1

LAMBDA THERAPEUTIC RESEARCH Delivering total drug development solutions

“The best companies outsource to win, not to shrink. They outsource to innovate faster…” - Thomas L. Friedman

GLOBAL PRESENCE

2

Warsaw, Poland 2007

London, UK 2008

Toronto, Canada 2010

Istanbul, Turkey 2011

Bangkok, Thailand 2011

Ahmedabad, India 1999

Mumbai, India 2003

New Delhi, India 2009

Hyderabad, India 2009

COMPREHENSIVE SOLUTIONS

3

0

10

20

30

40

50

60

70

80

90

100

phase I/BA-BE PHASE II PHASE III PHASE IV (PMS) Pharmacovigilance

EXPERIENCE MEDICAL IMAGING E-SUPPORT SERVICES

REGULATORY INSPECTIONS

4

EMA [01]

CDSCO [12]

US-FDA [30]

CAP [06] WHO [03]

UK-MHRA [04]

Thai MOH [03]

OGYI [01]

ANVISA [07]

ANSM [02]

HEALTH CANADA [01]

PHSS [01]

TURKEY MOH [01]

AGES [01]

POLISH [01]

TIME EFFICIENCIES-ACTUALLY RESEARCH ACCELERATED…

0 20 40 60 80

100

Lambda

Company X

5

LAMBDA

SERVICES

6

In-house facility of 600+ beds in clinic, including 36 Phase-I and 12 ICU beds

Sr. No

Country City No. of Beds Phase I Beds ICU Beds

1 India Ahmedabad 360 16 8

Mumbai 65 - 2

2 Canada Toronto 122 12 -

7

GLOBAL CLINICAL BED FACILITY & VOLUNTEER DATABASE

Global database of over 150K volunteers comprising of healthy male, female and geriatric

Population Ahmedabad Mumbai Toronto

Healthy Male 31781 8050 60,000

Healthy Female with childbearing potential 1985 300 30,000

PM & Surgically Sterile Women 1775 150 2,200

Elderly 620 50 3,500

Software – Biometric method for volunteer identification, BizNET for clinical operation

UNIQUE FEATURES

• Conducted 5000+ BA/BE Studies

• Having major experience with 20+ TC’s viz. CVS, CNS, GI, Musculo-skeletal,

Endocrinology, Dermatology and others

• Have worked with 150+ domestic and international sponsors

• 21 CFR compliant paperless solution (BizNET) for data capture of early phase

clinical trials – we are the pioneers

• Regulatory inspections: No critical observations till date

8

PHASE-I

Infrastructure

• Dedicated state-of-the-art ICU’s

• Central Cardiac Monitoring System

• Cardiac Telemetry/ Holters / IV Infusion Pumps

• X-ray, Ultrasound facilities

• TQT studies

• GE MUSE system for ECG processing and management

• GE Apex Pro Telemetry System / DASH 4000 Cardiac Monitors

• Multilevel ECG reading

• Internet access to ECG data through ECG web portal

Study offerings • SAD – MAD studies • PK / PD Studies • Drug – Drug Interaction • Drug – Food interactions

DDI

12%

First in

Man

38% Food-Drug

interaction

12%

SAD

20%

MAD

18%

Live attenuated H1N1 influenza vaccine, 1

Inactivated H1N1 influenza vaccine, 1

Anti Asthmatic drug, 1

Anti Infective agent, 6

Lipid Lowering agent, 3

Alzheimer’s disease, 6

Multiple Sclerosis, 1

Anti Hypertensive agent, 3

Anti diabetic drug, 2

Antifungal drug, 1

Hormonal agent, 1

Immunosuppressant, 1

Anti cancer( receptor modulator), 1

Anti obesity drug for Metabolic syndrome, 1

NCEs, 5

TC EXPERIENCE

• Largest GLP certified bioanalytical lab. with over 14 & 25 years of experience in Asia and North America respectively.

• Experience of analyzing > 3 million samples at India facility and > 3.5 million samples at Canada facility

• > 700 validated assays in different matrices (plasma, whole blood, serum, urine, CSF, bone, fecal, milk and food)

• Capabilities to handle analysis of pre-clinical studies

• Average of > 8 years experience for the analysts, reviewers and scientists

• > 5 validated methods with LLOQ of ≤ 2 pg/mL

11

BIO ANALYTICAL EXPERIENCE

• Rapid TAT for FTF opportunities

• Proactive identification & method development for FTF opportunities/molecules

• Two layer 100% data review process

• Synergy of systems and processes through global SOPs between locations

• Methods available for NCE molecules in CSF using as low as 25 µL aliquot volume

