SBH Sciences. Innovative Biotechnology Company Two Discovery Programs. Discovery and Pre-clinical Contract Research Organization

Transcription

1 SBH Sciences Innovative Biotechnology Company Two Discovery Programs Discovery and Pre-clinical Contract Research Organization Production and Bioassay Testing of Cytokines Bio-Incubator : An Innovative Business Model Models for Oncology and Inflammation Custom Process Development Biomarkers Analysis June, 2014

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3 We Partner with Customers to Create a Competitive Advantage by Delivering Precise and Reliable Services Project Initiation Consultation Budgeting Design Execution Initiation Updates Amendments Report Draft Discussion Final Report

4 Therapeutic Areas Supported Oncology Inflammation (In-Vitro Model using PBMC, THP-1 and human Liver cells) Metabolic diseases (Diabetes) Neurobiology (Neurodegeneration / Neuroprotection) Dermatology and connective diseases Bone and cartilage Target ID Assay Development Primry Screening Secondary Screening Lead Optimization PK/PD Clone Selection Cell Culture Optimization Purification BioProcess Scale-up Formulation Manufacturing Serving More Than 120 companies worldwide for 17 years

5 Core Capabilities Biological Resources 230 human tumor cell lines > 30 oncology drugs >280 cytokine potency assays 31 Recombinant cytokines 9 Recombinant enzymes 40 Monoclonal antibodies PBMC, THP-1 inflammation assays Other potency assays Instrumentation 2D Western Blot Luminex 200 Fully Automatic ELISA Workstation Analytical HPLC Radiation Capability Screening Services Biomarker Analysis Multiplex Kit Development 5

6 Extended Capabilities Biologics Support Bench-scale production Pilot scale-up Purification Basic CMC, stability Formulation In-Silco Biologics Development Services Facilities Cell culture lab Protein Purification lab Biomarker lab Bio-Incubator Partners In vivo services Kinase assays Consulting 6

7 7 Production of Biologics

8 Cell Culture Services (Mammalian & Insect Cells) Production of recombinant proteins, monoclonal antibodies, and vaccines Optimization of growth conditions (media optimization and serum-free adaptation) Supply any mammalian cell lines before and after cytokines stimulation Customized services (9 human primary cells and > 300 mammalian cell lines are currently available) 2D and 3D capabilities Protein Purification Services Development of scalable, well understood, and reproducible purification processes LC capability (Ion Exchange, HIC, Affinity, Metal, HA, SEC) HPLC (Preparative and Analytical methods development)

9 SBH Sciences has Produced and Commercialized 80 Cytokines and other Biologics 40 Recombinant proteins and 40 monoclonal antibodies TGF-Beta (TGF-b1, TGF-b2) Interleukins (IL-12, IL-23) Growth Factors (HGF) Activin-A GDF-15/MIC-1 Bone Morphogenic Proteins (BMP-2, BMP-7) Soluble receptors (s-il-6r) IGF-BPs (IGF-BP-6) Interferon (IFN-b) Enzymes (9 Glycosyltransferase) CD22 TNF Receptr (HVEM-Fc) Anti-Galectin Anti-TNFa Anti-VEGF All products are > 95% pure, tag-free, and carrier-protein free

10 Analysis of Biomarkers Drug Discovery and Analytical Services ELISA and RBA development and optimization Biomarkers discovery and profiling using Multi- Array Analysis (Multiplex) and 2D Western Blot Quantitative methods for early PK/ADME studies (Immunological & HPLC) Protein formulations and stability studies 10

11 OD (405nm nm) Development of Receptor Binding Assay for VEGF-165 Coating : VEGF-R1 Detection: Polyclonal anti-vegf Lot release based on active VEGF VEGF-165 (ng/ml) [log scale] Final Pool "UK" Day 39 (2/16/10) Day 41 (2/16/10) Day 42 (2/16/10)

12 12 Multiplex multi-array analysis (Luminex 2000)

13 2D Western for Biomarker Discovery Utilizing Protein Simple s Peggy an automated Western Blotting system, SBH can rapidly analyze multiple samples for a specific biomarker Peggy: For characterization of expressed proteins in a biologic sample.

14 Market Adoption SBH Diagnostics CLIA Certified Lab : 6-9 Month Development Process Certification CLIA Certification Documentation templates established Distribution channels identified Test Evaluation Validation 4 Tests in validation process, 5 Tests accepted Reproducibility, sensitivity, specificity, cost 2 tests rejected due to poor sensitivity KOLs identified and contacted MOU Signed 12 Tests in feasibility review Scientific review/due diligence of Diagnostic test IP Review Competitive assays identified Market analysis Commercialization KOLs contracted Sales team contracted Educational material developed and delivered Information disseminated geographically Optimization SOPs and Protocols established, HIPAA Training Bench marks established CLIA certification process (RSSLII) Cost structure defined License/JV Agreement signed Time (6-9 months)

