Ethically-donated fresh, functional human tissues can be used to better predict the likely effect of drugs during clinical trials. As the closest possible model of drug function in patients, fresh human tissues are playing an increasingly important role in de-risking the drug discovery process, helping pharmaceutical and biotechnology companies to make earlier go/no-go decisions based on human data.

1. The Use of Fresh Human Tissues to
Predict Drug Efficacy, Safety and
Absorption

2. Human Tissues Predict
Clinical Safety and Efficacy
• Functional data produced in ex vivo human tissue
• Provide information to pharmaceutical and biotechnology companies
about the behaviour of their compounds in human relevant systems
• Efficacy
• Do compounds work in human tissue
• Absorption
• Are compounds permeable through human gut, skin, bronchi
• Safety Pharmacology
• Do compounds show adverse effects in human tissue – e.g. human coronary arteries
• Comparative studies with other species strengthens this capability

3. Biopta- Leaders in Fresh
Human Tissue Research
Beltsville,
Maryland
Glasgow, UK• HQ and lab in Glasgow, UK
• Lab facility in Maryland
• Founded 2002
• First, and currently only, GLP
compliant functional human
tissue CRO
• Experts in human tissue
research and procurement
• 50% of scientists at PhD level
• Pharma and Biotech
customers worldwide
• Tailored human functional
studies with responsive and
flexible collaboration to achieve
clients’ goals

4. Biopta’s Tissue Network: Fresh Human
Tissues Sourced 24/7 in USA and UK
Surgical residual tissues
Nontransplantable
organs
• Biopta receives ethically donated fresh tissues via two
main routes:
- Surgical residual tissues (mainly UK)
-Non-transplantable organs (mainly USA)
• Biopta’s facilities are open 24/7 to receive the tissues,
dissect and conduct experiments – Laboratories ( )
placed strategically to minimise transport time
• Biopta is an ethically approved Research Tissue Bank

5. Biopta’s Scientific Expertise: Techniques
to Assess Human Tissue Pharmacology
• Biopta has a track record of producing high quality decision-making
data from human and animal tissue in a variety of functional assay
systems
• Experience with addressing complex issues across a broad range
of therapeutic areas and mechanistic pathways
• Staffed with highly trained laboratory scientists skilled in tissue
dissection and experimentation, and with experienced study
directors with a track record of coordinating complex programs of
work

6. Biopta – How we work
Fresh Human
Tissue
Pharmacology
Techniques
Scientific
Experience
Scientific
Question
BioptaClient
Protocol design
e.g. Blood pressure change e.g. Resistance arteries e.g. Tissue baths
-10 -9 -8 -7 -6 -5
0
25
50
75
100
log M [acetylcholine]
%Relaxation
-9 -8 -7 -6 -5 -4
0
25
50
75
100
log M [phenylephrine]
%Constriction
Decision-making data
Relaxation to
Acetylcholine
Constriction to
Phenylephrine
Raw data traces Analysed data Interim and final reports

7. Tissue baths Ussing
Chambers
Wire myographs Perfusion
myographs
Ex vivo
cultures
Biopta Techniques
• Contractility and relaxation of tissues
• vascular and myocardial tissue
• lung tissue
• gastrointestinal tissue
• genitourinary tissue
• Inflammation, cytokine and gene exp. analysis
• lung tissue
• gastrointestinal tissue
• Compound penetration and metabolism
• gastrointestinal tissue
• lung tissue
• skin tissue
• Ion channel activity
• lung tissue
• gastrointestinal tissue

8. Biopta Human Tissues
Blood Vessels: Gastrointestinal: Others:
- resistance arteries - large intestine - skin
- coronary arteries - small intestine - skeletal muscle
- renal arteries - oesophagus
- pulmonary arteries - stomach
- cerebral arteries
Cardiovascular: Genitourinary: Respiratory:
- atrial appendage - bladder - bronchus
- ventricular muscle - urethra - trachea
- uterus
From both healthy and diseased patients: heart failure, asthma, COPD, diabetes,
atherosclerotic tissue, ischaemic limbs, psoriatic and atopic dermatitis skin biopsies
Other tissues are available from Biopta’s wide tissue network. Contact us to check availability: info@biopta.com

9. Constriction
↑ blood pressure
Relaxation
↓ blood pressure
0 min 10 min 15 min 20 min 25 min5 min
Fresh human tissue
(heart shown here but many
tissue and organ types used)
Tissue transported
immediately to
laboratory
Scientist isolates
the tissues of
interest
The “living”
tissues are
exposed to
drugs
Small blood
vessels
isolated from
tissue sample
A Biopta project: patient > lab > translational data

10. Using human tissues de-risks development
by avoiding species differences
Sensitivity differences to the vasoconstrictor 5-HT
(serotonin) in subcutaneous resistance arteries of dogs
and humans
-10 -9 -8 -7 -6 -5 -4
0
25
50
75
100
Canine
Human
5-HT log [M]
%constriction
(ofKPSSresponse)
Where there are clear species differences between humans and animals, human
isolated tissues can avoid such differences
Relaxation CRC to PDE2 inhibitor in
canine and human subcutaneous
resistance arteries
-7.0 -6.5 -6.0 -5.5 -5.0 -4.5 -4.0
-10
15
40
65
90
**
**
** canine sc arteries
human sc arteries
Log M [PDE2 inhibitor]
Relaxationasa%of
300nMU46619preconstriction
Biopta collaboration with J&J demonstrating the involvement
of PDE2 in the control of subcutaneous artery tone
(results published at the Safety Pharmacology Society
Meeting, 2009)

11. Biopta’s data impacts across
the whole drug development process
Clinical trials
Discovery phase Development phase
Clinical trials
Phase 1 II III IV
Lead
optimisation
Lead
identification
Hit
identification
Target
validation
Nomination
phase
Target
validation
Compound
characterisation DMPK Safety Clinical observations

12. Why Biopta?
• Add commercial value and reduce risk of clinical failure
• Efficacy and safety data generated in target species eliminating species
differences
• Conduct experiments to directly compare animal and human data
• Biopta is the world leading GLP-compliant laboratory for testing in fresh,
functional human tissues
Email: KeithBowers@biopta.com
Tel: +44 141 330 3831
www.biopta.com