ABPI Conference 2016 - Dr Mene Pangalos on 'Driving innovation in the R&D Ecosystem'

1. Driving innovation in the
R&D ecosystem
Dr Menelas N Pangalos
Executive Vice President,
Innovative Medicines and Early Development Biotech Unit 21 April 2016

2. IMED Biotech Unit
Outline
Driving innovation in the R&D ecosystem
Case study: osimertinib
Reshaping our pipeline

3. IMED Biotech Unit
Outline
Driving innovation in the R&D ecosystem
Case study: osimertinib
Reshaping our pipeline

4. IMED Biotech Unit
Our focus is on achieving scientific leadership in three core
therapy areas
Neuroscience
Infection
& Vaccines
CV- Metabolism
Respiratory,
Inflammation
& Autoimmunity
Oncology
Core Therapy Areas Opportunity-focused
Heart
disease
17 million
deaths every
year
Cancer
7 million lives
lost every
year
Diabetes
350 million people
affected today
Asthma
235 million
sufferers today

5. IMED Biotech Unit

6. IMED Biotech Unit
Our 5R framework has helped us drive quality not quantity
Right target
Right safety
Right patients
Right commercial
potential
Right tissue
 Strong link between target and disease
 Differentiated efficacy
 Available and predictive biomarker
 Adequate bioavailability and tissue exposure
 Definition of PD biomarkers
 Clear understanding of preclinical and clinical PK/PD
 Understanding of drug–drug interactions
 Differentiated and clear safety margins
 Understanding of secondary pharmacology risk
 Understanding of reactive metabolites, genotoxicity, drug–drug interactions
 Understanding of target liability
 Identification of the most responsive patient population
 Definition of risk–benefit for given population
 Differentiated value proposition versus future standard of care
 Focus on market access, payer and provider
 Personalized healthcare strategy, including diagnostic and
biomarkers
Right culture  Truth seeking versus milestone seeking behaviours
Lessons learned from the fate of AstraZeneca's drug pipeline: a five-dimensional framework
Cook et al Nature Reviews Drug Discovery 13, 419–431 (2014)

7. Case study:
Osimertinib (AZD9291)
for non-small cell lung
cancer

8. IMED Biotech Unit
The evolution of genomics in lung cancer diagnosis
Unknown EGFR
KRAS ROS1
RET PIK3CA
AKT MET
BRAF Her2
ALK
201220041987Historical View
Adeno-
carinoma
Unknown
KRAS
EGFR
Unknown

9. IMED Biotech Unit
Structure-based design underpins the accelerated progress
of osimertinib
 Mutations in EGFR lead to an
oncogenic phenotype & acquired
resistance
 Drugs like gefitinib & Tarceva face
resistance with new mutations in EGFR
 66% of acquired resistance due to
T790M in exon 20 of EGFR
(gatekeeper mutation)
 Osimertinib designed to target T790M

10. IMED Biotech Unit
Structure-based design underpins the accelerated progress
of osimertinib
 Mutations in EGFR lead to an
oncogenic phenotype & acquired
resistance
 Drugs like gefitinib & Tarceva face
resistance with new mutations in EGFR
 66% of acquired resistance due to
T790M in exon 20 of EGFR
(gatekeeper mutation)
 Osimertinib designed to target T790M

11. IMED Biotech Unit
Structure-based design underpins the accelerated progress
of osimertinib
 Mutations in EGFR lead to an
oncogenic phenotype & acquired
resistance
 Drugs like gefitinib & Tarceva face
resistance with new mutations in EGFR
 66% of acquired resistance due to
T790M in exon 20 of EGFR
(gatekeeper mutation)
 Osimertinib designed to target T790M

12. IMED Biotech Unit
Osimertinib: Overall response rate 66.1% in T790M+
Median response rate 7.7 months and ongoing
By blinded independent central review. Evaluable for response analysis set (n=398). Mean best percentage change in target lesion size -45%, standard deviation 28.0 (median best percentage
change -47.6%; range: -100% to +90.8%). Poster #365 presented by Glenwood D. Goss at the ECC 2015 European Cancer Congress

