with multifunctionalities are being produced for delivering drugs, while

polymer composites with lipids and inorganic nanoparticles are also being developed.

Advantages

Cell mimicking properties

(certain polymers)

Wide range of drugs can

be loaded

Easy Functionalization

(surface modification)

Controlled Release

Kinetics

Low Cost/Scalable

Disadvantages

Hypersensitivity (certain

polymers)

Biocompatibility Issues

(synthetic)

Polymeric templates have been recently used to develop artificial cells, such as platelets and biomimetic vesicles for

targeted delivery. Use of more natural polymers and polymer conjugated with other delivery methods will witness

increased attention from drug delivery companies and pharmaceutical companies in the next 2 to 3 years.

Stimuli

Responsive

Polymers

Multifunctional

Polymers/

Co-Polymers

Artificial Cells Polymer

Composites


7

Technology Capability–Inorganic Nanoparticles

Advantages

Optical Properties

High Stability (over wide

temperature and pH

range)

Highly Tunable

Evade RES Clearance

Drawbacks

Toxicity Issues (Long-

Term Safety )

Non Biodegradable

(accumulation)

Definition: Inorganic nanoparticles comprise nanoscale particles made from silica. metals, metal hydroxides, carbon and so

on. A number of multifunctional, inorganic nanoparticles are being developed for targeted drug delivery and imaging

applications. Hybrid drug carriers combining stimuli sensitive hydrogels and inorganic nanoparticles, and conjugation of

biomolecules to nanoparticles are areas of interest.

Silica/Alumina

Nanoparticles Quantum

Dots

Gold Based

(AuNPs) Carbon Based

Particles

Metals/

Oxides/

Sulfides

Inorganic nanoparticles with multiple functionalities will prompt further research for development of effective cellular

delivery systems. A few gold-based colloids and nanoshells are in clinical trials for cancer applications.


8

Technology Capability–Cell-Based Systems

Microbial Ghosts

and Viral

Particles

Engineered

RBCs

Genetically

Engineered Stem

Cells

Definition: Cells have been found to act as potential drug delivery agents and they can be used to directly encapsulate the

drug or used with nanoparticles for better pharmacokinetic properties, biocompatibility and higher drug loading capacity. The

figure indicates some of the major types of cell-based delivery platforms in development.

Advantages

High Drug Loading

Capacity

Adjuvant Properties

Sustained Release

Biocompatible (except

microbial ghosts)

Scalable/Cost Effective

Drawbacks

Potential Immunogenicity

(viral, bacterial particles)

for non vaccine delivery

Storage and Formulation

Issues

Maintaining integrity

(RBCs, stem cells,

macrophages)

Dendritic Cells/

Tumor cells

While viruses and virus-like particles (VLPs) have been widely used for vaccine delivery, the use of engineered

bacterial ghosts (BG), engineered RBCs and stem cells is slowly moving to the clinic. Many of these cells and cell

derived-particles are conjugated with other delivery strategies to improve the efficacy of treatment. Stem cell-based

therapies provide a promising approach to the treatment of several diseases in humans, and extensive research on MSCs for targeted delivery is underway.


9

Technology Capability–Magnetic Particles

Biological Non-Biological

Advantages

Evade RES clearance

Image guided delivery

with MRI

Controlled Drug

Release

Highly targeted

Drawbacks

•Gradient loss for deep

seated tissues

•Accumulation of

magnetic material at

target site

•Requirement for

specialized

manufacturing and QC

system

Inorganic Organic

Definition: These are micro-and nano-scale particles loaded or conjugated with drugs that get activated when exposed to an

active magnetic field and release drug cargo at the target site. It is a highly controllable and effective form of drug targeting. In

addition to delivery, these particles are apt for safe image guided drug delivery.

Organic magnetic carriers include magnetoliposomes (ferrofluids entrapped in the liposome core) and polymer

magnetic particles. Iron oxide particles used directly with the drugs are inorganic magnetic particles. Incorporation of

magnetically responsive materials into microspheres makes them susceptible to applied magnetic field, so that they

are concentrated to the target site by the application of a magnetic field externally to that site. Ferriliposomes are

other magnetic particles that could be used in combination with magnetic resonance imaging (MRI) for targeted drug

delivery and also as theranostics. To improve biocompatibility and safety, biological magnetic particles, such as

magnetobiosomes and engineered erythrocytes are being designed, and these are highly promising platforms.


