Transcript Roadmapping as a Planning Tool to Assess r Bob McCarthy, Ph.D.

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Roadmapping as a Planning Tool to Assess
Strategies in a Rapidly Changing Market
Bob McCarthy, Ph.D.
Director, Strategic Market Planning
Roche Molecular Biochemicals
Phone: 317-576-7475, Fax: 317-576-7317
e mail: [email protected]
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“Commentators have sought to set the
“We used to think the
future was in the stars.
Now we know its in our
genes.”
James Watson, Visions (1997)
project in a historical context by
likening to the..Manhattan Project and
the moon shot...Rather, the Human
Genome project aims to produce
biology’s periodic table- not 100
elements, but 100,000 genes…. The
challenge ahead is to turn the periodic
table produced by the era of structural
genomics into tools for the coming era
of functional genomics”
Eric S. Lander, Science 274:536 (1996)
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“We used to think the
future was in the stars.
Now we know its in our
genes.”
James Watson, Visions (1997)
“There’s a gene rush on out there. In
the next three years or so, the entire
human genome will be known, and
all the interesting targets claimed.
Companies that don’t invest and
secure rights to disease-modifying
gene discoveries will be shut out.”
J Hartwig,WSJ 24 Sept. 1998
Scale of Human Genome Project
World
5.8
billion people
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Nucleus
23 chromosomes
3 billion base pairs
6 billion bases
USA
270 million
1 Chromosome
200 million bp
400 million bases
Indiana
5.8 million
Marion County
800 K
Marion County
Genes within
chromosome
1.5 to 2000 K bases
Analogy does not Reflect Complexity of Genome r
• Every cell contains entire genome
• Only 3% of genome codes for protein
• Cells function determined by proteins produced
DNA
mRNA
Protein
DNA
Blueprint
messenger RNA
protein synthesized
Extract portion of plans
Protein function
Structural Genomics: analysis of the blueprint = structure of DNA in the
genome
Functional Genomics: analysis of the work carried out by subcontractors =
biology
Cell Circuitry:Implications for Functional Genomics
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Ligands
Ion channels
DNA
mRNA
Protein
Pathways
Protein
Most cells are unique (differentiated state), live in communities
(tissue and organs) and have sensors to react to specific changes in
the environment (e.g., ligand receptor interactions, ion channels);
the appropriate response is mediated by pathways of complex
proteins (cellular circuitry)
Cell Circuitry:Implications for Functional Genomics
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Ligands
Ion channels
DNA
mRNA
Protein
Pathways
Protein
• Disease occurs when proteins in key pathways malfunction or
arechanged by mutation (e.g., cancer), this leads to an abnormal
state and these changes are detected by appearance of clinical
symptoms
• Goal of functional genomics is to first identify and analyze
the cellular circuits that control the cellular response, identify
changes in disease, then manipulate this circuitry with drugs
to control the disease
Proteins Key Focal Point for Functional Genomics r
A
A
B
C
B C
Key
Biological
Activity
A, B, and C are unique proteins, when aggregated into a complex, generate key
biological activity
•
•
Key proteins can be identified by an increasing number
of methods
The ultimate goal in genomic biology is to identify all
the proteins that participate in key biological pathways
Proteins Key Focal Point for Functional Genomics r
A
A
B
C
B C
Key
Biological
Activity
A, B, and C are unique proteins, when aggregated into a complex, generate key
biological activity
“It is important to note that the target validation process may determine that any
number of genes identified as gene targets are not appropriate as therapeutic
targets. However, during the process of target validation new genes
functionally related to the original gene targets may be identified as useful for
investigation as new prospective therapeutic targets.”
