This document discusses the rise of personalized medicines and their impact on drug development. It notes that nearly 1 in 4 new drugs approved in recent years were precision medicines, and the proportion of personalized medicines in clinical development is expected to increase to 70% over the next five years. The use of genomics is also increasing in clinical trials, with over half of phase 1 trials and nearly two-thirds of phase 2 trials including some aspect of genomic medicine. The role of biomarkers, pharmacogenomics, and other approaches are enabling more targeted patient selection and dosing in clinical development. While promising, precision medicines also present challenges including complex trial designs, regulatory hurdles, data management needs, and the integration of multiple types of genomic and clinical

1. © 2017 PAREXEL INTERNATIONAL CORP.
DEVELOPING DRUGS
IN THE NEW ERA OF
PERSONALIZED
MEDICINES
Anita Nelsen - Head of Genomic Medicine, Sr. Director,
PAREXEL International
Dr. Sy Pretorius - Sr. Vice President, Chief Scientific Officer,
PAREXEL International

2. © 2017 PAREXEL INTERNATIONAL CORP. / 2
PROPOSED AGENDA
WELCOME
• What is precision medicine?
• The rise & impact of precision medicine
• Impact on drug development
• Impact on clinical development
• Impact on clinical trials
• The role of genomics in development
• Case studies
• Emerging trends
• Summary and conclusion
• Q&A

3. © 2017 PAREXEL INTERNATIONAL CORP. / 3
WHAT ARE PRECISION OR PERSONALIZED MEDICINES
Leverage biomarkers,
often genetic, to
determine who is most
likely to benefit from
a treatment, who is at
higher risk of a side
effect, or who needs
a different dose
Source: Adapted from Bayer Healthcare, “Personalized Medicine.” https://pharma.bayer.com/en/research-and-
development/research-focus/oncology/personalized-medicine/index.php (accessed May 2105).
With
personalized medicine
Each patient receives the right medicine for them
Benefit No benefit Adverse effects
Patients
Therapy Therapy Therapy
Biomarker diagnostics
Each patient benefits from individualized treatment
Without
personalized medicine
Some benefit, some do not
Benefit No benefit Adverse effects
Therapy
Patients

4. © 2017 PAREXEL INTERNATIONAL CORP. / 4
RISE AND IMPACT OF PRECISION MEDICINES
Nearly 1 in 4 of the
new drugs approved
by the U.S. Food and
Drug Administration
between 2014-16
were
precision medicines.
¼
Currently the FDA lists
almost 200 approved
medicines with
pharmacogenomic
biomarker information
in their labeling.
200
132 of these are
considered precision
medicines leveraging
a biomarker to direct
treatment decisions.
132
Over the next five
years, the proportion
of personalized
medicines in clinical
development is
expected to increase
to nearly 70%.
70%
http://www.personalizebdmedicinecoalition.org/Res
ources/Personalized_Medicine_at_FDA. Accessed
04 May 2017
Tufts Center for the Study of Drug Development Impact
Report, Volume 17, No 3, May/June 2015

5. © 2017 PAREXEL INTERNATIONAL CORP. / 5
IMPACT ON DRUG DEVELOPMENT
• Precision medicines are impacting across a wide range of therapeutic areas including Psychiatry, Infectious
and Cardiovascular Diseases
• In the three therapeutic areas having a more robust base for analysis, Oncology followed by Immunology and
Neurology showed the greatest penetration in the three areas accounting for a majority of the Genomic
budget – Bioinformatics, Target Validation and Pharmacogenomics.
*Percentages reported for Pharmacogenomics and Data Analytics represent the mean of means for individual activities within these service areas. Detailed information for individual capabilities available in appendix.
Base: Oncology=38, CNS/Neurology=17, Immunology=17
Q. Considering the therapeutic area(s) your company works in, which of the following genomic medicine activities do you typically utilize for each? Please select all that apply for each therapeutic area.
79% 76%
64%
35%
29%
53%
59%
41%
24%
41%
71%
65%
51%
39%
29%
BIOINFORMATICS TARGET VALIDATION PHARMACOGENOMICS DATA ANALYTICS DRUG REPOSITIONING
Oncology CNS/Neurology Immunology

6. © 2017 PAREXEL INTERNATIONAL CORP. / 6
When asked to report on the proportion of studies including some aspect of
Genomic Medicine, utilization was found to be greatest in the earlier phases
of development and then declines in later phases, as expected.
N=55
PHASE II
N=45
PHASE III
57%
N=33
PHASE IV
IMPACT ON CLINICAL DEVELOPMENT
Q. Considering the following stages of clinical development, approximately what proportion of
studies your company does in each stage includes some aspect of genomic medicine?
N=50
PHASE I
Genomic Medicine Use by Study Phase
63% 57% 49% 30%

7. © 2017 PAREXEL INTERNATIONAL CORP. / 7
• Basket trials
• Umbrella trials
• Master trials
• Co-development of test
• Sub-populations/disease
sub-types
• Ethnic variation
• Safety/adverse events
• Targeted selection or
stratification using genetic/
biomarker
• Dose selection
• Smaller numbers of patients
IMPACT ON CLINICAL TRIALS
TRIAL
DESIGNS
EXPLAIN VARIABLE
RESPONSE TO
TREATMENT
PATIENT
SELECTION

