© 2009 IBM Corporation German CDISC User Group Meeting IBM Intro September 22 nd, 2009.

© 2009 IBM Corporation

German CDISC User Group Meeting

IBM Intro September 22nd, 2009


IBM‘s R&D Team @German CDISC User Group

Peter LEISTER

IBM Global Business Services

Head of Pharma & Life

Sciences R&D Group

IBM Deutschland GmbH

Jens WIENTGES


Pharma & Life Sciences R&D

Group


Markus STOLL



Group


Ute LADECK



Group


3 © 2009 IBM CorporationIBM

Creating Pharmaceutical Break-Throughs: - We believe there is no one magic bullet …

It takes a variety of data sources, ‘best of breed’ tools & technologies to really create break-throughs

… but one open & harmonized data-standard would help

4 © 2009 IBM CorporationIBM

A real life example taken from PoC on Hepatotoxic AE & CYP450 Marker

Med. Pub. As PDF-files

Genomic data

Combining the search with Genomic data of the patients finally led to signal

Study 0816

Clinical Data Management

Coding

Query Management

Clinical Trial Management

Statistical Programming

Electronic Data

Capture

Patient Diaries

Registries

Safety

Lab Data

Clinical Research

Organizations

Clinical Data Management

Coding

Query Management

Clinical Trial Management

Statistical Programming

Electronic Data

Capture

Patient Diaries

Registries

Safety

Lab Data

Clinical Research

Organizations

Oracle LSH

Study 0815

Study 4712

Pre-clin studStudy 4711

Study 4712

SAS, PL/SQL

This now needs to be confirmed by a statistician in a compliant manner, but

hopefully a marker was found

DDQB

Spotfire


Life Sciences Pharma R&D - Services Portfolio

Focused R&D services– R&D Strategy & Process Optimization

– Clinical Data Integration & Aggregation (CDA)

– Clinical Trial (CTMS) and Investigator Relationship Management (IRTM)

– Electronic Data Capture (EDC)

– Integrated Project Resource and Portfolio Management (IPRM)

– Solutions for Compliance in Regulated Environments (Score) (e.g. Submission management, content management, clinical portal, …)

– Chemsearch Patent Data-Base

– Biobank Support & Pharmacogenomics (PGx)

– Data Driven Drug discovery (4D) Modelling and Simulation

Data Mining, Web Mining, Text Mining, Target finder

Other services applicable to R&D– Pervasive computing

– Petaflop and Grid Computing

– Process Analytical Technologies (PAT)

– Training & Knowledge Management

– Computer System Validation (CSV)


IBM’s Deep Industry Knowledge – the R&D Group Embedded in the Larger Picture

IBM’s consulting capabilities are built around specific strategic and operational challenges facing pharmaceutical companies in the evolving global marketplace. With more than 1000 pharmaceutical industry specialists around the world, IBM Life Sciences consulting practice is part of the world’s largest consultant services organization with significant depth and breadth of industry experience.

World-Wide Industry Specialist Resources:Pharmaceutical Practice consists of > 2.000 industry specialists worldwide

Manufacturing Operations Materials & Product Flow

Management New Product/Package Introductions

in Operations Clinical Supply Chain Process Contract Manufacturing Regulatory Compliance & Validation Supply Chain Information

Management

Business Planning & Development Business Plan Development Strategy Valuation Strategy & Planning Competitive Positioning Due Diligence Mergers & Acquisitions

Financial Management Shared Services Performance Management Financial System Management &

Reporting

Information Management Management Information Systems Knowledge & Information

Management Structured Product Labeling Drug submission

Sales Account Management Health Care & Government Contract

Management Sales Operations Improvement Field Sales Management Sales Force Automation

Marketing Product Marketing Reimbursement Strategy DTC Strategy Rx-to-OTC switching Strategic Pricing

Research & Development Discovery/Pre-Clinical Clinical Development Clinical Data Aggregation Regulatory Compliance Pharmacovigilance Process Optimization


IBM is a values-based enterprise of individuals

who create and apply technology to make the world

work better.

Today, about 400,000 IBMers around the world invent and

integrate hardware, software and services to help

forward-thinking enterprises, institutions and people

everywhere succeed on a smarter planet.