13. IMED Biotech Unit
v
We continue to understand resistance mechanisms to
osimertinib to prolong patient benefit
Early responses with savolitinib (MET
inhibitor) / osimertinib combo in NSCLC
Pre-treatment 4 weeks
32-yr female showing neck metastasis
with high MET-amplification
 MET amplification (10–15% patients)
 MEK/ERK pathway switching
 C797S EGFR (~40% patients)
Nature Medicine, Thress et al, 2015
 Treating EGFRM+ NSCLC with brain
metastasis
 Combination with immuno-oncology
molecules

14. IMED Biotech Unit
1-3 yr
Ground-breaking timelines from discovery to approval together
with the world’s first plasma and tissue diagnostic approved
Pre-clinical Phase I Phase II Phase III RegistrationResearch
~8 yr1-3 yr4-5 yr
3.1
years
10
months
2.6 years
osimertinib
approved
in US Nov
2015
cobas®
EGFR
mutatio
n test -
V2
+
Timespan

15. IMED Biotech Unit
Achieving patient access to osimertinib
5 hours
37 minutes
US
NHS: 79 days
and counting…
UK
Available in
France and the
Netherlands
EU
Available to
private
patients
UK

16. IMED Biotech Unit
Outline
Driving innovation in the R&D ecosystem
Case study: osimertinib
Reshaping our pipeline

17. Personalised healthcare
Talent
Driving innovation in the R&D ecosystem
Technology
IMED Biotech Unit
Biohubs
Collaboration
Open innovation

18. Biohubs
Collaboration
Open innovation
Driving innovation in the R&D ecosystem
IMED Biotech Unit
GLAZGo Discovery
Centre for RIA
Karolinska Insitutet
Integrated Cardio
Metabolic Centre

19. Driving innovation in the R&D ecosystem
IMED Biotech Unit
Boston Gothenburg
Alderley
Park
Shanghai Cambridge
Biohubs
Collaboration
Open innovation

20. Driving innovation in the R&D ecosystem
IMED Biotech Unit
Drug repositioning AZ Open Innovation Portal
www.openinnovation.astrazeneca.com
Biohubs
Collaboration
Open innovation

21. Driving innovation in the R&D ecosystem
IMED Biotech Unit
CRISPR gene-editing to alter
any gene with high specificity
Working to create the first
‘human body-on-a-chip’
Personalised healthcare
Talent
Technology

22. Driving innovation in the R&D ecosystem
IMED Biotech Unit
Personalised healthcare
Talent
Technology
Working to create the first
‘human body-on-a-chip’

23. Driving innovation in the R&D ecosystem
IMED Biotech Unit
Personalised medicine is becoming a
healthcare reality for payers, phsyicians
and patients
 More than 80% of our clinical pipeline currently has
a PHC component
 1st circulating tumour DNA test approved
 7 diagnostic approvals in 2015 alone
 50% of pipeline will have a diagnostic at launch
over next 5 years (~30 launches)
 Basket trials will become even more important as
we stratify patient segments further
Personalised healthcare
Talent
Technology

24. Driving innovation in the R&D ecosystem
IMED Biotech Unit
>400
>70
120
30
university
collaborations
globally
university placement
students each year
post doc positions
across our sites
science graduates in
IMED programme
each year
STEM ambassadors
supporting school and
community activities
chief scientists
recruited in last 2 years
~50
>10
Attracting and developing IMED Talent
Personalised healthcare
Talent
Technology

25. IMED Biotech Unit
We are more committed than ever to basic science and
publishing our breakthrough research
High Impact = >15
High Quality = 5-15
All Other
1
103
275
97
446
151*
29
2010 2015
No.ofpublications
203
499
17
252
2014

26. Enhanced
collaboration
is a key
driver behind
our new UK
facility at the
Cambridge
Biomedical
Campus

27. Our new Cambridge research centre will be a catalyst for
innovation and collaboration

28. …will enable us to change the way we treat disease and transform lives
What science can do
Being open for
collaboration…
…creating an
environment where
science thrives
…and challenging
conventional thinking