• Readily available methods for current critical & FTF opportunity molecules

Fingolimod & Fingolimod Phosphate, Free & Total Dabigatran, Dronedarone, Prasugrel

• Methods available for Biomarkers like Prostaglandin metabolites 6-Keto PG1α, TxB2 and T-pgem

12

BIO ANALYTICAL USP

• Advantage of strategic locations (India & Canada) for servicing clients globally

• 30+ successful bioanalytical regulatory inspections with no critical observations

• Bioanalytical experience of measuring drug and metabolite for > 5000 studies

• Ability to analyze > 85K samples in India and >15K samples at Canada in a month

• Average reanalysis: 3-5 % of total samples

• > 95% of ISR samples met the acceptance criteria

• In-house, experienced team of engineers to ensure >95% uptime of instruments

• Capacity to store >3.5 million samples in India and > 1.5 million samples in freezers at Canada

• Global method validation and run acceptance SOP complying requirements of all regulatory bodies

• Canada facility approved for handling controlled substances

13

BIO ANALYTICAL STRENGTHS

CLINICAL DATA MANAGEMENT SYSTEM

14

BIZNET

Investigative Site Clinical Data

Management Biostatistics &

Reporting

Software Version Activity

BizNET® (CTM & BA/BE) 4.0 EDC / eCRF

MedDRA® 17.0 Medical Coding

SAS® Server 9.3 Statistical Software

Phoenix® / WinNonlin® 6.3 / 5.3 Pharmacokinetic Analysis

CDM & BIOSTATISTICS SERVICES

• CRF / eCRF designing

• CRF annotation as per CDISC

• Data Management Plan

• Database designing and UAT with dummy data

• Data validation & Query resolution

• External data upload & cleaning

• TMF management

• EDC Training for the site personals

15

BizNet BENEFITS • Cost Effective (~ 60%) • Locally available System Support

• Sample size and Study Design

• Protocol inputs / review, SAP & mock shells

• Statistical analysis & reporting

• Customized tables, graphs, and data listings

• Statistical interpretation of study results

• BA/BE Studies in multiple groups

• Scaled approach & replicate design

• Two stage design

• Pharmacokinetic & PD parameters

CDM BIOSTATISTICS

EXPERTISE IN SPECIAL TYPE OF DATA ANALYSIS

• In vitro data analysis for Equilibrium Binding & Kinetic Binding (e.g. Sevelamer, Colesevelam)

• Statistical testing for data on Particle size analysis (e.g. Azacytidine Inj.)

• Two-stage study design (Adaptive study / Group Sequential approach)

• Data Analysis based on latest OGD requirements like Scaling approach for NTI drug (e.g. Tacrolimus)

• CDISC, ADaM and SDTM compliant dataset preparation

• Data analysis for Phase-3 trials involving Non-inferiority, Superiority and Therapeutic / Clinical equivalence comparisons

• Involving single dose, multiple dose with different study designs, over 750 studies have been designed on EDC system

16

Module 1

Module 3

Quality

Module 4

Nonclinical Study Reports

2.7 Clinical Summary

Module 5

Clinical Study Reports

2.6 Nonclinical Summary

2.4 Nonclinical Overview

• Oncology

• Dermatology

• Musculoskeletal

• Cardiology

• Gastrointestinal

• Diabetology

• Respiratory

Therapeutic experience Complying with all current regulatory requirements

REPORT WRITING CREDENTIALS

Quality Overall

Summary

2.5 Clinical Overview

Regional Admin

Information

LAB - ACCREDITATIONS & OFFERINGS

BIOMARKERS & BIOSIMILARS

ASSAY DEVELOPMENT

IMMUNOGENICITY

SAFETY TESTING

ANTI MICROBIAL/ HYGIENE

CAP ACCREDITED SINCE 2005

(College of American Pathologists)

NABL (ISO 15189:2007) SINCE 2010

• First lab in India for Immunogenicity testing services for Biosimilar • Half a million tests performed/year

CAPABILITIES

Immunogenicity

Hematology

Immunology

• Special Cell Culture lab. • BioSafety Cabinet

Neutralizing

Antibodies

•Davinci Quatro (fully automated ELISA processors)

• Serology Testing [HIV, HBsAG, HCV, Infectious markers, Hormonal assays etc.] • COBAS e411 (ElectroChemiluminescence) • VITROS ECI from J&J (Chemiluminescence) • Davinci Quatro (fully automated ELISA processors) • Synergy HT Plate Reader (Biotek)

• CBC (Fully automated Sysmex, XT-2000i) • ESR (Fully automated SRS 100/II) • Platelet Aggregometer (Chronolog) • Urine analysis (Fully automated Urisys2400 Roche) • Immunophenotyping (BD, FACS-Calibur) • Coagulation studies (STA-Compact, Stago)

CLINICAL LABORATORY

CO2 Incubator

Anaerobic Incubator

Spiral Plater + Spiral Reader Platelet Aggregometer

RT-PCR

• Amongst the few labs. in India to own a Spiral Plater, Anaerobic & CO2 Incubators

• Covers all specialties of clinical

lab. tests & supports pan-India

Trials as a Central Lab.

