Indian Positioning

Biosimilars : Global Trend

Contents

MTR -Highlight

Global Therapeutic Overview

0%

2%

4%

6%

8%

10%

12%

-10% -5% 0% 5% 10%

Anti-hyperlipidaemics

Anti-bacterials

Bronchodilators

Anti-hypertensive

Oncology

Anti-diabetics

Anti-rheumatics

Anti-virals

Bone-calcium regulators

vaccines

Key Drivers

Avastin, Rituxan (Roche),

Erbitux (BMS/LLY/ Merck KgaA)

Glivec (NVS).

Patent Expiries

Taxotere (SAN), Eloxatin (SAN),

Arimidex (AZN), Gemzar (LLY)

Key Drivers

HPV vaccines (GSK & MRK),

Pneumo. (WYE,NVS & GSK) &

Herpes zoster vaccine (MRK). Plus

strong influenza sales.

Key Patent Expiry

Angiotensin II antagonists segment

Diovan (NVS) in 2012, Cozaar (MRK)

2010, Avapro (BMY/ SAN) in 2012

Key Patent Expiry

Lipitor (PFE) in 2011

% Sales Growth: CAGR 2008-14

WW

Mark

et S

hare

%

Bubble = WW Sales in 2014

$70bn

$29bn

$23bn $26bn

$15bn $15bn

$28bn

$37bn

$34bn

Analysis of Top 10 Therapy Areas in 2014, Market Share & Sales Growth (2008-14)

Oncology potentially outperforming market by both volume & value growth in the space

Global Market : Size & Potential

Ma

rke

t P

ote

nti

al

In the worst-case scenario, with an estimated price erosion of biologics of up to 30% , potential market

worth ~$40bn remains very appealing & attractive spread across next five years

Year Estimated Revenue of Patented

Drugs Only Biologics

2010 $23bn $2bn

2011 $36bn $1bn

2012 $44bn $8bn

2013 $22bn $17bn

2014 $14bn $9bn

2015 $16bn $20bn

Total $155 $59bn

2010-2015 : Golden period of Biosimilars space to derive advantages from patent expiry

Mc Kinsey report

As per the latest report, Mc Kinsey & Co. expects the average patent expiry at $39.6bn per annum between 2010-2015 as

compared to just $14.2bn in last decade and $16.5bn per annum between 2016-2020. This indicates that 2010-2015 is a

golden period for Global Biosimilars space

Source : US FDA website, Bloomberg, HDFC Securities Institutional Research

Why Biosimilars : SWOT Analysis

Based upon India Brand Equity Foundation , www.ibef.org

The Biosimilars industry is fast-growing and has a strong economic value proposition . However, there are a number of competitive threats that make a well-developed strategy critical to any company wishing to develop in this sector

Weaknesses Cost of Biosimilars products to consumers in emerging markets is still relatively high unlike small molecules generics . Extensive funding is required due to emerging rigorous regulatory requirements. Lack of widespread awareness and credibility of industry.

Strengths Lower price point and similar effectiveness to originator products. Shorter time to market than originator products. Higher probability of Return on Investment (ROI) than with new product R&D. Due to rapidly increasing healthcare costs, there is high consumer demand for discounted high quality treatments

Opportunities Large and growing market for biosimilar products. Emerging regulatory frameworks provide structured approval guidelines. High-revenue bio-pharmaceutical projects that have less equivalent Biosimilar approved/available in their portfolio

Threats Future regulations for Biosimilars is still being defined Particularly in US ,few Biosimilars have been formally approved , resulting in little precedence for future rulings. The industry will require greater focus on new investments for future growth

Indian Positioning

Biosimilars : Global Trend

Contents

MTR -Highlight

Income Growth

Medical

Infrastructure

Insurance

Penetration

Increased

Prevalence

Others

40%

20%

14%

14%

12%

Ref: IMS world review , McKinsey India pharma demand model-best case

Biosimilars : Indian Positioning

Global pipeline at different clinical stages

Ref: From pipeline to market. R&D Directions.

2009;15(6):4-89.

20

25

25

25

32

38

38

46

82

9

6

20

13

19

31

13

32

68

Brazil

India

Italy

Canada

UK

Germany

China

France

Japan

2005

2015

Top 10 Pharma markets expt. US : 2015

Values in $billion

Drivers for 5X Growth from 2010

Ref. Mckinsey India pharma outlook 2015

Goldmine to be explored

Indian companies to add $20bn by 2015

Value will be

driven by -

Derma.

BloodDis

GI

Resp.

Meta.Dis.

Cardio

Pain,Infla

Infec.

CNS

Onco

66

83

97

137

166

191

204

229

329

831

With Indian : Save Time & Cost

Why – Outsourcing is beneficial?

Outsourcing is in demands in recent years, many major Pharma/Biotech companies have remodeled their traditional drug R&D operations to de-risking their R&D efforts

Latest New Technologies And Services

Pharma/Biotech companies are focusing more on new services such as biosimilar characterization and

antibody screening, and cell-line development primarily through collaboration with specialty biotech CROs.

