Corporate Capabilities Presentation

www.diteba.com

Who We Are

• Founded in 2003– operating since October 2005

• cGMP/GLP laboratory located minutes from Toronto Airport– State-of-the-art 10,000 sq. ft. facility

• Licensed by Health Canada– as a GMP drug establishment– for Controlled Substances, Drugs and

Precursors

• Registered with U.S. FDA • Expertise in both small and large

molecules

What We Offer

• Analytical R&D Services• Bioanalytical Services• QC Release Testing• Stability Testing• Physical Testing• Analytical Support for Formulation Development• Cleaning Validation and Verification Testing• In Vitro Release Rate Testing Services

What We Offer

• We are committed to the success of our clients through the acceleration of their R&D intensive projects

• Diteba is uniquely positioned to deliver the R&D services and acumen our clients demand with our– Team of industry experts– World-class pharmaceutical laboratory– Comprehensive laboratory informatics infrastructure– Extensive academic network

• We strive to be an innovative and cost effective partner that delivers consistent and quality services with unmatched integrity

What We Offer

• Senior scientific staff offers impeccable credentials and experience in areas of:– cGMP Analytical Testing– GLP Bioanalytical Testing– Biologics Testing– In Vitro Release Rate Testing

• Custom designed and built laboratory with state-of-the-art instrumentation– Operational design and efficiencies allow for flexibility and

responsiveness– Complete e-lab informatics infrastructure to electronically

capture and store all data that is 21 CFR Part 11 compliant

What We Offer

• Senior scientists are involved directly with projects provides for:– Demonstrated creative, proactive approaches to solve the most

complex technical challenges– Individualized approach with quicker turnaround times

• Highly Responsive– Maintain available capacity for scheduling flexibility– Friendly attitude

• Cost-effective solutions to reduce overall costs and improve processing times

Our Organization

Dmitry BaranovPresident

Brian Atakhodjaev, CFAExecutive Vice President

Finance & Operations

Sam RicchezzaSenior Vice President

Business Development

Theo Kapanadze, DSc, PhDExecutive VP, Science

& Chief Scientific Officer

Steve Li, MD,MSci.(Pharm)Manager, Laboratory

Operations

Laboratory InfrastructureSupport Group

Accounting & Finance

Anca CiosaManager, Customer Service

& Administration

HR, H&SCustomer Service

Facility & Procurement

Laboratory Operations:QC Testing;

Stability Studies;Analytical Development.

LaboratorySystems & IT

Validation &Calibration

Dan WilliamsDirector,

Business Development

Slavica Mogic, MSc, BScQuality Assurance &

Regulatory Affairs

Dmitry BaranovPresident

Brian Atakhodjaev, CFAExecutive Vice President

Finance & Operations

Sam RicchezzaSenior Vice President

Business Development

Theo Kapanadze, DSc, PhDExecutive VP, Science

& Chief Scientific Officer

Steve Li, MD,MSci.(Pharm)Manager, Laboratory

Operations

Laboratory InfrastructureSupport Group

Accounting & Finance

Anca CiosaManager, Customer Service

& Administration

HR, H&SCustomer Service

Facility & Procurement

Laboratory Operations:QC Testing;

Stability Studies;Analytical Development.

LaboratorySystems & IT

Validation &Calibration

Dan WilliamsDirector,

Business Development

Slavica Mogic, MSc, BScQuality Assurance &

Regulatory Affairs

Management and Key Personnel

• Dr. Theo Kapanadze, D.Sc., Ph.D., Chief Scientific Officer, Executive VP Science – More than 30 years experience as an academic researcher,

university professor and leading research scientist at major pharmaceutical and CRO companies

– Has worked extensively in areas such as:• Pharmaceutical research and development• BA/BE and drug interaction studies

– Led projects that provided analytical support for:• Formulation development• Toxicology & clinical programs• Stability studies• Over 16 semisolid In Vitro Release Testing projects (SUPAC-SS)

– Credited with over 40 publications

• Dr. Steve Li, M.D., M.Sci. (Pharm), Manager of Laboratory Operations– More than 20 years of research experience in the fields

of:• Biomedical research• Clinical pharmacology• Biotechnology

– Has worked extensively in:• Method development and validation• Stability support• Cleaning validation

– Credited with over 35 publications and awards

Management and Key Personnel

Management and Key Personnel

• Slavica Mogic, MSc., BSc., Manager of QA & RA– Scientific strength is in the knowledge of biomacromolecules, including

methodologies utilized for the analysis of proteins, enzymes and immunoglobulins

– Over 15 years of industry QA/RA experience gathered in Global bio/pharma companies and leading CRO’s in the areas of:

