Regenerative Therapiesfor Neurological Disorders

Company Overview

Company Background

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

Mission StatementSanBio develops regenerative therapies addressing unmet medical needs

and creating value for stakeholders.

Financial Support

Clinical Trial & Development

Innovative Business Infrastructure

Innovative Science & Technology

Japan/U.S. Hybrid Innovation

Neurological Disorders: Market SizeNeurological Disorder Sector is Growing Rapidly, Faster Than Other Markets

Disease Prevalence in U.S. (2010)

U.S. Product Sales (2010)

Stroke 6.8MM

Parkinson’s Disease 1.6MM

Multiple Sclerosis 400,000

Spinal Cord Injury 300,000 N/A

We are researching the product sales and will add

Potential Market Value

Valuation Summary

Expected

Launch

Year

Target

patients

SB623

market

share

Patients

treatedPrice

Peak

sales

Peak

salesENPV

'000（ ） （％） '000（ ） $/ treatment（ ） MM)（＄ MM)（＄ MM)（＄

Stroke 2017 102 80% 81 25,000 2,032 10,377 4,585

Traumatic brain injury 2019 74 80% 60 25,000 1,493 6,781 2,298

Parkinson's disease 2019 63 80% 51 25,000 1,267 5,757 1,939

Spinal cord injury 2019 26 80% 21 25,000 528 2,399 765

Retinal disease 2019 92 80% 74 25,000 1,843 8,375 2,854

Total 12,441

* Indications limited to the ones with efficacy confirmation in animal model. Do not include anticipated indications such

as Alzheimer's or multiple sclerosis.

** Target patients, SB623 market share and patients treated are all taken at the peak sales year.

Indication

North America* World wide

Competitive Overview

• Neural Deficit Recovery™ (NDR) patented drug discovery platform

• Bone marrow-derived cells• Industrial scale expansion• Therapeutic potential

Management TeamKeita Mori, MBA

Co-CEO, Chairman, Co-Founder

Toru Kawanishi

Co-CEO, Co-Founder

Damien Bates MD, PhD, FRACS, MBA

Chief Medical Officer

Michael P. McGrogan, Ph.D.

Senior Vice President, Production Development

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Senior AdvisorsDonald Kennedy Former President of Stanford University, Commissioner of the United States Food and Drug Administration, and

Editor-in-Chief of Science

Mario Rosati Partner at Wilson Sonsini Goodrich & Rosati. Managing partner of WS Investments, an investment partnership composed of the partners and associates of the firm

Charles Garvin Principal, Palisades Associates, a merchant banking firm. A founding principal of The Beta Group, a Silicon Valley business development organization

Gary Snable Founder, Ex CEO, Layton Bioscience

George Martin Former Scientific Director, National Institute of Aging (NIH); SVP Fibrogen

Arnold Caplan Professor, Case Western Reserve

Martha Bohn Professor, Northwestern University, Past Member of RAC

Cesario Borlongan Professor, University of Southern Florida

Krys Bankiewicz Professor, UCSF

Yoichi Nabeshima Former Professor, Kyoto University; Director, IBRI

Scientific Advisory Board

Advisors

Partnerships

• Clinical Trial Partners

• Corporate Partners

• Innovation Awards

Approach to Brain Regeneration

Donor bone marrow stem cells

are harvested

Allogeneic Cell Transplant

Regenerative effect on recipient cells

Brain & body function restored

NDR™ Technology Platform

BoneMarrow

SB623

SB618

SB308

Products(“Cells-in-a-bottle”)

Production

...

Neural Deficit Recovery™

NDR™ Technology

Product Pipeline

Bone Marrow Derived Cells

Stroke, TBI, SCI,Retinal Disease,

PD, AD, etc.

Multiple Sclerosis,Peripheral Nerve,

SCI, etc.

Muscle Dystrophy, etc.

SB623 SB618 SB308

Bone Marrow-DerivedNeuroregenerative Cells

Enhanced Marrow Stromal Cells(eMSC)

Bone Marrow-DerivedMuscle Regenerative Cells

P-1/2 Nonclinical Research

Different image

Bone Marrow-Derived Regenerative Cell MedicinesDamien – Can you recommend an image for SB618?

