2. Agenda: Introduction to Pistoia
• Origins of Pistoia
– History
– Industry Drivers
– Technology Trends
• Scope and Operations of Pistoia
– Mission, Membership, Governance
– Projects and Deliverables
• Discussion: new Opportunities
3. Knowledge Management across R&D process
Preclinical studies Clinical studies
Discovery
Development
TARGET CHEMISTRY IND* PHASE I PHASE II PHASE III NDA** PHASE IV
DISCOVERY / PHARMA-
COLOGY
Search for Search for Regulatory Safety Efficacy Comparative Regulatory Continued
efficacious active review studies on studies on a studies on a review comparative
intervention substances *Investigational
healthy limited scale large number studies
points for a New Drug volunteers of patients
In vivo and in KNOWLEDGE &
disease or Application for 50–150
vitro 100–200
symptom permission to COST Registration,
toxicology & administer a new
persons patients
LEVEL market
efficacy drug to humans 500–5,000
introduction
studies patients
KNOWLEDGE &
**New Drug Application
COST Application for
LEVEL permission to market a
new drug
Approximately 10–15 years & $800m, from idea to marketable drug
3
4. Industry Drivers
Commercial Pressures
Cost, Time
25% of portfolio from collaborations
Commoditisation of services
Growing awareness of pre competitive, Open Collaboration and Open
Innovation e.g. ‘Innocentive’, Innovation brokers
Other industries have made these changes around collaboration:
Insurance, Telcom, Car
Mergers &
Some problems are too big for one company
Acquisitions
What would Life Science Industry look like in 2 years? Customer
Positioning Life Science groups to cope with larger Foundation Tools Sourcing/
changes. Its testing out the approach with alignment
High-Performance
Computing Platform for Calculated Properties
Collaborations/
Virtual Screening/Comp Chem DMPK Models
PC Flush ACES -
Chemical Available AZProasis
Clustering Chemicals/
Building
fRGS Blocks
R Group
Stripping Design
Library
Design
to mid term problems
Tools
CRO
DiGS DMPK
Database &
IBIS Explore & Query Tools
Test Service Test Make
SCOUT
Compound Reagent
& Sample Management
Registration
AZ Compound Database Chemical
ISAC & Query Tools Databases,
HTS Data Capture & Query,
Where is this heading?
Exploitation
Screening management ACMF Dispensary
Management Management
- HTS Plates Dispensary
- Cherry Picking Management
Virtual Pharma?
Public Private Initiatives
External
B2B integration requires more information/interface
standards Info
5. Example 3: Safety Front Loading
Life Science Knowledge Services
Hepatotox Knowledge Strategy
Public Reports In vitro Screens In vivo Screens Clinical Trial
Marts CRO Db Db
Tox Study Db Db Amos
& Services Content Db Db Amos
Marts
Adverse Event Reports Internal External Tox Reports Local Dbs
Books & File Servers
FDA Reports
Literature
User
Focussed Knowledge
Interfaces Local Environment
Services
Predictive
(SAR+)
models Species Why…
in in • Rapid access to Safety data
• Insight into chemical liability
Observation Causes Mechanism • Insight into mechanisms driving
• Assessment of screening cascade
Causes Affects/has
• Biomarkers discovery
Chemistry/Therapy • Prototype approach for other decisions.
