Simbec-Orion Clinical Pharmacology Brochure

EARLY PHASE RESEARCH

ALL YOUR EARLY PHASE RESEARCH NEEDS FROM A SINGLE RESEARCH CAMPUS

MISSION STATEMENT We are Simbec-Orion. An international, full service, boutique CRO; growing by bringing together the best possible 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.

OUR THERAPEUTIC EXPERIENCE

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> 1,500 PHASE I/IIa STUDIES SUCCESSFULLY COMPLETED Simbec-Orion Clinical Pharmacology’s 58 bed clinical pharmacology unit, is one of the largest in the UK. A fully MHRA accredited facility able to carry out all types of studies (including FiH) and offering client focused project management, experienced medical teams, on site pathology & bioanalytical laboratories (with ɣ-scintigraphy imaging services), integrated data management and biostatistics, medical writing, pharmacy and Qualified Person (QP).

A full service facility all on a SINGLE dedicated research campus in South Wales.

Mass Balance/ ADME

3%

Scintigraphy

SAD / MAD / PT

5%

SAD / MAD / PD / FE SAD / MAD / FE SAD / MAD SAD / FORMULATION SAD

35%

57% MAD / PT MAD / PD MAD / FE MAD

PK studies

0

2

4

6

8

10

12

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Combination Protocols SIMBEC-ORION

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CLINICAL PHARMACOLOGY UNIT 58 BED PHASE I CLINICAL UNIT WITH FULL SERVICE SUPPORT ALL ON A SINGLE CAMPUS SIMBEC-ORION’S FiH EXPERIENCED TEAM HAS DELIVERED >1,500 CLINICAL STUDIES

SIMBEC-ORION CLINICAL PHARMACOLOGY With 43 years of experience, Simbec-Orion Clinical Pharmacology is one of the oldest and most experienced First in Human (FiH) Phase I organisations, having successfully delivered >1,500 clinical studies.

As well as expertise in FiH studies including single and multi-dose tolerability Simbec-Orion Clinical Pharmacology has significant expertise in: • Drug-drug interactions • BioAvailability/BioEquivalence studies • PK/PD studies • Food/Gender effect • Gamma Scintigraphy • PoC Phase IIa studies • Mass Balance/ADME/Microdosing studies • Genotyping • Phenotyping studies • QTc studies

Located in South Wales, near Cardiff, and with easy access to Heathrow, Simbec-Orion Clinical Pharmacology commands almost exclusive, efficient access to a volunteer and patient population of 2-3 million people.

Simbec-Orion Clinical Pharmacology Volunteer Recruitment immediate sphere of influence 6

SIMBEC-ORION

SIMBEC-ORION CLINICAL PHARMACOLOGY’S FULL SERVICE RESEARCH CAMPUS

With a campus combining a 58 bed Phase I clinical unit, central pathology & bioanalytical laboratories (Simbec-Orion Laboratory Services), ɣ-scintigraphy imaging services, IMP management via pharmacy and our Qualified Person team, integrated data management & statistics, project management & medical writing, Simbec-Orion provides unprecedented service and delivery.

ACCREDITED TO THE HIGHEST STANDARDS Simbec-Orion Clinical Pharmacology has been successfully inspected by MHRA-GMP, MHRA-GLP, MHRA-GCP, MHRA-GCP for Laboratories, MHRA-Phase 1 Accreditation, US FDA and UK Clinical Pathology Accreditation.

“SIMBEC-ORION CLINICAL PHARMACOLOGY CONTINUALLY PERFORMS >20% OF THE FiH STUDIES APPROVED IN THE UK.” SOURCE MHRA STATISTICS SIMBEC-ORION

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PROJECT MANAGEMENT

BY HAVING THE FULL SERVICE SUPPORT IN A SINGLE CAMPUS ENVIRONMENT, DRIVEN BY EXPERIENCED PROJECT MANAGERS, SIMBEC-ORION CLINICAL PHARMACOLOGY CAN PROVIDE YOU WITH SIGNIFICANT BENEFITS: SPEED, RELIABILITY OF DATA AND COST EFFECTIVENESS

Project Management group is located on campus – allowing direct/face to face lines of communication and ensuring a hands on approach with the study team.

