Transcript Pharma R&D Innovation in China A New Model for Drug

3rd International Congress on Nutrition,
Fitness and Health
Innovation in Healthcare –
an Industry (Roche) Perspective
Andreas Tschirky
Shanghai
December 4, 2008
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Topics:
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1. The R&D Innovation Model
2. Botanical Drug / Traditional Chinese Medicine (TCM)
3. Quality Assurance
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Intensifying challenges in the Healthcare industry
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Political environment
Healthcare budgets
squeezed
Growing safety
requirements
Medical need grows faster
than healthcare budgets
Access
New competitors
Declining R&D productivity
Declining growth rate in
traditional markets
Patients Needs
Patent expiries
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Roche R&D pipeline today
Phase I - (38 NMEs + 1 AI)
R547
R1530
R4733
R7112
R7159
R7167
R7204
GEN
GEN
GEN
GEN
GEN
GEN
GEN
GEN
CHU
R1646
R1671
R3477
R4930
R7103
R7277
GEN
GEN
BTI
R7128
R7227
CHU
R1511
R1512
R1663
R4929
R7201
R7232
R7234
GEN
R1295
R1450
R4996
solid tumors
solid tumors
solid tumors
oncology
NHL
solid tumors
malignant melanoma
anti-cMET – cancer therapy
hedgehog ant. – solid tumors
anti-CD20 3rd gen. – hem. malig.
IAP ant. – cancer therapy
MEK inh. – cancer therapy
ABT-263–solid tumors & hem.
malig.
PI3
kinase inhibitor – cancer
therapy
CD40 Ab – NHL/MM/rel.large B-CL
CRC
pain
asthma
autoimmune diseases
OX40L - asthma
COPD
RA
IFN-alpha Ab - SLE
Anti-IL 13 - asthma
VAP-1 – inflammatory diseases
HCV
HCV
HCV
type 2 diabetes
PVD
anticoagulant
type 2 diabetes
type 2 diabetes
dyslipidemia
type 2 diabetes
Anti-oxLDL sec. prev CV events
MS
Alzheimer‘s
Alzheimer‘s
Phase II - (18 NMEs + 12 AIs)
R435
R435
R435
R1273
R1273
R1415+R4
35
R1507
R3502
GEN
GEN
GEN
GEN
GEN
GEN
GEN
ARQ
R667
R3421
GEN
ISO
R1626
R3484
R1439
R1579
R1583
R1594
R1678
MEM
R744
CHU
RMT presentation August 2004
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Phase III - (4 NMEs + 41 AIs)
Avastin - glioblastoma
R105 MabThera – CLL 1st line
Avastin - NSCLC squamous
R105 MabThera – CLL relapsed
Avastin - NSCLC mCNS treat.
R105 MabThera – iNHL maint. 1st line
pertuzumab – EBC HER2+
R105 MabThera + Avastin – NHL aggr.
pertuzumab – ovarian cancer
R340 Xeloda - adj. CC combo oxaliplatin
Tarceva + Avastin – NSCLC 1st
R340 Xeloda – adj. CC combo Avastin
line
Ewing‘s
sarcoma
R340 Xeloda – adj. BC
T-DM1 - mBC
R435 Avastin - adj. CC
CD40 Ab – diff. large B Cell lymph.
R435 Avastin – prostate cancer
Apomab - sarcoma
R435 Avastin – pancreatic cancer
Apomab - cancer
R435 Avastin – ovarian cancer 1st line
lineadj. rectal
cancer
Apo2L/TRAIL - cancer
R435 Avastin
- mBC
combo Taxot. 1st
ABT-869 – solid tumors
R435 line
Avastin–mBC combo std. chem.
1st l.
Avastin – extensive SCLC
R435 Avastin
– mBC combo Hercept.
1st. l.
Avastin - relapsed MM
R435 Avastin
– adj. NSCLC
solid tumors
R435 Avastin – m. gastric cancer
RAR gamma - emphysema
R435 Avastin – adj. BC HER2PNP inh. – AI / transplant
R597 Herceptin –m. gastric cancer
Raptiva - renal transplant
R1273 HER2+
pertuzumab – mBC Her2+
renal transplant
R1415 Tarceva – NSCLC maint 1st line
HCV pol - HCV
R1415 Tarceva – adj. NSCLC
HPV16 – cervical neoplasia
R1415+R43 Tarceva+Avastin–NSCLC
5 maint.1
l. Avastin – NSCLC 2nd
aleglitazar – type 2 diabetes
R1415+R43
Tarcevast +
5
line
DPP-IV (3) – type 2 diabetes
GEN Avastin – ovarian cancer 2nd line
GLP1 - type 2 diabetes
GEN Avastin – GIST recurr.
ocrelizumab – RRMS
GEN Avastin – adj. rectal cancer
schizophrenia
GEN Avastin – mBC 2nd line
Alzheimer‘s / schizophrenia
GEN Avastin – high risk carcinoid
CERA – chemo induced anaemia
R99 CellCept – pemphigus vulgaris
R105 MabThera – RA DMARD IR
gastroparesis / IBS
R1569 Actemra – sJIA
R1594 ocrelizumab - RA
R1594 ocrelizumab – SLE / LN
CHU ED-71 – osteoporosis
GEN MabThera – lupus nephritis
GEN MabThera – ANCA ass. vascul.