8. © 2017 PAREXEL INTERNATIONAL CORP. / 8
Application of genomics in developing
precision medicines

9. © 2017 PAREXEL INTERNATIONAL CORP. / 9
THE
RIGHT
PATIENT
THE
RIGHT
DRUG
THE
RIGHT
TIME
THE
RIGHT
DOSE
THE “RIGHT” REASONS TO INCLUDE GENOMICS IN DRUG DEVELOPMENT…
• Companion diagnostics
• Patient enrichment
• Novel clinical trial design
• PK Variability/ADME
• Genetic risk factors
• Drug combinations
• Drug target of specificity
• Targeted pathway
• Drug repurposing
• Drug resistance
• Disease progression
• Non-invasive biomarker

10. © 2017 PAREXEL INTERNATIONAL CORP. / 10
APPLICATION OF CUTTING-EDGE
METHODOLOGIES THAT
INTEGRATE GENOMICS DATA CAN
REVEAL NEW SCIENTIFIC INSIGHTS
• The human immune response system is
highly complex with cross-talk between multiple
immune-mediated pathways.
• Many currently available medicines that target the
immune system affect multiple pathways – some
desired, others not.
• Using cutting-edge methodologies (e.g., causal
reasoning, advanced network analysis) to integrate,
analyze, and interpret multi-omics experimental data
led to discovery of novel drug targets that may have
selectivity for IL23 pathways.
-300 -200 -100 0 100 200 300
Comp.1 [25.66%]
-200
-150
-100
-50
0
50
100
150
200
Comp.2[12.25%]
J Immunol (2014) 192: 2527-8
EBI Immunogenomics Conference 2015
Transcriptomics: IL23 vs IL12 Proteomics: IL23 vs. IL12
Integrated Multi-omics Network
Causal Reasoning & Inference
Novel Target Candidates

11. © 2017 PAREXEL INTERNATIONAL CORP. / 11
WHAT IS PHARMOCOGENOMICS?
• Pharmacogenomics is the study of DNA and RNA characteristics as they relate to drug response1
• Provides insights into drug exposure, efficacy, and safety
1 http://www.ich.org/products/guidelines/efficacy/efficacy-single/article/definitions-for-genomic-biomarkers-pharmacogenomics-
pharmacogenetics-genomic-data-and-sample-cod.html accessed 02Sep16
Pharmacogenomics helps us understand why
people who receive the same drug respond differently

12. © 2017 PAREXEL INTERNATIONAL CORP. / 12
PHARMACOGENETICS EXPLAINS EXPOSURE DIFFERENCES
• In a Phase I drug-drug interaction study,
a subset of healthy volunteers had elevated
levels of Drug X when administered with
the client’s medicine.
• Drug X is primarily metabolized by a CYP450
enzyme. Genetic variation in the CYP450
gene was evaluated to determine if genetic
variants that lead to reduced enzyme activity
might explain increased exposure of Drug X.
• The poor metabolizer CYP450 genotype was
associated with elevated exposure of Drug X.
• The client’s medicine likely did not impact
Drug X exposure.
IM intermediate metabolizer
PM poor metabolizer
WT wild-type metabolizer
Drug X plasma concentrations over time by CYP450 genotype
Concentration
PM
PM
PM
IM
WT
Time (hrs)

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Atopic Dermatitis PsoriasisAcne
Drug
Discovery
Today
(2014) 19
(9): 1364-71
DRUG REPURPOSING CAN ACCELERATE MEDICINE DEVELOPMENT
A comprehensive clinical transcriptomics analysis across multiple dermatologic conditions identified additional
dermatology indications for this medicine, discovered mechanistic connections between skin diseases and
generated new hypotheses to accelerate medicine development.

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PRECISION
MEDICINES
Big Data Analytics
New ‘OMES
e.g. microbiome
Electronic Health
Records
Co-Development
Partners
Patient Partnerships
New Technology
(cfDNA, CTC)
Data Sharing
Smart
Phones/Wearables
EMERGING TRENDS IMPACTING PRECISION MEDICINES

15. © 2017 PAREXEL INTERNATIONAL CORP. / 15
A JOURNEY WITH GREAT PROMISE…. AND CHALLENGES TOO
• Complex trial designs including co-development
of companion test
• Regulatory requirements are emerging in
global markets
• Reimbursement considerations for drug and test
• Ethics and local laws pose challenges for sampling
and testing
• Storage and computational resources for big data
• Ensuring accuracy of results from evolving
technologies such as NGS
• Integrating and analyzing multi-omics data
• Making big data accessible and understandable to
drug development scientists
• Creating and communicating reproducible workflows
for complex analyses
Clinical trials for Precision
Medicines may look very different
from traditional drug trials
Hard to have breadth of expertise
needed to capitalize on turning
GENES > TARGETS > PRECISION MEDICINES

16. © 2017 PAREXEL INTERNATIONAL CORP. / 16
THANK YOU
© 2017 PAREXEL INTERNATIONAL CORP. / 16