To speed studies along smoothly we have: • Established procedures and templates for management of dose escalation trials • Established trial management SOPs/ templates with a flexible approach to sponsor requirements • Direct liaison with analytical laboratory to ensure timely reporting of drug concentration/pharmacodynamic/biomarker data Quality and scientific integrity are assured because all protocols are reviewed alongside current guidelines to ensure appropriate design and to minimise regulatory risk.

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CLINICAL PHARMACOOGY CAMPUS BENEFITS TO SPONSORS Experienced medical teams

Subject Safety

Access to >2m healthy volunteers and patients

Meeting timelines cost effective

43 year history of safe and efficient delivery

Experience and expertise within the teams

On site Labs & MHRA GMP Pharmacy

Controlled environment for handling samples and IMP

E-clinical systems & LIMS

Real time access to better quality data

Full service phase I on a dedicated campus

Data (samples and CRFs) do not leave this site

Innovative and simple pricing model/structure

Efficient service delivery

KEY THERAPEUTIC AREAS The Project Management Team is highly experienced at managing early phase clinical trials.

To ensure deadlines are achieved Project Management work in close cooperation with on campus support departments including Volunteer Recruitment, IMP Management (Pharmacy), Central Laboratories and Biometrics. A risk management plan is put in place for each study. Simbec-Orion Clinical Pharmacology has established procedures for capture and tracking of non-compliances, CAPA and project issue escalation.

RESPIRATORY DERMATOLOGY OPHTHALMOLOGY CARDIOVASCULAR NEUROLOGICAL ENDOCRINE PAIN

RESEARCH ETHICS COMMITTEE (REC) SUBMISSIONS Established relationships of nearly 15 years with Wales REC and their administration office - providing a fast turnaround and minimising risk of delays. The use of established templates for Informed Consent, Participation Information Sheet, GP letters etc. speeds approvals.

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PHARMACY / IMP MANAGEMENT OUR PHARMACY HANDLES A WIDE RANGE OF IMP DOSAGE FORMS FOR ALL EARLY PHASE CLINICAL STUDIES OUR GOAL IS TO MAKE YOUR STUDY AS EASY AS POSSIBLE FOR YOU, NO MATTER WHAT DOSAGE FORM YOU USE

As active pharmaceutical ingredients are increasing in value, it is imperative that they can be managed effectively and efficiently.

Simbec-Orion Clinical Pharmacology offers an effective, GMP & GCP compliant, in-house solution.

Simbec-Orion Clinical Pharmacology specialist clinical trials pharmacy team are solely focused on the efficient management of your drug product. With 5 Qualified Persons named on Manufacturing Authorisation, Pharmacist & dedicated Clinical Trials Supplies Technicians, the team can manage your needs.

We can manage • Sterile Products

• Grade A Isolator for aseptic production

• Non-Sterile Products

• Oral solutions, suspensions, topicals hand filling capsules, radiopharmaceuticals, solutions for inhalation/nebulisation

• Importation of IMP from outside EU • MIA(IMP) No. 4757 manufacture, primary and secondary packaging, IMPD writing and review • Double-blind Randomisation and Code break Envelope Production • IMPD writing and review 10

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We are • GMP and GCP compliant • Annex 13 compliant IMP Label Design • Controlled Drug (CD) license holder

BIOMETRICS AND PK ANALYSIS At Simbec-Orion Clinical Pharmacology our in-house experts can work with you to ensure the data you want to collect can answer the questions you need answering. From development of the electronic Case Report Form (eCRF) through to PK analysis.