EXPERIENCE - INVITRO STUDIES

• Anti-microbial efficacy comparison of toothpastes containing triclosan against

Streptococcus mutans using in-house developed method of “Time kill assay” by

using HAP disc. Antimicrobial activity can be compare up to 12 hrs. Helps in claim

support and also during formulation of new products.

• Anti-microbial efficacy comparison of toothpastes containing triclosan by using

Streptococcus mutans using MIC Method (Minimum Inhibitory comparison). Helps

in claim support and also during formulation of new products.

• To evaluate the ability of toothpaste to reduce the amount of acid generated by

oral bacteria in presence of excess glucose by using “Salivary sediment pH drop

method” using hydroplates.

• Efficacy of the dentifrices evaluation by studying BDCOH (4, 4’-bis

(dimethylamino) diphenylcarbinol) levels in saliva. BDCOH an indicator of the level

of mal odour. Helps in claim support against Bad breath (Mal odour).

• 1000+ Database of Clinical Sites & Investigators

• Successful USFDA inspection at 23 Indian sites

• Bespoke Services

• Experienced with 20+ TCs

CLINICAL TRIAL MANAGEMENT (CTM)

22

50%

3% 6%

23%

9%

3% 6%

Oncology

Musculoskeletal

Gastrointestinal

Psychiatry

Respiratory

Gyneacology

Dermatology

NETWORK OF INVESTIGATIONAL SITES

23

5

20

50

17

15

43

60

20

65

15

45

20

10

44

0 10 20 30 40 50 60 70

Others

CNS

CVS

Arthritis & Pain

Dermatology

Endocrinology

Respiratory Disorder

Oncology

Opthalmology

Gasteroenterology

Pediatrics

Diabetology

Infectious diseases

ENT & Allergy

Th

era

pe

uti

c S

eg

me

nts

No. of Sites

18 Successful USFDA site inspections from year 2009 to 2014

Europe: • Poland • Estonia • Latvia • Lithuania • Belarus • Ukraine • Romania • Bulgaria • Czech Republic • Germany • France • Spain

India: • Andhra Pradesh • Bihar • Delhi • Gujarat • Haryana • Himachal Pradesh • Karnataka • Kerala • Madhya Pradesh • Maharashtra • Punjab • Rajasthan • Tamil Nadu • Uttar Pradesh • West Bengal

Investigator Sites

Asia: • Sri Lanka • Bangladesh • Taiwan

(* Many countries are covered by our own CRAs, in some countries freelance CRAs or partner CRAs)

New geographies • CIS countries • South East Asia • Latin America

North America • Canada • USA

GLOBAL NETWORK

24

CASE STUDY

• RHEUMATOID ARTHRITIS

• 15 patients enrolled in just 4 months from 10 sites

• Screen failure rate expected was 20% due to TB gold test criteria

• Total of 175 patients screened and 115 enrolled in 6 weeks time

• In-spite of high screen failure rate, recruitment completed well before time

• ONCOLOGY

• Planned target : 42 patients in 4 month from 6 sites

• Nature: Timeline critical for USFDA submission

• Change in protocol design by sponsor additional approval from all sites EC + regs only one month available for recruitment

• Extensive recruitment planning ensured completion in 4 weeks and report submitted 1 week before original committed timeline. 25

• Lambda Imaging Central Review PACS system

• “Validated” & 21 CFR Part 11 compliant

• Complete Audit trail till Data Export

• Automated calculations

• In built error checks to prevent reviewer mistakes

• Customizable iCRF: RECIST 1.0 / RECIST 1.1, IWG, iIRC, vDH etc. criteria

• iCRF for specific assessment criteria for Oncology, MSK, CNS, CVS etc.

26

MEDICAL IMAGING

IMAGE PROCESSING @ LAMBDA

• Images Received • Tracker checked • Images to Server • Quality Assurance

• IAM compliance • Confidential info

Accept or

Query

• QC 2 (unique ID) • Study specifics • Any Prelims

REVIEW

HOW IMAGING HELPS

Conventional Endpoints Imaging Endpoints Benefit

Subjective Objective Data Validity

Qualitative Quantitative More Precise

Potentially BIASED BLINDED Higher Confidence

Time consuming FAST SAVES TIME!!!

