Transcript Christine Deuschel - Pharma

Communicating Project and
Portfolio Risks and Rewards
8th Annual Project & Portfolio Management, Nov 2012
Debiopharm SA C. Deuschel
V.P. Project and Portfolio Management
© Debiopharm Group 2012
Drug development efficiency!
Cost per New molecular Entity
PCAST, Report to the President, Sept. 2012
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R&D Model to successfully discover and
develop a single new molecular entity
Target to hit
Hit to lead
Lead optimization
Preclinal
Phase I
Phase II
Phase III
Submission
to launch
Launch
Probability of successful transition from one stage to the next
80%
75%
85%
69%
54%
34%
70%
91%
24.3
19.4
14.6
12.4
8.6
4.6
1.6
1.1
1
Number of molecules per phase for one launch
 Capitalized cost for one NME launched: $ 1.8 billion
Source: Nature Review_Drug discovery_Volume 9_March 2010 : How to improve R&D Productivity: the pharmaceutical industry’s grand challenge?
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Attrition rates: Main reasons

Reason why compounds undergo attrition and how this has
changed over time
Source: Nature Reviews Drug Discovery 3, 711-716 (August 2004)) Can the pharmaceutical industry reduce attrition rates?
Copyright Nature
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Drug development challenges

Drug development is about the acquisition of information to
reduce the risks and increase the value of the compound
 Studies/experiments are designed to answer questions related to
the compound efficacy/safety.
 There is a risk that any experiment will fail.

One of the main challenges of drug development is to reduce
the risk of failures


Or to shift attrition to cheaper phases
Risk management is key to identify critical information
Value
COST
RISKS
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POS
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Debiopharm Group™

Over 30 year of experience in drug development in collaboration
with pharma

Two major marketed products

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
Eloxatin ® Gold standard & blockbuster

Decapetyl ® sustained release formulation (1, 3, 6 months)
About us

Based in Switzerland

Family owned

Financial independent

Team: staff over 300

Extensive international network of partners: over 400
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Business model: a bridge to develop therapies
Discovery
Academic institutions
Biotech
Start-up
Pharma
Inlicensing
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DEBIOPHARM GROUP™
Market
Fully funded
development
of therapies
Pharma
Outlicensing
© Debiopharm Group 2012
Our core business: Opportunity & risk management
7.5%
Target to hit
Cummulative probability of success up to launch
Hit to lead
Lead optimization
preclinal Phase I Phase II Phase III
Submission
Launch
from molecule
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to drug approval
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Key Expertise from Search to Registration
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Debiopharm Group’s achievements

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Two development programmes have led to…
…Five products currently commercialised internationally:

Eloxatin® / Elplat® / Dacotin® / Dacplat®

Decapeptyl® / Trelstar® / Pamorelin® 1-month

Decapeptyl® / Trelstar® / Pamorelin® 3-month

Decapeptyl® / Trelstar® / Pamorelin ® 6-month

Moapar® / Salvacyl® 3-month
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Marketed
Phase III
Phase II
Phase I
Preclinical
Debiopharm Group™: marketed & late clinical
Eloxatin® / Elplat® / Dacotin® / Dacplat® - Colorectal cancer
Decapeptyl® / Trelstar® / Pamorelin® (1, 3, 6M) - GnRH agonist, Prostate cancer
Moapar® / Salvacyl® - GnRH agonist, severe sexual deviation
G-SOX (oxaliplatin) - Advanced metastatic gastric cancer (Yakult, Japan)
Debio 025 - HCV,Cyclophilin inhibitor (worldwide licence to Novartis except Japan)
Debio 8206 CPP - GnRH agonist, Central Precocious Puberty
Debio 8206 SC - GnRH agonist, Prostate cancer
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Marketed
Phase III
Phase II
Phase I
Preclinical
Debiopharm Group™ Pipeline: Early development
Debio 025 - HCV , Cyclophilin inhibitor (Japan)
Debio 1143 - Oncology, SMAC mimetic (pro-apoptotic)
Debio 0932 - Oncology, Hsp90 inhibitor
Debio 1036 - Autoimmune diseases, undisclosed target
Debio 1144 - Oncology, tyrosine kinases inhibitor
Debio 0617 - Oncology, undisclosed target
Debio 0930 - Metabolic diseases, AMPK activator
Debio 0929 - Oncology, undisclosed target
Debio 0826 - Oncology, undisclosed target
Debio 1141 - Urothelial carcinoma, siRNA
Debio 1142 - Oncology, undisclosed target
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Global development plan