WE WORK WITH YOU FROM GETTING THE VOLUNTEER THROUGH THE DOOR TO DELIVERING THE ANSWERS TO YOUR STUDIES QUESTIONS. ALL WITHIN THE ONE RESEARCH CAMPUS

Data Management

Statistical Analysis

• Case Report Form (CRF) review

• Set up activities include protocol review and generation of randomisation scheme

• Data Management Plan • Annotation of CRFs and Data Specification • Database design • Data Entry,Verification, Comparison, Query Resolution • MedDRA and WHO Drug dictionaries

• Statistical Analysis Plan agreed with sponsor, prior to database lock • Statistical Analysis & TFLs • All PK output for the Clinical Study Report (tables, figures and listings) listed in the SAP will be produced by the Statistician using SAS

• CDISC experience

PK analysis is a core skill within Simbec-Orion Clinical Pharmacology - performed by our in-house scientists • Non compartmental PK analysis will be performed using validated WinNonLin Phoenix 32 software • PK analysis will be independently verified by second analyst and QC checked before issue • Rapid turnaround of PK analysis for dose escalation decisions • Routine PK analysis for demonstrating bioequivalence • Final PK analysis for the report QA audited prior to issue to Statisticians for further analysis SIMBEC-ORION

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SIMBEC-ORION LABORATORY SERVICES

ON CAMPUS CENTRAL PATHOLOGY & BIOANALYTICAL LABORATORIES

SIMBEC-ORION LABORATORY SERVICES FULL RANGE OF LC-MS & IMMUNOASSAY EQUIPMENT

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

BIOTEK SYNERGY 96-WELL PLATE READER

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

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.

API 5500 API 5000’S API 4000 API 365

“37% OF OUR LABORATORY

SERVICES EXPERIENCE HAS BEEN WITH NEW CHEMICAL ENTITIES...

...INCLUDING TRANSFER OF TECHNOLOGY FROM PRECLINICAL TO HUMAN MATRICIES”

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SIMBEC-ORION LABORATORY SERVICES

ON CAMPUS CENTRAL PATHOLOGY & BIOANALYTICAL LABORATORIES

PATHOLOGY EXPERTISE THERAPEUTIC AREA EXPERIENCE

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

REPRODUCTIVE MALE/FEMALE INFECTIOUS DISEASES 7 day per week analyses

ENDOCRINOLOGY

TECHNOLOGY

RHEUMATOLOGY Clinical Chemistry

Urinalysis DERMATOLOGY

Biochemistry, Immunology, Serology, Routine multi-parameter testing with Drugs of Abuse Screening microscopic analysis

Haematology

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

Logistics management

IMMUNOLOGY

Multiplex Assays

Flow Cytometry

Laboratory Computer System

Flow Cytometry - Lymphcyte Subset analysis etc.

Clinical Trial LIMS

Microbiology

Freezer Storage

Bacteria Identification and MIC Susceptibility

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

RESPIRATORY METABOLISM CARDIOLOGY ONCOLOGY UROLOGY

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HEALTHY VOLUNTEER & PATIENT RECRUITMENT KEY QUESTION FOR YOUR EARLY PHASE STUDIES IS “CAN YOU GET ENOUGH APPROPRIATE VOLUNTEERS FOR YOUR TRIAL FAST ENOUGH AND IN A COST EFFICIENT MANNER?” SIMBEC-ORION CLINICAL PHARMACOLOGY HAS THE TEAMS, PROCESSES, AND AN ALMOST EXCLUSIVE VOLUNTEER POOL TO ANSWER “YES!”

The biggest problem facing Phase I studies is getting the right volunteers at the right time in a cost efficient manner

Some other Phase I units center themselves like clusters in cities hoping to trawl enough volunteers from large transient populations, competing with each other for the finite number of potential volunteers.

At Simbec-Orion Clinical Pharmacology we’ve taken a different approach.

For the last 43 years we have been based in an area of the country with no competing Phase I operators. Within our catchment area there are 2-3 million potential healthy volunteers and patients.

With cities, large population centres, universities and a steady stream of young healthy participants our outreach programmes have a enthusiastic and engaged audience.