10

Technology Capability–Nucleic Acid/Peptide Carriers

Cell Penetrating

Peptides

Definition: In addition to peptides and nucleic acids being used as effective drugs, they are also being explored for targeting

drugs. Cell penetrating peptides, polypeptide membranes, and DNA Nanorobots are some of the technologies with immense

opportunities. Delivery of siRNA and other nucleic acid drugs, which is still a major challenge can be overcome with the use of

peptide and aptamer-based targeting.

Advantages

Highly Targeted

Biocompatible

Biodegradable

Drawbacks

Mode of administration

Aptamer Instability

Peptide

Conjugates

DNA/RNA

Aptamers

RNA/Peptide dual aptamer systems, polypeptide membranes are being developed for highly targeted delivery and being

extensively researched. DNA Origami is a promising technology area which will enable ‘smart delivery’ to become a near-term

reality. Overcoming aptamer instability via modifications is improving the clinical value of these systems.

DNA Origami(DNA

Nanorobots)


11

Conceptualization of Drug Delivery Carriers

Development of Drug Delivery System

Pre-formulation and Formulation

Clinical Trials

Scale Up and Large-Scale Manufacture (GMP)

Regulatory Approval and Marketing

Technology Value Chain


12

Trojan Horse CNS Targeting Technology for Stroke (ArmaGen

Technologies, CA, USA)

The TNF-alpha decoy receptor is engineered as a fusion protein with a BBB

molecular Trojan horse (MTH).

The MTH is an engineered monoclonal antibody (MAb) against the BBB

specific transferrin receptor (TfR).

Facilitates receptor mediated transport of the drug across the BBB.

Ensures effective and safe delivery of drugs to the brain.

Blood

Brain

Barrier

Key Innovations–Targeted Drug Delivery

Multistage Nanocarriers (Leonardo Biosystems, TX, USA)

Multi-stage nanocarrier-based delivery platform

Customized mesoporous silica nanoparticles are used

Functions better than single-stage systems

For delivering siRNA, small molecule and imaging agents to cancer cells.

Thermally Responsive Liposomes, Lysolipid Thermally Sensitive Liposomes

(LTSL) (Celsion Corporation, NJ, USA)

A patented liposomal tumor targeting delivery system

Delivers high concentrations of drug to target site (tumors) on exposure to local

hypothermia.

Currently carrying out Phase 3 clinical trials (HEAT Study) for its lead candidate

ThermoDox®, a formulation of doxorubicin for targeting HCC (hepatocellular

carcinoma).

Expanded applications to develop formulations for other chemotherapeutics,

such as docetaxel and carboplatin.

Hyperthermia

Drug release

into tumor


13

Key Innovations–Targeted Drug Delivery (continued)

IVECT Method , (Intezyne, Inc, FL, USA)

A multidisciplinary approach of drug delivery that has the potential to revolutionize cancer

treatment.

Developed proprietary polymeric micelles that deliver drugs to tumors using a triggered

release mechanism.

It is a highly tunable and cost-effective platform that can incorporate different targeting

ligands.

Currently has four cancer chemotherapeutics in its pipeline: two lead programs in final

preparation for IND submission and two others in earlier stages of preclinical development.

Resealed RBCs for Targeted Drug Delivery to Tumors , GRASPA (ERYTech Pharma,

France)

A tumor targeting therapeutic utilizing erythrocyte encapsulation technology.

Encapsulates a wide array of molecules such as peptides, proteins and small molecules for

delivery.

Targets the tumor microenvironment using the encapsulated L-asparginase which depletes

the circulating asparagine, a tumor growth factor thereby starving the tumor cells to death.

Currently tested in Acute Lumphoblastic Leukemia, Pancreatic cancer and Acute Myelod

Leukemia.

