RARE & ORPHAN EXPERT SUPPORTFOR CLINICAL DEVELOPMENT WORLDWIDE

1 ORION CLINICAL

We are Simbec-Orion. An international, full service, boutique CRO; growing by bringing together the bestpossible people, healthcare professionals and drug developers, from all areas of clinical development.

We focus on a defined series of core therapeutic areas, where we can make best use of our skills elegantly to design, execute and deliver our clients’ clinical development needs.

We are making Simbec-Orion a highly respected and profitable boutique CRO. We do this by working for our clients with excellence, commitment and passion for our trade. We provide an environment in which our colleagues can continue to grow and develop.

We will always remember that our work leads to the improvement of patients’ lives.

SIMBEC-ORION GROUP MISSION STATEMENT

2ORION CLINICAL

A FULL-SERVICEINTERNATIONAL CRO WITH THE IN-HOUSE CAPABILITIES TO SUPPORT EVERY ASPECT OF YOUR CLINICAL DEVELOPMENTPROGRAM

>30%PROJECTS

RARE & ORPHAN

DISSEMINATED INTRAVASCULARCOAGULATION

ORGANICACIDEMIAS

NO

N-H

OD

GKI

N'S

LY

MP

HO

MA

ORGANIC ACIDEMIAS (PAEDIATRIC)

CROHN’SDISEASE

CYSTIC FIBROSIS - GASTROINTESTINALAND RESPIRATORY ASPECTS

VERNAL KERATOCONJUNCTIVITIS (PAEDIATRIC)

HEREDITARYPALMOPLANTAR KERATODERMAS

N-ACETYL GLUTAMATESYNTHASE DEFICIENCY

NIEMANN - PICK DISEASE

RELAPSED/REFRACTORYT-CELL LYMPHOMA

GAUCHERDISEASE

ACUTE RESPIRATORYDISTRESS SYNDROME

HUNTINGTON’SDISEASE

NAGS DEFICIENCY(PAEDIATRIC)

HYPERLIPIDAEMIAS

PHENYLKETONURIA

DUCHENNE AND BECKERMUSCULAR DYSTROPHY

GASTROINTESTINAL STROMAL TUMOUR

FULMINANTHEPATITIS

LUPUS NEPHRITIS

DISSEMINATED INTRAVASCULAR COAGULATION

LYSOSOMAL STORAGE DISEASES

ACUTE LYMPHOBLASTICLEUKAEMIA

PO

MP

E’S

DIS

EA

SE

SEVERE HAEMOPHILIA

FABRY DISEASE

EXPERTISE IN RARE & ORPHAN CLINICAL RESEARCH

3 ORION CLINICAL

20 YEARS PHASE Ib-IV EXPERIENCE

PHASE I – IV

SIMBEC-ORION IS ONE OF THE MOST EXPERIENCED RARE & ORPHAN CRO’S IN THE WORLD

FULL CONTINUUM OF PHASE I – IV SERVICESincluding in-house central labs and IMPmanagement

WORLD–CLASS RARE & ORPHAN SITE NETWORKDemonstrable recruitment and study success with reputable sites globally

ACCESS TO LEADING RARE & ORPHAN KOLSPrivileged relationships with recognized Rare & Orphan opinion leaders

INTERNAL MEDICAL AND REGULATORY EXPERTISEWith track record of product approvals in Europe and the US

UNIQUE NETWORK OF RARE & ORPHAN INVESTIGATIVE SITES

GLOBAL RARE & ORPHAN ADVISORY GROUP

WORLD LEADING RARE & ORPHAN EXPERTISE IN-HOUSE

ORION CLINICAL

THE RARE & ORPHAN CHALLENGE FOR DRUG DEVELOPERSWith over 7000 rare diseases in the world, only 5% of which have FDA-approved medicines in the US, there is a enormous opportunity for drug developers to significantly change the lives of patients suffering from these conditions. And even though 82% of orphan drugs are approved by the FDA versus 35% of traditional medicines, the nature of rare diseases creates increased complexities for clinical trial design and patient recruitment.

The key to dealing with these challenges is expertise specific to rare & orphan clinical trials. Since 50 % of rare diseases affect children, paediatric expertise and considerations are also of paramount importance.

Orion Clinical is a leading CRO in Rare & Orphan development.

ORION CLINICAL – A FULL SERVICE BOUTIQUE CRO WITH UNIQUE RARE & ORPHAN EXPERTISEOrion Clinical is the clinical development division of Simbec-Orion Group, an international full-service boutique CRO covering first in human Phase I clinical studies through to pivotal Phase III studies and post-marketing studies.

Operations in the United Kingdom, France, USA, Germany and Italy. Operational staff across mainland Europe (Western, Eastern & Central) and throughout North America.

One of Simbec-Orion Group’s significant areas of expertise is the conduct of studies in Rare and Orphan indications. Over the last 20 years we have developed relationships with networks of specialist investigative sites and we have established and nurtured links with patient groups across Europe and North America.

4ORION CLINICAL

7,000 RARE DISEASES

ONLY 5% TREATED

82% APPROVAL RATE

50% PAEDIATRIC

RARE & ORPHAN EXPERTISE AND GLOBAL NETWORK FOR YOUR MOST CHALLENGING STUDIES

5 SIMBEC ORION

OUR SYSTEMS AND PROCESSES HAVE BEEN DESIGNED TO ENSURE RAPID AND EFFICIENT START-UP AND CONDUCT OF YOUR RARE & ORPHAN STUDY

Rare & Orphan clinical trials are complex and challenging. It is critical that the set-up, site selection and recruitment/retention strategies are developed and implemented based on experience and understanding of the issues involved at a granular level.After 20 years of developing Rare & Orphan studies we are considered as experts in ensuring efficient delivery within time-lines.