In a Word, IBM Stands for PROGRESS


IBM - Major Businesses

Global Technology

Services

Global Business Services

Systems and

Technology

Software

S&D and

Research

Provides outsourced IT infrastructure services and business process services

Provides professional services and application outsourcing services

Provides advanced computing, storage and semiconductor technology and products

Provides middleware that enables clients to integrate systems, processes and applications, as well as computer operating systems

Our Sales and Research, Development and Intellectual Property organizations provide a wide spectrum of client support and additional value

GlobalFinancing

Provides financing solutions that can be customized to address specific IT needs, from competitive rates to flexible payment plans and loans


A Leader in Technology

IBM maintains the world’s largest private-sector research arm. In 2008, for the 16th consecutive year, IBM was issued more U.S. patents (4,186) than any other company.

In the last six years IBM has aggressively complemented an investment of $35 billion in research and development with more than

100 acquisitions of hardware, services and software companies.


Gene expression analysis

= j -(j-1)j-1 jNjk(j,k,Ne,Ng,) ~ (Ng

k )(Ne

j )k(1-Ng-k

[1-(1+j ) ]-1 kk Ne-j p = 1-exp{-Njk}

microarray 1microarray 2microarray 3

microarray N e

ge

ne

1

ge

ne

2

ge

ne

3

ge

ne

Ng....................

pattern

Genes@ W ork

Genes@Work

A software environment for gene expression analysis and

machine learning

Other Selected Relevant Papers:Mateos, Dopazo, Jansen, Tu, Gerstein and Stolovitzky, “Systematic learning of gene functional classes from DNA array expression data by using multilayer perceptrons”, Genome Research 12, 1703-15 (2002). Califano, Stolovitzky and Tu, “Analysis of Gene Expression Microarrays for Phenotype Classification” , Proceedings of the 8th Annual Intelligent Systems in Molecular Biology (ISMB) 2000; 8:75-85 (2000).

Lepre, Rice, Tu, and Stolovitzky, “Genes@Work: an efficient algorithm for pattern discovery and multivariate feature selection in gene expression data”, Bioinformatics 20(7):1033-44 (2004).

http://www.research.ibm.com/FunGen/FGDownloads.htm


Data Mining

Simulation

Robustness, sparceness

Prediction andexperimental

design

ReverseEngineering

Malate Oxaloacetate Citrate

Ketoglutarate


Tricarboxylic Acid Cycle

Fumarate

Fumarate Isocitrate

Succinate Succinyl-CoA

Glyoxylate

Acetyl-CoACoA

Acetyl-CoACoA

MLS1MDH2 CIT2

ICL2

Glyoxylate Cycle


Ketoglutarate


Tricarboxylic Acid CycleTricarboxylic Acid Cycle

Fumarate

Fumarate Isocitrate

Succinate Succinyl-CoA

Glyoxylate

Acetyl-CoACoA

Acetyl-CoACoA

MLS1MDH2 CIT2

ICL2

Glyoxylate Cycle

Functional Genomics & Systems Biology GroupThe DREAM Project

DREAM (Dialogue on Reverse Engineering Analysis and Methods) aspires to collect data and techniques that researchers can use to understand how well their reverse engineering methods can infer the nature of the underlying biochemical networks in the cell.

Ideally, researchers would like to test their techniques on a "gold standard" biological network, where interactions are perfectly known.

Such networks are often artificial, may lack features found in real biological networks, and may include wrong and missing interactions.

Unlike most current approaches, the deepest biological insight will come from combining different types of information, including data on gene expression, proteins, and small molecules, among others.



Computational Chemistryand applications in Biochemistry

IBM help enhance your modeling & simulation framework for design of pharmaceutical products:– simulates complex enzymatic reactions (ADMET projects or enzyme engineering in general);– model ligand-protein interaction at the stage of lead identification and optimization.

Examples of systems under investigation are:– metal-activated enzymatic reactions and design of novel materials for organic electronics– ligand-protein interaction, such as HIV-protease inhibitors and simulating how progesterone interacts with its receptor in

the human body;– identifying molecules responsible for the degradation of flavor in foods.

