Drug Discovery in China



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Drug Discovery in China Media Visit to Roche in China Shanghai 30 October 2005 Li Chen, Ph. D. Head of Research, Chief Scientific Officer Roche R&D Center (China) Ltd.

Research Business Model in China Contract Research: Fee for Service (FFS) Outsourcing center for building block, intermediates, screening libraries standard compounds, API Exclusive Contract Research: FFS and technology transfer Synthetic chemistry work Wholly owned: Drug Discovery Research Drug design, synthesis evaluation and SAR development Share corporate data and knowledge Lead generation and optimization, Intellectual property creation Contract Research: Fee for Service (FFS) Cost driven No investment in infrastructure Get what you pay for Exclusive Contract Research: FFS and technology transfer Effectively manage the task Wholly owned: Drug Discovery Research High initial investment in infrastructure Operation within firewall Long term commitment to employees High value creation in pharma research

Discovery Research Shanghai PD Site Admin SRPL Chemo Informatics Site GM Discovery Research CSO RGMC RMT GCT GRI Research Admin outsourcing Res. Inventory Global Inventory Disease Biology RRDCC PR SRPL ETP Medicinal Chemistry MDO CADD Chemistry Technology Drug Safety Synthetic Chemistry Bio- Technology

Research Staff in Shanghai Knowledge Experience Culture Returnees local Roche good business practice Performance standard Reward and recognition Competency and career development plan returnees Educational Background Education Back Ground Passion Skills Performance Medicinal Chemistry Computation science Organic Chemistry Analytical Chemistry Information Science Inventory and logistics Automation technology MDO and biology phd ms bs Roche training Medicinal Chemistry Course Research Symposium Communication skill class

Drug Discovery at RRDCC Focus on value creation opportunities New Medicine Proposal Target Validation Lead Identification Lead Dev. Lead Optimization EIH Enabling Early Clinical Safety Early Clinical Efficacy Development Portfolio Preparation Phase II Phase III Launched Immediately Longer term IP Creation substance formulation New Medicines NCE Biopharmaceuticals

Drug Discovery Research SH HT HT Design Design Multiple Multiple hypothesis hypothesis Diversity Diversity & similarity similarity ADME ADME prediction prediction Inform Informatics Data Data archiving archiving Data Data presentation presentation Data Data analysis analysis Data Data mining mining Genentech Palo Alto Nutley HT HT C h he em istry istry Synthetic Synthetic m etho ethods ds HT HT Synth Synthesis esis pro proc cess HT HT An Analyti c cal al & p purifi c ca atio tion n Pre- Pre- & Post Post Syn. Syn.. autoa utom ation a tion Bohdan Bohdan Weighing Weighing Synthesizers Synthesizers LC/MS LC/MS analytical analytical LC/MS LC/MS preparative preparative HT HT Ev Evalu alua atio tion Bohdan n HT HT Bio- Bio-activity Bohdan Bar-coding Bar-coding a c HT HT Dru Drug-like g Tecan Tecan Liquid Liquid Handler Handler HT HT DMPK DMPK HT HT Phenotypic n o c Basel Penzberg Chem Info HTC Chugai Shanghai gy Corporate Scientific Information Environment Desk Top BB Reagent ACD PDT Project Library TM MDL Rodin IRCI Products Crossfire D IRCI Rodin PDT 全 球 研 究 数 据 和 信 息

Our 1 st year experience Set up a fully functional research site in China Can be done in 1 year from scratch Talent from overseas and China 10 returnees to form scientific core team >50% Ph. D and < 10% BS Technology transfer Quality of technical supporting team is a key for successful operation Best microwave and LCMS Prep technology at Roche

Our 1 st year experience Research supply 7-10 day from global suppliers: time is a issue 1-3 day from local supplies: quality is still an issue Knowledge transfer Training program at Roche sites Global team membership Data and Information sharing at global standard Scientific information Pharma R&D data and information Research information

Our 10 month experience in research Achieved real time medicinal chemistry research in lead generation 1 st reaction on Dec 23, 2004 1 st compound registered to IRCI on Dec 29, 2004 1 st lead molecule tested in Jan 2005 1 st nanomolar lead identified in March 1 st X-ray structure of ligand/target complex in June 1 st 1000 lead molecules created in July 1 st patent filed in September and more to come in 2005 Achieved better understanding of China Biotech and Pharma Industry Good performance in chemistry research Strong desire to create biomedical research base Integration is key for future success Talent pool Highly motivated research scientists at MS and Ph.D level Lack of experienced research leaders in drug discovery

RRDCC Project Portfolio RRDCC is currently working with of colleagues in the following areas Target based anticancer medicines that target on cancer cell cycle regulation and apoptosis: Nutley and Penzberg Anti HIV targets for ACIDS: Palo Alto Novel therapy for Alzheimer disease: Basel New treatment of obesity medicine: Nutley

Conclusion Pharma R&D in China 2000: Research collaboration 2002: Outsourcing 2005: Best sourcing and all above Roche is a leader in Pharma R&D in China Genomic center collaboration Outsourcing to Shanghai Institute of Organic Chemistry Basic research in drug discovery