Resealed Erythrocytes for targeted and Controlled Dryg delivery, Erydex (Erydel Spa,

Italy)

An erythrocyte based drug delivery system for sustained release of drugs

Encapsulaties autologous red blood cells with glucocorticoid analoguedexamethasone

sodium phosphate (Dex 21-P).

Used for treatment of chronic disorders such as cystic fibrosis, Ataxia Telangiectasia.

Ventured in to diagnostics and targeted drug delivery (EryTargeting) aimed at delivery of drug

cargo only to targeted macrophages.


14

• Need for effective delivery of biologics

• Patenting opportunities for targeted therapies

• Quicker time to market/ease of approval

• Discovery of disease biomarkers

• Development of spatially/temporally controlled systems

• Advances in Nanotechnology

• Improve patient compliance

• Competition from medical devices for targeting

• High costs of several types of systems

• Potential long-term effects of nano particles

• Lack of multipronged/ combinatorial targeting approaches

• Poor funding scenario

Targeted Drug Delivery Systems–Drivers and Challenges


15

Technology Development— Lipid Based Carriers

Below listed are some of the areas being developed by universities and research institutions

• Dual response sensitive liposomes

• Self assembling nanoemulsions

• Zwitterionic oligopeptide liposomes targeting mitochondria

• Liposomes fused on inorganic nanoparticles

• Targeted liposomes for intracellular delivery

Technology Development 0

1

2 3

4

5

4.0

Key

0 - 2 Less than 10 company

developments

2 - 3.5 Between 10 and 20 company

developments

3.5 - 5 More than 20 company

developments

Company Key Developments

Silence Therapeutics (UK)

Silence's siRNA delivery platform is based on the proprietary lipid moeities that

embed siRNA into lipid-bi-layer particles. The siRNA is combined with Silence's

developed lipid moieties containing cationic lipids, co-lipids and PEGylated lipids to

form nanoscale structures.

Celsion Corporation(NJ, USA)

ThermoDox, the patented heat sensitive liposomal formulation of doxorubicin is in

clinical trials for liver cancer and also being tested for a number of oncology

indications.

LiPlasome Pharma ApS (Denmark)

The tumor targeting drug loaded lipid nanocarriers are designed to be susceptible to

degradation by phospholipase A2 (PLA2), which is high in the cancer environment.

The prodrug lipids are degraded by PLA2 and get converted to

active drugs such as anticancer lysolipids and/or fatty acid drug derivatives. The

degraded entities also enhance the permeability of the drugs across cancer cell

membranes to deliver high doses of drug to the target site.


16

Technology Development—Polymer Based Carriers


PolyTherics Limited (UK)

Flexible polymer platform for targeted, sustained delivery of biopharmaceuticals.

GlycoPol TM is a targeting glycopolymer developed by attachment of saccharides a

poly(methacrylate) backbone. Drugs can be attached to the backbone for targeted

delivery.

Intezyne, Inc. (FL, USA)

IVECT Copolymer Micelles that are based on the IVECT Method offer a lost cost,

modular and highly targeted delivery platform. It is highly tunable and can be used to

deliver a number of drugs for varied indications.

The lead candidate IT-141, has demonstrated significant activity against a diverse

number of cancer cell lines. Another formulation IT-143, is the encapsulated

daunorubicin, is being assessed for treatment of lung cancer, osteosarcoma, and

ovarian cancer.

Arrowhead Research Corporation (CA, USA)

The company has a portfolio of in house developed and acquired targeted delivery

platforms, of which DPCs(Dynamic polyconjugates) and RONDEL are based on

polymer nanoparticles. Both are being explored for delivery of siRNA therapeutics.


• Artificial Cells, Synthetic Platelets (Scripps Research Institute and Sanford-Burnham Institute)

• Dual Stimuli Responsive „Smart‟ Capsules (University of Melbourne)

• Protein Polymer Drug Conjugates

• Polymer drug depot in liposomal nanoparticles

• Multifunctional polymeric vesicles

• Stealth particles coated polymers, Amphiphilic Biodegradable Dendrimer-Like Star Polymers


1

2 3

4

5 4.5


17

Technology Development— Inorganic Nanoparticles

The adoption of inorganic nanoparticles is on the rise with the development of gold and silica

nanoshells, nanowires, nanorods, and many more. They are emerging as an important and useful

class of targeted entities that can be functionalized for specific needs. These inorganic nanoparticles

can also be used for simultaneous imaging and delivery applications. Iron oxide, silica, gold,

fullerenes, and carbon are the most widely researched materials.


