SHED Master Cell Bank Completed

Kidswell Bio Corporation

Cautionary Statement

This information material is provided for understanding Kidswell Bio
Corporation (“KWB”), not for soliciting investment in KWB shares.
Information provided in this material may contain so-called “forwardlooking statements.”
These statements are based on current
expectations, forecasts and assumptions that are subject to risks anduncertainties, which could cause actual outcomes and results to differ
materially from these statements. Risks and uncertainties include
success rate of R&D projects, new regulations and rules, relations withpartners in the future, etc.
This material includes information on pharmaceutical products andregenerative medicine (or related products), etc., which is being
developed or launched. However, this is not intended to promote ourproducts or provide medical advices.

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SHED Master Cell Bank

3

What’s SHED Master Cell Bank?

Essential component for high-quality cell therapy

Process
Extract※SHED

Isolation culture
Selectively
increase SHED

Cell expansion

Isolation culture of SHED・Formulated criteria forChallenges

extraction of deciduous teeth
・Improved appropriate culture
condition
・Improved whole process fromSEHD extraction to isolation
cultureCell (SHED) expansion

・ Improved conditions during
culture days and culture
methods (cell density, etc.)
・Improved whole manufacturing
process of cell expansion

SHEDMaster Cell Bank※※ For the purpose ofpharmaceuticalmanufacturing,
specific cells arecultured and frozen instorage tube

⇒ Solved various issues and improved processes byaccumulated KWB’s know-how※

SHED:Stem cells from Human Exfoliated Deciduous teeth 4

SHED Master Cell BankSHEDFrozen SHED MCB in a storage tube*

Microscope image ofSHEDs**Sample5: Stable manufacturing & supply system established

From teeth donation to SHED Master Cell Bank
Check donors’ healthcondition
Extract deciduous teeth
University of Tokyo Hospital
Showa University Dental Hospital• Declaration of Consent• Donor information management• Donor screening (medicalexamination）• Store and supply extracted
teeth, etc.

Manufacture SHED
Master Cell Bank incompliance with GMP
Nikon CeLL innovation(Cell and gene therapy processdevelopment and cell and gene therapy
manufacturing service）• Receive extracted teeth• Extract SHED from pulp tissue andculture• Manufacture SHED Master Cell BankDeciduousteeth

Celltherapy
products
Development

Master Cell Bank

Secure sufficient teeth donor
candidates

Demandof rawmaterials
6Business strategies
Launch the world’s first SHED cell & gene therapy
SHED: 1st generation
Strive to establish SHED
business
Target diseases: Diseases
related to nervous,
muscular and bone system
Market potential:
Expect to grow 700 to 800
billion yen market size by※12040（Global)SHED:
2nd generation

SHED Supply Business

Designer cells

For other modalities

Target diseases:
Genetic disease,neurodegenerative diseaseand cancer• Products utilizing SHEDderived cell organs andextracellular vesicles(exosome andmitochondria, etc.)• Drug Delivery Systemutilizing SHED

Market potential:
Expect to grow over 1trillion yen market size by※22028(e.g. CAR-T cell therapy: over
13.5 billion dollars in the world)Market potential:
Expect hundreds of billions※3
yen market size

SHED Master Cell Bank
※1: KWB’s research (Page 13)、 ※2,3: Estimated by KWB based on public information fromvarious related institutions and organizations

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Road map: Mid-Term Strategic Plan KWB2.0
For improvement of corporate value
University ofTokyo Hospital &Showa University
Dental Hospital

Nicon CeLL
innovation

KIDS WELL, ALL WELL

Launching cellular medicine/cell therapy products

SHED Master Cell Bank Competed
Accelerating cell therapy
products development

Establishment of revenue base
Establishment of biosimilar
development technology• Strong sales of GBS-007• Progress of the developmentof the 4th BS

Aiming to launch the world's
first SHED medicine/ therapy
by FY2030

Focusing on SHED development• Steady development progress inJapan and overseas• Accelerating development inoverseas. in addition to domesticdevelopment• Active investment in humanresources and capital• Accelerating R&D by fund-raisingfrom overseas investors• Establishment of SHED platform• Strengthening SHED businessactivities• Diverse personnel structure,including experts of cell medicine
development and human resources
with knowledge of new modalities

SHED + Human Resource Development

Maintaining stable revenue from biosimilar business
Founded (2001)
to FY 2021

FY 2022

FY 2025(3 billion yen of sales and 1 billion
yen of operating profit)

FY 2030 onward8

Appendix

10Business strategies• Apply to various products utilizing SHED Master Cell Bank
• Established stable manufacturing and supply system for regenerative
medicine products

SHED Master Cell Bank
SHED: 1st Generation

SHED: 2nd Generation

SHED Supply Business

Strive to establish SHEDbusiness

Designer cells• Introduce the next
generation technologies (invivo/ex vivo, virus, artificial
chromosome, etc.)

