Discovery and Pre-clinical Contract Research Organization (CRO)

Innovative Biotechnology Company with Discovery Programs

Production and Bioassay Testing of Cytokines & Enzymes

Bio-Incubator : An Innovative Business Model

Models for Oncology and Inflammation

Custom Process Development

Biomarkers Analysis

September 2019

Discovery Research Products & Services

Therapeutic Areas Supported by SBH In-Vitro Models • Oncology (350 human cancer cell lines) • Inflammation (human PBMC, THP-1, Liver and BEAS-2B cells) • Metabolic diseases (Diabetes, NASH) • Neurobiology (Neurodegeneration / Neuroprotection)

Serving More Than 200 companies worldwide for 22 years

Clone Selection Cell Culture Optimization Purification Bioprocess Scale-up Formulation Manufacturing

Target ID

Assay Development Primary

Screening Secondary Screening Lead Optimization PK/PD

Instrumentation • 2D Western Blot • Luminex 200 • Simple Plex (Ella) • Fully Automatic ELISA Workstation • Analytical HPLC • qRT-PCR • Vitros 350 analyzer • Irradiation Capability • FACS

Biological Resources • 350 human tumor cell lines • > 30 oncology drugs • > 300 cytokine potency assays • 30 Recombinant cytokines • 8 Recombinant enzymes • 40 Monoclonal antibodies • Inflammation assays

Screening Services

Biomarker Analysis

Multiplex Kit Development

Capabilities

Facilities • Cell culture lab • Protein purification • Biomarker lab

Biologics Development

Services

Bio-Incubator ABI-LAB

Currently supports 16 companies

Consulting

Biologics Support • Bench-scale production • Pilot scale-up • Purification • Basic CMC, stability • Formulation • In-Silico

Partners • In-vivo services (oncology & NASH) • CLIA Certification • GLP

Extended Capabilities

Production of Biologics

• Production of recombinant proteins, enzymes and monoclonal antibodies • Optimization of growth conditions (media optimization and serum-free adaptation) • Supply any mammalian cell lines before and after cytokines stimulation • Customized services (> 10 human primary cells and > 400 mammalian cell lines are

currently available) • 2D and 3D capabilities • Irradiation experiments (combination therapy)

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) • Protein formulation and stability studies

Cell Culture Services (Mammalian & Insect Cells)

SBH Sciences has Produced and Commercialized 78 Cytokines and other Biologics

38 Recombinant proteins and 40 monoclonal antibodies

TGF-Beta (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 (8 Glycosyltransferase)

CD22 TNF Receptor (HVEM-Fc)

Anti-Galectin Anti-TNFa Anti-VEGF

All products are > 95% pure, tag-free, and carrier-protein free

Oncology and inflammation are the therapeutic areas where SBH Sciences is best positioned to assist you. • 300 cell-based assays to measure cytokine activity

(cytokine-induced proliferation, cytokine-induced killing, cytokine release assays and cytokine neutralization).

• Screening of therapeutic antibodies for specific activity (includes receptor binding assays , CDCC, ADCC and ADCP assays).

• 350 different human cancer cell lines to facilitate in-vitro lead drug optimization (cytotoxicity, invasion, and migration assays).

• Cell-based disease models for compound selection (inflammation / fibrosis – PBMC, THP-1, RAW 264.7, BEAS-2B and immortalized liver cell line).

Cell-Based Assay Capabilities

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Antibody Concentration (ug/ml) [log scale]

Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) Promega Kit (G7010 ; 12.8-Fold Effector-to-Target)

Using SK-BR-3 Cells

Non Drug Herceptin - Drug

R&D Systems : Measured by its ability to induce hemoglobin expression in K562 human chronic myelogenous leukemia cells. Schwall, R.H. et al. (1991) Method Enzymol. 198:340. The ED50 for this effect is typically 2-10 ng/mL.

R&D Systems : Measured in a cell proliferation assay using BaF3 mouse pro-B cells transfected with mouse Flt-3. No ED50.