J.W. Hawkins, Genomics: A Brave New World for Therapeutics
Development, Drug & Market Dev. 9 (3) p. 72 (1998)
Pre-Genomic
Genomic Era
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DNA
Universal Code
of Life
E. coli
S.
cerevisiae
S.
cerevisiae
E. coli
Paradigm Shift: Biological information and function strongly conserved
Regulatory
1970
1975
1980
Gene Therapy
Gudielines
1985
1990
SKB-HGS alliance
Combinatorial chemistry
1995
2000
Abbott-Genset
PE/Ventner collaboration
S cerev. Seq. 12 Mb.icrorg. Seq
6 microrg. seq
Pace for Development is Accelerating
NIH target for HGP
PE/Ventner target for HGP
Pharmacogenomics
DNA Microchip, H. Infl 1.8 M
Yeaset chromo. 3 3.2 Mb
HGP initiated
Humulin marketed
Two hybrid system in yeast
Automated DNA seq.
PCR, phage display
Lambda DNA seq 48 Kb
Genentech IPO
Hybritech formed
DNA seq. Improved
Somatostatin produced
Genentech fromed
DNA SV40 seq 5 Kb
Technology/
Milestones
Guidelines relaxed
Guidelines relaxed
Asilomar Conf.
Funding/
Commerical
Development
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2005
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45.0%
90
50.0%
Pharmaceutical
Growth Knowledge
Dependent
70
60
40.0%
35.0%
30.0%
50
25.0%
40
20.0%
30
15.0%
20
500 drug targets
R&D as % Sales
U.S. Sales $ billions
80
10.0%
10
3000-10,000
drug targets
5.0%
Innovations
Genetic
Engineering
NSAID’s
Biotech Drugs
H-2 Antgonists
Beta blockers
New Therapeutic Cycles
Lipid Lowerers
ACE inhibitors
2020
Cell pharmacology/
molecular biology
Enzymes
Receptors
2015
2010
2005
2000
1995
1990
1985
1980
1975
0.0%
1970
0
Chronic
degenernative
disease associated
with aging,
inflammation, & cancer
Changes in the Pharmaceutical Industry r
Vertical industry 1950-1970’s
•
Expertise kept in house
•
Drug development based on serendipity
Biotech era 1980’s
Big Pharma
•
Collaborations established to protect existing
markets and expand into new markets
•
Drug development move towards applying fruits of
biotechnology
Genomic era 1990’s
•
Collaborations essential to gain knowledge about
key biological pathways
•
Drug development restructured to gain knowledge
faster than competition
Changes in the Pharmaceutical Industry r
Gene
Hunters
Big Pharma
Testing
Services
RB
Reagent
RB
Reag/Inst.
Collaborations
based on focus
& speed
Anal.
Instrum.
Combinat.
Chem.
Chem.
Company
Assemblers
Animal/clinical studies
Testing drug libraries
Regulat. & reimbursement
Sales and marketing
Tier 1
I.d. biological targets
Provide chem. libraries
Toxicology testing
Tier 2
Special reagent/instrum.
Platforms increase thruput
Andy Grove’s Strategic Inflection Point
Business goes to
new heights
Inflection
Point
1993
2010?
Genomic Era
Business
Declines
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“Let’s not mince words:
A strategic inflection point
can be deadly when
unattended to. Companies
that begin a decline as a
result of its changes
rarely recover their
previous greatness.” (p. 4,
Only the Paranoid
Survive)
Composition of Roadmap Teams
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Team Composition
Team Composition
R&D, Marketing (central)
German & U.S. Biounit (country)
Roadmap
Working
Team
Internal
Molecular biologists
Proteomics experts
Cell biologists
Developmental biologists
Bioinformatics experts
Roadmap
Expert
Group
InternalExternal.
Functions
Recommend & approve experts
Review format of surveys
Review raw & condensed data
Input conclusions into roadmap
Functions
Respond to surveys
Review drafts of roadmap
Participate in discussion groups
Provide updated knowledge
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Roadmap Process
Market Trends
M1
M2
RN1
Root Needs
RN2
RN3
Technology
T1
T2
T3
T4
Competitive
Assessment
CA
CA
CA
CA
Technology
Projects
Planning
P1
RN?
T?
