Specialist Preclinical Formulation &

Drug Delivery Services

Who Are We?

• A specialist contract research organisation offering bespoke preclinical and

early-stage formulation and drug-product development services to the

pharma, biotech and healthcare industries

• Core expertise in applying formulation strategies to enhance API

solubility / bioavailability and control / modulate drug release in

preclinical models

• Expertise in oral, parenteral and pulmonary dosage form development

and routes of administration

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• Founded in June 2007 as a consultancy-based organisation supporting start-

up and virtual organisations

• Initially offering study design, data review and outsourced project

management

• Opened new R&D facility in 2009 in Potters Bar, UK (ex Generics UK labs)

• Operate an organic growth model

• Remain 100% privately owned (client focussed, not shareholder driven)

• Small business, global reach.

• Worked with over 75 organisations worldwide on over 600 research

programs and > 250 NCEs

• Strong client partnerships (>90% repeat business) 3

History

Where Can We Support You?

Preformulation testing

Dose vehicle screening for first-time-in-animal PK testing

Formulation development and optimisation for preclinical safety assessment

Enabling technology screening for bioavailability enhancement and controlled release

Technology transfer for cGMP manufacture and clinical trials supply

01. Preformulation

A COMPREHENSIVE PREFORMULATION STUDY HELPS IN UNDERSTANDING THE PHYSICO-CHEMICAL PROPERTIES OF THE DRUG MOLECULE AND PROVIDES THE FOUNDATION FOR

DEVELOPMENT OF A ROBUST AND STABLE PRECLINICAL DOSAGE FORM

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• pKa / ionisation constant determination

• Partition coefficient and distribution coefficient as a

function of pH

• pH-solubility profiling

• Solubility / stability in biorelavant fluids (SGF,

FaSSIF/FeSSIF, FaSSCoF, SLF, blood plasma)

• Full physicochemical properties testing

• Salt formation / polymorph screening

• Excipient compatibility studies

• Accelerated stability studies with controlled storage at

25º C/60% RH, 30º C/65% RH 40º C/75% RH, 60º C

• Dissolution studies

02. Preclinical Formulations

AT THIS STAGE OF DEVELOPMENT, THE AIM IS TO IDENTIFY A STABLE AND SAFE DOSE VEHICLE TO ENABLE MEANINGFUL EFFICACY AND TOXICITY ASSESSMENT BY MAXIMIZING EXPOSURE

UPON ADMINISTRATION

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• CO-SOLVENT SYSTEMS

• INCLUSION COMPLEXATION (CYCLODEXTRINS ETC)

• LIPID-BASED SELF-EMULSIFYING SYSTEMS (SEDDS /

SMEDDS)

• PARTICLE SIZE REDUCTION (MICRONISED AND

NANOPARTICULATE SUSPENSIONS)

• PH ADJUSTMENT / SALT FORMATION

• AMORPHOUS SOLID DISPERSIONS

• EMULSIONS / MICELLAR SOLUBILISATION

✓ ✓

✓ ✓

✓

✓

✓ ✓

✓

✓ ✓

03. Enabling Technologies

EFFECTIVE TECHNOLOGY SELECTION FOR IMPROVING BIOAVAILABILITY (BA) CAN ACCELERATE THE DEVELOPMENT OF PROMISING COMPOUNDS AND REDUCE THE OVERALL COST AND

COMPLEXITY OF DRUG DEVELOPMENT

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Our capabilities for preparation of solubilised intermediates include:

• Spray-dried dispersions (SDDs)

• Hot-melt extrusion (HME)

• Matrix microspheres (controlled and sustained release)

• Aqueous and organic nano-suspensions by wet-bead milling

• Solid nano-crystalline dispersions (SNCDs)

• API Micronisation (wet and dry)

• Amorphous multi-particulates (immediate and controlled release)

• Solubilised liquids (including emulsions/ micro-emulsions,

complexation (e.g. cyclodextrins), lipids and oily dispersions,

liposomes, co-solvents)

• Lyophilisation

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Technology Instrumentation Oral Parenteral Pulmonary

Nanoparticles (aqueous and organic suspensions and redispersable powders)

• Fritsch Pulverisette 6• NETZSCH Laboratory Mill MiniCer• Lena V15• Lena V500 and V1000 (R&D and GMP rigs)

✓ ✓ ✓

Spray drying • Buchi B290 (aqueous solutions)• Procept 4M8Trix (organic solutions)

✓ ✓

Liquids/ emulsions / suspensions

• ESCO-Labor (high shear mixing with vacuum/temp control)• Silverson (LM2 and LM4 series)• Heidolph mixers (low shear)

