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Regenerative Therapies for Neurological Disorders. Company Overview. Company Background. Mission Statement SanBio develops regenerative therapies addressing unmet medical needs and creating value for stakeholders. Quick Facts Clinical-stage regenerative medicine company Founded in 2001
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Company Background Mission Statement SanBio develops regenerative therapies addressing unmet medical needs and creating value for stakeholders. • Quick Facts • Clinical-stage regenerative medicine company • Founded in 2001 • Headquartered in Mountain View, Calif. • Funding to Date: $53 million • 35 patents issued, 41 patents pending
Japan/U.S. Hybrid Innovation Innovative Science & Technology Clinical Trial & Development Innovative Business Infrastructure Financial Support
Neurological Disorders: Market Size Neurological Disorder Sector is Growing Rapidly, Faster Than Other Markets We are researching the product sales and will add
Potential Market Value Valuation Summary
Competitive Overview • Neural Deficit Recovery™ (NDR) patented drug discovery platform • Bone marrow-derived cells • Industrial scale expansion • Therapeutic potential
Management Team Keita Mori, MBA Co-CEO, Chairman, Co-Founder Placeholder: Headshot Toru Kawanishi Co-CEO, Co-Founder Placeholder: Headshot Michael P. McGrogan, Ph.D. Senior Vice President, Production Development Placeholder: Headshot Damien Bates MD, PhD, FRACS, MBA Chief Medical Officer Placeholder: Headshot
Advisors Scientific Advisory Board Senior Advisors
Partnerships • Clinical Trial Partners • Corporate Partners • Innovation Awards
Approach to Brain Regeneration Allogeneic Cell Transplant Donor bone marrow stem cells are harvested Regenerative effect on recipient cells Brain & body function restored
NDR™Technology Platform Products (“Cells-in-a-bottle”) Production Neural Deficit Recovery™ NDR™ Technology SB623 SB618 Bone Marrow SB308 . . .
Damien – Can you recommend an image for SB618? • Bone Marrow-Derived Regenerative Cell Medicines Bone Marrow Derived Cells SB623 SB618 SB308 Bone Marrow-Derived Muscle Regenerative Cells Bone Marrow-Derived Neuroregenerative Cells Enhanced Marrow Stromal Cells (eMSC) Different image Stroke, TBI, SCI, Retinal Disease, PD, AD, etc. Multiple Sclerosis, Peripheral Nerve, SCI, etc. Muscle Dystrophy, etc. P-1/2 Nonclinical Research
Therapy Overview • Developed as treatment for chronic neurological deficits – stable stroke, advanced Parkinson’s disease, traumatic brain injury • Reverses neural damage when injected into neural tissue • Single allogeneic donor cell can be used to treat thousands of patients. • Shown to restore function to damaged neurons associated with stroke, spinal cord injury and Parkinson's disease SB623 Cells
Manufacturing Process & Product Preparation Scalable Production Methods Reduced to Practice • Cells are expanded, formulated and cryopreserved in vials stored in vapor phase of liquid nitrogen • Final product is a sterile frozen suspension containing at least 10 million viable cells per mL in a cryovial • Shipped to clinical sites using a Dry Nitrogen Cryo shipper with adsorbed liquid nitrogen • Cells will grow with a doubling time of 3 to 4 days after thaw
Damien – Please note that we will have our creative team rework this slide to make it look more polished Multiple Modes of Action Trophic Factors Angiogenesis SB623 Modes of Action Extracellular Matrix Stimulating Migration Anti-inflammation
Product Characteristics Bulk Substance Specifications
Product Characteristics Drug Product Specifications
Loss of NICD with Continued Passages Disappearance of The Plasmid During Expansion (prior to phase 2) Plasmid pN-2 was measured using qPCR and expressed as copies per diploid genome. Passage number is represented as P1, P2, etc. The negative control is buffer alone. Lanes 1, 2, 5 and 6 are unactivated/unstabilized negative controls. Lanes 3 and 4 show activated and stabilized samples and indicate the location of the endogenous NICD. Lane 7 shows high levels of NICD protein 3 days post transfection. Lane 8 shows no detectable NICD in the final product.