Leonardo Biosystems (TX, USA)

Multistage mesoporous silica nanoparticle based platform for spatio-

temporally controlled drug release is attracting a lot of interest from investors

and pharma companies. The system is undergoing optimization and

enhancements.

CytImmune Sciences Inc.

The technology is based on pegylated colloidal gold nanoparticles that can be

used directly as drugs via tumor targeting molecules or can be used as

carriers for cancer drugs.


• Mesoporous nanoparticles conjugated with peptides, antibodies, and other entities

• Stimuli sensitive nanoparticles

• Surfactant functionalized nanoparticles

• Aptamer gated nanoparticles

• Multistage nanoparticles


1

2 3

4

5

3.5


18

Technology Development— Cell Based Carriers

The adoption of cell-based drug carriers is relatively low despite research being carried out for more

than a decade. Modified RBCs form the majority of therapeutic carriers, while stem-cell based drug

targeting is showing promising results in clinical trials. Microbial cells have been used for targeting

vaccines and drugs for several years, and modified forms of these cells are now being developed for

more effective and safe targeting.


EryDel SpA (Italy), EryTech Pharma (France) Erythrocyte loaded drugs for multiple disease areas currently in clinical

development. These are being used for controlled delivery as well as targeting.

Pevion Biotech AG (Germany)

Proprietary virosome-based platform for targeted drug delivery and adjuvant

activity for subunit vaccines. A number of vaccines are in advanced phases of

clinical trials using their VLP technology, and has also been outlicensed to

several pharma majors.

Engene IC (Australia)

EDV (Engene Delivery Vehicle) technology basically consists of inert bacterial

cell derived nanoscale minicells conjugated with bispecific antibodies for highly

targeted intracellular delivery of cancer drugs/siRNA. Immune stimulating

properties enhance performance and the drugs using this platform are currently

in clinical trials.


• Resealed erythrocytes/ Engineered erythrocytes with viral fusion proteins (for example, Erythro-magneto-HA virosomes)

• Engineered mesenchymal/ neural stem cells (for example, Silica nanorattle-drug anchored mesenchymal stem cells

• Virosomes/Bacterial ghosts for DNA vaccine and subunit vaccines

• iPSCs reprogrammed for organelle specific targeting

• Magnetotactic bacteria

• Prodrugs/Drugs bound to RBCs in circulation for long-term thrombosis treatment


1

2 3

4

5

2.5


19

Technology Development—Magnetic Particles


1

2 3

4

5

1.5


Vascular Magnetics, Inc, (PA, USA)

Biodegradable, magnetic drug-loaded particles in combination with a magnetic

targeting catheter and a magnetic field generating device that guides the

particles to narrowed arteries in PAD (Peripheral Artery Disease).

Nanobiomagnetics Inc. (SW R and D) (OK,USA) Magnetic vectored drug delivery using magnetically responsive therapeutic

constructs.

nanoTherics (UK)

Magnetic transfection method MagnetofectionTM using DNA, siRNA coupled

with magnetic nanoparticles to form a complex. Upon exposure to oscillating

magnetic arrays, cells show uptake of the complex via rapid endocytosis.

MagForce AG ( Berlin, Germany) Iron oxide nanoparticles with aminosilane coating that safely delivers drugs to

tumors upon activation by their proprietary NanoActivator™ magnetic field.


• Bacterial magnetosomes from magnetotactic bacteria for drug targeting that can be functionally superior

to artificial magnetic particles

• Ocular magnetic drug targeting

• Magnetic resealed erythrocytes

• Enzyme and temperature responsive magnetic nanoparticles

• Multifunctional nanoparticles for delivery and imaging (for example, multilayered nanorattles)


20

Technology Development— Aptamers/Peptides/Nucleic

Acids


Savara Inc. (TX, USA)

Condensed nanoparticles of cell penetrating peptides and RNA

therapeutics for targeted intracellular delivery. This is known as

Nanonucleic technology used primarily for RNAi therapy.