6. Pistoia Background – How it all started
2007 2008 2009 Now
Informal Met in Create Pistoia as Not for Official 5 of top 10 Pharma as
meeting Pistoia profit company Launch members
Stanhope 20 members
Gate Pistoia
Curzon Domains Established
Lhasa Collaboration/project
Informal Collaborations meeting
Initial Meeting with GSK, AZ, Pfizer and Novartis –
outlined similar challenges and frustrations in the
IT/Informatics sector of Discovery
Pistoia Description
The primary purpose of the (Pistoia) Alliance
The advent of Web Services and Web2.0 allows for
decoupling of Proprietary data from technology is to streamline non-competitive elements
of the life science workflow by the
Publicly available structural and biological DBS allow
for a non-IP related analysis and as a scientific test specification of common standards, business
suite. terms, relationships and processes
Sponsorship from R&D IS heads within Life Science
industry •Goal –
to allow this framework to encompass/support most
pre-competitive work between the organisations
to support life science workflow prior to submission
to work with other Standards organisations
7. Pistoia Collaborative Working e.g. 3 parties working together
Past - Independence Emerging – Open Collaboration
X Y X Y More X Y
Z
overlap
We have all worked
separately on our Z Agreeing the pre competitive
space, allows for
Z environments and with
partners since we had collaboration on Standards
budget and people and Services
As Is - Sequence Services Vision - Sequence Services
X Y X Y
3rd
Party
Service Develop Services that allow
Companies replicate much
of the same functionality decommissioning of internal
and internally host external Sequences services at lower or
Sequences content to ensure high equivalent costs. Also allows
Z service levels and privacy
Z for future enhancement
costs to be shared
8. Open Collaboration - Process
Solution
Problem Demand Request Develop
Delivery
Collaborating
Companies
input
Decide how
to develop
together
Elaborate
Share Decide to Decide how Prepare 3rd 3rd party
Common
beyond AZ collaborate to develop party hosting
Needs
Prepare
tender/RFP
Open
Collaborations
Open opens Traditional
Collaboration opportunities Company
Interface Interface
earlier
9. Pistoia Standards Process
Governance & Working Pistoia
Operations Groups Community
Board of Software and
Directors submit
Service
Providers
propose,
Technical & comment
Standards Pharma/
Operational Teams BioTech/Agro
publish
Team
Not for
coordinate Profit
(e.g. IMI, EBI)
10. Pistoia Governance
Tom Flores GlaxoSmithKline Ramesh Durvasula BMS
• BoD Chris Waller Pfizer Alex Drijver ChemAxon
Martyn Wilkins AstraZeneca Frank Brown Accelrys
Patrick Warren Novartis Claus Stie Kallesøe Lundbeck
Arun Kumar InfoSys Bryn Roberts F. Hoffmann-La Roche
Jon McCarthy Symyx
Michael Stapleton CambridgeSoft
• Operational Team
Ashley George GlaxoSmithKline Treasurer
Kevin Hebbel Pfizer Programme Manager
Nick Lynch AstraZeneca President
Ramesh Durvasula BMS Communications
Michael Braxenthaler Roche External Liaison
• Technical Committee Chair
Vacant
Supported by Working Group Chairs and Operational Team
• Pistoia Company Itself
– Not for Profit Membership organisation (Incorporated in Delaware)
– Bye laws and IPR policy defined
– http://pistoiaalliance.org
12. Pistoia Domains – help group areas of interest and
deliver projects
Pistoia Groups – Pistoia Domain – high level External
as defined in byelaws grouping of WGs with common Groups
themes
outside of
Domain Allows governance across
a domain using Working Pistoia
Board of Steering Group chairs and
Directors Groups Technical Committee reps •Could join Pistoia
•Influence Pistoia
members
The main project delivery
Working
Working mechanism in Pistoia. All
•Influence through
other standards
Officers Groups
Groups standards will be groups and activities
(Operational delivered by WGs •Through
Collaboration on
Team) standards’ feasibility
studies
Provide experience into •Option for non
Pistoia Workings groups and executive positions
Technical Members
running Pistoia. in Pistoia could be
Define: formed
Committee •Requirements
•Technical Standards
•Service Standards
13. Pistoia Domains – focused on business
workflows/supply chains
Enabling
Knowledge and Information Services
Vocabulary
Visualisation
Workflow Application Integration
Others
Biology Chemistry Translational
Data Data Data
Services Services Services
14. Pistoia Alignment
Industry
Standards Members
Groups
Board of
Domain
Industry & Directors Technical
Science Domain Steering
Challenges Committee Classification
Groups
Enabling
Disease
Knowledge and Information Services
Vocabulary
Pharmacology
Visualisation
Application Integration Standards
DMPK
Workflow
Biology Chemistry Translational
Safety Others Data Data Working
Data
Services Services Services
Groups
15. Nature Reviews Drug Discovery 8,
701-708 (September 2009) |
doi:10.1038/nrd2944
Opinion: Lowering industry
firewalls: pre-competitive
informatics initiatives in drug
discovery
Michael R. Barnes1, Lee Harland2,
Steven M. Foord1, Matthew D. Hall1,
Ian Dix3, Scott Thomas4, Bryn I.