Our network and expertise helps you identify, recruit and retain patients from the very small populations;

• Integrated processes regarding site relationships, with access to patient registries

• Broad understanding of patient advocacy issues

• Rigorous feasibility analysis of potential sites, e.g. site competency in the targeted indication and logistical considerations

• Access to noted physicians and paediatricians

RAPID AND EFFICIENTSTUDY START-UP

Access to intenal and external Rare & Orphan

experts

Right strategic direction; faster regulatory approval

Patient recruitment and retention expertise

Rapid start-up; keeping timelines

Rigorous feasibility and study planning

Motivated sites/investigators - ensuring study success

Engagement of KOLs and patient advocacy groups

Innovative and executable development plans

Oracle e-clinical systems Real time access to reliable data

In-house central labs Control of logistical challenges

5 ORION CLINICAL

RARE & ORPHAN EXPERTISE AND GLOBAL NETWORK FOR YOUR MOST CHALLENGING STUDIES

6SIMBEC ORION

Orion Clinical’s internal experts in clinical research and development for paediatric and rare diseases therapeutic options, is combined with extensive and successful regulatory interaction and outstanding achievements of product approvals by the EMA and FDA.

ORION CLINICAL PROVIDES:• Regulatory advice to meet conditions for

future marketing, necessitating input from authorities at the onset

• Strategic Development and Regulatory Planning for orphan indications – to help you achieve approvals as quickly as possible

• Innovative, efficient study designs

• Full submission package addressing key focus area per region

• Review and gap analysis of customer prepared packages

• Full regulatory agency interaction

PROJECT AND SITE MANAGEMENT Our experienced project managers specialise in Rare & Orphan studies. Despite challenging logistics and complex issues, they will ensure that your study is on track by;

• Motivating investigators via close site management and motivational visits

• Developing country and site-specific monitoring strategy

• Working with investigators and patients to manage patients’ adherence to the study protocol

• Coordination and prioritisation of all study aspects

• Provision of one-stop in-house central labratories

6ORION CLINICAL

ORION CLINICAL CAN HELP YOU ACHIEVE FASTER APPROVALS THROUGH OUR STRATEGIC DEVELOPMENT AND REGULATORY PLANNING FOR ORPHAN INDICATIONS

FAST AND EFFICIENT PHASE I – III STUDIESUTILISING IN–HOUSE FULL-SERVICE CAPABILITIES

7 SIMBEC ORION

SEIRIAN LABORATORIESSIMBEC-ORION’S CENTRAL PATHOLOGY & BIOANALYTICAL LABORATORIES

SEIRIAN LABORATORIES

“37% OF SEIRIAN’S EXPERIENCE HAS BEEN WITH NEW CHEMICAL ENTITIES...

...INCLUDING TRANSFER OF TECHNOLOGY FROM PRECLINICAL

TO HUMAN MATRICIES”

Is an integrated element of the Simbec-Orion Group based from the Simbec campus. Fast efficient reliable delivery for your complex studies

• Developing and validating complex assays• Highly selective and sensitive methods• Supporting all types of clinical study

THE BIOANALYTICAL LABORATORY DELIVERS

RADIOISOTOPES LABORATORY

Our Radioisotopes Laboratory performs radioactivity measurements for human ADME and mass balance studies. Radio-HPLC and LC-MS/MS techniques are then used to investigate metabolite profiles and to assist the identification of putative metabolites.

BIOANALYTICAL & PATHOLOGY

API 5000’S

API 5500

API 4000

API 365

FULL RANGE OF LC-MS & IMMUNOASSAY EQUIPMENT

BIOTEK SYNERGY 96-WELL PLATE READER

7 ORION CLINICAL

8SIMBEC ORION

Dedicated pathology support for clinical trials. Designed exclusively for the biopharmaceutical industry with over 30 years of consistent, high quality delivery.

SEIRIAN PATHOLOGY EXPERTISE

INFECTIOUS DISEASES

RESPIRATORY

REPRODUCTIVE MALE/FEMALE

CARDIOLOGY

ENDOCRINOLOGY

DERMATOLOGY

ONCOLOGY

METABOLISM

IMMUNOLOGY

RHEUMATOLOGY

THERAPEUTIC AREAEXPERIENCE

UROLOGY

TECHNOLOGY

Clinical Chemistry Biochemistry, Immunology, Serology, Drugs of Abuse Screening

Urinalysis Routine multi-parameter testing with microscopic analysis

Haematology Full Blood Count with Differential Routine and Specialised Haemostasis Markers e.g. Thrombin Generation Assay

Multiplex Assays Cytokine Assays

Flow Cytometry Flow Cytometry - Lymphcyte Subset analysis etc.

Laboratory Computer System Clinical Trial LIMS

Microbiology Bacteria Identification and MIC Susceptibility

Freezer Storage Rees Scientific System Monitoring Storage Temperatures i.e. 4C, -20C, -80C and Room Temperature

Logistics management

8ORION CLINICAL

7 day per week analyses

NOTES

NOTES

www. SimbecOrionCRO.com

ORION CLINICALBUSINESS DEVELOPMENTT +44 1753 578080A 7 Bath Road, Slough SL1 3UA United Kingdom

Info@SimbecOrionCRO.com

100 Overlook Center2nd FloorPrincetonNJ 08540USAT +1 215 345 5004

Simbec HouseMerthyr Tydfil Industrial ParkMerthyr Tydfil CF48 4DR United KingdomT +44 1443 690977

7 Bath RoadSloughSL1 3UAUnited Kingdom

T +44 1753 578 080

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T +33 1 40 83 40 83

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T +49 2241 97398 204

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