GEN MabThera – SLE
GEN Xolair – pediatric asthma
R127 Valcyte – CMV extension
R1658 1 CETP inh. - dyslipidemia
GEN MabThera – PPMS
GEN TNKase – catheter clearance
GEN Lucentis – diabetic macular
edema – renital vein occlusion
GEN Lucentis
CHU Epogin – chemo induced anaemia
Registration - (2 NMEs + 3 AIs)
R340
R340
R435 1
R1569
CHU
Xeloda – mCRC combo 1st line
Xeloda–mCRC combo 2nd line
Avastin – RCC
Actemra - RA
Antevas – subarach. haemorr.
Notes
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Approved in EU, US to file in
2008
Additional Indication
NME
DBA Oncology
DBA Inflammation
DBA Virology
DBA Metabolic
DBA CNS
Others
R-No.
GEN
CHU
ARQ
Roche managed
Genentech managed
Chugai managed
ArQule opt-in
BTI
MEM
ISO
BioTie opt-in
Memory opt-in
Isotechnika opt-in
Status as of March 31, 2008
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Current R&D Model at Roche
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Disease Biology Areas (DBAs)
Idea
Market
DBA Oncology
DBLT
DBA Metabolic
DBLT
DBA CNS
DBLT
DBA Inflammatory
DBLT
DBA Viral
DBLT
• Integrate exploratory development
expertise in cross-functional
projects
• Deliver translational medicine
approaches to select high-quality
compounds for full development
• Apply and implement better-profiled
and differentiated molecules in latestage development
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Starting point: the Medical Needs in China
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Basic Medical care Needs for Chinese People
 Huge population (1.3 Billion)
 From 10% to 80% healthcare insurance coverage within 11th 5 Year State Plan
 3000 pharmaceutical companies produce generic and TCM based drugs
 Product Quality
New Medicine for Emerging Diseases
 20 % population will become affluent in 2015
 Cancer, Obesity and Type 2 Diabetes, Viral Diseases
 Alzheimer Disease, Cardio-vascular Diseases
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Change the way of doing drug discovery
Phase
III
Launched
MILESTONE
Phase
II
MILESTONE
MILESTONE
Development
Portfolio
Preparation
MILESTONE
Early
Clinical
Efficacy
MILESTONE
Early
Clinical
Safety
EIH
Enabling
MILESTONE
Lead
Optimization
MILESTONE
Lead
Dev.
MILESTONE
Lead
Identification
MILESTONE
MILESTONE
Target
Validation
MILESTONE
New
Medicine
Proposal
• One size fit all and do it all internally
• Extrapolation from test tubes to cells to animal to human
• Fix defects vs select the best
CN Academic
Diseases
Targets
MedSch
Hospital
Drug projects
Discovery Project
Teams
Leads
Assays
CRO
FTIM
POC
China Pharma
Ro/Rw
China Biotech
The purpose of drug discovery is to help our patients to live their lives and
improve the quality of their lives. Drug Discovery will lose its drive when we lost 7
our sight on patients.