Existing Platforms to Assist with Biomarker Analysis AlphaScreen and AlphaLISA Simple Plex: ProteinSimple ELLA ELISA [Freedom EVO; TECAN] Flow Cytometry HTRF / TR-FRET Luminex 200 [Multiplex] Automated Western Blot [PeggySue / Wes] Analytical HPLC RT-PCR Chemical analyzer, VITROS 350

•SBH offers 10 platforms that have been utilized to analyze thousands of clinical samples (> 150 biomarkers). •First CRO to offer automated simple western blot services on “PeggySue” and “WES”.

•First CRO to offer Simple Plex assays on “ELLA”.

•SBH Diagnostics, our strategic partner, is a contract research organization providing analysis under Clinical Laboratory Improvement Amendments [CLIA] certifications and GLP.

Comprehensive Biomarker Analysis Services

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VEGF-165 (ng/ml) [log scale]

Development of Receptor Binding Assay for VEGF-165 Coating : VEGF-R1

Detection: Polyclonal anti-VEGF

Lot release based on active VEGF

Final Pool "UK" Day 39 (2/16/10)

Day 41 (2/16/10) Day 42 (2/16/10)

Multiplex – multi-array analysis

(Luminex 200)

2D Western for Biomarker Discovery Utilizing Protein Simple’s “PeggySue” and “WES” -automated Western Blotting systems, SBH can rapidly analyze multiple samples for a specific biomarker

PeggySue: For characterization of expressed proteins in a biologic sample.

Comprehensive Pathway Analysis (Companion Biomarkers)

Pathways

MAP Kinases

Apoptosis

NFkB

Cell Cycle

Stress Response

JAK/STAT

p44/42 MAPK (Erk1/2)

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A549 Cells

Drug A Drug B

Drug Response in FNAs

Day 0 No Treatment

Day 3 Gleevec

α-Phospho-STAT 5

Oncology a strategic collaboration

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Cancer Cell Cytotoxicity (72 hours)

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350 human cancer cells are ready for immediate studies

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!

8 2 1 3 4 7

8 2 1 3 4 7 Spheroid outgrowth over 8 days (boxes = 250 um) 1 represents initial spheroid plated

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.

Untreated GBM

Irradiation Capability

U87MG cell line

Integrated in-vitro and in-vivo Services

Inflammation and Liver Fibrosis In-Vitro Services: In-Vivo Services: - TLR-4 - Fatty Liver (NAFLD) - TLR-7 / TLR-8 - NASH - iNOS - Fibrosis - M1 / M2 - Diet-Induced-Obesity - T-Cell Activation - Immuno-oncology

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Control 1 Control 2 LPS 25 LPS 50 LPS 100 LPS 200

Area

Sample

RAW 264.7 Cells iNOS Peak Area

WES Analysis [Protein Simple]

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Drug (uM) [log scale]

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

100% Neutralization Drug

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

4 Patents have been submitted so far

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

• 2011 – Submission of IND and First-In-Human for Toxicity studies

SBH Sciences is an innovative biotechnology company and pre-clinical contract research organization which has been in operation for 22 years, providing over 200 companies with quality products and services.

SBH Sciences supported and guided 3 companies through all stages of drug development, bringing 7 NCE’s to clinical trials. One NDA was submitted (08/2018) and was approved by the FDA on 07/2019 [Xpovio (selinexor)].

Significant Impact

President & CSO

Regulation – QA / QC

Operations & Safety Manager

Office Manager and Treasurer

Director of Business

Development Website & IT

President & CSO

Cell Culture

Supervisor

Associate Scientist

Associate Scientist

Protein Purification

Supervisor

Associate Scientist

Biomarker

Supervisor

Senior Scientist

Associate Scientist

Associate Scientist

Bioassay

Supervisor

Associate Scientist

Associate Scientist

Discovery

Supervisor

Associate Scientist

Cell Therapy

Scientist

Ex-Vivo

Scientist

Scientist

Raphael Nir, Ph.D. President and CSO Tel: 508-650-6218

E-mail: rnir@sbhsciences.com www.sbhsciences.com

Discovery Research Products & Services