For other modalities• Research collaboration withacademia• Drive activities for starting
clinical research and trials• Combine SHED with otherdevices with synergistic
effects• Products utilizing SHEDderived cell organs andextracellular vesicles(exosome andmitochondria, etc.)• Drug Delivery Systemutilizing SHED

Various academia
Master Cell Bank

Accelerate to launch new cell & gene therapy

Strengthen SHED
Supply Business
11Development of cell therapy with SHED
Strive to launch the world’s first cell therapy fully utilizing the characteristics of SHED
1st generation

Companies of cell medicine development (Japan)

Pulp stem cells from neural crests are expected to be particularly
applicable to diseases of the nervous and muscle/bone systems.
Features of SHED

Application for regenerative medicine※1,2High proliferative ability

Sufficient cells in a short period of time

Expression of neurogenesis-related
genes※1, 3, high secretion of nervous
system growth factor※1, 4and high nerve regenerative※1,5
abilityHigh bone regenerative ability※1,6Diseases related to nerve regeneration(Ex. Spinal cord injury, brain infarction,
cerebral palsy, etc.)
Diseases required bone regeneration(Ex. Non-union fracture, osteonecrosisof the femoral head, etc.))

出所:※1: Data from KWB & Research collaboration, ※2: Miura et al. PNAS. 2003, ※3: Terunuma et al. J StemCell Regen Med. 2019, ※4: Mead et al. PLoS One. 2014, ※5: Sakai et al. J Clin Invest. 2012, ※6:
Nakajima et al. BBRC. 2018

Tissue type

ProductnameTargetdisease

Company

Deciduous
teeth-derived(Non-clinicalstudies)

Nervous andmuscle/bonediseases

KWB

Bone marrowderived(Allogenic)

Temcell(Launched)

Acute GVHD

JCR
Pharmaceuticals

Bone marrowderived(Autologous)

Stemirac(Launched)Spinal cord
injuryNiproCorporation

Adipose-derived(Allogenic)

Alofisel(Launched)

Perianal
fistulaTakedaPharmaceuticals

Expect to launch an epoch-making cell (SHED)
therapy for severe diseases

2nd generation
Focus on develop reinforced SHED with enhanced therapeutic efficacy

Design Technology
Development of new gene transfermethods（Ex: NanoCarrier）
Development of new culture methods(Ex: BioMimetics Sympathies Inc.）
Verification of the effects of various
types of transgenes (Ex: Nagoya
Univ., Hamamatsu University Schoolof Medicine, etc ）Target diseases of※development
Genetic diseases

Cost-effective cell therapy※（Evaluation results of NICE ）Tissue type

Product
nameTarget disease

Company

Modifiedimmune cells

Kymriah(Launched)• Diffuse large B-celllymphoma• Follicular lymphomas

Novartis

Degenerative (Nerve)
Cancer, etc.

※ In addition to nervous andmuscle/bone diseases in the list oftarget diseases of 1st generation
SHED

KWB focuses on the development of a costeffective cell (SHED) therapy.
※National Institute for Health and Care Excellence

12Global Market Potential: SHED
Estimation: Nervous system and muscle/ bone diseases
targeted by SHED will grow from 700 billion to 800 billion yen
market by 2040.

25,00020,000Estimation for market size in2040 (100 million yen)（100 million yen）

15,000Autologous

Allogeneic

stem cells:

stem cells:

18,53820,193

RespiratoryMetabolic Disorders
Immunology
Genetic Disorders
Gastrointestinal
Dermatology
Central Nervous System

10,000

Cardiovascular※Including Japan, the U.S.
Europe, China and India in
global market (Targeted
10% of the population in
China and India）

5,000

02022 2023 2024 2025 2026 2027 2028 2029 2030 2031 2032 2033 2034 2035 2036 2037 2038 2039 2040 （年）Estimation for global market size of allogeneic stem cells

Accelerate SHED research & development as KWB’s growth driver,expecting high profitability in growing global cell medicine market
KWB’s research based on Regenerative medicine and gene therapy market research in 2019 Final report from the website of Japan Agency for Medical Research andDevelopment, Global Data from epidemiological literature and websites from rare diseases (Orphanet, NORD, Japan Intractable Diseases Information Center, ClinicalDevelopment Success Rates 2006-2015, BIO Industry Analysis」 and related documents from general meeting of Central Social Insurance Medical Council13

Technical Terminology
TermExplanation

Cell therapy is the transplantation of human or animal cells to replace or repair damaged
Cell therapy
tissue. It includes utilizing immune cells in the blood, adipose-derived and born-derived(Regenerative Medicine) mesenchymal stem cells.

Designer cells

ExosomeGMP

Master Cell Bank(MCB)SHEDDesigner cells can enhance therapeutic efficacy and cell directionality for disease sites. They
are of interest in the field of diseases without radical cure as a medical treatment of next
generation.
A tiny vesicle created and released from the plasma membrane of various types of cells,
especially immune cells, and capable of inducing antigen-specific immune responses.
Exosomes are of special interest in the field of medicine with their special ability.

Good Manufacturing Practice (GMP) is minimum required guidelines that amanufacturer must meet to assure that their products are consistently high in quality
and work for their intended use. GMP is a part of a quality system covering the
manufacture and testing of pharmaceutical ingredients, foods, pharmaceuticalproducts, diagnostics, and medical devices.
Master Cell Bank (MCB) is cells for medical treatments that are expanded under theconstant culture condition and divided into several vials for long frozen storage.
Frozen MCB can be expanded again after thawing and utilized for regenerative
medicine products as a raw material.
SHED:Stem cells from Human Exfoliated Deciduous teeth
SHED is a mesenchymal stem cell (MSC) extracted from a dental pulp cavity inside
exfoliated deciduous teeth and is easy to differentiate into bone and nerve cells.
Especially SHEDs from young donors have shown higher proliferative activity andsecretory capacity of various growth factors (particularly neurotrophic factors)
compared to stem cells from other tissues.
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