3DS.COM/BIOVIA3DS.COM/BIOVIA © © DassaultDassault Systèmes Systèmes| |Confidential Confidential InformationInformation | |3/16/2019 3/16/2019| BIOVIA Discovery Discovery BIOVIA COMPREHENSIVE MODELING 創源生技 FOR FOR SCIENCESLIFE ANDSIMULATIONS 經理 陳冠文 分子視算中心 Studio (Gene) 3DS.COM/BIOVIA © Dassault Systèmes | Confidential Information | 3/16/2019 | Copyright©2019 GGA Corp., All rights reserved. AllCorp., GGA Copyright and Disclaimer • Copyright © 2019 GGA corp. All rights reserved. • This presentation and/or any related documents contains statements regarding our plans or expectations | for future features, enhancements or functionalities of current or future products (collectively "Enhancements"). Our plans or expectations are subject to change at any time at our discretion. 3/16/2019 Accordingly, GGA Corp. is making no representation, undertaking no commitment or legal obligation to create, develop or license any product or Enhancements. • The presentation, documents or any related statements are not intended to, nor shall, create any legal | Confidential Information | Information | Confidential obligation upon GGA Corp., and shall not be relied upon in purchasing any product. Any such obligation shall only result from a written agreement executed by both parties. Systèmes • In addition, information disclosed in this presentation and related documents, whether oral or written, is © Dassault Dassault © confidential or proprietary information of GGA Corp.. It shall be used only for the purpose of furthering our business relationship, and shall not be disclosed to third parties. 3DS.COM/BIOVIA Copyright©2019 GGA Corp., All rights reserved. GGA is part of the BIONET Group (訊聯生物科技) | CEO: Christopher Tsai, Ph.D. 蔡政憲 博士 3/16/2019 Established: Nov. 2008 Main Product & Service Areas: | Confidential Information | Information | Confidential 1. Genetic Testing Systèmes 2. Molecular Diagnosis © Dassault Dassault © 3. Scientific Informatics & Bio IT IPO Date: September 17, 2012 3DS.COM/BIOVIA Stock Ticker: 4160 (Taiwan OTC) Copyright©2019 GGA Corp., All rights reserved. About Dassault Systèmes | 3/16/2019 190,000 enterprise a Scientific customers 3,500 partners company • 12 industries in 140 countries | Confidential Information | Information | Confidential • >10 million on premise users • Research & Education Combining Science, Te Long-term 12,400 • >100 million online users • Software & Technology Systèmes chnology and Art for a • Sales & Services driven sustainable society passionate people • Majority shareholder control © Dassault Dassault © • 112 nationalities • Revenue: $ 2.8 Bn* • One global R&D / 53 labs • Operating margin: 31.5%* • Game changing 3DEXPERIENCE 3DS.COM/BIOVIA solutions Copyright©2019 GGA Corp., All rights* reserved. Non-IFRS 10 BIOVIA Perfect Discovery Optimize for Sustainable Discover new materials and ingredients in Performance & silico to enhance new product offerings Manufacture | Link chemical structure and 3/16/2019 3 performance, and optimize Validate trade-offs between multiple Breakthrough requirements Perfect | Confidential Information | Information | Confidential Materials 2 Discovery Systèmes Rapidly test and validate virtual material samples that may be too expensive, © Dassault Dassault © complicated, or risky to synthesize experimentally 1 3DS.COM/BIOVIA Screen Candidate Rapidly screen large volumes of molecules to find new leads, and Molecules avoid IP conflicts Copyright©2019 GGA Corp., All rights reserved. Agenda • Introduction to Predictive Science • Challenges of the Life Science Industry | • Small Molecules and Macromolecule Solution 3/16/2019 • Hands-on 基本介面操作教學 (實機演練) • Discovery Studio: Receptor-Ligand Interactions | Confidential Information | Information | Confidential 小分子化合物接合模擬 Systèmes • Hands-on操作教學 (實機演練) © Dassault Dassault © 3DS.COM/BIOVIA Copyright©2019 GGA Corp., All rights reserved. Life Sciences R&D Top Level Workflow Small | Molecule 3/16/2019 Disease Target ID and PreClinical To Clinical Biologic Selection Validation Development and ADQM | Confidential Information | Information | Confidential Systèmes Conjugate © Dassault Dassault © 3DS.COM/BIOVIA Target Target Screen “Lead “Preclinical” Hit ID Hit Validation “Hit to Lead” Identification Validation Development Optimisation” Development Copyright©2019 GGA Corp., All rights reserved. “Making” Biotherapeutics Is Different Small Molecule Biotherapeutics | 3/16/2019 | Confidential Information | Information | Confidential Systèmes Versus © Dassault Dassault © 3DS.COM/BIOVIA Chemist synthesizes the molecule Biological systems make the molecule Copyright©2019 GGA Corp., All rights reserved. Extensive experimentation, random variation and screening intrinsic to the process Biotherapeutic Discovery is Labor and Time Intensive! Select