Risks and opportunity management shall be fully integrated in
the global development plan
Target Product Profile
Risks
Cost
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Time
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Opportunity Management

Risk
assessment
tools
Culture
Value
creation
Assess all the key
assumptions made
for the drug
development
Keep the risk
assessment
“emotion free”
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Project risk management approach and tools
Strategic Decisions
Decision Tree
Probability of Success meetings
Preclinical
Phase I
Phase II
Phase III
Filing
Market
Risk management action plan and monitoring
Risk landscape Impact /Probability
Mitigation /Contingency
Systematic Risk approach
“RADAR”
Operational Decisions
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Risk assessment tool: Risks Landscape

GOAL
 Identify relevant risks of a project
 Assess impact and probability
 Establish Mitigations plan (if
necessary)

Neutralized examples

Risk # 1 Clinical: slow patient
inclusion will dramatically delay
human POC
 Mitigation: increase trial centers

Risk#2 Business: Fierce competition
at the same level of development
 Mitigation: monitor advancement
of competition and verify
competitive advantage (USP)
Mitigation Plan
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Risk assessment tool: Consistent and
Systematic approach RADAR Science
Radar
A systematic approach: project risks
are categorized into individual criteria
which are scored
Radar example: categories for
preclinical project: Science

All regulatory requirements are covered
in a questionnaire (Pharmacodynamics,
toxicology, reprotoxicity,…)
API
100.00%
Kinetics
Process Chemistry
50.00%
Metabolism
API supply

Additional crucial criterias for the project
development were added (formulation, API
supply, …)
0.00%
Reprotoxicity
Formulation
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
 All these data provide a factual
analysis of the strength and weakness
of the product
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Safety Pharmaco
Pharmacodynamics
Genetic tox
General Toxicology
Science
© Debiopharm Group 2012
Systematic approach RADAR allows follow up
of project
API
API
100.00%
100.00%
Kinetics
Process Chemistry
Kinetics
50.00%
Metabolism
Metabolism
API supply
Process Chemistry
50.00%
0.00%
0.00%
Reprotoxicity
Reprotoxicity
Formulation
Formulation
5
5
Safety Pharmaco
Safety Pharmaco
Pharmacodynamics
Genetic tox
API supply
Pharmacodynamics
Genetic tox
General Toxicology
General Toxicology
Situation February 2012
Situation February 2011
API
100.00%
Kinetics
Process Chemistry
50.00%
Metabolism
API supply
0.00%
Reprotoxicity
Formulation
5
Safety Pharmaco
Pharmacodynamics
Genetic tox
General Toxicology
Evolution 2011/2012
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Systematic approach RADAR Economy
Competition
10.0
Example of RADAR categories
for preclinical project: Economy
8.0
COGs
This questionnaire cover all topics
impacting the economical viability
of the project:
• Competition
• Market
• Development cost
• IP protection (when launched)
•…
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Market.
4.0
2.0
0.0
IP
Economy
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6.0
Dev. Cost
Est. Sales
© Debiopharm Group 2012
Risks analysis: Systematic approach RADAR:
Economy
Competition
Competition
10.0
10.0
8.0
8.0
COGs
6.0
COGs
Market.
6.0
Market.
4.0
4.0
2.0
2.0
0.0
0.0
IP
IP
Dev. Cost
Dev. Cost
Est. Sales
Est. Sales
Situation February 2012
Situation February 2011
Competition
10.0
8.0
COGs
6.0
Market.
4.0
2.0
0.0
IP
Dev. Cost
Est. Sales
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Evolution 2011/2012
© Debiopharm Group 2012
Risk assessment tool: Decision tree
Attrition rates Phase I to market approval
30.00%

Probability of Success
 Decision tree meetings are
performed at each project gate
(Go/NoGo next project gate)
 Outside expertise to ensure
objectivity