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• Dedicated Volunteer Recruitment group comprising of clinical and marketing staff

DEDICATED ENROLMENT SERVICES TEAM FOCUSED ON ENSURING TIMELY AND EFFICIENT VOLUNTEER RECRUITMENT AND SCREENING

• Driving both study specific and general volunteer engagement and recruitment activities

— Focus of healthy volunteer recruitment via social media and digital channels, to increase engagement and drive down recruitment costs

— Significant links with both hospital centres of excellence and General practitioners to reach patient populations

“Our current % rate of scheduled FSFD is 99.3% and our current average screening ratio is 2:1” ONLINE & SOCIAL MEDIA • Twitter posts • Facebook ads and posts • Google Adwords TRADITIONAL MEDIA ADVERTS – PRINT & ONLINE • Local and regional newspapers MEDIA – BROADCAST • Radio adverts DIRECT MARKETING • Phone calls • Emails SITE SPECIFIC • Rail stations and trains • Bus Terminus and buses

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WHY CHOOSE THE UK FOR YOUR CRITICAL FiH STUDIES?

POSITIVE REGULATORY ENVIRONMENT, STRONG SAFETY GUIDELINES, EXPERIENCED RESEARCH PERSONNEL AND AN ACTIVE VOLUNTEER POOL, ALL COMBINE TO HELP FIRST IN HUMAN PHASE I STUDIES BE MORE EFFICIENT IN SOUTH WALES THAN THE USA

ONLY 1 IN 10 DRUGS ENTERING PHASE 1 WILL RECEIVE AN NDA Probability Of Drug (All Molecules) Progressing Between Clinical Development Phases*

No. of Products in Development Phase

Phase I

Phase II

10

6

Phase III

<2 Drugs 1 NDA

* Hay M et al. Clinical development success rates for investigational drugs. Nature Biotechnology 2014

ONLY 60% OF ALL MOLECULES ENTERING INTO PHASE I MAKE IT TO PHASE II With these facts in mind, strategically for your business, where is the best place for you to conduct your early phase clinical studies?

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TOP QUALITY RESEARCHERS, SPEED TO GETTING DATA & COST EFFICIENT

“WITHOUT THE NEED FOR EXPENSIVE IND APPLICATIONS, AT SIMBEC-ORION YOU CAN HAVE DATA COMING BACK FROM THE CLINIC BEFORE YOU’VE EVEN STARTED ENROLLING VOLUNTEERS IN THE USA.”

FOR FiH STUDIES IN THE US YOU MUST HAVE THE IND WRITTEN BEFORE YOU ENTER THE CLINIC – UP TO 6 MONTHS TO PREPARE & SUBMIT Regulatory Costs Prior to First Phase I Study Per Molecule USA

UK

IND Preparation/Submission

CTA Preparation/Submission

$120,000

$30,000

Regulatory Time Prior to First Phase I Study Per Molecule USA

UK

Cost Saving

$90,000

IND Preparation/Submission

CTA Preparation/Submission

Cost Saving to Reach NDA

$900,000

~ 4 – 6 Months

~ 2 Months

FOR FiH STUDIES IN THE UK YOU NEED A CTA ONLY BEFORE YOU ENTER THE CLINIC – 2 MONTHS TO PREPARE & SUBMIT.

Time Saving

2 – 4 Months

Extra Revenue Generated*

Up to $83,000,000

*assuming drug gets to market with sales of $1b / year

“Having been the CEO of several biotech companies, I see now the huge upside in running early phase clinical studies at Simbec-Orion Clinical Pharmacology, without the expense or delays of the IND process before the studies start. Upfront fees, earlier milestones, more sales value in the patent life. I wish I’d known this then...”

Ronald Openshaw former biotech CEO now CEO Simbec-Orion SIMBEC-ORION

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www.SimbecOrion.com i n fo r m at i o n @ S i m b e c O r i o n .c o m SimbecOrionCRO

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@SimbecOrion

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