Why is Drug Target Identification important for Drug Discovery? I. Introduction

Target Identification Bioactivity Adverse Drug Reaction Target-based Efficacy Target-based Toxicity Precise drug target identification is needed for increasing efficacy and decreasing toxicity for Drug R&D Success! Confidential 1. Drug Target Identification is a critical issue for drug discovery

Investor Relations Drug Target Discovery Methods Traditional Methods… 1.Genomics DNA / RNA Chip 2.Proteomics Protein Chip Traditional Methods… 1.Genomics DNA / RNA Chip 2.Proteomics Protein Chip Final Goal is… Discovering the Genome-wide Involvement via the Cellular Response to Drugs Drug-induced Haploinsufficiency (DIH) in Yeast is a good surrogate system! Final Goal is… Discovering the Genome-wide Involvement via the Cellular Response to Drugs Drug-induced Haploinsufficiency (DIH) in Yeast is a good surrogate system!

II. Principle of Drug Target Identification By GPScreen™ : Proprietary Fission Yeast S. pombe Genome-wide Knockout Library

Investor Relations Proprietary S. pombe Heterozygous Genome-wide Knockout Library X This mutant library enables true genome-wide drug target screening!!! #1 gene

Investor Relations (Giaever et al., 2004; Lum et al., 2004; Parsons et al., 2004) 2. Drug-induced Haploinsufficiency (DIH) Screening is based on Heterozygous Genome-wide Knockout Library Reducing the copy number of a gene from two copies to one often results in a strain that is sensitized to drugs that act on the product of this gene. Time Cell Growth Time Cell Growth

Investor Relations Small moleculeActivitySource Target PoteinsReference dhMotC (dihydromotuporamine C) Anti-cancer, anti-invasive activity Synthetic CSG1 or CSG2; genes required for mannosylation of inositolphosphorylceramide-C, targets sphingolipid metabolism PNAS, 2004 Fenpropimorph / alverine citrate Antifungal activity, Anti-cholinergic Agricultural plant ERG24 (human homolog LBR) PNAS, 101, 2004 Atorvastatin Inhibit cholesterol synthesis SyntheticHMG1 PNAS, 101, 2004 Papuamide B anti-HIV activity a marine sponge DNF1, DNF2, DRS2 defective for flipping PS from the outer bilayer of the cell membrane to the inner bilayer, resulting in an excess of PS in the outer membrane Cell 126, 2006 Examples in budding yeast S. cerevisiae 3. Examples of Drug Target Identification using DIH

Investor Relations S. pombe is an Ideal Model Organism for Mammalian Cells ( * Merck co. uses S. cerevisiae mutant library for their drug discovery & development.) Fission yeast S. pombe is considered superior to budding yeast S. cerevisiae as a model organism, because its cell division pattern is more similar to that of mammalian cells.

Investor Relations Covering 98.5% of S. pombe genome (Full genome size; 4,914 genes) Barcode-labeled in each mutant (Next Generation Barcode Sequencing is possible) World’s Only Genome-wide Knockout Library of Cell Division Model Organism Each mutant can be individually screened (Pathway or gene family screening is also possible) Features of BIONEER’s S. pombe Heterozygous Genome-wide Knockout Library S. pombe Heterozygous Genome-wide Deletion Mutant Library (4,840 strains) S. pombe has similar biochemical processes as mammalian cells (contains human cancer genes and over 30% homology) (Nature Biotech, 2010)

Investor Relations GPScreen™ Service Workflow S. pombe Genome-wide Knockout Library (Functional genomics) GPScreen™ (Drug Target Identification) S. pombe Heterozygous Genome-wide Knockout Library (4,840 strains) (Nature Biotech, 2010) Gene #1 Gene #2 Gene #3. Gene #?. Gene #4840 Gene #1 Gene #2 Gene #3. Gene #?. Gene #4840 Drug Target? No. Yes. No Discovering Human Orthologs & GO Analysis Genome-wide Drug Target Screening in S. pombe Knockout Library Identification of Drug Targets Reports to Customers GPScreen™ using S. pombe heterozygous genome-wide knockout library enables realistic genome-wide screening for drug target identification.

III. Genome-wide Drug Target Discovery - Services - GPScreen ™ Services

Investor Relations Flow Chart of GPScreen ™  GI 50 means the concentration of drugs for 50% inhibition of the growth of control cells.  GPScreen™ will be performed according to the dose of GI 50 of compounds in a primary activity test. Primary Activity Test in wild-type S. pombe GPScreen™ in Genome-wide knockout library Analysis 1 st Step of GPScreen™ 2 nd Step of GPScreen™

Investor Relations GPScreen ™ : Drug Target Identification Services 2. Products and Services 2) GPScreen™ Service using S. pombe Genome-wide Mutant Set Cat. No.Full Screening Service No. of Genes Price GPS-01-GW S. pombe Genome-wide Heterozygous Deletion Mutant Screening Service4840 Inquire 3) GPScreen™ Service using S. pombe Essential gene Mutant Set Cat. No.Essential Gene Screening Service No. of Genes Price GPS-02-ESS S. pombe Essential Gene Heterozygous Deletion Mutant Screening Service1259 Inquire 1) Primary Test Service for Determination of Growth-inhibitory Activity (GI 50 ) in Wild Type S. pombe Primary Test Service will be performed to all compounds requested in advance of GPScreen™. Cat. No.Primary Test ServiceCell TypePrice GPS-00 Primary Test Service in Wild Type S. pombeSP286 $ / Compound * Price of primary test will be dramatically discounted when the number of compounds is ≥ 2.