• Raw material testing• Finished product release testing• Stability testing• Analytical method development and validation

– Has knowledge of regulatory guidelines such as:• Health Canada• U.S. FDA• EMA• ICH Guidelines

Regulatory History

DATEREGULATORY

AGENCYCATEGORY RATING/Status

Sep 2005 Health Canada Pharmaceuticals C (Compliant)

July 2006 Health CanadaControl Drugs

and SubstancesStatus: licensed

Feb 2008 Health CanadaBiologicals;

PharmaceuticalsC (Compliant)

Feb 2009 Health Canada Class A

PrecursorsStatus: licensed

Mar 2010 Health Canada Biologicals;

PharmaceuticalsC (Compliant)

Analytical R&D Services

• Method development and validation for:– Drug substances and intermediates– Raw materials and excipient ingredients– Drug products– Stability-indicating methods

• Forced degradation studies

• Impurities & degradation

• Equally adept at small or large molecules

QC Release Testing Services

• Characterization or release testing of:– Drug substances and intermediates– Raw material compendial testing

• USP/NF, EP, JP

– Impurity, Metabolite and Degradation Product Identification

– Reference materials– CTM supplies and comparator products– In-process lots– Commercial finished product release– Controlled substances and precursors

Physical Testing Services

• Loss on Drying, ROI• Moisture (Karl Fisher Titration & Coulometric)• Color Determination• Deliverable Volume• Density & Specific Gravity• Disintegration• pH and Conductivity• Product & Package Appearance• Tablet Hardness & Friability• Viscosity, Osmolarity, Particulates, TOC

Bioanalytical Testing Services

• Custom Assay method development and validation• Pre-clinical animal and human clinical trials sample

testing– Healthy patient/volunteer samples– Infectious populations samples

• Sample analysis technologies in multiple biological species and matrices for preclinical animal studies

• Bioanalysis of drug and metabolites in biological fluids• Clinical trials support (TK, PK, BA/BE, Drug Interaction)

Bioanalytical Testing Services

• Expertise in many proven validated methods to measure all types of small or large molecule compounds using:– UPLC/MS/MS

– HPLC - GFC

– UPLC – UV, FI, ECD

– Capillary and Gel Electrophoresis

– Gel Image analysis

– ELISA assays

– DNA hybridization

• Metabolite identification using LC/MS/MS• Ultra-Low freezers with generator back-up for storage• All work completed under GMP & GLP guidelines

Formulation Development Testing

• Vehicle compatibility testing• Solubility testing• Excipient compatibility studies• Bench level formulation development contract services

available• Feasibility batch testing:

– Assay– Content and blend uniformity testing

Stability Testing Services

• Drug substances and intermediates• IND, NDA, ANDA Registration batches• CTM batches and comparator products• Commercial product• Controlled substances and precursors• Formulation evaluation stability testing• Forced degradation studies• Photo stability (UV and Daylight) per ICH Q1B• Temperature cycling (freeze/thaw)• Transportation studies• Protocol design and report writing

Stability Storage Services

• Long-term and accelerated storage conditions per ICH Guidelines:– 25oC/60% RH– 30oC/65% RH– 40oC/75% RH– 5oC, -20oC, -80oC

• Special storage conditions available• Stability chambers on automated

generator back-up

Dissolution and In Vitro Release Testing

• Method development and validation• Immediate and controlled release testing• Testing per USP monograph articles• Content uniformity testing• Drug release testing

Semisolids In Vitro Release Testing

• In Vitro Release Testing (IVRT) of semisolids and transdermals using Franz Cell system– Conforms to

FDA Scale-up and Post Approval Changes for Semisolids Guidelines (SUPAC-SS)

– Conforms to USP Pharmacopeial Forum Vol. 35(3) May - June 2009 Product Quality and product performance tests for topical and transdermal products

• Defined product quality tests in General Chapter <3>• Defined product performance tests <725>

Semisolids In Vitro Release Testing

• IVRT testing valuable for:– In-process testing for formulation optimization– QC on lot-to-lot variability– Comparison testing for pre and post-change

formulations– Skin penetration studies

• Full method development and validation of IVRT and HPLC/UPLC assay methods

• Preparation of data interpretation and submission reports

• State-of-the-art instrumentation including:– HPLC– UPLC, UPLC-MS/MS– GC– AA– UV, FT-IR– Dissolution systems

• Franz Cell and Enhancer Cell systems

– ELISA readers– Capillary & Gel Electrophoresis– SDS-Page EP– TOC– Stability chambers– Physical testing equipment

Key Equipment

State-of-the-Art Laboratory Infrastructure’.