Williams-Jones5 & Cory R. Brouwer5
16. Discussion Points
• How can industry groups like Pistoia be of
benefit to groups in shaping your strategy?
• Is there an opportunity to take a commom
theme and work on it together?
– What projects would align well?
• What does it mean longer term for how these
works with groups like Pistoia?
18. Pistoia Domains –
focused on business workflows/supply chains
Enabling
Knowledge and Information Services
Vocabulary
Visualisation
Workflow Application Integration
Others
Biology Chemistry Translational
Data Data Data
Services Services Services
19. Pistoia Domains –
focused on business workflows/supply chains
Enabling
Knowledge and Information Services
Vocabulary
Visualisation
Workflow Application Integration
Others
Biology Chemistry Translational
Data Data Data
Services Services Services
20. A Cross Domain ‘Biology Portfolio’
No. Name Description Lead Status
Sequence Service, data & technology stds for access Ashley George Project starting soon
•2 Services to sequence services, including sequence,
genome, genetic, RNAi etc data & assays
(GSK) & TBD
Vocabulary Semantic standards and associated Ian Dix (AZ) & Project scoping
•3 Services* governance/change processes for
biological/pharmacological vocabularies
Lee Harland
(Pfizer)
Disease Proof of principle service evaluation for a I Dix (AZ), W Filsell Funding secured and
Knowledge push model for access to disease knowledge (Unilever), M project kick off 15th Oct.
•4 Services (SESL
proposal)
(gene-disease assertions) Braxenthaler (Roche), A
George (GSK) & I
Harrow (Pfizer)
Open IMI KM round 2 call. Development of service Mike Barnes (GSK) & IMI call. P-C remit is to
•5 Pharmacology
Space
and standards for access to publicly
available SAR content and associated
Bryn Williams-Jones
(Pfizer)
observe and ensure fit
of standards with other
analysis/summation tools P-C work packages.
Translational Service, data & technology standards TBD & TBD Idea. Not developed.
•6 Data
Management
required for cross pharma / academic /
institute collaborations involving samples &
‘omic data analysis (common in IMI)
Visualisation Service & application standards for pathway Lee Harland (Pfizer) & Idea. Not developed.
•7 & network visualisation in biology. TBD
•2 •4 •5 •6 •4
Target Lead Phase
Hit ID Lead ID Phase I Phase II
ID Opt III
•3 •7
21. Sequence Services
Industry agreed core services
• Challenge:
– Current internal platforms aging – expectation that refresh required in next 2-3 yrs
– Current internal platform difficult to extend to Next Gen Seq, personalised genomes, tumour
genome data mgmt, viz & analysis services.
• Opportunity:
– Adoption of public services & infrastructure
• Problem: Historic service non-functional requirements unacceptable
• Problem: Integration of internal content difficult
• Problem: Current services incomplete & usability needs reviewing
– Cross-pharma service specification for seq services
– Do we need a commercial service wrapper over public services?
• Current Situation in Pistoia:
– GSK spearheading initiative (assigned PM). AZ supporting
– Phase 1 proposal (Q409)
• Develop full set of non-functional rqmts by end of Sept09
• Develop broad areas of sequence services by end of Sept
• Contract 3rd party to host secure Ensembl, gene aliasing + example application hosting (Q4)
• Develop full set of requirements (Jan10) (ensuring scope will mean we are able to
decomission internal systems on completion (ie 2011))
– Phase 2 proposal (Q110 onwards, £?K, more companies involved
• Contract 3rd party to provide common services to all pharma engaged?