Method used:– combined quantum mechanics/molecular mechanics (QM/MM),– classical molecular dynamics using quantum-refined force-fields.

This activity involves diverse technical steps: •development of new algorithms•code optimization, particularly for massive parallel computing, eg CPMD (Power, PowerLinux and Blue Gene/L.•data analysis•selected applications aimed at unraveling the physics and chemistry of the system•virtual design of novel materials for advanced technologies•development of interfaces for Grid computing.

During the past 10 years IBM established scientific collaborations with a number of industrial labs.

Contact: Wanda Andreoni & Alessandro Curioni, IBM Zurich Research Labs



Fighting AIDS virus

IBM and University of Edinburgh use World's most advanced supercomputer combined with lab experiments to speed the design of drugs aimed at inhibiting infection by the HIV virus.

The project is focused on how the human HIV-1 virus attaches to cells in the body and injects its genetic material and to speed the design of inhibitors for the part of the virus responsible for allowing the virus' genetic material to enter the human cell

In 2007, IBM's Haifa Research Laboratories and some European partners developed an integrated system for anti-HIV treatment called EuResist. Enabled by the integration of comprehensive databases, advanced data analytics and prediction tools, the system can forecast how genetic HIV variants will respond to specific antiretroviral treatments. It can therefore help doctors to choose the most effective drugs and drug combinations for their HIV patients

http://www.ibm.com/avianflu


Scripps Research Institute and IBM Partner Tackle the Global Pandemic Challenge

Conduct advanced research on pandemic viruses

Goals Include1. Develop a means to anticipate, manage and contain

infectious diseases

2. Leverage Scripps world class research and IBM’s expertise in computational biology and supercomputing

3. Attract advanced research talent to the state of Florida through collaborations associated with the pandemic work

Components of Collaboration1. Exploit an IBM Blue Gene supercomputer to conduct

advanced disease modeling

2. Provide access to talent and resources of IBM’s Computational Biology Center

Have a look at www.ibm.com/avianflu

http://domino.research.ibm.com/comm/research.nsf/pages/r.ai.innovation.euresist.html


Reconstruction of whole heart by Peter Hunter, U. of Auckland

Heart disease is the leading killer in the developed worldHeart will allow better therapies for heart disease…...but will require bridging between organ level and molecular level

Sarcomere contracts by cyclical interactions of myosin on thick filament (red) and actin in thin filament (green).

In each cell of heart, a lattice of sarcomeres produce contraction on every heart beat.

Organ level Cell level Molecular level

Building Multiscale Heart Models (1/2)

Collaborators - University of Auckland, JHU, Loyola, UCSD, UIC, Oxford, others


FDA’s JANUS Submission Data Repository Model – by IBM

Grew out of CDISC and HL7 data standardization efforts FDA and IBM designed the JANUS clinical data submission repository

– Worked under a Cooperative R&D Agreement (CRADA), completed in 2004

– JANUS logical data model published: http://www.fda.gov/oc/datacouncil/

IBM implemented a JANUS prototype for FDA and NCI– FDA and NCI cooperating through an Interagency Operational Task Force (IOTF)

– Testing completed in January 2006

IBM is currently implementing a JANUS Operational Prototype for FDA and NCI

CurrentClinicalStudy

PastClinicalStudies

JANUS


Today, IBM is helping our clients to change the way the world

literally works – and to make the planet not just smaller and

“flatter,” but smarter. IBM is applying its expertise, global scope

and creativity to build the backbone of 21st century industries and

public institutions.

Leading the Transition to a Smarter Planet

Our world is becoming

INSTRUMENTEDOur world is becoming

INTERCONNECTEDVirtually all things, processes and ways of working are becoming

INTELLIGENT


Building a Smarter Planet

An opportunity for life sciences organizations to think and act in new ways.

+ + =InterconnectedIntelligent Instrumented

Smarter R&D

© 2009 IBM Corporation German CDISC User Group Meeting IBM Intro September 22 nd, 2009.

Documents

submission management

content management

business process services

ibm corporation ibms

services applicable

professional services

infrastructure services

clinical portal