Artificial Cell Technologies, Inc (CT, USA)

Layer by layer assembly of polypeptide artificial biofilm nanoparticles for

developing synthetic vaccines. The synthetic nanoparticles incorporate

immunogenic epitopes and give rise to “Artificial Virus” like structures

that can be used for vaccine delivery.

Aptagen, LLC (PA, USA)

Aptabodies™ developed by the company are proprietary, functionalized

aptamers that can be used for drug delivery or diagnostics. The

company is a good collaborative partner for pharma/biotech companies

for delivery of peptide therapeutics.


• Peptide Dendrimer Conjugates

• Engineered Oleosin–Self assembled to form Biomimetic Vesicles (University of Pennsylania)

• Peptide and Aptamer Functionalized Nanoparticles; Aptamer nanoparticle Bioconjugates

(PANOPTES project --novel peptide-based nanomaterials for ocular delivery)

• Cell penetrating peptides (HIV TAT peptide, human calcitonin (hCT) hormone)

• Carbohydrate mimetic peptides (UC, Berkeley)

• Cell specific aptamers, peptide conjugated environment sensitive particles


1

2 3

4

5

2.5


21

Life Cycle Analysis of Drug Delivery Systems

Maturity Development Growth

Magnetic nanoparticles

Stem cell carriers

DNA Nanorobots

Decline

Time

Ma

rket

Po

sit

ion

Biological Magnetic carriers

Conjugates/Hybrid Carriers/ Composite particles

Stimuli sensitive liposomes

Stimuli responsive polymers

Artificial cells/ Biomimetic particles

Multistage/Multifunctional

nanoparticles

Functionalized Polymersomes

Inorganic nanorods, nanoshells, nanowires

Engineered peptides/Aptamers

Conventional Liposomes Non Biodegradable Polymers


22

Demand Side Analysis

End-User Requirements

Applications Versatility

Tunability

Market Exclusivity

Biocompatibility

Cost Effectiveness and Scalability

‘Smart’ Delivery


23

Potential Applications - Ocular

InSite Vision Inc. Integral BioSystems Quark

Pharmaceuticals

Novagali Pharma Ocular Therapeutix

• Challenges with regard to topical administration include poor access to the posterior portion of the eye,

need for frequent doses, and poor controlled delivery.

• Ophthalmic inserts developed for sustained release suffer from limitations, such as high costs and difficulty

with insertion.

• Liposomes and polymers - most widely used vehicles for ophthalmologic delivery. Targeting ligands that

can cross the Blood Retinal Barrier(BRB) explored for a number of orphan retinal diseases.

• Identification of ocular transporters and development of transporter targeted drugs modified with targeting

ligands

• Other commonly deployed delivery systems - functionalized nanoparticles, in situ forming gels, and

colloidal dosage forms


24

Potential Applications - CNS

Serina Therapeutics Inc. ArmaGen Technologies Lauren Sciences LLC

to-BBB VECT-HORUS

• Systemically administered drugs have limited access across the BBB, while local administration is painful

and challenging.

• Most innovative drug developments for neurological disorders are biologicals, such as cell based therapy,

RNAi or gene therapy.

• Drug delivery systems that can cross the BBB (blood brain barriers) primarily include nanoparticles with

targeting ligands and CNS targeting vectors that can bind to receptors on the BBB and cross the barrier in

order to improve efficacy and increase safe therapeutic window.

• Most of the research is in the basic research or pre-clinical stage

• A number of partnerships and collaborations have been witnessed in the last 1 to 2 years. (For example,

Genzyme Pharmaceuticals and Pharmidex Pharmaceutical Services Ltd)

Angiochem Inc. Advectus Life

Sciences Inc.


25

Potential Applications - Oncology

Celsion Corp BIND Biosciences LiPlasome Pharma

Alchemia Savara

Pharmaceuticals

• Oncology is the most well penetrated area - more than 80% of targeted drug delivery activity is focused on

safe and effective delivery of chemotherapeutics to cancerous cells.