Examples:

Tumors Patient Survival

RECIST IWG 2007 criteria

Accelerated Approval

Rheumatoid Arthritis Patient pain & function diary

MRI for joint space, erosion & inflammation

Faster changes, Reproducible data

PHARMACOVIGILANCE SERVICES AT LAMBDA

29

UK (HQ)

Poland (Local

literature surveillance)

Canada (US Call centre)

AHM PV (Global

back-end operations)

OPERATIONS – ‘HUB & SPOKE’ MODEL

LAMBDA PHARMACOVIGILANCE SUMMARY

• The global safety team comprises of Physicians, Pharmacists and PV specialists

(150+ Globally) with wealth of therapeutic expertise, to provide proficient services

for client’s products (~200 plus active moieties).

• Proprietary, Cost effective, customizable, user friendly, regulatory compliant web

based database PvNET.

• Experienced at low risk transitions of PV responsibilities for products with change of

ownership with expertise in handling legacy data

• Highly scalable: 3 months is the optimal lead-time period for you to effectively plan

and resource for an increase in volume

• Help you to achieve sustainable cost savings

• Successfully underwent multiple Regulatory and Vendor audits for PV functionality.

31

Our Global Presence

Study Design Phase of the Trial: Clinical Study

Name of the Drug: Confidential

Indication: Food study

Objective Identification of one or more flour composition(s) that give a statistically significant reduction in positive incremental area under the plasma glucose curve (+iAUC0 120 min), relative to the control product by at least 40 mmol. minutes

The effect of the study products on positive incremental area under the serum insulin curve (+iAUC0-120 min)

No. of subjects 56 (male and female)

Outcome Positive results obtained @ Lambda helped the sponsor decide future strategy for the product

Current status – Client is already working @ second level of product development program

OTC/NEUTRACEUTICALS CASE STUDY 1

Study Design Phase of the Trial: Clinical Study

Name of the Drug: Confidential

Indication: Food study

Objective Reduction in venous post-prandial blood glucose (PPG) positive incremental area under the venous glucose versus time curves, during the 2 hours after study product intake (+iAUC0-2hours)

Insulin lowering effect (tAUC0-2hours) of extract added to different types of rice

No. of subjects 120 (male and female)

Outcome Positive outcome

Expected to move from level 3 to level 4 of sponsor’s product development program

Diversified product line offering also planned based on this study’s results

OTC/NEUTRACEUTICALS CASE STUDY 2

Study Design Phase of the Trial: Clinical Study

Name of the Drug: Confidential

Indication: Oral Care

Objective Anti-bacterial effect evaluation of toothpaste by checking viability of bacteria – Total viable bacterial count (Aerobic and Anaerobic), Streptococcus mutans, Anaerobic Streptococci measured in plaque samples taken 4h post intervention, and in saliva samples taken 2h and 4h post intervention

No. of subjects 45 (male and female)

Outcome Conclusive data generated by Lambda for the legal case

Legal case: Court ruled in sponsor’s favor

Claim now part of a famous oral care advertisement

CASE STUDY 3

• Physically present: India, UK, Europe, North America Global footprint and world class

infrastructure

• End to End: Phase 1 / BA/BE / Late Phase / Bioanalytical / CDM / Central Laboratory / Pharmacovigilance / Medical Imaging

Customized full spectrum services

• Clearances from all major regulatory bodies Impeccable Regulatory track record

• Live database of healthy and patient populations Large Volunteer Database

• BA/BE studies and Phase I to IV clinical trials EDC Platform

• Capability to handle large multi-centric trials Late Phase Studies

• Biosimilars / Vaccines / Nutraceuticals / Cosmetics Niche expertise

35

ADVANTAGE LAMBDA

CONTACT US

36

• Global:

Dr. Mrinal Kammili Executive Director Global Head-Business Development

mrinal@lambda-cro.com

Akshaya Nath

Senior Vice President

Global Operations and Business Development

akshayanath@lambda-cro.com

Dr. Nermeen Varawalla Executive Vice President Global Clinical Trials nermeenvarawalla@lambda-cro.com

• North America:

Cathy Lopez

Director -Business Development cathy.Lopez@lambdacanada-cro.com Roger Stein Director -Business Development roger.stein@lambdacanada-cro.com

Christopher Ore

Executive Vice President North American Operations christopher.Ore@lambdacanada-cro.com

• Europe:

Elzbieta Zyto Head-Clinical Trial Operations-Poland ezyto@lambda-cro.com

• Biometrics

Dr. Kamlesh Patel Associate Vice President kamleshpatel@lambda-cro.com

• Turkey:

Devrim Sabuncuoglu Manager - Business Development devrim@lambda-cro.com

37