22. SESL:
Biomedical Knowledge Brokering
• Challenge:
– No single system for retrieving gene to disease relationships contained in both published & db
content.
– Need a ‘push model’ for biomedical knowledge access: the current model requires the consumer to
search 1000s of content sources.
• Opportunity:
– Pilot the a ‘push model’ for biomedical knowledge brokering.
– Engage multiple consumers, content providers and a single, public group to develop the necessary
infrastructure to explore the stds required for the model to work in production
• Current Situation in Pistoia:
– SESL proposal:
• Consumer companies: AZ, Pfizer, GSK, Roche, Unilever
• Hosting group: EBI
• Publishers: NPG (tbc), OUP, Elsevier & RSC.
• 12 mth project, £200K direct funding ( + PM & Architecture support)
• Deliverables: Stds required to make such a model production, Focused engagement with key
content suppliers in moving to such a push model for content.
– SESL timelines:
• Funding agreed in Sept
• Kick off meeting 15th Oct, EBI
• Initiate in Oct09.
23. Open Pharmacology Space
Screening Knowledge Services
• Challenge:
– No single system (or standards) for accessing target – compound relationships contained in both
published & db content.
• Opportunity:
– Build open access public domain resources to support Drug Discovery
– Use IMI as a vehicle to integrate public domain biology and chemistry data
• Two Major Work Streams:
– WS1: Development of an OPS service layer and resource integration
– WS2: Development of exemplar work packages
– Project Initiation for WS2 will be staggered to allow implementation of WS1
– Companies involved:
– Lead by Pfizer & GSK
– AZ, BI, Roche, Lundbeck, Esteve, Merck-Serono
– 10M Euro EU + 10M Euro in-kind from Pharma
– 3 years, Q2 2010.
• Current Situation in Pistoia:
• Pistoia – ensuring uniform standards with other Pistoia projects
24. Vocabularies
A single language
• Issue: Plethora of vocabulary ‘standards’ in biology/ pharmacology.
• Goal: Agreeing a single open vocabulary standard for the Pharma information supply chain
along with the infrastructure and processes required to keep it current.
• Opportunity: OBO Foundry – a long standing public group of ontologists/scientists who
have recognised the need for the controlled use of language to describe biology.
– Coordinating extensive vocabulary assets as well as running/developing processes to
ensure managed change.
– Key issues: Funding, Focus, Quality, Coverage, Accreditation
• Current Situation:
– Pistoia reps have met 4 times with OBO board, including 1 day f-f.
– AZ/Pfizer leading Pistoia WG, documenting v0.1 Pharma service rqmnts re vocabs.
– OBO foundry documenting 5 yr plans & objectives
– Nov/Dec 2009: Closed workshop involving OBO board, pharma & key information supply
chain companies (KM, publishers & aggregators), key public groups to discuss sustainable
business models for pre-competitive vocabulary services.
– 2010: Expect to pilot model involving selected vocabularies, OBO & vocab suppliers.
• Presuming pilot success, in 2010 will need to secure PPP funding for:
– Pre-clinical vocabulary coordination
– Pre-clinical vocabulary curation services
– Vocabulary infrastructure services
25. Biomedical Knowledge Brokering
•Multiple
•Consumers
•4 •5 •5 •4 •7
•Target •Compound •Disease •Network •Knowledge
•‘Consumer’ •Dossier •Dossier •Dossier •Viz •Applications
•Firewall
•Service Layer •Std Public •Common
•Open •Assertion & Meta Data Mgmt
•3
•Vocabularies •Service
•Stds •Transform / Translate •Business Broker
•Integrator •Rules
•Supplier
•Content
•Firewall
•Suppliers
•2 •Db 2
•6 •Db 4 •Effort required to
fit DBs to service
•Corpus 1 layer
•Db 3 •Corpus 5