HPLC, UPLC, UPLC/MSGC

EMPOWERDatabase

HPLC, UPLC, UPLC/MSGC

EMPOWERDatabase

ELN- TBDELN- TBD

SDMS: NuGenesis SDMS: NuGenesisDatabase

UV, TOC, FTIR,AA, ELISA & Other

applications without Database

UV, TOC, FTIR,AA, ELISA & Other

applications without Database

NuGenesis can also capture files from various

applications that do not have their own database

Final document for submission to client by Web access (in development) or

in paper format.

Balances & pH meter

MS Office applications

Temperature and Humidity Monitoring system for

Stability Chambers by Rees Scientific

Key Partnership: Thesis Chemistry

• Analysis and separations• Custom preparations• Process chemistry development • Chemical synthesis and manufacturing• CMC development• Commercial scale production

Key Partnership: Thesis Chemistry

• cGMP compliant• Glass reactors: 2-L to 72-L• Pressure vessels: 4-L & 20-L• 20-L rotary evaporators• Dedicated gowning area

• Dedicated chemical storage area

• HEPA filtered isolation room • Tray and vacuum ovens• Water filtration system

Our ExperienceMethods Developed in the Last 36 Months

HPLC / UPLC Stability Indicating Methods - Oral

Activity/Phase Oral Tablet Oral LiquidOral Softgel

CapsuleOral Hard

Gel Capsule ODTPreclinical 10 6 4 4 2Phase I – II 4 4 3 2 1Phase III –commercial 3 3 4 2 1

HPLC / UPLC Stability Indicating Methods Developed - Injectable

Activity/PhaseInjectable Solution

Injectable Lyophilized

Injectable Depot Stents

Preclinical 3 3 - 1Phase I – II 3 2 1 1Phase III –commercial 1 2 - -

HPLC / UPLC Stability Indicating Methods Developed - Other

Activity/Phase Tox Supplies API

Topical, Semisolids,

GelsTransdermal

Patches DPI Nasal OpthalmicPreclinical 3 6 4 1 2 2 1Phase I – II 6 6 4 1 2 2 1Phase III –commercial 5 6 4 1 2 2 1

Our ExperienceRecent Analytical Projects

• Humanized mAb for oncology therapy– Method development & validation, release testing for CB, PK & TK bioanalytical

studies, stability of CTM batches

• Small molecule for cardio-protection therapy– Method development & validation, impurity characterization, TK & PK studies,

Phase I & III bioanalytical studies

• Oligonucleotide drug product for blocking P-53 apoptosis in oncology treatment

– Method development & validation, stability of CTM batches

• Recombinant single fusion protein drug product (86 KDa)– Complete peptide mapping by UPLC-UV and UPLC-MS-MS

• Clotrimazole analog for oncology treatment– Formulation support, method development & validation, pre-clinical tox bio-

analytical, stability of API & product

Our ExperienceRecent Analytical Projects

• Multiple antigens used in biomarker assay kits– Method development & verification of multiple methods for QC of assay kits

Transfer methods to kit & instrument manufacturer

• Anti-retroviral microbicide for HIV treatment– Method development & validation, dissolution studies, stability testing

• Aerosol fentanyl pain relief product– Method development & validation, In vitro release studies

• Aerosol bucchal insulin product– Method development & validation, raw material compendial testing

• Toll-like receptor (TLR) blocker for autoimmune therapies– Method development & validation, Phase I bioanalytical trial samples

• Multiple raw material characterization for large biotech– Dozens of compendial tests for characterization and release

Our ExperienceRecent Bioanalytical Projects

• Determination of a vitamin B metabolite and two other primary vitamers in human plasma by UPLC/HPLC with post column derivatization and fluorescence

• Determination of an oncology compound in rat and dog serum by UPLC with UV Detection

• Determination of humanized mAb in monkey and human serum by ELISA

• Determination of caffeine in human plasma by LC/MS/MS• Determination of ASA & SA in rat by UPLC/MS/MS

Our ExperienceRecent In Vitro Release Testing Projects

• Liposome encapsulated analgesic for pulmonary inhaled delivery– Comparison study between Franz cell and Enhancer cell techniques for the

calculation of drug release

• Anti-retroviral microbicide for HIV prevention (vaginal capsule suppository)– IVRT study for a reliable QC method to discriminate release characteristics in lot

to lot uniformity and discriminate formulation changes

• Anti-retroviral microbicide for HIV prevention (vaginal gel)– IVRT study comparing Franz cell vs. Enhancer cell techniques for best IVRT

methodology– Developed and validated IVRT and HPLC assay methods

• Vaginal cream– Developed and validated IVRT method for comparison study for site transfer– Study for FDA approval and SUPAC related changes

Thank you!