Focusing On Emerging Markets/CRO

The new model of "more achievements for less cost" has forced many drug companies to investment into

these emerging countries especially true in India and China .

The global Pharma outsourcing industry will experience fast growth in the next five years, $85 B in 2011 to as much as $150B by 2015 with a CAGR of about 12% .

Total CRO market value, which is about $40.5B in 2011 will grow up to $65B by 2015 with a

CAGR of about 13% . The biology-related services, preclinical and clinical development will

account for about 75% of total outsourcing .

Financial Outlook

Focusing On CRO

1.Vertical growth, partnerships (including joint ventures) or

2. Acquisitions with major Pharma/Biotech players .

Indian Positioning

Biosimilars : Global Trend

Contents

MTR -Highlight

Challenges for Sponsor & Strategy via MTR

Challenges Strategy

High development cost

Clinical complexity

Stringent guidelines

Partnership for cost effective development

Well designed trials & protocols

Strong developmental capabilities in India

Development

Sponsor alone

Sponsor with MTR

High promotional spend

Uptake by stakeholders

Market competition

Patent Barriers

Regulatory Barriers

Competition from Brands

Enter marketing agreements

Right product for right indication

Low cost manufacturing

Gain legal expertise

strong product positioning

Gain experience in emerging

markets

Profitability

Marketing

Strengths meter

Technical Barriers

Lack of Manufacturing facilities

Cost Barriers

Early planning & analysis

Team up with companies having expertise

Access to GMP facilities

Manufacturing

Based upon qualitative analysis on dynamics of developed markets

Corporate Office & Biosimilars Research Centre

S

e

r

v

i

c

e

s

Company Overview

MTR was founded in 2005, in Chennai, India.

MTR having a dedicated team of around 150

+ Scientist for R&D, Analytical & Bioanalytical,

Preclinical , Clinical trail for Biosimilars .

MTR is a world’s class global contract

research organization (CRO) dedicated

exclusively to R&D, Pre-clinical, Bioanalytical

and Clinical services for large molecule.

MTR is already a well-established, recognized

CRO in India.

MTR have conducted more than 150 Pre-

Clinical Trial , 12 Clinical trial projects and

750 BA/BE studies for Biopharmaceutical

Products and supported around 180

successful FDA/WHO/EMEA/ANVISA/TPD-

Canada submissions.

CHENNAI - PADI

CHENNAI - PADI

Our R&D centre is spreads over 16,000 square feet for Biosimilar services

CHENNAI - SELAIYUR

Our Selaiyur Corporate/R&D centre

spreads over 45,000 square feet, one stop

centre for Clinical & Bioanalytical services.

CHENNAI - PADI

BioPharmaceutical Services

Specialist Services for:

• Recombinant Proteins & Glycoproteins

• Monoclonal Antibodies

• Antibody-Drug Conjugates

• Biosimilars

• Oligonucleic Acid Therapeutics

• Vaccine

Spectrum of Services

SPECTRUM OF SERVICES

RESEARCH & DEVELOPMENT

PRECLINICAL

BIOANALYTICAL

CLINICAL SPECTRUM

OF SERVICES

R & D

BIO ANALYTICAL

PRECLINICAL

CLINICAL

Ensuring the purity, identity, safety and quality of your biopharmaceutical product is critical to success.

CHENNAI - PADI

Research & Development

Develop to Outsource

Out-license biosimilars after establishing the POC

Synthesis of Biosimilars (Monoclonal antibody, Insulin)-

Structure Identification

Purification

Heterogeneity

Activity

Stability

Manufacturing Process- (Should be optimized to minimize differences between the biosimilar

and innovator) Up-stream process

Downstream process

Develop & Out-license after POC (establish proof of concept and outsource fully or look partnership

for Clinical phase trail & commercialization)

CHENNAI - PADI

Bioanalytical Services

1) Biosimilar Comparability Studies 2) Protein Analysis 3) Stability Testing of Biologics and Biosimilars 4) Biopharmaceutical Process and Product Related

Impurities Analysis 5) Biologics and Biosimilar Product Release Testing

Structural Characterization

Physicochemical Properties

Comparability Studies

Process Residuals Determination

Product Related Impurities

Aggregation Studies

Immunochemistry

Potency Testing

Extractables / Leachables

QC Release Testing

ICH Stability Studies

Method Development & Validation

INSTRUMENTS

Waters Alliance HPLC systems with UV & PDA.

Gas chromatography-Mass spectrometry (GC-MS)

Horizontal gel electrophoresis units of various sizes

Vertical electrophoresis for PAGE & Western blotting analysis

PCR machine; General and Gradient PCR with RAMP rate

Stability chambers.