Indications Overview

Indication SB623 SB618 SB308

Stroke Recovery √

Parkinson’s Disease √

Spinal Cord Injury √ √

Multiple Sclerosis √

Muscular Dystrophy √

Trauma √ √ √

SB623

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

• 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

Scalable Production Methods Reduced to PracticeManufacturing Process & Product Preparation

Multiple Modes of Action

SB623Modes of Action

Trophic Factors

Extracellular Matrix

Anti-inflammation

Stimulating Migration

Angiogenesis

Damien – Please note that we will have our creative team rework this slide to make it look more polished

Product CharacteristicsBulk Substance Specifications

Product CharacteristicsDrug Product Specifications

Attribute Specification

Purity and Impurities

Purity ≥ 80% PositiveCD29, CD90, CD105

Impurities ≤ 5% PositiveCD31, CD34, CD45

Quality

Cell Viability ≥ 70% viable

Total Viable Yield ≥ 8x106 viable cells/mL

Plating ≥ 50%

Cell Growth Rate Doubles in ≥ 1 to ≤ 5 days

Safety

Colony Growth in Soft Agar No Colonies

Sterility No Growth

Bacterial No Growth

Fungal No Growth

Endotoxin ≤ 5 EU/mL

Loss of NICD with Continued PassagesDisappearance 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 ChangesCpG Methylation Status of 5 Different Genes for 3 Donors

Homogeneity and Identity of SB623 CellsCells are Positive for MSC Markers and Negative for Hematopoietic Markers

Proteomic Analysis of the Extracellular MatrixCharacterization of the ECM Produced by SB623

Extracellular Matrix Produced by Bone Marrow Stromal CellsECM Promotes Neural Growth

Extracellular Matrix Produced by Bone Marrow Stromal CellsSupports Growth of Different Neural Cell Types

Comparison of The Neuropoietic ActivityDerived ECM Supports Nestin Growth; Mediated by TGM2

Human Mesenchymal Stromal Cells and Their DerivativeMultiple Growth Factors Released

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Human Mesenchymal Stromal Cells and Their DerivativeReduces Cell Death In Vitro Model Ischemia

Quantitative Microplate Assay for StudyingMSCs Promote Neural Cell Growth and Differentiation

Comparison of The Neuropoietic ActivitySB623 Promotes More Neural Cell Growth and Differentiation Than MSCs

Comparison of The Neuropoietic ActivitySB623 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 PotencyDecreases Cell Mediated Immune Response

Effect on Peripheral and Nervous System Innate Immune CellsSB623 Cells Reduce The Percentage of Pro-Inflammatory Peripheral Blood Monocytes

Comparing The Immunosuppressive PotencySB623 Induces Regulatory T Lymphocytes

Comparing The Immunosuppressive PotencySB623 Inhibits Differentation of Monocytes to Dendritic Cells

Stem Cell Recruitment of Newly Formed Host CellsSB623 Supports Robust Migration and Proliferation of Endogenous Stem Cells in Traumatic Brain Injury Model

Effect of SB623 on Neural Progenitor Cell MigrationDose Response of SB623 Conditioned Medium on NPC Migration

SafetyCells Are Not Tumorigenic

Absence of Growth on Brain Slices SB623 Cells Do Not Exhibit Signs of Tumorigenic Transformation

SafetyTransient Persistence of SB623 Cells In Vivo and No Migration Away From Site of Implantation

Rapid Disappearance of SB623 Cells In Vivo

Safety

Differentiation Potential of MSCs and SB623

SB623 Cells Have Limited Differentiation Potential

Clinical Trials and Data

SB308

Muscle Degeneration

Development StagesDamien – Please note that we will have our creative team rework this slide to make it look more polished

Research Non-clin. IND Approval

P1 P2 P3

Traumatic Brain Injury

Retinitis Pigmentosa

Dry AMD

Parkinson’s Disease

Spinal Cord InjuryAlzheimer’s Disease

Stable Stroke

SB623: Clinical Trial Overview

SB623 Tested in Chronic Stroke Rat Model to Determine Functional RecoverySB623: Stroke Preclinical Program

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

SB623: Stroke Phase 1 & 2 Clinical Trials

Stereotactic Frame Positioning

Needle tracks for cell implantation and suggest implant sites

Stereotactic Frame Positioning

Needle Tracks for Cell Implementation and Suggest Implant

Sites

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

NIHSS

Months Post-treatment

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ESS

Months Post-treatment

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Fugl-Meyer

Months Post-treatment

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SB623: Statistically Significant Efficacy Endpoints