15 Oncology a strategic collaboration 15

16 MM.1S BL-41 BL-40 Jurkat A-375 MM.1R LnCap HCT-116 RWPE-1 HS-Sultan BL-2 PC3 AML-5 MG-63 Colo-201 SW-480 U2OS SJSA Colo-205 NCI-H460 NCI-H226 LoVo Colo-205 SW-403 Colo-320HSR HTB-119 RPMI8226 NCI-H28 SW-620 PANC-1 LS-123 Colo-320DM SW-1417 MCF-7 C2BBe1 HEL HCT-15 SW O U266 SW-948 Paca-2 HCT-15 Raji 4T1 PL-45 Hela HPAC Hut-78 Caov-3, HTB-75 DLD-1 T47D DU-145 SW-626 LS-180 KG-1 HCT-8 HTB-38 WiDr Hep-G2 Cytotoxicity (IC50 [mm]) Cancer Cell Cytotoxicity Broad, Potent, Selective (72 hours) human cancer cells are ready for immediate studies Normal Cells 3T3 mouse fibroblasts - 6 mm Human PBMCs >20 mm 21

17 Integrated in vivo and in vitro Services Streamlined data transfer into animal models Efficacy studies ; PK/PD modeling Standard to advanced modeling, including primary patient tumors Shorter development time and enhanced project success!

18 Radiation Capability U87MG cell line

19 Untreated GBM GBM spheroid 3D culture system with U87MG Glioblastoma cell line The radial spread in two dimensions is reminiscent of the natural disease. Not shown here is the invasion down into the substrate as well Spheroid outgrowth over 8 days (boxes = 250 um) 1 represents initial spheroid plated

20 SBH Sciences is collaborated with Cell Assay Innovations ClariCELL cell-based kinase testing service Quantification of kinase/protein phosphorylation events Tyrosine and serine/ threonine kinase targets Full-length human kinases expressed in human cells 13 assays currently available, including drug-resistant mutants

21 %INH %INH %INH %INH Abl Cellular Data - Validation wt Abl Abl [E255V] [cmpd] M dasatinib ~0.006uM imatinib - 0.3uM ponatinib - 0.1uM ref inhib 1 >6uM [cmpd] M dasatinib ~0.006uM imatinib - 0.3uM 100 ponatinib - 0.1uM 80 ref inhib 1 >6uM 60 Abl [T315I] dasatinib >1uM imatinib >10uM ponatinib uM ref inhib 1 >6uM [cmpd] M dasatinib ~0.01uM imatinib >10uM ponatinib uM ref inhib 1 >6uM [cmpd] M 21

22 Integrated in vivo and in vitro Services Inflammation and Liver Fibrosis

23 OD ( nm) Development of In-Vitro Inflammation Model using Human PBMC Evaluation of potential Drug in the presence of LPS OD from ELISA measurement of h-tnfa ng/ml 0.4 ng/ml Drug (um) [log scale] 100% Neutralization Drug 23

24 NASH Activity score Steatosis Score Fibrosis Score In-Vivo model for NASH / Fibrosis (Fatty Liver Disease) Control NASH Liver Control NASH Liver Control NASH Liver

25 The Problem: Chronic Inflammation & Associated Immunosuppression The Solution: A collaborative project based on the innovative discovery of a set of biomarkers that will enable the quantitative measurement of the immune status under chronic diseases and the development of diagnostic kits amenable to FACS analysis.

26 Significant Impact Three major collaborations / partnership resulted in advancement of three therapeutics programs to the clinical trials. Two on-going internal discovery programs. Serving over 120 customers worldwide for 17 years. Offering > 280 cell based assays to measure biological activity of cytokines. Production of 80 biologics using mammalian cells. Offering 4 platform tools for analysis of biomarkers.

27 Clinical Product Development - Case Study: human IL-12 a Novel Radiation Medical Countermeasure Proprietary human IL-12 production process was developed by SBH Sciences COA established for commercial release to the R&D market Neumedicines, Inc. (CA) licensed the technology from SBH Sciences In 2008, both companies collaborated to secure a Biomedical Advanced Research and Development Authority (BARDA) contract to develop IL-12 for Acute Radiation Syndrome In 2009, SBH Sciences optimized the process, scale-up, and transferred the technology to a GMP manufacturing April 2011 Submission of IND June 2011 First-In-Human for Toxicity studies 27

28 January 27, 2014 Galectin Therapeutics and SBH Sciences, Announce the Formation of Galectin Sciences, LLC, a Collaborative Venture to Research and Develop Galectin Inhibitors for Oral Administration 28

29 Science (PhD) Regulation QC (PhD) BD (PhD & MBA) Website & IT Consultants President Facility & Safety Manager Office Manager (Accounting and HR )

30 President & CSO Cell Culture Protein Purification Bioassay Diagnostics Discovery Supervisor Supervisor Supervisor Supervisor Senior Scientist Associate Scientist Scientist Scientist Associate Scientist Scientist Molecular Modeling Associate Scientist Associate Scientist Associate Scientist Associate Scientist

31 In vitro laboratories in Natick, MA Location

32 In vitro laboratories SBH Sciences Principal lab space for in vitro operations at in Natick, MA Facilities In vivo laboratories Woodland Pharmaceuticals Animal rooms are within the AAALAS accredited facilities at WPI, located in the Gateway Park in Worcester, MA

33 Raphael Nir, Ph.D. President and CSO Tel: Ext