1. Regenerative Therapies for Neurological Disorders

2. Company
Overview

3. Company Background Mission Statement Quick Facts
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

4. Japan/U.S. Hybrid Innovation
Innovative Science
& Technology
Clinical Trial & Development
Financial Support
Innovative Business
Infrastructure

5. Neurological Disorders: Market Size
Damien – Our team was unable to find updated product sales. Perhaps this is something your commercial team has?
Neurological Disorder Sector is Growing Rapidly, Faster Than Other Markets
Disease
Prevalence in U.S. (2010)1
U.S. Product Sales (2010)
Stroke
6.8MM
Parkinson’s Disease
1.6MM
Multiple Sclerosis
400,000
Spinal Cord Injury
300,000
N/A
Worldwide market size of the neurological disorder therapeutic arena was approximately $XX billion in 2010.
Second largest pharmaceutical sector after cardiovascular disease.
Neurological disorder sector is growing rapidly, faster than other markets. Most neurological disorders are diseases of aging, and most industrialized countries have an aging population distribution.
Currently no effective regenerative medicine therapies on the market for neurological disorders.
Stroke is one of the leading causes of death in the United States.
Of the approximately 700,000 new cases of acute stroke each year in the U.S., approximately one-third die, one-third recover most of their function and one-third are permanently disabled.
1American Heart Association; Alzheimer’s Association; National Parkinson Foundation; Multiple Sclerosis Foundation; The Foundation for Spinal Cord Injury, Prevention, Care & Cure

6. Potential Market Value
Valuation Summary
North America*
Worldwide
Indication
Expected Launch Year
Target Patients
SB623 Market Share
Patients Treated
Price ($/treatment)
Peak Sales (MM)
ENPV (MM)
Stroke
2017
102,000
80%
81,000
25,000
$2,032
$10,377
$4,585
Traumatic Brain Injury
2019
74,000
80$
60,000
$1,493
$6,781
$2,298
Parkinson’s Disease
63,000
51,000
$1,267
$5,757
$1,939
Spinal Cord Injury
26,000
21,000
$528
$2,399
$765
Retinal Disease
92,000
$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.

7. Competitive Overview Advantages Disadvantages Autologous Safety
Variability (yield, identity, purity, potency) across donors
Time to produce and administer
Cost (expensive to produce and deliver)
Allogeneic
Less variability (identity, purity and potency)
Potential immune reactions
Availability (immediate)
Repeat dosing (no yield issues)
No separate harvesting procedure required for recipient
Amenable to scale up lowering COGS
Proprietary NDR™ technology offers a competitive advantage in the preclinical stage.
SanBio can identify promising potential drugs for applications for which there is no existing effective therapy at a much lower cost and in much less time than the drug development methods used by most other pharmaceutical companies.
SanBio is the only company pursuing adult bone marrow-derived cells as the product.
SanBio believes that this will be an advantage in development and commercialization, since bone marrow has already been widely used in the medical community.

8. Damien Bates MD, PhD, FRACS, MBA
Management Team
Keita Mori, MBA
Co-CEO, Chairman, Co-Founder
Toru Kawanishi
Co-CEO, Co-Founder
Damien Bates MD, PhD, FRACS, MBA
Chief Medical Officer, Interim Head, R&D
Michael P. McGrogan, Ph.D.
Senior Vice President, Production Development

9. Advisors Scientific Advisory Board Senior Advisors 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
Senior Advisors
Donald 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

10. Partnerships Clinical Trial Partners Corporate Partners
Innovation Awards

11. Approach to Regeneration
Damien – Please let us know which image you’d like to use for the Allogeneic Cell Transplant section
Allogeneic Cell Transplant
Regenerative Effect on Recipient Cells
Donor Bone Marrow Stem Cells are Harvested
Body
Function Restored

12. Bone Marrow Donation & Stem Cell Isolation
Production
Modification
Products
Technology
SB623
Bone
Marrow
SB618
Proprietary Transfection and Selection and/or Growth Factor Treatment
SB308

13. Product
Pipeline

14. SanBio Stem Cell Technology Platform – Application
SB623
SB618
SB308
Bone Marrow-Derived
Neuroregenerative Cells
Enhanced Marrow Stromal Cells
(eMSC)
Bone Marrow-Derived
Muscle Regenerative Cells
Stroke, Traumatic Brain Injury, Spinal Cord Injury, Retinal Disease (Dry Age-Related Macular Degeneration), Parkinson’s Disease, Alzheimer’s Disease
Multiple Sclerosis,
Peripheral Nerve, Spinal Cord Injury
Muscular Dystrophy