• Strategies based on differences in tumor cell metabolism, tumor microenvironment, and expression of

receptors on tumor cell surfaces are being developed.

• Most of them in clinical development are conjugates of polymers, liposomes, and inorganic nanoparticles,

while magnetic targeting and imaging is also being explored by a few Participants.

• Cell-based delivery systems that can trigger the immune system against cancer cells and multifunctional,

multiple ligand targeting strategies will take predominance.

Silence

Therapeutics

CytImmune

Sciences Inc.

Intezyne EnGene IC ERYTECH Pharma Cerulean Pharma Inc.

MagForce AG


26

Potential Applications – Infectious Diseases

Artificial Cell

Technologies Inc. EryDel

• High degree of noncompliance to therapy in a number of infectious diseases - led to development of

targeted drugs that can specifically target the pathogen and associated pathways.

• TB, HIV, and malaria are some of the highly researched areas.

• Virosomes and bacterial ghosts have been widely used for vaccine delivery.

• By developing different nanoparticle formulations with cell penetrating peptide conjugates, glycomimetic

peptides, and other moieties, intracellular delivery to pathogens is becoming possible.

Arrowhead Research

Corporation

Xenetic Biosciences Pevion Biotech AG


27

Potential Applications – Cardiovascular

Vascular Magnetics Inc. Spheringenics Inc.

• Eluting stents and cardiovascular implants – invasive drug delivery methods – strong need for non-invasive

drug delivery systems.

• Targeted immunoliposomes and biodegradable targeted polymeric particles are being developed for

cardiac delivery and imaging.

• Cell-selective targeted drug delivery - key research area for cardiovascular applications.

• In atherosclerosis and other ischemic conditions, it is necessary to develop systems that can release drugs

on sensing difference in shear stress or tissue injury.

BIND Biosciences


28

Potential Applications – Pulmonary

MannKind Corporation BioParticle

Technologies

• Most appropriate route for the treatment of asthma, cystic fibrosis and other pulmonary diseases such as

tuberculosis, COPD, and lung cancer; explored for systemic diseases like diabetes.

• Useful for developing inhalable vaccines, which hold huge market potential as a needle-free vaccination

strategy for a number of respiratory infections.

• Peptide and protein drugs are ideal for pulmonary delivery as they undergo degradation in the

gastrointestinal (GI) tract).

• Liquidia‟s PRINT (Particle Replication In Non-Wetting Templates) and MannKind‟s Technosphere have

demonstrated success for pulmonary delivery.

• Liposomes are the most extensively studied system for controlled drug delivery to the lungs.

• Emerging areas of interest are magnetic aerosol droplets, bioresponsive nanoparticles, and co-polymers

with better release profiles.

Liquidia Technologies

Pulmatrix Insmed Inc.


29

Potential Applications–Mapping

Disease prevalence and

criticality of delivery challenges Funding Research Initiatives

Company

Developments

Cardiovascular Medium Medium Medium Low

Ocular Medium Medium Low Low

CNS High Medium Medium Medium

Oncology High High High High

Infectious Diseases

(Targeting Pathogens) Medium Low Low Low

Pulmonary High High Medium Medium Criteria

Key - Funding

Low Less than $100 million

federal and private funding

Medium Between $100 - $200

million federal and private

funding

High More than $200 million

federal and private funding

Key – Research Initiatives

Low Less than 50 published

research projects by

academia

Medium Between 50 and 100

published research projects

by academia

High More than 100 published

research projects by

academia

Key – Company Developments

Low Less than 10 companies

working on TDD

Medium Between 10 and 30

companies working on TDD

3.5 - 5 More than 30 companies

working on TDD


30

Assignee-wise Patent Distribution

Total Number of Patents/applications – 1080 (100 unique patent families).