RRDCC – A Novel Model for Drug Discovery
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Management Model that captures the Best of Both Worlds
Phase
III
MILESTONE
Early Development
Clinical Portfolio Phase
Efficacy Preparation II
MILESTONE
MILESTONE
MILESTONE
New
Early
Medicine Target
Lead
Lead
Lead
EIH
Clinical
Proposal ValidationIdentificationDev. Optimization
Enabling Safety
MILESTONE
MILESTONE
MILESTONE
MILESTONE
MILESTONE
MILESTONE
MILESTONE
Traditional Innovation Model:
• Comprehensive Setup
• Limited Flexibility
• Majority are fixed costs
(>90%)
External
research
Internal
research
Launched
RRDCC Model:
• Core Competencies
In-house
• Strong external Network
• >50% of Research work
conducted externally (at
CROs, Biotechs and
Hospitals
Management Model that captures the Best of Both Worlds:
All of the benefits of being a part
All of the advantages of being “Biotech-Like”
of a global R&D organization:
a. Information and Knowledge
b. Access to expertise
c. Common standards and best practices
d. Budget
a. Highly focused and in house expertise
b. Rapid decision making to drive quality
and value
c. Strong common sense of purpose
d. Avenue for growth expanding globally
e. Empowerment
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Reach out to China Basic Research Groups
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Our analysis lead to a conclusion that active drug discovery efforts in China are
focused on Oncology, Virology and Metabolic Disease
● Oncology
●
● Virology
● Metabolic
Disease
Bohai Zone
●●●●●
●
●
●
●●
Yangtze Delta● ●●
●●
●●●
● ●
●●
●●●
●
●
●●●Zhujiang
Delta
●
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Individualized Medicine
Responders
Non-Responders
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A drug does not work
in every patients
Efficacy rate ranging
from 25-80%
Adverse Drug Events
A
Now we look closer to
patient differentiation
=> Individualized Medicine
Responders
Molecular
Diagnosis
B
Non-Responders
C
Adverse Drug Events
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A growing Need for a range of Healthcare solutions
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Medical therapies
Consultation with the
medical community:
Patient focus
Diagnostics:
Predisposition
RMT presentation August 2004 Research activities
Self testing: Prevention
Prescriptions & consumption
of drugs: Reimbursement and
Product Distribution
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Topics:
r
1. The R&D Innovation Model
2. Botanical Drug / Traditional Chinese Medicine (TCM)
3. Quality Assurance
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The Botanical Drug / TCM in Drug Discovery
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6
4
2
0
Preclinical
Clinical
Phase I
Phase II
•PHY-X, Hemorrhagic Stroke,
PhytoCeutica (Originator)
•PLT-732, Lipoprotein Disorders,
Gene Smarth Health (Originator)
•QR-440, QR-443, QR-449,
Antiarthritic Drugs, Type 2 Diabetes,
Quigley Pharma (Originator)
Search from http://integrity.prous.com
Launched
PMI-001,
Rheumatoid
Arthritis,
Phytomedics
(Originator)
Not
Applicable
•Veregen , Sinecatechins, Treatment for
Genital Warts and Inflammatory etc.,
Polyphenon Pharma (Originator)
•NIX-0699, Multi-herbals, Sickle Cell
Anemia, National Inst. Pharm. Res. and
Develop. (Originator)
•THC-CBD, Cannabinoids Herbals,
Inflammatory Bowel Disease etc., Bayer GW
Pharmaceuticals (Originator)
•Piceid Polydatin Resveratrol-O3'-glucoside,
Antiinfectives, Shanghai Amadis BioTechnology etc.
•HMPL-002, Radiosensitizers, Hutchison13
China MediTech (Originator)
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Natural Products in Roche
Globally, Roche screening library (synthetic compounds) has passed the "magic"
line of 1 million compounds in October, 2007!
Locally in Chugai, Natural Products screening library (extracts and isolated
compounds) has passed the line of 100K samples in September, 2007
M yxobacteria
88
Purified
Compound
4,767
Actinomycetes
33,778
99,533 samples as of Sept.
2008
Fungi
60,900
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Exploration of TCM with Modern Science
and Technology
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Traditional Usage
Current Research
Drug Discovery
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TCM at RRDCC
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Natural product base drug discovery
-- Compound from natural product
-- Assay compound bio-activity
-- Hit generation and validated
-- Lead identification and optimization
-- Clinical Candidates Selection
Folk Medicine
-- TCM base drug discovery project
-- TCM effect on metabolic disease, such as Type 2 diabetes,
hyperlipidemia etc. (Collaboration research with Ruijin Hospital)
-- TCM for liver health, (Collaboration research with Shanghai
University of Traditional Chinese Medicine)
-- Evaluation of other programs on TCM research
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Topics:
r
1. The R&D Innovation Model
2. Botanical Drug / Traditional Chinese Medicine (TCM)
3. Quality Assurance
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What is the Quality Assurance?
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Represents the sum total of the organized
arrangements made with the objective of ensuring that all
products are of the quality required for their intended
use
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What is the scope of QA?
Focus Raw/Packing
Areas
Material
Management
GMP
Compliance
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Qualification
Finished
Cold chain
Validation
Goods
distribution
Management Management management
Desired Good supplier
outcome management
Establish Facilitate and Provide good To manage
GMP
organize the
service to
cold chain
to achieve the awareness in Q/V activities customer to distributors to
quality raw
the
in Tech
add value to ensure good
material
organization
Division
our product
product
quality.
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What is the global Roche standard of QA?
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Quality Policy of Roche Pharmaceuticals division
An effective and comprehensive Quality Assurance must be
designed to avoid faulty products and services thus ensuring
the effective protection of our customers and at the same
time protecting our company and its employees
from economic damage or legal consequences.
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Acknowledgement
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• RRDCC TEAM
• Lee Babiss, Head of Pharma Research
• Li Chen, Chief Scientific Officer
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