ACTIVITY

Bioanalysis Services in line with ICH guidelines

CHENNAI - PADI

Bioanalytical Services

Expertise in Protein Analysis

•Immunochemistry Services •Immunochemistry Assays •Ligand-Binding Assays

Bioanalytical Services (cont)

Protein Sequencing by Mass Spectrometry

N-Terminal Protein Sequencing by Mass Spectrometry

Peptide mapping (Xevo TQMS or Q-TOF)

INSTRUMENTS

INSTRUMENTS SPECIFICATION NO OF INSTRUMENTS

LC-MS/MS ( Waters Xevo TQMS, Quattro Micro Mass, API –5500,4000,3200& 3000)

16

ICPMS 01

AB Sciex-Q-TOF 01

GC-MS/HS

01

CHENNAI - PADI

Bioanalytical Services (cont)

MTR has Validated nearly 160 molecules at our Bio-analytical facility which includes

challenging Biopharmaceutical molecules like

Molecules Method Diseases Mechanism Albumin Colorimetric General

Bismuth ICP-MS Minerals

Calcium ICP-MS Minerals

Cholecalciferol LC-MS/MS Health Supplement

Cholesterol Enzymatic Lipid

Estradiol and its metabolite LC-MS/MS Steroid

Ethinyl Estradiol LC-MS/MS Steroid

Growth Hormone Human ELISA Hormone

Hormonal drugs LC-MS/MS Hormone

Niacin LC-MS/MS Vitamin

Omega 3 –Fatty Acids and Esters LC-MS/MS Fatty Acids

Potassium ICP-MS Minerals

Progesterone LC-MS/MS Hypertension

Testosterone GC-MS/MS Steroid

Vitamin D3 and its metabolite- LC-MS/MS Vitamin

19

Preclinical facility in a total area of 7500 Sq.ft .Completed more than 150 studies in compliance

with guidelines.

Registered with )nstitutional Bio Safety Committee – Ministry of Science and Technology,

department of Biotechnology.

Registered with Committee for the Purpose of Control and Supervision of Experiments on

Animals CPCSEA . Ministry of Environment & Forests, Government of India .

ADME Assays Non GLP pharmacokinetics studies Effect of food and Gender difference on pharmacokinetics studies Solubility studies Permeability studies Plasma Protein binding Metabolic stability Plasma stability CYP inhibition/induction studies

Microbiological Studies Microbial Limit Test (MLT) Sterility Test Antibiotics Microbial Assays Antimicrobial Activity Test Time Kill Assay

Preclinical Services

20

Toxicology GLP IND submission package studies Non-GLP discovery studies Acute/Sub acute / Sub chronic

studies In vitro and in vivo genotoxicity Toxicokinetics studies Medical device testing Biological assay.

Pharmacology

In vivo efficacy studies Inflammation & autoimmune disease Metabolic disorders Transfer and validation of new efficacy

models

Bioanalytical Method development & validation Cassette analysis ADME assay screening High throughput LCMS-MS analysis

Preclinical Services (cont)

21

Clinical Services

THERAPEUTIC AREAS OF EXPERTISE

Oncology

Cosmetology

Dermatology

Cardiology

Obstetrics and Gynecology

Diabetology

Gastroenterology

Endocrinology and

Metabolic Disorders

OUR STRENGTH

Investigator Selection

Study conduct

Clinical study monitoring

Clinical trial co-ordination

Clinical trial site training

Submission and approval from DCGI for trials in India

Investigational Product and Material accountability

Tie-up with major hospitals all over India to conduct clinical Trials.

Oncology;

60%

Cosmetology ; 25%

Cardiology; 10%

Others; 5%

Quality Compliance * Quality Assurance systems are supported by our Quality Policy and Quality Manual

Robust SOPs.

Adhere to ISO and GCP compliance

Prompt follow up & resolution

Highly qualified, well trained, dedicated & experienced QA department.

Focused Leadership*

Competent

Cope with rapid growth

Flexibility to undertake out-of-scope activity

Values in MTR that Sponsor Looks For

Communications to Sponsor*

Accurate, Timely

Effective Project Management

Regulatory*

Responsibility / Ownership and Authority

Accreditation from local & Global Regulatory Bodies

Dedicated Research & Development team under

professional leadership

Nationally and Internationally accredited

Central Lab Facility

Experience the true sense of Business

partnership

Helps Sponsor to obtained various NOC from

Regulatory Authorities

Advantage MTR

Transparent systems with sponsors, still maintaining utmost confidentiality

MTR has effectively undergone numerous audits and certificated by various

global regulatory bodies

MTR provide intergraded services for Biopharmaceuticals as well as

customized services depending on the clients need

Contact Us

CORPORATE OFFICE & MAIN SITE

MICRO THERAPEUTIC RESEARCH LABS PRIVATE LIMITED

Rajam Bhavanam, Door No.6,

Kamarajar Salai, Selaiyur, East Tambaram, Chennai – 600 059.Tamilnadu, India

Tel: (91 44) 22390070,71,72 & 64625721

Fax: 044-22390069

Email:info@microtheraps.com

www.microtheraps.com

Research Centre CHENNAI - PADI

Door No.50,51, Balaji Nagar, 3rd Street, Padi. Chennai – 600 050, India. Tel: (91 44) 26548475