✓ ✓

Micronisation • Food Pharma Systems Labomill• Food Pharma Systems Pilotmill• Fritsch Pulverisette 6

✓ ✓

Hot-melt extrusion Thermo Scientific HAAKE MiniCTW ✓

Powder blending and manufacture of pellets / granules

Turbular mixerCaleva multilabGEA Pharma Systems - Aeromatic-Fielder

✓

Lyophilisation Thermo Scientific MicroModulyo ✓ ✓

Tableting (inc minitablets) GTP 1 Gamlen Tablet Press ✓

Capsule / tablet/ pellet enteric coating

Caleva mini-coaterGEA Pharma Systems - Aeromatic-Fielder

✓

03. Enabling Technologies

Drug Delivery Technologies

• Kuecept has developed and in-

licensed a portfolio of enabling

technologies to improve

bioavailability of poorly

soluble / permeable drugs or

modulate drug-release for

improved gastro-intestinal

targeting

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I

High SolubilityHigh Permeability

III

High SolubilityLow Permeability

II

Low SolubilityHigh Permeability

IV

Low SolubilityLow Permeability

1 10 100 250 1,000 10,0000 100,000

Volume (mL) required to dissolve the highest dose

Perm

eabi

lity

(1 x

10-6

cm

per

s)

100

10

1

0.1

Drug Delivery Technologies

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ProRelease™

• Route: Oral

• Benefits: Microencapsulation technology which

can be applied to enhance drug solubility /

dissolution, modulate release kinetics (targetted

and sustained release applications), reduce PK

variability through improved transit performance

and provide taste masking benefits

• Dosage forms: Tablets, capsules, suspensions

• Patent status: Granted (EU, JP and US)

Drug Delivery Technologies

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Lena Nano™

• Route: Oral and parenteral

• Benefits: Wet-milling technology for rapid

production of fine suspensions and nano-

suspensions in both aqueous and non aqueous

liquids. Suitable for difficult to micronise drugs,

e.g. abrasive or ductile

• Dosage forms: Tablets, capsules, suspensions,

creams

• Patent status: Granted (Worldwide)

Drug Delivery Technologies

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DuoCoat™

• Route: Oral

• Benefits: Novel enteric coating technology that

can be applied to a wide range of conventional

oral dosage formulations to speed up drug release

and reduce PK variability. Ideal for drugs which

have a narrow absorption window in proximal

small intestine or require precise gastro-intestinal

targeting (e.g. ileo-colonic delivery).

• Dosage forms: Tablets, capsules, pellets / granules

• Patent status: Granted (worldwide)

Drug Delivery Technologies

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Combisphere™ & MicronEase ™

• Route: Pulmonary

• Benefits: Highly respirable crystalline drug

combination particles allowing co-deposition of

single agents or multiple active ingredients in the

alveolar airways

• Dosage forms: DPI, pMDI and nebulisation

• Patent status: Pending (worldwide)

Continuous Innovation

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• BBSRC award to investigate use of pH responsive microspheres for oral targeted

delivery of peptides / proteins

• KESS award in partnership with Institute of Life Sciences (Swansea) to fund a PhD

to investigate use of gastro-intestinal targeting systems to improve delivery of

steroidal hormones

• Technology Strategy Board and Bio-Medical Catalyst grants to develop oral

formulations of a novel Transcription Factor Decoy oligonucleotides (ProCarta

BioSystems) for treatment of C.difficile

• Framework-7 Program: Nanotherapeutics for Antibiotic Resistant Emerging

Bacterial pathogens (NAREB)- improve the therapy of multi-drug resistant (MDR)

tuberculosis (TB) and MRSA infections

Working With Us

• Dedicated project manager from quote proposal to final delivery of results and report

• Frequent communication

• Communication plan defined prior to commencement of project

• On-line data access to BaseCamp project management portal

• Flexible approach.

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Contact Information

Kuecept LtdResearch & Innovation Centre16-17 Station ClosePotters BarHertfordshire EN6 1TLEngland, UK

Tel: 00 44 (0) 845 084 0553Fax: 00 44 (0) 844 443 5344Website: www.kuecept.com

Dr Mark SaundersDevelopment DirectorTel: +44 (0) 7813 680602E-mail: msaunders@kuecept.com

Dr Alastair PatonBusiness Development ManagerTel: +44 (0) 7867 523340E-mail: apaton@kuecept.com

Dr Cristina FreireFormulation DirectorTel: +44 (0) 7585 334775E-mail: cfreire@kuecept.com

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