Safety Parameters• SB623- and surgical-related adverse events using WHO toxicity criteria• Adverse changes imaged by head MRI• Serum chemistry and hematology• 2 yrs. post-implant follow-up

Analysis of Safety• 17 patients had at least one treatment-emergent adverse event (TEAE)

– No trends observed with dose level and majority of TEAEs

– Overall, assessed as mild or moderate

– Higher number of patients had TEAEs that were assessed as related to the surgical

procedure when compared with TEAEs related to study treatment

– Five patients experienced severe TEAEs

SB623: Clinical Safety

“... This trial represents an important advance in bringing restorative therapeutics for neurologic disorders into the clinical arena. Three measures of efficacy (NIHSS, ESS, Fugl‐Meyer) all show a trend toward improvement. We are looking forward to the next clinical trial.”

Gary K. Steinberg, M.D., Ph.D.Chairman, Department of Neurosurgery

Stanford University School of Medicine

SB623: Results Presented at Key Industry Event

Test

Control

SB623 Reduced TBI Core and Peri-Injury AreaSB623: Traumatic Brain Injury Preclinical Efficacy

Test Control

Nestin

SB623 Increased Nestin+ Cells

SB623: Traumatic Brain Injury Preclinical Efficacy

SB623 Increased MMP-9 Gelatinolytic Activity

SB623: Traumatic Brain Injury Preclinical Efficacy

SB623 Stimulated New Cells to Migrate

SB623: Traumatic Brain Injury Preclinical Efficacy

Elevated Body Swing Test BedersonRotarod

Significant Motor and Sensory Function Recovery in TBI Rat Model

SB623: Traumatic Brain Injury Preclinical Efficacy

SB623: Traumatic Brain Injury Clinical Study Design

We reviewed the materials but may have missed this information. Can you let us know where to locate?

SB623 Tested in RCS Rat: Subretinal Transplantation

SB623: Retina Preclinical Program

Electroretinogram (a-wave, b-wave) in SB623 Intravitreal Administration

Significant Vision Preservation in RCS Rat Model

SB623: Retina Preclinical Efficacy

Azide Response @ 8 wks post transplantation

Significant Vision Preservation in RCS Rat Model

SB623: Retina Preclinical Efficacy

Retinal Structure @ 9 wks Post Transplantation

SB623 Preserved Outer Nuclear Layer

SB623: Retina Preclinical Efficacy

Intravitreal Administration as Effective as Subretinal

Favorable Administration as Effective

SB623: Retina Preclinical Efficacy

SB618

• Potential to treat conditions that affect the myelin sheath of neurons

• Bone marrow-derived, Schwann-like cells• Allogeneic cells

SB618: Therapy Overview

Myelin Sheaths Surrounding Regenerated Neurons

• SB618 cells labeled with Green Fluorescent Protein (GFP) and engrafted into transected sciatic nerve

• 6 months later, transverse sections of regenerated were stained for neuronal marker NF

• NF positive axons shown in the photomicrograph above staining red• GFP positive implanted Schwann-like cells shown as green• Green cells clearly surround red cells

SB618: Promising Therapy Approach

Mimura et al. (2004) J. Neurosurg. 101:806-812.

Repair of Injured Peripheral Nerve

• Sections of the sciatic nerves of rats replaced with matrix-filled tubes of SB618 cells or vehicle control

• 6 months later, implant site sectioned transversely to count number of nerve cells (axons)

•  Measure of hind limb function after spinal cord injury

• Animals were subjected to complete transection of spinal cord

• SB618-treated animals recovered more quickly and to a greater extent than untreated

Spinal Cord Injury Repair (SB618)

SB618: Promising Therapy Approach

* indicates p < .05. Mimura et al. J. Neurosurg. (2004) 101:806-812. * indicates p < .05. Kamada et al. (2005) J. Neuropathol. Expt. Neurol. 64:37.

SB308

• Extended core technology beyond nervous system• Bone marrow to stimulate muscle regeneration • Potential to treat conditions such as muscular dystrophy;

recovery from trauma and surgery• Tested in rat model with positive results• External funding required for development beyond animal

studies• Commercialization through larger pharmaceutical company

partnerships

Therapy Overview

Scientific Publications

Scientific Publications

Q&A