31

Top Countries for Publishing Patent Applications

US = United States

EP = European Union

WO = WIPO

AU = Australia

CA = Canada

JP = Japan

CN = China

AT = Austria

DE = Germany

ES = Spain

Most of the innovations in targeted drug delivery is happening in the US and European Union, which is clearly indicated by the number of patent

applications published from these regions. Source: Frost & Sullivan

32

Patent Publishing Trends

This chart shows the patenting trends in the last 4 years and the patenting trend has been quite stable. On an average 250 patents were published

every year. Source: Frost & Sullivan

Questions

34

Disclaimer

Frost & Sullivan takes no responsibility for any incorrect information supplied to us by

manufacturers or users. Quantitative market information is based primarily on interviews and

therefore is subject to fluctuation. Frost & Sullivan research services are limited publications

containing valuable market information provided to a select group of customers. Our

customers acknowledge, when ordering or downloading, that Frost & Sullivan research

services are for customers‟ internal use and not for general publication or disclosure to third

parties. No part of this research service may be given, lent, resold or disclosed to

noncustomers without written permission. Furthermore, no part may be reproduced, stored in

a retrieval system, or transmitted in any form or by any means, electronic, mechanical,

photocopying, recording or otherwise, without the permission of the publisher.

For information regarding permission, write to:

Frost & Sullivan

331 E. Evelyn Ave. Suite 100

Mountain View, CA 94041

© 2012 Frost & Sullivan. All rights reserved. This document contains highly confidential information and is the sole property of Frost & Sullivan.

No part of it may be circulated, quoted, copied or otherwise reproduced without the written approval of Frost & Sullivan.

35

Tel: +91 (0) 44 61606666 (Extn: 4097)

Fax: +91 (0) 44 4230 0369

Email: [email protected]

State your need, we would be happy to serve you…

www.frost.com

Frost & Sullivan (I) Pvt. Ltd.

ASV HANSA

No.53, Greams Road

Thousand Lights

Chennai 600 006

AISWARIYA CHIDAMBARAM

Senior Research Analyst – Life Sciences

Your Growth Partner

Contact Information

36

Who is Frost & Sullivan

Frost & Sullivan, the Growth Partnership Company, enables clients to accelerate growth and

achieve best-in-class positions in growth, innovation and leadership. The company's Growth

Partnership Service provides the CEO and the CEO's Growth Team with disciplined

research and best-practice models to drive the generation, evaluation, and implementation

of powerful growth strategies. Frost & Sullivan leverages 50 years of experience in

partnering with Global 1000 companies, emerging businesses and the investment

community from more than 40 offices on six continents.

To join our Growth Partnership, please visit http://www.frost.com.

http://www.frost.com/

37

What Makes Us Unique

All services aligned on growth to help clients develop and implement

innovative growth strategies

Continuous monitoring of industries and their convergence, giving clients first

mover advantage in emerging opportunities

More than 40 global offices ensure that clients gain global perspective to

mitigate risk and sustain long term growth

Proprietary TEAM Methodology integrates 7 critical research perspectives to

optimize growth investments

Career research and case studies for the CEOs‟ Growth Team to ensure

growth strategy implementation at best practice levels

Close collaboration with clients in developing their research-based visionary

perspective to drive GIL

Focused on Growth

Industry Coverage

Global Footprint

Career Best Practices

360 Degree Perspective

Visionary Innovation Partner

38

TEAM Methodology

Frost & Sullivan‟s proprietary TEAM Methodology ensures that clients have a complete 360 Degree

PerspectiveTM from which to drive decision making. Technical, Econometric, Application, and Market

information ensures that clients have a comprehensive view of industries, markets, and technology.

Technical

Real-time intelligence on technology, including emerging technologies, new

R&D breakthroughs, technology forecasting, impact analysis, groundbreaking

research, and licensing opportunities.

Econometric

In-depth qualitative and quantitative research focused on timely and critical

global, regional, and country-specific trends, including the political,

demographic, and socioeconomic landscapes.

Application

Insightful strategies, networking opportunities, and best practices that can be

applied for enhanced market growth; interactions between the client, peers,

and Frost & Sullivan representatives that result in added value and

effectiveness.

Market

Global and regional market analysis, including drivers and restraints, market

trends, regulatory changes, competitive insights, growth forecasts, industry

challenges, strategic recommendations, and end-user perspectives.

39

Our Global Footprint 40+ Offices Scanning the Globe for Opportunities and Innovation

Health & Medicine

Targteted Drug Delivery - Technologies and Applications