EARLY PHASE RESEARCH

ALL YOUR EARLY PHASE RESEARCH NEEDSFROM A SINGLE RESEARCH CAMPUS

Simbec Research’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.

> 1,500 PHASE I/IIa STUDIES SUCCESSFULLY COMPLETED

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SIMBEC RESEARCH HAS UNPRECEDENTED ACCESS TO A POPULATION POOL OF 2-3 MILLION POTENTIAL HEALTHY VOLUNTEERS AND PATIENTS

32%

49%

6%13%

Large Pharma

Biotech & Mid Cap Pharma

Academic Institutions

CRO/Other

TYPES OF CUSTOMER

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58 BED PHASE I CLINICAL UNIT WITH FULL SERVICE SUPPORT ALL ON A SINGLE CAMPUS

SIMBEC RESEARCH’S FiH EXPERIENCED TEAM HAS DELIVERED >1,500 CLINICAL STUDIES

CLINICAL PHARMACOLOGY UNIT

With 40 years of experience, Simbec Research 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 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 commands almost exclusive, efficient access to a volunteer and patient population of 2-3 million people.

SIMBEC RESEARCH

Simbec Research

Volunteer Recruitment immediate sphere of influence

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SIMBEC RESEARCH’S FULL SERVICE RESEARCH CAMPUS

“SIMBEC RESEARCH CONTINUALLY PERFORMS >20% OF THE FIH STUDIES

APPROVED IN THE UK.” SOURCE MHRA STATISTICS

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ACCREDITED TO THE HIGHEST STANDARDSSimbec Research 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.

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

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

PROJECT MANAGEMENT

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.

SIMBEC RESEARCH CAMPUS BENEFITSTO SPONSORS

Experienced medical teams Subject Safety

Access to >2m healthy volunteers and patients

Meeting timelines cost effective

40 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

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KEY THERAPEUTIC AREAS

RESPIRATORY

DERMATOLOGY

OPHTHALMOLOGY

PAIN

ENDOCRINE

CARDIOVASCULAR

NEUROLOGICAL

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 has established procedures for capture and tracking of non-compliances, CAPA and project issue escalation.

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

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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 Research offers an effective, GMP & GCP compliant, in-house solution.

Simbec’s Research 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

We are

• GMP and GCP compliant

• Annex 13 compliant IMP Label Design

• Controlled Drug (CD) license holder

BIOMETRICS AND PK ANALYSIS

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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

• Case Report Form (CRF) review

• Data Management Plan

• Annotation of CRFs and Data Specification

• Database design

• Data Entry, Verification, Comparison, Query Resolution

• MedDRA and WHO Drug dictionaries

• CDISC experience

PK analysis is a core skill within Simbec - 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

Statistical Analysis

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

• 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

At Simbec 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.

SEIRIAN LABORATORIESON CAMPUS 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

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

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7 day per week analyses

HEALTHY VOLUNTEER & PATIENT RECRUITMENT

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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 RESEARH HAS THE TEAMS, PROCESSES, AND AN ALMOST EXCLUSIVE VOLUNTEER POOL TO ANSWER “YES!”

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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 Research we’ve taken a different approach.

For the last 40 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

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

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DEDICATED ENROLMENT SERVICES TEAM

FOCUSED ON ENSURING TIMELY AND EFFICIENT

VOLUNTEER RECRUITMENT AND SCREENING

“Our current % rate of scheduled FSFD is 99.3% and our current average screening ratio is 2:1”

• Dedicated Volunteer Recruitment group comprising of clinical and marketing staff

• 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

ONLINE & SOCIAL MEDIA• Twitter posts• Facebook ads and posts• Google Adwords • Simbec Research Website - post with links to sign-up.

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

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

ONLY 60% OF ALL MOLECULES ENTERING INTO PHASE I MAKE IT TO PHASE II

With these facts in mind, strategically for your business, where isthe best place for you to conduct your early phase clinical studies?

Probability Of Drug (All Molecules) Progressing Between Clinical Development Phases*

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

10 6 <2 Drugs

No. of Products in Development Phase

Phase I Phase II Phase III

1 NDA

TOP QUALITY RESEARCHERS, SPEED TO GETTING DATA & COST EFFICIENT

FOR FiH STUDIES IN THE US YOU MUST HAVE THE IND WRITTEN BEFORE YOU ENTER THE CLINIC – UP TO 6 MONTHS TO PREPARE & SUBMIT

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

SIMBEC RESEARCH 14

“WITHOUT THE NEED FOR EXPENSIVE IND APPLICATIONS,

AT SIMBEC YOU CAN HAVE DATA COMING BACK FROM THE

CLINIC BEFORE YOU’VE EVEN STARTED ENROLLING

VOLUNTEERS IN THE USA.”

“Having been the CEO of several biotech companies, I see now the huge upside in running early phase clinical studies at Simbec, 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 Group

Regulatory Costs Prior to First Phase I Study Per Molecule

USA

INDPreparation/Submission

Cost Saving to Reach NDA $900,000

$120,000

Cost Saving $90,000

CTA Preparation/Submission

$30,000

UK

Regulatory Time Prior to First Phase I Study Per Molecule

Extra Revenue Generated* Up to $83,000,000

Time Saving 2 – 4 Months

USA

INDPreparation/Submission

~ 4 – 6 Months

CTA Preparation/Submission

~ 2 Months

UK

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

www. SimbecOrionCRO.com

SIMBEC RESEARCH LIMITED BUSINESS DEVELOPMENTT: +44 1443 690977A: Simbec House Merthyr Tydfil Industrial Park, Merthyr Tydfil CF48 4DR United Kingdom

ACCREDITATIONS

UK GLP/GCP COMPLIANCEMHRA PHASE 1 CLINICAL TRIALS

SUPPLEMENTARY ACCREDITATIONCLINICAL PATHOLOGY ACCREDITATION UK

EXTERNAL QUALITY ASSESSMENT SCHEME

Info@SimbecOrionCRO.com

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