15. SB623

16. SB623: Therapy Overview Regenerates neural tissue
Single allogeneic donor cell can be used to treat thousands of patients
Shown to improve function in animal models of stroke, traumatic brain injury, Parkinson’s disease and retinal disease
Clinical stage development for chronic stroke and traumatic brain injury
Derived from adult human bone marrow.
Function by promoting the body's natural regenerative process.
May also be useful in other diseases and conditions associated with neurological deficit, such as traumatic brain injury, Huntington's disease and amyotrophic lateral sclerosis.

17. SB623: 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
Final Product Formulation
SB623 cells are transiently-transfected stem cells derived from human bone marrow aspirate (BMA) using SanBio's proprietary technology.
Marrow Adherent Stem Cells (MASCs) are isolated from bone marrow and expanded for production.
Cells are generated from MASC cells by transfection with a plasmid containing the intercellular domain of the human Notch1 gene and the transfected cells are then selected with G418.
The product is suspended and frozen in CryoStore CS5® solution to provide a sterile suspension of ≥10 million viable cells/mL in 1mL cryovials.
The final sterile product formulation is stored in the vapor phase of liquid nitrogen. The final product cryovials containing frozen cells are shipped to the clinical site using a Dry Nitrogen Cryo shipper with adsorbed liquid nitrogen.
Prior to use, the product is thawed, isolated by centrifugation, washed and re-suspended in Plasma-Lyte A® at the specified concentration needed for injection using aseptic techniques.
Prior to implantation, a Gram stain and an endotoxin assay, along with a sample for testing, ensure continued sterility.
San Bio Incorporated. (2014). Investigator's drug brochure [Brochure]. Mountain View

18. SB623: Multiple Modes of Action

19. SB623: Product Characteristics
Attribute
Specification
Purity and Impurities
Purity
≥ 80% Positive CD29, CD90, CD105
Impurities
≤ 5% Positive CD31, 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
Fungal
Endotoxin
≤ 5 EU/mL
Mycoplasma
Negative
Viral (qPCR Assay): HIV-1 & HIV-2, HTLV-1 & HTLV-2, HBV, HCV, CMV, EBV-1 & EBV-2, Human Parvo Virus B19, Polyomavirus JCV
SB623: Product Characteristics
Drug Product Specifications
San Bio Incorporated. (2014, May 15). Type B meetings background/briefing materials [SB623 Cells]. Mountain View

20. SB623: Identity and Purity of SB623 Cells
Cells are Positive for MSC Markers and Negative for Hematopoietic Markers
SB623 Lot Number
CD29
CD90
CD105
CD31
CD34
CD45
PQ02
97.1
96.6
93.8
1.6
2.0
2.3
PQ03
98.2
95.5
91.9
1.8
2.2
3.2
SB01
99.9
99.8
99.5
1.2
1.5
SB06
99.3
2.5
CD29 = Beta-1 Integrin
CD90 = Thy-1
CD105 = Endoglyn
CD31 = PECAM-1
CD34 = Hematopoietic Progenitor Marker
CD45 = Leukocyte Common Antigen
San Bio Incorporated. (2014). Investigator's drug brochure [Brochure]. Mountain View

21. SB623 Derived ECM Promotes Neural Cell Growth
Aizman. I, J Neurosci Res. 2009, 87(14):

22. SB623 Secreted Proteins Decrease Cell Death
In Vitro Model of Ischemia
Tate CC. Cell Transplant. 2010,19(8):973-84

23. SB623 Action Mediated by FGF2 and BMP4
Comparison of The Neuropoietic Activity
Aizman I, Stem Cell Res Ther. 2014, 5(1):29