P3
P2
P4
Time
Years
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M1
•
Biological information restricted to
specific applications/model systems
•
Biological studies based on
phenomenology
•
M2
•
Ultimate goal is to understand
function of biological molecules in
their proper context
•
Assembling biological information
infrastructure, data mining to focus
on biological and/or disease models
•
Developing integrated knowledge of
biological pathways and networks in
context of cell and organism
•
Performing detailed structurefunction studies in context of
biological disease model
•
Goal is to understand differential
gene expression in disease states or
biological model systems
•
Saturation mutagenesis to evaluate
function of specific molecules
Shotgun mutation methods screened
for gross observable changes
Root
Needs
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RN1
 Manipulate and access relevant biological data
just in time
RN2
 Rapid universal system to detect modification
of macromolecules
RN3
 Detect changes in biological activity within a
pathway
RN4
 Protein expression systems which allow rapid
production of recombinant protein with
appropriate modifications
RN5
 Improved methods to detect differential gene
expression
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Technolog
y
Weight
Importance Technology 1 Technology 2 Technology 3
Protein Expression
Systems
Customer Needs
Total Score
Technology Characteristics
Technological Maturity
Match with internal skills
Technology ROI
Total Score
Comments on strategic fit, market opportunity, competitive position
Conclusions & Recommendations
Comments
Technolog
y
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Technology characteristics
• Pacing: potential to change entire basis of competition
• Key: critical to competitive success, differentiation
• Base: necessary/essential, little competitive advantage
Technology maturity
• Embryonic: visionary, scientific tumult & contradiction
• Growth: vision sharpened, realistic forecasts
• Mature: advances slow down, technology shared
• Aging: only small incremental changes in technology
Technology return on investment
• Amount of $ spent to gain competitive position (H, M, L)
Match with internal skills = synergies
Competitive
Assess.
Preparation of Technology Brief, 1
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Description & state of technology

Characteristics, maturity, ROI, internal synergies
Rationale for technology investment: gaps, unmet needs, etc...
Competitive advantage: ability to influence environment
Dominant
Powerful leader by technology commitment & reputation (dominant
design?), others always catching up
Strong
Able to set take independent action, set new technological direction;
committed to support development and distinguished from competitors by
this action
Favorable
Can sustain technological competitiveness and can exploit technology to
improve position, not leader but focus on niche
Tenable
Catch up mode, unable to set independent course, can maintain
competitiveness but weak at differentiation
Weak
Declining quality of technical output, short term/firefighting
Competitive
Assess.
Preparation of Technology Brief, 2
• Sources of competitive advantage: intellectual property,
know how, etc...
• Competitor profiles by company




Intellectual capital
Breadth of products, number of new introductions
Evaluation of past and future strategy
Response against introduction of technology
• Recommendations, next steps
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Projects
Project Proposal for Investment
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• Fit with business strategy (excellent to poor)
• Inventive merit, strategic importance to business (high to low)
 Improves competitive position?
 Applicable to more than one business?
 Provides foundation for new business?
• Reward: NPV’s: worst, base, and best case
• Competitive impact of technology
 Technology characteristics and maturity
• Uncertainty
 Probability of technical success (0.1-0.9)
 Probability of commercial success (0.1-0.9)
 Probability of overall success (0.1-0.9)
Projects
Project Proposal for Investment, 2
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• Implementation plan
 Proposal for resources and competencies required to complete the
project
 Propose timing for technology reviews: agreement on specifics that
drives the review (e.g, time, dollars, achievements, etc…)
• Risk
 R&D costs to first milestone and costs to completion (range if
appropriate)
 Time to first milestone and to completion (range if appropriate)
 Capital and/or marketing investment required to exploit technical
success (range if appropriate)
Technology Portfolio Maps
NPV
Long
Time to Launch
Zero
Builds on competency, improves position
Builds new competency & extends business
Builds new competency & new business
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Benefits of Roadmaps
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• Cross-functional understanding of strategic issues
• Sensitization to following
• Technology trends
• Gaps in technology in meeting needs
• Competitive position for technology
• Easily understood process to communicate issues regarding
allocation of resources
• Proposal that includes management of projects through
structured technology review
• Learning that can be applied when evaluating future
technology opportunities