Comparison with benchmark
 There is no unique benchmark!
25.00%

20.00%
15.00%
10.00%
Is the PoS of the project higher
or lower than the benchmark? If
yes, why?
5.00%
0.00%
2002
(Buchanan
2002)
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period 81-86 period 87(DiM asi
92 (DiM asi
2001)
2001)
period 9304 (Parexel
2011/2012
p221)
period 9304 (Parexel
2011/2012,
p270)
2004 (Tufts
oct 2010,
vol12, n° 5)
2004 (Kola 2011 (Parexel period 95-10
et al 2004)
2011/2012,
(Paul et al,
p265)
2010)
average
© Debiopharm Group 2012
Risks Analysis Overview per project
API
100.00%
Kinetics
Process Chemistry
50.00%
Metabolism
API supply
0.00%
Reprotoxicity
Formulation
5
Safety Pharmaco
Pharmacodynamics
Genetic tox
General Toxicology
Science
Competition
10.0
8.0
COGs
6.0
Market.
4.0
2.0
0.0
IP
Risks Landscape
• Risk 1:
• Mitigation
• Risk 2:
• Mitigation
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Probability of Success
Reflecting current development stage
Dev. Cost
Est. Sales
Economy
Radar
• Science
• Economy
© Debiopharm Group 2012
Opportunity Management
Risk
assessment
tools
Assess all the key
assumptions made
for the drug
development
Keep the risk
assessment
emotional free
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Culture
Value
creation
Give confidence to
everyone to ask right
questions
Strong involvement of
project team
Integrate opportunity
and risk management
into project lifecycle
© Debiopharm Group 2012
Drug development
Stage Gate methodology
Preclinical Phase
Phase 1
Phase 2
Phase 3
Go TOX
GoFIM
Go POC
GoPIII
Decision to
initiate
development
project
Decision
to
proceed
in man
Decision
to enter
efficacy
trials
Decision
to enter
pivotal
trials
Go
Filing
Decision
to
register
Level 1 (L1) project gate milestones
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Differentiation of the level of responsabilities
L1
Project
Gate
risks
L1: Top management needs a clear
overview on the value creation
milestones
L2
Critical
risks network activities
L2: Project team is responsible for
reaching the objectives/deliverables
associated with the critical activities
L3
risks
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Detailed tasks
L3: Team members are accountable
for the detailed tasks to complete
the critical network activities
Risk assessment
Relevant Go/NoGo and “what if scenarios” are discussed at each level© Debiopharm Group 2012
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Opportunity Management
Risk
assessment
tools
Assess all the key
assumptions made
for the drug
development
Keep the risk
assessment
emotional free
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Culture
Give confidence to
everyone to ask
right questions
Integrate
opportunity and
risk management
into project
lifecycle
Value
creation
Report the relevant
questions to the top
management
Ensure
approximately right
decisions rather than
precisely wrong
decisions
© Debiopharm Group 2012
Project Review Committee
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Project Review
Committee
Decision/feedback
Reporting and escalation

Top Management
Project Team
Project Review committee responsabilities
 Go/No Go for next phase
 Decisions on Portfolio composition and prioritization
 Risk management is key to identify critical information
© Debiopharm Group 2012
Preparation for the Project review Committee
Critical information for each L1 gate
Early
Project
•…
•…
•…
GoTox.
•…
•…
•…
GoFIM
•…
•…
•…
GoPOC
•…
•…
•…
Clear decision criteria
Risk analysis
of
Go/NoGo criteria
for decision making
Recommendation
of the project team
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Project review committee
© Debiopharm Group 2012
PoS of projects within the portfolio

Portfolio analysis --- prioritization…
Debiopharm Portfolio NCE-Neutralized
80%
Probability of Success (POS) %
70%
60%
Debio XXXX
50%
2028
40%
Debio XXXX
30%
2028
Debio XXXX
Debio XXXX
Debio XXXX
2028
20%
2029
10%
2029
0%
-9
-7
-5
-3
-1
1
3
5
7
9
11
Time to market and Data exclusivity
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
External diameter represents the estimated peak sales

Internal diameter represents the cost of development
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© Debiopharm Group 2012
Value creation
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
Project risks are categorized into individual criterias which are
scored

Project and portfolio metrics are based on risk and opportunity
management

3 level of responsibilities (L1, L2, L3) are established to
optimize project monitoring and management

Opportunity and risk management needs to be integrated into
project lifecycle

Transparent view of risks and opportunities is shared through
the whole organization

Focus on relevant risks which are escaladed to the top
management

Check that the warning about the relevant risks and their
associated opportunities are well understood by the top
management
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© Debiopharm Group 2012
Change behavior toward risk :
Look for opportunities
Risk
Management
(Anticipation)
Issue Management
(Firefighting)
Today
Tomorrow
Risk Management
(Anticipation)
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Issue
Management
(Firefighting)
Improve profit
expectation

More anticipation… less problem resolution

Be opportunistic focus by taking more acceptable risks to
improve profit expectation
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Effort/
Cost
© Debiopharm Group 2012
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© Debiopharm Group 2012
Special thanks to

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Pierre Daram - Project Manager
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© Debiopharm Group 2012