24. SB623 Cells Recruit Host Neural Progenitor Cells to Sites of Injury
SB623 Supports Robust Migration and Proliferation of Endogenous Stem Cells in Traumatic Brain Injury Model
Figure 3. At three months post-TBI, the brains from vehicle-infused animals displayed a disparate pattern of cell fate in
that the newly formed Ki67 positive and nestin labeled cells were sequestered within the corpus callosum (A) and the SVZ
(B) and only sporadic cells were able to reach the impacted cortex (A’ and B’), with likely resident DCX cells seen around
the impacted cortex (C). In contrast, at three months post-TBI, the brains from transplanted animals exhibited a much more
massive cell proliferation and neural differentiation encasing the peri-injured cortical areas accompanied by a solid stream of nestin
(D, D’) and DCX labeled cells (E) migrating not just along, but across the corpus callosum from the SVZ to the impacted cortex.
doi: /journal.pone g003
Tajiri, N. PLoS ONE 2013, 8(9):e74857

25. Dose Response of SB623 Conditioned Medium on NPC Migration*
300
250
200
150
100 50
* in millions
San Bio Incorporated. (2014, May 15). Type B meetings background/briefing materials [SB623 Cells]. Mountain View

26. SB623: Safety Cells Are Not Tumorigenic
Absence of Growth on Brain Slices
SB623 Cells Do Not Exhibit Signs of Tumorigenic Transformation
San Bio Incorporated. (2014). Investigator's drug brochure [Brochure]. Mountain View

27. Rapid Disappearance of SB623 Cells In Vivo
SB623: Safety
Transient Persistence of SB623 Cells In Vivo and No Migration Away From Site of Implantation
Rapid Disappearance of SB623 Cells In Vivo
San Bio Incorporated. (2014). Investigator's drug brochure [Brochure]. Mountain View

28. Clinical Trials
And Data

29. SB623: Clinical Trial Overview
Research
Non-clinical
IND
Approval P1 P2 P3
Traumatic Brain Injury
Retinitis Pigmentosa
Dry AMD
Parkinson’s Disease
Spinal Cord Injury
Alzheimer’s Disease
Stable Stroke

30. 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
San Bio Incorporated. Data on file

31. SB623: Statistically Significant Efficacy Endpoints
European Stroke Scale
Quantification of impairment caused by stroke.
A sum of scores in 14 items (consciousness, comprehension, speech, visual, facial movement, arm, wrist, fingers, leg, foot, gait)
0-100 (impaired-normal)
NIH Stroke Scale
Quantification of impairment caused by stroke
A sum of scores in 11 items (consciousness, visual, facial palsy, arm, leg, sensory, language)
0-31* (normal-impaired)
Fugl-Meyer Assessment of Physical Performance
Physical therapy assessment to evaluate progress from stroke
A sum of scores in 155 items, 5 sub-scales (Motor, Balance, Sensation, Joint Range of Motion, Pain)
0-226 (impaired-normal)
* Theoretical maximum is 42. However, since stroke is unilateral, practical maximum is 31.
San Bio Incorporated. Data on file

32. SB623: Clinical Safety Safety Parameters Analysis of Safety
SB623- and surgical-related adverse events using WHO toxicity criteria
Adverse changes imaged by head MRI
Serum chemistry and hematology
Immunology (anti-HLA antibodies; mixed lymphocyte reaction; TNF-α; IL-6; IFN-γ)
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 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
San Bio Incorporated. Data on file

33. SB623 Injection Decreases Zones of Injury
Test
Control
San Bio Incorporated. Data on file

34. SB623: Traumatic Brain Injury Preclinical Efficacy
SB623 Stimulates Neural Progenitor Cell Proliferation & Migration “Biobridge” Concept
San Bio Incorporated. Data on file

35. SB623: Traumatic Brain Injury Clinical Study Design
Overall Design
Open Label
12 Traumatic Brain Injury Patients
1 Year
Patient Population
Male, Female, Age 18-75
Patients with traumatic brain injury who have remained stable during the prior 3 weeks
Between 12 and 36 months post-traumatic brain injury with focal injury and fixed motor deficit
Endpoints
Safety determined during 1 year post-implant
Efficacy endpoints will be determined at 6 months post-implant; measures will also be at 1 week, and months 1, 2 and 12
San Bio Incorporated. Data on file

36. SB623: Retina Preclinical Program
SB623 Tested in RCS Rat: Subretinal Transplantation
San Bio Incorporated. Data on file

37. SB623: Retina Preclinical Efficacy
Significant Vision Preservation in RCS Rat Model
Azide 8 Wks Post Transplantation
San Bio Incorporated. Data on file

38. Q&A