fAbs that Associate Inoculation and Create fAb phage Identify soluble bind to target Sequence fAbs sequence data tissue harvest display library fAbs (ELISA) with binding data Create full length LC | 12-20 weeks and HC plasmid constructs, store these 3/16/2019 Select top expressing Transfect E. coli w clones, test binding to plasmids, harvest cell lines that express and lyse Predictive Sciences the target | Confidential Information | Information | Confidential can reduce cycles Optimization: Systèmes and improve quality of Kinetics and Sequence the LC Affinity multiple cycles and HC from candidates to Development measurements these clones © Dassault Dassault © 9-12 months or more 3DS.COM/BIOVIA Select and store 12-20 weeks Measure expression clones that match of LC and HC by conceptual batch/clone Purify Ab Transfect HEK cells sequences Record purification details, Scale up top performing w selected To constructs, track expression levels, buffer clones Development formulation, SEC retention batch IDs (HEK time, % main peak clones) Sequencing Facility Cell Culture Lab Animal Lab Molecular Biology Lab Copyright©2019 GGAAnalytical Corp., All Lab rights reserved. Pharma And Predictive Sciences… • Example: AstraZeneca | 3/16/2019 “The right target, the right exposure, the right drug” At AstraZeneca, we’re spearheading the model-based approach to drug research and development. In our | Confidential Information | Information | Confidential mission to bring life-changing medicines to the global Systèmes population, we’re doubling our investment in Predictive © Dassault Dassault © Sciences – so we can tackle illness and disease with even more effective drugs. 3DS.COM/BIOVIA Improve Quality, Save Time, Save Money 16 Biotherapeutics Development Challenges • Examples of failures in Development include: | 3/16/2019 | Confidential Information | Information | Confidential Purification Problems Poor solubility/ Systèmes High viscosity BIOVIA Predictive Sciences Can Helpstability Identify These Problems Earlier © Dassault Dassault © Can Help to Avoid Costly Development Failures 3DS.COM/BIOVIA Immunogenicity Low thermal stability Poor serum half-life Copyright©2019 GGA Corp., All rights reserved. 3DS.COM/BIOVIA © Dassault Systèmes | Confidential Information | 3/16/2019 | Generational with 3DEXPERIENCE changes Generational Copyright©2019 Copyright©2019 GGA Corp., All rights reserved.Corp., GGA Vision: Multiscale Life Modeling & Simulation HOLISTIC & INTERDISCIPLINARY approach to apprehend the complexity of biological systems which aims at understanding the spatio-temporal | interactions between components of a cell, between cells, and their interaction with the environment. 3/16/2019 | Confidential Information | Information | Confidential Systèmes © Dassault Dassault © 3DS.COM/BIOVIA Copyright©2019 GGA Corp., All rights reserved. 3DS.COM/BIOVIA © Dassault Systèmes | Confidential Information | 3/16/2019 | What’s What’s Discovery Studio Copyright©2019 GGA Corp., All rights reserved. AllCorp., GGA Discovery Studio: A Comprehensive Portfolio Protein Virtual X-ray | docking screening 3/16/2019 Protein Stability Specialist: In-situ lead QSAR, Homology and Membrane enumera- | Confidential Information | Information | Confidential ADME and modeling Binding Proteins tion Toxicity affinity Systèmes © Dassault Dassault © Simulation Specialist: Specialist: Protein and Scaffold Ligand Antibody Quantum hopping profiling 3DS.COM/BIOVIA aggregation design Mechanics Copyright©2019 GGA Corp., All rights reserved. Protein design tool includes: 1. Advanced homology modeling tools Data Support Different 2. Protein docking and epitope detection integration Data Formats 3. pH-based protonation | 4. Protein aggregation 3/16/2019 5. Virtual mutation 6. … Rational Structure-Based Protein Design of design | Confidential Information | Information | Confidential Benefit Biologics Systèmes 1. Increase the efficiency in sample preparation © Dassault Dassault © stage Automatic 2. Epitope prediction Chemical 3. Optimize protein Molecular 3DS.COM/BIOVIA design Modelling Tools Copyright©2019 GGA Corp., All rights reserved. Science and Functionality Highlights • Template identification • Sequence alignment and analysis | • Advanced homology modeling tools 3/16/2019 • Rigorous model verification • Implicit or explicit solvent-based MD simulations • Specialist tools for Antibody modeling | Confidential Information | Information | Confidential • Antibody loop modeling and refinement Systèmes • Protein docking and epitope detection © Dassault Dassault © • Optimizing protein-protein binding affinity • Predicting and guiding protein stability 3DS.COM/BIOVIA • Managing aggregation risk • Disulfide bridge prediction • Humanization Copyright©2019 GGA Corp., All rights reserved.