Transient Transfection with NICD Causes Epigenetic Changes CpG Methylation Status of 5 Different Genes for 3 Donors
Homogeneity and Identity of SB623 Cells Cells are Positive for MSC Markers and Negative for Hematopoietic Markers
Proteomic Analysis of the Extracellular Matrix Characterization of the ECM Produced by SB623
Extracellular Matrix Produced by Bone Marrow Stromal Cells ECM Promotes Neural Growth
Extracellular Matrix Produced by Bone Marrow Stromal Cells Supports Growth of Different Neural Cell Types
Comparison of The Neuropoietic Activity Derived ECM Supports Nestin Growth; Mediated by TGM2
Human Mesenchymal Stromal Cells and Their Derivative Multiple Growth Factors Released Placeholder: We are simplifying the table per your notes and will add in
Human Mesenchymal Stromal Cells and Their Derivative Reduces Cell Death In Vitro Model Ischemia
Quantitative Microplate Assay for Studying MSCs Promote Neural Cell Growth and Differentiation
Comparison of The Neuropoietic Activity SB623 Promotes More Neural Cell Growth and Differentiation Than MSCs
Comparison of The Neuropoietic Activity SB623 Action Mediated by FGF2 and BMP4
Comparing The Angiogenic PotencySB623 and MSCs Secrete Proangiogenic Factors
Comparing The Angiogenic PotencySB623 Promotes More Branching in Aortic Ring Assay
Comparing The Immunosuppressive Potency Decreases Cell Mediated Immune Response
Effect on Peripheral and Nervous System Innate Immune Cells SB623 Cells Reduce The Percentage of Pro-Inflammatory Peripheral Blood Monocytes
Comparing The Immunosuppressive Potency SB623 Induces Regulatory T Lymphocytes
Comparing The Immunosuppressive Potency SB623 Inhibits Differentation of Monocytes to Dendritic Cells
Stem Cell Recruitment of Newly Formed Host Cells SB623 Supports Robust Migration and Proliferation of Endogenous Stem Cells in Traumatic Brain Injury Model
Effect of SB623 on Neural Progenitor Cell Migration Dose Response of SB623 Conditioned Medium on NPC Migration
Safety Cells Are Not Tumorigenic SB623 Cells Do Not Exhibit Signs of Tumorigenic Transformation Absence of Growth on Brain Slices
Safety Transient Persistence of SB623 Cells In Vivo and No Migration Away From Site of Implantation Rapid Disappearance of SB623 Cells In Vivo
Safety SB623 Cells Have Limited Differentiation Potential Differentiation Potential of MSCs and SB623
Damien – Please note that we will have our creative team rework this slide to make it look more polished Development Stages SB308 Muscle Degeneration
SB623: Clinical Trial Overview Stable Stroke Traumatic Brain Injury Dry AMD Retinitis Pigmentosa Parkinson’s Disease Spinal Cord Injury Alzheimer’s Disease
SB623: Stroke Preclinical Program SB623 Tested in Chronic Stroke Rat Model to Determine Functional Recovery
SB623: Stroke Phase 1 & 2 Clinical Trials Overall Design • Open Label • 18 Stroke Patients • 6 Mo. Efficacy, 2-Year Follow-Up Patient Population • 6-36 Months Post-Ischemic Stroke • Stable Deficits • Moderate to Severe Patients Endpoints • Safety • Efficacy: Motor, Sensory, Cognitive • Brain Activity by PET Trial Sites 12 Patients Enrolled & Good Safety
SB623: Stroke Phase 1 & 2 Clinical Trials Approach Damien – We’ve reviewed all the materials and can’t find a better image. We can pull a stock image and then add the arrows to the sites if you’re okay with that Stereotactic Frame Positioning Needle Tracks for Cell Implementation and Suggest Implant Sites