Investor Relations GPScreen ™ : Drug Target Identification Services Cat. No.Functional Group-based Subset Services No. of Genes Price INFORMATION STORAGE AND PROCESSING GPS-03K-A A: RNA processing and modification Screening Service210Inquire GPS-03K-B B: Chromatin structure and dynamics Screening Service97Inquire GPS-03K-J J: Translation, ribosomal structure and biosis Screening Service378Inquire GPS-03K-K K: Transcription Screening Service239Inquire GPS-03K-L L: Replication, recombination and repair Screening Service180Inquire CELLULAR PROCESSES AND SIGNALING GPS-03K-D D: Cell cycle control, cell division, chromosome partitioning Screening Service183Inquire GPS-03K-M M: Cell wall/membrane/envelope biosis Screening Service48Inquire GPS-03K-N N: Cell motility Service2Inquire GPS-03K-O O: Posttranslational modification, protein turnover, chaperones Screening Service396Inquire GPS-03K-T T: Signal transduction mechanisms Screening Service285Inquire GPS-03K-U U: Intracellular trafficking, secretion, and vesicular transport Screening Service292Inquire GPS-03K-V V: Defense mechanisms Screening Service21Inquire GPS-03K-W W: Extracellular structures Screening Service5Inquire GPS-03K-Y Y: Nuclear structure Screening Service31Inquire GPS-03K-Z Z: Cytoskeleton Screening Service109Inquire 4) GPScreen™ Service using KOG analysis-based Functional Group Subsets

Investor Relations METABOLISM GPS-03K-E E: Amino acid transport and metabolism Screening Service187Inquire GPS-03K-F F: Nucleotide transport and metabolism Screening Service66Inquire GPS-03K-G G: Carbohydrate transport and metabolism Screening Service142Inquire GPS-03K-H H: Coenzyme transport and metabolism Screening Service79Inquire GPS-03K-I I: Lipid transport and metabolism Screening Service118Inquire GPS-03K-C C: Energy production and conversion Screening Service163Inquire GPS-03K-P P: Inorganic ion transport and metabolism Screening Service82Inquire GPS-03K-Q Q: Secondary metabolites biosynthesis, transport and catabolism Screening Service48Inquire POORLY CHARACTERIZED GPS-03K-R R: General function prediction only Screening Service551Inquire GPS-03K-S S: Function unknown Screening Service284Inquire 5) GPScreen™ Service using Human Disease-related Subsets Cat. No.Human Disease-related Subset Services No. of Genes Price GPS-04H-A Cell Cycle Regulator Screening Service321Inquire GPS-04H-B DNA Damage Repair Screening Service376Inquire GPS-04H-C Cytokinesis Screening Service124Inquire GPS-04H-D Chromatin Remodeling Screening Service257Inquire GPS-04H-E Histone Modification Screening Service 63 Inquire GPS-04H-F Protein Kinase Screening Service223Inquire GPS-04H-G GTPase Proteins Screening Service90Inquire GPS-04H-H ABC Transporter Screening Service31Inquire GPS-04H-I Transcription Factor Screening Service362Inquire GPS-04H-J Neurological Disease Screening Service19Inquire GPScreen ™ : Drug Target Identification Services

Investor Relations Performance of GPScreen TM 1 st Step of GPScreen™: Determination of GI 50 in wild-type S. pombe 2 nd Step of GPScreen ™: High Throughput Screening in Genome-wide knockout library * Fitness score: ratio of drug treated cells to non-treated control

IV. Toxicity Profiling – Service GPScreen ™ HT Service through Next Generation Sequencing

Investor Relations Flow Chart of NGS-based GPScreen™ HT Determination of GI 50 in wild type S. pombe Drug Treatment on Genome-Wide Knockout Library gDNA Preparation & Barcode PCR NGS (Barcode Sequencing) Data Analysis Toxicity Evaluation based on Drug Targets Reports to Customer Customer Drugs or Drug Candidates

Investor Relations In-vivo Toxicity StatusGI 50 Drug A Non- toxic In Market 200  M Drug B Cardio- toxic Dropped in Phase III 100  M Number of genes In genome-wide drug target profiling with GPScreen TM HT, in-vivo toxic compound ‘Drug B’ showed more broad spectrum of target profile than that of a non-toxic RTK inhibitor ‘Drug A’, implying that ‘Drug B’ be possibly more toxic than ‘Drug A’ in vivo, which is correlated well to its known in- vivo toxicity. 2. Genome-wide Toxicity Profiling of Anti-Cancer RTK Inhibitors Using GPScreen™ HT

Investor Relations In-vivo Toxicity StatusGI 50 Drug C Non- toxic In Market 30  M Drug D Cardio- toxic Market withdrawal 3 M3 M In genome-wide drug target profiling with GPScreen TM HT, in-vivo toxic anti-dyslipidemic compound ‘Drug D’ showed more broad spectrum of target profile than that of a non-toxic anti-dyslipidemic agent ‘Drug C’, implying that ‘Drug D’ be possibly more toxic than ‘Drug C’ in vivo, which is correlated well to its known in-vivo toxicity. Number of genes 3. Genome-wide Toxicity Profiling of Anti-dyslipidemic Drugs Using GPScreen™ HT

Investor Relations Applications of GPScreen™ & GPScreen™ HT

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